Effective treatment with recombinant factor VIIa of severe bleeding due to acquired factor VIII inhibitor and acquired thrombocytopathy

Abstract

To the Editor: Rituximab, a chimeric murine-human monoclonal anti CD20 antibody, is approved for the treatment of relapsed or refractory, CD20(+) B-cell, low-grade or follicular non-Hodgkin's lymphoma (NHL). This antibody is also being used and evaluated against other CD20-expressing hematological malignancies and autoimmune disorders [1]. Recently, D'Arcy and Mannick [2] reported the first case of serum sickness occurring 10 days after the patient started a protocol of 4 weekly infusions of rituximab for refractory autoimmune polyneuropathy. The patient presented with fever, polyarthritis, and transient decrease of C3 and C4 levels. IgG antibodies directed to the murine FabЈ fragments of the rituximab were found [2]. We observed a similar clinical presentation in a 48-year-old woman with refractory immune thrombocytopenia (anti-nuclear factor negative). Six days after the second course of rituximab on a weekly protocol, the patient was admitted because of fever (38.5°C), malaise, symmetric polyarthritis of large and small joints, and a morbilliform skin eruption. At the same time, her platelet count dropped to 2,000, and she was treated with methylprednisolone 500 mg (i.v.) for 2 days. The patient responded favorably to the treatment, and less than 48 h after the treatment was started the symptoms and the signs of serum sickness resolved.Although rituximab is a chimeric murine-human antibody, only 3 patients out of more than 300 patients who were treated with rituximab and were tested for human anti-chimeric antibodies showed detectable antibodies levels [3]. None of them was reported to develop serum sickness. This is the second case reported of rituximab-induced serum sickness; both cases occurred a few days after the second course of rituximab for an autoimmune disorder, and both of them responded favorably to glucosteroid treatment. We believe that with increasing clinical experience with rituximab more cases of serum sickness will occur; therefore, the clinicians should be aware of this adverse effect. YAIR HERISHANU Effective Treatment With Recombinant Factor VIIa of Severe Bleeding Due to Acquired Factor VIII Inhibitor and Acquired ThrombocytopathyTo the Editor: Acquired hemophilia is a rare, severe hemorrhagic diathesis in nonhemophiliac patients [1]. Moreover, the appearance of a coagulation factor VIII inhibitor and alteration in the platelet function are exceptional. Activated recombinant factor VII (rVIIa) has been used recently in the antihemorrhagic treatment of patients with factor VIII inhibitors and thrombopathies [2]. We present, to the best of our knowledge, the first case of a nonhemophiliac patient, with acquired hemophilia and thrombopathy secondary to a malignant hemopathy, who was treated satisfactorily with rVIIa.A 65-year-old nonhemophiliac man presented a large hematoma of his right arm following extraction for arterial gasometry test. The activated partial thromboplastin time was 118 sec (control 25-40 sec), which was not corrected by normal fresh plasma; factor VIII:C 3%; factor V...

Treatment of acquired haemophilia with recombinant activated FVII: a critical appraisal

“…The use of concomitant haemostatic agents was reported for 44 patients [3,19–39,41–47,49,50,52–54,57–60]. The most commonly reported haemostatic agents were activated prothrombin complex concentrates (seven patients), FVIII concentrates (seven patients), porcine FVIII (seven patients), fresh frozen plasma (five patients) and tranexamic acid (four patients).…”

“…Published reports for patients included in the compassionate use programmes or HTRS registry were excluded. Forty‐three publications, including scientific meeting abstracts and one electronic case publication, met inclusion criteria and describe the use of rFVIIa in 69 acquired haemophilia patients with 91 reported bleeding episodes [3,19–60].…”