Bleeding tendency in chronic neutrophilic leukemia.

To define the clinical and pathologic features and natural history of chronic neutrophilic leukemia (CNL), as defined by the World Health Organization (WHO), Elliott critically reviewed the literature and identified a total of 34 patients meeting strictly defined WHO criteria for CNL [1]. Of the 34 patients, 9 died of intracranial hemorrhage and 3 demonstrated easy bruising. Elliot indicated that a disproportionate number of reports of intracranial hemorrhage must be considered in the context of an association with chemotherapy-induced thrombocytopenia during treatment of progressive disease. Furthermore, he described that excess hemorrhagic events were not a significant finding in chronic stable-phase disease in the absence of chemotherapy-induced thrombocytopenia. Here, we describe platelet dysfunction in a patient with CNL complicated by bleeding tendency. At the time this patient showed bleeding symptoms, she had not received chemotherapy and her platelet count was normal. On 20 August 2003, an 83-year-old Japanese woman was referred to our department for examination of bleeding tendency. She had a 3-year history of recurrent purpura and occasional nasal bleeding. Neither the patient nor any members of her family had a history of bleeding tendencies. On physical examination, purpura was detected on the face, back and extremities. A CT scan of the abdomen demonstrated splenomegaly. Peripheral blood showed: hemoglobin, 9.7 g/dl; platelets, 284 9 10/l; leukocytes, 29.0 9 10/l with 0.2% myelocytes, 0.6% metamyelocytes, 2.0% stabs, 90.8% segments, 1.0% eosinophils, 2.2% basophils, 1.2% monocytes and 2.0% lymphocytes. Neutrophil alkaline phosphatase (NAP) score was 352 (normal, 190–370). The serum concentration of granulocyte colonystimulating factor (G-CSF) was under 10.0 pg/ml. Immunoelectrophoresis did not show any M protein in serum or urine. The bone marrow was grossly hypercellular with marked myeloid hyperplasia and 1.0% blasts. There were no dysplastic features, minimal fibrosis, normal megakaryocytes and erythropoiesis. Chromosomal analysis demonstrated a normal karyotype. Reverse transcriptasepolymerase chain reaction (RT-PCR) studies failed to demonstrate the presence of BCR-ABL fusion. The patient was diagnosed as having CNL. Routine hemostatic tests demonstrated: bleeding time, more than 8 min (normal, 1–5 min); prothrombin time, 14.9 s (normal, 10.0–13.5 s); activated partial thromboplastin time, 39.8 s (normal, 25.0–40.0 s); plasma fibrinogen level, 295 mg/dl; plasma FDP concentration, 4.1 lg/ml (normal, below 10 lg/ml). Factor VIII activity was 180% (normal, 62–145%), von Willebrand factor antigen was 136% (normal, 50–150%), and ristocetin cofactor activity was 133% (normal, 50–150%). Activities of factor XIII and a2-plasmin inhibitor were 76% (normal, over 70%) and 86% (normal, 85–118%), respectively. Platelet aggregation induced by ADP, collagen, epinephrine or ristocetin was decreased when compared to that in the control. In contrast, arachidonic acid induced platelet aggregation was normal (Fig. 1). Similar patterns of abnormal platelet aggregation were repeatedly demonstrated on three different occasions. Flow cytometric analyses of her platelets for CD41 and CD42b expression showed normal patterns. These findings suggested that this patient had storage pool disease. In this disease, platelet aggregation induced by ADP, collagen, or epinephrine is impaired, but that induced by arachidonic T. Shigekiyo (&) J. Miyagi M. Chohraku K. Kawauchi E. Sekimoto A. Shirakami H. Shibata Department of Internal Medicine, Tokushima Prefectural Central Hospital, 1-10-3 Kuramoto-cho, Tokushima 770-0042, Japan e-mail: shigekiyo@tph.gr.jp