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Physiological changes in membrane-expressed platelet factor 4: implications in heparin-induced thrombocytopenia.

Abstract：

BACKGROUND:Many heparin-induced thrombocytopenia (HIT) antibodies cause platelet activation in the serotonin release assay (SRA) in the absence of heparin. This in vitro observation may help unravel the mechanism of delayed-onset HIT, where seropositive patients develop thrombocytopenia and associated thrombosis after cessation of heparin. OBJECTIVE:Studies were conducted to examine the relationship between platelet environment, surface PF4 expression, and the extent of heparin-independent platelet activation in the SRA. METHODS:Ex vivo platelets were washed and labeled for SRA, then used either before or after 45 minutes of recovery at 37 degrees C. HIT antibody-mediated serotonin release in the absence of heparin was compared to the extent of surface staining of the platelets with fluorescent anti-human PF4 antibodies. RESULTS:Handling of platelets for in vitro studies resulted in transient expression of surface PF4, and it was during this interval that platelets were most sensitive to activation by HIT antibodies in the absence of heparin. Heparin-independent platelet activation was attenuated when SRA-positive specimens were retested after platelets were incubated 45 minutes at 37 degrees C. Surface PF4 expression was diminished on the rested platelets, compared to the same platelets labeled immediately after handling. Thus compared to rested platelets, mildly activated platelets had elevated surface PF4 expression and a higher level of HIT antibody-mediated, heparin-independent platelet activation. CONCLUSION:Surface expression of PF4 reflects HIT antigen presentation, and varies with the physiological state of platelets. Thus there can be differences in HIT antibody target availability among patients which may explain the variability in consequences of HIT antibody seropositivity.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Prechel MM,Jeske WP,Walenga JM

doi

10.1016/j.thromres.2009.10.021

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

e143-8

issue

eissn

0049-3848

issn

1879-2472

pii

S0049-3848(09)00499-X

journal_volume

125

pub_type

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Physiological changes in membrane-expressed platelet factor 4: implications in heparin-induced thrombocytopenia.