FactorVIIa and its potential therapeutic use in bleeding-associated pathologies

TY - JOUR

T1 - FactorVIIa and its potential therapeutic use in bleeding-associated pathologies

AU - Hedner, Ulla

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Emergency medicine/Medicine/Surgery (013240200)

PY - 2008

Y1 - 2008

N2 - Recombinant FVIIa (rFVIIa) was developed for treatment of haemophilia patients with inhibitors against FVIII/FIX. The haemostatic efficacy rate of 80-90% including major orthopaedic surgery (dosing of 90-120 mu g/kg every other hour [h] for at least the first 24 h) was achieved in these patients. In a home-treatment setting the efficacy rate of haemostasis in mild-moderate bleedings was 92% (average number of 90 mu g/kg doses was 2.2). A wide individual variation regarding recovery of rFVIIa (46 12%; median 43%) as well as of clearance rate (36 8 ml/kg/h; median 32 ml/kg/h in adults; children 2-3 times higher) has been observed. Thus children may require higher doses than adults. Accordingly the use of a dose of 270 mu g/kg in one single injection was approved in the EU. Recent experience indicates that repeated doses of rFVIIa may decrease the number of bleeds in,,target joints", and thus may be useful as prophylaxis in severe hemophilia with inhibitors. Pharmacological concentrations of rFVIIa have been shown to enhance the thrombin generation on thrombin activated platelets in a cell-based model. By doing so a tight structured fibrin haemostatic plug resistant against premature lysis is formed. rFVIIa has been shown to induce haemostasis not only in haemophilia but also in other situations characterized by an impaired thrombin generation such as platelet defects, dilution coagulopathy developed as a result of trauma and extensive surgery. A special form of profuse bleeding, that may cause extensive problems is postpartum haemorrhage.

AB - Recombinant FVIIa (rFVIIa) was developed for treatment of haemophilia patients with inhibitors against FVIII/FIX. The haemostatic efficacy rate of 80-90% including major orthopaedic surgery (dosing of 90-120 mu g/kg every other hour [h] for at least the first 24 h) was achieved in these patients. In a home-treatment setting the efficacy rate of haemostasis in mild-moderate bleedings was 92% (average number of 90 mu g/kg doses was 2.2). A wide individual variation regarding recovery of rFVIIa (46 12%; median 43%) as well as of clearance rate (36 8 ml/kg/h; median 32 ml/kg/h in adults; children 2-3 times higher) has been observed. Thus children may require higher doses than adults. Accordingly the use of a dose of 270 mu g/kg in one single injection was approved in the EU. Recent experience indicates that repeated doses of rFVIIa may decrease the number of bleeds in,,target joints", and thus may be useful as prophylaxis in severe hemophilia with inhibitors. Pharmacological concentrations of rFVIIa have been shown to enhance the thrombin generation on thrombin activated platelets in a cell-based model. By doing so a tight structured fibrin haemostatic plug resistant against premature lysis is formed. rFVIIa has been shown to induce haemostasis not only in haemophilia but also in other situations characterized by an impaired thrombin generation such as platelet defects, dilution coagulopathy developed as a result of trauma and extensive surgery. A special form of profuse bleeding, that may cause extensive problems is postpartum haemorrhage.

KW - tissue

KW - haemophilia A / B

KW - haemostasis

KW - FactorVIIa

KW - haemophilia therapy

KW - factor / factorVII

U2 - 10.1160/TH08-07-0434

DO - 10.1160/TH08-07-0434

M3 - Article

VL - 100

SP - 557

EP - 562

JO - Thrombosis et diathesis haemorrhagica

JF - Thrombosis et diathesis haemorrhagica

SN - 0340-6245

IS - 4

ER -