Case Report of a Primary Splenic Marginal Zone Lymphoma Patient Presenting with Factor VII Inhibitor

Abstract 4927

We present the case report of a 38 year old female presenting with primary splenic marginal zone lymphoma and a Factor VII inhibitor. She presented with pancytopenia (WBC 2.1 × 10@9/L, Hemoglobin 74 g/L, platelets 122× 10@9/L), an elevated INR 3.2 (0.8-1.2) and a normal aPTT 25 sec (22 - 36), and massive splenomegaly. Spleen measured 33 cm in length on coronal CT images. The liver was slightly prominent. There were no masses in liver or spleen, nor any abnormal adenopathy. Her IgM was elevated at 16.2 g/L(0.46-3.04), immunofixation positive for IgM Kappa. Bone marrow biopsy revealed patchy infiltrates of small lymphocytes strongly positive for CD 20. CD 5, Cyclin D1, CD10, CD23, CD138 and DBA44 were negative. Flow cytometry revealed a monoclonal infiltrate positive for CD19, CD20, FMC7, CD23, and kappa light chain restricted. Flow cytometry was negative for CD11c, CD25, and CD103. With this information, the diagnosis of primary splenic marginal zone lymphoma was made, despite the positive CD23 on flow cytometry. Splenectomy was not possible because of the coagulopathy.

Mixing studies at 60 minutes did not correct the coagulopathy. Factor VII was low at 0.37 [0.5-2.0], Fibrinogen 2.78 g/L [2.00 - 4.00], Lupus anticoagulant was negative, Factor II 0.40 U/mL, [0.50-2.00], Factor V 0.37 U/mL [ 0.50– 2.00], Factor X 0.09 U/ml [0.50-2.00], and Factor VII inhibitor was elevated at 4.8 Bethesda units. Factor VII inhibitor showed cross reactivity with factors II, V, and VII.

She was initially treated with fresh frozen plasma (> 8 units) and IV Vitamin K (10 units × 2) without correction of her INR. She underwent five days of plasma-pharesis with partial correction of her INR to 2.6.

With concerns regarding bleeding risks, cytotoxic chemotherapy was avoided and patient was given single agent Rituximab at 375 mg/m2 for four weekly doses. The initial infusion was complicated with severe thrombocytopenia: 13,000 × 10@9. The platelet count recovered to > 75×10@9/L by day 4 post her first infusion. She received her second infusion on day 10. Her platelet count nadir was 50×10@9 this time. Her spleen had a remarkable response, shrinking to 15 cm below the costal angle following the first infusion and only splenic tip palpable by the fourth. Her INR continued to normalize and was at 1.4 by the end of the fourth cycle. The patient received four more weekly cycles of Rituximab with complete resolution of splenomegaly and coagulopathy. Following that the patient underwent splenectomy. Pathology on this spleen revealed no malignancy indicating complete remission to treatment. She received two years of maintenance Rituximab (one dose every 3 months) and remains disease free without recurrence of splenomegaly nor coagulopathy at 2.5 years followup.

To our knowledge, only a handful of previous cases factor VII inhibitor have been reported. We report the successful management of a difficult case using anti-CD20 monoclonal antibody treatment alone.