The myelodysplastic syndromes ‐ A study of haemostatic function and platelet ultrastructure

Abstract

The myelodysplastic syndromes (MDS) are characterised by dysplastic marrow and cytopenia. Clinically detectable bleeding is uncommon and usually attributed to thrombocytopenia. We have investigated some aspects of haemostatic function in 17 patient5 with MDS and compared the results with findings from 17 control patients matched for age and sex. No specific disorder of blood coagulation or fibrinolysis was identified. The main abnormalities observed in the patients were: prolongation of the bleeding time which was greater than could be explained on the basis of thrombocytopenia in 13 patients; absent, or severely impaired platelet aggregation in response to collagen in 7 patients; impaired platelet production of malondialydehyde when stimulated with collagen and abnormal release of I4C-5 hydroxytryptamine in 5 patients; and abnormalities of ultrastructure in all 5 patients whose platelets were viewed by electron microscopy. Accepred f o r publicalion September 7, 1984 ABREVIATIONS BT = bleeding time mg FDP l=PA ELT MDA MDS PPP PRP PT m Pm = fibrinogen = fibrinogen degradation products = fibrinogen peptide A = euglobulin clot lysis time = malondialdehyde = myelodysplastic syndrome = platelet poor plasma = platelet rich plasma = prothrombin time = partial thromboplastic time = ~thromboglobulin CLINICAL BEARINGThe myelodysplastic syndromes are now diagnosed with increasing frequency, particularly in the elderly. Throm-bocytopenia is common and we have demonstrated that serious defects in platelet function as judged by laboratory tests can co-exist in the absence of clinically apparent bleeding. These patients may suffer from haemorrhagic episodes, but routine tests for platelet function are apparently not much help in identifying those at greatest risk. Most likely, management of patients with myelodysplasia should include avoidance of drugs which inhibit platelet function. Whether or not platelet transfusions may be of any help in treating traumatic or spontaneous bleeding and covering surgical procedures remains to be shown.The myelodysplastic syndromes (MDS) are characterised by normo-or hypercellular bone marrow, varying degrees of cytopenia, and morphological evidence of dysplasia in the bone marrow

Platelet Proteome Analysis Reveals Integrin-dependent Aggregation Defects in Patients with Myelodysplastic Syndromes

“…Recently, a detailed study of the clinical features of 2900 patients with MDS reported that even among patients with platelet counts of Ͼ50,000/l, 19% had signs of bleeding at the time of diagnosis (4). Taken together, these data suggest a platelet count-independent functional platelet defect in MDS, which is supported by sporadic reports indicating insufficient platelet aggregation (3,(5)(6)(7)(8). The existence of such a functional platelet defect may very well contribute to the high rate of hemorrhagic complications observed in patients with MDS.…”

Defective Platelet Aggregation in Myelodysplastic Syndromes

“…The initial research in this field goes back to 1969, when Caen et al [11] studied platelet function in 7 patients with RA. Since 1984, several studies have concluded that there is no strong association between impaired aggregation and hemorrhagic events [12]. …”

Effect of platelet count on secretion capacity: formulization and use of the formulae for evaluation of platelet secretion in thrombocytopenic patients

“…Bleeding manifestations are relatively rare in patients with idiopathic thrombocytopenic purpura (ITP) as compared with equally thrombocytopenic patients with megakaryocyte deficiency. Hemorrhage may occur at apparently acceptable platelet levels in various thrombocytopenic patients, probably due to associated platelet dysfunction [4][5][6][8][9][10][11][12]. It is difficult to evaluate platelet functions in patients with thrombocytopenia and no routine method has been described for this purpose.…”

“…Clinical data suggest that platelet functional capacity and consequently bleeding risk are heterogeneous in various causes of thrombocytopenia [4][5][6][7]. Bleeding manifestations are relatively rare in patients with idiopathic thrombocytopenic purpura (ITP) as compared with equally thrombocytopenic patients with megakaryocyte deficiency.…”