Association Between Inherited Thrombophilias, Antiphospholipid Antibodies, and Lipoprotein A Levels and Venous Thromboembolism in Pregnancy

Dotun Ogunyemi; Francisco Cuellar; Wayne Ku; Yale Arkel

doi:10.1055/s-2003-37947

American Journal of Perinatology, Table of Contents

Am J Perinatol 2003; 20(1): 017-024
DOI: 10.1055/s-2003-37947

Association Between Inherited Thrombophilias, Antiphospholipid Antibodies, and Lipoprotein A Levels and Venous Thromboembolism in Pregnancy

Dotun Ogunyemi^1,2 , Francisco Cuellar² , Wayne Ku³ , Yale Arkel³

¹Perinatology Unit, Morristown Memorial Hospital, New Jersey
²Division of Obstetrics, King Drew Medical Center, UCLA School of Medicine, Los Angeles, California
³New York University, NY, New York

Abstract

ABSTRACT

The objective of this study is to evaluate the association between venous thromboembolism (VTE) in pregnancy with thrombophilic factors. Thirty pregnant women with VTE were compared with 30 pregnant women matched by age and race without VTE and evaluated for risk factors and thrombophilia. Statistical analysis used two-tailed Fisher's exact test. VTE distribution was 30% in first trimester, 9% in 2nd trimester, 26% in 3rd trimester and 35% postpartum. Seventeen (57%) of VTE cases versus 2 (7%) of control cases had specific thrombophilia diagnosis (p <0.001). The results were: Factor V Leiden mutation (27 vs. 3%) p = 0.026, MTHFR homozygous 677 mutation (10 vs. 44%) p = 0.017, prothrombin gene mutation (11 vs. 0%), protein C deficiency (7 vs. 0%), antiphospholipid antibodies (27 vs. 3%) p = 0.026, mean lipoprotein levels 49 versus 23 mg/dL, p = 0.008, mean homocysteine levels 7.8 versus 7.1 umol/L. An association is suggested between thromboembolic events in pregnancy and thrombophilia, especially Factor V Leiden gene mutation and elevated antiphospholipid antibodies. A new finding is the association of elevated lipoprotein A levels with thromboembolic events in pregnancy.

KEYWORD

Pregnancy - venous thromboembolism - inherited thrombophilia - lipoprotein A - antiphospholipid antibodies

Full Text

References

REFERENCES

1 Rosendaal F R. Thrombosis in the young: epidemiology and risk factors. A focus on venous thrombosis. Thromb Haemost . 1997; 78 1-6
2 Laros R. Thromboembolism in pregnancy. ACOG Educational bulletin . 1997; 234
3 Rosendaal F R. Venous thrombosis: a multicausal disease. Lancet . 1999; 353 1167-1173
4 Greer I A. Thrombosis in pregnancy: maternal and fetal issues. Lancet . 1999; 353 1258-1265
5 Ogunyemi D. Venous thrombosis in pregnancy. Female patient . 2000; 25 70-77
6 Bertina R M. Factor V Leiden and other coagulation factor mutations affecting thrombotic risk. Clin Chemist . 1997; 43 1678-1683
7 Rees D C, Cox M, Clegg J B. World distribution of factor V Leiden. Lancet . 1995; 346 1133-1134
8 Poort S R, Rosendaal F R, Reitsma P H, Bertina R M. A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated prothrombin levels and an increase in venous thrombosis. Blood . 1996; 88 3698-3703
9 Den Heijer M, Koster T, Blom H J. et al . Hyperhomocystenemia as a risk factor for deep venous thrombosis. N Engl J Med . 1996; 33 759-762
10 Arruda V R, von Zuben M P, Chiaparini L C. et al . The mutation ALA677 in the methylene tetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis. Thromb Hemost . 1997; 77 818-821
11 Greaves M. Antiphospholipid antibodies and thrombosis. Lancet . 1999; 353 1348-1353
12 Djurovic S, Berg K. Epidemiology of Lp(a) lipoprotein: its role in atherosclerotic disease. Clin Genet . 1997; 52 281-292
13 Harris E D. Lipoprotein (a): a predictor of atherosclerotic disease. Nutr Rev . 1997; 55 61-64
14 Kuperminc M J, Eldor A, Steinman N. et al . Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl Med . 1999; 340 9-13
15 Ogunyemi D. The association of factor-V Leiden mutation and acquired antibodies with obstetrical complications. Am J Obstet Gynecol-SPO abstracts . 1999; 180 481
16 Lubencho L O, Hansman C, Boyd E. Intrauterine growth in length and head circumference as estimated from live births at gestational ages from 26-42 weeks. Pediatrics . 1966; 37 403-408
17 Dilley A, Austin H, El-Jamil M. et al . Genetic factors associated with thrombosis in pregnancy in a United States population. Am J Obstet Gynecol . 2000; 183 1271-1277
18 Grandone E, Margaglione M, Colaizzo D. et al . Genetic susceptibility to pregnancy-related venous thromboembolism: roles of factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations. Am J Obstet Gynecol . 1998; 179 1324-1328
19 Gerhardt A, Scharf R, Eberhard B. et al . Prothrombin and Factor V Mutations in Women with a History of Thrombosis during Pregnancy and the Puerperium. N Engl J Med . 2000; 342 374-380
20 Gharavi A E, Pierangeli S S, Levy R A, Harris E N. Mechanisms of pregnancy loss in antiphospholipid syndrome. Clin Obstet Gynecol . 2001; 44 11-19
21 Leeda M, Riyazi N, de Vries J. et al . Effects of folic acid and vitamin B6 supplementation on women with Hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. Am J Obstet Gynecol . 1998; 179 135-139
22 Wang J, Mimuro S, Lahoud R. et al . Elevated levels of lipoprotein (a) in women with preeclampsia. Am J Obstet Gynecol . 1998; 178 146-149
23 Husby H, Schjetlein R, Nesheim B, Berg K. High levels of Lp(a) lipoprotein in a family with severe preeclampsia. Clin Genet . 1996; 50 47-49
24 Leerink C B, de Vries C, van der Klis F. Elevated levels of serum lipoprotein (a) and apolipoprotein (a) phenotype are not related to preeclampsia. Acta Obstet Gynecol Scand . 1997; 76 625-628
25 Szczepanski M, Bauer A, Gardas A, Duchinski T. Antiphospholipid antibodies and lipoprotein (a) in women with recurrent fetal loss. Int J Obstet Gynecol . 1998; 61 39-44
26 Berg K, Roade B, Sande H. High Lp(a) lipoprotein level in maternal serum may interfere with placental circulation and cause fetal growth retardation. Clin Genet . 1994; 46 52-56