Thromb Haemostasis
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In the present study we assessed the effect of platelet counts and rFVIIa on thrombin generation, platelet activation and clot formation after tissue factor pathway activation in human plasma aiming to investigate the mechanism by which rFVIIa induces haemostasis in patients with severe thrombocytopenia. Plasma samples with platelet counts from 5 x 10(9)/l to 150 x 10(9)/l were spiked with rFVIIa (1 micro g/ml) or buffer. Clotting was initiated in the presence of diluted thromboplastin. ⋯ Recombinant FVIIa enhanced platelet activation in a TF and thrombin dependent manner since its effect on the studied parameters was abolished when TF was omitted or when hirudin was added into the experimental system respectively. Recombinant FVIIa normalized the velocity of clot formation but it did not modify clot firmness, which depended mainly on platelets' count. In conclusion, in experimental conditions simulating severe thrombocytopenia rFVIIa in the presence of low amounts of TF, accelerates thrombin generation, without increasing the maximum amount of generated thrombin, thus leading in enhanced platelet activation and rapid clot formation.
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Comment Letter
Mechanism of action of drotrecogin alfa activated (rhAPC).
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Comparative Study
Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score.
The overt DIC score of the DIC subcommittee of the ISTH includes a fibrin-related marker (FRM) as indicator of intravascular fibrin formation. The type of marker to be used has not been specified, but D-dimer antigen, or fibrin degradation products are used by most investigators. Soluble fibrin complexes have been suggested as more specific indicators of acute intravascular fibrin formation. ⋯ Using MDA D-dimer, and TINAquant D-dimer, 28-day mortality was between 35.5% and 39.3% in patients with overt DIC, and 15.5% to 15.6% in patients without overt DIC. Selection of the FRM as component of the DIC score has a small, but relevant impact on the prognostic performance of the overt DIC score. The present data on the distribution of values may provide a basis for the selection of appropriate cutoff points for assigning 2, and 3 points in the score.
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We investigated age- and sex-specific incidence, risk factors, and latency period of a perioperative acute thromboembolism syndrome (PATS) in a large cohort study. We prospectively analyzed data on 21903 consecutive surgery patients to determine the incidence of myocardial infarction, pulmonary embolism, deep venous thrombosis, stroke, and cardiovascular death within 30 postoperative days. Among 255 (1.2 percent) patients with thromboembolism, 105 (0.48 percent) suffered myocardial infarction (mean latency: 5 days), 30 (0.14 percent) suffered pulmonary embolism (6 days), 23 (0.11 percent) suffered deep venous thrombosis (10 days), 97 (0.44 percent) suffered stroke (11 days), and 13 (0.06 percent) died (12 days). ⋯ Risk of thromboembolic event was higher (P<0.0001) in patients with a history of arterial thrombotic events or cancer. Trend analysis indicates that thromboembolic events will increase 3-fold over the next decade. Our findings enable identification of higher risk patients for prophylactic anti-thromboembolic treatment and awareness of the critical postoperative period.
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Randomized Controlled Trial Clinical Trial
Plasma MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2 during human orthotopic liver transplantation. The effect of aprotinin and the relation to ischemia/reperfusion injury.
Uncontrolled activation of matrix metalloproteinases (MMPs) can result in tissue injury and inflammation, yet little is known about the activation of MMPs during orthotopic liver transplantation (OLT). OLT is associated with increased fibrinolytic activity due to elevated plasmin generation. The serine-protease plasmin not only causes degradation of fibrin clots but is also thought, amongst others, to play a role in the activation of some matrix metalloproteinases. ⋯ MMP-2, TIMP-1 and TIMP-2 gradually decreased during OLT. The composition of these MMPs was not altered by the use of aprotinin, suggesting that serine-protease/plasmin-independent pathways are responsible for MMP regulation during OLT. In addition, only MMP-9 seems to be involved in I/R injury during human liver transplantation.