Journal of thrombosis and haemostasis : JTH
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J. Thromb. Haemost. · Nov 2006
Anticoagulant and anti-inflammatory effects after peritoneal lavage with antithrombin in experimental polymicrobial peritonitis.
In sepsis, coagulation inhibition using high-dose systemic antithrombin (AT) tends to improve survival. However, systemic AT use is complicated by increased risk of bleeding (odds ratio 1,7) and clinically important survival increase is seen only in the non-heparinized subgroup. Local (intra-abdominal) inhibition of coagulation with AT may be more effective. ⋯ High-dose rhAT lavage inhibited coagulation activation, and reduced inflammatory responses in both abdominal and pulmonary compartments, ultimately improving survival.
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Hereditary fibrinogen disorders include type I deficiencies (afibrinogenemia and hypofibrinogenemia, i.e. quantitative defects), with low or unmeasurable levels of immunoreactive protein; and type II deficiencies (dysfibrinogenemia and hypodysfibrinogenemia, i.e. qualitative defects), showing normal or altered antigen levels associated with reduced coagulant activity. While dysfibrinogenemias are in most cases autosomal dominant disorders, type I deficiencies are generally inherited as autosomal recessive traits. ⋯ This review focuses on the genetic bases of type I fibrinogen deficiencies, which are invariantly represented by mutations within the three fibrinogen genes (FGA, FGB, and FGG) coding for the three polypeptide chains Aalpha, Bbeta, and gamma. From the inspection of the mutational spectrum of these disorders, some conclusions can be drawn: (i) genetic defects are scattered throughout the three fibrinogen genes, with only few sites appearing to represent relative mutational hot spots; (ii) several different types of genetic lesions and pathogenic mechanisms have been described in affected individuals (including gross deletions, point mutations causing premature termination codons, missense mutations affecting fibrinogen assembly/secretion, and uniparental isodisomy associated with a large deletion); (iii) the possibility to express recombinant fibrinogen mutants in eukaryotic cells is rapidly shedding light into the molecular mechanisms responsible for physiologic and pathologic properties of the molecule; (iv) though mutation analysis of the fibrinogen cluster does not yield precise information for predicting genotype/phenotype correlations, it still provides a valuable tool for diagnosis confirmation, identification of potential carriers, and prenatal diagnosis.
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J. Thromb. Haemost. · Sep 2006
Clinical Trial Controlled Clinical TrialRecombinant factor VIIa reverses the inhibitory effect of aspirin or aspirin plus clopidogrel on in vitro thrombin generation.
Antiplatelet drugs constitute the therapy of choice for acute coronary syndromes, but bleeding can be a side-effect requiring treatment. Restoration of normal platelet activity is also mandatory before urgent surgery. This study investigated: (a) whether a regimen of aspirin or clopidogrel plus aspirin significantly inhibited platelet thrombin generation (TG); and (b) the reversal of this inhibition by recombinant activated factor VII (rFVIIa). ⋯ Platelets activated by AA, ADP, collagen or FVIIa triggered TG. This effect was inhibited by aspirin plus clopidogrel, suggesting an additional benefit of this drug combination for preventing thrombosis. rFVIIa reverses the inhibitory effect of aspirin or aspirin plus clopidogrel, and could be useful for bleeding complications or when acute surgery is needed during treatment with these antiplatelet drugs.
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J. Thromb. Haemost. · Sep 2006
Fatal pulmonary embolism and fatal bleeding in cancer patients with venous thromboembolism: findings from the RIETE registry.
To examine the clinical characteristics and outcomes of cancer patients with venous thromboembolism (VTE) in order to identify factors that place these patients at an increased risk for fatal pulmonary embolism (PE) or fatal bleeding. ⋯ Both fatal PE and fatal bleeding are more common in cancer patients with VTE than in those patients without cancer. In cancer patients, abnormal renal function, metastatic disease, recent major bleeding and recent immobility for >or= 4 days are associated with an increased risk for both fatal PE and fatal bleeding.