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

Abstract

Extensive microvascular platelet aggregation is characteristic of thrombotic thrombocytopenic purpura (TTP). Previous studies have indicated that abnormalities of von Willebrand factor (vWf) are often present in TTP patient plasma. There has not been previously any direct evidence linking these abnormalities to the process of intravascular platelet aggregation in TTP. We used flow cytometry to analyze the binding of vWf to single platelets, and the presence of platelet aggregates, in the blood of 4 children with chronic relapsing (CR) TTP and 5 adults with single episode or recurrent TTP. vWf on the single platelets of CRTTP patients at all time points studied was significantly increased compared to controls, and was increased further as platelet counts decreased to levels below 40,000/microl. The single episode and recurrent adult TTP patients had platelet aggregates in the blood, as well as increased vWf on single platelets, before therapy commenced and thereafter until recovery was in process. In the one unresponsive single episode TTP patient, vWf on single platelets remained elevated, and platelet aggregates persisted, until her death. The platelet alpha-granular protein, P-selectin, was not increased on the single platelets of most TTP blood samples, suggesting that it is vWf from plasma (rather than from alpha-granules) that attaches to platelet surfaces in association with platelet aggregation. These results suggest that vWf-platelet interactions are involved in the platelet clumping process that characterizes TTP.

Laboratory abnormalities in thrombotic thrombocytopenic purpura

“…Earlier work (Rock et al, 1988) showed that platelets from patients with TTP were unable to absorb VWF, indicating that the binding site was blocked. This suggested that VWF from plasma was bound to the platelets as has recently been confirmed (Chow et al, 1998). This VWF binding to platelets may account for some of the variability seen in the VWF pattern.…”

Management Of Thrombotic Thrombocytopenic Purpura

“…However, our finding that absorption of normal VWF multimers from plasma was impaired in three out of three patients with TTP gives support to an alteration in a surface membrane receptor which is either quantitatively or functionally diminished ( Rock et al , 1988 ). This suggestion that VWF is bound to the platelets in TTP has recently been confirmed by others using flow cytometry ( Chow et al , 1998 ).…”

Does cryosupernatant plasma improve outcome in thrombotic thrombocytopenic purpura? No answer yet

“…Interestingly, in our series, ‘although the total VWFwas increased’ we could not demonstrate the presence of ULVWF in plasma even when blood was collected into solutions of protease inhibitors. As we and others have shown that VWF binds to platelets in TTP (Rock et al , 1988; Chow et al , 1998), it is possible that all of the larger forms are instantly bound to platelets upon release from the endothelium. However, the logistics of such a rapid and complete absorption are difficult to understand.…”