Pregnancy complicated with deficiency of antithrombin: Review of current literature
Miroslava Gojnic, Zoran Vilendecic, Stefan Dugalic, Igor Pantic, Jovana Todorovic, Milan Perovic, Mirjana Kovac, Irena Djunic, Predrag Miljic and Jelena Dotlic*
Published: 31 August, 2020 | Volume 3 - Issue 2 | Pages: 103-108
Antithrombin deficiency, although the rarest thrombophilia, carries the highest risk of thromboembolism. This risk is increased especially for pregnant women due to physiological coagulation changes in pregnancy. Therefore, in cases of positive personal and/or family history of thromboembolic events as well as recurrent pregnancy loss women should be tested for antithrombin deficiency. Antithrombin deficiency is caused by numerous mutations of serpin peptidase inhibitor clade C 1 gene (SERPINC) and is classified according to antithrombin plasma activity and antigen levels into Type I (quantitative defect) and Type II (qualitative defect). Complications during pregnancy can be divided into those regarding the mother and those concerning the fetus. The main clinical manifestation of antithrombin deficiency regarding the mother is thromboembolism occurring spontaneously or recurrently during pregnancy. Numerous major gestational complications such as miscarriage, intrauterine growth restriction or fetal death, placental abruption, preeclampsia and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome can be linked to antithrombin deficiency. Close monitoring with early and adequate prophylaxis and treatment nowadays can mostly assure the positive pregnancy outcome for both mother and child. Prophylaxis/therapy with both low molecular weight heparin and antithrombin concentrate should start as soon as pregnancy is planned or at least as early as possible in pregnancy and continue until the end of the puerperium.
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Antithrombin deficiency; SERPINC 1 gene mutations; Pregnancy outcome; Pregnancy complications; Thromboembolism; LMWH and antithrombin concentrate
- American College of Obstetricians and Gynecologists Women's Health Care Physicians. ACOG Practice Bulletin No. 138: inherited thrombophilias in pregnancy. Obstetrics and Gynecology. 2013; 122: 706-707. PubMed: https://pubmed.ncbi.nlm.nih.gov/23963422/
- Pabinger I. Thrombophilia and its impact on pregnancy. Thromb Res. 2009; 123: S16-S21.
- Croles FN, Borjas-Howard J, Nasserinejad K, Leebeek FWG, Meijer K, et al. Risk of Venous Thrombosis in Antithrombin Deficiency: A Systematic Review and Bayesian Meta-analysis. Semin Thromb Hemost. 2018; 44: 315-326. PubMed: https://pubmed.ncbi.nlm.nih.gov/29452444/
- Stevens SM, Woller SC, Bauer KA, Kasthuri R, Cushman M, et al. Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. J Thromb Thrombolysis. 2016; 41: 154-164. PubMed: https://pubmed.ncbi.nlm.nih.gov/26780744/
- Patnaik MM, Moll S. Inherited antithrombin deficiency: a review. Haemophilia. 2008; 14: 1229-1239. PubMed: https://pubmed.ncbi.nlm.nih.gov/19141163/
- Yamada T, Yamada H, Morikawa M, Kato EH, Kishida T, et al. Management of pregnancy with congenital antithrombin III deficiency: two case reports and a review of the literature. J Obstet Gynaecol Res. 2001; 27: 189-197.
- Norlelawati AT, Rusmawati I, Naznin M, Nadia OR, Aizzani RR, et al. Inherited Anti-Thrombin Deficiency in A Malay-Malaysian Family: A Missense Mutation at Nucleotide g.13267C>A aka anti-thrombin Budapest 5 (p.Pro439Thr) of the SERPINC 1 gene. Med J Malaysia. 2014; 69: 27-30. PubMed: https://pubmed.ncbi.nlm.nih.gov/24814625/
- Sharma A, Bhakuni T, Ranjan R, Kumar R, Kishor K, et al. Polymorphisms in factor V and antithrombin III gene in recurrent pregnancy loss: a case-control study in Indian population. J Thromb Thrombolysis. 2015; 39: 481-488. PubMed: https://pubmed.ncbi.nlm.nih.gov/25771983/
- Reitsma PH, Rosendaal FR. Past and future of genetic research in thrombosis. J Thromb Haemost. 2007; 5: S264-S269.
- Maclean PS, Tait RC. Hereditary and acquired antithrombin deficiency: epidemiology, pathogenesis and treatment options. Drugs. 2007; 67: 1429-1440. PubMed: https://pubmed.ncbi.nlm.nih.gov/17600391/
- James AH, Bates SM, Bauer KA, Branch W, Mann K, et al. Management of hereditary antithrombin deficiency in pregnancy. Thromb Res. 2017; 157: 41-45. PubMed: https://pubmed.ncbi.nlm.nih.gov/28689083
- Schumacker-Blay C, Fischer F, Appert A, Lallia A, Carlon M, et al. Repeated thromboembolism during pregnancy with constitutional antithrombin deficiency. J Gynecol Obstet Biol Reprod. 2004; 33: 330-333. PubMed: https://pubmed.ncbi.nlm.nih.gov/15170430/
- Xia Y, Lu QY, Lu YL, et al. Molecular basis of type I antithrombin deficiency in two women with recurrent venous thromboembolism in the first trimester of pregnancy. Blood Cells Mol Dis. 2012; 48: 254-259.
- Rogenhofer N, Bohlmann MK, Beuter-Winkler P, Würfel W, Rank A, et al. Prevention management and extent of adverse pregnancy outcomes in women with hereditary antithrombin deficiency. Ann Hematol. 2014; 93: 385-392. PubMed: https://pubmed.ncbi.nlm.nih.gov/23999648/
- Sabadell J, Casellas M, Alijotas-Reig J, Arellano-Rodrigo E, Cabero L. Inherited antithrombin deficiency and pregnancy: maternal and fetal outcomes. Eur J Obstet Gynecol Reprod Biol. 2010; 149: 47-51. PubMed: https://pubmed.ncbi.nlm.nih.gov/20047788/
- Thomsen AJ, Greer IA. Thromboembolic disease in pregnancy and the puerperium. Green-top guideline no. 37b. Royal College of Obstetricians and Gynaecologists. 2015: 1-32.
- Pearson-Stuttard B, Bagot C, Ciantar E, Myers B, Davies R, et al. Severe antithrombin deficiency in pregnancy: Achieving adequate anticoagulation. Obstet Med. 2019; 12: 45-51. PubMed: https://pubmed.ncbi.nlm.nih.gov/30891093/
- James AH, Konkle BA, Bauer KA. Prevention and treatment of venous thromboembolism in pregnancy in patients with hereditary antithrombin deficiency. Int J Womens Health. 2013; 5: 233-241. PubMed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647601/
- Sharpe CJ, Crowther MA, Webert KE, Donnery C. Cerebral venous thrombosis during pregnancy in the setting of type I antithrombin deficiency:case report and literature review. Transfus Med Rev. 2011; 25: 61-65. PubMed: https://pubmed.ncbi.nlm.nih.gov/21134627/
- Morange PE, Suchon P, Tregouet DA. Genetics of Venous Thrombosis: update in 2015. Thromb Haemost. 2015; 114: 910-919. PubMed: https://pubmed.ncbi.nlm.nih.gov/26354877/
- Ilonczai P, Oláh Z, Selmeczi A, Kerényi A, Bereczky Z, et al. Management and outcome of pregnancies in women with antithrombin deficiency: a single-center experience and review of literature. Blood Coagul Fibrinolysis. 2015; 26: 798-804. PubMed: https://pubmed.ncbi.nlm.nih.gov/26226254/
- Pascual C, Munoz C, Huerta AR. A new case of successful outcome of pregnancy in a carrier of homozygous type II (L99F) antithrombin deficiency. Blood Coagul Fibrinolysis. 2014; 25: 74-76. PubMed: https://pubmed.ncbi.nlm.nih.gov/24158114/
- Alguel G, Jochmans K, Simanek R, Ay C, Quehenberger P, et al. Successful outcome in a pregnant woman with homozygous antithrombin deficiency. Thromb Haemost. 2007; 98: 1377-1378.
- Hajsmanova Z. Pregnancy and delivery in type II hereditary antithrombin deficient patients. Cas Lek Cesk. 2008; 147: 535-537. PubMed: https://pubmed.ncbi.nlm.nih.gov/19177736/
- Durai S, Tan LK, Lim S. Antithrombin deficiency in pregnancy. BMJ Case Rep. 2016.
- Niklassen US, Ingerslev J, Birkebaek NH. Hereditary antithrombin deficiency resulting in severe neonatal thrombosis. Ugeskr Laeger. 2000; 162: 6081-6082.
- Bauer KA, Nguyen-Cao TM, Spears JB. Issues in the Diagnosis and Management of Hereditary Antithrombin Deficiency. Ann Pharmacother. 2016; 50: 758-767. PubMed: https://pubmed.ncbi.nlm.nih.gov/27281301/
- Gammaro L, Lippi G, Bottini E. Severe preeclampsia in antithrombin III deficiency with no history of venous thromboembolism. J Nephrol. 2001; 14: 312-315.
- Brenner B. Clinical management of thrombophilia-related placental vascular complications. Blood. 2004; 103: 4003-4009.
- Greer IA. Clinical Practice. Pregnancy Complicated by Venous Thrombosis. N Engl J Med. 2015; 373: 540-547.
- Croles FN, Nasserinejad K, Duvekot JJ, Kruip MJ, Meijer K, et al. Pregnancy, thrombophilia, and the risk of a first venous thrombosis: systematic review and bayesian meta-analysis. BMJ. 2017.
- Ozsener S, Terek MC, Saydam G. Intracranial venous thrombosis associated with severe antithrombin-III deficiency in pregnancy. J Obstet Gynaecol Res. 2001; 27: 81-84
- Sabzi F, Khosravi D, Faraji R. Congenital antithrombin deficiency in a pregnant woman with right atrium thrombosis. Ethiop J Health Sci. 2015; 25: 385-389. PubMed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762980/
- Rheaume M, Weber F, Durand M, Mahone M. Pregnancy-related venous thromboembolism risk in asymptomatic women with antithrombin deficiency: A systematic review. Obstet Gynecol. 2016; 127: 649-656. PubMed: https://pubmed.ncbi.nlm.nih.gov/26959206/
- Kovac M, Mikovic Z, Rakirevic L, Srzentić S, Mandić V, et al. Successful outcome of pregnancy in a patient with congenital antithrombin deficiency. Vojnosanit Pregl. 2011; 68: 175-177. PubMed: https://pubmed.ncbi.nlm.nih.gov/21452673/
- Kraft J, Sunder-Plassmann R, Mannhalter C, Quehenberger P, Tews G, et al. Women with homozygous AT deficiency type II heparin-binding site (HBS) are at high risk of pregnancy loss and pregnancy complications. Ann Hematol. 2017; 96: 1023-1031. PubMed: https://pubmed.ncbi.nlm.nih.gov/28361296/
- Szilagy A, Nagy A, Tamas P. Two successful pregnancies following eight miscarriages in a patient with antithrombin deficiency. Gynecol Obstet Invest 2006; 61: 111-114.
- Fuller KP, Turner G, Polavarapu S, Prabulos AM. Guidelines for use of anticoagulation in pregnancy. Clin Lab Med. 2013; 33: 343-356. PubMed: https://pubmed.ncbi.nlm.nih.gov/23702122/
- Villani M, Ageno W, Grandone E, Dentali F. The prevention and treatment of venous thromboembolism in pregnancy. Expert Rev Cardiovasc Ther. 2017; 15: 397-402. PubMed: https://pubmed.ncbi.nlm.nih.gov/28425765/
- Paidas MJ, Forsyth C, Quere I. Perioperative and peripartum prevention of venous thromboembolism in patients with hereditary antithrombin deficiency using recombinant antithrombin therapy. Blood Coagul Fibrinolysis. 2014; 25: 444-450.
- Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Ph ysicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl): e691S-e736S. PubMed: https://pubmed.ncbi.nlm.nih.gov/22315276/