An unusual platelet function defect: report of 19 cases.

Selective impairment in platelet responsiveness to epinephrine has been seen in certain acquired conditions and very rarely as a hereditary disorder. To the best of our knowledge this hereditary defect has been described in a single family and in two other individuals. We describe here 19 cases of this defect. Subjects with history of generalized bleeding with a prolonged bleeding time, PF3 availability or prothrombin consumption index and a normal platelet count, prothrombin time, activated partial thromboplastin time, clot solubility were subjected to platelet aggregation. Those of these who showed a normal aggregation with ADP, collagen, arachidonic acid and an absent aggregation with epinephrine were included in our study group. Subjects with history or findings suggestive of antiplatelet drug intake or any acquired condition giving rise to this abnormality were excluded from this study. 74% of the patients had onset of bleeding manifestations since childhood (<14 years) with a mean age at onset of 10.4 years. All patients presented with mild bleeding manifestations, the commonest symptom being appearance of recurrent ecchymotic spots. In females, menorrhagia was the commonest symptom. We present here probably the first report of the occurrence of hereditary platelet aggregation defect selectively with epinephrine in Indian patients.

A chronic hypercoagulable state and life-long platelet activation in beta thalassemia major.

Increased frequency of thromboembolic events has been recently observed in patients with thalassemia major (TM), causing hypoxemia and cor pulmonale. Autopsy findings demonstrated "old" and recent pulmonary and renal infarcts as well as premature atherosclerosis. Studies to determine hypercoagulability showed: impaired platelet aggregation, increased circulating platelet aggregates, shortened platelet survival, enhanced excretion of urinary metabolites of thromboxane A2 (TXA2) and prostacyclin and decreased plasma levels of Protein C, Protein S or anti-thrombin III. Erythrocytes from TM patients enhanced thrombin formation in a "prothrombinase" assay (using a chromogenic substrate). Chronic anti-thrombotic therapy may be indicated in thalassemic patients to prevent the cardiac and pulmonary complications.

The effect of Norplant on some hemostatic parameters in Indonesian women.

Many reports have indicated that oral contraceptives can increase the incidence of thromboembolic disorders. Norplant, an implant contraceptive containing levonorgestrel, has been developed recently. The aim of this study is to observe the effect of Norplant on some hemostatic parameters. The subjects in this study were divided into 5 groups. Group 1 (control) consisted of 25 female blood donors. Group 2 (N = 25), group 3 (n = 25), group 4 (n = 17) and group 5 (N = 20) consisted of subjects who had been using Norplant for 2, 3, 4, and 5 years, respectively. Prothrombin time, activated partial thromboplastin time, fibrinogen level, assay of F VII and X, antithrombin III activity, plasminogen activity, alpha 2-plasmin inhibitor activity and platelet aggregation test were done in all subjects. Our results showed that there was a significant difference (p < 0.05) on platelet aggregation induced by 10 microM of ADP between the control group and Norplant users for more than 2 years, while the other parameters did not differ significantly. It is concluded that 5 years users of Norplant did not alter blood coagulability, but increased platelet response to 10 microM of ADP.

Pulmonary and platelet function in mild form of Hb H disease.

Pulmonary function abnormality, arterial hypoxemia and platelet hyperaggregation were commonly seen in severe or moderately severe thalassemic patients. In previous studies, these abnormalities were found in beta-thalassemia, beta-thalassemia/Hb E disease and Hb H disease in 62, 40 and 52%, respectively. However these functional abnormalities in mild form of Hb H disease have not yet been reported. Pulmonary function test by using standard spirometry, platelet aggregation and arterial blood gases were performed in 23 children with mild form of Hb H disease, whose age ranged from 6-18 years (average 11 years), and hematocrit status was 30-40%. Mild to moderate degree of restrictive lung disorder was found in 48% of these patients, 5% had mild platelet hyperaggregation and none of these had arterial hypoxemia. This study showed that a pulmonary function defect was noted as one significant finding in thalassemic patients, being noted even in the very mild form and early age of life. This information will lead to further exploration of the pathogenesis of pulmonary function defects as well as their role is the patients' future health and prognosis.

Response of patients with bleeding disorder to DDAVP administration.

DDAVP has been shown to provide hemostasis in patients with bleeding disorder. Thirty-one episodes of intravenous DDAVP administration (0.3-0.4 microgram/kg) in 22 patients with bleeding disorder were studied. There were 13 patients with hemophilia A, 1 with type I vWD and 8 with inherited and acquired platelet dysfunction. The age ranged from 2.3-26 yrs (mean +/- SD = 10 +/- 4.8). None of the 3 severe hemophilia A patients responded to the treatment. Two out of five episodes in 4 moderate hemophilia A patients responded clinically and had minute increments of F VIII:C. Ten out of eleven episodes (91%) in 6 mild hemophilia A patients had good responses. The dental procedures for these patients were successfully performed without blood component transfusion. The increments of F VIII:C ranged from 1.5-6.8 folds over the baseline levels (mean +/- SD = 2.5 +/- 1.4). In addition, two episodes of epistaxis in a vWD patient responded excellently and one dental procedure was successfully performed by giving DDAVP. The increments of F VIII:C and vWF:Ag ranged from 2.8-12.5 and 2.9-8 fold over the baseline levels respectively. The prolonged bleeding times were shorten to 6.5-7 minutes. Only three out of eight episodes in 8 inherited and acquired platelet dysfunction patients showed temporary responses. The bleeding time responses did not correlate with in vitro platelet aggregation.

Platelet volume analysis for differential diagnosis of malignant versus reactive thrombcytosis

Platelet characteristics were assessed in 20 patients with malignant thrombocytosis 55 patients with reactive thrombocytosis and 46 normal subjects. Patients with malignant thrombocytosis showed in comparison with controls significantly higher rates of both megathrombocytes [P<0.05] and microthrombocytes [P< 0.005], increased heterogenecity of platelet volume and increased platelet distribution width [PDW]. [P< 0.001].Patients with reactive thrombocytosis showed in comparison with controls significantly higher rate of microthrombocytes [P< 0.001], significantly lower rate of megathrombocytes [P< 0.001] with a significantly lower mean platelet volume [MPV] [P< 0.001]. Their platelet distribution width is similar to that of normal controls. Patients with malignant thrombocytosis showed significantly higher rates of megathrombocytes, MPV, and PDW than cases with reactive thrombocytosis [P< 0.001, P< 0.005, and P< 0.001 respectively]. A platelet distribution width more than 17 fl can help in discrimination of cases with malignant thrombocytosis from cases with reactive thrombocytosis with a 95% sensitivity and 91.1% specificity rates. The positive predictive value was 79.17% and the negative predictive value was 98.2%. Cases with malignant thrombocytosis showed significantly higher rate of failure of aggregation of Adenosine Diphosphate [ADP] than either cases with reactive thrombocytosis or controls. [P< 0.001 for each]. The failure of aggregation was also significantly higher in reactive thrombocytosis than in controls [P< 0.01]. Eliminated aggregation rate in the two disease groups and controls increased significantly with increasing MPV [r = 0.54, P< 0.0001] and was inversely correlated with the number of small platelets less than 7.5 fl [r =0.37, P< 0.02]. In conclusion, an increased platelet heterogenecity was found in most patients with malignant thrombocytosis. A normal PDW in patients with platelet count 500 X 10[9/L] strongly suggests reactive thrombocytosis

Increase in spontaneous platelet aggregation in beta-thalassemia/hemoglobin E disease: a consequence of splenectomy.

Clinical symptoms related with disturbances of the circulatory system are often observed in beta-thalassemia/hemoglobin E (beta-thal/HbE) patients after splenectomy. Pulmonary thrombosis is one of the important contributing factors. However, the pathogenesis of this phenomenon was not known. Previous studies on platelet functions were controversial as platelet-rich plasma (PRP) was employed for all of the studies. By centrifugation, most of the hyperactive platelets were excluded before platelet aggregation tests were performed. Besides, the role of red cells related to platelet aggregation was not investigated. In this study, a platelet function test was designed to avoid these two handicaps of previous work as mentioned, by using whole blood from 15 normal and 40 beta-thal/HbE patients (15 nonsplenectomized and 25 splenectomized) to study spontaneous platelet aggregation. The principle of the test was to evaluate platelet number in whole blood by electronic platelet counter at time 0 (45 minutes after blood collection) and this number was used as 100% of free unaggregated platelets. Then the same specimen of whole blood was incubated at 37 degrees C with continuous stirring by magnetic stirrer in an aggregometer for 8 minutes; at 1 minute intervals free unaggregated platelets were evaluated and calculated as a percentage of the initial control value. The results indicated increased spontaneous platelet aggregation in whole blood of post-splenectomized beta-thal/HbE patients. The residual free platelet number were 24% at 8 minutes after incubation. Effects of red blood cells on spontaneous platelet aggregation were studied by mixing autologous beta-thal/HbE red cells obtained from splenectomized and non-splenectomized patients with platelet rich plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous platelet aggregation in thalassemic children and adolescents.

Spontaneous platelet aggregation was studied in 51 children and adolescents, comprising 30 nonsplenectomized thalassemic patients, 12 splenectomized thalassemic patients and 9 normal children. Spontaneous platelet aggregation was significantly increased in whole blood and platelet-rich plasma of splenectomized thalassemic patients but not in nonsplenectomized cases.

Functional platelet defects and their laboratory evaluation.

Primary diseases of platelet function include Glanzmann's thrombasthenia, hereditary platelet release abnormalities (storage pool disease and release defect), Bernard-Soulier giant platelet syndrome, and platelet factor 3 defects. Qualitative defects of platelets are associated with many diseases, notably of the liver and kidney, and with the use of many drugs, particularly aspirin.