Haemostatic changes related to fibrin formation and fibrinolysis during the first trimester in normal pregnancy and in recurrent miscarriage

Rita Marchi; Ysabel López Ramirez; Chandrasekaran Nagaswami; Leona Masova; Anibal Pulido; José López Mora; Aixa Muller; Carmen Luisa Arocha-Piñango; John W. Weisel

doi:10.1160/TH06-09-0542

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(04): 552-557
DOI: 10.1160/TH06-09-0542

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Haemostatic changes related to fibrin formation and fibrinolysis during the first trimester in normal pregnancy and in recurrent miscarriage

Rita Marchi

¹Centro de Medicina Experimental, Laboratorio de Hemostasia, Instituto Venezolano de Investigaciones Científicas, IVIC, Caracas, República Bolivariana de Venezuela

,

Ysabel López Ramirez

¹Centro de Medicina Experimental, Laboratorio de Hemostasia, Instituto Venezolano de Investigaciones Científicas, IVIC, Caracas, República Bolivariana de Venezuela

,

Chandrasekaran Nagaswami

²Department of Cell and Developmental Biology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA

,

Leona Masova

²Department of Cell and Developmental Biology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA

,

Anibal Pulido

³Facultad de Medicina, Escuela Luis Razetti, Departamento de Obstetricia y Ginecología, Cátedra de Clínica Obstétrica A, Hospital Universitario de Caracas, Caracas, República Bolivariana de Venezuela

,

José López Mora

³Facultad de Medicina, Escuela Luis Razetti, Departamento de Obstetricia y Ginecología, Cátedra de Clínica Obstétrica A, Hospital Universitario de Caracas, Caracas, República Bolivariana de Venezuela

,

Aixa Muller

³Facultad de Medicina, Escuela Luis Razetti, Departamento de Obstetricia y Ginecología, Cátedra de Clínica Obstétrica A, Hospital Universitario de Caracas, Caracas, República Bolivariana de Venezuela

,

Carmen Luisa Arocha-Piñango

¹Centro de Medicina Experimental, Laboratorio de Hemostasia, Instituto Venezolano de Investigaciones Científicas, IVIC, Caracas, República Bolivariana de Venezuela

,

John W. Weisel

²Department of Cell and Developmental Biology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA

› Author Affiliations

Abstract

Summary

We have studied some biophysical properties of the fibrin network during the normal state of pregnancy and in patients with recurrent miscarriage (RM), in the first trimester of pregnancy. The fibrin polymerization process, followed by turbidity, showed that the rate of fibrin monomer assembly and the final turbidity was increased in the pregnant group (normal and with history of RM) compared to non-pregnant women (normal and RM), which is consistent with the increased fibrinogen concentration during pregancy. No changes were observed in the Darcy constant (Ks) of RM clots, pregnant or not; however, in pregnant control subjects the Ks increased (p=0.03).The fibrin lysis rate was increased in pregnant women compared to non-pregnant, being faster in women with RM. The rheological properties of the fibrin network in the non-pregnant group (control and RM patients) were similar; in the pregnant state, the fibrin network of the control group was 1.3 times stiffer compared to the control non-pregnant women, and almost unchanged in RM patients. In this study we have found changes in the clot structure that seem to be related to normal pregnancy and an increased rate of the fibrin lysis process in the RM patients, which may have clinical relevance.

Keywords

Pregnancy - recurrent miscarriage - clot structure - internal fibrinlysis - rheological properties

Full Text

References

References
1 Stirling Y. et al. Haemostasis in normal pregnancy. Thromb Haemost 1984; 52: 176-182.
2 Kjellberg U. et al. APC resistance and other haemostatic variables during pregnancy and puerperium. Thromb Haemost 1999; 81: 527-531.
3 Cerneca F. et al. Coagulation and fibrinolysis changes in normal pregnancy. Increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis. Eur J Obstet Gynecol Reprod Biol 1997; 73: 31-36.
4 Clark P. et al. Activated protein C sensitivity, protein C, protein S and coagulation in normal pregnancy. Thromb Haemost 1998; 79: 1166-1170.
5 Clark P. Changes of hemostasis variables during pregnancy. Semin Vasc Med 2003; 3: 13-24.
6 Condie RG. A serial study of coagulation factors XII, XI and X in plasma in normal pregnancy and in pregnancy complicated by pre-eclampsia. Br J Obstet Gynaecol 1976; 83: 636-639.
7 Lindoff C. et al. Fibrinolytic components in individual consecutive plasma samples during normal pregnancy. Fibrinolysis 1993; 7: 190-194.
8 Chabloz P. et al. TAFI antigen and D-dimer levels during normal pregnancy and at delivery. Br J Haematol 2001; 115: 150-152.
9 Wright JG. et al. Fibrinolysis during normal human pregnancy: complex inter-relationships between plasma levels of tissue plasminogen activator and inhibitors and the euglobulin clot lysis time. Br J Haematol 1988; 69: 253-258.
10 Phillips LL. et al. Changes in plasma factor XI (plasma thromboplastin antecedent) levels during pregnancy. Am J Obstet Gynecol 1973; 116: 1114-1116.
11 Hayano Y. et al. Studies on the physiological changes of blood coagulation factor XIII during pregnancy and their significance. Nippon Sanka Fujinka Gakkai Zasshi 1982; 34: 469-477.
12 Espana F. et al. Complexes of activated protein C with alpha 1-antitrypsin in normal pregnancy and in severe preeclampsia. Am J Obstet Gynecol 1991; 164: 1310-1316.
13 Lefkowitz JB. et al. Comparison of protein S functional and antigenic assays in normal pregnancy. Am J Obstet Gynecol 1996; 175: 657-660.
14 Hayashi M. et al. Characterization of five marker levels of the hemostatic system and endothelial status in normotensive pregnancy and pre-eclampsia. Eur J Haematol 2002; 69: 297-302.
15 Delorme MA. et al. Thrombin regulation in mother and fetus during pregnancy. Semin Thromb Hemost 1992; 18: 81-90.
16 Bremme K. et al. Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium. Obstet Gynecol 1992; 80: 132-137.
17 Reinthaller A. et al. Thrombin-antithrombin III complex levels in normal pregnancy with hypertensive disorders and after delivery. Br J Obstet Gynaecol 1990; 97: 506-510.
18 Ayhan A. et al. Beta-thromboglobulin and platelet factor 4 levels in pregnancy and preeclampsia. Gynecol Obstet Invest 1990; 30: 12-14.
19 Bellart J. et al. Endothelial cell markers and fibrinopeptide A to D-dimer ratio as a measure of coagulation and fibrinolysis balance in normal pregnancy. Gynecol Obstet Invest 1998; 46: 17-21.
20 Holmes VA, Wallace JM. Haemostasis in normal pregnancy: a balancing act?. Biochem Soc Trans 2005; 33: 428-432.
21 Bick RL. Recurrent miscarriage syndrome and infertility caused by blood coagulation protein or platelet defects. Hematol Oncol Clin North Am 2000; 14: 1117-1131.
22 Bick RL, Hoppensteadt D. Recurrent miscarriage syndrome and infertility due to blood coagulation protein/ platelet defects: a review and update. Clin Appl Thromb Hemost 2005; 11: 1-13.
23 Dossenbach-Glaninger A. et al. Plasminogen activator inhibitor 1 4G/5G polymorphism and coagulation factor XIII Val34Leu polymorphism: Impaired fibrinolysis and early pregnancy loss. Clin Chem 2003; 49: 1081-1086.
24 Inbal A, Muszbek L. Coagulation factor deficiencies and pregnancy loss. Sem Thromb Hemost 2003; 29: 171-174.
25 Frenkel E. et al. Congenital hypofibrinogenemia in pregnancy: report of two cases and review of the literature. Obstet Gynecol Surv 2004; 59: 775-779.
26 Kumar M, Mehta P. Congenital coagulopathies and pregnancy: Report of four pregnancies in a factor X-deficient woman. Am J Hematol 1994; 46: 241-244.
27 Valnicek S. et al. Hemotherapeutic safeguarding of induced abortion in inborn proconvertin insufficiency (hemagglutination factor VII) using exchange plasmapheresis. Zentralbl Gynakol 1972; 94: 931-935.
28 Bick RL, Baker WF. Antiphospholipid syndrome and thrombosis. Semin Thromb Hemost 1999; 25: 333-350.
29 Schved JF. et al. Factor XII congenital deficiency and early spontaneous abortion. Fertil Steril 1989; 52: 335-336.
30 Klein M. et al. Obstetrical management of dysfibrinogenemia with increased thrombophilia. Geburtshilfe Frauenheilkd 1992; 52: 442-444.
31 Barkagan ZS, Belykh I S. Protein C deficiency and the multi-thrombotic syndrome associated with pregnancy and abortion. Gematol Transfuziol 1992; 37: 35-37.
32 Hellgren M. et al. Pregnancy in women with congenital antithrombin III deficiency: experience of treatment with heparin and antithrombin. Gynecol Obstet Invest 1982; 14: 127-141.
33 Simioni P. et al. Hereditary heparin cofactor II deficiency and trombosis: report of six patients belonging to two separate kindreds. Blood Coagul Fibrinolysis 1990; 1: 351-356.
34 Gris JC. et al. Plasma fibrinolytic activators and their inhibitors in women suffering from early recurrent abortion of unknown etiology. J Lab Clin Med 1993; 122: 606-615.
35 Glueck CJ. et al. Plasminogen activator inhibitor activity: an independent risk factor for the high miscarriage rate during pregnancy in women with polycystic ovary syndrome. Metabolism 1999; 48: 1589-1595.
36 Ingram GIC. The determination of plasma fibrinogen by the clot weight method. Biochem J 1952; 51: 583-585.
37 Blombäck B, Okada M. Fibrin gel structure and clotting time. Thromb Res 1982; 25: 51-70.
38 Janmey PA. A torsion pendulum for measurement of the viscoelasticity of biopolymers and its application to actin networks. J Biochem Biophys Methods 1991; 22: 41-53.
39 Lopez Ramirez Y. et al. Prevalence of the coagulation factor XIII polymorphism Val34Leu in women with recurrent miscarriage. Clin Chim Acta 2006; 374: 69-74.
40 Langer BG. et al. Deglycosylation of fibrinogen accelerates polymerization and increases lateral aggregation of fibrin fibers. J Biol Chem 1988; 263: 15056-15063.
41 Ebert RF. Index of variant human fibrinogens Press Boca Raton. 1991
42 Gralnick HR. et al. Dysfibrinogenemia associated with hepatoma. Increased carbohydrate content of the fibrinogen molecule. N Engl J Med 1978; 299: 221-226.
43 Weisel JW, Nagaswami C. Computer modeling of fibrin polymerization kinetics correlated with electron microscope and turbidity observations: clot structure and assembly are kinetically controlled. Biophys J 1992; 63: 111-128.
44 Maghzal GJ. et al. The sialic acid content of fibrinogen decreases during pregnancy and increases in response to fibrate therapy. Thromb Res 2005; 115: 293-299.
45 Schubring C. et al. Fibrinolysis and factor XIII in women with spontaneous abortion. Eur J Obstet Gynecol Reprod Biol 1990; 35: 215-221.
46 Rai R. et al. Thromboelastography, whole blood haemostasis and recurrent miscarriage. Hum Reprod 2003; 18: 2540-2543.