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DOI: 10.1055/a-2791-6450
Decreasing Platelet Aggregation Despite Increasing Soluble P-selectin during Pregnancy in Women with and without Heterozygous Factor V Leiden Mutation
Authors
Funding Information This work was funded by the Department of Laboratory Medicine/Department of Medical Biochemistry and Pharmacology MBF, Haukeland University Hospital, Helse Bergen except for sP-selectin, which was funded by the University of Oslo, Oslo. Ann Helen Kristoffersen received postdoctoral fellowship from the Western Norway Regional Health Authority.

Abstract
Background
Risk of venous thromboembolism (VTE) is increased in pregnancy and postpartum, and 40% of VTEs in pregnancy (Caucasians) are associated with heterozygous factor V Leiden mutation (FVL). Thrombin generation is increased in individuals with FVL and in pregnant women, and thrombin amplifies both platelet and coagulation activation. Although both contribute to VTE pathophysiology, the mechanisms of platelet activation in pregnant women, particularly with heterozygous FVL, remain poorly understood.
Objectives
To describe the physiological course of the platelet activation marker plasma soluble P-selectin (sP-selectin), whole blood platelet aggregation, and thromboelastography (TEG) parameters throughout pregnancy and postpartum, and assess differences between women with and without heterozygous FVL.
Patients/Methods
A total of 22 pregnant women with heterozygous FVL and 22 without were enrolled. Blood samples were collected at multiple time points during and after pregnancy. Platelet activation and aggregation were evaluated using sP-selectin, multiple electrode aggregometry (MEA) with adenosine diphosphate, arachidonic acid, thrombin receptor-activating peptide-6 as agonists, and TEG.
Results
sP-selectin levels increased significantly during pregnancy, while platelet aggregation decreased in response to all agonists (P < 0.005). TEG maximum amplitude (MA) increased throughout pregnancy. No significant differences were observed between women with and without FVL.
Conclusion
In late pregnancy, decreased platelet aggregation responses were observed alongside increased sP-selectin levels, with no differences in levels between women with and without heterozygous FVL. These findings indicate that the presence of heterozygous FVL does not significantly influence platelet function during pregnancy. The cause of the unexpected, reduced platelet aggregation remains unclear and warrants further investigation.
Publication History
Received: 22 April 2025
Accepted: 18 January 2026
Article published online:
02 February 2026
© 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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References
- 1 Sultan AA, West J, Tata LJ, Fleming KM, Nelson-Piercy C, Grainge MJ. Risk of first venous thromboembolism in and around pregnancy: a population-based cohort study. Br J Haematol 2012; 156 (03) 366-373
- 2 Kourlaba G, Relakis J, Kontodimas S, Holm MV, Maniadakis N. A systematic review and meta-analysis of the epidemiology and burden of venous thromboembolism among pregnant women. Int J Gynaecol Obstet 2016; 132 (01) 4-10
- 3 Cresswell JA, Alexander M, Chong MYC. et al. Global and regional causes of maternal deaths 2009-20: a WHO systematic analysis. Lancet Glob Health 2025; 13 (04) e626-e634
- 4 Varrias D, Spanos M, Kokkinidis DG, Zoumpourlis P, Kalaitzopoulos DR. Venous thromboembolism in pregnancy: challenges and solutions. Vasc Health Risk Manag 2023; 19: 469-484
- 5 Kujovich JL. Factor V Leiden thrombophilia. Genet Med 2011; 13 (01) 1-16
- 6 Wood JP, Baumann Kreuziger LM, Ellery PER, Maroney SA, Mast AE. Reduced prothrombinase inhibition by tissue factor pathway inhibitor contributes to the factor V Leiden hypercoagulable state. Blood Adv 2017; 1 (06) 386-395
- 7 Gerhardt A, Scharf RE, Beckmann MW. et al. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium. N Engl J Med 2000; 342 (06) 374-380
- 8 Posma JJ, Posthuma JJ, Spronk HM. Coagulation and non-coagulation effects of thrombin. J Thromb Haemost 2016; 14 (10) 1908-1916
- 9 Heestermans M, Poenou G, Duchez AC, Hamzeh-Cognasse H, Bertoletti L, Cognasse F. Immunothrombosis and the role of platelets in venous thromboembolic diseases. Int J Mol Sci 2022; 23 (21) 13176
- 10 McLean KC, Bernstein IM, Brummel-Ziedins KE. Tissue factor-dependent thrombin generation across pregnancy. Am J Obstet Gynecol 2012; 207 (02) 135.e1-135.e6
- 11 Dong F, Lv Z, Di P. Use of thrombomodulin-modified thrombin generation in uncomplicated pregnancy: the normal range and prothrombotic phenotype. Scand J Clin Lab Invest 2023; 83 (02) 79-85
- 12 Billoir P, Duflot T, Fresel M, Chrétien MH, Barbay V, Le Cam Duchez V. Thrombin generation profile in non-thrombotic factor V Leiden carriers. J Thromb Thrombolysis 2019; 47 (03) 473-477
- 13 Tripodi A, Martinelli I, Chantarangkul V, Battaglioli T, Clerici M, Mannucci PM. The endogenous thrombin potential and the risk of venous thromboembolism. Thromb Res 2007; 121 (03) 353-359
- 14 Selmeczi A, Roach RE, Móré C. et al. Thrombin generation and low-molecular-weight heparin prophylaxis in pregnant women with thrombophilia. Thromb Haemost 2015; 113 (02) 283-289
- 15 Eichinger S, Weltermann A, Philipp K. et al. Prospective evaluation of hemostatic system activation and thrombin potential in healthy pregnant women with and without factor V Leiden. Thromb Haemost 1999; 82 (04) 1232-1236
- 16 Su X, Zhao W. Platelet aggregation in normal pregnancy. Clin Chim Acta 2022; 536: 94-97
- 17 Schmuckenschlager A, Pirabe A, Assinger A, Schrottmaier WC. Platelet count, temperature and pH value differentially affect hemostatic and immunomodulatory functions of platelets. Thromb Res 2023; 223: 111-122
- 18 Müller MR, Salat A, Pulaki S. et al. Influence of hematocrit and platelet count on impedance and reactivity of whole blood for electrical aggregometry. J Pharmacol Toxicol Methods 1995; 34 (01) 17-22
- 19 Hanke AA, Roberg K, Monaca E. et al. Impact of platelet count on results obtained from multiple electrode platelet aggregometry (Multiplate). Eur J Med Res 2010; 15 (05) 214-219
- 20 Shams Hakimi C, Fagerberg Blixter I, Hansson EC, Hesse C, Wallén H, Jeppsson A. Effects of fibrinogen and platelet supplementation on clot formation and platelet aggregation in blood samples from cardiac surgery patients. Thromb Res 2014; 134 (04) 895-900
- 21 Baidildinova G, Nagy M, Jurk K, Wild PS, Ten Cate H, van der Meijden PEJ. Soluble platelet release factors as biomarkers for cardiovascular disease. Front Cardiovasc Med 2021; 8: 684920
- 22 Purdy M, Obi A, Myers D, Wakefield T. P- and E-selectin in venous thrombosis and non-venous pathologies. J Thromb Haemost 2022; 20 (05) 1056-1066
- 23 Li X, Ma Y, Wang D. The role of P-selectin/PSGL-1 in regulating NETs as a novel mechanism in cerebral ischemic injury. Front Neurol 2024; 15: 1442613
- 24 Xu Q, Shi M, Ding L. et al. High expression of P-selectin induces neutrophil extracellular traps via the PSGL-1/Syk/Ca2+/PAD4 pathway to exacerbate acute pancreatitis. Front Immunol 2023; 14: 1265344
- 25 Li W, Wang Z, Su C. et al. The effect of neutrophil extracellular traps in venous thrombosis. Thromb J 2023; 21 (01) 67
- 26 Rectenwald JE, Myers Jr DD, Hawley AE. et al. D-dimer, P-selectin, and microparticles: novel markers to predict deep venous thrombosis. A pilot study. Thromb Haemost 2005; 94 (06) 1312-1317
- 27 Gremmel T, Ay C, Seidinger D, Pabinger I, Panzer S, Koppensteiner R. Soluble p-selectin, D-dimer, and high-sensitivity C-reactive protein after acute deep vein thrombosis of the lower limb. J Vasc Surg 2011; 54 (6, Suppl): 48S-55S
- 28 Holmes VA, Wallace JM, Gilmore WS, McFaul P, Alexander HD. Soluble P-selectin levels during normal pregnancy: a longitudinal study. BJOG 2002; 109 (09) 997-1002
- 29 Chaiworapongsa T, Romero R, Yoshimatsu J. et al. Soluble adhesion molecule profile in normal pregnancy and pre-eclampsia. J Matern Fetal Neonatal Med 2002; 12 (01) 19-27
- 30 Peerschke EI, Castellone DD, Stroobants AK, Francis J. Reference range determination for whole-blood platelet aggregation using the Multiplate analyzer. Am J Clin Pathol 2014; 142 (05) 647-656
- 31 Hartweg J, Gunter M, Perera R. et al. Stability of soluble adhesion molecules, selectins, and C-reactive protein at various temperatures: implications for epidemiological and large-scale clinical studies. Clin Chem 2007; 53 (10) 1858-1860
- 32 Lacom C, Tolios A, Löffler MW. et al. Assay validity of point-of-care platelet function tests in thrombocytopenic blood samples. Biochem Med (Zagreb) 2022; 32 (02) 020713
- 33 Gomez-Lopez N, StLouis D, Lehr MA, Sanchez-Rodriguez EN, Arenas-Hernandez M. Immune cells in term and preterm labor. Cell Mol Immunol 2014; 11 (06) 571-581
- 34 O'Brien WF, Saba HI, Knuppel RA, Scerbo JC, Cohen GR. Alterations in platelet concentration and aggregation in normal pregnancy and preeclampsia. Am J Obstet Gynecol 1986; 155 (03) 486-490
- 35 Blomqvist LRF, Strandell AM, Baghaei F, Hellgren MSE. Platelet aggregation in healthy women during normal pregnancy—a longitudinal study. Platelets 2019; 30 (04) 438-444
- 36 Andersson LI, Sjöström DJ, Quach HQ. et al. Storage of transfusion platelet concentrates is associated with complement activation and reduced ability of platelets to respond to protease-activated receptor-1 and thromboxane A2 receptor. Int J Mol Sci 2024; 25 (02) 1091
- 37 Boehlen F, Hohlfeld P, Extermann P, Perneger TV, de Moerloose P. Platelet count at term pregnancy: a reappraisal of the threshold. Obstet Gynecol 2000; 95 (01) 29-33
- 38 Thompson CB, Eaton KA, Princiotta SM, Rushin CA, Valeri CR. Size dependent platelet subpopulations: relationship of platelet volume to ultrastructure, enzymatic activity, and function. Br J Haematol 1982; 50 (03) 509-519
- 39 Hayashi M, Kiumi F, Mitsuya K. Changes in platelet ATP secretion and aggregation during pregnancy and in preeclampsia. Am J Med Sci 1999; 318 (02) 115-121
- 40 Sheu JR, Hsiao G, Lin WY. et al. Mechanisms involved in agonist-induced hyperaggregability of platelets from normal pregnancy. J Biomed Sci 2002; 9 (01) 17-25
- 41 Valera M-C, Parant O, Vayssiere C, Arnal J-F, Payrastre B. Physiologic and pathologic changes of platelets in pregnancy. Platelets 2010; 21 (08) 587-595
- 42 Bolliger D, Seeberger MD, Tanaka KA. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transfus Med Rev 2012; 26 (01) 1-13
- 43 Harr JN, Moore EE, Ghasabyan A. et al. Functional fibrinogen assay indicates that fibrinogen is critical in correcting abnormal clot strength following trauma. Shock 2013; 39 (01) 45-49
- 44 Jacobsen AF, Skjeldestad FE, Sandset PM. Incidence and risk patterns of venous thromboembolism in pregnancy and puerperium—a register-based case-control study. Am J Obstet Gynecol 2008; 198 (02) 233.e1-233.e7