A Double-Blind Trial of Ticlopidine in Sickle Cell Disease

Abstract

SummaryBaseline studies of 111indium oxine labelled platelet life-span, platelet α-granule release products, β-thromboglobulin (βTG) and platelet factor 4 (PF4), and factor VIII related activities were performed on 9 asymptomatic patients with sickle cell disease, who were subsequently randomised in a prospective double-blind trial of ticlopidine (250 mg. b. d.) or placebo for one month and the investigations repeated. Control studies indicated that 5 of the 9 patients had shortened platelet survivals: mean βTG (50.8 ng/ ml) and PF4 (19.5 ng/ml), factor VIII: C (283.4 i. u./dl) and factor VIIIR: AG (168.7 u/dl) levels were raised. Ticlopidine treatment did not significantly improve platelet life-span or factor VIII levels, though it was associated with reduced values of βTG and PF4. One patient taking ticlopidine developed an infarctive sickle crisis. Although ticlopidine blocked platelet activation, this alone did not improve platelet survival or prevent sickle crisis: in view of evidence of platelet activation in sickle cell disease, however, a longer trial of prophylactic antiplatelet drugs might be warranted.

Morphological and functional platelet abnormalities in Berkeley sickle cell mice

“…While a single study found thrombocytosis to be associated with impaired cognitive dysfunction in children with SCD (74), epidemiological studies have not reported thrombocytosis to be associated with increased overall severity of SCD, (75)(76)(77)(78)(79)(80), although such studies did not consider platelet size or mass. Despite the evidence for increased platelet consumption during painful crises (9), there are few data to support a role for platelets in microvascular obstruction, and small studies of aspirin, aspirin with dipyridamole, and ticlopidine failed to show a definitive benefit in reducing the frequency of pain crises (20)(21)(22)(23)(24). One potential link is through platelet surface expression of P-selectin and the recruitment of leukocytes since the latter have been implicated in contributing to vasoocclusion (81;82).…”

Redox-dependent impairment of vascular function in sickle cell disease

“…Long term minidose heparin adminstration to four SCD patients with severe recurrent painful crises caused a 73% reduction in hospitalization days and 74% reduction in hours spent in emergency rooms per year (165). A randomized double-blinded trial using ticlopidine blocked platelet activation, but did not improve platelet survival or prevent sickle crisis in asymptomatic patients with SCD (166). A pilot study of low-dose acenocoumarol in 22 patients with SCD demonstrated significant decreases in prothrombin fragment 1.2 levels, thrombin-antithrombin complexes and D-dimer fragments, but displayed no impact on the occurrence of vasoocclusive crises (167).…”

Hypercoagulability in Sickle Cell Disease: New Approaches to an Old Problem

“…39 Decreases in platelet lifespan and platelet counts have been reported during acute pain episodes. 35,36 Furthermore, acute pain episodes appear to be associated with increased platelet activation compared with the non-crisis steady state. 26,27 These findings suggest that decreased platelet survival and increased consumption occur during acute pain episodes, a likely result of platelet deposition at sites of vascular injury.…”