Cross‐reacting recombinant porcine FVIII inhibitors in patients with acquired haemophilia A

Abstract

Acquired haemophilia A (AHA) is a rare haemostatic disorder caused by the production of autoantibodies to clotting factor VIII (FVIII). These antibodies primarily bind to the A2, C1 or C2 domains of endogenous FVIII, neutralizing the cofactor function. 1,2 The incidence of AHA is estimated at 1.48 per million population per year, of which 80%-90% of patients are elderly, 3 although there is also a reported association with pregnancy. 4 Patients with AHA often present with spontaneous bleeding and extensive soft tissue haematoma 3 with a high risk of morbidity or mortality. 5 Many patients require treatment of active bleeding which may include the use of FVIII bypassing agents, activated prothrombin complex concentrate (APCC), recombinant activated factor VII (rFVIIa) or, more recently, recombinant

Recombinant porcine factor VIII: Lessons from the past and place in the management of hemophilia A with inhibitors in 2021

“…It is well tolerated, and the most frequent adverse event is the development of antibodies against r‐pFVIII. Two recent independent studies reported that cross‐reacting inhibitors were more frequent in people with anti‐hFVIII inhibitor titers >100 BU/mL 45,46 . Following drug approval, some case reports and studies on cohorts of people with acquired hemophilia A treated with r‐pFVIII have been published, all confirming susoctocog alfa good efficacy and safety for the management of severe bleeding episodes 47‐49 .…”

“…Two recent independent studies reported that cross-reacting inhibitors were more frequent in people with anti-hFVIII inhibitor titers >100 BU/mL. 45,46 Following drug approval, some case reports and studies on cohorts of people with acquired hemophilia A treated with r-pFVIII have been published, all confirming susoctocog alfa good efficacy and safety for the management of severe bleeding episodes. [47][48][49] A retrospective case series (n = 4 individuals with acquired hemophilia A) showed that this molecule is effective and safe.…”

Laboratory coagulation tests and recombinant porcine factor VIII: A United Kingdom Haemophilia Centre Doctors’ Organisation guideline

“…These inhibitors to human FVIII may cross‐react with porcine FVIII in some patients, though the affinity is lower than towards human FVIII 3 . Two European studies reported similar baseline cross‐reacting inhibitor incidence of approximately 44%–49% in patients diagnosed with AHA 24,25 …”

“…There are limited detailed reports of the time course of cross‐reacting rpFVIII inhibitors in patients undergoing treatment with rpFVIII out‐with clinical trials 25–31 . In some patients treated with rpFVIII no increase in cross‐reacting rpFVIII inhibitors were observed following therapy 26,28,29 .…”

“…A heat inactivation step may be included if the patient is suspected to have measureable human or porcine FVIII:C in their plasma REF. A range of patient plasma dilutions should initially be included because the titres vary greatly between individuals 24,25 . The kinetic pattern of FVIII inhibitors in inhibitor positive patients may be either type 1 or type 2; the inclusion of multiple plasma dilutions will indicate the time course of inactivation of FVIII in individual patients 25 .…”