bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Use of Recombinant Activated Factor VII in the Management of Life-Threatening Post Partum Bleeding
Authors: Herrada Juan , Jobe Jeff T. , Long Kristin , Alvarade Jobee , Galvan Carmen 
Published: April 2020

Abstract
Background: Recombinant activated factor VII (rFVIIa) is a novel hemostatic agent, originally developed for the treatment of hemorrhage in hemophiliacs with inhibitors, which has been successfully used recently in an increasing number of nonhemophilic bleeding conditions. We report on the use of this hemostatic agent in a case of severe postpartum bleeding, associated with disseminated intravascular coagulation, and unresponsive to standard treatment.
Case report: A healthy 39-year-old female presented with vaginal bleed and underwent emergency cesarean delivery of a full term baby. During the surgical procedure she was found to have an abruptio placentae, complicated with uncontrollable uterine bleeding that required a total hysterectomy. During the immediate post operative period the patient continued with profuse bleeding from the surgical wound. The diagnosis of clinical disseminated intravascular coagulopathy (DIC) was confirmed by the presence of thrombocytopenia, and a marked elevation of both prothrombin time (PT) and partial thromboplastin time (PTT) levels (both more than 100 seconds). During the first two postoperative days the patient required multiple transfusions of platelets, packed red blood cells (about 30 units), fresh frozen plasma, and cryoprecipitate. On the third postoperative day, she was taken to the operative room and a massive retroperitoneal clot was evacuated, although no specific bleeding site was found during the surgical exploration. After the procedure, and in addition to the usual hemostatic interventions, the patient was given three doses of rFVIIa (each dose consisted of 4.8 mg given intravenously over 2 minutes) over an eight-hour period. During the four subsequent days, the patient’s coagulopathy gradually improved, and eventually corrected. Although the clinical course was complicated with sepsis, renal failure, and respiratory failure, the patient was finally discharged home on stable condition twenty-six days after delivery. She is currently without any sequelae.
Conclusion: Severe post partum bleeding unresponsive to standard hemostatic therapy is associated with a high mortality. This case suggests a potential role of rFVIIa in the management of this complex medical condition.
Fatal Bleeding Caused by Congenital Factor XIII Deficiency and Development of An Inhibitor in a Hispanic Male
Authors: Lorenzo Filipe R. , Haslem Derrick , Prchal Josef T. , Greenberg Charles 
Published: April 2020

Abstract
We report a case of fatal bleeding in a patient with mild congenital Factor XIII deficiency who also developed an inhibitor that interfered with fibrin stabilization. Plasma Factor XIII circulates as a tetramer composed of two A-chain and two B-chains and is bound to fibrinogen. After thrombin cleaves the A-chain at Arg 37, the B-chain dissociate producing Factor XIIIa. Factor XIIIa catalyzes covalent linkages between the fibrin molecules aligned in the fibrin clot. Factor XIIIa makes the fibrin resistant to disruption by urea and plasmin. Factor XIIIa levels greater than 1 % are needed to covalently stabilize a clot. We studied a 39 year old Hispanic male that presented with altered mental status, headache and a large left frontal parietal hemorrhage. Ultimately, he became non-responsive and was intubated. He had no major bleeding history but did have frequent nosebleeds. Routine blood counts and coagulation laboratory tests were normal. However, a qualitative Factor XIII assay was abnormal and the clot dissolved in 5M Urea. Furthermore, a 1:1 mixing study did not correct the defect suggesting the presence of an inhibitor. A small dose of cryoprecipitate was administered to the patient and this corrected the clot stability defect. Four days later, the defect recurred and 150 ml of cryoprecipitate was administered and despite correction of the fibrin stabilizing abnormality the patient died. Two of his sisters had a history of repeated hemorrhagic miscarriages in Mexico a finding consistent with congenital Factor XIII deficiency. DNA sequencing of the factor XIII a-chain gene was performed from the propositus’ mononuclear cells. A reverse transcription was done using an oligo(dT) 12–18 primer followed by nested PCR amplification and a heterozygous missense mutation was observed at codon 35 (G226T; Val35Leu). This mutation was than confirmed in propositus’ platelet cDNA. The Val35Leu substitution is close to the thrombin cleavage site, the G226T substitution is in the catalytic core domain. This case demonstrates that in some cases of Factor XIII deficiency there is residual Factor XIIIa activity in the mutant molecule that can prevent serious bleeding. However, patients may develop autoantibodies that further interfere with Factor XIII function and may suffer serious bleeding complications. Additional cases of Factor XIII deficiency may exist in patients that have mild bleeding problems.
Rituximab in the Treatment of Acquired Hemophilia a (AHA): A Novel Eradicating Therapy?
Authors: Mota Karla O. , Bastos Silvia Nakanishi 
Published: April 2020

Abstract
Background: Acquired inhibitors against factor VIII (FVIII), also termed Acquired Hemophilia A (AHA), occur rarely in the nonhemophilic population. Its incidence is approximately 1 to 4 per million/year. The incidence of AHA increases with age and a major peak is seeing in patients aged 68 to 80 years. These autoantibodies are associated with high rate of morbidity (90% of severe bleeding in affected patients) and mortality (8–22% of the cases). The diagnosis of AHA is based on the demonstration of an isolated prolongation of the activated partial thromboplastin time (APTT), not corrected by incubating the patient’s plasma with equal volumes of normal plasma (mixing study), associated with FVIII reduced levels and formal evidence of a FVIII inhibitor in a patient with no previous personal or family history of bleeding. In approximately half of affected patients there is no identification of relevant concomitant diseases. The bleeding pattern in AHA is characterized by hemorrhages into the skin, muscles or soft tissues, and mucous membranes. Rituximab (Mabthera®; Roche; Switzerland) is a chimeric monoclonal antibody against the pan B-cell antigen CD20 that induces a rapid in vivo depletion of normal B lymphocytes. Primarily developed to treat B-cell non Hodgkin Lymphomas, more recently, Rituximab has demonstrated effectiveness in a number of autoantibody-mediated diseases including AHA. Case Report: We treated a 69-year-old diabetic and hypertensive patient with AHA. In March 2007, the diagnosis was made by a prolonged APTT (ratio 2.74 sec), not corrected by the mixing study, and FVIII inhibitor 320 Bethesda units. The patient had no evidence of malignancy, autoimmune disease or use of drugs. His bleeding manifestations were large ecchymosis of upper and lower extremities for almost a year, and at admission to the hospital, a hematoma of left calf and gengival bleeding. First line therapy consisted of steroids and cyclophosphamide (CFM). The steroids had to be withdraw after one week of use, because of very difficult glycemic control. The CFM were use in the dose of 50mg/day adding an total accumulative dose of 3g. This protocol were used considering the incapacity of the patient to tolerate higher dose of CFM due to leukopenia. After treatment, the patient was evaluated and neither normalization of APTT nor improvement of clinical findings happened. Therefore, considering all the above, it was decided to use Rituximab 375mg/m2, weekly, for four weeks. In June 2007, the patient received and tolereted very well all the infusions. In August 2007, he had no bleeding symptoms and his APTT was normal. At his laterest visit to the clinic in July 2008, an year after finishing his treatment, he was still very well and his bleeding tests were normal.
Conclusion: Rituximab should be considered a treatment option for AHA.
Seroprevalence of PF4/Heparin Antibodies among Blood Bank Donors
Authors: Pai Poulomi J. , McCracken Julianna E , Arepally Gowthami M 
Published: April 2020

Abstract
Heparin-Induced Thrombocytopenia (HIT) is classically viewed as a drug-induced immune disorder triggered by exposure to the anticoagulant drug, heparin. However, HIT may also be considered a dysregulated autoimmune response to two naturally occurring substances, Platelet Factor 4 (PF4), a platelet protein, and heparin, a tissuederived glycosaminoglycan. Until recently, studies of HIT and PF4/heparin antibody seroconversion have been exclusively focused on patients exposed to heparin or heparinlike drugs, including low-molecular weight heparin, the heparinoids and the synthetic agent, fondaparinux. Recent reports, however, indicate that PF4/heparin antibodies may arise spontaneously in some individuals in the absence of heparin (Warkentin Am J Med 2008; Hursting J Thromb Thrombolysis, 2008). We undertook this study to document the seroprevalance of “naturally-occurring” PF4/heparin antibodies in healthy subjects without prior heparin exposure. To study “healthy” subjects, we used blood bank donors as a surrogate population. Samples from blood bank units were obtained through Duke Transfusion services/American Red Cross (ARC). Donors met eligibility criteria for blood donation to the ARC and generally, represent a healthy population (http://www.redcross.org/services/biomed/0,1082,0_557_,00.html#hem). A Duke IRB waiver was issued due to use of anonymous samples. Plasma from donor units/segments were assayed in duplicate for the presence of PF4/heparin antibodies using a commercially available PF4/heparin ELISA (PF4 enhanced IgG,A,M kits, Genetics Technology Institute, Waukesha, WY). Positivity was defined by the manufacturer as A405nm ≥0.4. Positive samples were stratified into low, (A405nm=0.4–0.6), intermediate (A405nm=0.61–0.99) or high-positive values (A405nm≥1.0). High and intermediate positive samples were further isotyped using IgG and IgM specific antibodies (Sigma, St. Louis, MO). Of the 970 blood bank donors tested to date, 31 samples (3.2%) were positive using the manufacturer’s cut-off value. Repeat testing confirmed positivity in all 31 samples. Of those testing positive, 26 were low-positive (2.3% of overall cohort; 84% of all positive samples), 1 sample was intermediate positive (0.1% of overall cohort; 3.2% of positive samples) and 5 samples were high-positive (0.5% overall cohort; 16% of positive samples). Isotyping of 6 high/intermediate positive samples revealed IgG in 3 patients, IgM in the remainder. There was no correlation between antibody positivity and ABO blood type. In summary, our data reveals a high prevalence of PF4/heparin antibodies, the majority of which are low-positive values (~84%). Many of these low-positive samples likely reflect background “noise” of the assay and could be eliminated using a higher cut-off for positivity. We also found a seroprevalance of 0.5% of high positive antibodies, of IgG and IgM isotype, supporting the notion that some individuals may have “naturally-occuring”
Burden of Thrombocytopenia in Cancer Patients Undergoing Chemotherapy: a Retrospective Database Analysis
Authors: Aravind Suresh , Wu Ying , Ranganathan Gayatri , Nalysnyk Luba 
Published: April 2020

Abstract
Background. Along with anemia and neutropenia, thrombocytopenia is a common hematological adverse effect of chemotherapy. Prolonged and severe thrombocytopenia increases the risk of bleeding episodes. The goal of this study was to evaluate the epidemiology of thrombocytopenia among cancer patients on chemotherapy.
Methods. Pooled data over the period 2000–07 from a large electronic database of 15 community and 3 hospital-based outpatient oncology clinics in the US was analyzed. For this analysis, adult patients with a cancer diagnosis were grouped as: lung, breast, ovarian, H&N, colorectal, other solid cancers, hematologic and mixed cancers. Chemotherapies used were grouped into platinum, anthracycline, gemcitabine, taxane-based and other regimens. Incidence of Thrombocytopenia (defined as &lt;150,000/μl) was examined by tumor and regimen.
Results. 47,159 patients [mean age 61, male 42%] who met inclusion criteria and 75,243 chemotherapy regimens were analyzed. Breast cancer patients constituted 19.5%, followed by NSCLC (14.9%), colorectal (11.9%), ovarian (3.1%), and H&N (2.5%). Platinum-based regimens accounted for 27.8% of all regimens. The incidence of post-chemo thrombocytopenia was highest among gemcitabine treated patients (64.2%), followed by platinum (55.5%). The lowest incidence was with taxane-based regimens (21.9%). Grade 3–4 (&lt;50×109/L) thrombocytopenia was seen in 11% of patients on platinum or gemcitabine regimens, 2% of taxane-treated patients, and 5% of anthracycline-treated patients. Patients with NSCLC and ovarian cancer experienced highest incidence of thrombocytopenia. Thirty percent of patients (14,103) developed both anemia and thrombocytopenia during their chemotherapy. More than 90% of patients with thrombocytopenia grade 1–3 also had concomitant anemia grade 1 or 2. Twenty percent of patients with grade 4 thrombocytopenia also presented with anemia grade 3–4. Of these, 16.7% had NSCLC, 16.2% were breast cancer patients, and 9.1% were colorectal cancer patients. However, platelet transfusions were relatively rare (&lt;5%) in these chemotherapy-treated patients.
Conclusions. Thrombocytopenia was relatively common in this large cohort of cancer patients undergoing chemotherapy. A substantial proportion of patients with thrombocytopenia also had anemia.
TPO Mimetics: Can More Than One Agent Be Used in a Patient?
Authors: Cromwell Caroline , Aledort Louis M. 
Published: April 2020

Abstract
Recently, advances in TPO mimetics have expanded therapeutic options for adult patients with chronic ITP. Seven second generation TPO agonists have been reported in the literature. Evidence suggests that non-peptide versus peptide TPO mimetics bind differently to the TPO receptor. Romiplostim, a subcutaneous peptide TPO mimetic has recently been FDA approved. Eltrombopag, Ligand L4665-08, and Aka-Rx 501 are oral non-peptide TPO mimetics undergoing clinical study.
The question arises if a patient fails or succeeds one TPO mimetic can the patient be treated with another agent and have a response. We present two cases of patients who were treated with two agents.
Patient #1 was initiated on Aka-Rx 501 as she could not tolerate steroids and refused splenectomy. She was able to maintain a platelet count &gt;50,000 for a period of six months without any bleeding. As the study did not have an extension, following a washout period she was enrolled in Ligand L4665-083 with a platelet count of 1,000. Within a week her platelet count rose to 97,000. Her platelet count, on a stable dose of Ligand progressively fell over two weeks and dropped to 2,000 with bleeding. She was then initiated on a higher dose of study medication.
The second patient had an eight year history of ITP refractory to IVIG and steroids. She was initially enrolled in AMG 531, and was able to maintain a platelet count greater than 50,000 for over six months. Her platelet count began to progressively decline to zero. Antibody tests were negative and a bone marrow biopsy was normal.
After a washout period, the patient was enrolled in AkaRx 501 Cl-003. One week later her platelet count rose to 64,000. She sustained a platelet count of greater than 30,000 and was initiated on the rollover study after four weeks. At week twelve, her platelet count as in the prior study fell to 0 with a concomitant CNS bleed.
These two cases demonstrate the use of two different TPO mimetics in a given patient. The first patient was treated with two oral non-peptide TPO mimetics, with a sustained response to one agent and a quick response followed by a rapid loss of response to the second agent. The second patient was treated initially with a peptide TPO mimetic followed by a non-peptide TPO mimetic, both times demonstrating an initial brisk response, long with one and short-lived with the second, which was eventually lost. These data suggest that more than one agent can be used in a given patient.
Use of the Platelet Indices for Differential Diagnosis of Pediatric Immune Thrombocytopenic Purpura (ITP)
Authors: Nakadate Hisaya , Kaida Miho , Furukawa Shinsuke , Ishii Masahiro , Higashihara Masaaki 
Published: April 2020

Abstract
Introduction: The prognosis of pediatric immune thrombocytopenic purpura ( ITP ) has a favorable prognosis, about 80 % of ITP children will be cured in 6 months with or without therapy, the rest of patients develop to chronic ITP. However, it is difficult to predict the course of this disease at the time of diagnosis. Recent advances of automated blood cell analyzer enable to measure various blood cell parameters. Among these parameters, platelet indices such as mean platelet volume (MPV), platelet size deviation width (PDW) and platelet-large cell ratio (P-LCR) has brought about some information for thrombocytopenia. We studied the significance of such platelet indices in the differential diagnosis of immune thrombocytopenic purpura ( ITP ) and their ability to discriminate the clinical courses of ITP.
Methods: Ninety-three patients were enrolled this study at our institution from 2004 to 2006. Their ages ranged from 1 to 17 years ( media 4.3 years ). Of 93, patients were divided into two goups for analysis, according to the diagnosis of ITP. 34 were diagnosed as ITP and 59 were diagnosed various blood diseases other than ITP. In these 59 non-ITP patients, five were with thrombocytopenia ( platelet count &lt; 100.0 × 109/L ), the other without thrombocytopenia. Of 34 ITP patients, 29 were acute subtype and 5 were chronic. The Sysmex-XE2100 automated blood cell analyzer (Sysmex, Kobe, Japan) was used to measure the blood parameters, including the platelet indices.
Results: According to MPV, PDW and P-LCR, there were no significant differences between ITP patients and non-ITP. In children with ITP, there were significant inverse correlations between the platelet count and evaluated parameters, MPV (R2=0.376), PDW (R2=0.26) and P-LCR(R2=0.338). But no significant correlations were found between the platelet count and these evaluated platelet indices in non-ITP. Also, we have found all platelet indices were significantly higher in chronic ITP than in acute ITP. In particular, PDW (9.910 vs 13.080) and P-LCR (21.071 vs 33.220) showed marked differences between the two groups.
Conclusions: ITP is considered as a result of hyper-destruction of platelets. Increase of platelet count is regarded as decrease of destruction of platelets. Our data suggested that platelet indices, MPV, PDW and P-LCR showed the useful information for the degree of platelet destruction and the ability to predict the clinical courses of ITP.
Thyroid Disorder-Related Immune Thrombocytopenia: Clinical and Laboratory Characteristics
Authors: Cheung Eric M. , Naik Rahul , Keng Michael , Liebman Howard A. 
Published: April 2020

Abstract
Thyroid disorders have been associated with immune thrombocytopenia. However, there is little published data regarding the clinical and laboratory manifestations of patients with hyper- and hypothyroidism-related thrombocytopenia (Th-ITP) compared with those with euthyroid chronic immune thrombocytopenia (E-ITP). We reviewed the medical records for 135 patients who fulfilled American Society of Hematology criteria for chronic ITP.
Results: Of the 135 patients, 71 (52.6%) were screened for thyroid disorders. Of these 71 patients, 17 (23.9%) were diagnosed with thyroid disorders, including 5 (29.4%) with overt hyperthyroidism, 5 (29.4%) with subclinical hyperthyroidism, 4 (23.5%) with overt hypothyroidism, and 3 (17.6%) with subclinical hypothyroidism. Four patients were diagnosed with thyroid disorders prior to their diagnosis of immune thrombocytopenia while 13 were diagnosed after. The duration of ITP follow-up was similar for the E-ITP (46.1 mo; range: 1– 333 mo) and Th-ITP patients (50.5 mo; range: 1– 173 mo). Age (49.9 yrs for Th-ITP vs. 45.9 for E-ITP), gender (82.3% females for Th-ITP vs. 70.3% for E-ITP), initial platelet counts (17.27 × 109/L for Th-ITP vs. 18.87 × 109/L for E-ITP), and initial bleeding manifestations (64.7% for Th-ITP vs. 66% for E-ITP) were not significantly different between the two groups. Significantly fewer Th-ITP than E-ITP patients had platelet counts &lt;50k at diagnosis (76.5% vs. 85.6%, p = 0.021). There was a trend for Th-ITP to have platelet counts &lt;50k at the end of follow-up (23.5% vs. 8.5%, p = 0.064), despite having a similar duration of follow-up and receiving a similar numbers of individual therapies (2.82 vs. 3.13). However, fewer Th-ITP patients underwent splenectomy (17.65% vs. 38.98%, p = 0.087). Lupus anticoagulant and anti-cardiolipin antibodies were more common in Th-ITP than E-ITP patients, although this difference was not statistically significant (40% vs. 26.2%; p=0.086).
Conclusions: Thyroid disorders are commonly observed in patients with immune thrombocytopenia, but do not appear to significantly affect the response to therapy or long-term outcome in ITP patients.
The Investigation of the Clinical Values of Platelets Hemostatic Activity on Predicting Prophylactic Platelet Transfusion
Authors: Ding Jia-hua , Qian Hou-ming , Huang Cheng-yin 
Published: April 2020

Abstract
Objective To investigate the clinical values of platelets hemostatic activity on predicting the bleeding risk due to thrombocytopenia and threshold of prophylactic platelet transfusion.
Methods Activated plasma clotting time (APCT) and thrombelastography (TEG) were used to evaluate the platelets hemostatic activity of 127 patients with platelet count (Plt)&lt;50×109/L.37/127 patients with bleeding symptoms and 90/127 patients without were involved in the test.4.5ml venous blood was collected in the tubes with 0.5ml 3.2% sodium citrate and detected the Plt,APCT and TEG.
Results Plt and APCT in the bleeding group and the non-bleeding group were(7.9±3.6)×109/L,104.0±6.1s and(23.0±10.1)×109/ L,68.4±9.4s, respectively. There were statistically significant differences between the two groups, P&lt;0.01. The APCT was negatively correlated with Plt,r=−0.7613. The TEG maximum amplitude (TEG-MA)were 20.5±5.3mm in the bleeding group(n=15)and 43.4±6.3mm in non-bleeding group(n=20),p&lt;0.01. Using APCT≥90s,TEG-MA≤30mm as the cut-off point to predict the bleeding due to thrombocytopenia, the sensibility and specificity were 100%,98.9% and 100%,93.3%, respectively. Using Plt ≤20×109/L, the sensibility was 100% and the specificity was 56.7%.
Conclusion The specificity of APCT or TEG-MA for predicting bleeding due to thrombocytopenia was better than that of Plt. APCT≥90s or TEG-MA≤30mm as trigger for prophylactic platelet transfusion would effectively prevent bleeding due to thrombocytopenia.