Management of acquired haemophilia A

Summary

Acquired haemophilia A (AHA) is caused by autoantibody inhibitors of coagulation factor VIII (FVIII : C). Recent onset of bleeds and isolated prolongation of the activated partial thromboplastin time (aPTT) are characteristic features of the disorder. Reduced FVIII : C activity and a detectable FVIII : C inhibitor in the Bethesda assay confirm the diagnosis. Patients should be referred to expert centres, whenever possible, and invasive procedures with a high risk of bleeding must be avoided, until haemostasis has been secured by adequate therapy.

Bypassing agents capable of inducing sufficient thrombin formation in the presence of FVIII : C inhibitors are treatment of choice, including currently available recombinant factor VIIa (NovoSeven™) and activated prothrombin complex concentrate (FEIBA™). These agents represent first line therapy to control acute or severe bleeds. To eradicate inhibitors, immunosuppressive treatment (IST) is indicated in patients with AHA. Glucocorticoids, cytotoxic agents and rituximab are most widely used. However, an ideal IST regimen has not been established so far. Adverse events of IST, including infections as the foremost cause death, are frequent complications in AHA.

Zusammenfassung

Die erworbene Hämophilie A wird durch Auto - antikörper gegen den Gerinnungsfaktor VIII (FVIII : C) verursacht. Eine neu aufgetretene Blutungsneigung und isolierte Verlängerung der aktivierten partiellen Thromboplastinzeit (aPTT) sind Hinweise auf die Erkrankung. Die Diagnose wird durch reduzierte FVIII : C-Aktivität und im Bethesda-Test nachweisbaren FVIII : C- Inhibitor bestätigt. Die Patienten sollten in erfahrenen Zentren behandelt werden. Invasive Prozeduren mit hohem Blutungsrisiko sind unbedingt aufzuschieben, bis die Hämostase durch adäquate Behandlung wieder gewährleistet ist.

Therapie der Wahl ist der Einsatz so genannter Bypass-Produkte, die auch in Anwesenheit von FVIII:C-Inhibitoren eine ausreichende Thrombinbildung bewirken. Zur Verfügung stehen gegenwärtig rekombinanter Faktor VIIa (NovoSeven^®) und aktiviertes Prothrombinkomplex- Konzentrat (FEIBA^®). Bei akuten oder schweren Blutungen haben sich diese Medikamente als Erstlinientherapie bewährt. Zur Eradikation des Inhibitors sollten Patienten mit erworbener Hämophilie eine immunsuppressive Therapie (IST) erhalten. Glucokortikoide, Zytostatika und Rituximab sind die am häufigsten eingesetzten Substanzen. Allerdings existiert bislang kein optimales IST-Regime. Unerwünschte Arzneimittelwirkungen der IST, vor allem Infektionen als häufigster Todesursache, sind oftmals auftretende Komplikationen bei Patienten mit erworbener Hämophilie.

Keywords

Factor VIII : C - inhibitor - bleeding - recombinant factor VIIa - activated prothrombin complex concentrate - immunosuppression

Schlüsselwörter

Faktor VIII : C - Hemmkörper - Blutungsneigung - rekombinanter Faktor VIIa - aktiviertes Prothrombi nkomplex-Konzentrat - Immunsuppression

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