Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
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Blood Coagul. Fibrinolysis · Oct 1994
Relationship of fibrinolysis and platelet function to bleeding after cardiopulmonary bypass.
In order to study the effects of cardiopulmonary bypass (CPB) on fibrinolysis and platelet function and the possible relationship of these effects on post-operative blood loss, 127 patients undergoing CPB were examined. There was a significant reduction in the median levels of fibrinogen, plasminogen, alpha 2-antiplasmin, fibrinolytic potential and platelet aggregation during CPB (P < or = 0.001). Median levels of soluble fibrin, fibrinogen degradation products, D-dimer and PAI-1 were increased, while the level of t-PA activity remained constant. ⋯ The increase in PAI-1 levels intra-CPB appeared to result in mean t-PA activity remaining unchanged 1 h post-CPB. Post-CPB increases in soluble fibrin were paralleled by increases in fibrinogen degradation products and D-dimer, suggesting that intra-operative contact activation is related to activation of the fibrinolytic system. The present findings indicate the greater the fibrinolytic activation, the greater the post-CPB blood loss.
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Blood Coagul. Fibrinolysis · Aug 1994
A lupus anticoagulant neutralization procedure using the patient's own platelets.
An auto platelet neutralization procedure (APNP) which assists identification of lupus anticoagulants (LA) is described. Patient platelet-rich plasma is frozen then thawed (PRPF) and an activated partial thromboplastin time (aPTT) is performed on both platelet-poor plasma and PRPF. The degree of correction between the two plasmas is calculated and the percentage APNP is obtained. ⋯ In three patients with normal aPTT, LA was suspected and APNP ranged from 21 to 28%. An intermediate APNP range of 20-25% may be suggestive of LA in patients with normal aPTT. The APNP did not appear to be effected by platelet count in the samples tested unless the platelet count in PRP was less than 175 x 10(9)/1.(ABSTRACT TRUNCATED AT 250 WORDS)
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Blood Coagul. Fibrinolysis · Aug 1994
Studies on the mechanisms of action of aprotinin and tranexamic acid as plasmin inhibitors and antifibrinolytic agents.
Both aprotinin and tranexamic acid are effective inhibitors of fibrinolysis in vitro and in vivo and both agents can act as plasmin inhibitors in purified systems, although there is some debate on their exact mechanism of action in vivo. The studies reported here using an in vitro clot lysis system designed to provide precise inhibition constants show that aprotinin remains a very potent inhibitor of plasmin even in the presence of fibrin with Ki = 2 nM. Plasmin-aprotinin interactions in solution are not affected by a number of kringle binding ligands, aminohexanoic acid, tranexamic acid or CNBr-fibrinogen fragments with Ki = 0.4 nM. ⋯ Inhibition of fibrinolysis by tranexamic acid is not readily analysed by a simple inhibition model which may be due to multiple overlapping ligand-kringle interactions or tranexamic-fibrin interactions. Experiments using combinations of aprotinin and tranexamic acid in the clot lysis system confirm the complementary nature of inhibitory mechanisms and suggest a slight synergism. These results support the idea that aprotinin inhibition of plasmin is a primary mode of action in vivo, and suggest that combination therapy of aprotinin with tranexamic acid might be more effective than either inhibitor alone.
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Blood Coagul. Fibrinolysis · Feb 1994
Levels of fibrinolytic activators and inhibitors in plasma after severe trauma.
Levels of tissue plasminogen activator antigen (t-PA:ag), tissue plasminogen activator inhibitor 1 antigen (PAI-1:ag) and tissue plasminogen activator inhibitor activity (PAI activity), and alpha-2-antiplasmin (AAP) were measured in plasma from 19 patients with severe trauma on admission and on days 1, 2, 3 and 7 after the incident. In all patients the Injury Severity Score (ISS) and the number of blood transfusions were recorded. The development of post-traumatic pulmonary dysfunction was observed in four patients. ⋯ Levels of APP increased significantly during the first week. t-PA:ag, PAI-1:ag or PAI activity levels were not correlated with the ISS on any day, but levels of AAP showed a weak correlation with the ISS on day 7. Post-traumatic levels of t-PA:ag and PAI-1:ag were higher in patients who had 6 or more units of blood transfusions for resuscitation. The fibrinolytic markers were not significantly different in patients who had pulmonary dysfunction compared with patients without.
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Blood Coagul. Fibrinolysis · Feb 1993
The effect of aprotinin on the response of the activated partial thromboplastin time (APTT) to heparin.
Aprotinin, a broad spectrum serine proteinase inhibitor, is becoming increasingly used to control bleeding during surgery. Heparinized patients treated with aprotinin for cardiac surgery have a much longer activated clotting time (ACT) than expected for the dose of heparin used and a similar effect has been observed with the activated partial thromboplastin time (APTT). Since APTT reagents vary in their sensitivity to heparin we compared the effect of aprotinin on 25 commercially available products with respect to the APTT response to heparin. ⋯ The prolongation of the APTT by heparin was markedly increased by aprotinin. For example, APTT ratios at 0.5 IU/ml heparin increased up to eight-fold in the presence of 'therapeutic' levels of aprotinin (200 KIU/ml) and this effect was even more pronounced at higher heparin levels. The activator used did not significantly influence the effect of aprotinin on the APTT although there was a trend for kaolin-activated reagents to be less affected by the addition of aprotinin to heparinised plasma.(ABSTRACT TRUNCATED AT 250 WORDS)