Reizo Nagayama

Primary Thrombocythemia in Japan: A Survey of 225 Patients

Data on 225 Japanese patients with primary or essential thrombocythemia (ET) were analyzed in an attempt to characterize the clinical and laboratory features in subgroups with thrombosis (T), hemorrhages (H), thrombohemorrhagic events (TH) or a non-thrombohemorrhagic (O) group, and in order to examine survival and the incidence of blastic transformation in the entire group and in the different subgroups. Higher platelet and leukocyte counts were related to hemorrhage (H and TH), prolonged activated partial thromboplastin times and high LDH levels to H while elevated FDP levels were more frequently linked to T. Increased spontaneous platelet aggregation (SPA) was noted in 80.3% of the entire group, independent of whether there was a tendency for thrombohemorrhagic events or not. Bleeding time, as measured by the Duke method, and hemoglobin levels were not different in the various subgroups. Transformation occurred in 11 patients (1.9% per year); seven developed acute leukemia (myeloblastic 4, lymphoblastic 2, megakaryoblastic 1) at a rate of 1.2% per year; and 4 developed other types of chronic myeloproliferative disorders. Nineteen patients died (3.3% per year), six from leukemia (32%), 4 from bleeding (21%) and 9 from unrelated diseases (47%). Survival was estimated to be 65% at ten years, and was significantly longer in females, younger individuals, and the groups with lower leukocyte counts, but did not differ between the subgroups when platelet count and hemoglobin level were considered. Survival was similar in patients with platelet counts between 700-1000 × 10(9)/L and in those with an even higher platelet count. These findings suggest that (1) young female patients with low leukocyte counts may survive longer, (2) SPA is not indicative of either a thrombotic or an hemorrhagic tendency and (3) the limit of the platelet count for establishing the diagnosis of this disorder could perhaps be lowered to 700 × 10(9)/L.

Heat-Treated Factor VIII/von Willebrand Factor Concentrate in Platelet-Type von Willebrand’s Disease

Cryoprecipitate has proved to correct the hemostatic defects in von Willebrands disease (vWD) and platelet-type vWD. However, recent studies have revealed that transmission of the AIDS retrovirus (HIV) occurs through exposure to blood products including cryoprecipitate. Treatment with heat-treated factor VIII/von Willebrand factor (vWf) concentrates may have certain advantages over treatment with nonheated products, if these preparations are efficacious in these disorders. We found that a commercially available factor VIII/vWf concentrate, Haemate P, contained the high-molecular-weight multimers of vWf and had a ratio of ristocetin cofactor (RCof) to vWf antigen (vWf:Ag) close to unity. In addition, its capacity to directly induce aggregation of platelet-type vWD platelets in vitro was similar to that for cryoprecipitate. When infused into a patient with platelet-type vWD, Haemate P shortened the prolonged bleeding time and caused spontaneous platelet aggregation in vitro with a mild diminution of platelet count. These results indicate that some of the heat-treated factor VIII/vWf concentrates may provide a safer, yet still effective, treatment for platelet-type vWD.

Complement receptor type 1 (CR1) deficiency on neutrophils in myelodysplastic syndrome

Summary. We present a patient with myelodysplastic syndromes (MDS) whose neutrophils exhibited defective expression of complement receptor type 1 (CR1). A 73‐year‐old man was admitted with an evolution of MDS from RA into RAEBT according to the FAB classification of MDS. The neutrophil alkaline phosphatase (NAP) score was zero. The surface expression of membrance effector melecules on neutrophils was determined by indirect immunofluorescence using flow cytometry and monoclonal antibodies. The expression of CR1 on neutrophils as identified by staining with CD35 was defective in the patient, and the expression of other complement receptors (CR3 and CR4), Fc receptors and adhesion molecules was normal. CR1 deficiency and defective NAP score on neutrophils in the patient might account for impairment of common storage pool, presumably novel intracellular secretory vesicles.

Perinuclear peroxidatic activity in erythroblasts

PIatelet peroxidase (PPO) is synthesized early during megakaryocytic maturation and thought to be an enzymatic marker of this cell lineage (Breton-Gorius & Guichard, 1972; Breton-Gorius et al, 1978). PPO is useful for the diagnosis of megakaryoblastic leukaemia (Breton-Gorius & Guichard, 1972: Breton-Gorius et aJ, 1978; Bain et al, 1981; Koike, 1984). PPO has characteristics distinct from myeloperoxidase. PPO activity is located in the perinuclear space and endoplasmic reticulum and can be easily inhibited by aldehyde fixation at a high concentration. We report a patient with ‘acute myelodysplasia with myelofibrosis’ (Sultan et aJ, 1981) in which circulating erythroblasts exhibited peroxidase similar to PPO. Until the present report, true peroxidatic activity, to our knowlege, has not been detected in the erythrocytic series by either optical or electron microscopical cytochemistry, although haemoglobin has been known to react nonenzymatically with diaminobenzidine (DAB) and dense reaction products are seen throughout the cytoplasm of polychromatic erythroblasts (Dvorak et al, 1972). A 60-year-old man was admitted to our hospital in September 1982 with ecchymoses. On physical examination he appeared anaemic and had numerous petechiae on his body. There was no lymphoadenopathy or hepatosplenomegaly. Laboratory findings on admission were as follows: RBC 2.65 x 10l2/1, Hb 8-2 g/dl, platelets 25-109/1, reticulocytes 0*1%, WBC 2.4 x 109/1 with 5% bands, 53% segmented PMNs, 39% lymphocytes 2% basophils and 1% monocytes. Occasional blasts were seen. A bone marrow aspiration was nearly a dry-tap but showed relative erythroid hyperplasia and a marked left shift in the myeloid series with about 10% blasts. A trephine biopsy revealed a normoor hypo-cellular marrow with focal fibrotic areas. Reticulin fibres were increased. The clinical findings and the entire blood picture were indicative of ‘acute myelodysplasia with myelofibrosis’. From October 1982 the patient was treated with anabolic steroids, which were continued until the terminal stage. This treatment, however, was not effective. He was supported with red cell and platelet transfusions, but the pancytopenia gradually progressed. In January 1983 blast cells began to increase rapidly in the peripheral blood. Interestingly, dysplastic erythroblasts also increased in the peripheral blood, accompanied by an increase in blasts. On the day before he died of sepsis with disseminated intravascular coagulation, the WBC count was 2 x 109/1 with 50% blasts, and erythroblasts were seen at a ratio of 150 per 100 WBC. These erythroblasts showed various morphological abnormalities, such as megaloblastoid features. irregular nuclear shape, and multinuclearity. Peripheral blood erythroblasts obtained at the terminal phase were examined by electron microscopy. Peroxidatic activity was detected using a slight modification (Koike, 1984) of the method described by Anderson et d (1975). The specimens were prefixed using a tannic acidformaldehyde-glutaraldehyde mixture. The pH of the DAB medium was adjusted to 7.6 and