Acquired factor VIII inhibitors

Abstract

Acquired hemophilia A is a rare bleeding diathesis caused by autoantibodies directed against clotting factor VIII and associated with an increased morbidity and mortality. This autoimmune disorder most commonly occurs in the elderly. Although it may be associated with several underlying pathologies, up to 50% of reported cases remain idiopathic. In contrast with congenital hemophilia, which is commonly characterized by hemarthroses, hemorrhages in patients with acquired hemophilia involve most frequently soft tissues. The 2 treatment priorities are to arrest the acute bleeding and to eradicate the factor VIII autoantibody. Acute bleeding episodes in patients with low-titer inhibitors can be treated using human factor VIII concentrates, whereas factor VIII bypassing agents, such as activated prothrombin complex concentrates or recombinant activated factor VII, are effective for the treatment of those with hightiter inhibitors. An analysis of the literature shows that the most effective first-line treatment for the eradication of factor VIII autoantibodies is the combination of steroids and cyclophosphamide. However, there is increasing evidence on the effectiveness of other treatment approaches, such as immune tolerance regimens and rituximab. If confirmed by large controlled studies, these innovative therapies might become a valid option for long-term eradication of factor VIII inhibitors. (Blood. 2008;112:250-255)

Autoimmune hemophilia at rescue

“…The recommended dosages and schedules of administration are very similar: bolus injections of rFVIIa, 90 µg/kg every 2-3 hours (Franchini and Lippi mention the possible usage of dosages up to 120 µg/kg), 7 and 50-100 U/kg FEIBA every 8 to 12 hours, (Huth-Kühne et al 6 recommend not exceeding a maximum daily dosage of 200 IU/Kg). On the whole, it would appear that both the agents are able to control as many as 80-90% of bleeding episodes (spontaneous and post-traumatic), even though there is no face-to-face comparison.…”

Quality in coagulation and haemostasis testing

“…Mo re cli ni cal ly im por ta nt is that the se pa tien ts can su er se rious blee di ng prob le ms (45). Whi le so me pa tien ts can de ve lop in hi bi to rs af ter treat me nt wi th plas ma pro duc ts (e.g., hae mop hi lia pa tien ts that de ve lop al loan ti bo dies), ot he rs can de ve lop in hi bi to rs se con da ry to so me ot her di sease pro ce ss (e.g., au toan ti bo dies that lead to an acqui red hae mop hi lia), and ot he rs can be idio pathic (un known cau se).…”

Desenvolvimento de inibidores do fator VIII na hemofilia A

“…57,58 Esta opção de tratamento tem se mostrado bastante eficiente e uma grande quantidade de estudos relaciona a sua eficácia no tratamento de anticorpos inibidores de FVIII em indivíduos com hemofilia adquirida. [59][60][61][62] Entretanto, notificações de reações adversas relacionadas ao uso do medicamento têm sido emitidas e casos de síndrome de liberação excessiva de citocinas com resultado fatal já foram relatados. 63 Desta forma, estudos clínicos ainda devem ser realizados para se obterem mais informações sobre o uso deste tipo de tratamento neste grupo de indivíduos.…”