bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring of Rheologic Variables During Postoperative High-Dose Brachytherapy for Uterine Cancer
Authors: von Tempelhoff Georg-Friedrich , Heilmann Lothar , Pollow Kunhard , Hommel Gerhard
Published: March 2006

Oxygenation of tumor tissue has recently been assed an important prerequisite for the effectiveness of radiotherapy in cervical cancer. Hyperviscosity is a common phenomenon in malignancy and a cause of reduced oxygen transport capacity that would favour tissue hypoxia. Hemorheological variables were serially tested preoperatively, during four cycles of fractionated adjuvant IR192 HDR after loading radiation (HDR-AL) of the vaginal vault (weekly intervals), and 6 months postoperatively in patients with cervical (n=12) and endometrial cancer (n=26). Women who were scheduled for benign tumor surgery served as controls (n=29). Preoperatively, in cervical and endometrial cancer patients, mean plasma viscosity (PV: 1.31±0.1 mPa s; p<0.05; 1.35±0.13 mPa s; p<0.001) and fibrinogen levels (383±46 mg/dL; p<0.05; 379±117 mg/dL; p<0.05) were higher as compared to the controls (1.25±0.07 mPa s; 314±89 mg/dL). Red blood cell aggregation at low shear and stasis (RBC agg.: 15.7±5.6; p<0.05; 29.6±9.1; p<0.05) was higher in endome-trial cancer patients as compared to the controls (13.7±3.4; 25.3±5.6). Postoperatively PV decreased in endometrial cancer patients and transiently increased in cervical cancer patients. After the third session of irradiation in both cancer groups, PV regained and at the 6-month checkup, levels were higher as compared to the values before surgery. Postoperatively fibrinogen levels increased and remained higher throughout HDR-AL and 6 months postoperatively. After surgery and during irradiation, anemia persisted in both cancer groups while hematocrit recovered after 6 months in endometrial cancer patients. Thrombosis was diagnosed in three patients postoperatively (7.9%) but in none during HDR-AL. While a temporary reduction of hyperviscosity is found postoperatively and during HDRAL in uterine cancer patients, 6 months after surgery RBC aggregation, PV, and hematocrit returned to the pretreatment range.
Effect of Age on Oral Contraceptive-Induced Venous Thrombosis
Authors: Girolami A. , Spiezia L. , Girolami B. , Zocca N. , Luzzatto G.
Published: March 2006

This study was undertaken to investigate the effect of age on oral contraceptive-induced venous thrombosis. All women seen in the University of Padua Department of Medical and Surgical Science who had had two courses of oral contraceptive therapy at different ages were included. A total of 28 subjects met these criteria. Fifteen patients had a congenital or acquired prothrombotic condition, whereas 13 women were normal subjects. The mean age at which thrombosis occurred was 33.3 and 36.3 years for women with or without a prothrombotic condition, respectively. The ages during which the women remained asymptomatic were 23.1 and 23.3 years for women with or without a predisposing defect, respectively. Thrombosis occurred, during the second course of oral contraceptive therapy, after the mean duration of 6.5 cycles or 18.4 cycles in women with or without prothrombotic defects, respectively. During the asymptomatic course, approximately the same number of women took old progestins or third-generation compounds. On the contrary, during the second period, 21 of 28 women took progestins with third-generation compounds. Age seems to plays an important role in oral contraceptive-induced venous thrombosis. In normal women, thrombosis occurred after a greater number of oral contraceptive cycles as compared with the women with prothrombotic defects. Because the majority of women took preparations that contained third-generation progestins during the second course of therapy, concomitant contributing effects of these compounds cannot be excluded.
Is the Circulating Urokinase Plasminogen Activator Upregulated by the Circulating p105 Fraction of the HER-2/neu Proto-oncogene in Patients with Cervical Cancer?
Authors: Contreras Diana N. , Cobos Everardo , Lox Charles
Published: March 2006

It has been suggested that urokinase plasminogen activator (uPA) in cancer cells is upregulated by the p185 kD form of the HER-2/ neu oncogene. This study was performed to see if the extracellular domain of HER-2/ neu, the p105 fraction, which is found in the circulation, has any regulatory influence on uPA in patients with cervical cancer. Levels of uPA and p105 HER-2/ neu were determined in blood from age-matched controls and patients with early and advanced cervical cancer. In the patients with cervical cancer, samples were obtained before treatment only. No significant increase in either uPA or HER-2/neu was seen in the patients before their treatment for cervical cancer. Additionally, correlation analysis of circulating uPA and HER-2/ neu against each other in both the controls and cervical cancer indicated no relationship except in early stage disease. It appears that circulating uPA and HER-2/ neu are not altered in patients with cervical cancer, either early or advanced stages. The upregulation of uPA by HER-2/ neu seen in cancer cells in vitro appears to occur in vivo in early stage cervical cancer.
Effect of Smoking on Platelet Count and Platelet Parameters: An Observation
Authors: Suwansaksri Jamsai , Wiwanitkit Viroj , Soogarun Suphan
Published: March 2006

Arterial thrombosis occurs with increased frequency in cigarette smokers. It is believed that disturbance of platelet function, especially aggregation, is the essential mechanism responsible for this pathology. However, the effect of smoking on the quantity of platelets might be another contributing factor. The effect of smoking on platelet count is still controversial. We performed a cross sectional study to compare the platelet count and platelet parameters in Thai police who are smokers and non-smokers. A total of 30 Thai police in Bangkok were included in this study. Of the 30 police, there are 5 non-smokers and 25 smokers. The platelet counts and platelet parameters of the subjects were not significantly different between smokers and non-smokers.
A Life-Threatening Second Trimester Disseminated Intravascular Coagulopathy with Protein S Deficiency
Authors: Seckin N. C. , İnegöl İ. , Turhan N. Ö. , Bavbek N. , Koşar A.
Published: March 2006

Disseminated intravascular coagulopathy (DIC) is an uncommon but serious complication of pregnancy. Placental abruption is the most common associated condition among the causes of acute obstetrical DIC. We present a case of life-threatening DIC complicating placental abruption in the second trimester of pregnancy with protein S deficiency as a triggering factor, which necessitated urgent termination of pregnancy.
Sapheno-Femoral Junction Pathology: Molecular Mechanism of Saphenous Vein Incompetence
Authors: Urbanek Tomasz , Skop Barbara , Ziaja Krzysztof , Wilczok Tadeusz , Wiaderkiewicz Ryszard , Pal/asz Artur , Mazurek Urszula , Wielgus Ewa
Published: March 2006

A molecular mechanism responsible for varicose vein occurrence was investigated. The role of potential cell cycle regulator p21 and programmed cell death in the pathology leading to the proximal long saphenous vein (LSV) incompetence was investigated. Proximal LSV specimens were obtained from 40 patients with primary varicose veins who had undergone crossectomy. The expression of the p21, p53, and fas encoding genes was investigated by the means of real-time RT-QPCR. Immunostaining for gene product presence, proliferating cell nuclear antigen (PCNA), and apoptotic cells (TUNEL assay) was carried out. The results were compared to the control healthy vein specimens and correlated with pathologic examination findings (of the valve and vein structure). A significant increase in p21, p53, and fas mRNA expression were reported in the proximal incompetent veins. The expression of p21 correlated with expression of p53 (r = 0.658; p<0.05) and negative correlation between media apoptotic index and p21 mRNA expression was found (r = -0.493; p<0.05). Decrease in the muscular component within the media and disturbances of the local structure in the incompetent LSVs were reported. Fas overexpression did not correlate with p53 expression level and did not correlate with apoptotic cell number in the respective vein layers. PCNA-positive cells were present more frequently in the media of the control veins, especially in young subjects. Apoptosis downregulation, cell cycle inhibition and smooth muscle cell hypertrophy are important factors influencing vein wall disturbances related to sapheno-femoral junction incompetence.
Prevalance of Heparin-Dependent Platelet-Activating Antibodies in Preterm Newborns After Exposure to Unfractionated Heparin
Authors: Kumar Praveen , Hoppensteadt Debra A. , Prechel M. Margaret , Deddish Ruth B. , Walenga Jeanine M.
Published: March 2006

Heparin is frequently used in preterm infants to prolong the patency of intravascular catheters. The aim of this study was to evaluate the prevalence of heparin-dependent platelet-activating antibodies in newborns. A cross-section of all preterm newborn infants expected to require heparin to maintain patency of a central venous access line were enrolled. A blood sample was obtained soon after birth before heparin exposure to exclude the possibility of placental transfer of maternal heparin-dependent platelet-activating antibodies. A second sample was obtained at termination of heparin use (mean duration of heparin exposure was 23 ± 13 days; range, 6-67). Paired samples, at birth and after heparin use, were available for 42 infants with a mean gestational age of 27.8 ± 2.2 weeks and birth weight of 1036 ± 267 g. Thrombocytopenia developed in 57% (24/42) of the infants. None of these infants had clinical suspicion of thrombosis during the study period. The etiology of thrombocytopenia was confirmed sepsis in six, presumed sepsis in three, necrotizing enterocolitis in one, and unclear in 14 infants. Anti-heparin/platelet factor 4 antibodies measured using the standard assays for heparin-induced thrombocytopenia (two commercially available enzyme-linked immunosorbent assay tests and the functional platelet serotonin release assay) were negative on all infants. Although it could be related to the poor ability of these infants to mount an immunologic response, further research is necessary to fully understand this lack of response to heparin and to elucidate further the reasons for thrombocytopenia in very-low-birth-weight infants.
Hemostatic Abnormalities and Changes Following Bone Marrow Transplantation
Authors: Matsumoto Takeshi , Wada Hideo , Nishiyama Hiroyoshi , Hirano Tomomi , Sakakura Miho , Nishii Kazuhiro , Masuya Masahiro , Kageyama Shinichi , Tamaki Shigehisa , Nakase Kazunori , Nobori Tsutomu , Shiku Hiroshi
Published: March 2006

Hemostatic parameters were examined in 39 patients who underwent allogeneic bone marrow transplantation (BMT). Twenty-six patients survived and 13 patients died within 6 months after BMT. The main causes of death were acute graft-versus-host disease (GVHD: n=6), veno-occlusive disease (VOD: n=2), and thrombotic microangiopathy (TMA: n=2). Plasma levels of D-dimer and thrombomodulin (TM) were significantly elevated in the non-survivor group. Plasma levels of soluble fibrin (SF) and Fas were significantly elevated in the non-survivor group at 1 to 4 weeks after BMT. Plasma levels of thrombin-antithrombin complex (TAT), D-dimer, and tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPA-PAI-1 complex) were significantly elevated in patients with complications after BMT. Plasma levels of TAT, D-dimer, and tPA-PAI-1 complex were significantly elevated in patients with GVHD. These results suggest that abnormalities of hemostatic parameters might predict poor outcomes or complications in patients with BMT.
Thrombosis-free Surgical Procedures in Severe(Homozygote) Factor XII Deficiency: Report of Four Additional Cases and Literature Review
Authors: Girolami A. , Ruzzon E. , Lombardi A. M. , Cabrio L. , Randi M. L.
Published: March 2006

The outcome of various surgical procedures carried out in patients with severe (homozygote) factor XII deficiency were investigated for the appearance of blood coagulation-related complications with particular emphasis on thrombotic complications. The surgical procedures were total mastectomy, tonsillectomy and adenoidectomy, placement of a hip prosthesis, and double hernia repair. None of the patients slowed any complication. Several other reported cases of surgical procedures carried out in several patients ware found in the literature. Bleeding or thrombotic complications were noted in none of these cases. The surgical procedures in some cases were minor such as adenoidectomy, tonsillectomy, or nasal polyp removal. However several major surgical procedures were carried out in some patients (cholecystectomy, gastrectomy, repair of atrial septal defect, coronary bypass). All patients remained asymptomatic. In some cases whole blood and/or plasma were used as requested by the caring surgeons. In a few patients, the plasma was given prophylactically because of the long partial thromboplastin time. Finally, three patients (two for cardiac surgery and one after hip replacement) received heparin prophylaxis as foreseen by accepted procedures without the undue sequels. These data supply further evidence that factor XII deficiency does not only show any bleeding tendency but also can withstand even major surgical procedures without thrombotic complications.
Tissue Factor Pathway Inhibitor and Thrombin Activatable Fibrinolytic Inhibitor Plasma Levels following Burnand Septic Injuries in Rats
Authors: Ravindranath Thyyar M. , Goto Masakatsu , Demir Muzaffer , Tobu Mahmut , Kujawski M. Florian , Hoppensteadt D. , Samonte V. , Iqbal Omer , Sayeed M. M. , Fareed J.
Published: March 2006

Burn and septic injuries induce profound changes in coagulation status. This study examined the changes in plasma tissue factor pathway inhibitor (TFPI) and thrombin activatable fibrinolytic inhibitor (TAFI) levels in a rat model of burn and septic injuries. Rats underwent 30% TBSA cutaneous scald burn injury and septic insult was induced by caecal ligation and puncture (CLP). CLP was superimposed on burn injury to mimic the clinical model of sepsis complicating burn injury. Rats were pretreated with Cprofloxacin orally to colonize their gut with Enterococcus faecalis. TFPI and TAFI plasma levels were measured using functional activity assay kit with a chromogenic method at 24 and 72 hours following the injuries. TFPI levels decreased significantly at 24 hours in burn, CLP, and burn+CLP groups, followed by incomplete rebound recovery at 72 hours in all three groups. On the other hand, TAFI levels increased significantly at 24- and 72-hour time points in all three groups. These results suggest that burn, septic, and their combined injuries perturb coagulation cascade and thrombotic process toward the procoagulant pathway by impairing fibrinolysis.
Antiphospholipid Syndrome Associated with Malignant Mesothelioma Presenting with Superior Vena Cava Thrombosis: A Case Report
Authors: Ozkan Metin , Eser Bulent , Er Ozlem , Altuntas Fevzi , Coskun Ramazan , Topsakal Ramazan , Mavili Ertugrul , Kala Mehtap , Altinbas Mustafa
Published: March 2006

A 59-year-old woman who had dyspnea and neck swelling for 10 days was admitted to the hospital. Malignant peritoneal mesothelioma was diagnosed previously. According to the clinical findings, and laboratory and pathologic examination, the patient was found to have disseminated venous thrombosis and antiphos pholipid syndrome, which is treatment-resistant autoimmune paraneoplastic syndrome.
Bleeding and Other Presentations in Thai Patients with Dengue Infection
Authors: Wiwanitkit Viroj
Published: March 2006

Dengue infection is a major public health problem, affecting the general population in Southeast Asia. Hematologic aberrations in dengue infection include atypical lymphocytosis, coagulopathy, and predominant thrombocytopenia. Bleeding and other presentations in 30 Thai patients with dengue infection during an endemic season (2003) are presented. A review of the clinical presentation of these patients was performed. All had fever as a chief complaint. The three most common complaints were fever (100%), vomiting (90%), and cough (90%), respectively. Concerning bleeding, only eight cases (26.6%) had signs of bleeding. Those manifestations included petechiae (seven cases, 23.3%) and melena (one case, 3.3%). Skin bleeding (petechiae) due to thrombocytopenia is the most common bleeding manifestation in dengue infection. However, physicians should not overlook bleeding from other less common sites such as the gastrointestinal tract and genitourinary tract.
The Importance of Platelet Counts in Dengue Infection: 35 Cases and Literature Review
Authors: Wiwanitkit Viroj
Published: March 2006

Dengue infection is a major vector-borne disease. The classical form of this infection has an incubation period of 5 to 8 days followed by fever, violent headache, and chills, with rash developing after 3 to 4 days. A summative report on the platelet count and its clinical correlation to duration of fever in 35 Thai children is presented. Most of the subjects visited to the physician with a complaint for fever. Most patients went to see the physician between the 3rd and the 5th day from the onset of fever. There is no significant correlation between platelet count and duration of fever (ANOVA test, p = 0.28). However, there is a trend of increase platelet count in the later days. In addition, an overview on the previous literatures on platelet count and dengue infection is presented.
Endothelial Injury Markers With High-dose IntravenousIron Therapy in Renal Failure
Authors: Borawski Jacek , Gozdzikiewicz Joanna , Abramowicz Pawel , Naumnik Beata , Mysliwiec Michal
Published: March 2006

Endothelial injury is prevalent in patients with chronic renal failure (CRF) and may be exacerbated by commonly used intravenous (IV) iron therapy. The effects of high-dose IV iron sucrose treatment (200 mg daily in 250 mL of 0.9% saline, administered over 1 hour, median treatment duration 5 days) on circulating endothelium and/or tissue injury markers such as hepatocyte growth factor, thrombomodulin, von Willebrand factor, and C-reactive protein levels were studied. The markers were determined in 24 anemic (mean hemoglobin 9.48 g/dL) pre-dialysis (median creatinine clearance 21.5 mL/min) patients with CRF and defined absolute and/or functional iron deficiency. The measurements were performed before iron administration and 24 hours after the last infusion. All the markers remained unchanged following the IV iron therapy (all p < 0.172); no thrombotic or other adverse effects were observed. In conclusion, the above high-dose IV iron sucrose supplementation does not cause evident endothelial or other tissue injury in patients with CRF, and is clinically safe.
Recurrent Miscarriage Syndrome and Infertility Due to Blood Coagulation Protein/Platelet Defects: A Review and Update
Authors: Bick Rodger L. , Hoppensteadt Debra
Published: March 2006

Three-hundred fifty-one women were referred for thrombosis and hemostasis evaluation after suffering recurrent miscarriages. All patients were referred by a high-risk obstetrician or reproductive medicine specialist after anatomic, hormonal or chromosomal defects had been ruled out. These patients were assessed over a three year period. The mean patient age at referral was 34 years and the mean number of miscarriages was 2.9 (2-9). All patients underwent a thorough evaluation for thrombophilia and, when indicated, a hemorrhagic disorder. Of the 351 patients, 29 (8%) had no defect. Of the remaining 322 patients, 7 (2%) had a bleeding disorder: 3 with platelet dysfunction, 1 with Factor XIII deficiency, 3 with von Willebrand’s and 3 with Osler-Weber-Rendu. The remainder of the patients had a thrombophilia as follows: 195 (60%) had antiphospholipid syndrome, 64 (20%) had Sticky Platelet Syndrome, 38 (12%) had MTHFR mutation, 23 (7.1%) had PAI-1 polymorphism, 12 (3.7%) had Protein S deficiency, 12 (3.7%) had Factor V Leiden, 3 (1%), had AT deficiency, 3 (1%) had Heparin-Cofactor II deficiency, 3 (1%) had TPA deficiency, and 6 (2%) had Protein C deficiency. There were a total of 364 defects found in the 312 patients harboring thrombophilia; thus, several harbored two and a few harbored three separate defects. All patients with thrombophilia were treated with preconception ASA at 81 mg/day with the immediate post-conception addition of heparin or LMW heparin (Dalteparin). Both ASA and heparin/LMW heparin were used to term. The first 120 patients were treated with unfractionated heparin at 5,000 U every 24 hours, subcutaneously and the last 192 have been treated with Dalteparin at 5,000 U/day subcutaneously. The patients with MTHFR were also treated with folate at 5 mg/day + pyridoxine at 50 mg/day. All patients were carefully monitored with CBC and platelet counts, anti-Xa levels, frequent ultrasounds and physical exams. Only 2 of the thrombophilia patients suffered another miscarriage; all others had a normal term delivery. There were no pregnancy-related thromboses, no delivery complications and no episodes of post-partum thrombosis. The only bleeding consisted of 1-4 cm bruises at injection sites. No episodes of thrombocytopenia (HIT) were noted. In our experience, thrombophilia is a common cause of recurrent miscarriage and all patients with no anatomical, hormonal or chromosomal defect should be evaluated for thrombophilia or a bleeding disorder. The success rate of normal term delivery in these 312 patients was 94% using ASA + heparin or Dalteparin. In addition, side effects of therapy were minimal.
Myocardial Infarction and Arterial Thrombosis in Severe (Homozygous) FXII Deficiency: No Apparent Causative Relation
Authors: Girolami A. , Morello M. , Girolami B. , Lombardi A. M. , Bertolo C.
Published: March 2006

Twenty-one patients (12 female and 9 male) with severe (homozygous) factor XII (FXII) deficiency and 58 (32 female and 26 male) with heterozygous FXII deficiency were observed for an average 16.2 years. No patient with homozygous FXII deficiency experienced myocardial infarction or any other arterial thrombosis. The same was true for heterozygotes. The cases of FXII deficiency and arterial thrombosis reported in the literature were evaluated. In every instance, associated risk factors were present that could justify the arterial thrombosis. Dyslipidemia, hypertension, smoking, and diabetes mellitus were the most frequent findings. The examination of the few papers that dealt with the prevalence of arterial thrombosis in patients with severe FXII deficiency showed that only 1 patient of 61 experienced myocardial infarction. In conclusion, it seems that the role of FXII deficiency in the pathogenesis of arterial thrombosis is minor.
Plasminogen Activator Inhibitor 1 Activity and Other Coronary Risk Factors
Authors: von Eyben Finn Edler , Mouritsen Ejvind , Holm Jan , Montvilas Paulius , Dimcevski Georg , Suciu Gabriel , Rasmussen Inger Helleberg , Kristensen Lisbeth Langholz , von Eyben Rie
Published: March 2006

Because only some coronary risk factors have been evaluated for an association with plasma plasminogen activator inhibitor 1 (PAI-1) activity, this cross-sectional study examined the association between 27 coronary risk factors and PAI-1 in 24 healthy persons without coronary heart disease (control persons) and 22 patients who had survived myocardial infarction (cases). The coronary risk factors included major coronary risk factors such as age, anthropometric measures such as intraabdominal fat, and biochemical analytes such as serum concentration of triglyceride and plasma von Willebrand factor activity. The associations were analyzed in univariate and multiple linear regression analyses. For the control persons, triglyceride and von Willebrand factor were significantly associated with PAI-1 activity (p=0.0002, R2=0.55). In contrast for the 24 cases, age and intraabdominal adipose tissue were significantly associated with PAI-1 (p=0.0011, R2=0.51). Coronary risk factors explained more than half the variation of PAI-1 activity for both study groups. However, healthy persons and patients with previous myocardial infarction differed regarding coronary risk factors associated with PAI-1.
Factor V Leiden Mutation and Other Thrombophilia Markers in Childhood Ischemic Stroke
Authors: Duran Rıdvan , Biner Betül , Demir Muzaffer , Çeltik Coşkun , Karasalihoğlu Serap
Published: March 2006

The aim of this study was to evaluate the association between ischemic childhood stroke and thrombophilia. The prevalence of thrombophilia risk factors in 30 unrelated children with ischemic stroke were compared with 33 age-matched control subjects. Patients and control group were tested for the presence of activated protein C (APC) resistance, antiphospholipid antibodies (APLA), increased factor VIII levels, and for the deficiency of protein C (PC), protein S (PS), and antithrombin. When APCR was detected in patients or in controls, factor V Leiden (FVL) mutation was also tested. Seventeen of 30 patients (56.6%) had at least one thrombophilia marker compared with only 5 of 33 control subjects (15.1%). Three children with ischemic stroke (10%) were affected with a combination of two or more thrombophilia markers whereas none of the children in the control group had a combination of risk factors. Seven of 30 children with ischemic stroke (23.3%) and one of 33 control subjects (3.03%) had APC resistance and in all of them FVL mutation were found. The prevalence of FVL mutation was higher among pediatric stroke patients than among control subjects (p < 0.05). None of the patients but one child from the control group (3.03%) had PS deficiency. Antithrombin and PC deficiencies and the presence of APLA and increased factor VIII levels were more frequent in the pediatric stroke patients than in controls but the difference was not statistically significant (p > 0.05). These data confirm that stroke in children is commonly associated with a combination of multiple risk factors and especially the prevalence of FVL mutation is increased in children with ischemic stroke compared with control subjects.
Gene Frequencies of the Human Platelet Antigen-3in Different Populations
Authors: Wiwanitkit Viroj
Published: March 2006

Human platelet antigen (HPA) systems consist of more than 12 biallelic antigen polymorphisms in which a base pair substitution leads to change in an amino acid of a glycoprotein expressed on the platelet. HPA-3 is a HPA that is mentioned for possible induction of neonatal alloimmune thrombocytopenia, posttransfusion purpura, and platelet refractoriness. A summary is presented of previous reports on the gene frequencies of HPA-3 among different populations. The frequency of HPA-3a and -3b ranges from 0.50 to 0.61 and 0.38 to 0.50, respectively. A significant correlation between the population ethniticity and the gene frequencies was detected in this study. However, it is quite difficult to use HPA-3 gene as a gene marker to determine the similarity of gene population in different populations. In addition, the comparison of the heterogenicity of HPA-3 frequencies to another well-known HPA gene, HPA-1 gene demonstrates that there is a greater variation in HPA-3 frequencies than in the HPA-1 gene. There was no significant correlation between the incidence of autoimmune thrombocytopenia disorder and the HPA-3 gene polymorphism pattern.
Severe Thrombotic Microangiopathy Associated with Brucellosis: Successful Treatment with Plasmapheresis
Authors: Altuntas Fevzi , Eser Bülent , Sarı İsmail , Yildiz Orhan , Çetin Mustafa , Ünal Ali
Published: March 2006

Brucellosis is a disease that may lead to changes in hematologic parameters such as anemia, neutropenia, and thrombocytopenia; however, thrombotic microangiopathy (TMA) is a rare finding. Severe TMA may be associated with life-threatening hematologic, renal, and neurologic disorders. To prevent this mortality caused by brucellosis, prompt recognition of this complication and prompt therapy are essential. A patient with TMA associated with Brucella melitensis is presented who initially presented with fever, skin purpura, epistaxis, confusion, microangiopathic hemolytic anemia, and thrombocytopenia. TMA was treated with plasmapheresis with cryosupernatant plasma replacement, energetically. A rapid improvement in platelet count, lactate dehydrogenase level, hemolytic anemia, and neurologic symptoms was observed with this treatment. For cases with infection-induced thrombotic microangiopathy, short-term plasmapheresis may be applied as an urgent therapy in addition to antimicrobial therapy.
Endothelial Damage and Hemostatic Markers in Patients with Uncomplicated Mild-to-Moderate Hypertension and Relationship with Risk Factors
Authors: Arikan Ender , Sen Saniye
Published: March 2006

Endothelial damage, high fibrinogen levels, and platelet activity are the important accelerating factors for the development of hypertension (HT). von Willebrand factor (vWF; endothelial damage marker), fibrinogen levels, and platelet aggregability were compared between patients with uncomplicated, mild-to-moderate hypertension and healthy subjects. The relationship between traditional cardiovascular risk factors and endothelial damage and prothrombotic state was evaluated. One hundred sixty-nine (54 males, 115 females) patients with untreated and uncomplicated mild-to-moderate HT, and age, gender, and body mass index-matched 124 (58 males, 83 females) healthy subjects were enrolled in this study. Plasma vWF, fibrinogen levels, adenosine diphosphate-induced platelet aggregability, insulin, glucose, serum lipids, and uric acid were measured. Patients with HT had significantly increased fibrinogen, vWF, platelet number and aggregability induced by adenosine diphosphate, triglycerides, total/HDL-C, glucose, uric acid levels, and insulin resistance than control group. vWF and hemostatic markers were comparable between smoker and nonsmoker subjects. Platelet aggregability was positively related to systolic and diastolic blood pressure, and vWF. Fibrinogen was positively associated with body mass index (BMI), systolic and diastolic blood pressure, total cholesterol (TC), uric acid, vWF, and insulin resistance. vWF was significantly related to age, systolic blood pressure, TC, LDL-C, and total/HDL-C. Systolic blood pressure was independently related to vWF. vWF and diastolic blood pressure were significant predictors for adenosine diphosphate-induced platelet aggregability. Systolic blood pressure and vWF were independent predictors for fibrinogen levels. Uncomplicated mild-to-moderate HT had endothelial damage and is associated with a prothrombotic state. Traditional cardiovascular risk factors such as age, BMI, dyslipidemia, and insulin resistance are important contributors to the development of endothelial damage and a prothrombotic state. Therefore, it is important to control these cardiovascular risk factors along with proper treatment of HT for preventing target organ damage in mild-to-moderate HT.
Prognostic Impact of Aortic Calcification Index and Ankle-Arm Blood Pressure Indexin Patients under Hemodialysis
Authors: Kushiya Fumihiko , Wada Hideo , Sakakura Miho , Mori Yoshitaka , Gabazza Esteban C. , Nishikawa Masakatsu , Nobori Tsutomu , Noguchi Mitsuya , Izumi Kazuo , Nakasaki Takahiro , Takagi Mikio , Shiku Hiroshi
Published: March 2006

The mortality rate is high in patients receiving hemodialysis (HD), atherosclerotic diseases being the major cause of death. As marker of clinical outcome, a prospective examination of atherosclerotic tests and atherosclerotic risk factors in patients receiving HD was performed. On April 2000, 84 patients receiving HD were followed up until April 2002. At entry to the study, several atherosclerotic tests, including ankle-arm blood pressure index (API), aortic calcification index (ACI), and atherosclerotic risk factors, were performed. In 36 patients with old thrombotic events, 26 had new thrombotic events. Of 48 patients without previous thrombotic events, 15 had new thrombotic events. During 2 years, 41 patients had new thrombotic events and 15 patients died due to thrombotic disorders. The HD durations were significantly longer in non-survivors than survivors and the body mass index was lower in non-survivors than survivors. There was a significant difference in the values of ACI and API between survivors and non-survivors, and between patients with and without thrombotic events. These findings suggest that the ACI and API have a prognostic value because they might predict the occurrence of thrombosis.
The Increase of Blood Anticardiolipin Antibody Depends on the Underlying Etiology in Cerebral Ischemia
Authors: Chen Wei Hsi , Kao Yi-Fen , Lan Min-Yu , Chang Yung-Yee , Chen Shun-Sheng , Liu Jia-Shou
Published: March 2006

Although anticardiolipin antibody (aCL) has been suggested to be a potent risk factor for thrombosis and atherosclerosis in multiple arterial beds, conflicting results still exist between aCL and cerebral ischemia in the general stroke population. To elucidate if this discrepancy relates to the heterogeneity of underlying etiologies, blood beta2-glycoprotein I dependent-aCL was evaluated in 432 Taiwanese adults associated with cerebral ischemia who were classified into five subtypes according to their causes of cerebral ischemia. The results were compared with those in 100 healthy controls. A definite increase of aCL-IgG isotype was found in 41 patients (9.35%) and four controls (4.0%). The relative risk was 2.52. The frequency of increased aCL-IgG was 12.2%, 12.8%, 8.8%, 3.9%, and 3.5% in patients with large-artery atherosclerotic disease, stroke of unknown etiology, small-artery occlusive disease, cardioembolism, and stroke of other known etiology, respectively. Only patient with large-artery atherosclerotic disease (p<0.025) and stroke of unknown etiology (p<0.05) had a higher frequency of increased aCL than control. The frequencies of abnormal result of activated partial thromboplastin time, antinuclear factor, Coombs’ test, and venereal disease research laboratory were 2.84%, 1.22%, 1.02%, and 1.34% in these 41 patients, respectively. Accordingly, aCL-IgG selectively increases in patients with large-artery atherosclerosis and stroke of unknown etiology, reflecting selective activation of humoral immunity for aCL in the pathogenesis of cerebral ischemia.
Amaurosis Fugax: Associations with Heritable Thrombophilia
Authors: Glueck C. J. , Goldenberg Naila , Bell Howard , Golnik Karl , Wang Ping
Published: March 2006

The aim of this study was to prospectively assess associations between amaurosis fugax, inherited thrombophilia, and acquired thrombophilia. Thrombophilia and hypofibrinolysis were studied in 11 cases (eight women, three men; all white) with amaurosis fugax, 57 ± 17 years old, selected by the absence of abnormal brain magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), magnetic resonance venography (MRV), ipsilateral internal carotid artery plaque, atrial fibrillation, or cardiac thrombus. Cases were compared to 78 healthy adult white controls (53 ± 18 years old) for serologic measures, and by polymerase chain reaction to 248 healthy white controls (78 adults, 170 children) for gene mutations. All 11 cases had one or more familial thrombophilic coagulation disorder including one heterozygous for the G1691A factor V Leiden mutation, two with low free protein S, four with high factor VIII, three with resistance to activated protein C, three homozygous for the C677T methylenetetrahydrofolate reductase (MTHFR) mutation, two compound C677T-A1298C MTHFR heterozygotes, and three with hypofibrinolytic 4G4G homozygosity for the PAI-1 gene. The case with factor VIII of 160% had two other thrombophilias (compound MTHFR C677T-A1298C heterozygosity, resistance to activated protein C), and hypofibrinolytic high Lp(a). Thrombophilic C677T MTHFR homozygosity or compound C677T-A1298C heterozygosity was present in five of 10 (50%) cases vs. 30 of 248 (12%) controls, Fisher’s p (pf) = .005. Thrombophilic factor VIII was high in four of 10 (40%) cases vs. 0 of 38 controls, pf = .001. Thrombophilic hyperestrogenemia in five of the eight women (four exogenous estrogen, one pregnant) may have interacted with inherited thrombophilia-hypofibrinolysis, promoting thrombus formation. In cases selected by the absence of abnormal brain magnetic resonance imaging, significant ipsilateral internal carotid artery plaque, atrial fibrillation, or cardiac thrombus, we speculate that amaurosis fugax can be caused by reversible (by anticoagulation) retinal artery thrombi associated with heritable thrombophilia and/or hypofibrinolysis, often augmented by estrogen-driven acquired thrombophilia.
Usefulness of Measurement of Reticulated Platelets for Diagnosis of Idiopathic Thrombocytopenic Purpura
Authors: Sakakura Miho , Wada Hideo , Abe Yasunori , Nishioka Junji , Tomatsu Hiroaki , Hamaguchi Yukio , Oguni Shinichiro , Shiku Hiroshi , Nobori Tsutomu
Published: March 2006

Reticulated platelets (RP) and large platelets (LP) were measured by an automated hematology analyzer (modified R-2000) in 287 healthy volunteers and 131 patients with thrombocytopenia or thrombocytosis. RP was significantly higher in patients with idiopathic thrombocytopenic purpura (ITP), especially in active phase, while RP was markedly lower in patients with essential thrombocytosis (ET) or chronic myelocytic leukemia (CML). LP was significantly higher in patients with ITP, especially in active phase, while LP was markedly lower in patients with aplastic anemia (AA), ET, or CML. In ITP, RP and LP were significantly higher in patients positive for anti-glycoprotein (Gp) IIb/IIIa antibody. RP and LP were poorly correlated with platelet-associated IgG (PAIgG). RP and LP were poorly correlated with plasma thrombopoietin levels, and negatively correlated with platelet count. These results show that RP reflects the pathology of thrombocytopenic disorders, and that measurement of RP is useful for the differential diagnosis and analysis of platelet kinetics.
Functional Determination of Plasminin Arginine-stabilized Plasma
Authors: Stief T. W. , Richter A. , Bünder R. , Maisch B. , Renz H.
Published: March 2006

Reliable data on plasmin activities in blood of patients during fibrinolytic treatment are lacking. This is due to continuing plasminogen activation by plasminogen activators after blood withdrawal. The purpose of this study was to establish a new method for stabilization of blood and to detect plasmin activity in stabilized plasma. For optimization of plasma stabilization by arginine, 50 μL pooled normal citrated plasma was incubated with 50 μL of 0 to 1500 m M arginine, pH 8.7, and 25 μL 100 IU/mL u-PA, 1250 IU/mL t-PA, 10000 U/mL reteplase, 400 U/mL plasminogen-streptokinase-activator complex, 10 μg/mL tenecteplase in 6% BSA-PBS or 25 μL 25 μg/mL plasmin in 20% glycerol. Twenty-five microliters 3 m M HDVal-Leu-Lys-pNA were added immediately (1 step) or after 90 minutes (room temperature [RT]). The same experiment was performed with pooled normal citrated plasma supplemented with 3.2 mg/mL EDTA, preoxidized with 0 m M or 20 m M chloramine-T for 10 minutes (37°C). For optimization of plasmin activity, the oxidation time of the arginine-stabilized plasma sample containing 0.5 U/mL active plasmin and the chloramine-T amount was varied. Citrated plasma is stabilized against the in vitro action of all six plasminogen activators tested if the final arginine concentration is greater than 500 mM. Neither the addition of EDTA nor the addition of chloramine-T changes this plasma-stabilizing power of arginine. The optimized functional plasmin assay consists of incubation of 10 μL arginine-stabilized plasma with 10 μL 1.5 M arginine, pH 8.7, and 10 μL 100 m MCT in PBS. After 30 minutes (37°C), 75 μL 1.2 M KCl, 1.6 M Arg, 0.75 m M Val-Leu-Lys-pNA (Stop-CS Reagent), and 175 μL 6% BSAPBS are added and the absorbance increase (ΔA) at 405 nm is determined. With the present arginine stabilization procedure of plasma and the determination of plasmin activity in arginine-stabilized plasma as described, it is feasible to determine the activity of plasmin in blood of patients receiving fibrinolytic treatment without artefactual in vitro changes in the samples.
Spectrum of Inherited Bleeding Disorders in Indians
Authors: Gupta Meenal , Bhattacharyya Maitreyee , Choudhry V. P. , Saxena Renu
Published: March 2006

The incidence of hereditary hemorrhagic disorders may vary according to the country and ethnic origin. Von Willebrand disease has emerged as the most common hereditary hemorrhagic disease in the industrialized world. In this series of 966 patients diagnosed to have inherited bleeding disorders, hemophilia A was the most common and was seen in 410 (42.4%) of the patients followed by platelet function defects seen in 380 (39.4%) of the patients. It is thus concluded that, similar to the white population, hemophilia A remains the most common bleeding disorder in the Indian population, although this is closely followed by platelet function defects in India, which are quite rare in whites. Von Willebrand disease is relatively rare in the Indian population.
Severe Hemophilia and Physiologic Inhibitors of Coagulation
Authors: Kubisz Peter , Staško Ján , Dobrotová Miroslava , Ivanková Jela , Meško Dušan
Published: March 2006

Patients with hemophilia demonstrate quite variable clinical phenotype even in cases with the same level of deficient factor or the same molecular abnormality. Different interacting factors including congenital and acquired alterations of coagulation inhibitors can modulate both clinical expression and severity of hemophilia. In this study, plasma levels of factor VIII (FVIII), factor IX (FIX) as well as protein C (PC), protein S (PS), and antithrombin (AT) plasma levels were measured in 80 patients with severe hemophilia A and B. Patients were divided into two groups according to the risk of bleeding: the first group (n = 32) with mild bleeding (< 2 bleeds/year), and the second group (n = 48) with severe bleeding (≥ 2 bleeds/year). Both hemophilia groups showed significantly decreased PC plasma levels compared to levels in healthy control subjects (the first group: p < 0.0001 and second group: p < 0.01). The difference in PC plasma levels between the first and second hemophilia group was significant (p < 0.05). Moreover, there was positive correlation between age and the functional PC in both hemophilia groups. Our results suggest that decreased PC plasma levels can testify to a slightly protective effect of the PC pathway on the severity and frequency of bleeding in patients with severe hemophilia A and B.
Factor V Leiden Mutation in Cerebrovascular Disease
Authors: Buyru Nur , Altinisik Julide , Somay Goksel , Ulutin Turgut
Published: March 2006

Several studies indicate a high prevalence of factor V Leiden mutation as the most frequent coagulation defect found in patients with venous thrombosis. The relationship between this mutation and cerebrovascular disease has not been established in adults. In this investigation, we studied 29 patients with ischemic stroke and 20 with intracerebral hemorrhage, all of whom were compared with 20 controls. A region of the factor V gene containing the Leiden mutation site was amplified with polymerase chain reaction and the presence of mutation was determined with restriction enzyme digestion. We found no evidence of an association between factor V Leiden mutation and ischemic stroke or intracerebral hemorrhage. There was no evidence of association in subgroup the analysis by age, smoking status, myocardial infarction, hypertension, diabetes mellitus, or coronary disease. Factor V Leiden mutation doesn’t seem to be associated with a risk of cerebrovascular disease.
Elevated Plasma Levels of Fibrin Degradation Productsby Granulocyte-Derived Elastase in Patients with Disseminated Intravascular Coagulation
Authors: Matsumoto Takeshi , Wada Hideo , Nobori Tsutomu , Nakatani Kaname , Onishi Katsuya , Nishikawa Masakatsu , Shiku Hiroshi , Kazahaya Yumiko , Sawai Tokio , Koike Kaoru , Matsuda Michio
Published: March 2006

Plasma levels of granulocyte-derived elastase (GE-XDP), D-dimer, and soluble fibrin (SF) were examined in 177 patients with disseminated intravascular coagulation (DIC) of various etiologies. Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in patients with sepsis and solid cancer. The ratio of GE-XDP/D-dimer was significantly high in patients with trauma, burn, and sepsis, suggesting that fibrinolysis due to GE-XDP may be dominant in DIC. Plasma levels of GE-XDP and D-dimer, but not SF, were significantly high in patients with overt DIC and correlated with DIC score. Plasma levels of GE-XDP, but not SF, correlated significantly with D-dimer. Plasma levels of D-dimer, but not SF, correlated significantly with plasmin plasmin inhibitor complex (PPIC). Plasma levels of GEXDP and D-dimer, but not SF, were significantly high in nonsurvivors. Plasma levels of GE-XDP, but not SF, correlated significantly with sepsis-related organ failure assessment (SOFA) score. These results suggest that GE-XDP is a potentially useful marker for the diagnosis of overt-DIC and as a predictor of organ failure-related outcome.
Increased Tyrosine Phosphorylation of Platelet Proteins Including pp125FAK Suggests Endogenous Activation and Aggregation in Pulmonary Hypertension
Authors: Maeda Nair Y. , Bydlowski Sergio P. , Lopes Antonio A.
Published: March 2006

Despite of several lines of evidence indicating a pathophysiologic role of platelets in pulmonary hypertension, the occurrence of chronic endogenous platelet activation has been a matter of debate. It was hypothesized that the pattern of tyrosine phosphorylation of platelet proteins examined ex vivo could provide information on the state of platelet activation. This was examined in 10 patients with pulmonary arterial hypertension aged 18 to 53 years. Phosphotyrosine density and the amounts of specific proteins were analyzed in resting platelets after reaction with anti-phosphotyrosine, anti-pp60c-src, anti-pp125FAK, and anti-αIIbβ3 antibodies. There was a 79% increase in protein-associated phosphotyrosine in patients in comparison to levels in controls (p<0.05). In particular, phosphorylation on tyrosine residues of pp120 and pp125FAK increased 24% and 57%, respectively (p<0.05). Although pp60c-src-associated phosphotyrosine was not altered in the patient group as a whole, it was clearly decreased in three subjects. Platelet content of β3 integrin, pp60c-src, and pp125FAK, was not altered. This pattern of phosphorylation suggests an ongoing process of platelet activation. Because phosphorylation of pp125FAK is a late, integrin-dependent event, results suggest that platelet activation and aggregation occur in vivo in these patients.
Significance of αIIbβ3 in Subacute Stent ThrombosisAfter Percutaneous Coronary Intervention
Authors: Inami Norihito , Nomura Shosaku , Kajiura Takayuki , Yamada Kohichi , Nakamori Hisato , Takahashi Nobuyuki , Tsuda Nobuyuki , Fukuhara Shirou , Iwasaka Toshiji
Published: March 2006

Soluble P-selectin and whole blood aggregation (WBA) were measured after percutaneous coronary intervention in patients who then received antiplatelet therapy. One had subacute thrombosis on day 7. This patient’s WBA exhibited time-dependent enhancement. In addition, the accentuation of WBA on day 3 was observed when anti-αIIbβ3 antibody was added. The remaining 22 patients were divided according to WBA results on day 3 with anti-αIIbβ3 antibody added (A group, WBA enhanced; B group, WBA did not enhance). WBA on day 3 was similar in the two groups. The ratio of WBA with and without anti-αIIbβ3 antibody was higher in group A than in group B. A significant time-dependent increase of soluble P-selectin was observed in the A group. These results suggest that enhancement of WBA with anti-αIIbβ3 antibody after percutaneous coronary intervention predicts subacute thrombosis.