Platelet activation in patients with thrombotic thrombocytopenic purpura

Abstract

Thrombotic thrombocytopenlc purpura (TTP) Is a rare syndrome of unknown etiology. It Is characterized by platelet microthrombi in small vessels, which results In tissue dysfunction and a microanglopathic hemolytic anemia. Activation of coagulation Is not a prominent feature of TTP. It is not known whether the process which results in platelet aggregate formation might also activate platelets. Using GMP-140 as a marker of activation, we examined the activation state of circulating platelets In seven l T P patients and three normal controls, as well as the ability of purlfled platelets from three l T P patients and three controls to be activated in vitro. There was no statistically significant difference In the percentage of activated platelets clrculatlng In patients and controls (4% vs. 2%). Both TTP and control platelets Increased GMP-140 expression and procoagulant activity after stimulation with thrombin or the calcium ionophore A23187. Thus, we conclude that TTP patients do not have a slgnlflcantly Increased proportion of clrculatlng activated platelets, and their platelets can be activated normally by thrombin or a calcium lonophore.

Characterization of platelet glycoproteins and platelet/endothelial cell antibodies in patients with thrombotic thrombocytopenic purpura

“…Although a small amount of VWF is present, the thrombi formed in TTP are primarily composed of platelets, and at least a part of the VHMW material found in the plasma in some patients with TTP might result from release from activated platelets or leakage from damaged endothelial cells. The current results support the findings of Hoffman et al (1993 ) that there is an increase in activated platelets in many patients with TTP and it has been suggested that activated platelet aggregates may be a marker for disease activity in TTP ( Ahn et al , 1996 ; Valant et al , 1998 )…”

“…Although a small amount of VWF is present, the thrombi formed in TTP are primarily composed of platelets, and at least a part of the VHMW material found in the plasma in some patients with TTP might result from release from activated platelets or leakage from damaged endothelial cells. The current results support the ®ndings of Hoffman et al (1993) that there is an increase in activated platelets in many patients with TTP and it has been suggested that activated platelet aggregates may be a marker for disease activity in TTP (Ahn et al, 1996;Valant et al, 1998) In addition to activation, abnormalities of platelet membrane glycoproteins may affect platelet function. The platelet receptor for VWF is mainly GPIb and Rock et al (1988) and Murphy et al (1987) have suggested that the platelet membrane content of GPIb is reduced in some patients with TTP and this has been attributed to the action of the enzyme calpain (Murphy et al, 1987;Kelton et al, Fig 6.…”

Activated platelet aggregates in thrombotic thromboctyopenic purpura: decrease with plasma infusions and normalization in remission

“…Previous publications reported impaired aggregation and secretion of platelets from patients with haemolytic uraemic syndromes, a disorder similar to TTP in pathophysiology, and suggested that platelets were exhausted by prior in vivo activation (Kaplan & Fong, 1980;Fong & Kaplan, 1982;Walters et al, 1988). However, a recent study employing CD62p as an activation marker failed to find evidence of platelet activation in TTP (Hoffman et al, 1993). In the present study we found that absolute numbers of CD62 free platelets were not significantly elevated in TTP, but their percentages were increased (Table I, column iv) due to severe thrombocytopenia.…”

Increased von Willebrand factor binding to platelets in single episode and recurrent types of thrombotic thrombocytopenic purpura

“…Circulating vWf, rather than any vWf released from the ␣-granules of animal platelets, is required for this phenomenon [42]. The lack of concurrence of vWf and P-selectin expression on single platelets in all samples during acute episodes from 3 of the adult TTP patients may also be the result of binding to platelets of vWf from the plasma of these individuals, rather than release onto their platelet surfaces of the contents of ␣-granules [43,44].…”