The correct answer is 1. The statement perfectly defines a tolerance phenomenon in which the patient has become "used to" the dose and needs more in order to have the same analgesic effect.

The [HIDDEN] The statement perfectly defines a tolerance phenomenon in which the patient has become "used to" the dose and needs more in order to have the same analgesic effect.

The patient comes to the home of an oncology patient whose pain has not been well controlled lately. On physical examination there appears to be no evidence of tumor progression, and no previously known data of interest is revealed. In the anamnesis, the main caregiver states that the patient has pain 8 hours after receiving the prescribed basal dose of morphine every 12 hours. This clinical situation is referred to as:

Patient-controlled analgesia

With a PCA the patient is protected from overdose by the caregiver programming the PCA to deliver a dose at set intervals. If the patient presses the button sooner than the prescribed intake pressing the button does not operate the PCA. (The PCA can be set to emit a beep telling the patient a dose was NOT delivered). Dosage is also controlled when the patient is too sedated to press the button; preventing the patient from receiving needless doses and keeping the patient safe from overdosing. Epidural Patient-controlled epidural analgesia (PCEA) is a related term describing the patient-controlled administration of analgesic medicine in the epidural space, by way of intermittent boluses or infusion pumps. This can be used by women in labour, terminally ill cancer patients or to manage post-operative pain.

Cancer pain

Analgesics should not be taken "on demand" but "by the clock" (every 3–6 hours), with each dose delivered before the preceding dose has worn off, in doses sufficiently high to ensure continuous pain relief. People taking slow-release morphine should also be provided with immediate-release ("rescue") morphine to use as necessary, for pain spikes (breakthrough pain) that are not suppressed by the regular medication. Oral analgesia is the cheapest and simplest mode of delivery. Other delivery routes such as sublingual, topical, transdermal, parenteral, rectal or spinal should be considered if the need is urgent, or in case of vomiting, impaired swallow, obstruction of the gastrointestinal tract, poor absorption or coma. Current evidence for the effectiveness of fentanyl transdermal patches in controlling chronic cancer pain is weak but they may reduce complaints of constipation compared with oral morphine.

Opioid-induced hyperalgesia

activation (desensitization of antinociceptive mechanisms) and opioid receptor down-regulation (internalization of membrane receptors). In opioid-induced hyperalgesia, sensitization of pronociceptive mechanisms occurs, resulting in a decrease in the pain threshold, or allodynia. In addition, what appears to be opioid tolerance can be caused by opioid-induced hyperalgesia lowering the baseline pain level, thus masking the drug's analgesic effects. Identifying the development of hyperalgesia is of great clinical importance since patients receiving opioids to relieve pain may paradoxically experience more pain as a result of treatment. Whereas increasing the dose of opioid can be an effective way to overcome tolerance, doing so to compensate for opioid-induced hyperalgesia may worsen the patient's condition by increasing sensitivity to pain while escalating physical dependence.

[Outpatient opiate therapy in cancer patients during their last days of life].

Pain is one of the symptoms that many tumor patients are especially afraid of in the final phase of their illness. Symptoms can change rapidly, making quick adaptation of the therapy necessary. This poses particular challenges to organizational structures in outpatient treatment if the patients' desire to spend their last days of life in their accustomed surroundings is to be realized. Pain intensity and the associated symptoms in a WHO step III opiate therapy during the last 3 days of life were investigated retrospectively among 601 tumor patients who had received medical care from Home Care Berlin. Differences in gender, age, living conditions/care situation and place of death were evaluated with due consideration for the different pain medications administered and for the different forms and routes of administration. More than 80% of the patients reported freedom from pain or only moderate pain during the opiate therapy. Care provided by the hospice-at-home medical service Home Care Berlin allowed excellent control of tumor patients' symptoms with only moderate side-effects in their final days of life. Among patients receiving opioids by the transdermal route there were significantly more frequent complaints of pain (p=0.004) and nausea (p=0.001). During the last days of life continuous subcutaneous infusions containing opiates facilitated good analgesia within an acceptable spectrum of side-effects. Most problems with controlling symptoms in outpatients were encountered in younger patients. Morphine emerged as the drug of first choice in this investigation, because it can be given parenterally and also because of its price. The use of subcutaneous and intravenous administration systems such as PCA pumps requires trained nursing services and regular house visits by physicians experienced in palliative medicine.

Racotumomab

Treatment administration and side effects Racotumomab is administered in patients who have previously received the oncospecific treatment established in the oncological therapeutic standards (surgery, chemotherapy and radiation therapy). A Racotumomab-alum solution is administered by intradermal injection every 14 days for the first 2 months (5 doses), followed by monthly booster doses. Racotumomab is well tolerated by patients. The overall toxicity of the vaccine has been classified as grade 1 and 2, according to the NCI Common Toxicity Criteria (version 3.0). Treatment is mostly associated with mild to moderate injection-site reactions (local erythema, induration and pain), which disappear within 24–48 hours. Systemic reactions, such as flu-like symptoms and chills are less frequent, reversible, and self-limited. Approvals and indications

[Terminal care of the cancer patient at home--patient and family spending the last moments together].

Some 129 cancer patients were taken care of at home by the visiting nurse team of our hospital since 1994 to 1997; 116 patients have already died, 50 of them at home (group A), and 66 at the hospital (group B). We analyze the differences the between two groups in nutritional assistance, pain control and manpower in looking after a patient. Twice as many patients in group A took nutritional medication (drip infusion or intravenous hyperalimentation, for example) than group B. More patients in group A used oral and suppository morphine than group B. In group A 70% of patients (56% in group B) had more than two persons looking after at home. The important factors for a good recuperation at home are: 1. Available nutritional assist available. 2. Good control. 3. Less burden and anxiety of the person looked after. To spend pain desirable last moments together, it is important for the visiting nurse team to take proper care and to confirm the wishes of the patient and family, considering the rapidly changing conditions of the individual patient.

Ubrogepant

The effectiveness of ubrogepant for the acute treatment of migraine was demonstrated in two randomized, double-blind, placebo-controlled trials. In these studies, 1,439 adult patients with a history of migraine, with and without aura, received the approved doses of ubrogepant to treat an ongoing migraine. In both studies, the percentages of patients achieving pain freedom two hours after treatment (defined as a reduction in headache severity from moderate or severe pain to no pain) and whose most bothersome migraine symptom (nausea, light sensitivity or sound sensitivity) stopped two hours after treatment were significantly greater among patients receiving ubrogepant (19–21% depending on the dose) compared to those receiving placebo (12%). Patients were allowed to take their usual acute treatment of migraine at least two hours after taking ubrogepant. 23% of patients were taking a preventive medication for migraine.

Patterns of high-dose morphine use in a home-care hospice service: should we be afraid of it?

Management of cancer pain is one of the most important goals of palliative care. Relieving pain is often problematic. High doses of morphine at home may be required to relieve patients' pain, and is therefore feared. The goals of the current study were to assess the feasibility of high-dose morphine use at home, to characterize the patients, and to examine whether the use of high-dose morphine might affect their survival. The authors retrospectively studied the medical charts of 661 outpatients, which were completed by a home-care hospice team. The authors collected data regarding demographic parameters, medical diagnosis, pain type, morphine dosage, use of rescue doses in addition to regular doses, use of coanalgesics and adjuvant treatments, and survival time as associated with morphine dosage. The authors also compared the data of patients receiving high-dose morphine with those of a group of patients receiving regular doses. The authors identified 435 patients (65.8%) who received morphine for pain relief. Of these, 396 patients (91%) received a dose of 5-299 mg of morphine per day), 32 patients (7.4%) received 300-599 mg of morphine per day), and 7 patients (1.6%) received very high doses (> or = 600 mg of morphine per day). Overall, 39 patients (9%) received > 299 mg per day. Morphine dosage was found to be inversely correlated (r) with age (r = -0.254; P < 0.001). Male patients required slightly higher dosages than female patients (62.5% of high-dose and 71% of very high-morphine groups, respectively). Primary gastrointestinal (P = 0.015) and lung (P = 0.027) carcinomas, as well as metastatic bone disease (P = 0.001), ovarian carcinoma (P = 0.037), and brain tumors (P = 0.0053) were associated with higher and very higher morphine dosages. Adverse effects were similar in the groups receiving regular, high, and very high doses of morphine. The median survival of patients treated with high doses of morphine was 27 days and was 37 days for those treated with very high doses. Patients treated with low doses of morphine survived for 18 days. Patients not treated with morphine survived for 22 days (P = 0.001 by Mantel-Cox analysis; P = 0.029 by Breslow analysis). The use of high and very high morphine doses at home proved safe and did not appear to affect the patients' life expectancy adversely. The use of high or very high-dose morphine should not be a barrier to providing palliative terminal care for home-care hospice patients.

Opioid-induced hyperalgesia

The use of an NSAID, especially some COX-2 inhibitors, or acetaminophen either as monotherapy or combination therapy is also suggested as a possible treatment option. Research needs It can be difficult to apply research into OIH to average patients, because some research focused on people taking very high doses or in methadone rehabilitation programs. Opioid-induced hyperalgesia has also been criticized as overdiagnosed among chronic pain patients, due to poor differential practice in distinguishing it from the much more common phenomenon of opioid tolerance. The misdiagnosis of common opioid tolerance (OT) as opioid-induced hyperalgesia (OIH) can be problematic as the clinical actions suggested by each condition can be contrary to each other. Patients misdiagnosed with OIH may have their opioid dose mistakenly decreased (in the attempt to counter OIH) at times when it is actually appropriate for their dose to be increased or rotated (as a counter to opioid tolerance).

Opioid use and effectiveness of its prescription at discharge in an acute pain relief and palliative care unit.

The aim of this study was to present how opioids are used in an acute pain relief and palliative care unit (APRPCU), where many patients with difficult pain conditions are admitted from GPs, home palliative care programs, oncology departments, other hospitals or emergency units, and other regional places. From a consecutive sample of cancer patients admitted to an APRPCU for a period of 6 months, patients who had been administered opioids were included in this survey. Basic information was collected as well as opioid therapy prescribed at admission and, subsequently, during admission and at time of discharge. Patients were discharged once stabilization of pain and symptoms were obtained and the treatment was considered to be optimized. One week after being discharged, patients or relatives were contacted by phone to gather information about the availability of opioids at dosages prescribed at time of discharge. One hundred eighty six of 231 patients were specifically admitted for uncontrolled pain, with a mean pain intensity of 6.8 (SD 2.5). The mean dose of oral morphine equivalents in patients receiving opioids before admission was 45 mg/day (range 10-500 mg). One hundred seventy five patients (75.7 %) were prescribed around the clock opioids at admission. About one third of patients changed treatment (opioid or route). Forty two of 175 (24 %), 27/58 (46.5 %), 10/22 (45.4 %), and 2/4 (50 %) patients were receiving more than 200 mg of oral morphine equivalents, as maximum dose of the first, second, third, and fourth opioid prescriptions, respectively. The pattern of opioids changed, with the highest doses administered with subsequent line options. The mean final dose of opioids, expressed as oral morphine equivalents, for all patients was 318 mg/day (SD 798), that is more than six times the doses of pre-admission opioid doses. One hundred eighty six patients (80.5 %) were prescribed a breakthrough cancer pain (BTcP) medication at admission. Sixty five patients changed their BTcP prescription, and further 27 patients changed again. Finally, eight patients were prescribed a fourth BTcP medication. Of 46 patients available for interview, the majority of them (n = 39, 84 %) did not have problems with their GPs, who facilitated prescription and availability of opioids at the dosages prescribed at discharge. For patients with severe distress, APRPCUs may guarantee a high-level support to optimize pain and symptom intensities providing intensive approach and resolving highly distressing situations in a short time by optimizing the use of opioids.

Mistresses (American season 1)

Karen After her patient, Thomas Grey, reveals that he is dying of lung cancer and that he has been in love with her for a year, Karen begins having an affair with him. To help him end his life when the pain becomes too much, Karen prescribes Thomas fatal doses of morphine, which his wife, Elizabeth, helps to administrate. The insurance company begins to investigate Thomas' death, going so far as to approach Karen for the notes from her sessions with Thomas. However, Karen had destroyed anything relating to Thomas being her patient. While grieving his father's death, Thomas' son Sam turns to Karen for advice as he has discovered that his father was having an affair. Even though Savi advises Karen to cut all ties with the Grey Family, Karen begins helping Sam. Things take a dangerous turn after Sam falls in love with Karen and begins stalking her.

Agkistrodon contortrix phaeogaster

CroFab antivenin has been used successfully to treat Osage copperhead bites, although a lack of complete cross-tolerance requires careful administration and close supervision during the full course of treatment to ensure that the lowest effective dose is administered (a lower dose would not fully treat the envenomation, and a higher dose may be particularly dangerous to children, the elderly, and infirm adults). Not uncommonly, opiate/opioid narcotic analgesics (ex. morphine, fentanyl), muscle relaxerss (ex. diazepam, tizanidine, orphenadrine), and broad-spectrum antibiotics are administered. A few days' supply of weaker analgesics and muscle relaxers may be prescribed for the patient to control pain after he or she returns home as the pain resolves completely within one to three days. Patients also receive a prescription for an intensive antibiotic therapy, which much be taken until the supplies are depleted, giving the drug enough time to fully treat any opportunistic infections

[Opioid rotation in the home medical care service].

Pain relief is a quite important subject for maintaining the home medical care of patients with terminal cancer. Therefore, the opioid rotation should be made in conjunction with an individual medical condition, which is of growing importance in a proper pain management. We considered what opioid rotation is desirable in the home medical care service by analyzing the cases at our clinic. The most important thing in the opioid rotation at home is to perform a rotation before exacerbation of pain becomes apparent. For this purpose, morphine hydrochloride injection is thought to be the best dosage form because it has advantages of: (1) quickness in varying the amount, (2) immediate rescue efficacy, and (3) usefulness in case of ingestion.

Oxycodone

Oxycodone has a half-life of 4.5 hours. It is available as a generic medication. The manufacturer of OxyContin, a controlled-release preparation of oxycodone, Purdue Pharma, claimed in their 1992 patent application that the duration of action of OxyContin is 12 hours in "90% of patients." It has never performed any clinical studies in which OxyContin was given at more frequent intervals. In a separate filing, Purdue claims that controlled-release oxycodone "provides pain relief in said patient for at least 12 hours after administration." However, in 2016 an investigation by the Los Angeles Times found that "the drug weans off hours early in many people," inducing symptoms of opiate withdrawal and intense cravings for OxyContin. One doctor, Lawrence Robbins, told journalists that over 70% of his patients would report that OxyContin would only provide 4–7 hours of relief. Doctors in the 1990s often would switch their patients to a dosing schedule of once every eight hours when they

[Patient-controlled analgesia in outpatients with severe cancer pain.].

In this case report, we describe continuous subcutaneous infusion of opiates as PCAO (patient controlled analgesia in outpatients) in one patient with metastatic carcinoma of the rectum (liver and bone metastases, partial bowel obstruction) with severe cancer pain and vomiting in the terminal phase. The parenteral administration of opioids extended over 58 days. The infusion was powered by an external portable clockwork-driven syringe pump (Perfusor M, Braun Medical/Germany). The open-accessible pump has a syringe volume of 10 ml, and its maximal infusion time is 24 h. The 27-G infusion needle (Sub-Q-Set, Baxter/USA) was inserted in the side of the abdomen and was left in the same position for 10 to 20 days. It took the patient and his family only 1.5 h to familiarize themselves with the use of the pump. They were trained in its use in our outpatient pain department. For pain control both the variable continuous infusion and the extra injection doses could be administered by the way of the syringe driver. The patient was given a stock of 120 ampoules of morphine for further treatment at home. For optimal pain control he decided to raise the daily dose of opioid infusion from the initial 60 mg to 240 mg morphine within 48 h. In this way, PCAO-besides rapid titration of the opioid dose to achieve analgesia-allows the use of opioids controlled by the patient himself. In the present case this procedure was also important when an outpatient radiation therapy became urgently necessary to prevent a fracture of the spine because of metastasis. The pain control by the patient himself was the main factor to get free of pain during the transport to the hospital. Even positioning for radiation was possible without pain. When he received outpatient radiation therapy the patient needed extra injection doses of up to 360 mg morphine a day. The PCAO procedure by continuous subcutaneous infusion with opiates is a safe and efficient method of pain management for outpatient patients suffering from severe cancer pain and intractable nausea in the terminal phase. Its validity has also been proven especially for radiation treatment of bone metastases.

Neutron capture therapy of cancer

was well tolerated by the 30 patients who were enrolled in this study. All were treated with 2 fields, and the average whole brain dose was 3.2–6.1 Gy (weighted), and the minimum dose to the tumor ranged from 15.4 to 54.3 Gy (w). There has been some disagreement among the Swedish investigators regarding the evaluation of the results. Based on incomplete survival data, the MeST was reported as 14.2 months and the time to tumor progression was 5.8 months. However, more careful examination of the complete survival data revealed that the MeST was 17.7 months compared to 15.5 months that has been reported for patients who received standard therapy of surgery, followed by radiotherapy (RT) and the drug temozolomide (TMZ). Furthermore, the frequency of adverse events was lower after BNCT (14%) than after radiation therapy (RT) alone (21%) and both of these were lower than those seen following RT in combination with TMZ. If this improved survival data, obtained using the higher dose of BPA

Intravenous titration with morphine for severe cancer pain: report of 28 cases.

In a multicenter study, 28 patients with cancer pain and insufficient pain relief with analgesic treatment according to step II of the guidelines of the World Health Organization (WHO) were switched to oral slow-release morphine. Patients received intravenous morphine through a patient-controlled pump (PCA) for the first 24 hours (bolus = 1 mg, lockout interval = 5 minutes, maximum dose = 12 mg/hour). From day 2 patients were treated with oral slow-release morphine. Daily doses were calculated from the requirements of the day before. Breakthrough pain was treated with PCA until stable doses were reached (<2 boluses/day) and then with oral immediate-release morphine solution. Pain intensity was reported in a diary four times a day, in addition to mood, activity, and quality of sleep once daily. Mean duration until adequate pain relief reported (<30 on a 101-step numerical scale; NRS) was 5 hours (range = 80-620 minutes). Mean pain intensity was reduced from 67 NRS to 22 NRS. Mean doses of oral morphine were 133 mg/day initially and then 154 mg/day on day 14. Serious adverse events such as respiratory depression were not observed. Two patients terminated the study due to progressive symptoms of gastrointestinal obstruction. Seventy-five percent of the patients evaluated the effectiveness of the analgesic regime as good. Dose finding with intravenous PCA may be appropriate for a small minority of patients with severe pain. Higher treatment costs and the risk of complications are drawbacks of this method compared with conventional oral titration.

Bland embolization

After embolization, patients are observed in the post-anesthesia care unit for several hours. Patients are discharged from the hospital when taking adequate nutrition by mouth, when pain is adequately controlled with oral narcotics and when the temperature is lower than 38.5 for 24 hours. Post-procedure evaluation Follow-up triple phase CT is performed 2 to 4 weeks after treatment is complete and reviewed for any evidence of persistent untreated disease. If there is no evidence of enhancement of the treated tumor, these patients are monitored with triple phase CT every 3 months for the first year and every 6 months thereafter. When there is evidence of untreated disease, recurrent disease, or new disease elsewhere within the liver the patient is scheduled for additional embolization. References Hepatology Diseases of liver

Analgesic use in home hospice cancer patients.

Pain control in hospice patients in the home may be compromised by concerns about overuse of analgesics, particularly narcotics. A retrospective chart audit of analgesic type and amount was performed on the medical records of 100 cancer patients receiving hospice care in the home. Different types and amounts of analgesics were converted to a common standard, an oral morphine equivalent (OME) relative to 1 mg of oral morphine sulfate. Descriptive statistics were used to characterize patient analgesic use during the entire course of hospice care and the last 5 days of life. Associations between analgesic use and select patient characteristics (age, sex, cancer site, metastases, and pain intensity at admission) were explored. Ninety-one percent of the sample had used analgesics at some time during hospice care. The proportion of patients using analgesics increased as death approached. The mean and median daily analgesic use over the entire period were 114 and 82 OMEs and during the last 5 days 140 and 84 OMEs, respectively. The range of mean daily analgesic use was between 10 and 735 OMEs. Individual variability in analgesic use was demonstrated. Not all patients required analgesics, and among those who did there was remarkable variation in the amount used. Large and even enormous doses of analgesics may sometimes be required to control cancer pain.

Breathlessness with pulmonary metastases: a multimodal approach.

Case Study  Sarah is a 58-year-old breast cancer survivor, social worker, and health-care administrator at a long-term care facility. She lives with her husband and enjoys gardening and reading. She has two grown children and three grandchildren who live approximately 180 miles away. SECOND CANCER DIAGNOSIS  One morning while showering, Sarah detected a painless quarter-sized lump on her inner thigh. While she thought it was unusual, she felt it would probably go away. One month later, she felt the lump again; she thought that it had grown, so she scheduled a visit with her primary care physician. A CT scan revealed a 6.2-cm soft-tissue mass in the left groin. She was referred to an oncologic surgeon and underwent an excision of the groin mass. Pathology revealed a grade 3 malignant melanoma. She was later tested and found to have BRAF-negative status. Following her recovery from surgery, Sarah was further evaluated with an MRI scan of the brain, which was negative, and a PET scan, which revealed two nodules in the left lung. As Sarah had attended a cancer support group during her breast cancer treatment in the past, she decided to go back to the group when she learned of her melanoma diagnosis. While the treatment options for her lung lesions included interleukin-2, ipilimumab (Yervoy), temozolomide, dacarbazine, a clinical trial, or radiosurgery, Sarah's oncologist felt that ipilimumab or radiosurgery would be the best course of action. She shared with her support group that she was ambivalent about this decision, as she had experienced profound fatigue and nausea with chemotherapy during her past treatment for breast cancer. She eventually opted to undergo stereotactic radiosurgery. DISEASE RECURRENCE  After the radiosurgery, Sarah was followed every 2 months. She complained of shortness of breath about 2 weeks prior to each follow-up visit. Each time her chest x-ray was normal, and she eventually believed that her breathlessness was anxiety-related. Unfortunately, Sarah's 1-year follow-up exam revealed a 2 cm × 3 cm mass in her left lung, for which she had a surgical wedge resection. Her complaints of shortness of breath increased following the surgery and occurred most often with anxiety, heat, and gardening activities, especially when she needed to bend over. Sarah also complained of a burning "pins and needles" sensation at the surgical chest wall site that was bothersome and would wake her up at night. Sarah met with the nurse practitioner in the symptom management clinic to discuss her concerns. Upon physical examination, observable signs of breathlessness were lacking, and oxygen saturation remained stable at 94%, but Sarah rated her breathlessness as 7 on the 0 to 10 Borg scale. The nurse practitioner prescribed duloxetine to help manage the surgical site neuropathic pain and to assist with anxiety, which in turn could possibly improve Sarah's breathlessness. Several nonpharmacologic modalities for breathlessness were also recommended: using a fan directed toward her face, working in the garden in the early morning when the weather is cooler, gardening in containers that are at eye level to avoid the need to bend down, and performing relaxation exercises with pursed lip breathing to relieve anxiety-provoked breathlessness. One month later, Sarah reported relief of her anxiety; she stated that the fan directed toward her face helped most when she started to feel "air hungry." She rated her breathlessness at 4/10 on the Borg scale. SECOND RECURRENCE: MULTIPLE PULMONARY NODULES  Sarah's chest x-rays remained clear for 6 months, but she developed a chronic cough shortly before the 9-month exam. An x-ray revealed several bilateral lung lesions and growth in the area of the previously resected lung nodule. Systemic therapy was recommended, and she underwent two cycles of ipilimumab. Sarah's cough and breathlessness worsened, she developed colitis, and she decided to stop therapy after the third cycle. In addition, her coughing spells triggered bronchospasms that resulted in severe anxiety, panic attacks, and air hunger. She rated her breathlessness at 10/10 on the Borg scale during these episodes. She found communication difficult due to the cough and began to isolate herself. She continued to attend the support group weekly but had difficulty participating in conversation due to her cough. Sarah was seen in the symptom management clinic every 2 weeks or more often as needed. No acute distress was present at the beginning of each visit, but when Sarah began to talk about her symptoms and fear of dying, her shortness of breath and anxiety increased. The symptom management nurse practitioner treated the suspected underlying cause of the breathlessness and prescribed oral lorazepam (0.5 to 1 mg every 6 hours) for anxiety and codeine cough syrup for the cough. Opioids were initiated for chest wall pain and to control the breathlessness. Controlled-release oxycodone was started at 10 mg every 12 hours with a breakthrough pain (BTP) dose of 5 mg every 2 hours as needed for breathlessness or pain. Sarah noted improvement in her symptoms and reported a Borg scale rating of 5/10. Oxygen therapy was attempted, but subjective improvement in Sarah's breathlessness was lacking. END OF LIFE  Sarah's disease progressed to the liver, and she began experiencing more notable signs of breathlessness: nasal flaring, tachycardia, and restlessness. Opioid doses were titrated over the course of 3 months to oxycodone (40 mg every 12 hours) with a BTP dose of 10 to 15 mg every 2 hours as needed, but her breathlessness caused significant distress, which she rated 8/10. The oxycodone was rotated to IV morphine continuous infusion with patient-controlled analgesia (PCA) that was delivered through her implantable port. This combination allowed Sarah to depress the PCA as needed and achieve immediate control of her dyspneic episodes. Oral lorazepam was also continued as needed. Sarah's daughter moved home to take care of her mother, and hospice became involved for end-of-life care. As Sarah became less responsive, nurses maintained doses of morphine for control of pain and breathlessness and used a respiratory distress observation scale to assess for breathlessness since Sarah could no longer self-report. A bolus PCA dose of morphine was administered by Sarah's daughter if her mother appeared to be in distress. Sarah died peacefully in her home without signs of distress.

[Emergency pain treatment--ambulatory intravenous morphine titration in a patient with cancer pain].

Even when the guidelines for cancer pain management are followed, acute severe pain requiring immediate treatment will occur in some patients. Titration with intravenous morphine may provide fast and efficient pain relief and give an indication of the amount of opioid necessary for continuous treatment. In cooperation with a general practitioner we performed an intravenous morphine titration in a patient with severe cancer pain at home. Adequate analgesia was reached with 20 mg intravenous morphine. Blood pressure, cardiac frequency and oxygen saturation did not change. No side effects were reported during the titration, and the previous regimen with tramadol 150 mg per day was switched to slow release morphine 300 mg per day. This medication was prescribed by the general practitioner and provided good pain relief until the patient died two weeks later. We conclude that intravenous morphine titration may be performed even in cancer patients at home, adequate monitoring, however, should be available.

Opioid

The initial 24 hours after opioid administration appear to be the most critical with regard to life-threatening OIRD, but may be preventable with a more cautious approach to opioid use. Patients with cardiac, respiratory disease and/or obstructive sleep apnoea are at increased risk for OIRD. Increased pain sensitivity Opioid-induced hyperalgesia – where individuals using opioids to relieve pain paradoxically experience more pain as a result of that medication – has been observed in some people. This phenomenon, although uncommon, is seen in some people receiving palliative care, most often when dose is increased rapidly. If encountered, rotation between several different opioid pain medications may decrease the development of increased pain. Opioid induced hyperalgesia more commonly occurs with chronic use or brief high doses but some research suggests that it may also occur with very low doses.

Intravenous morphine consumption in outpatients with cancer during their last week of life--an analysis based on patient-controlled analgesia data.

Studies on opioid use in terminally ill cancer patients have shown a prefinal dose increase in the majority of patients. Mostly oral opioids were used. Due to the pharmacokinetic properties of opioids, it is rather difficult to get a reliable estimate of the true opioid need from those results. Retrospectively, we analyzed opioid use during the last week of life of 30 consecutive outpatients with cancer on intravenous (i.v.) morphine patient-controlled analgesia (PCA). A dose increase (decrease) was defined as an increase (decrease) of the patient's individual daily dose by at least 30% with respect to their prior daily dose. We also analyzed circadian variations in morphine use. Thirty patients fulfilled the primary study inclusion criteria. Fulfilling the exclusion criteria, seven patients had to be excluded from analysis (n = 3, on PCA for less than 7 days; n = 4, PCA was finished before death). Twenty-three patients with a total of 161 treatment days were analyzed. The patients' median age was 57 years (range, 4 to 72). The median duration of intravenous morphine PCA was 19 days (range, 8 to 58). The median daily intravenous morphine dose during the last week of life was 96 to 115 mg, without significant change over time/from day to day (Friedman test). On 144/161 days (89.2%), morphine dose remained stable. On 9 treatment days (5.6%), the dose increased, and on 8 days (5.0%), it decreased. In three patients, only dose increases, and in four patients, only dose decreases were observed. In four patients, both dose increases and decreases were observed. Twelve patients showed no change in daily morphine dose. Opioid use lacked a diurnal pattern. During their end-of-life phase, cancer patients on i.v. morphine PCA showed a stable daily opioid need.

Buprenorphine

Both buprenorphine and methadone are medications used for detoxification and opioid replacement therapy, and appear to have similar effectiveness based on limited data. Both are safe for pregnant women with opioid use disorder, although preliminary evidence suggests that methadone is more likely to cause neonatal abstinence syndrome. In the US and European Union, only designated clinics can prescribe methadone for opioid use disorder, requiring patients to travel to the clinic daily. If patients are drug free for a period they may be permitted to receive "take home doses," reducing their visits to as lilttle as once a week. Alternatively, up to a month's supply of buprenorphine has been able to be prescribed by clinicians in the US or Europe who have completed a basic training (8–24 hours in the US and received a waiver/licence allowing prescription of the medicine. In France, buprenorphine prescription for opioid use disorder has been permitted without any special training or

[How to palliate the symptoms of terminally ill patients at home].

We reported the kind of symptoms and how they could be palliated in terminally ill patients at home based on our experience of about 9 years. Cancer pain, which was the most frequent symptom, appeared in 67 among 126 patients receiving home care, and it could be effectively controlled with morphine; no patient returned to the hospital because of aggravation of pain. Very few patients stayed in the hospital and never returned home due to uncontrollable pain. Home parenteral infusion was done for 63 patients who were unable to eat or drink because of peritonitis carcinomatosa or cancer cachexia. High fever in the tumor mass was controlled by glucocorticoid hormone, and ascites was drained continuously when the patients suffered from abdominal distension. From analysis of the cases in which home care was interrupted or those in which patients were unable to transfer to home care, symptoms that were difficult to palliate at home were nausea caused by bowel obstruction, acute symptoms (bleeding, disturbance of consciousness, and so on), and dyspnea. But if the patients and family are eager for home care and an adequate medical support system is in place, home care may be possible despite these symptoms.

Oxytrex

A phase III clinical trial has shown that the combination of ULD (ultra-low dose) naltrexone with oxycodone has been nearly as effective in providing pain relief while causing less physical dependence than oxycodone alone. The trial has been criticized for its confounding and limiting factors which include the huge dropout rate (54%), lack of demographic stratification of pain intensity amongst the study arms, and that patients received varying amounts of oxycodone which would influence their overall dependence. The lack of an on-board break-through-pain agent also hurts their external validity and likely contributed to their high dropout rate. References Webster et al., "Oxytrex Minimizes Physical Dependence While Providing Effective Analgesia: A Randomized Controlled Trial in Low Back Pain", The Journal of Pain, Vol 7, No 12, 2006:937-946 Expert Opin. Investig. Drugs (2007) 16(8):1277-1283 Mu-opioid receptor agonists Semisynthetic opioids Combination drugs Experimental drugs

[Cancer-pain management in home care].

Patient was 58 year old female with severe uterus cancer pain who refused to take the oral morphine in hospital because doctor should be hesitated to discharged patient whose pain is particularly difficult to manage in home. A few days later, she returned back home with her family irritably and recovered from hallucination by morphine-intake in home. The oral morphine is the prepared route of analgesic administration in home care. When patient can not take medications orally, continuous intravenous infusion provides the most consistent level of analgesia. In future, transdermal route offers a practical alternative in the hospice and home.

Pharmacokinetics and clinical efficacy of oral morphine solution and controlled-release morphine tablets in cancer patients.

Twenty-three adult patients with chronic pain due to cancer completed a double-blind, randomized, two-phase crossover trial comparing plasma morphine concentrations and analgesic efficacy of oral morphine sulfate solution (MSS) and controlled-release morphine sulfate tablets (MS Contin [MSC], Purdue Frederick, Inc., Toronto, Ontario, Canada). MS Contin was given every 12 hours to all patients except those whose daily morphine dose could not be equally divided into two 12-hour doses with the tablet strengths available. MSS was given every 4 hours. Patients received both of the test drugs for at least 5 days, and, on the final day of each phase, peripheral venous blood samples for morphine analysis were obtained. Eighteen patients received MSC every 12 hours, and five received it every 8 hours. The same total daily morphine dose was given in both phases. In the 18 patients who received MSC every 12 hours, the daily morphine dose was 183.9 +/- 140.0 mg (mean +/- SD). In this group, the mean area under the curve (AUC) with MSC was 443.6 +/- 348.4 ng/ml/hour, compared with 406.8 +/- 259.7 ng/ml/hour for MSS (P greater than 0.20). Mean maximum morphine concentrations (Cmax) for MSC and MSS were 67.9 +/- 42.1 and 58.8 +/- 30.3 ng/ml, respectively (P greater than 0.05). Mean minimum morphine concentrations (Cmin) were 17.0 +/- 17.7 and 18.3 +/- 15.0, respectively (P greater than 0.30). There was a significant difference (P less than 0.001) between the two drugs in time required to reach maximum morphine concentration (Tmax). Mean Tmax after MSC occurred at 3.6 +/- 2.3 hours. After MSS, it occurred at 1.3 +/- 0.4 hours. In the five patients who received MSC every 8 hours, the findings paralleled those in the principal group, with no significant differences between MSC and MSS in Cmax or Cmin and a highly significant difference between the two in Tmax. However, in this small group of patients, the AUC with MSC was significantly (P = 0.04) greater than that with MSS. All patients had very good pain control throughout the study and both formulations were well tolerated. There were no significant differences between MSC and MSS in pain scores or side effects. Under the conditions of this study there was no clinically significant difference in bioavailability between MSC and oral MSS. When given on a 12-hourly basis in individually titrated doses, the MSC provided therapeutic plasma morphine concentrations throughout the dosing interval.

[What can we do for cancer patients with pain to go home].

When patients suffering from cancer pain wish to stay at home, the most important condition is to relieve the cancer pain. But it is not enough; decreasing the fear of pain is another important problem. From these viewpoints, we have tried to assist these patients to go home. In this paper we report two cases of 61-year-old and 57-year-old women with severe leg pain caused by pelvic recurrence of cancer of the uterus and rectum. At first, we needed high doses of morphine by intravenous administration all day long. To control their mental condition, we talked personally with them to understand their distress and asked them to put in writing anything about their anxiety in a special notebook. After that, we advised them on how to use anodyne, how to deal with side effects of the drugs and how to use various social services in their home. Then, after their cancer pain was controlled by radiotherapy and appropriate anodyne, they overcame their anxiety and at last they could go home.

Patient-reported utilization patterns of fentanyl transdermal system and oxycodone hydrochloride controlled-release among patients with chronic nonmalignant pain.

Although use of long-acting opioid analgesics has increased for chronic nonmalignant pain management, little is known about patient-reported utilization patterns. To assess patient-reported utilization patterns of fentanyl transdermal system and oxycodone hydrochloride (HCl) controlled-release among patients with chronic nonmalignant pain and to compare these patterns to standard dose administration guidelines recommended in the manufacturers. prescribing information (PI). Cross-sectional, observational, multicenter study of English-speaking patients who were seeking chronic nonmalignant pain management from 6 outpatient pain clinics. The inclusion criteria for the study were (1) diagnosis of chronic nonmalignant pain, (2) prescription for and current use of either transdermal fentanyl or oxycodone HCl controlled-release, and (3) duration of use for either transdermal fentanyl or oxycodone HCl controlled-release of at least 6 weeks. Patients completed either an oxycodone HCl controlled-release or transdermal fentanyl utilization questionnaire. A conversion table was used to standardize opioid analgesic doses from transdermal fentanyl or oxycodone HCl controlled-release to daily oral morphine equivalents. The principal outcome measures were the average interval between oxycodone HCl controlled-release administrations, the number of days the current transdermal fentanyl patch would be worn, and the percentage of oxycodone HCl controlled-release and transdermal fentanyl patients whose administration frequency exceeded the standard recommendation in the manufacturer.s PI (every 12 hours for oxycodone HCl controlled-release or every 72 hours for transdermal fentanyl). Other outcome measures included the number of oxycodone HCl controlled-release tablets per administration, the daily dose of long-acting opioid, the duration of adequate pain relief, and the difference in daily oral morphine equivalents between transdermal fentanyl and oxycodone HCl controlled-release patients, after adjusting in a multivariate regression model for demographic and clinical characteristics. A total of 690 patients were enrolled in this study; 437 (63.4%) received oxycodone HCl controlled-release and 253 (36.6%) received transdermal fentanyl. Oxycodone HCl controlled-release patients reported taking a median of 1 tablet 3 times per day or a median of 3 tablets per day. A mean of 1.6 tablets per administration and 4.6 tablets per day were taken. The average interval between administrations of oxycodone HCl controlled-release was 7.8 hours, and the median daily dose was 80.0 mg (mean 155.6 mg). Among oxycodone HCl controlled-release patients, 17.5% had an average interval between administrations of 12 or more hours, whereas 1.9% reported the duration of pain relief as 12 or more hours. Transdermal fentanyl patients reported wearing the patch, on average, for 2.5 days (median 2.5),and 41.2% reported wearing the patch for at least 3 days, whereas 14.1% reported the duration of pain relief as at least 3 days. The median daily dosage strength of transdermal fentanyl was 75.0 mcg/hour. In the multivariate regression analysis, oxycodone HCl controlled-release patients had, on average, roughly 22 mg additional oral morphine equivalents per day relative to transdermal fentanyl patients (not statistically significant); the probability that oxycodone HCl controlled-release patients had higher oral morphine equivalents was 82.6%, which suggests a trend toward higher oral morphine equivalents per day in the oxycodone HCl controlled-release group. Transdermal fentanyl and oxycodone HCl controlled-release both appear to be used by patients in a manner that is inconsistent with the standard recommendation in the manufacturers' PI;however, the difference between patient-reported utilization and the PI recommendation is more pronounced with oxycodone HCl controlled-release.

[Continuous spinal analgesia in home care of oncologic pain].

The authors in this study, after a short survey of the most important therapeutic techniques for cancer pain, report their results in the treatment of 18 patients suffering from incurable disease. It was impossible to dismiss them from hospital care on account of a painful symptomatology not controllable by oral morphine or owing to excessive collateral morphinic consequences. The analgetic technique employed was continuous intrathecal infusion of morphine, clonidine, droperidol and, in 10 cases, bupivacaine. Drug delivery systems, totally internalized, except infusion pump, were always utilized. Adequate pain relief was obtained, within - 5 days, in all the patients. Family membres, in the same period, learnt the infusion circuit action. At this point the patients were dismissed and treated with home care. The average time of assistance was 140 days, and very moderate variations in posology were necessary. Hospital reentrance, really little numerous, happened only when no member of palliative care service was present. Reasons were no bodily pain, but the total suffering of cancer disease. No complication nor collateral consequences were never found.

Opioid rotation

Opioid rotation or opioid switching is the process of changing one opioid to another to improve pain control or reduce unwanted side effects. This technique was introduced in the 1990s to help manage severe chronic pain and improve the opioid response in cancer patients. In order to obtain adequate levels of pain relief, patients requiring chronic opioid therapy may require an increase in the original prescribed dose for a number of reasons, including increased pain or a worsening disease state. Over the course of long term treatment, an increase in dosage cannot be continued indefinitely as unwanted side effects of treatment often become intolerable once a certain dose is reached, even though the pain may still not be properly managed. One strategy used to address this is to switch the patient between different opioid drugs over time, usually every few months. Opioid rotation requires strict monitoring in patients with ongoing levels of high opioid doses for extended periods of time,


In the presence of isolated thrombocytopenia we must not lose sight of the physical examination; thus, the presence of lymphadenopathy forces us to rule out the presence of lymphoma, for example. 1 is correct. When performing a bone marrow biopsy-aspirate it is seen that the number of megakaryocytes is normal or even increased, the failure is not in the marrow but in the peripheral blood, where platelets are destroyed. So. The false answer is 2.

In the presence of isolated thrombocytopenia we must not lose sight of the physical examination; thus, the presence of lymphadenopathy forces us to rule out the presence of lymphoma, for example. [HIDDEN] When performing a bone marrow biopsy-aspirate it is seen that the number of megakaryocytes is normal or even increased, the failure is not in the marrow but in the peripheral blood, where platelets are destroyed. So. [HIDDEN]

A 33-year-old woman consults for repeated epistaxis, petechiae and ecchymosis. Laboratory tests show thrombocytopenia with a platelet count of 4000 platelets/microliter. The initial presumptive diagnosis is chronic immune thrombocytopenic purpura (ITP). Which of the following statements is FALSE regarding the diagnosis of ITP?

The presence of lymphadenopathy or splenomegaly in the physical examination suggests a different diagnosis of ITP.

Bone marrow analysis shows a decreased number of megakaryocytes without other alterations.

Complete blood count shows isolated thrombocytopenia with often large platelets, without anemia unless there is significant bleeding or associated autoimmune hemolysis (Evans syndrome).

The diagnosis of ITP is established by exclusion of other processes causing thrombocytopenia.

The determination of antiplatelet antibodies is not accurate to establish the diagnosis.

Immune thrombocytopenic purpura

Despite the destruction of platelets by splenic macrophages, the spleen is normally not enlarged. In fact, an enlarged spleen should lead to a search for other possible causes for the thrombocytopenia. Bleeding time is usually prolonged in ITP patients. However, the use of bleeding time in diagnosis is discouraged by the American Society of Hematology practice guidelines and a normal bleeding time does not exclude a platelet disorder. Bone marrow examination may be performed on patients over the age of 60 and those who do not respond to treatment, or when the diagnosis is in doubt. On examination of the marrow, an increase in the production of megakaryocytes may be observed and may help in establishing a diagnosis of ITP. An analysis for anti-platelet antibodies is a matter of clinician's preference, as there is disagreement on whether the 80 percent specificity of this test is sufficient to be clinically useful.

Immune thrombocytopenic purpura

ITP is an autoimmune disease with antibodies detectable against several platelet surface structures. ITP is diagnosed by identifying a low platelet count on a complete blood count (a common blood test). However, since the diagnosis depends on the exclusion of other causes of a low platelet count, additional investigations (such as a bone marrow biopsy) may be necessary in some cases. In mild cases, only careful observation may be required but very low counts or significant bleeding may prompt treatment with corticosteroids, intravenous immunoglobulin, anti-D immunoglobulin, or immunosuppressive medications. Refractory ITP (not responsive to conventional treatment or constant relapsing after splenectomy) requires treatment to reduce the risk of clinically significant bleeding. Platelet transfusions may be used in severe cases with very low platelet counts in people who are bleeding. Sometimes the body may compensate by making abnormally large platelets.

[Idiopathic thrombocytopenic purpura in children].

Idiopathic (immune) thrombocytopenic purpura (ITP) is the most frequent hemorrhagic disease in children. It represents the acquired megakaryocytic thrombocytopenia with the shortened life of platelets because of immunologic damage (antibodies absorbed by platelets). In the case of this acquired hemorrhagic disorder, in spite of compensatory increased function of the bone marrow, there is a reduced number of platelets because of their increased destruction by the reticuloendothelial system (destructive thrombocytopenia). There are three forms of ITP: acute, chronic and intermittent. The acute form occurs in 80-90% of cases with bleeding episodes lasting a few days or weeks, but no longer than 6 months. The chronic form occurs in 10-15% of children, while the rarest-intermittent form is characterized by periods of normalization in regard to the number of platelets but also with relapse in intervals of 1-3 months. The disease is caused by an immunological disorder in the sense of an imbalanced immune response. Immunologic damages of platelets cause shortening of the opsonized platelets life span. The most frequent platelet opsonins are the immumoglobulin G (IgG) antibodies directed at the platelet membrane in the form of autoantibodies, alloantibodies or possibly absorbed antigen caused by microorganism infection or drug intake. It is typical for the phenomenon of bleeding that it starts suddenly and without any other sign of illness. The most frequent acute form appears between the second and fourth year, and is characterized by seasonal occurrence usually after acute viral infections. Children older than 10 years of age, like adults, often have the chronic form associated with other immunologic disorders. The disease affects girls more often than boys (about three times more often) with moderate and constant increase of antiplatelet antibodies. Hemorrhagic manifestations include: petechiae, purpura, epistaxis, gastrointestinal and genitourinary bleeding. They depend on the grade of thrombocytopenia, although there is no strict correlation between the number of platelets and volume of bleeding. Low mortality of the acute ITP is almost exclusively due to intracranial hemorrhage. LABORATORY STUDIES: Thrombocytopenia represents a decrease in the number of blood platelets being a basic abnormality of the blood count. The half-life of platelets in ITP is shortened. Detection of antiplatelet antibodies is connected with technical difficulties, so they are established in about 30% of cases. Bleeding time is prolonged and so is the coagulum retraction which may be completely missed. The Rumpel-Leede test is positive. Clinical differentiation of drug-induced thrombocytopenia is not possible. However, other differential diagnostic possibilities are thrombotic-thrombocytopenic purpura and hemolytic-uremic syndrome. A child with aplastic anemia or acute leukemia, beside thrombocytopenia, has a characteristic finding of white and red blood cell count. Thrombocytopenia with absent radii syndrome is associated with skeletal system abnormalities. New knowledge about the role of the immune system in ITP determines the modern therapeutic modalities. In cases of acute ITP in children, there are two therapeutic options or therapies of choice: corticosteroids and high doses of intravenous immunoglobulin. Immunosupressive therapy means anti Rh(D) immunoglobulin, cyclosporine, cytostatics, danazol, loaded platelets. In cases of distinctive hemorrhagic syndrome there are also indications for platelet transfusion. Nowadays splenectomy is more restricted, because one third of cases is unsuccessful, whereas plasmapheresis is rarely used in children because of possible complications. ITP is the most frequent hemorrhagic disease in children. The disease is basically caused by an immunologic disorder with platelet destruction due to increased immunoglobulin on their membrane. (ABSTRACT TRUNCATED)

Initial laboratory findings useful for predicting the diagnosis of idiopathic thrombocytopenic purpura.

To identify initial laboratory findings useful for the later diagnosis of idiopathic thrombocytopenic purpura (ITP) in adult patients with thrombocytopenia. We studied 62 consecutive adult patients who had thrombocytopenia and whose peripheral blood film was normal except for thrombocytopenia at presentation. Each patient underwent physical examination and routine laboratory tests and was prospectively followed for 22.5 +/- 9.8 months (range, 8 to 41 months). The frequency of antiglycoprotein (GP) IIb/IIIa antibody-producing B cells, the presence of platelet-associated and plasma anti-GPIIb/IIIa antibodies, the percentage of reticulated platelets, and the plasma thrombopoietin level were examined at the first visit. The final diagnosis was based on the clinical history, physical examination, complete blood test, bone marrow findings, and the clinical course at last observation. Forty-six patients were diagnosed as having ITP and 16 as having another disorder, including myelodysplastic syndrome, aplastic anemia, amegakaryocytic thrombocytopenia, and reduced platelet production, with or without other cytopenias, and without dysplasia or evidence for destruction. Six initial laboratory findings discriminated ITP from other diagnoses: the absence of anemia, absence of leukocytopenia, increased frequency of anti-GPIIb/IIIa antibody-producing B cells, increased platelet-associated anti-GPIIb/IIIa antibodies, elevated percentage of reticulated platelets, and a normal or slightly increased plasma thrombopoietin level. Three or more of these ITP-associated findings were found at presentation in 44 patients (96%) with thrombocytopenia later diagnosed as ITP, compared with only 1 patient (6%) whose disorder was non-ITP. Initial laboratory findings can well predict future diagnosis of ITP. Further studies prospectively evaluating these same diagnostic criteria on another, independent set of patients are necessary.

The role of the bone marrow examination in the diagnosis of immune thrombocytopenic purpura: case series and literature review.

The need for a bone marrow examination was assessed in patients with clinical and laboratory features consistent with ITP; the literature was reviewed. The records of all patients undergoing a bone marrow examination between January 1988 to January 1998 were retrospectively reviewed to determine which were motivated by the suspicion of ITP. Data were collected from hospital and outpatient medical and pathology records. Eighty-six patients with isolated thrombocytopenia (i.e., normal white blood cell count, hemoglobin, peripheral smear and clotting studies) were studied. The bone marrow was consistent with ITP in 82 patients, (i.e., normal or increased megakaryocytes and other hemopoietic lineages normal.) Four patients had decreased megakaryocytes, but all patients responded to corticosteroids. All 86 patients were followed up for a median of 22 months after bone marrow aspiration (range, 2-76 months.) During that time, none of the patients developed features to suggest an alternative diagnosis to ITP. The initial clinical and laboratory findings of 99 patients with acute leukemia were also reviewed; all had features atypical of ITP. These data suggest that routine performance of a bone marrow examination for the diagnosis of ITP is not necessary, provided that a thorough history and physical examination are performed and that the complete blood cell count, peripheral blood smear, and routine clotting studies show no abnormalities apart from thrombocytopenia. The findings of seven prior retrospective studies, two in adults and five in children are consistent with the previous findings. However, the value of marrow investigation in ITP remains unresolved and data from a large prospective study would be helpful.

Thrombocytopenia

Immune thrombocytopenic purpura Many cases of immune thrombocytopenic purpura (ITP) also known as idiopathic thrombocytopenic purpura, can be left untreated, and spontaneous remission (especially in children) is not uncommon. However, counts under 50,000 are usually monitored with regular blood tests, and those with counts under 10,000 are usually treated, as the risk of serious spontaneous bleeding is high with such low platelet counts. Any patient experiencing severe bleeding symptoms is also usually treated. The threshold for treating ITP has decreased since the 1990s; hematologists recognize that patients rarely spontaneously bleed with platelet counts greater than 10,000, although exceptions to this observation have been documented.

Assessment and Management of Immune Thrombocytopenia (ITP) in the Emergency Department: Current Perspectives.

Immune thrombocytopenia (ITP) is characterized by a platelet count less than 100 × 10^9/L without anemia or leukopenia. Patients with ITP may be asymptomatic, or they may have mild bleeding like petechiae, purpura, or epistaxis. In rare cases, they may present to the emergency department (ED) with life-threatening bleeding as a result of their thrombocytopenia. The emergency physician should thus be prepared to diagnose ITP and treat the bleeding that can result from it. The diagnosis of ITP requires excluding secondary causes of thrombocytopenia, and in the ED, the bare minimum workup for ITP includes a complete blood count and a peripheral blood smear. The peripheral blood smear should show a small number of large platelets with normal morphology, and there should not be an increased number of schistocytes. Many patients with ITP require no emergent treatment. However, if a patient with suspected ITP presents to the ED with critical hemorrhage, the emergency physician should initiate treatment with a platelet transfusion, corticosteroids, and intravenous immune globulin (IVIG) as soon as possible. For less severe bleeding, platelet transfusions are not recommended, and the treatment consists of corticosteroids by themselves or in conjunction with IVIG.

[The diagnosis of ITP].

Idiopathic thrombocytopenic purpura(ITP) is a hematologic disorder which causes thrombocytopenia. The diagnosis of ITP is based on the history, physical examination and, complete blood count, and examination of the peripheral smear. The diagnostic criteria of ITP established by the Ministry of Health, Welfare, and Labor in Japan requires the bone marrow examination and the measurement of platelet associated IgG, but those tests are not always necessary according to the guidelines developed by the American Society of Hematology. The appropriate strategies for the diagnosis of ITP need to be established. In this paper, some new examinations which may help the diagnosis of ITP are also demonstrated.

Immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is a type of thrombocytopenic purpura defined as an isolated low platelet count with a normal bone marrow in the absence of other causes of low platelets. It causes a characteristic red or purple bruise-like rash and an increased tendency to bleed. Two distinct clinical syndromes manifest as an acute condition in children and a chronic condition in adults. The acute form often follows an infection and spontaneously resolves within two months. Chronic immune thrombocytopenia persists longer than six months with a specific cause being unknown. ITP is an autoimmune disease with antibodies detectable against several platelet surface structures.

Immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by isolated thrombocytopenia (platelet count <150,000 u/L), which is not associated with a systemic illness. ITP is reported in approximately 2 per 100,000 adults. The mean age of diagnosis is 50 years. ITP is more common in females of childbearing age and in pregnancy. In adults, the course is more chronic although spontaneous remission can also occur within months of initial diagnosis. A thorough and timely workup of thrombocytopenia is imperative to rule out other differentials of ITP as it is considered a diagnosis of exclusion. Primary care physicians encounter patients who exhibit signs of thrombocytopenia such as petechiae or purpura on a regular basis. A high index of clinical suspicion is required to accurately diagnose ITP and commence the appropriate treatment including glucocorticoids to increase the chances of a favorable prognosis as described by the authors.

Teetering on a liver's edge: a case report highlighting clinical decision-making in thrombocytopenia.

This report illustrates the importance of a detailed history and physical exam and careful analysis of hematologic parameters when diagnosing ITP. This case demonstrates that even with subtle deviations from typical ITP findings one must promptly reevaluate the diagnosis. This case also highlights the importance of peripheral smear review by an expert in pediatric hematopathology. A previously healthy 10 year-old Asian boy presented with 2 months of easy bruising. Review of systems was negative for any constitutional symptoms. On examination, he appeared well but had numerous large ecchymoses. He had no appreciable lymphadenopathy or splenomegaly. The liver was palpable 1.5 cm below the costal margin. A complete blood count (CBC) showed: platelets = 17 × 109/L, hemoglobin = 128 g/L, white blood cell count = 5.43 × 109/L, and neutrophils = 1.63 × 109/L. A blood smear was reported as normal. Urate was 370 umol/L and lactate dehydrogenase (LDH) was 803 U/L. The child was admitted with a presumptive diagnosis of immune thrombocytopenic purpura (ITP) and treated with intravenous immunoglobulin. The following day, the blood smear was reviewed by a hematopathologist who identified blasts. A bone marrow aspiration (BMA) confirmed the diagnosis of precursor B-cell acute lymphoblastic leukemia. In children presenting with suspected ITP, leukemia should always be considered. A BMA was historically performed on all patients with presumed ITP to rule out leukemia. In 2011, the American Society of Hematology (ASH) stopped recommending routine BMA in patients suspected of having ITP. ASH advises in cases with unusual findings on history, physical examination or CBC, it is reasonable to perform a BMA. Our patient had mild hepatomegaly, which may have qualified him for a BMA. He also had an elevated LDH and urate, which are not listed as criteria for BMA by ASH but were considered atypical for ITP by the clinical team. A literature search did not reveal any primary data assessing these markers. While corticosteroids are a first line treatment in ITP, they must be reserved for when clinicians are confident that the patient does not have leukemia. Steroid administration prior to diagnosing leukemia results in delayed diagnosis and may increase the risk of complications and decrease survival.

Present-day problems of diagnosis and treatment in the idiopathic thrombocytopenic purpura.

A review is made of the data in the literature and of the authors' experience regarding the etiology and pathogenesis, diagnosis and therapy of the chronic form of idiopathic thrombocytopenic purpura (ITP). The mechanisms of production (after McMillan et al.) are presented schematically and the five criteria of ITP diagnosis suggested by Karpatkin are discussed: 1) decreased blood platelet count with direct or indirect signs of thrombocytolysis; 2) increased number of megakaryocytes in the bone marrow and/or signs of intramedullary thrombocytolysis; 3) direct or indirect signs of antiplatelet autoantibody presence in the plasma; 4) exclusion of a primary disorder and 5) absence of splenomegaly. The results of corticotherapy, splenectomy, platelet transfusion and immunosuppression (including "target" immunosuppressive therapy) in 188 patients with ITP, admitted to the clinic of Hematology--Bucharest between 1966 and 1978, are presented and analysed.

Immune thrombocytopenic purpura

It is recommended that pregnant women with thrombocytopenia or a previous diagnosis of ITP should be tested for serum antiplatelet antibodies. A woman with symptomatic thrombocytopenia and an identifiable antiplatelet antibody should be started on therapy for their ITP which may include steroids or IVIG. Fetal blood analysis to determine the platelet count is not generally performed as ITP-induced thrombocytopenia in the fetus is generally less severe than NAIT. Platelet transfusions may be performed in newborns, depending on the degree of thrombocytopenia. It is recommended that neonates be followed with serial platelet counts for the first few days after birth.

First_Aid_Step2

ITP is associated with a range of conditions, including lymphoma, leukemia, SLE, HIV, and HCV. The clinical presentation is as follows: Acute: Abrupt onset of hemorrhagic complications following a viral illness. Commonly affects children 2–6 years of age, with males and females affected equally. Chronic: Insidious onset that is unrelated to infection. Most often affects adults 20–40 years of age; women are three times more likely to be affected than men. A diagnosis of exclusion, as the test for platelet-associated antibodies is a poor one. Once other causes of thrombocytopenia have been ruled out, a diagnosis can be made on the basis of the history and physical, a CBC, and a peripheral blood smear showing normal RBC morphology. Most patients do not require bone marrow biopsy, which would show ↑ megakaryocytes as the only abnormality. Most patients with acute childhood ITP spontaneously remit, but this is rarely the case in chronic ITP.

Immune thrombocytopenic purpura

Diagnosis The diagnosis of ITP is a process of exclusion. First, it has to be determined that there are no blood abnormalities other than a low platelet count, and no physical signs other than bleeding. Then, secondary causes (5–10 percent of suspected ITP cases) should be excluded. Such secondary causes include leukemia, medications (e.g., quinine, heparin), lupus erythematosus, cirrhosis, HIV, hepatitis C, congenital causes, antiphospholipid syndrome, von Willebrand factor deficiency, onyalai and others. All patients with presumed ITP should be tested for HIV and hepatitis C virus, as platelet counts may be corrected by treating the underlying disease. In approximately 2.7 to 5 percent of cases, autoimmune hemolytic anemia and ITP coexist, a condition referred to as Evans syndrome.

Immune Thrombocytopenic Purpura Detected with Oral Hemorrhage: a Case Report.

Immune thrombocytopenic purpura (ITP) is an immune-mediated acquired disease found in both adults and children. It is characterized by transient or persistent decreases in the platelet count. We report a case of ITP detected based on oral hemorrhagic symptoms. The patient was a 79-year-old female with no significant past medical history. She presented with sudden onset of gingival bleeding and hemorrhagic bullae on the buccal mucosa. Gingival bleeding was difficult to control. Laboratory tests revealed severe thrombocytopenia with a platelet count as low as 2000/μL. Under a provisional diagnosis of a hematological disorder, she was referred to a hematologist. A peripheral smear showed normal-sized platelets. A bone marrow examination revealed increased numbers of megakaryocytes without morphologic abnormalities. The patient was diagnosed with ITP and treated with a combination of pulsed steroid therapy and high-dose immunoglobulin therapy. However, her severe thrombocytopenia was refractory to these treatments. Then, a thrombopoietin receptor agonist was begun as a second-line treatment. Her platelets rapidly increased, and no bleeding complications were reported. Because oral symptoms can be one of the initial manifestations of ITP, dentists should be familiar with the clinical appearance of ITP, and attention must be paid to detect and diagnose unidentified cases.

Development and internal validation of a clinical prediction model for the diagnosis of immune thrombocytopenia.

Immune thrombocytopenia (ITP) is a diagnosis of exclusion that can resemble other thrombocytopenic disorders. To develop a clinical prediction model (CPM) for the diagnosis of ITP to aid hematogists in investigating patients presenting with undifferentiated thrombocytopenia. We designed a CPM for ITP diagnosis at the time of the initial hematology consultation using penalized logistic regression based on data from patients with thrombocytopenia enrolled in the McMaster ITP registry (n = 523) called the Predict-ITP Tool. The case definition for ITP was a platelet count less than 100 × 10<sup9</sup /L and a platelet count response after high-dose corticosteroids or intravenous immune globulin, defined as the achievement of a platelet count above 50 × 10<sup9</sup /L and at least a doubling of baseline. Internal validation was done using bootstrap resampling. Model discrimination was assessed by the c-statistic, and calibration was assessed by the calibration slope, calibration-in-the-large, and calibration plot. The final model included the following variables: (1) platelet count variability (based on three or more platelet count values), (2) lowest platelet count value, (3) maximum mean platelet volume, and (4) history of major bleeding (defined by the ITP bleeding scale). The optimism-corrected c-statistic was 0.83, the calibration slope was 0.88, and calibration-in-the-large for all performance measures was <0.001 with standard error <0.001, indicating good discrimination and excellent calibration. The Predict-ITP Tool can estimate the likelihood of ITP for a given patient with thrombocytopenia at the time of the initial hematology consultation. The tool had high predictive accuracy for the diagnosis of ITP.

InternalMed_Harrison

laboratory testing in itp Laboratory testing for antibodies (serologic testing) is usually not helpful due to the low sensitivity and specificity of the current tests. Bone marrow examination can be reserved for those who have other signs or laboratory abnormalities not explained by ITP or in patients who do not respond to initial therapy. The peripheral blood smear may show large platelets, with otherwise normal morphology. Depending on the bleeding history, iron-deficiency anemia may be present.

InternalMed_Harrison

Laboratory testing is performed to evaluate for secondary causes of ITP and should include testing for HIV infection and hepatitis C (and other infections if indicated). Serologic testing for SLE, serum protein electrophoresis, immunoglobulin levels to potentially detect hypogammaglobulinemia, selective testing for IgA deficiency or monoclonal gammopathies, and testing for H. pylori infection should be considered, depending on the clinical circumstance. If anemia is present, direct antiglobulin testing (Coombs’ test) should be performed to rule out combined autoimmune hemolytic anemia with ITP (Evans’ syndrome). The treatment of ITP uses drugs that decrease reticuloendothelial uptake of the antibody-bound platelet, decrease antibody production, and/or increase platelet production. The diagnosis of ITP does not necessarily mean that treatment must be instituted. Patients with platelet counts >30,000/μL appear not to have increased mortality related to the thrombocytopenia.

Immune thrombocytopenic purpura

Pregnancy Anti-platelet autoantibodies in a pregnant woman with ITP will attack the patient's own platelets and will also cross the placenta and react against fetal platelets. Therefore, ITP is a significant cause of fetal and neonatal immune thrombocytopenia. Approximately 10% of newborns affected by ITP will have platelet counts <50,000/uL and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with neonatal alloimmune thrombocytopenia (NAIT). No lab test can reliably predict if neonatal thrombocytopenia will occur. The risk of neonatal thrombocytopenia is increased with: Mothers with a history of splenectomy for ITP Mothers who had a previous infant affected with ITP Gestational (maternal) platelet count less than 100,000/uL

Platelet

Disorders Adapted from: The three broad categories of platelet disorders are "not enough"; "dysfunctional"; and "too many". Thrombocytopenia Immune thrombocytopenias (ITP) – formerly known as immune thrombocytopenic purpura and idiopathic thrombocytopenic purpura Splenomegaly Gaucher's disease Familial thrombocytopenia Chemotherapy Babesiosis Dengue fever Onyalai Thrombotic thrombocytopenic purpura HELLP syndrome Hemolytic–uremic syndrome Drug-induced thrombocytopenic purpura (five known drugs – most problematic is heparin-induced thrombocytopenia (HIT) Pregnancy-associated Neonatal alloimmune associated Aplastic anemia Transfusion-associated Pseudothrombocytopenia idiopathic thrombocytopenic purpura Vaccine induced immune thrombocytopenia Gilbert's syndrome

Evans syndrome

Causes Although Evans syndrome seems to be a disorder of immune regulation, the exact pathophysiology is unknown, but a gradual loss of self-tolerance is postulated. Autoantibodies targeted at different antigenic determinants on red cells and platelets are assumed to cause isolated episodes of hemolytic anemia and thrombocytopenia, respectively. Diagnosis The diagnosis of primary Evans syndrome is made upon blood tests to confirm not only hemolytic anemia and immune thrombocytopenic purpura, but also a positive direct antiglobulin test (DAT) and an absence of any known underlying cause. In 27% to 50% of cases there is an associated malignancy or a predisposing autoimmune disease (e.g. systemic lupus erythematosus), it is then common to denote it as secondary Evans syndrome. Other antibodies may occur directed against neutrophils and lymphocytes, and "immunopancytopenia" has been suggested as a term for this syndrome.

[Myelodysplastic syndrome mimicking idiopathic thrombocytopenic purpura].

In patients with isolated thrombocytopenia, but without significant dysplasia, diagnosis of idiopathic thrombocytopenic purpura (ITP) rather than myelodysplastic syndrome (MDS) may be taken into account. It is important to make an accurate diagnosis because different treatments are used for ITP and MDS. The purpose of this study was to investigate the clinical and hematologic features of patients who were initially diagnosed as ITP but had cytogenetic abnormalities. We retrospectively reviewed cytogenetic studies of 100 patients who were diagnosed as ITP from 2004 to 2009 at Mokdong Hospital of Ewha Womans University based on clinical features and hematologic studies. Bone marrow pathology was re-evaluated based on 2008 WHO classification. Cytogenetic analysis was performed by 24-48 hr culture of bone marrow aspirates without using mitogens and 20 metaphases were analyzed. Of the 100 patients diagnosed as ITP initially, three patients (3%) had cytogenetic abnormalities. They had no thrombocytopenia-related symptoms and thrombocytopenia was found accidentally. The numbers of megakaryocytes in bone marrow were increased and dysplasia was not found in megakaryocyte, erythroid, and myeloid cell lineages. The proportion of blasts was within normal limits. Clonal chromosomal abnormalities found were der(1;7)(q10;p10), add(9)(q12), or t(7;11)(p22;q12). Presumptive diagnosis of MDS or diagnosis of idiopathic cytopenia of undetermined significance (ICUS) was made according to 2008 WHO classification. During the follow up, disease progression was not found. In patients with suspected ITP, cytogenetic analysis should be done. If specific clonal chromosomal abnormality is found, presumptive diagnosis of MDS has to be considered and close follow up is needed.

Harrington–Hollingsworth experiment

The Harrington–Hollingsworth experiment was an experiment that established the autoimmune nature of the blood disorder immune thrombocytopenic purpura. It was performed in 1950 by the academic staff of Barnes-Jewish Hospital in St. Louis, Missouri. Experiment The experiment was undertaken in 1950 by William J. Harrington and James W. Hollingsworth, who postulated that in patients with idiopathic thrombocytopenic purpura (ITP), it was a blood factor that caused the destruction of platelets. To test this hypothesis, Harrington received 500 ml of blood from a patient with ITP. Within three hours, his platelets dropped to dangerously low levels and he experienced a seizure. His platelet count remained extremely low for four days, finally returning to normal levels by the fifth day. Bone marrow biopsy from Harrington's sternum demonstrated normal megakaryocytes, the cells necessary for platelet production.

Pediatrics_Nelson

Diagnosis. The diagnosis of ITP usually is based on clinical presentation and the platelet count and does not often require a bone marrow examination. If atypical findings are noted, however, marrow examination is indicated to rule out an infiltrative disorder (leukemia) or an aplastic process (aplastic anemia). In ITP, an examination of the bone marrow reveals increased megakaryocytes and normal erythroid and myeloid elements.

Immune thrombocytopenic purpura

Epidemiology A normal platelet count is considered to be in the range of 150,000–450,000 per microlitre (μl) of blood for most healthy individuals. Hence one may be considered thrombocytopenic below that range, although the threshold for a diagnosis of ITP is not tied to any specific number. The incidence of ITP is estimated at 50–100 new cases per million per year, with children accounting for half of that number. At least 70 percent of childhood cases will end up in remission within six months, even without treatment. Moreover, a third of the remaining chronic cases will usually remit during follow-up observation, and another third will end up with only mild thrombocytopenia (defined as a platelet count above 50,000). A number of immune related genes and polymorphisms have been identified as influencing predisposition to ITP, with FCGR3a-V158 allele and KIRDS2/DL2 increasing susceptibility and KIR2DS5 shown to be protective.

Thrombocytopenia

In severe thrombocytopenia, a bone marrow study can determine the number, size, and maturity of the megakaryocytes. This information may identify ineffective platelet production as the cause of thrombocytopenia and rule out a malignant disease process at the same time. Treatment Treatment is guided by the severity and specific cause of the disease. Treatment focuses on eliminating the underlying problem, whether that means discontinuing drugs suspected to cause it or treating underlying sepsis. Diagnosis and treatment of serious thrombocytopenia is usually directed by a hematologist. Corticosteroids may be used to increase platelet production. Lithium carbonate or folate may also be used to stimulate platelet production in the bone marrow. Platelet transfusions Platelet transfusions may be suggested for people who have a low platelet count due to thrombocytopenia.

Upshaw–Schulman syndrome

Diagnosis A diagnosis of TTP is based on the clinical symptoms with the concomitant presence of thrombocytopenia (platelet count below 100×109/L) and microangiopathic hemolytic anemia with schistocytes on the blood smear, a negative direct antiglobulin test (Coombs test), elevated levels of hemolysis markers (such as total bilirubin, LDH, free hemoglobin, and an unmeasurable haptoglobin), after exclusion of any other apparent cause. USS can present similar to the following diseases, which have to be excluded: fulminant infections, disseminated intravascular coagulation, autoimmune hemolytic anemia, Evans syndrome, the typical and atypical form of hemolytic uremic syndrome, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, pre-eclampsia, heparin-induced thrombocytopenia, cancer that is often accompanied with metastasis, kidney injury, antiphospholipid antibody syndrome, and side effects from hematopoietic stem cell transplantation.

Physiology, Spleen -- Clinical Significance

ITP appears to be an autoimmune condition resulting in thrombocytopenia, petechiae/purpura, and bleeding from mucosal surfaces. There have been many antibodies implicated in the pathogenesis of ITP with the two main autoantibodies being against IgG and the glycoprotein (GP) IIb/IIIa complex on platelets. Platelets tagged by these autoantibodies then get broken down by phagocytes in the spleen, resulting in thrombocytopenia. Without platelets to form the platelet plug, which is the first step of hemostasis, the patient becomes more susceptible to bleeding. Most patients with ITP only have minor bleeds, such as nosebleeds or conjunctival bleeds. However, these patients are at risk of severe bleeds, and that risk helps guide management. ITP tends to affect children around five years old or older adults. In children, ITP typically presents with a sudden onset, usually following a microbial illness and is brief. In adults, it typically presents with insidious onset and is a chronic condition. In both patient populations, there must be a high index of suspicion, and ITP is usually a diagnosis of exclusion. A CBC and peripheral blood smear are typically performed in the initial evaluation. In adults, it is essential to rule out ITP secondary to other autoimmune diseases, so an anti-nuclear antibody (ANA) and autoantibodies specific for other conditions may be tested as well. A more specific test for ITP would be autoantibodies against IgG and GP IIb/IIIa. In children, treatment is generally conservative, as ITP is typically transient. Adults usually require treatment. Prednisone is the first-line treatment in adults and can also be used to treat children. IVIG can also be used to reduce or eliminate causative autoantibodies and is typically used before steroids in children and after steroids in adults. In cases refractory to medical management, a splenectomy is an option as most platelet breakdown occurs there. [28]

Role of <i>Helicobacter pylori</i> Eradication Therapy on Platelet Recovery in Chronic Immune Thrombocytopenic Purpura.

<iBackground</i. Idiopathic thrombocytopenic purpura (ITP) is a bleeding disorder in which the immune system destroys native platelets. In this condition an autoantibody is generated against a platelet antigen. ITP affects women more often than men and is more common in children than adults. <iObjective</i. To assess the effect of <iHelicobacter pylori</i eradication therapy (HPET) on platelet count in <iHelicobacter pylori</i associated chronic immune thrombocytopenic purpura (chronic ITP) in adult. <iMaterials and Methods</i. It is an interventional prospective study conducted at Liaquat University of Medical and Health Sciences, Jamshoro, from 2014 to 2015. A set of 85 patients diagnosed with chronic ITP were included in the study via convenient sampling. Patients with platelets count < 100 × 10<sup9</sup/L for >3 months were selected. They were posed to first-line investigations which comprised complete blood count (CBC) and peripheral blood smear examination followed by second-line tests including bone marrow examination and <iHelicobacter pylori</i stool specific antigen (HpSA-EIA). Standard <iH. pylori</i eradication therapy was offered and the patients were assessed at regular intervals for 6 months. <iResults.</i Of the 85 study patients, 32 (37.6%) were male and 53 (62.3%) were female. Mean ages of <iH. pylori</i positive and negative subjects were 43.89 ± 7.06 and 44.75 ± 7.91 years, respectively. Bone marrow examination confirmed the diagnosis and excluded other related BM disorders. <iH. pylori</i stool antigen (HpSA) was detected in 34 (40%) patients and hence regarded as <iH. pylori</i positive; the rest were negative. Treatment with eradication therapy significantly improved the mean platelet counts from 48.56 ± 21.7 × 10<sup9</sup/l to 94.2 ± 26.8 × 10<sup9</sup/l. <iConclusion.</i We concluded that the <ianti-H. pylori</i eradication therapy improves blood platelet counts in chronic immune thrombocytopenia.

InternalMed_Harrison

Thrombocytopenia results from one or more of three processes: (1) decreased bone marrow production; (2) sequestration, usually in an enlarged spleen; and/or (3) increased platelet destruction. Disorders of production may be either inherited or acquired. In evaluating a patient with thrombocytopenia, a key step is to review the peripheral blood smear and to first rule out “pseudothrombocytopenia,” particularly in a patient without an apparent cause for the thrombocytopenia. Pseudothrombocytopenia (Fig. 140-1B) is an in vitro artifact resulting from platelet agglutination via antibodies (usually IgG, but also IgM and IgA) when the calcium content is decreased by blood collection in ethylenediamine tetraacetic (EDTA) (the anticoagulant present in tubes [purple top] used to collect blood for complete blood counts [CBCs]). If a low platelet count is obtained in EDTA-anticoagulated blood, a blood smear should be evaluated and a platelet count determined in blood collected into sodium

ITP-Immune Thrombocytopenic Purpura -- Differential Diagnosis

One should consider the following in the differential thrombocytopenias due to increased platelet destruction and those due to decreased platelet production. [1] [24] [25]