Heart transplant in a factor VIII‐deficient patient with a high‐titre inhibitor: perioperative management using high‐dose continuous infusion factor VIII and recombinant factor VIIa

Abstract

Four years prior to transplantation, a 14-year-old boy with severe haemophilia A and a high-responding factor VIII (FVIII) inhibitor developed an anteroseptal myocardial infarct while receiving high doses of an activated prothrombin complex concentrate (PCC). Cardiac transplantation was required for survival because of the ensuing cardiomyopathy. At surgery, the patient's inhibitor titre was 1.8 Bethesda units (BU). High-dose bolus therapy, followed by a continuous infusion of FVIII provided excellent operative and initial postoperative haemostasis without additional blood-product support. Once anamnaesis developed on day 6 postoperatively, recombinant factor VIIa (rFVIIa) therapy was initiated. Haemostasis remained excellent, except for the transient increase in chest-tube bleeding that was noted on day 7. epsilon-Aminocaproic acid was added and haemostasis was re-established. On day 15, rFVIIa was replaced with alternate day infusions of prothrombin complex concentrates (PCCs). On day 21 following the transplant, the patient was discharged, remaining on daily FVIII immune tolerance and thrice-weekly PCC prophylaxis. He remains well 24 months after transplant with an inhibitor titre of 39 BU. This paper describes the second case of cardiac transplantation complicated by haemophilia and an inhibitor, and discusses preoperative planning and operative and postsurgical haemostasis management.

Extracorporeal membrane oxygenation as a bridge to cardiac transplantation in a patient with cardiomyopathy and hemophilia A

“…Successful cardiac transplantation in two patients and ventricular septal defect repair in one patient with hemophilia A have been reported [6,7,8]. All three patients were known to have factor VIII inhibitors from prior exposure to factor VIII products.…”

“…Inhibitors are most common in patients with severe hemophilia A. Occasionally inhibitors to normal exogenous factor VIII arise in mild or moderate hemophiliacs with mutant native factor VIII who receive high-dose factor therapy [7] because the patient's immune system recognizes as foreign epitopes that differ between the mutant native factor VIII and the infused normal protein. The development of factor VIII inhibitors in these patients can be associated with serious life-threatening bleeding complications [12,13].…”

Factor VIIa: Use in Patients With Hemophilia

“…Rare surgical interventions involving the use of rFVIIa in hemophilic inhibitor patients include major surgery for gastric cancer, 15 resection of a massive pseudotumour, 16 and heart transplantation 17 in a 14 year-old patient who had suffered a myocardial infarction and subsequent cardiomyopathy following use of aPCC. …”

Successful Aortic Valve Replacement Surgery in a Patient with Severe Haemophilia a with Low Titre Inhibitor

“…With multidisciplinary team approach the morbidity and mortality of cardiac surgeries in haemophilia patients have substantially reduced. However there are only a few instances of performing cardiac surgery in severe haemophilia patients with presence of inhibitors [6]. Here we describe a patient of severe haemophilia with low titre inhibitors, successfully undergoing aortic valve replacement under the cover of recombinant factor VIII support only without any intra-or post-operative complications.…”