Thrombosis and bleeding in myeloproliferative disorders: identification of at‐risk patients with whole blood platelet aggregation studies

Abstract

Summary.Seventy-five patients with chronic myeloproliferative disorders were studied to investigate platelet function by simultaneous measurement of platelet aggregation by the impedance method and ATP dense granule release using a whole blood platelet lumi-aggregometer, in an attempt to identify patients at risk for thrombosis and bleeding.Thirty-nine patients had at least one abnormal result indicating platelet hyperactivity (i.e. impedance or release with one agonist being above the reference range); 16 patients had platelet hypoactivity (i.e. at least one result was below the reference range), whilst 14 had co-existence of hyper-and hypoactivity. Six patients had normal results. 20/ 53 patients with platelet hyperactivity (alone or mixed) had a positive history of venous and/or arterial thrombosis; in comparison, only two of the other 22 patients had a positive history. During a median follow-up of 33 months, nine patients with and one patient without platelet hyperactivity respectively developed new thrombotic events before the addition of specific therapy. A total of 50 patients with and eight patients without platelet hyperactivity respectively received specific treatment including aspirin and/or cytotoxic therapy. All but one elderly patient with platelet hyperactivity have remained free of new thrombotic events on specific therapy. Two of the 17 patients with platelet hypoactivity had major clinical bleeding.These observations highlight the need to test platelets for hyper-as well as hypo-function and suggest a useful role for routine whole blood platelet aggregation studies to identify the patients at risk for thrombosis or bleeding.

Bcl-2 family proteins are essential for platelet survival

“…The ability of compounds to induce aggregation was determined by measuring the impedance (Ohms) of the whole blood which is directly proportional to the aggregatory response. 20 As expected, collagen alone elicited a robust response at all the time points illustrating the stability of the platelets over the course of the study. The ability of the platelets to form aggregates was confirmed both before and after the course of the study by the addition of collagen ( Figure 3c; PRE and POST conditions).…”

Abnormalities of platelet aggregation in chronic myeloproliferative disorders

“…The thrombohaemorrhagic complications occurring in MPD incited many authors to investigate the function of platelets and to correlate the detected abnormalities with these clinical aspects and with changes of bleeding time [3,4,[23][24][25][26][27].…”

Increased platelet activation and abnormal membrane glycoprotein content and redistribution in myeloproliferative disorders

“…The bleeding tendency may in part be related to an acquired von Willebrand factor (VWF) deficiency associated with consumption of high molecular weight VWF multimers, abnormalities in platelet membrane glycoprotein (GP) and agonist receptor contents and defective agonistmediated platelet aggregation (Kaywin et al, 1978;Mazzucato et al, 1989;Balduini et al, 1991;van Genderen et al, 1997). Likewise, a propensity for thrombosis might be multifactually explained by a variety of abnormalities, implying increased platelet activation such as abnormal eicosanoid metabolism, increased granule secretion as assessed by serological measurement of alpha-granule products and spontaneous platelet aggregation (Cortelazzo et al, 1981;Landolfi et al, 1992;van Genderen et al, 1999;Manoharan et al, 1999). Furthermore, coagulation studies have revealed increased markers of the activated coagulation system and abnormal levels of the natural anticoagulants antithrombin, protein C and protein S in a proportion of patients (Falanga et al, 1994;Bucalossi et al, 1996).…”

“…Recently, Manoharan et al (1999) demonstrated a correlation between agonist-induced platelet hyperactivation and a history of thrombosis, using whole blood aggregometry, thus omitting the potential artefacts associated with platelet centrifugation.…”