Evaluation of the Efficacy and Safety Immunosuppressive Therapy in Patients with Acquired Factor VIII and IX Inhibitor

Abstract

Objectives: Acquired factor inhibitor is a rare disorder and can cause life-threatening bleeding. Consequently, we report the efficacy and safety of our patients with acquired factor inhibitor treated with immunosuppressive drugs. Materials and Methods: We retrospectively investigated acquired factor inhibitor patients who were followed and treated in our center between November 2018 and March 2022. Results: A total of seven patients, four of whom were male, with a median age of 65 (43-76) were included. Acquired factor inhibitor was associated with malignancy (n=3), advanced age (n=2), postpartum period (n=1) and lupus anticoagulant (n=1). Median follow-up time was 9 months (range, 2-46). High inhibitor titres were detected in four patients [median: 7.06 BU/mL (range, 5.76-100)] and all of them were treated with immunosuppressive drugs (metilprednisone in combination with cyclophosphamide, rituximab). The overall response rate was 100% (n=4) with 50% complete response and 50% partial response and one patient who developed the inhibitor in the postpartum period responded to single agent rituximab. To achieve the hemostatic target, recombinant activated clotting factor VII (rFVIIa) and activated prothrombin complex concentrate (aPCC) were used in two out of four patients with active bleeding. Hemostasis was achieved successfully. Three patients developed a low-titre factor inhibitor and immunosuppressive drugs were not started for inhibitor elimination. Coagulation assays disappeared when the underlying condition was self-limited. Conclusion: Clinical presentation of factor inhibitors is highly variable and optimal treatment is not clearly established. Rituximab might be a promising treatment for therapy-resistant factor inhibitor and bleeding control was achieved with rFVIIa and aPCC. Treatment plan of patients with low-titre factor inhibitor should be provided considering the clinical situation and underlying disease.

Keywords

• Factor Inhibitor
• Immunosuppressive Theraphy
• Hemostasis

Kazanılmış Faktör VIII ve IX İnhibitörü Olan Hastalarda İmmünosüpresif Tedavi Etkinlik ve Güvenilirliğinin Değerlendirilmesi

Abstract

Amaç: Mortalitesi yüksek kanamalara yol açabilen ve nadir gözlemlenen kazanılmış faktör inhibitörü olan hastalarda, immünosüpresif tedavi etkinlik ve güvenilirlik sonuçlarının değerlendirilmesidir. Gereç ve Yöntem: Kasım 2018-Mart 2022 tarihleri arasında merkezimizde kazanılmış faktör inhibitörü ile takip ve tedavi edilmiş hastalar çalışmaya dahil edildi. Bulgular: Çalışmaya ortanca yaşı 65 (aralık, 43-76) dördü erkek toplam yedi hasta dahil edildi. Faktör inhibitör gelişim nedenleri; postpartum dönem (n=1), lupus antikoagülan (n=1), ileri yaş (n=2) ve malignite (n=3) olup, tüm hastalarda ortanca takip süresi 9 ay (aralık, 2-46 ay) idi. Dört hastada tanıda yüksek titreli inhibitör vardı [ortanca: 7,06 BÜ/mL (aralık, 5,76-100)] ve tümü immünosüpresif tedavi (metilprednizolon ve siklofosfamid kombinasyonu, rituximab) almıştı. Hastaların tamamı immünosüpresif tedaviye yanıt verirken (toplam yanıt oranı %100; tam yanıt %50, kısmi yanıt %50), postpartum dönemde faktör inhibitörü gelişmiş bir hastada rituximab tedavisine yanıt alınmıştır. Hastaların ikisinde kanama sırasında rekombinant aktive-faktör VII (rFVIIa) ve aktive protrombin kompleks konsantreleri (aPCC) hemostazı sağlamıştır. Düşük titrede faktör inhibitörü saptanan üç hasta ise kanama olmadığından immünosüpresif tedavi almamış, hastalarda ihibitör gelişiminden sorumlu neden ortadan kalktığında koagülasyon testleri düzelmiştir. Sonuç: Kazanılmış yüksek titreli faktör inhibitörü olan hastalarda bilinen tedavi seçeneklerinin birbirine üstünlüğü kanıtlanmamıştır. Dirençli faktör inhibitör tedavisinde rituximab alternatif bir seçenek olabilir ve hastalarda hemostazı sağlamada rFVIIa ve aPCC kullanımı etkindir. Düşük titrede faktör inhibitörü olan hastaların tedavisinde ise klinik durum ve altta yatan hastalık göz önünde bulundurularak tedavi planı yapılmalıdır.

Keywords

• Faktör İnhibitör
• İmmünosüpresif Tedavi
• Hemostaz

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