Flow cytometric detection of circulating activated platelets and platelet hyper-responsiveness in pre-eclampsia and pregnancy.
1. Platelet activation status and response to stimulation with agonists ex vivo were studied by whole blood flow cytometry in 15 women with pre-eclampsia, 20 age- and gestational-age-matched women who completed a normal pregnancy, and 20 age-matched non-pregnant women. 2. Women with proteinuric pre-eclampsia showed evidence of activated, degranulated platelets in the circulation, with increased platelet-bound fibrinogen, increased expression of the lysosomal granule membrane antigen, CD63, and raised plasma levels of beta-thromboglobulin. 3. CD63 expression and beta-thromboglobulin per platelet were also significantly higher in normal pregnant women than in non-pregnant women, but in these subjects fibrinogen binding was normal. 4. There was good correlation for all subjects in degranulation, measured by CD63 antigen expression, and by plasma beta-thromboglobulin levels corrected for platelet count (r = 0.65; P < 0.01). 5. Platelet responsiveness to ADP in vitro showed a heightened degranulation response (CD63 expression) in normal pregnancy compared with the non-pregnant control group, which was increased further in women with non-proteinuric and proteinuric pre-eclampsia. 6. However, this response was not accompanied by an increased binding of fibrinogen to GPIIb-IIIa. Fibrinogen binding in response to 'weak' agonist stimulation, by low concentrations of ADP or, in a subgroup by adrenaline, was in fact lower in the normal pregnant women than in the non-pregnant women. 7. It is postulated that women at risk of developing pre-eclampsia may have hyper-reactive platelets, primed to undergo release by passage through the abnormal placenta.
Janes
S L
SL
Academic Department of Haematology, Royal Free Hospital, London, U.K.
Goodall
A H
AH
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D001792:Blood Platelets / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D015539:Platelet Activation / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D011225:Pre-Eclampsia / Q000097:blood* / Q000276:immunology; D011247:Pregnancy; D011507:Proteinuria / Q000097:blood / Q000276:immunology; D060149:Tetraspanin 30; D001620:beta-Thromboglobulin / Q000032:analysis
D015703:Antigens, CD; C554586:CD63 protein, human; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D001620:beta-Thromboglobulin; D000244:Adenosine Diphosphate; D005340:Fibrinogen