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

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The effects of dazoxiben on finger-blood flow in response to cold challenge were studied in normal subjects and patients with Raynaud's phenomenon. In normal subjects concentrations of TXB2 and 6-oxo-PGF1 alpha were measured in blood taken from dorsal hand veins following cold challenge. In a parallel multicentre study we examined the effects of dazoxiben on finger temperature and capillary blood cell velocity in patients with Raynaud's phenomenon. Dazoxiben did not affect finger arterial inflow at rest or during cold challenge in patients or controls. However in both groups, recovery was quicker after cold challenge on dazoxiben treatment. In patients median flow was 5 ml (100(-1) ml) min-1 (range 1-10) v. 2 (0.5-15), P less than 0.05 dazoxiben v. placebo at 15 min after cold challenge. However, in normal subjects this did not prove to be statistically significant. In normal subjects there was a fall in TXB2 concentrations and relative rise in 6-oxo-PGF1 alpha following dazoxiben treatment indicating redirection of prostaglandin endoperoxides towards synthesis of PGI2. Comparison of the sum-total output of each eicosanoid following treatment with dazoxiben revealed a 65% reduction in TXB2 concentrations (P less than 0.025 compared with placebo) and a 40% increase in 6-oxo-PGF1 alpha concentrations (P less than 0.05 compared with placebo). However a simultaneous increase in concentrations of FPA indicated generation of thrombin, probably at the needle tip. Long-term treatment with dazoxiben resulted in no significant change in finger-skin temperature or capillary blood cell velocity, duration, or severity of attacks of Raynaud's phenomenon.

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The effects of ZK 36374, a prostacyclin analogue, were studied on adhesion of rabbit platelets to damaged rabbit aorta and on activation of platelets (judged by release of serotonin and formation of thromboxane-B2) in response to the processes of adhesion to the vessel surface and aggregation in response to microfibrillar collagen in suspension. In the presence of ZK 36374 (10-100 nmol/l), platelet adhesion and thromboxane-B2 formation were progressively reduced. The extent of serotonin release from adherent platelets was similar to that found for platelets aggregated with collagen. However, higher concentrations of ZK 36374 were required to inhibit serotonin release from adherent platelets than from aggregated platelets. The results indicate that ZK 36374 acts similarly to native prostacyclin on adhesion and collagen-induced aggregation and unlike previously described analogues is equipotent. The mechanism of release of serotonin induced by adhesion of platelets is less sensitive to the action of ZK 36374 than that of release induced by aggregation in response to microfibrillar collagen in suspension.