摘要:

We undertook this investigation to assess alterations in shear-mediated platelet function during cardiac surgery and to determine the potential for the PFA-100®to predict post-operative bleeding. Platelet aggregation and PFA-100®closure times were determined in 18 adult patients at five intervals during cardiac surgery. Associations between post-operative bleeding and closure times were examined in an additional 58 patients. Statistical analysis consisted of Student'st, Wilcoxon signed rank, and Spearman correlation tests. All results are reported as mean ± SEM. Collagen/epinephrine closure times were prolonged prior to and throughout surgery. Collagen/adenosine-5′-diphosphate (ADP) closure times were significantly prolonged by heparin administration, 141 ± 15 s versus 115 ± 10 s (P= 0.01), and subsequent initiation of cardiopulmonary bypass (CPB), 203 ± 12 s (P= 0.0001); however, 15 min after protamine administration, closure times returned to near pre-operative values, 138 ± 12 s (P= not significant). In contrast, platelet aggregation in response to ADP remained impaired in 17 of 19 patients after CPB. Neitherex vivocorrection of sample hematocrits nor supplementation with Humate P1 affected closure times. Positive and negative predictive values for post-CPB collagen/ADP closure times to predict bleeding were 18 and 96%, respectively. These results suggest that factors both intrinsic and extrinsic to the platelet contribute to reversible shear-mediated platelet dysfunction during CPB, and that the PFA-100®may prove useful after CPB to identify patients unlikely to benefit from platelet transfusions.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

One hundred and thirteen consecutive Japanese patients with deep venous thrombosis (DVT) were studied for the incidences of antithrombin III (AT-III), protein C (PC) and protein S (PS) deficiencies, and the results were compared with those of normal subjects. Ten of the 392 normal Japanese subjects were found with PS deficiency (n= 8, 2.02%) or PC deficiency (n= 2, 0.5%). PS deficiencies comprised type I (1/8, 12.5%), type II (4/8, 50%), and type III (3/8, 37.5%). All PC deficiencies were type I. Among patients with DVT, 32 (28.3%) were deficient in AT-III, PC and PS. These patients consisted of two AT-III deficiency (1.77%), nine PC deficiency (7.96%), 20 PS deficiency (17.7%), and one combined deficiency of PC and PS (0.88%). Both of the patients with AT-III deficiency were classified as type II, all those with PC deficiency as type I, and those with PS deficiency as type I in 25% (5/20), type II in 55% (11/20) and type III in 20% (4/20). The frequency of PC and PS deficiencies in patients with DVT were 15.6 and 7.38 times the control population frequency, respectively, and this difference was statistically significant (P< 0.05). These data suggest that the Japanese population has a high frequency of PC and PS deficiencies. We recommend that PS activity should be measured for screening of thrombosis since type II deficiency accounted for approximately 50% of PS deficiency cases in both patients and the normal group in the Japanese.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Reduced factor XIIIA levels and decreased clot strength have been associated with increased bleeding after cardiopulmonary bypass (CPB). The purpose of this study was to evaluate the relationship between hemostatic factors, including factor XIIIA, and clot strength before, during and after CPB. Factor XIIIA antigen, platelet counts, fibrinogen, factor V activity, tissue plasminogen activator and clot strength (by thromboelastograph) were measured at baseline, after 45 min of CPB, at the end of CPB and 4 h post-operatively in 34 patients. Baseline factor XIIIA antigen was 5.2 ± 1.4 mg/l. On average, factor XIIIA levels dropped to 64% and clot strength to 77% of baseline values after 45 min on CPB and remained below baseline during the immediate post-operative period. Clot strength was significantly correlated (r= 0.81) with platelet count and fibrinogen but not plasma factor XIIIA levels. Addition of 10 mg/l recombinant factor XIII{a2} significantly increased clot strength. Postoperative bleeding at 2 h was inversely correlated with platelet count, factor XIIIA antigen and clot strength measured at the end of CPB. Maintenance of adequate platelet counts and factor XIIIA levels at the end of CPB may play a role in maintaining clot strength and reducing blood loss.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The aim of this study was to examine if acute hyperglycemia (an oral glucose tolerance test) activates platelet function, endothelial cells or thrombin generation in diabetic patients and healthy controls. Eleven males with mild type II diabetes mellitus and 11 healthy male volunteers, matched for age and body mass index, were investigated before and after the glucose load. Soluble P-selectin, von Willebrand factor antigen and markers of thrombin generation in plasma were determined by immunoassays, and platelet P-selectin expression (unstimulated and agonist-stimulated) by flow cytometry in whole blood. Acute hyperglycemia elevated plasma soluble P-selectin from 32.5 to 50.9 ng/ml in the diabetic group (P= 0.05) but not in the controls (from 27.3 to 28.8 ng/ml;P= 0.6). Also, soluble P-selectin levels were higher in patients with diabetes than in healthy controls during hyperglycemia, but not in the fasting state. Adenosine diphosphate- and thrombin-induced platelet P-selectin expression was slightly, but significantly, decreased by the glucose load, whereas platelet P-selectin expression in unstimulated samples was not affected. Plasma levels of von Willebrand factor and thrombin generation were similar in patients and controls, and were not altered by hyperglycemia. In conclusion, we found that acute hyperglycemia elevates soluble P-selectin in plasma in males with mild type II diabetes mellitus. Our observation of unaltered plasma levels of the endothelial marker von Willebrand factor is in agreement with platelets being the main source of P-selectin released into plasma following hyperglycemia. Thus, platelets in individuals with type II diabetes may be more susceptible to hyperglycemia than platelets in non-diabetic individuals.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

It is a matter of debate whether postprandial activation of blood coagulation factor VII (FVII) is associated with an increased risk of thrombosis. To clarify this question, an animal model in which consequences of dietary FVII activation can be studied in a more detailed way would be an important tool. We studied postprandial FVII activation in seven non-fasting Göttingen minipigs. Intralipid (4 g/kg) was administered through a gastric tube in two fractions at 9.00 a.m. (one-third of total dose) and 10.30 a.m. (two-thirds of total dose). Blood samples were drawn 0.5 h before (baseline) and 2, 3, 3.5, 4, 5, and 6 h after the first fat load. Triglycerides, activated FVII (FVIIa), FVII coagulant activity (FVIIc), FVII amidolytic activity (FVIIam) and prothrombin fragment 1 + 2 (F1 + 2) were analysed in plasma samples. Median plasma triglycerides were significantly raised from 0.67 mmol/l (baseline) to 2.56 mmol/l 5 h postprandially (P< 0.001). There were no significant changes in FVIIa (9.6 U/l at baseline), FVIIam (142% at baseline) and F1 + 2 (0.13 nmol/l at baseline). FVIIc decreased from 141% at baseline to 114% 6 h postprandially (P< 0.001). As a high-fat meal does not seem to activate blood coagulation FVII in minipigs, the pig is apparently not a relevant model for the study of dietary FVII activation and thrombin generation.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Thrombin is the key serine proteinase of the coagulation cascade and therefore a suitable target for inhibition of blood coagulation. A number of pharmacologically active secondary metabolites from mushrooms have already been isolated, thus providing the rationale for screening for new thrombin inhibitors in mushrooms. In this study, inhibitory activities of mushroom extracts on thrombin and trypsin were measured using the chromogenic substratesH-d-phenylalanine-l-pipecolyl-l-arginine-paranitroaniline dihydrochloride (S-2238) for thrombin andN-benzoyl-d,l-Arg-p-nitroanilide (BAPNA) for trypsin. The inhibitory activities of extracts from 95 Basidiomycete species have been determined. The majority of samples inhibited trypsin and thrombin with various potencies; however, some extracts showed no activity against one or both of the enzymes. An aqueous extract ofGleophyllum odoratumexhibited high inhibitory activity on both thrombin and trypsin (72 and 60%, respectively), while extracts ofClitocybe gibba, Amanita virosa, Cantharellus lutescens, Suillus tridentinus, Hypoloma fasciculareandLactarius badiosanguineusconsiderably inhibited thrombin (49, 48, 36, 34, 32 and 31%, respectively) and showed no inhibitory activity on trypsin. The results at this point are promising for further research with the objective of finding an effective and safe thrombin inhibitor.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

This double-blind, randomized study compared the mechanisms by which low-dose aprotinin and epsilon-aminocaproic acid (EACA) inhibited fibrinolysis during cardiopulmonary bypass surgery. D-dimer levels during and after bypass were similar, indicating an equivalent inhibition of fibrinolysis. Effects on tissue plasminogen activator release were not associated with the inhibition of fibrinolysis by either drug. Treatment with EACA was associated with a substantial release of endogenous α2-antiplasmin, particularly 1 h after bypass. Compared with the aprotinin group, higher levels of the plasmin–α2-antiplasmin complex in the EACA group confirmed an increased inhibition of plasmin by α2-antiplasmin. In conclusion, it is hypothesized that EACA inhibited fibrinolysis by stimulating the release of the patients’ own α2-antiplasmin.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

A new, fully automated, one-step, immuno-turbidimetric assay of free protein S (fPS) in plasma (STA®Liatest®Free Protein S; Diagnostica Stago, Asnières, France) has been developed for STA®analysers. This technique combines the advantages of a direct assay of fPS using two monoclonal antibodies, which specifically recognize fPS but not protein S (PS)–C4b-binding protein complexes, and the advantages of automation. The assay has good analytical performances, with intra- and inter-assay variation coefficients below 5% for normal values, and slightly higher for abnormal values. In a comparison study with a one-step enzyme-linked immunosorbent assay for fPS (Asserachrom®Free Protein S; Diagnostica Stago), a correlation coefficient of 0.93 with a regression line close to 1 was found between the two techniques (n= 166 normal or PS-deficient plasma samples collected from healthy subjects and individuals with a personal or family history of thrombosis). This new technique is specific, reproducible, easy to perform, and provides a useful tool in the diagnosis of PS deficiency.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

There is a recognized association between von Willebrand's disease and gastrointestinal angiodysplasia. Most previous publications have been reports of the association itself and there is little published on the management and long-term follow-up of affected patients. We report our experience and follow-up of six patients, and review the previous literature.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

A history of thromboembolism is associated with an increased risk of new thromboembolic events during pregnancy. Prophylaxis with heparin during pregnancy implicates long-term treatment with daily injections with either unfractionated heparin (UFH) or low molecular mass heparin (LMMH). Prolonged treatment with heparin may result in endothelial absorption and drug accumulation. In order to test this hypothesis, anti-FXa activity during pregnancy was measured in four women allergic to conventional UFH, who were treated with LMMH (dalteparin; Pharmacia). It was found that, at the commencement of treatment, it took more than 8 days to reach a steady maximum peak value, located 3 h after the given dose. One daily dosage of 5000 IU anti-Xa resulted in a measurable level of FXa for 24 h in pregnancy week 40, compared with 17 h at pregnancy week 37. The implications of an elevated anti-FXa activity during pregnancy, especially during the third trimester and at partus, are discussed. We present a reduced dose regime near term and during delivery.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID