Factor VIII and IX deficiencies related to acquired inhibitors in a patient with chronic hepatitis C virus infection receiving treatment with pegylated interferon plus ribavirin

Abstract

The development of clotting factor inhibitor autoantibodies is rarely observed, but can result in a potentially life-threatening haemorrhagic disorder. These acquired inhibitors are most frequently against factor VIII (FVIII), whilst the detection of inhibitors against other clotting factors is rarer. Inhibitors against FVIII and FIX are mostly observed in patients with classical hereditary haemophilia after receiving factor replacement therapy. We report a rare case of acquired FVIII and factor IX (FIX) inhibitors in a single, non-haemophilic patient with chronic hepatitis C virus (HCV) infection who was receiving antiviral treatment with pegylated interferon plus ribavirin. The FVIII and FIX activities were <1% and high titres of inhibitors autoantibodies were found in his serum samples. After achieving a sustained virological response, combined immunosuppression with oral corticosteroids (prednisone) and azathioprine was introduced, eradicating the inhibitory autoantibodies. The development of these inhibitors in association with antiviral therapy for chronic hepatitis C is poorly understood, and particular attention must be given to HCV-infected patients with worsening coagulopathy, particularly if coexistent with treatment related thrombocytopenia.

Symptomatic Acquired Haemophilia Due to Circulating Antibodies Against Both Factor VIII and IX in a Non-haemophiliac Patient

“…One of the earliest reports is by Reussi C et al [5] [8] reports the occurrence of combined inhibitors in a patient with Sjogren's syndrome, Campos-de-Magalhaes's [9] patient developed the antibodies during therapy with pegylated interferon with ribavirin for chronic hepatitis C infection. All these instances appear to be cases of secondary acquired inhibitors.…”

“…However the haemorrhages which are hallmark of congenital haemophilia seldom occur in these patients [1, 3, [4]. The literature survey shows only about five case reports of simultaneous occurrence of acquired inhibitors to both factor VIII and IX [5][6][7][8][9]. To the best of our knowledge this is the first case report of occurrence of idiopathic acquired haemophilia with inhibitors to both factor VIII and IX in adults.…”

Acquired FVIII and FIX Inhibitors after Pregnancy: A Case Report

“…An explanation is that the smaller FIX protein may be less immunogenic than the FVIII molecule and therefore less likely to provoke antibody formation [1]; the co-occurrence of inhibitors to multiple coagulation factors, as in our case, is uncommon. Only 6 case reports that describe FVIII and FIX codeficiencies have been published to date [2,3,4,5,6,7]. These autoantibodies may induce spontaneous life-threatening bleeding in patients who have no previous history of bleeding disorder.…”

Acquired factor VIII inhibitor associated with chronic untreated hepatitis C

“…3 However, when a cause is identified, AHA is often associated with interferon-α exposure, or with concurrent X-linked hemophilia A, cancer, autoimmune disease, HIV, pregnancy, or other immune-modulating conditions and treatments. [3][4][5][6][7][8] As low-titer cases suspected to go unnoticed without a significant inciting bleeding event. 2 These cases are found in 15% of the known patient population with acquired factor VIII inhibitors and depend upon the subtype of autoantibody and the domain of factor VIII that they recognize.…”