bluuebunny/crossref_metadata_2025 huggingface dataset:
Facilitated Thrombolysis: Dethrombosis?
Authors: Luciardi Héctor , Berman Sofía , Muntaner Juan , De La Serna Fernando , Altman Raúl
Published: June 2007

Intracoronary thrombus formation results from the combined effects of platelet aggregation and fibrin formation. Fibrinogen plays a significant role in each of these components. Dethrombosis is a therapeutic approach that allows dissolution of a recent thrombus while avoiding the potent fibrinolytic therapies. The less aggressive strategies suggested to achieve dethrombosis are antifibrin, antiplatelet, and defibrinogenation. Glycoprotein receptor antagonists have been beneficial in patients undergoing percutaneous transluminal coronary angioplasty; however, little is known about their potency of inducing reperfusion in acute myocardial infarction. Early use of the strategies suggested to induce dethrombosis (antifibrin, antiplatelet, and defibrinogenation) may facilitate fibrinolysis and primary angioplasty and further induce reperfusion. Nevertheless, the theoretical arguments of facilitated thrombolysis (dethrombosis) have not yet been fruitful as a major clinical benefit except in patients undergoing primary percutaneous coronary intervention.
Postprandial Lipemia is Associated With Platelet and Monocyte Activation and Increased Monocyte Cytokine Expression in Normolipemic Men
Authors: Hyson Dianne A. , Paglieroni Teresa G. , Wun Theodore , Rutledge John C.
Published: June 2007

The activation of platelets and monocytes has been implicated in the development of cardiovascular diseases. We asked the question if postprandial lipemia following a fatcontaining meal is associated with platelet and monocyte activation and increased platelet-monocyte interaction. Thirteen healthy, normal weight, normolipemic males, 20 to 49 years, consumed a 40% fat meal of whole foods. Blood samples were obtained at fasting and 3½ and 6 hours after ingestion. Triglyceride levels increased to 48% over baseline at 3½ hours postconsumption and returned to fasting levels by 6 hours. Multiparameter flow cytometry using monoclonal antibodies showed that the percentage of platelets expressing surface P-selectin and the activated conformation the GPIIb-IIIa receptor was significantly higher at 3½ hours compared to fasting. The percentage of platelet-monocyte aggregates increased by 36% at 3½ hours and 43% at 6 hours postconsumption. The percentage of monocytes expressing intracellular tumor necrosis factor-tx (TNF-ax) increased seven and eightfold at 3½ and 6 hours, respectively. The expression of interleukin-l,B (IL-1p increased in a similar manner. These data suggest activation of platelets and monocytes after a moderate fat meal. Repetitive activation of platelets and monocytes could be an early event in the initiation and development of atherosclerosis.
MIXCON-LA: A Precise, Sensitive and Specific aPTT-Based Assay for Detection of Lupus Anticoagulant
Authors: Lindhoff-Last Edelgard , Humpich Marek , Schmitt Jörn , Rödiger Sabine , Seifried Erhard , Bauersachs Rupert
Published: June 2007

Lupus anticoagulants (LA) are associated with an increased risk of thrombosis and laboratory detection is of major importance. Multiple tests are available for screening and confirmation, but they differ in sensitivity and specificity, frequently lacking the ability to discriminate between the presence of LA, heparin, and oral anticoagulants. Based on the test-principle of the Lupus Ratio-test, an automated, sensitive APTT-based assay, using mixtures of a lupussensitive and a lupusinsensitive APTT-reagent with normal plasma for detection of lupus anticoagulants was developed. Ninety-nine healthy volunteers, ten patients treated with unfractionated heparin intravenously, 19 patients taking stable oral anticoagulation, five patients with hemophilia A, and 15 patients with antiphospholipid-antibody-syndrome (APS) were investigated. In all patients, two APTTs were performed, one with each reagent, on 1:1 mixtures of test plasma and normal plasma (MIXCON-LA assay). The ratio between the two clotting times was divided by the corresponding ratio for the normal plasma. This final lupus ratio (LR) was used for evaluation. The within-series imprecision and the between-series imprecision were excellent with coefficients of variation between 1.5% and 1.9%. The mean Ñ2 SD of the LR of the 99 healthy volunteers was used as reference range (LR: 0.95-1.07). All patients treated either with heparin or oral anticoagulants remained negative in the MIXCON-LA assay (specificity, 100%), while one of five patients with hemophilia A, in whom a factor VIII-inhibitor developed, showed a false-positive result. In 13 of 15 patients with APS, an increased ratio was observed (sensitivity, 87%). This assay system allows precise, specific, and sensitive detection of lupus anticoagulants.
Thrombocytopenia in Patients Receiving Oral Anticoagulant Therapy
Authors: Sottilotta Gianluca , Oriana Vincenzo , Latella Caterina , Lombardo Vincenzo Trapani
Published: June 2007

The aim of this report was to determine the frequency of thrombocytopenia in a cohort of 1,126 patients receiving oral anti- coagulant therapy (OAT), and to compare the grade of thrombocy- topenia and the severity of bleeding complications. Severe thrombo- cytopenia was observed in five patients, and moderate and light thrombocytopenia were observed in 208 patients. Thrombocytopenic patients receiving OAT presented five major and six minor hemor- rhages. The presence of hepatitis markers and autoantibodies was assessed. All parameters at the time of the bleeding complication were in the therapeutic range.
Effects of Atorvastatin Treatment on sICAM-1 and Plasma Nitric Oxide Levels in Hypercholesterolemic Subjects
Authors: Sardo Maria A. , Castaldo Maria , Cinquegrani Maurizio , Bonaiuto Michele , Maesano Antonella , Versace Antonio , Spadaro Miriam , Campo Salvatore , Nicocia Giacomo , Altavilla Domenica , Saitta Antonino
Published: June 2007

This study investigated the behavior of soluble intercellular adhesion molecule-1 (sICAM-1) and serum nitric oxide (NO) products, nitrite/nitrate (NO 2-NO,-), in subjects with primary hypercholesterolemia (HCh) without other risk factors and atherosclerosis. The effect of a short-term cholesterol-lowering treatment with atorvastatin, an HMG-CoA reductase inhibitor, on the levels of sICAM-1 and NO2-/NO3 were also investigated. After 4 weeks of placebo administration, 40 HCh (15 males and 25 females) were randomized in 2 groups: 20 subjects (atorvastatin group) received 10 mg/day of atorvastatin and the remaining 20 (placebo group) continued to take placebo. At baseline and after 4 and 12 weeks of atorvastatin or placebo administration, serum sICAM-1 and NO2-/NO3-levels were evaluated. The basal levels of these parameters were compared with those of 20 healthy subjects (C), matched for sex and age. Hypercholesterolemic subjects showed sICAM-1 and NO2-/NO3-basal values that were higher (331.7 ± 60.3 ng/mL vs. 202.3 ± 32.3 ng/mL, p<0.001) and lower (10.4 ± 2.5 μmol/L vs. 20.7 ± 4.4 μmol/L, p<0.01) than controls. No correlation between sICAM-1 or NO products and plasma cholesterol values was found, whereas there was an inverse correlation between sICAM-1 and NO2-/NO3-levels. Atorvastatin administration significantly decreased sICAM-1 and increased NO2-/NO3-levels, however these changes were not correlated with the reduction of plasma cholesterol. These data support the hypothesize that patients with HCh with no signs of arterial lesions, may have latent atherosclerosis, expressed as an increase of sICAM-1 and decrease in NO product levels. An improvement in the levels of these parameters after a short-time treatment with atorvastatin was also demonstrated.
Plasma Levels of Heparin Cofactor II (HCII) and Thrombin-HCII Complex in Patients with Disseminated Intravascular Coagulation
Authors: Noda Ayako , Wada Hideo , Kusiya Fumihiko , Sakakura Miho , Onishi Katsuya , Nakatani Kaname , Gabazza Esteban C. , Asahara Naomi , Tsukada Minoru , Nobori Tsutomu , Shiku Hiroshi
Published: June 2007

Plasma levels of heparin cofactor II (HCII), thrombin-HCII complex (THC), antithrombin (AT), and thrombin-AT complex (TAT) were evaluated in patients with disseminated intravascular coagulation (DIC) associated with several underlying diseases. Plasma levels of AT were significantly reduced in almost all underlying diseases associated with DIC, but the plasma levels of HCII and HCII/AT ratio were significantly reduced only in patients with infections. While the plasma level of TAT was significantly increased in patients with all underlying diseases associated with DIC, the increase of THC was not significant. Plasma levels of AT were significantly reduced in DIC and pre-DIC associated with almost all underlying diseases, but those of HCII were significantly reduced only in DIC and pre-DIC patients with inflammatory diseases. The plasma levels of TAT were significantly increased in DIC, pre-DIC, and non-DIC patients with all underlying diseases, and those of THC were significantly increased in DIC and pre-DIC patients with inflammatory diseases. The plasma levels of THC were not significantly increased in non-DIC patients of any disease group. The decrease of AT may be caused by thrombin generation or inflammatory reaction that occurs in DIC associated with underlying diseases, while the decrease of HCII might be caused by both thrombin generation and inflammatory reaction. Finally, AT inhibits thrombin more strongly than HCII in several underlying diseases associated with DIC except for inflammatory diseases. In inflammatory diseases, HCII might play an important role in preventing the onset of DIC.
Endothelial Dysfunction Associated with Chronic Intravascular Coagulation in Secondary Pulmonary Hypertension
Authors: Lopes Antonio Augusto , Caramurú Lúcia Helena , Maeda Nair Yukie
Published: June 2007

Altered endothelial anti-thrombotic properties have been observed in primary and secondary pulmonary hypertension. In the Eisenmenger syndrome, correlations of these abnormalities with the clinical status and occurrence of chronic intravascular coagulation (CIC) have not been confirmed. The purpose of this study was to investigate whether the occurrence of CIC, as determined by circulating levels of D-dimer is associated with changes in endothelial markers in Eisenmenger patients; and to identify variables that correlate with the severity of clinical presentation. Twenty-one patients were enrolled (ages, 4-52 years). Plasma levels of D-dimer, tissue plasminogen activator (t-PA), thrombomodulin, and von Willebrand factor antigen (vWF:Ag) were measured with enzyme-linked immunosorbent assay. Univariate and multivariate analyses were used to differentiate patients with stable (group 1, N= 12) from those with unstable disease (group 2, N=9). Increased t-PA (p<0.0001) and vWF:Ag (p=0.001) and decreased thrombomodulin (p<0.0001) were associated with increased D-dimer levels (p=0.0201) in patients. Group 2 had a higher prevalence of affected women (p=0.0242), lower arterial oxygen saturation, and higher t-PA levels compared with group 1 (p<O.OOOl, discriminant analysis). t-PA and vWF:Ag correlated positively in group 2 (r=0.71, p=0.0309), but not in group 1 (r=0.25, p=NS). Two patients in group 2 but none in group 1 had episodes of pulmonary arterial thrombosis. Endothelial dysfunction is associated with evidence of CIC and correlates to some extent with the severity of symptoms in these patients.
The Effect of Plasma Depletion of Platelet Concentrates on Platelet Aggregation and Phosphatidylserine Expression
Authors: Zilber Moshe , Friedman Ziva , Shapiro Hava , Shapira Shirley , Radnay Judith , Ellis Martin H.
Published: June 2007

Plasma-reduced platelet concentrates are commonly administered to prevent febrile transfusion reactions and to avoid fluid overload in neonates. Because little is known about the influence of centrifugation and resuspension on functional aspects of platelets, we examined the effects of plasma-reduction on platelet aggregation and platelet-dependent thrombin generation. Our results show that plasma reduction and resuspension of the platelet pellet in saline or plasma results in a significant reduction in platelet aggregation to a combination of the platelet agonists adenosine diphosphate and epinephrine (p < 0.001). In contrast, when a combination of the more potent agonists collagen and thrombin was used, platelet aggregation was maintained. Likewise, no decline was observed in plateletdependent thrombin generation as measured by the functional prothrombinase assay or Annexin V binding. We conclude that centrifugation and resuspension of platelets to render the concentrate plasma-free, as a routine procedure in blood banking, variably affects in vitro platelet aggregability but does not significantly affect plateletdependent thrombin generation.
Thromboembolic Disease and Present Oral Contraception
Authors: Belicová Margita , Lukáč Bohdan , Dvorský Ján , Peter Galajda , Mokáň Marián , Kubisz Peter
Published: June 2007

Since their introduction, oral contraceptives have been linked to an increased incidence of thromboembolic events. Epidemiologic studies have shown that women who use third-generation oral contraceptives containing desogestrel, gestodene, or norgestimate have a higher risk of venous thrombosis than women who use second-generation oral contraceptives containing levonorgestrel. Women who use oral contraceptives are significantly less sensitive to activated protein C. From January 1996 to December 2001, 17,577 patients were hospitalized in our department, 177 of them (1%) had confirmed diagnosis of venous thromboembolism and 15 of those (177) were women on oral contraceptive therapy. Oral contraceptives were taken from 28 days to 18 months. No other potential congenital or acquired causes of thrombosis were present before thromboembolic events occurred in these women. The discontinuation of the pill combined with usual heparin (in one patient thrombolysis) and coumarin therapy was effective in all cases. After the discontinuation of coumarin (3-6 months), every patient was screened for hereditary thrombophilia. All women on oral contraceptive therapy had confirmed hereditary risk factors for venous thrombosis. Acquired resistance to activated protein C may explain the epidemiologic observation of increased risk of venous thrombosis in oral contraceptive users, especially in women using third-generation oral contraceptives who had other risk factors (hereditary or acquired) for venous thrombosis.
Atherosclerotic and Hemostatic Abnormalities in Patients Undergoing Hemodialysis
Authors: Kushiya Fumihiko , Wada Hideo , Sakakura Miho , Mori Yoshitaka , Gabazza Esteban C. , Nishikawa Masakatsu , Nobori Tsutomu , Noguchi Mitsuya , Izumi Kazuo , Shiku Hirosi
Published: June 2007

Vascular events caused by atherosclerosis are the major cause of death in patients undergoing hemodialysis (HD). The relationship between the tests of atherosclerosis and hemostasis in 84 patients with HD was examined. Abnormal test results indicating the occurrence of atherosclerosis were found in 66% by the Fontaine score, in 33% by ankle blood pressures, and in 79% by aortic calcification index (ACI). When HD was prolonged, the mean Fontaine score and ACI were further increased. Particularly, the ACI tended to correlate with HD duration. The ankle-brachial index (ABI) was decreased in patients with HD duration of more than 10 years. Before HD, the plasma levels of fibrinogen, plasmin-plasmin inhibitor complex (PIC), thrombomodulin (TM), and D-dimer were increased, while the plasma levels of protein C (PC), antithrombin (AT), thrombin-antithrombin complex (TAT), and tissue plasminogen activator (tPA)-plasminogen activator inhibitor-I (PAI-I) complex (tPA-PAI-1 complex) were decreased. With prolonged HD, the plasma levels of AT and PC were decreased, while those of D-dimer were increased. The plasma levels of TAT and TPA-PAI-1 complex were significantly increased and those of PIC, soluble fibrin (SF) and D-dimer tended to be high in patients with less than 0.7 of ABI. The plasma levels of Ddimer, TPA-PAI-1 complex, TAT, PIC, and SF tended to be high in patients with more than 0.5 in ABI. These findings suggest that patients undergoing HD have progressive atherosclerosis and that this is associated with some hemostatic abnormalities.
Influence of the Alu-Repeat I/D Polymorphism in t-PA Gene Intron 8 on the Stimulated t-PA Release After Venous Occlusion
Authors: Sartori Maria Teresa , Saggiorato Graziella , Spiezia Luca , Varvarikis Costantino , Carraro Gianni , Patrassi Giovanni Maurizio , Girolami Antonio
Published: June 2007

Tissue type plasminogen activator (t-PA) is released from endothelium in both a constitutive and regulated fashion. In healthy subjects, an association between net t-PA release rate and a few t-PA gene polymorphisms, including the Alu-repeat I/D polymorphism in intron 8, was described. The possible influence of the Alu-repeat polymorphism on t-PA release was evaluated after a venous occlusion test (VO) in 82 patients showing an impaired fibrinolytic capacity associated with different arterial disease or with previous venous thrombosis, and in 50 healthy controls. Euglobulin lysis time, t-PA antigen (t-PA:Ag) and activity, PAI-1 antigen and activity plasma levels were assayed before and 20 minutes after VO; the Alurepeat I/D polymorphism was determined by PCR. Defective fibrinolysis was due to reduced t-PA release in 40 patients (t-PA group) and to PAI-1 excess in 42 patients (PAI group). No differences in both genotype distribution and allele frequencies were observed between patients and controls. The t-PA:Ag increase after VO (20/0-minute levels ratio adjusted for hematocrit) was considerably higher both in controls and in PAI group patients carrying the I allele than in the DD genotype carriers (II, ID, DD: 3.77∓0.62, 3.43∓0.44, 2.06∓0.32 in controls, and 3.67∓0.23, 2.80∓0.50, 1.62∓0.29 in PAI group, respectively). The difference was significant between the DD and both the ID and II genotypes in controls (p<0.05), and between the DD and II genotypes in PAI-I group (p<0.05). A slight and nonsignificant trend of association between genotype and t-PA:Ag 20/0 ratio was seen in the t-PA group patients. In conclusion, these data suggest a possible genetic modulation of t-PA-regulated secretion.
Effects of PEG-Hirudin in Clotting Parameters and Platelet Function and its Interaction with Aspirin in Healthy Volunteers
Authors: Esslinger Hans-Ulrich , Köhne Stephan , Radziwon Piotr , Walenga Jeanine M. , Breddin Hans Klaus
Published: June 2007

The purpose of this study was to investigate the pharmacodynamics of PEG-Hirudin and its potential interactions with acetylsalicylic acid (ASA 325 mg once daily from days 1-3). In a randomized, 2-way cross-over trial, 6 healthy volunteers received PEG-Hirudin (IV bolus of 0.2 mg/kg + 0.02 mg/kg/h for 24 hours) and placebo (IV bolus + 24-hour infusion). In a further randomized, 3way cross-over trial another 9 healthy volunteers received ASA (325 mg) or oral placebo from days 1 to 3 and PEG-Hirudin (0.2 mg/kg + 0.02 mg/kg/h for 24 h) or IV placebo on day 3. Assessments included bleeding time (BT), collagen (1 μg ml-1)-induced platelet aggregation (CIPA), platelet adhesion, ecarin clotting time (ECT), activated clotting time (ACT), plasma anti-factor Ila activity (aIla), and activated partial thromboplastin time (aPTT). Ten minutes after the PEG-Hirudin injection/starting the infusion, mean plasma concentration was 3.1 μg/mL and aPTT, ECT, and ACT were prolonged up to 80, 309, and 233 seconds, respectively. During the last 8 hours of the 24-hour infusion mean PEG-Hirudin plasma concentration was 1.3 μg/mL. In the interaction study, ASA significantly inhibited CIPA. At 6 hours after administration, on day 3 mean BT was 6.5 minutes after PEG-Hirudin alone, 18.2 minutes after ASA alone, and 32.9 minutes after combined administration of ASA and PEG-Hirudin. PEG-Hirudin (0.2 mg/kg + 0.02 mg/kg/h for 24 hours) administered alone or together with 325 mg ASA proved to be safe in healthy volunteers. Combined use of PEG-Hirudin and ASA significantly increased the mean bleeding time compared to ASA or PEG-Hirudin monodrug administration. None of the clotting parameters or platelet function tests correlated with the prolongation of the bleeding time.
Flight Microangiopathy on Long-Haul Flights: Prevention of Edema and Microcirculation Alterations with Venoruton
Authors: Cesarone M. R. , Belcaro G. , Geroulakos G. , Griffin M. , Ricci A. , Brandolini R. , Pellegrini L. , Dugall M. , Ippolito E. , Candiani C. , Simeone E. , Errichi B. M. , Di Renzo A.
Published: June 2007

The aim of this study was the evaluation of the effects of Venoruton (HR) on the prevention and control of flight microangiopathy and edema in subjects with varicose veins flying for more than 7 hours. A group of 80 patients with varicose veins, edema, and initial skin alterations due to chronic venous hypertension were included. Measurements of skin laser Doppler (LDF) resting flux (RF), Po2 and rate of ankle swelling (RAS), were made before and after the flights (within 2 hours before the flights and within 2 hours after the flights). The length of the flights was between 7 and 9 hours; all seats were in coach class. The two groups (treatment and control) were comparable for age and sex distribution. The variation (decrease) in PO2 was significant in both groups. In subjects treated with HR the decrease in Po2 was smaller (p<0.05). The decrease in LDF-RF was significant in both groups with a higher flux at the end of the flight in the treated subjects (p<0.05). The venoarteriolar response was decreased at the end of the flights. The decrease was less evident in the treatment group (p<0.05). The increase in RAS was significant in the control group while it was limited in the HR group. In conclusion, HR is useful for reducing the increased capillary filtration and in controlling edema in patients with chronic venous disease in long-haul flights. HR is effective to control flight microangiopathy associated with edema.
The Prevalence of Protein C, Protein S, and Antithrombin III Deficiency in non-APS/SLE Chinese Adults with Noncardiac Cerebral Ischemia
Authors: Chen Wei-Hsi , Lan Min-Yu , Chang Yung-Yee , Chen Shun-Sheng , Liu Jia-Shou
Published: June 2007

Protein C (PC), protein S (PS), and antithrombin III (AT-III) are vital thrombin antagonists in circulation. However, the prevalence of these natural inhibitors for cerebral ischemia is barely mentioned in the Chinese population. The prevalence of PC, PS, and AT-III deficiency in Chinese adults with cerebral ischemia is reported. The study subjects were free of antiphospholipid antibody syndrome or systemic lupus erythrematosus. Cardiac, liver, and renal function were normal. An overall rate of thrombophilia was 27%. PS deficiency was the most common disorder, followed by PC with PS and PC deficiency. There was only one patient with AT-Ill deficiency. No gender was specific for thrombophilia. However, PS deficiency was predilected in young adults. A positive correlation between PC and AT-III was achieved in patients with a normal PC activity but not PC deficiency. There was no correlation between AT-III or PS. The odds ratios of PC and PS were 5.29 and 2.86, respectively. Accordingly, an inability for thrombin antagonization by the PC/PS axis may relate to the occurrence of cerebral ischemia in the Chinese population. AT-III seems to display a minor role only.
Platelets as Predictors of Vascular Risk: Is There a Practical Index of Platelet Activity?
Authors: Tsiara Stavroula , Elisaf Moses , Jagroop I. Anita , Mikhailidis Dimitri P.
Published: June 2007

Activated platelets play a role in the pathogenesis of coronary heart disease (CHD). Following activation, platelets change shape, aggregate, and release several bioactive substances. The aim of this review is to identify if there is a simple and cost-effective method that indicates platelet activation and predicts the risk of CHD and vascular events. The rationale for identifying high-risk patients is to reduce their risk of vascular events by administering appropriate and effective antiplatelet treatment, like aspirin, clopidogrel, or combination regimens. Many laboratory tests estimating platelet activity have been described. Some are relatively simple, such as spontaneous or agonist-induced platelet aggregation. Other tests include measuring the mean platelet volume (MPV) or plasma soluble P-selectin levels. Some more complex tests include flow cytometry to determine platelet GP Ilb/Illa receptors, platelet surface P-selectin, plateletmonocyte aggregates, and microparticles. Only few prospective studies assessed the predictive value of platelet activation in healthy individuals. Although the MPV seems an 'easy method, there are insufficient data supporting its ability to predict the risk of a vascular event in healthy adults. Platelet aggregation, in whole blood or in platelet-rich plasma was not consistently predictive of vascular risk. Soluble P-selectin measurement is a promising method but it needs further evaluation. Flow cytometry methods are costly, time-consuming, and need specialized equipment. Thus, they are unlikely to be useful in estimating the risk in large numbers of patients. There is as yet no ideal test for the detection of platelet activation. Each currently available test has merits and disadvantages. Simple methods such as the MPV and the determination of platelet release products need further evaluation.
Prevention of Venous Thrombosis with Elastic Stockings During Long-Haul Flights: The LONFLIT 5 JAP Study
Authors: Belcaro G. , Cesarone M. R. , Nicolaides A. N. , Ricci A. , Geroulakos G. , Shah S. S. G. , Ippolito E. , Myers K. A. , Bavera P. , Dugall M. , Moia M. , Di Renzo A. , Errichi B. M. , Brandolini R. , Dugall M. , Griffin M. , Ruffini I. , Ricci A. , Acerbi G.
Published: June 2007

The aim of this study was to evaluate deep venous thrombosis (DVT) prophylaxis with specific elastic stockings in longhaul flights (11-13 hours), in high-risk subjects. A group of 300 subjects was included; 76 were excluded for several problems including concomitant treatments; 224 were randomized into two groups (stockings vs. controls) to evaluate prophylaxis with below-knee stockings. An exercise program was used in both groups. Scholl (UK) Flight Socks (14-17 mmHg of pressure at the ankle) were used. DVT was diagnosed with ultrasound scanning. The femoral, popliteal, and tibial veins were scanned before and within 90 minutes after the flights. Of the 205 included subjects, 102 controls and 103 treated subjects completed the study. Drop-outs were due to flight connection problems. Age, gender, and risk distributions were comparable in the two groups. In the treatment group (103 subjects; mean age, 42; SD 9; M:F, 55:48), one limited, distal DVT was observed (0.97%). In the control group (102 subjects; mean age, 42.1; SD 10.3; M:F, 56:46), six subjects (5.8%) had a DVT. There were no superficial thromboses. The difference in DVT incidence is significant (p<0.0025; six times greater in the control group). Intention-to-treat analysis counts 18 failures in the control group (12 lost to follow-up + six thromboses) of 112 subjects (15.8%) versus eight failures (7.3%) in the treatment group (p<0.05). The tolerability of the stockings was very good and there were no complaints or side effects. All events were asymptomatic. Considering these observations, Scholl Flight Socks are effective in reducing the incidence of DVT in high-risk subjects.
In vitro Simulation of Therapeutic Plasmatic Fibrinolysis
Authors: Stief T. W. , Buinder R. , Richter A. , Maisch B. , Renz H. , Fareed J.
Published: June 2007

One type of therapy for thromboembolism is plasmatic thrombolysis. Several plasminogen activators (PA) are clinically available, including urokinase (u-PA), tissue plasminogen activator (t-PA), streptokinase (SK), plasminogen-streptokinase-activator-complex (PSAC), or mutants of t-PA such as reteplase (RP) or tenecteplase (TP). Therapeutic plasmatic fibrinolysis was simulated, using the PA at relevant plasma concentrations, and plasmin (Pli) and PA activities were determined. Normal citrated plasma was supplemented with 31 to 1,000 IU/mL u-PA, 0.31 to 20 μg/mL t-PA, 125 to 4,000 IU/mL SK, 12.5 to 400 U/mL PSAC, 125 to 4,000 U/mL RP, or 0.31 to 10,μg/mL TP. Ten IU/mL urokinase was also incubated with pooled plasma of stroke patients, that was previously oxidized with the singlet oxygen (1O2) donor chloramine T® (CT), to destroy plasmatic PAI-1 and a2-antiplasmin. After 0 to 80 minutes (37°C), 50-μL samples were withdrawn and added to 100 μL 1.5 M arginine, pH 8.7, and oxidized with 50 μL of 20 mM CT. For determination of plasmin activity, 10 μL thereof was incubated with 150 μL 1.5 M arginine, pH 8.7, and 100 μL 20 mM CT preoxidized (15 minutes 37°C) pooled normal citrate buffered EDTA-plasma for 30 minutes (37°C). For determination of [PA+Pli]-activity, arginine was added after this incubation. 25-μL 6 mM Val-Leu-Lys-pNA were added and AA/h at room temperature (RT) was monitored, using a microtiterplate reader. [PA+Pli]-Pli = PA. The PA concentration required to induce 25% [ED25] of the maximally inducible Pli-activity in plasma (= 1 U/mL = 45 mg/L = 0.53 Amol/L active Pli; AA = 363 + 8 mA/h RT) after 10 minutes (37°C) were 320 IU/mL u-PA, 8 μg/mL t-PA, 140 U/mL PSAC, 6,000 IU/mL SK, 720 U/mL RP, and approximately 150 μg/mL TP. The approximate activity half-lives of the PA in plasma were 30 minutes for u-PA, 30 minutes for t-PA, greater than 80 minutes for SK, greater than 80 minutes for PSAC, 50 minutes for RP, and 80 minutes for TP. The present study shows-for the first time-a combined kinetic in vitro simulation of the plasmatic activity of six different PAs. At clinically used concentrations, RP induces the highest plasmatic Pli activity. Due to unselective generation of plasmin in plasma, all PA are of some danger in inducing severe hemorrhagias. Clinical thrombolysis might be improved by usage of more physiologic activators of thrombolysis, such as activators of polymorphonuclear neutrophils.
Detection of Factor V Leiden by PCR-SSCP using GMATM Precast Elchrom Scientific Gels
Authors: Simundic Ana-Maria , Topic Elizabeta , Stefanovic Mario
Published: June 2007

Genetic abnormalities in hemostatic proteins associated with hypercoagulability are an important hereditary risk factor for venous thrombosis. Several genetic mutations that cause hereditary disorders predisposing to thrombosis have been described, point mutation in the coagulation factor V gene (FV:R506Q), called factor V Leiden, being the most common of them. A new inexpensive and simple polymerase chain reaction-single-strand polymorphism (PCRSSCP) based method for detection of this genetic abnormality is reported. The study population consisted of 150 subjects whose factor V genotype was previously determined by PCR-RFLP method using the Mnl I restriction endonuclease. A 223-bp fragment containing the G1692-A (Arg 506-Gln) polymorphic site in exon 10 of the factor V gene was amplified, denatured, and run overnight on the commercially available GMA gels for SSCP. PCR-SSCP analysis showed reproducible and uniform band patterns for FV mutant and wild type alleles. Furthermore, PCR-SSCP results were consistent with those obtained with PCR-RFLP analysis (100%). The described PCR-SSCP procedure is reliable, time-saving, and cost-effective. The method may be considered as a potentially powerful new tool in the routine detection of factor V Leiden.
Increased Soluble Fibrin in Plasma of Patients with Disseminated Intravascular Coagulation
Authors: Wada Hideo , Sase Tomohiro , Matsumoto Takeshi , Kushiya Fumihiko , Sakakura Miho , Mori Yoshitaka , Nishikawa Masakatsu , Ohnishi Katsuya , Nakatani Kaname , Gabazza Esteban C. , Shiku Hiroshi , Nobori Tsutomu
Published: June 2007

Plasma levels of soluble fibrin (SF) were measured in 1184 patients with disseminated intravascular coagulation (DIC) according to Japanese Ministry of Health and Welfare (JMHW) criteria. The usefulness of SF for the diagnosis of DIC was compared with other hemostatic molecular markers. Most hemostatic markers were significantly increased in patients with DIC than in those without DIC. Plasma levels of fibrin and fibrinogen degradation products, thrombin-antihtrombin complex, plasmin-plasmin inhibitor complex, D-dimer, thrombomodulin, and SF levels were also significantly higher in those with pre-DIC than in those without DIC. In classification of overt DIC by International Society of Thrombosis and Haemostasis (ISTH) criteria, most hemostatic markers were significantly increased in patients with overt DIC than in those without overt DIC. Plasma levels of SF 'in patients with DIC were significantly higher than those in patients with pre-DIC, which were significantly higher than in those without DIC. Plasma levels of SF were also significantly higher in patients with overt DIC than in those with non-overt DIC. The correlation between plasma SF levels and DIC score according to JMHW criteria or ISTH criteria was good. Receiver operating characteristic analysis shows that SF was the best marker for the diagnosis of DIC or overt DIC. These findings suggest that plasma SF might be useful marker for the diagnosis of DIC or overt DIC.
Generic Forms of Low-Molecular-Weight Heparins: Some Practical Considerations
Authors: Leong Wendy , Hoppensteadt Debra A.
Published: June 2007

This commentary briefly reviews the controversies of therapeutic and generic interchangeability, as they apply to the antithrombotic drug class called low-molecular-weight heparin (LMWH). Recommendations are prepared for the generic LMWH approval process by various regulatory bodies.
P-selectin and Platelet-Derived Microparticles Associated with Monocyte Activation Markers in Patients with Pulmonary Embolism
Authors: Inami Norihito , Nomura Shosaku , Kikuchi Hiraku , Kajiura Takayuki , Yamada Kohichi , Nakamori Hisahito , Takahashi Nobuyuki , Tsuda Nobuyuki , Hikosaka Makoto , Masaki Motoko , Iwasaka Toshiji
Published: June 2007

Platelet activation markers (platelet-derived microparticles and P-selectin on activated platelets), chemokines (monocyte chemotactic peptide and regulated on activation normally T-cell expressed and secreted), and soluble markers (sP-selectin, sE-selectin, sVCAM-1, and sCD14) were measured and compared in patients with pulmonary embolism (PE). These substances are thought to participate in the pathogenesis of PE. Levels of all of the platelet activation markers, chemokines, and soluble markers were higher in the patients with PE than in normal controls. Levels of platelet activation markers were also significantly increased postoperatively after total knee arthroplasty. Anti-platelet therapy significantly inhibited the elevation of platelet activation markers after total knee arthroplasty. These findings suggest that antiplatelet therapy may be useful for PE-related interaction of platelets, leukocytes, and endothelial cells.
Acquired Protein C and Protein S Deficiency in HIV-Infected Patients
Authors: Erbe Matthias , Rickerts Volker , Bauersachs Rupert Martin , Lindhoff-Last Edelgard
Published: June 2007

Infection with human immunodeficiency virus (HIV) may lead to hemostatic imbalances. Forty-nine consecutive patients with acute opportunistic infections were screened for thrombophilic parameters. A follow-up investigation was performed after 10 8 weeks in 26 patients. In acutely ill patients, the incidence of protein S deficiency was 67% (33/49) and of protein C deficiency 25% (12/49), while at the follow-up visit the incidences were 54% (14/26) and 8% (2/26), respectively. Protein S and protein C levels increased significantly from initial to follow-up visit (p < 0.05). Lupus anticoagulants were not detected and anticardiolipin IgG antibodies were present in 11.4% (5/44). Three patients presented with deep venous thrombosis on admission; in two, protein S or protein C deficiency was observed. In conclusion, an acquired protein S and protein C deficiency often develop in patients with HIV and acute illness; this may be reversible after treatment for opportunistic infections.
A Trend of Platelet Indices in Patients with Green Pit Viper Toxin
Authors: Soogarun Suphan , Wiwanitkit Viroj , Suwansaksrit Jamsai
Published: June 2007

The green pit viper (Trimeresurus albolabris and Trimeresurus macrops) is a common venomous snake in Thailand. The green pit viper venom has major effects on the hematologic system. The venom is found to have a thrombin-like effect in vitro but cause a defibrination syndrome in vivo. Unlike other pit viper snakes (such as Malayan pit viper and Russel's pit viper), the venomous effect on red blood cells is rarely mentioned. Clinical features of venomous snake bites vary from asymptomatic to fatal bleeding. In this study, an attempt was made to discern hematologic parameters in green pit viper envenomation and to characterize the changes in blood cells. The study included data from 40 patients who were hospitalized at the King Chulalongkorn Memorial Hospital during 1995 to 1999 and 40 normal, healthy subjects as control. Concerning platelet determination, significantly decreased (p < 0.05) total platelet count and mean platelet volume (MPV) were demonstrated in envenomous blood. The changes in blood cells may be partly due to the effect of green pit viper toxin on the platelet morphology. However, the explanation of this phenomenon requires further investigation for the specific pathophysiology. The components of green pit viper venom that have these hematologic effects in humans are interesting and should be further identified.
Seasonal Variation in Onset of Pulmonary Embolism is Independent of Patients' Underlying Risk Comorbid Conditions
Authors: Manfredini R. , Gallerani M. , Boari B. , Salmi R. , Mehta R. H.
Published: June 2007

As for many cardiovascular events, pulmonary embolism (PE) is not randomly distributed over time, but shows rhythmic patterns. The purpose of this study was to investigate whether such temporal pattern of occurrence varied in subgroups of patients according to different risk comorbid conditions. All cases of PE observed at the Hospital of Ferrara, Italy, from 1998 to 2001, were considered. After determination of the day of onset, the population was grouped by gender and the most common underlying risk comorbid conditions, e.g., deep vein thrombosis (DVT), neoplasms, cardiomyopathies, traumas/surgical operations, diabetes mellitus, pulmonary diseases, hypertension, cerebrovascular diseases, heart failure, hematologic diseases. For statistical analysis, chi-square test for goodness of fit and partial Fourier series were used. A total of 784 cases (mean age 71 ± 14 years) were included. Frequency of onset was higher in winter for total population (p=0.002), men (p=0.004), DVT (p=0.001), pulmonary disease (p=0.008), cardiomyopathies (p=0.011), and major traumas/surgical operations (p=0.049). Chronobiologic analysis identified a winter peak for total population (p=0.008), men (p<O.OOl), DVT (p=0.006), pulmonary diseases (p=0.017), and hypertension (p=0.026). This study confirms the winter peak of PE and provides evidence that it is not influenced by the underlying clinical conditions, but probably by endogenous variations.
Laboratory Diagnosis of Heparin-Induced Thrombocytopenia in Asian Indians as Investigated With Functional and Immunologic Methods
Authors: Kannan Meganathan , Ahmed Rafeeq , Kale Shailaja , Ahmad Sarfraz , Fareed Jawed , Saxena Renu
Published: June 2007

Heparin-induced thrombocytopenia (HIT) was looked for in 33 Indian patients undergoing cardiovascular surgery who received unfractionated heparin (UFH). Platelet counts were performed before the initiation of UFH therapy and 5 to 16 days after administration of the therapy. A decrease in patients' platelet count >35% of the baseline value or <100,000/μL was considered to be suggestive of HIT syndrome. Heparin-induced platelet aggregation (HIPA) and enzyme-linked immunosorbent assay (ELISA) tests were performed in all the patients to detect antibodies against heparin/PF4 complex. Thrombocytopenia was found to be present in 10 (30%) patients. Of these, two patients were found to be positive as detected by HIPA and ELISA tests. These two patients were considered to have classic HIT syndrome. One of these had bleeding while the other was asymptomatic. Among the 23 non-thrombocytopenic patients and controls, HIT antibodies were not detectable by HIPA test in all but absent by ELISA in only 21 of them. Two of 23 non-thrombocytopenic patients had positive results on the ELISA test. Because the latter had negative test results on HIPA, they were considered to be false-positive results. Thus, HIT syndrome develops in approximately 6% of Indian patients treated with UFH.
The Role of Adiponectin in Atherosclerosis and Thrombosis
Authors: Ekmekci Hakan , Ekmekci Ozlem B.
Published: June 2007

Obesity is a major risk factor for morbidity and mortality from cardiovascular causes. Adiponectin has been identified recently as one of the adipocytokines with important metabolic effects. It can suppress atherogenesis by inhibiting the adherence of monocytes, reducing their phagocytic activity, and suppressing the accumulation of modified lipoproteins in the vascular wall. In addition, as adiponectin decrease endothelial damage and stimulates production of NO from vascular endothelial cells, hypoadiponectinemia may be partially contribute to thrombus formation.
Does Hemophilia Protect Against Atherosclerosis? A Case-Control Study
Authors: Bilora Franca , Zanon Ezio , Petrobelli Francesco , Cavraro Monica , Prandoni Paolo , Pagnan Antonio , Girolami Antonio
Published: June 2007

Whether carriers of hemophilia are protected against the development of atherosclerosis is controversial. In a case-control study, the presence of atherosclerosis was assessed and quantified with echo-color Doppler of all explorable arterial districts in 50 carriers of hemophilia and in 50 age-matched control individuals. All participants submitted to echo-color Doppler of carotid and femoral axis, of brachial arteries, and of the abdominal aorta. The presence and grade of atherosclerotic plaques were assessed, as well as the intima-media thickness (IMT). At least one atherosclerotic plaque was found in six cases (12.0%) versus 15 controls (30.0%); referring to the total number of plaques, 30% of them were evaluated in patients affected by decreased coagulation while 70% in subjects with normal levels of FVIII. In all the examined districts, the mean IMT was significantly lower in patients with hemophilia than in controls. Hemophilia protects against asymptomatic atherosclerosis.
Prevalence of Prothrombin Gene Mutation (G-A 20210 A) in General Population: A Pilot Study
Authors: Naeem Muhammad Abdul , Anwar Masood , Ali Waqar , Ayyub Muhammad , Nasiruddin
Published: June 2007

The objective of this study was to determine the prevalence of prothrombin gene mutation in a sample population from Pakistan. Two hundred apparently healthy unrelated adults (older than 18 years) were included in the study. The sample population comprised 100 Punjabis (male 50, female 50) and 100 Pathans (male 50, female 50). Patients with a history of previous thromboembolism were excluded from the study. Five milliliters (5 mL) of whole blood was drawn in an EDTA bottle. The DNA was extracted by the standard phenol-chloroform method. The DNA was amplified between exon number 14 and the 3’-untranslated region of the prothrombin gene by a polymerase chain reaction in a thermal cycler. Amplified products were digested overnight with HindIII at 37°C. The digested products were electrophoresed on 6% polyacrylamide gel. The fragments were visualized by silver nitrate staining. A heterozygous wild type and an uncut amplified product were included in the electrophoresis strip for quality control. The wild type of DNA ran as a 350-bp fragment and internal control was cut as 550- and 150-bp fragments. The abnormal prothrombin gene was cut into 350-, 322-, and 28-bp fragments. Only two cases of heterozygous prothrombin gene mutation G-A 20210A were found in the sample studied, giving an overall carrier rate of 01% (95% CI 0.4-2.4%) in the target population. Prothrombin gene mutation is present in our population but at a lower frequency than in the white population.
C-Reactive Protein in Hypertensive Disorders in Pregnancy
Authors: Paternoster Delia M. , Fantinato Sara , Stella Andrea , Nanhornguè Kimta Ngaradoumbe , Milani Massimo , Plebani Mario , Nicolini Umberto , Girolami Antonio
Published: June 2007

Hypertension is the most frequent medical complication of pregnancy. A recent report demonstrates the flogistic pathogenesis of pregnancy-induced hypertension. Because C-reactive protein (CRP) is a marker of inflammation, it can be used in the differential diagnosis of hypertensive disorders of pregnancy. A total of 322 pregnant women at 24 to 32 weeks’ gestation were enrolled. The control group (A) comprised 190 women. Sixty-three women had preeclampsia (PE, group B), 31 women presented transient hypertension (TH, group C), 19 had HELLP syndrome (HS, group D) and 19 had chronic hypertension (CH, group E). CRP serum concentrations were significantly higher in groups B, C, and D in comparison with the group A. In the whole population, systolic and diastolic pressure value inversely correlate with weight at delivery and weeks of gestation at delivery. CPR levels in patients with PE and HS inversely correlate with birth weight and gestational week at delivery. Normal plasma levels of CRP may be an important marker of differential diagnosis between TH and CH. In TH, PE, and HS, CRP levels were higher than in the control and CH groups, suggesting that inflammation may be the common pathogenetic cause of TH and PE. Finally CRP levels in preeclampsia are believed to correlate with preeclamptic process severity.
Diagnosis and Follow-up of Thrombotic Thrombocytopenic Purpura by Means of von Willebrand Factor Collagen Binding Assay
Authors: Casonato A. , Fabris F. , Pontara E. , Cattini M. G. , Zocca N. , Gallinaro L. , Girolami A. , Pagnan A.
Published: June 2007

Thrombotic thrombocytopenic purpura (TTP) is characterized by intravascular thrombosis leading to consumption of large or unusually large von Willebrand factor (VWF) multimers. The usefulness of VWF collagen binding (VWF:CB) assay was assessed in detecting the decrease/absence of large VWF multimers or the presence of abnormally large forms in patients with TTP. Nine patients with TTP were studied during the acute phase of the disorder and the absence of large VWF multimers was demonstrated by means of the VWF:CB assay. These findings were confirmed by VWF multimer pattern analysis; VWF:CB deficiency appeared to correlate with abnormalities in large VWF multimers. The diagnostic potency of VWF:CB was especially evident when the values were expressed as VWF:CB/VWF:Ag ratio. VWF:CB was also used during the follow-up of the disorder to document improvement or restoration of large VWF multimers. VWF:CB was able to detect the absence or decrease of large VWF multimers better than VWF ristocetin cofactor (VWF:RCo); in fact, VWF:CB was defective when large VWF multimers persisted to be decreased, in contrast with what observed with VWF:RCo. In conclusion, VWF:CB is a simple test that appears to be useful, together with clinical symptoms and reduced platelet count, for the diagnosis and follow-up of TTP.
Report of a Patient With Heparin-induced Thrombocytopenia Type II Associated With IgA Antibodies Only
Authors: Meyer Oliver , Aslan T. , Koster A. , Kiesewetter H. , Salama A.
Published: June 2007

Heparin-induced thrombocytopenia type II (HIT II) is usually mediated by immunoglobulin G (IgG) antibodies that lead to platelet activation via the FcγIIA-receptor. Here we describe a patient who developed HIT II after aortocoronary bypass surgery. His serum contained an antibody that was detectable by the heparin-induced platelet activation assay (HIPA) and by the ID-HPF4 particle agglutination assay. The flow cytometric analysis showed that the antibody was of the IgA class.