Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
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Blood Coagul. Fibrinolysis · Jun 2004
Clinical TrialBleeding prophylaxis for major surgery in patients with type 2 von Willebrand disease with an intermediate purity factor VIII-von Willebrand factor concentrate (Haemate-P).
The parameters to diagnose von Willebrand disease (vWD) include factor VIII coagulant activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), von Willebrand factor ristocetin cofactor activity (vWF:RCo), and von Willebrand factor collagen binding activity (vWF:CB). Type 2 vWD is associated with a moderate bleeding diathesis due to low levels of vWF:RCo and vWF:CB as compared with near normal or normal values for FVIII:C and vWF:Ag. As the factor VIII/von Willebrand factor (vWF) concentrate, Haemate-P, is featured by a vWF:RCo/FVIII:C ratio of about 2.2, the recommended loading dose of 50 U/kg FVIII:C followed by 25 U/kg FVIII:C every 12 h for several days for bleeding prophylaxis in type 2 vWD patients undergoing major surgery demonstrated a predicted significant over-treatment reaching vWF:RCo levels above 2 U/ml. ⋯ Mean in vivo recoveries per transfused IU vWF:RCo/kg were 1.45% for FVIII:C, 1.7% for vWF:RCo and 1.25% for vWF:CB. The biological half-life times after transfused Haemate-P were about 12 h for both vWF:RCo and vWF:CB. Based on these pharmacokinetic data, we propose to adapt the loading dose factor VIII/vWF concentrate (Haemate-P) to 60-80 U/kg vWF:RCo followed by 30-40 U/kg vWF:RCo every 12 h for no longer than several days (less than 1 week) for bleeding prophylaxis during major surgery or trauma, and to one loading dose of 40-60 U/kg vWF:RCo for minor surgery, trauma or mucotaneous bleedings in patients with type 2 vWD unresponsive to DDAVP.
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Blood Coagul. Fibrinolysis · Jun 2004
Biophysical characterization of fibrinogen Caracas I with an Aalpha-chain truncation at Aalpha-466 Ser: identification of the mutation and biophysical characterization of properties of clots from plasma and purified fibrinogen.
Fibrinogen Caracas I is a dysfibrinogenemia with a mild bleeding tendency; a novel nonsense mutation, in the gene coding the Aalpha-chain, identified in this study as G4731T, giving rise to a new stop codon at Aalpha-Glu 467. Fibrinogen from two family members, the mother and sister of the propositus, both heterozygous for the mutation were studied, analyzing clots made from both plasma and purified fibrinogen. Clot structure and properties were characterized by turbidity, permeation, scanning electron microscopy and rheological studies. ⋯ Viscoelastic measurements revealed that fibrinogen Caracas I plasma clots were much stiffer and less subject to compaction. These results demonstrate a key role of the carboxyl-terminal alpha chains of fibrin in lateral aggregation during polymerization and reinforce the utility of studying plasma clots. It is important to point out that the biophysical studies with fibrinogen purified by two different methods yielded contradictory results, which can be accounted for by selective purification of certain molecular species as seen by two-dimensional electrophoresis.
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Child protection is a priority, and the medical community has a responsibility to detect cases of abuse and to intervene using the appropriate measures. Bruises are the most common manifestation of physical abuse, although their interpretation can be extremely challenging for paediatricians as the evidence base is limited. As a history of abuse is a strong risk factor for further non-accidental injury, a correct diagnosis is vital. ⋯ The paediatrician must also consider the combined probabilities of individual bruises being due to abuse. Our scoring system, which uses a Bayesian approach to evaluate these probabilities and assess bruising patterns, is a potentially useful tool for discriminating between abused and non-abused children. We recommend that paediatricians and haematologists should work together to reach a diagnostic consensus that is acceptable in both the clinic and a court of law.
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Blood Coagul. Fibrinolysis · May 2004
Review Randomized Controlled Trial Clinical TrialRecombinant activated factor VII in cardiac surgery.
Adult cardiac surgery has an incidence of 1-1.25 million procedures per year. Overall costs are in the range of 50 billion US dollars per year and are increasing. Included in these costs is an increasing burden from the use of blood and blood products. ⋯ The primary endpoints of the study are use of blood and blood products. Secondary endpoints are blood loss, length of stay in the intensive care unit and in the hospital, and survival. This study will give us further information on the potential efficacy and safety of rFVIIa in cardiac surgery.
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Blood Coagul. Fibrinolysis · May 2004
ReviewRole of the tissue factor pathway in the pathogenesis and management of multiple organ failure.
Sepsis is caused by a dysregulated immune response to infection and, without intervention, can lead to septic shock and multiple organ failure. A leading cause of morbidity and mortality in intensive care units worldwide, severe sepsis is also associated with a considerable cost burden that places significant strain on global healthcare budgets. ⋯ This paper will examine the pathophysiology of sepsis and multiple organ dysfunction before reviewing trials recently undertaken to investigate three potential anticoagulant therapies: antithrombin III, activated protein C, and tissue factor pathway inhibitor. Finally, other recent developments in the care of sepsis patients will be briefly examined.