Acquired factor V inhibitor in a patient with mantle cell lymphoma presenting with hematuria followed by thrombosis: a case report
A 64-year-old man initially presented to us with complaints of fatigue and joint discomfort for several months prior to December 2008. He denied experiencing any fever, night sweats, and weight loss, and did not notice any swelling, recurrent infection, easy bleeding, or bruising. Further, he did not have a family history of any hematological disorder. His past medical history included hernia repair, renal colic, gastroesophageal reflux, and osteoarthritis.\nUpon examination, one left axillary lymph node was swollen to approximately 1–2 cm, and was firm and slightly tender. His spleen was palpable on inspiration, and Castell’s sign was positive; however, his liver was not enlarged. A complete blood count showed normal platelet and hemoglobin levels of 206 × 10−9/L and 155 g/L, respectively, but a high white blood cell count of 18 × 10−9/L. A leukocyte differential indicated the following: lymphocytes 10.3; neutrophils 6.75; monocytes 0.58; eosinophils 0.23; and basophils 0.05. Peripheral blood flow cytometry revealed a CD19+, CD20+, CD5+, CD23−, CD10− clonal B-cell population. Additionally, 37% of gated lymphocytes were FMC7-positive. The proportion of this FMC7-positive population reduced to 17% during a second flow analysis one month later, suggesting the possibility of mantle cell lymphoma or CD23-negative chronic lymphoid leukemia. Given that the patient was asymptomatic and showed no signs of bone marrow failure, a strategy of watchful waiting was implemented.\nIn August 2009, 8 months after his initial visit, the patient was admitted to the emergency room with a 2-day history of hematuria. Evaluation of his blood plasma revealed a prolonged international normalized ratio (INR) of 6 and an activated partial thromboplastin time of 160 seconds. Except for some minor skin bruising on his face, the patient had no other bleeding or bruising, nor was any area abnormal on examination. Further, he had no past history of bleeding, with uneventful surgical procedures and tooth extractions in the past. On careful investigation of his coagulopathy, a prothrombin time mixing study was abnormal at −43 partially corrected to 30 seconds only (normal 12.5–15.7 seconds), suggesting the presence of an inhibitor. The thrombin time was 15.8 seconds (normal 15.5–18.3 seconds), serum fibrinogen level was 5.8 g/L (normal 2.00–4.30 g/L), factor V level was <0.01 U/mL (normal 0.5–1.5 U/mL), factor VIII level was 3.23 U/mL (normal 0.5–1.5 U/mL), factor X level was 1.08 U/mL (normal 0.5–1.5 U/mL), and factor IX level was 1.17 U/mL (normal 0.5–1.5 U/mL). Lupus anticoagulant testing could not be interpreted owing to the presence of the inhibitor. Serum protein electrophoresis did not indicate the presence of a monoclonal protein. Based on these results, a factor V inhibitor test was performed and indicated a factor V inhibitor titer of 80 Bethesda units. The patient was started on prednisone (1 mg/kg, 80 mg daily), and after 2 weeks of treatment, the bleeding had stopped and serial measurement of factor V levels showed a dramatic increase; moreover, within 7 weeks, factor V levels were normal and factor V inhibitor was undetectable.\nSurprisingly, 7 weeks after initiation of steroid treatment, the patient developed an unprovoked severe pain with swelling in his right leg. A week prior to this event, his prothrombin time was 17 seconds, activated partial thromboplastin time was 28 seconds, INR was 1.4, and the factor V assay value was 0.62 Bethesda units/mL, but factor V inhibitor was undetectable. Doppler ultrasound revealed deep venous thrombosis, and low-molecular-weight heparin (dalteparin, 12,500 U) and coumadin (7.5 mg) were administered orally once daily. The patient’s condition continued to improve with no further bleeding or thrombotic events, and anticoagulation was successfully discontinued after 8 months. The use of prednisone was gradually decreased over several weeks after confirmation of the disappearance of the inhibitor, and was discontinued completely in December 2009 (). Screening assays to rule out inherited thrombophilia were negative for antithrombin, protein C, protein S, factor V Leiden, and prothrombin 20210 gene mutations. Fluorescence in situ hybridization analysis of a peripheral blood sample showed IGH/CCND1 t(11;14), which confirmed the presence of a clonal B-cell population characteristic of mantle cell lymphoma.