Prevalence of elevated levels of lipoprotein (a) in complicated pregnancies with intrauterine fetal grow restriction
Keywords:
LIPOPROTEIN (A), FETAL GROWTH DELAY, PREGNANCY COMPLICATIONSAbstract
Background: An adequate placental circulation is vitally important to fetus grow.
Fibrinolytic mechanism play an important role in placental circulation.
Defective placental circulation is frequently seen in pregnant women with intrauterine fetal grow restriction (IFGR). Lipoprotein(a)[Lp(a)] is an antifibrinolytic activator when competing with plasminogen due to their structural similarities. Lp(a) levels are genetically determined: women with high levels of Lp(a) may present an environment of poor fibrinolytic balance in the placenta, that produces repercussions of fetal grow.
Objective: To determine the prevalence of Lp(a) excess in women with IFGR and no ginecologic, endocrine or autoimmune related causes.
Methods: Control population: 50 women with at least 2 normal pregnancies and no lost pregnancies. Study population: 30 pregnant women with IFGR (p<10%).
Intrauterine fetal grow was determined by conventional or color Doppler echography in both fetal and placental uterine arteries. Serum Lp(a) was measured by immunoturbidimetric metyhods with anti-human Lp(a) antibodies (rabbits) [Tina-quant lipoprotein(a) – (Diagnostica Stago)]. Cut value of Lp(a) was 300 mg/L. The elevated levels of Lp(a) were confirmed after pregnancy when values found were pathologic. All patients were interviewed to focus on familial heart disease history.
Results: Lp(a) was higher than 300 mg/L in 3/50 (6%) of the control population compared to 11/30 (36.6%) of the study population. High levels of Lp(a) in women with IFGR ranged from 930 to 2 020 mg/L. These levels were confirmed after pregnancy in 100% of women with IFGR. All these women had a familial history of heart disease.
Conclusion: high levels of Lp(a) are associated with women with IFGR. Further studies on fibrinolytic mechanisms should be of interest for women with IFGR.
References
1) Kupferminc MJ, Eldor A, Steinman N, Many A, Bar-Am A, Jaffa A, et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 1999; 340(1): 9-13.
2) Martinelli P, Grandone E, Colaizzo D, Paladini D, Scianname N, Margaglione M, et al. Familial thrombophilia and the occurrence of fetal growth restriction. Haematologica 2001; 86(4): 428-31.
3) Infante-Rivard C, Rivard GE, Yotov WV, Genin E, Guiguet M, Weinberg C, et al. Association of thrombophilia polymorphisms with intrauterine growth restriction. N Engl J Med 2002; 347(1): 19-25.
4) Roberts D, Schwartz RS. Clotting and hemorrhage in the placenta: a delicate balance. N Engl J Med 2002; 347(1): 57-9.
5) Many A, Schreiber L, Rosner S, Lessing JB, Eldor A, Kupferminc MJ. Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia. Obstet Gynecol 2001; 98(6): 1041-4.
6) Sikkema JM, Franx A, Bruinse HW, van der Wijk NG, de Valk HW, Nikkels PG. Placental pathology in early onset pre-eclampsia and intra-uterine growth restriction in women with and without thrombophilia. Placenta 2002; 23(4): 337-42.
7) Mousa HA, Alfirevicl Z. Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome? Hum Reprod 2000; 15(8): 1830-38.
8) Vern TZ, Alles AJ, Kowal-Vern A, Longtine J, Roberts DJ. Frequency of factor V (Leiden) and prothrombin G20210A in placentas and their relationship with placental lesions. Hum Pathol 2000; 31(9): 1036-43.
9) Gerke V, Moss SE. Annexins: from structure to function. Physiol Rev 2002; (8282): 331-71.
10) Rand JH, Wu X-X, Andree HAM, Lockwood CJ, Guller S, Scher J, et al. Pregnancy loss in the antiphospholipid-antibody syndrome: a possible thrombogenic mechanism. N Engl J Med 1997; 337(18): 154-60.
11) Naeye RL. Placental infarction leading to fetal or neonatal death: a prospective study. Obstet Gynecol 1977; 50(5): 583-8.
12) Sibai BM. Thrombophilias and adverse outcomes of pregnancy: what should a clinician do? N Engl J Med 1999; 340(1): 50-2.
13) Gagnon R. Placental insufficiency and its consequences. Eur J Obstet Gynecol Reprod Biol 2003; 110(Suppl 1): S99-107.
14) Mardi K, Sharma J. Histopathological evaluation of placentas in IUGR pregnancies. Indian J Pathol Microbiol 2003; 46(4): 551-4.
15) Brenner B. Inherited thrombophilia and fetal loss. Curr Opin Hematol 2000; 7(5):290-5.
16) Many A, Schreiber L, Rosner S, Lessing JB, Eldor A, Kupferminc MJ. Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia. Obstet Gynecol 2001; 98(6): 1041-4.
17) Sikkema JM, Franx A, Bruinse HW, van der Wijk NG, de Valk HW, Nikkels PG. Placental pathology in early onset pre-eclampsia and intra-uterine growth restriction in women with and without thrombophilia. Placenta 2002; 23(4): 337-42.
18) Mousa HA, Alfirevicl Z. Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome? Hum Reprod 2000; 15(8): 1830-3.
19) Otero AM, Pou-Ferrari R, Pons E, Lens D, De-Lisa E, Dellepiane M, et al. Trombofilia y pérdida recurrente de embarazo. Rev Med Uruguay 2004; 20(2): 106-13.
20) Marcovina SM, Koschinsky M. Evaluation of lipopro-tein(a) as a prothrombotic factor: progress from bench to bedside. Curr Opin Lipidol 2003; 14(4): 361-6.
21) Danesh J, Collins R, Peto R. Lipoprptein(a) and coronary heart disease: meta-analysis of prospective studies. Circulation 2000; 102(10): 1082-5.
22) Scanu AM, Lawn RM, Berg K. Lipoprotein(a) and atherosclerosis. Ann Intern Med 1991; 115(3): 209-18.
23) Peros E, Geroldi D, D’Angelo A, Falcone C, Montagna L, Carabela M, et al. Apolipoprotein(a) phenotypes are reliable biomarkers for familial aggregation of coronary heart disease. Int J Mol Med 2004; 13(2): 243-7.
24) Biemond BJ, Friederich PW, Koschinsky ML, Levi M, Sangrar W, Xia J, et al. Apolipoprotein(a) attenuates endogenous fibrinolysis in the rabbit jugular vein thrombosis model in vivo. Circulation 1997; 96(5): 1612-5.
25) Hancock MA, Boffa MB, Marcovina SM, Nesheim ME, Koschinsky ML. Activation of plasminogen activation by lipoprotein(a). J Biol Chem 2003; 278(26): 23260-9.
26) Kang C, Domínguez M, Loyau S, Miyata T, Durlach V, Angles-Cano E. Lp(a) particles mold fbrin-binding properties of apo(a) in size-dependent manner: a study with different-length recombinant apo(a), native Lp(a), and monoclonal antibody. Arterioscler Thromb Vasc Biol 2002; 22(7): 1232-8.
27) Hervio L, Chapman JM, Thillet J, Loyau S, Anglés-Cano E. Does apolipoprotein(a) heterogeneity influence lipoprotein(a) effects on fibrinolysis? Blood 1993; 82(2): 392-7.
28) Hervio L, Durlach V, Girard-Globa A, Anglés-Cano E. Multiple binding with identical linkage: a mechanism that explains the effect of lipoprotein(a) on fibrinolysis. Biochemistry 1995; 34(41): 13353-8.
29) Rouy D, Koschinsky ML, Fleury V, Chapman J, Anglés-Cano E. Apolipoprotein(a) and plasminogen interactions with fibrin: a study with recombinant apolipoprotein(a) and isolated plasminogen fragments. Biochemistry 1992; 31(27): 6333- 9.
30) Etingin O, Hajjar D, Hajjar KA, Harpel PC, Nashman RL. Lipoprotein(a) regulates plasminogen activator inhibitor-1 expression in endotelial cells. J Biol Chem 1991; 266(4): 2459-65.
31) Buechler C, Ullrich H, Ritter M, Porsch-Oezcueruemez M, Lackner K, Barlage S, et al. Lipoprotein(a) up-regulates the expression of the plasminogen activator inhibitor 2 in human blood monocytes. Blood 2001; 97(4): 981-6.
32) Caplice NM, Panetta C, Peterson TE, Kleppe LS, Mueske CS, Kostner GM, et al. Lipoprotein(a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis. Blood 2001; 98(10): 2980-7.
33) Ichikawa T, Unoki H, Sun H, Shimoyamada H, Marcovina S, Shikama H, et al. Lipoprotein(a) promotes smooth muscle cell proliferation and dedifferentiation in atherosclerotic lesions of human apo(a) transgenic rabbits. Am J Pathol 2002; 160(1): 227-36.
34) Lawn RM, Wade DP, Hammer RE, Chiesa G, Verstuygt JC, Rubin EM. Atherogenesis in transgenic mice expressing human apolipoprotein(a). Nature 1992; 360(6405): 670-2.
35) McLennan IS, Koishi K. Fetal and maternal transforming growth factor-beta 1 may combine to maintain pregnancy in mice. Biol Reprod 2004; 70(6): 1614-8.
36) Uszynski M, Maciejewski K, Uszynski W, Kuczynski J. Placenta and myometrium—the two main sources of fibrinolytic components during pregnancy. Gynecol Obstet Invest 2001; 52(3): 189-93.
37) Madazli R, Somunkiran A, Calay Z, Ilvan S, Aksu MF. Histomorphology of the placenta and the placental bed of growth restricted foetuses and correlation with the Doppler velocimetries of the uterine and umbilical arteries. Placenta 2003; 24(5): 510-6.
38) Viero S, Chaddha V, Alkazaleh F, Simchen MJ, Malik A, Kelly E, et al. Kingdom JC. Prognostic value of placental ultrasound in pregnancies complicated by absent end-diastolic flow velocity in the umbilical arteries. Placenta 2004; 25(8-9): 735-41.
39) Baschat AA, Hecher K. Fetal growth restriction due to placental disease. Semin Perinatol 2004; 28(1): 67-80.
40) Bogdanovich RN, Chikalovets IV. Trophoblastic beta1-glycoprotein and hemostasis system in pregnant women with antiphospholipid syndrome. Bull Exp Biol Med 2002; 134(4): 397-9.
41) Kramarenko OP. Prognosis, prophylaxis, and early therapy of fetoplacental insufficiency. Lik Sprava 2002; 2: 50-3.
42) Lanir N, Aharon A, Brenner B. Haemostatic mechanisms in human placenta. Best Pract Res Clin Haematol 2003; 16(2): 183-95.
43) Lanir N, Aharon A, Brenner B. Procoagulant and anticoagulant mechanisms in human placenta. Semin Thromb Hemost 2003; 29(2): 175-84.
44) McLean JW, Tomlinson JE, Kuang WJ, Eaton DL, Chen EY, Fless GM, et al. cDNA sequence of human apolipopro-tein(a) is homologous to plasminogen. Nature 1987; 330(6144): 132-7.
45) Koschinsky ML, Marcovina SM. Structure-function relationships in apolipoprotein(a): insights into lipoprotein(a) assembly and pathogenicity. Curr Opin Lipidol 2004; 15(2): 167-74.
46) 46.Thomas HP, Steinhagen-Thiessen E. Lipoprotein(a): aspects of pathophysiology, epidemiology and treatment. Z Kardiol 2003; 92(Suppl 3): III53-8.
47) Scanu AM. Lipoprotein(a) and the atherothrombotic process: mechanistic insights and clinical implications. Curr Atheroscler Rep 2003; 5(2): 106-13.
48) Olson ST, Swanson R, Raub-Segall E, Bedsted T, Sadri M, Petitou M, et al. Accelerating ability of synthetic oligosaccharides on antithrombin inhibition of proteinases of the clotting and fibrinolytic systems. Comparison with heparin and low-molecular-weight heparin. Throm Haemost 2004; 92(5): 929-39.
2) Martinelli P, Grandone E, Colaizzo D, Paladini D, Scianname N, Margaglione M, et al. Familial thrombophilia and the occurrence of fetal growth restriction. Haematologica 2001; 86(4): 428-31.
3) Infante-Rivard C, Rivard GE, Yotov WV, Genin E, Guiguet M, Weinberg C, et al. Association of thrombophilia polymorphisms with intrauterine growth restriction. N Engl J Med 2002; 347(1): 19-25.
4) Roberts D, Schwartz RS. Clotting and hemorrhage in the placenta: a delicate balance. N Engl J Med 2002; 347(1): 57-9.
5) Many A, Schreiber L, Rosner S, Lessing JB, Eldor A, Kupferminc MJ. Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia. Obstet Gynecol 2001; 98(6): 1041-4.
6) Sikkema JM, Franx A, Bruinse HW, van der Wijk NG, de Valk HW, Nikkels PG. Placental pathology in early onset pre-eclampsia and intra-uterine growth restriction in women with and without thrombophilia. Placenta 2002; 23(4): 337-42.
7) Mousa HA, Alfirevicl Z. Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome? Hum Reprod 2000; 15(8): 1830-38.
8) Vern TZ, Alles AJ, Kowal-Vern A, Longtine J, Roberts DJ. Frequency of factor V (Leiden) and prothrombin G20210A in placentas and their relationship with placental lesions. Hum Pathol 2000; 31(9): 1036-43.
9) Gerke V, Moss SE. Annexins: from structure to function. Physiol Rev 2002; (8282): 331-71.
10) Rand JH, Wu X-X, Andree HAM, Lockwood CJ, Guller S, Scher J, et al. Pregnancy loss in the antiphospholipid-antibody syndrome: a possible thrombogenic mechanism. N Engl J Med 1997; 337(18): 154-60.
11) Naeye RL. Placental infarction leading to fetal or neonatal death: a prospective study. Obstet Gynecol 1977; 50(5): 583-8.
12) Sibai BM. Thrombophilias and adverse outcomes of pregnancy: what should a clinician do? N Engl J Med 1999; 340(1): 50-2.
13) Gagnon R. Placental insufficiency and its consequences. Eur J Obstet Gynecol Reprod Biol 2003; 110(Suppl 1): S99-107.
14) Mardi K, Sharma J. Histopathological evaluation of placentas in IUGR pregnancies. Indian J Pathol Microbiol 2003; 46(4): 551-4.
15) Brenner B. Inherited thrombophilia and fetal loss. Curr Opin Hematol 2000; 7(5):290-5.
16) Many A, Schreiber L, Rosner S, Lessing JB, Eldor A, Kupferminc MJ. Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia. Obstet Gynecol 2001; 98(6): 1041-4.
17) Sikkema JM, Franx A, Bruinse HW, van der Wijk NG, de Valk HW, Nikkels PG. Placental pathology in early onset pre-eclampsia and intra-uterine growth restriction in women with and without thrombophilia. Placenta 2002; 23(4): 337-42.
18) Mousa HA, Alfirevicl Z. Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome? Hum Reprod 2000; 15(8): 1830-3.
19) Otero AM, Pou-Ferrari R, Pons E, Lens D, De-Lisa E, Dellepiane M, et al. Trombofilia y pérdida recurrente de embarazo. Rev Med Uruguay 2004; 20(2): 106-13.
20) Marcovina SM, Koschinsky M. Evaluation of lipopro-tein(a) as a prothrombotic factor: progress from bench to bedside. Curr Opin Lipidol 2003; 14(4): 361-6.
21) Danesh J, Collins R, Peto R. Lipoprptein(a) and coronary heart disease: meta-analysis of prospective studies. Circulation 2000; 102(10): 1082-5.
22) Scanu AM, Lawn RM, Berg K. Lipoprotein(a) and atherosclerosis. Ann Intern Med 1991; 115(3): 209-18.
23) Peros E, Geroldi D, D’Angelo A, Falcone C, Montagna L, Carabela M, et al. Apolipoprotein(a) phenotypes are reliable biomarkers for familial aggregation of coronary heart disease. Int J Mol Med 2004; 13(2): 243-7.
24) Biemond BJ, Friederich PW, Koschinsky ML, Levi M, Sangrar W, Xia J, et al. Apolipoprotein(a) attenuates endogenous fibrinolysis in the rabbit jugular vein thrombosis model in vivo. Circulation 1997; 96(5): 1612-5.
25) Hancock MA, Boffa MB, Marcovina SM, Nesheim ME, Koschinsky ML. Activation of plasminogen activation by lipoprotein(a). J Biol Chem 2003; 278(26): 23260-9.
26) Kang C, Domínguez M, Loyau S, Miyata T, Durlach V, Angles-Cano E. Lp(a) particles mold fbrin-binding properties of apo(a) in size-dependent manner: a study with different-length recombinant apo(a), native Lp(a), and monoclonal antibody. Arterioscler Thromb Vasc Biol 2002; 22(7): 1232-8.
27) Hervio L, Chapman JM, Thillet J, Loyau S, Anglés-Cano E. Does apolipoprotein(a) heterogeneity influence lipoprotein(a) effects on fibrinolysis? Blood 1993; 82(2): 392-7.
28) Hervio L, Durlach V, Girard-Globa A, Anglés-Cano E. Multiple binding with identical linkage: a mechanism that explains the effect of lipoprotein(a) on fibrinolysis. Biochemistry 1995; 34(41): 13353-8.
29) Rouy D, Koschinsky ML, Fleury V, Chapman J, Anglés-Cano E. Apolipoprotein(a) and plasminogen interactions with fibrin: a study with recombinant apolipoprotein(a) and isolated plasminogen fragments. Biochemistry 1992; 31(27): 6333- 9.
30) Etingin O, Hajjar D, Hajjar KA, Harpel PC, Nashman RL. Lipoprotein(a) regulates plasminogen activator inhibitor-1 expression in endotelial cells. J Biol Chem 1991; 266(4): 2459-65.
31) Buechler C, Ullrich H, Ritter M, Porsch-Oezcueruemez M, Lackner K, Barlage S, et al. Lipoprotein(a) up-regulates the expression of the plasminogen activator inhibitor 2 in human blood monocytes. Blood 2001; 97(4): 981-6.
32) Caplice NM, Panetta C, Peterson TE, Kleppe LS, Mueske CS, Kostner GM, et al. Lipoprotein(a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis. Blood 2001; 98(10): 2980-7.
33) Ichikawa T, Unoki H, Sun H, Shimoyamada H, Marcovina S, Shikama H, et al. Lipoprotein(a) promotes smooth muscle cell proliferation and dedifferentiation in atherosclerotic lesions of human apo(a) transgenic rabbits. Am J Pathol 2002; 160(1): 227-36.
34) Lawn RM, Wade DP, Hammer RE, Chiesa G, Verstuygt JC, Rubin EM. Atherogenesis in transgenic mice expressing human apolipoprotein(a). Nature 1992; 360(6405): 670-2.
35) McLennan IS, Koishi K. Fetal and maternal transforming growth factor-beta 1 may combine to maintain pregnancy in mice. Biol Reprod 2004; 70(6): 1614-8.
36) Uszynski M, Maciejewski K, Uszynski W, Kuczynski J. Placenta and myometrium—the two main sources of fibrinolytic components during pregnancy. Gynecol Obstet Invest 2001; 52(3): 189-93.
37) Madazli R, Somunkiran A, Calay Z, Ilvan S, Aksu MF. Histomorphology of the placenta and the placental bed of growth restricted foetuses and correlation with the Doppler velocimetries of the uterine and umbilical arteries. Placenta 2003; 24(5): 510-6.
38) Viero S, Chaddha V, Alkazaleh F, Simchen MJ, Malik A, Kelly E, et al. Kingdom JC. Prognostic value of placental ultrasound in pregnancies complicated by absent end-diastolic flow velocity in the umbilical arteries. Placenta 2004; 25(8-9): 735-41.
39) Baschat AA, Hecher K. Fetal growth restriction due to placental disease. Semin Perinatol 2004; 28(1): 67-80.
40) Bogdanovich RN, Chikalovets IV. Trophoblastic beta1-glycoprotein and hemostasis system in pregnant women with antiphospholipid syndrome. Bull Exp Biol Med 2002; 134(4): 397-9.
41) Kramarenko OP. Prognosis, prophylaxis, and early therapy of fetoplacental insufficiency. Lik Sprava 2002; 2: 50-3.
42) Lanir N, Aharon A, Brenner B. Haemostatic mechanisms in human placenta. Best Pract Res Clin Haematol 2003; 16(2): 183-95.
43) Lanir N, Aharon A, Brenner B. Procoagulant and anticoagulant mechanisms in human placenta. Semin Thromb Hemost 2003; 29(2): 175-84.
44) McLean JW, Tomlinson JE, Kuang WJ, Eaton DL, Chen EY, Fless GM, et al. cDNA sequence of human apolipopro-tein(a) is homologous to plasminogen. Nature 1987; 330(6144): 132-7.
45) Koschinsky ML, Marcovina SM. Structure-function relationships in apolipoprotein(a): insights into lipoprotein(a) assembly and pathogenicity. Curr Opin Lipidol 2004; 15(2): 167-74.
46) 46.Thomas HP, Steinhagen-Thiessen E. Lipoprotein(a): aspects of pathophysiology, epidemiology and treatment. Z Kardiol 2003; 92(Suppl 3): III53-8.
47) Scanu AM. Lipoprotein(a) and the atherothrombotic process: mechanistic insights and clinical implications. Curr Atheroscler Rep 2003; 5(2): 106-13.
48) Olson ST, Swanson R, Raub-Segall E, Bedsted T, Sadri M, Petitou M, et al. Accelerating ability of synthetic oligosaccharides on antithrombin inhibition of proteinases of the clotting and fibrinolytic systems. Comparison with heparin and low-molecular-weight heparin. Throm Haemost 2004; 92(5): 929-39.
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2005-10-31
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Otero AM, Bianchi A, Dellepiane M, Pou R, Storch E, Pons E, et al. Prevalence of elevated levels of lipoprotein (a) in complicated pregnancies with intrauterine fetal grow restriction. Rev. Méd. Urug. [Internet]. 2005 Oct. 31 [cited 2024 Oct. 18];21(3):236-41. Available from: https://revista.rmu.org.uy/index.php/rmu/article/view/809
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