Platelet Function in Pre-Eclampsia

ABSTRACT

Pronounced hemostatic changes occur during pregnancy, and the balance shifts markedly in favor of hypercoagulability. Although primarily a result of a marked rise in the levels of several procoagulants and a fall in some natural anticoagulants, platelet activation also contributes to this prothrombotic tendency. Several studies have confirmed the accentuation of platelet activation in pre-eclampsia (P-EC), which remains an important obstetric complication affecting ~2 to 4% of pregnancies. Although there is still a long way to go, significant inroads have been made in the understanding of this enigmatic condition. Whereas the pathogenesis of P-EC is protean and involves a complex interplay of placental and maternal tissues, platelet activation is likely to contribute to several clinical features. Several techniques have been used to assess platelet activation in P-EC. Detection of aberrations of platelet function and activation appear to have predictive value for its diagnosis. The findings also lend support to the use of antiplatelet agents as prophylaxis in those women with a high risk of developing the condition.

KEYWORDS

Pre-eclampsia - platelet activation

REFERENCES

• 1 Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy . Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy.  Am J Obstet Gynecol. 2000;  183 (1) S1-S22
• 2 American College of Obstetricians and Gynecologists .Hypertension in Pregnancy. ACOG Technical Bulletin No. 219. Washington, DC: The College; 1996: 1-8
• 3 Khan K S, Wojdyla D, Say L, Gülmezoglu A M, Van Look P F. WHO analysis of causes of maternal death: a systematic review.  Lancet. 2006;  367 (9516) 1066-1074
• 4 Sibai B, Dekker G, Kupferminc M. Pre-eclampsia.  Lancet. 2005;  365 (9461) 785-799
• 5 Roberts J M, Taylor R N, Musci T J, Rodgers G M, Hubel C A, McLaughlin M K. Preeclampsia: an endothelial cell disorder.  Am J Obstet Gynecol. 1989;  161 (5) 1200-1204
• 6 Redman C W, Sacks G P, Sargent I L. Preeclampsia: an excessive maternal inflammatory response to pregnancy.  Am J Obstet Gynecol. 1999;  180 (2 Pt 1) 499-506
• 7 Roberts J M, Taylor R N, Goldfien A. Clinical and biochemical evidence of endothelial cell dysfunction in the pregnancy syndrome preeclampsia.  Am J Hypertens. 1991;  4 (8) 700-708
• 8 Szecsi P B, Jørgensen M, Klajnbard A, Andersen M R, Colov N P, Stender S. Haemostatic reference intervals in pregnancy.  Thromb Haemost. 2010;  103 (4) 718-727
• 9 Holthe M R, Staff A C, Berge L N, Lyberg T. Different levels of platelet activation in preeclamptic, normotensive pregnant, and nonpregnant women.  Am J Obstet Gynecol. 2004;  190 (4) 1128-1134
• 10 Sill P R, Lind T, Walker W. Platelet values during normal pregnancy.  Br J Obstet Gynaecol. 1985;  92 (5) 480-483
• 11 Sejeny S A, Eastham R D, Baker S R. Platelet counts during normal pregnancy.  J Clin Pathol. 1975;  28 (10) 812-813
• 12 Ahmed Y, van Iddekinge B, Paul C, Sullivan H F, Elder M G. Retrospective analysis of platelet numbers and volumes in normal pregnancy and in pre-eclampsia.  Br J Obstet Gynaecol. 1993;  100 (3) 216-220
• 13 Rinder H M, Bonan J L, Anandan S, Rinder C S, Rodrigues P A, Smith B R. Noninvasive measurement of platelet kinetics in normal and hypertensive pregnancies.  Am J Obstet Gynecol. 1994;  170 (1 Pt 1) 117-122
• 14 Milman N, Bergholt T, Byg K E, Eriksen L, Hvas A M. Reference intervals for haematological variables during normal pregnancy and postpartum in 434 healthy Danish women.  Eur J Haematol. 2007;  79 (1) 39-46
• 15 Fay R A, Hughes A O, Farron N T. Platelets in pregnancy: hyperdestruction in pregnancy.  Obstet Gynecol. 1983;  61 (2) 238-240
• 16 Rabini R A, Salvolini E, Staffolani R et al. Biochemical-morphological modifications of platelet membranes during pregnancy-induced hypertension.  Exp Mol Pathol. 1995;  63 (3) 175-185
• 17 Damron D P, Bouchard B A, Shapiro R E, Schonberg A L, Bernstein I M. Platelet activation, sympathetic tone, and plasma volume in nulligravid women of reproductive age.  Obstet Gynecol. 2004;  103 (5 Pt 1) 931-936
• 18 Morrison R, Crawford J, MacPherson M, Heptinstall S. Platelet behaviour in normal pregnancy, pregnancy complicated by essential hypertension and pregnancy-induced hypertension.  Thromb Haemost. 1985;  54 (3) 607-611
• 19 Sheu J R, Hsiao G, Shen M Y, Lin W Y, Tzeng C R. The hyperaggregability of platelets from normal pregnancy is mediated through thromboxane A2 and cyclic AMP pathways.  Clin Lab Haematol. 2002;  24 (2) 121-129
• 20 Hayashi M, Kiumi F, Mitsuya K. Changes in platelet ATP secretion and aggregation during pregnancy and in preeclampsia.  Am J Med Sci. 1999;  318 (2) 115-121
• 21 Gerbasi F R, Bottoms S, Farag A, Mammen E. Increased intravascular coagulation associated with pregnancy.  Obstet Gynecol. 1990;  75 (3 Pt 1) 385-389
• 22 Jungi T W, Spycher M O, Nydegger U E, Barandun S. Platelet-leukocyte interaction: selective binding of thrombin-stimulated platelets to human monocytes, polymorphonuclear leukocytes, and related cell lines.  Blood. 1986;  67 (3) 629-636
• 23 Sarma J, Laan C A, Alam S, Jha A, Fox K A, Dransfield I. Increased platelet binding to circulating monocytes in acute coronary syndromes.  Circulation. 2002;  105 (18) 2166-2171
• 24 Kageyama K, Nakajima Y, Shibasaki M, Hashimoto S, Mizobe T. Increased platelet, leukocyte, and endothelial cell activity are associated with increased coagulability in patients after total knee arthroplasty.  J Thromb Haemost. 2007;  5 (4) 738-745
• 25 Robb A O, Din J N, Mills N L et al. The influence of the menstrual cycle, normal pregnancy and pre-eclampsia on platelet activation.  Thromb Haemost. 2010;  103 (2) 372-378
• 26 Henn V, Slupsky J R, Gräfe M et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells.  Nature. 1998;  391 (6667) 591-594
• 27 Henn V, Steinbach S, Büchner K, Presek P, Kroczek R A. The inflammatory action of CD40 ligand (CD154) expressed on activated human platelets is temporally limited by coexpressed CD40.  Blood. 2001;  98 (4) 1047-1054
• 28 Oron G, Ben-Haroush A, Hod M, Orvieto R, Bar J. Serum-soluble CD40 ligand in normal pregnancy and in preeclampsia.  Obstet Gynecol. 2006;  107 (4) 896-900
• 29 Darmochwal-Kolarz D, Kolarz B, Surdacka A, Rolinski J, Leszczynska-Gorzelak B, Oleszczuk J. The expression and concentration of CD40 ligand in normal pregnancy and pre-eclampsia.  J Reprod Immunol. 2009;  79 (2) 215-219
• 30 Heilmann L, Rath W, Pollow K. Hemostatic abnormalities in patients with severe preeclampsia.  Clin Appl Thromb Hemost. 2007;  13 (3) 285-291
• 31 Redman C W, Bonnar J, Beilin L. Early platelet consumption in pre-eclampsia.  BMJ. 1978;  1 (6111) 467-469
• 32 Dundar O, Yoruk P, Tutuncu L et al. Longitudinal study of platelet size changes in gestation and predictive power of elevated MPV in development of pre-eclampsia.  Prenat Diagn. 2008;  28 (11) 1052-1056
• 33 Howarth S, Marshall L R, Barr A L, Evans S, Pontre M, Ryan N. Platelet indices during normal pregnancy and pre-eclampsia.  Br J Biomed Sci. 1999;  56 (1) 20-22
• 34 Coata G, Frusca T, Baranzelli D, Cosmi E V, Di Renzo G C, Anceschi M M. Abnormal platelet lipid membrane composition in pregnancy induced hypertension.  J Perinat Med. 1992;  20 (2) 123-127
• 35 Shang T, Qiao C. Study on the activity of platelets protein kinase C in patients with pregnancy induced hypertension.  [in Chinese] Zhonghua Fu Chan Ke Za Zhi. 1998;  33 (4) 201-203
• 36 Takeuchi T, Yoneyama Y, Suzuki S, Sawa R, Otsubo Y, Araki T. Regulation of platelet aggregation in vitro by plasma adenosine in preeclampsia.  Gynecol Obstet Invest. 2001;  51 (1) 36-39
• 37 Socol M L, Weiner C P, Louis G, Rehnberg K, Rossi E C. Platelet activation in preeclampsia.  Am J Obstet Gynecol. 1985;  151 (4) 494-497
• 38 Mellembakken J R, Solum N O, Ueland T, Videm V, Aukrust P. Increased concentrations of soluble CD40 ligand, RANTES and GRO-alpha in preeclampsia—possible role of platelet activation.  Thromb Haemost. 2001;  86 (5) 1272-1276
• 39 Peraçoli M T, Menegon F T, Borges V T, de Araújo Costa R A, Thomazini-Santos I A, Peraçoli J C. Platelet aggregation and TGF-beta(1) plasma levels in pregnant women with preeclampsia.  J Reprod Immunol. 2008;  79 (1) 79-84
• 40 Louden K A, Broughton Pipkin F, Heptinstall S, Fox S C, Mitchell J R, Symonds E M. Platelet reactivity and serum thromboxane B2 production in whole blood in gestational hypertension and pre-eclampsia.  Br J Obstet Gynaecol. 1991;  98 (12) 1239-1244
• 41 Norris L A, Gleeson N, Sheppard B L, Bonnar J. Whole blood platelet aggregation in moderate and severe pre-eclampsia.  Br J Obstet Gynaecol. 1993;  100 (7) 684-688
• 42 Nisell H, Grunewald C, Berglud M, Karlberg K E, Lunell N O, Sylven C. Platelet aggregation in vitro and ex vivo in normal pregnancy, pregnancy-induced hypertension and pre-eclampsia.  Hypertens Pregnancy. 1998;  17 (2) 147-155
• 43 Lev P R, Salim J P, Marta R F, Osorio M J, Goette N P, Molinas F C. Platelets possess functional TGF-beta receptors and Smad2 protein.  Platelets. 2007;  18 (1) 35-42
• 44 Janes S L, Kyle P M, Redman C, Goodall A H. Flow cytometric detection of activated platelets in pregnant women prior to the development of pre-eclampsia.  Thromb Haemost. 1995;  74 (4) 1059-1063
• 45 Konijnenberg A, van der Post J A, Mol B W et al. Can flow cytometric detection of platelet activation early in pregnancy predict the occurrence of preeclampsia? A prospective study.  Am J Obstet Gynecol. 1997;  177 (2) 434-442
• 46 Konijnenberg A, Stokkers E W, van der Post J A et al. Extensive platelet activation in preeclampsia compared with normal pregnancy: enhanced expression of cell adhesion molecules.  Am J Obstet Gynecol. 1997;  176 (2) 461-469
• 47 Harlow F H, Brown M A, Brighton T A et al. Platelet activation in the hypertensive disorders of pregnancy.  Am J Obstet Gynecol. 2002;  187 (3) 688-695
• 48 Yoneyama Y, Suzuki S, Sawa R, Kiyokawa Y, Power G G, Araki T. Plasma adenosine levels and P-selectin expression on platelets in preeclampsia.  Obstet Gynecol. 2001;  97 (3) 366-370
• 49 Barnard M R, Linden M D, Frelinger III AL et al. Effects of platelet binding on whole blood flow cytometry assays of monocyte and neutrophil procoagulant activity.  J Thromb Haemost. 2005;  3 (11) 2563-2570
• 50 Macey M, McCarthy D, Azam U, Milne T, Golledge P, Newland A. Ethylenediaminetetraacetic acid plus citrate-theophylline-adenosine-dipyridamole (EDTA-CTAD): a novel anticoagulant for the flow cytometric assessment of platelet and neutrophil activation ex vivo in whole blood.  Cytometry B Clin Cytom. 2003;  51 (1) 30-40
• 51 Del Conde I, Shrimpton C N, Thiagarajan P, López J A. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation.  Blood. 2005;  106 (5) 1604-1611
• 52 Holthe M R, Lyberg T, Staff A C, Berge L N. Leukocyte-platelet interaction in pregnancies complicated with preeclampsia.  Platelets. 2005;  16 (2) 91-97
• 53 Srinivas S K, Edlow A G, Neff P M, Sammel M D, Andrela C M, Elovitz M A. Rethinking IUGR in preeclampsia: dependent or independent of maternal hypertension?.  J Perinatol. 2009;  29 (10) 680-684
• 54 Kühne T, Ryan G, Blanchette V et al. Platelet-surface glycoproteins in healthy and preeclamptic mothers and their newborn infants.  Pediatr Res. 1996;  40 (6) 876-880
• 55 Klein B, Faridi A, Amo-Takyi B K, Heilmann L, Von Tempelhoff G F, Rath W. Neonatal platelet activation in preeclampsia.  Clin Appl Thromb Hemost. 2001;  7 (1) 29-32
• 56 Clark D A. Tolerance signaling molecules.  Chem Immunol Allergy. 2005;  89 36-48
• 57 Sato Y, Fujiwara H, Zeng B X, Higuchi T, Yoshioka S, Fujii S. Platelet-derived soluble factors induce human extravillous trophoblast migration and differentiation: platelets are a possible regulator of trophoblast infiltration into maternal spiral arteries.  Blood. 2005;  106 (2) 428-435
• 58 Falconer J, Pineo G, Blahey W, Bowen T, Docksteader B, Jadusingh I. Essential thrombocythemia associated with recurrent abortions and fetal growth retardation.  Am J Hematol. 1987;  25 (3) 345-347
• 59 Vantroyen B, Vanstraelen D. Management of essential thrombocythemia during pregnancy with aspirin, interferon alpha-2a and no treatment. A comparative analysis of the literature.  Acta Haematol. 2002;  107 (3) 158-169