Thromb Haemost 1995; 74(04): 1059-1063
DOI: 10.1055/s-0038-1649882
Original Article
Clinical Studies
Schattauer GmbH Stuttgart

Flow Cytometric Detection of Activated Platelets in Pregnant Women Prior to the Development of Pre-Eclampsia

Sarah L Janes
1   The Haemostasis Unit, Academic Department of Haematology, London, UK,
,
Phillipa M Kyle
3   The Nuffield Department of Obstetrics & Gynaecology, John Radcliffe Hospital, Oxford, UK
,
Christopher Redman
3   The Nuffield Department of Obstetrics & Gynaecology, John Radcliffe Hospital, Oxford, UK
,
Alison H Goodall
2   The Vascular Cell Biology Laboratory, Department of Chemical Pathology & Human Metabolism, Royal Free Hospital School of Medicine, London, UK
› Author Affiliations
Further Information

Publication History

Received 21 March 1995

Accepted 02 June 1995

Publication Date:
09 July 2018 (online)

Summary

Pre-eclampsia is a common complication of pregnancy, in which platelets may have an early pathogenetic role. In this prospective study a whole blood flow cytometric method has been used to detect circulating activated platelets in pregnant women prior to the development of pre-eclampsia. Activated platelets were identified by bound fibrinogen or by CD63 antigen expression. Of 121 healthy primiparous women studied at 28 weeks of pregnancy, 18 (15%) developed clinical pre-eclampsia six to thirteen weeks later. The platelets of these women showed increased fibrinogen binding ex vivo (5.1% platelets positive, compared with 3.4% in those who completed a normal pregnancy, p <0.02), and increased CD63 antigen expression (0.73% positive compared to 0.45%, p = 0.01). In contrast, no differences between the women with different outcomes were detected at 28 weeks in platelet counts, or plasma ß-thromboglobulin levels. These findings confirm that whole blood flow cytometry is a sensitive technique for investigating platelet activation in a clinical setting and support the hypothesis that platelets have a critical role in the pathogenesis of pre-eclampsia

 
  • References

  • 1 Redman CW. Platelets and the beginnings of preeclampsia. N Engl J Med 1990; 323: 478-480
  • 2 Roberts JM, Redman CW G. Pre-eclampsia: more than pregnancy-induced hypertension. Lancet 1993; 341: 1447-1451
  • 3 Janes SL, Goodall AH. Flow cytometric detection of circulating activated platelets and platelet hyper-responsiveness in pre-eclampsia and pregnancy. Clin Sci 1994; 86: 731-739
  • 4 Redman CW, Bonnar J, Beilin L. Early platelet consumption in pre-eclampsia. Br Med J 1978; 1: 467-469
  • 5 Ahmed Y, van Iddekinge B, Paul C, Sullivan MH F, Elder MG. Retrospective analysis of platelet numbers and volumes in normal pregnancy and in pre-eclampsia. Br J Obstet Gynaecol 1993; 100: 216-220
  • 6 Zemel MB, Zemel PC, Berry S, Norman G, Kowalczyk C, Sokol RJ, Standley PR, Walsh MF, Sowers JR. Altered platelet calcium metabolism as an early predictor of increased peripheral vascular resistance and preeclampsia in urban black women. N Engl J Med 1990; 323: 434-438
  • 7 Kyle PM, Jackson MC, Buckley DC, De Sweet M, Redman CW G. Response to arginine vasopressin is similar in preeclampsia and normal pregnancy. Am J Obstet Gynecol 1995; 172: 654-660
  • 8 Abrams C, Shattil SJ. Immunological detection of activated platelets in clinical disorders. Thromb Haemost 1991; 65: 467-473
  • 9 Nieuwenhuis HK, van Oosterhout JJ G, Rozemuller E, van Iwaarden F, Sixma JJ. Studies with a monoclonal antibody against activated platelets: Evidence that a secreted 53,000-molecular weight lysosome-like granule protein is exposed on the surface of activated platelets in the circulation. Blood 1987; 70: 838-845
  • 10 Tschoepe D, Roesen P, Esser J, Schwippert B, Niewenhuis HK, Kehrel B, Gries FA. Large platelets circulate in an activated state in diabetes mellitus. Semin Thromb Hemost 1991; 17: 433-438
  • 11 Crook M, Crawford N. Platelet surface charge heterogeneity: characterization of human platelet subpopulations separated by high voltage continuous flow electrophoresis. Br J Haematol 1988; 69: 265-273
  • 12 Martin JF, Bath PM W, Burr ML. Influence of platelet size on outcome after myocardial infarction. Lancet 1991; 338: 1409-1411
  • 13 Abrams CS, Ellison N, Budzynski AZ, Shattil SJ. Direct detection of activated platelets and platelet-derived microparticles in humans. Blood 1990; 75: 128-138
  • 14 Janes SL, Wilson DJ, Chronos N, Goodall AH. Evaluation of whole blood flow cytometric detection of platelet bound fibrinogen in normal subjects and patients with activated platelets. Thromb Haemost 1993; 70: 659-666
  • 15 Redman CW, Jefferies M. Revised definition of pre-eclampsia. Lancet 1988; 1: 809-812
  • 16 Shattil SJ, Cunningham M, Hoxie JA. Detection of activated platelets in whole blood using activation- dependent monoclonal antibodies and flow cytometry. Blood 1987; 70: 307-315
  • 17 Warkentin TE, Powling MJ, Hardisty RM. Measurement of fibrinogen binding to platelets in whole blood by flow cytometry: a micromethod for the detection of platelet activation. Br J Haematol 1990; 76: 387-394
  • 18 Cox AD, Goodall AH. Activation-specific neo-antigen on platelet detected by monoclonal antibodies. Albcrtini A, Lenfant CL, Mannucci PM, Sixma JJ. eds Basel; Karger: 1991. pp 194-199
  • 19 Goodall All. Platelet activation during preparation and storage of concentrates: detection by flow cytometry. Blood Coag Pibrinolysis 1991; 2: 377-389
  • 20 Janes SL, Wilson DJ, Cox AD, Chronos NA F, Goodall AH. ADP causes partial dcgranulalion of platelets in the absence of aggregation. Br J Haematol 1994; 86: 568-573
  • 21 Chronos NA F, Wilson DJ, Bullet NP, Goodall AH. Platelet activation and platelet hyper-responsiveness in patients with stable angina. Thromb Haemost 1993; 60: 1531
  • 22 Fox H. Development and structure of placenta and fetal membranes. In: Scientific Poundations of Obstetrics and Gynaecology. Philipp L, Selchell M, Ginsburg J. eds. Butterworth Heinemann; London: 1001. pp 287-297
  • 23 Ballcgcer VC, Spitz B, De Baene LA, van Assclie AF, Hidajat M, Criel AM. Platelet activation and vascular damage in gestational hypertension. Am J Obstet Gynecol 1002; 166: 620-633
  • 24 Rinder CS, Student LA, Bonan JL, Rinder HM, Smith BK. Aspirin does not inhibit adenosine diphosphate-induced platelet α-granule release. Blood 1003; 82: 505-512
  • 25 Chronos NA F, Wilson DJ, Janes SL, Mutton KA, Duller NP, Goodall AH. Aspirin does not affect the flow cytometric detection of fibrinogen binding to, or release of α-granules or lysosomes from, human platelets. Clin Sci 1004; 87: 575-580
  • 26 CLASP Collaborative Group. HASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre eclampsia among 0364 pregnant women. Lancet 1004; 343: 610-620