Increased Plasma Levels of Platelet Factor 4 and β-thromboglobulin in Women with Recurrent Pregnancy Loss.

Thrombosis in decidual vessels is one of the mechanisms of pregnancy loss. However, few studies have assessed the relation between platelet activation, which is known to cause of thrombosis, and recurrent pregnancy loss (RPL). We investigated platelet activation in women with RPL compared to controls by measuring plasma levels of platelet factor 4 (PF4) and β-thromboglobulin (βTG), and assessed correlations between PF4/βTG and coagulative risk factors associated with RPL. The study group included 135 women who had experienced two or more consecutive pregnancy losses. The control group included 28 age-matched healthy women who had never experienced pregnancy loss. PF4 and βTG plasma levels were significantly higher in the women with RPL than controls (PF4: 14.0 [8.0-20.0] vs. 9.0 [6.0-12.0] ng/ml, p=0.043; βTG: 42.0 [24.3-59.8] vs. 31.5 [26.6-36.4] ng/ml, p=0.002). There was a significant association between βTG and anti-phosphatidylethanolamine antibody immunoglobulin M (aPE IgM) (p=0.048). Among the women with RPL, 18 of those who were positive for PF4 (45%) and 18 of those who were positive for βTG (37%) were negative for all known coagulative risk factors associated with RPL. Measurements of PF4 and βTG may be important because they help identify women who are at risk of RPL.

[1]  S. Simavlı,et al.  Levels of thrombin-activatable fibrinolysis inhibitor and platelet-activating factor in recurrent pregnancy loss patients. , 2016, Taiwanese journal of obstetrics & gynecology.

[2]  R. Storey,et al.  The role of platelets in inflammation , 2015, Thrombosis and Haemostasis.

[3]  T. Sugi,et al.  Autoantibodies to Factor XII and Kininogen‐Dependent Antiphosphatidylethanolamine Antibodies in Patients with Recurrent Pregnancy Loss Augment Platelet Aggregation , 2015, American journal of reproductive immunology.

[4]  Y. Jeve,et al.  Evidence-based management of recurrent miscarriages , 2014, Journal of human reproductive sciences.

[5]  S. Dendrinos,et al.  Role of coagulation factor XII in unexplained recurrent abortions in the Greek population. , 2014, The Journal of reproductive medicine.

[6]  M. Goddijn,et al.  Antithrombotic therapy for pregnancy loss. , 2013, Human reproduction update.

[7]  M. Khamashta,et al.  Seronegative antiphospholipid syndrome. , 2013, Rheumatology.

[8]  T. Sugi.  Kininogen‐dependent antiphosphatidylethanolamine antibodies and autoantibodies to factor XII in patients with recurrent pregnancy losses , 2013, The journal of obstetrics and gynaecology research.

[9]  R. Demirtunç,et al.  The levels of β-thromboglobulin in female rheumatoid arthritis patients as activation criteria , 2013, Rheumatology International.

[10]  M. Khamashta,et al.  Anti-phosphatidylethanolamine antibody, thromboembolic events and the antiphospholipid syndrome. , 2012, Autoimmunity reviews.

[11]  Evaluation and treatment of recurrent pregnancy loss: a committee opinion. , 2012, Fertility and sterility.

[12]  M. Sanmarco.  Is Testing for Antiphosphatidylethanolamine Antibodies Clinically Useful? , 2011, Current rheumatology reports.

[13]  L. Morin-Papunen,et al.  Thromboprophylaxis for recurrent miscarriage in women with or without thrombophilia , 2010, Thrombosis and Haemostasis.

[14]  H. Büller,et al.  Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. , 2010, The New England journal of medicine.

[15]  F. Malone,et al.  Platelet reactivity and pregnancy loss. , 2009, American journal of obstetrics and gynecology.

[16]  D. Arduini,et al.  Low-dose aspirin and omega-3 fatty acids improve uterine artery blood flow velocity in women with recurrent miscarriage due to impaired uterine perfusion. , 2009, Fertility and sterility.

[17]  D. Schust,et al.  Recurrent pregnancy loss: etiology, diagnosis, and therapy. , 2009, Reviews in obstetrics & gynecology.

[18]  U. Tiemann.  The role of platelet-activating factor in the mammalian female reproductive tract. , 2008, Reproduction in domestic animals = Zuchthygiene.

[19]  R. Tamagawa‐Mineoka,et al.  Elevated platelet activation in patients with atopic dermatitis and psoriasis: increased plasma levels of beta-thromboglobulin and platelet factor 4. , 2008, Allergology international : official journal of the Japanese Society of Allergology.

[20]  B. Brenner,et al.  A randomized study of thromboprophylaxis in women with unexplained consecutive recurrent miscarriages. , 2006, Fertility and sterility.

[21]  L. Regan,et al.  Recurrent miscarriage. , 2006, Lancet.

[22]  J. Deutinger,et al.  Platelet specific protein (β-thromboglobulin and platelet factor 4) in normal pregnancy and in pregnancy complicated by preeclampsia , 2004, Archives of Gynecology and Obstetrics.

[23]  H. Carp,et al.  Prevalence of circulating procoagulant microparticles in women with recurrent miscarriage: a case-controlled study. , 2004, Human reproduction.

[24]  L. Regan,et al.  Thromboelastography, whole-blood haemostasis and recurrent miscarriage. , 2003, Human reproduction.

[25]  G. Emons,et al.  Factor XII deficiency is strongly associated with primary recurrent abortions. , 2003, Fertility and Sterility.

[26]  D. Camerini,et al.  Platelet Chemokines and Chemokine Receptors: Linking Hemostasis, Inflammation, and Host Defense , 2003, Microcirculation.

[27]  M. Hellgren.  Hemostasis during Normal Pregnancy and Puerperium , 2003, Seminars in thrombosis and hemostasis.

[28]  Teruo Inoue,et al.  Characterization of five marker levels of the hemostatic system and endothelial status in normotensive pregnancy and pre‐eclampsia , 2002, European journal of haematology.

[29]  N. Sakuragi,et al.  Recurrent Pregnancy Loss: Etiology of Thrombophilia , 2001, Seminars in thrombosis and hemostasis.

[30]  C. Nemeroff,et al.  Platelet reactivity in depressed patients treated with paroxetine: preliminary findings. , 2000, Archives of general psychiatry.

[31]  J. Gris,et al.  Antiphospholipid and Antiprotein Syndromes in Non-thrombotic, Non-autoimmune Women with Unexplained Recurrent Primary Early Foetal Loss , 2000, Thrombosis and Haemostasis.

[32]  H. Cohen,et al.  Increased thrombin generation in women with recurrent miscarriage , 1998, The Lancet.

[33]  V. Salomaa,et al.  Correlation of Specific Platelet Activation Markers with Carotid Arterial Wall Thickness , 1995, Thrombosis and Haemostasis.

[34]  E. Matteson,et al.  Connective tissue activation. XXXVI. The origin, variety, distribution, and biologic fate of connective tissue activating peptide-III isoforms: characteristics in patients with rheumatic, renal, and arterial disease. , 1993, Arthritis and rheumatism.

[35]  M. C. Liu,et al.  Platelet activation in the lung after antigen challenge in a model of allergic asthma. , 1992, The American review of respiratory disease.

[36]  E. Minar,et al.  Influence of acetylsalicylic acid (1.0 g/day) on platelet survival time, beta-thromboglobulin and platelet factor 4 in patients with peripheral arterial occlusive disease. , 1987, Thrombosis research.

[37]  B. Lämmle,et al.  Platelet Aggregation, β-Thromboglobulin and Platelet Factor 4 in Diabetes Mellitus and in Patients with Vasculopathy , 1984, Thrombosis and Haemostasis.

[38]  T. Meade,et al.  Haemostasis in Normal Pregnancy , 1984, Thrombosis and Haemostasis.

[39]  R. Reed.  Connective-tissue activation. , 1982, The American Journal of dermatopathology.

[40]  C. Chesney,et al.  Effect of platelet-activating factor (PAF) on human platelets. , 1982, Blood.

[41]  E. Frenkel,et al.  Elevated beta thromboglobulin in peripheral venous blood of patients with acute myocardial ischemia: direct evidence for enhanced platelet reactivity in vivo. , 1981, The American journal of cardiology.

[42]  J. Lindenfeld,et al.  Increased Plasma Concentrations of Platelet Factor 4 in Coronary Artery Disease: A Measure of In Vivo Platelet Activation and Secretion , 1981, Circulation.

[43]  K. Kaplan,et al.  Plasma levels of beta-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo. , 1981, Blood.

[44]  R. N. Pinckard,et al.  Platelet activating factor (PAF) induced release of platelet factor 4 (PF4) in vitro and during IgE anaphylaxis in the rabbit. , 1979, Journal of immunology.