The cases of antithrombin (AT)-deficient pregnant women with a homozygous HBS II mutation are relatively rare and are accompanied by an increased thrombophilic risk, which is manifested by increased thrombin generation (TG). It is very difficult to ensure their prophylactic treatment during pregnancy. We aimed to determine the utility of the thrombin generation assay (TGA) and anti-factor Xa (anti-FXa) test to monitor the effects of a prophylactic dose of low-molecular-weight heparin (LMWH) in a 28-year-old woman with homozygous AT deficiency caused by mutation c.391C > T#, (p.Leu131Phe†) in the SERPINC1 gene and to compare the findings with those from a group of pregnant and non-pregnant women also treated with LMWH. TG monitoring was chosen due to severe AT deficiency that was manifested by low levels of anti-FXa activity when monitoring the efficacy of LMWH treatment. A significant decrease in TG was detected in all monitored groups (P < .05). There were no thrombotic complications during the whole pregnancy of the woman with AT deficiency. Consistent monitoring of TG with LMWH anticoagulant therapy administration during pregnancy together with AT administration before and after delivery may improve the overall condition of pregnant women and the quality of their care.

Central Hematological Laboratory General University Hospital and Charles University 1st Faculty of Medicine Prague Czech Republic

Institute of Hematology and Blood Transfusion Prague Czech Republic

Thrombotic Centre of Institute of Medical Biochemistry and Laboratory Diagnostics General University Hospital and Charles University 1st Faculty of Medicine Prague Czech Republic

Zobrazit více v PubMed

Kvasnička J. Trombofilie a trombotické stavy v klinické praxi. 1. vydání ed. Grada Publishing a.s.; 2003. 300 p.

Bremme KA. Haemostatic changes in pregnancy. Best Pract Res Clin Haematol. 2003;16(2):153-168. PubMed

Brenner B. Haemostatic changes in pregnancy. Thromb Res. 2004;114(5-6):409-414. PubMed

Čápová I, Salaj P, Hrachovinová I. Hereditary antithrombin deficiency in pregnancy - severe thrombophilic disorder as a danger for mother and foetus. Ceska Gynekol. 2021;86(3):175-182. PubMed

Hart C, Rott H, Heimerl S, Linnemann B. Management of antithrombin deficiency in pregnancy. Hamostaseologie. 2022;42(5):320-329. PubMed

Patnaik MM, Moll S. Inherited antithrombin deficiency: a review. Haemophilia. 2008;14(6):1229-1239. PubMed

James AH, Bates SM, Bauer KA, et al. Management of hereditary antithrombin deficiency in pregnancy. Thromb Res. 2017;157:41-45. PubMed

Queenan JT, Spong CY, Lockwood CJ. Management of high-risk pregnancy : an evidence-based approach. 5th ed. Blackwell; 2007.

Van Cott EM, Orlando C, Moore GW, et al. Recommendations for clinical laboratory testing for antithrombin deficiency; communication from the SSC of the ISTH. J Thromb Haemost. 2020;18(1):17-22. PubMed

Chowdary P, Adamidou D, Riddell A, et al. Thrombin generation assay identifies individual variability in responses to low molecular weight heparin in pregnancy: implications for anticoagulant monitoring. Br J Haematol. 2015;168(5):719-727. PubMed

Ismail SK, Norris L, Higgins JR. Thrombin generation assays for optimizing low molecular weight heparin dosing in pregnant women at risk of thrombosis. Br J Haematol. 2016;172(4):642-643. PubMed

de Laat-Kremers RMW, Ninivaggi M, Devreese KMJ, de Laat B. Towards standardization of thrombin generation assays: inventory of thrombin generation methods based on results of an international society of thrombosis and haemostasis scientific standardization committee survey. J Thromb Haemost. 2020;18(8):1893-1899. PubMed

Ninivaggi M, de Laat-Kremers R, Tripodi A, et al. Recommendations for the measurement of thrombin generation: communication from the ISTH SSC subcommittee on lupus anticoagulant/antiphospholipid antibodies. J Thromb Haemost. 2021;19(5):1372-1378. PubMed

Johns MB, Paulus-Thomas JE. Purification of human genomic DNA from whole blood using sodium perchlorate in place of phenol. Anal Biochem. 1989;180(2):276-278. PubMed

Provazníková D, Matýšková M, Čápová I, et al. Seventeen novel SERPINC1 variants causing hereditary antithrombin deficiency in a Czech population. Thromb Res. 2020;189:39-41. PubMed

Szecsi PB, Jørgensen M, Klajnbard A, Andersen MR, Colov NP, Stender S. Haemostatic reference intervals in pregnancy. Thromb Haemost. 2010;103(4):718-727. doi:10.1160/TH09-10-0704 PubMed DOI

Berresheim M, Wilkie J, Nerenberg KA, Ibrahim Q, Bungard TJ. A case series of LMWH use in pregnancy: should trough anti-Xa levels guide dosing? Thromb Res. 2014;134(6):1234-1240. PubMed

Sarig G, Brenner B. Monitoring of low molecular weight heparin (LMWH) in pregnancy. Thromb Res. 2005;115(Suppl 1):84-86. PubMed

Durai S, Tan LK, Lim S. Antithrombin deficiency in pregnancy. BMJ Case Rep. 2016;2016. PubMed PMC

Kottke-Marchant K, Duncan A. Antithrombin deficiency: issues in laboratory diagnosis. Arch Pathol Lab Med. 2002;126(11):1326-1336. PubMed

Hron G, Kollars M, Binder BR, Eichinger S, Kyrle PA. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA. 2006;296(4):397-402. PubMed

Segers O, van Oerle R, ten Cate H, Rosing J, Castoldi E. Thrombin generation as an intermediate phenotype for venous thrombosis. Thromb Haemost. 2010;103(1):114-122. PubMed

Toglia MR, Weg JG. Venous thromboembolism during pregnancy. N Engl J Med. 1996;335(2):108-114. PubMed

Tripodi A, Martinelli I, Chantarangkul V, Battaglioli T, Clerici M, Mannucci PM. The endogenous thrombin potential and the risk of venous thromboembolism. Thromb Res. 2007;121(3):353-359. PubMed

Hemker HC, Al Dieri R, De Smedt E, Béguin S. Thrombin generation, a function test of the haemostatic-thrombotic system. Thromb Haemost. 2006;96(5):553-561. doi:10.1160/TH06-07-0408 PubMed DOI

Joly B, Barbay V, Borg JY, Le Cam-Duchez V. Comparison of markers of coagulation activation and thrombin generation test in uncomplicated pregnancies. Thromb Res. 2013;132(3):386-391. PubMed

Kraft J, Sunder-Plassmann R, Mannhalter C, 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(6):1023-1031. PubMed

Bates SM, Rajasekhar A, Middeldorp S, et al. American society of hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Adv. 2018;2(22):3317-3359. PubMed PMC

Gutiérrez García I, Pérez Cañadas P, Martínez Uriarte J, García Izquierdo O, Angeles Jódar Pérez M, García de Guadiana Romualdo L. D-dimer during pregnancy: establishing trimester-specific reference intervals. Scand J Clin Lab Invest. 2018;78(6):439-442. PubMed

Bruzzese A, Santoro C, Baldacci E, et al. Antithrombin concentrate during pregnancy in congenital antithrombin deficiency: a single-center experience. Blood Coagul Fibrinolysis. 2019;30(6):304-307. PubMed