Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
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Blood Coagul. Fibrinolysis · Dec 2008
Impact of fibrinogen concentration in severely ill patients on mechanical properties of whole blood clots.
Fibrinogen concentration influences mechanical and functional properties of the clot. The purpose of the present study was to identify threshold concentrations of fibrinogen resulting in relevant changes in whole blood clot elastic modulus and platelet contractile force, as well as plasma prothrombin time and activated partial thromboplastin time. We measured clot elastic modulus, platelet contractile force, and other hemostasis parameters in whole blood samples from 552 patients admitted to a surgical intensive care unit. ⋯ In contrast, clotting time assays such as prothrombin time, thrombin time, or activated partial thromboplastin time are influenced by the fibrinogen concentration only at levels below 1 g/l. In linear regression analysis, clot elastic modulus was mainly influenced by fibrinogen concentration (F = 185.4, P < 0.0001), whereas platelet contractile force was influenced by fibrinogen (F = 197.0, P < 0.0001) and platelet count (F = 104.7, P < 0.0001). The present data show that 1 g/l is a threshold fibrinogen concentration for an effect on coagulation assays such as prothrombin time, thrombin time, or activated partial thromboplastin time, but increasing fibrinogen concentrations above this level results in further continuous improvement of mechanical properties of the whole blood clot.
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Blood Coagul. Fibrinolysis · Dec 2008
Argatroban enhances fibrinolysis by differential inhibition of thrombin-mediated activation of thrombin activatable fibrinolysis inhibitor and factor XIII.
Direct thrombin inhibitors enhance fibrinolysis more efficiently than heparin. Direct thrombin inhibitors and heparin enhance fibrinolysis by inhibition of activation of thrombin activatable fibrinolysis inhibitor (TAFI); however, the role played by other thrombin-activated proteins [e.g., factor XIII (FXIII)] in fibrinolysis remained to be elucidated. Our goal was thus to define the roles of TAFI and FXIII in direct thrombin inhibitor-mediated fibrinolysis enhancement. ⋯ When changes in maximum rate of lysis were related to changes in the maximum rate of thrombus generation, argatroban was associated with a greater increase in maximum rate of lysis per decrease in maximum rate of thrombus generation compared with heparin. Experiments with TAFI-deficient and FXIII-deficient plasma demonstrated a sparing of thrombin-mediated FXIII activation with concurrent inhibition of TAFI activation. The mechanism by which argatroban more efficiently enhanced fibrinolysis was via a differential inhibition of thrombin-mediated activation of TAFI and FXIII.
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Blood Coagul. Fibrinolysis · Dec 2008
Rotational thromboelastography for monitoring of fibrinogen concentrate therapy in fibrinogen deficiency.
To characterize a functional assay for circulating fibrinogen based on rotational thrombelastography. Maximum clot firmness was determined by rotational thrombelastography in normal human plasma pool, fibrinogen-deficient plasma pool, normal whole blood, and individual plasma samples from 17 patients with fibrinogen deficiency. Plasma samples spiked with varying concentrations of exogenous fibrinogen were also measured. ⋯ Maximum clot firmness was the only evaluated method of fibrinogen assessment to yield consistent results across all categories of fibrinogen deficiency. These in-vitro results suggest the potential clinical utility of rotational thromboelastography as a versatile method for monitoring the response to fibrinogen concentrate among patients with fibrinogen deficiency. Clinical investigations using rotational thromboelastography after in-vivo fibrinogen administration to patients with congenital fibrinogen deficiency are warranted.
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Blood Coagul. Fibrinolysis · Dec 2008
Correlation between the potency of a beta2-glycoprotein I-dependent lupus anticoagulant and the level of resistance to activated protein C.
The antiphospholipid syndrome is characterized by the occurrence of vascular thrombosis combined with the presence of antiphospholipid antibodies in plasma of patients. It has been published that antibeta2-glycoprotein I (beta2-GPI) antibodies, with lupus anticoagulant activity (LAC), highly correlate with thrombosis. Resistance related to antiphospholipid antibodies against activated protein C (APC) is one of the proposed mechanisms responsible for thrombosis. ⋯ Surface plasmon resonance analysis was used to investigate binding between APC and beta2-GPI. We observed that beta2-GPI was able to bind APC directly, especially in the presence of a monoclonal antibeta2-GPI antibody. In conclusion, our observations show a direct correlation between a major clinical symptom of antiphospholipid syndrome (thrombosis), a diagnostic assay (beta2-GPI-dependent LAC) and a potential mechanism responsible for thrombosis in the antiphospholipid syndrome (increased APC resistance).
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Blood Coagul. Fibrinolysis · Oct 2008
Hematologic effects of recombinant factor VIIa combined with hemoglobin-based oxygen carrier-201 for prehospital resuscitation of swine with severe uncontrolled hemorrhage due to liver injury.
The combination of traumatic injury, hemorrhage, and fluid resuscitation results in consumption and dilution of coagulation factors, adversely impacting hematology outcome in trauma patients. The hemostatic effects of escalating doses of recombinant factor VIIa added to hemoglobin-based oxygen carrier-201 were assessed as prehospital fluid resuscitation in swine with severe uncontrolled hemorrhage. Swine underwent liver injury causing severe uncontrolled hemorrhage and shock. ⋯ Platelets and thromboelastography-maximum amplitude decreased (P < 0.01) with the 4x group. In swine with severe uncontrolled hemorrhage, prehospital resuscitation with escalating doses of recombinant factor VIIa in combination with hemoglobin-based oxygen carrier-201 did not change survival or hemostasis. However, there were trends toward possible benefits of low recombinant factor VIIa doses, whereas high recombinant factor VIIa doses adversely affected hemostasis.