Prevention of Venous Thromboembolism during Pregnancy and the Puerperium with a Special Focus on Women with Hereditary Thrombophilia or Prior VTE—Position Paper of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH)

Christina Hart; Rupert Bauersachs; Ute Scholz; Rainer Zotz; Frauke Bergmann; Hannelore Rott; Birgit Linnemann

doi:10.1055/a-1132-0750

Hämostaseologie, Table of Contents

Hamostaseologie 2020; 40(05): 572-590
DOI: 10.1055/a-1132-0750

Review Article

Prevention of Venous Thromboembolism during Pregnancy and the Puerperium with a Special Focus on Women with Hereditary Thrombophilia or Prior VTE—Position Paper of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH)

Christina Hart

¹Department of Hematology and Oncology, Internal Medicine III, University Hospital Regensburg, Regensburg, Germany

,

Rupert Bauersachs

²Department of Vascular Medicine, Klinikum Darmstadt GmbH, Darmstadt, Germany

³Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany

,

Ute Scholz

⁴MVZ Labor Dr. Reising-Ackermann und Kollegen, Zentrum für Blutgerinnungsstörungen, Leipzig, Germany

,

Rainer Zotz

⁵Centrum für Blutgerinnungsstörungen und Transfusionsmedizin, Düsseldorf, Germany

,

Frauke Bergmann

⁶MVZ Wagnerstibbe, Amedes-Gruppe, Hannover, Lower Saxony, Germany

,

Hannelore Rott

⁷Gerinnungszentrum Rhein-Ruhr, Duisburg, Germany

,

Birgit Linnemann

⁸Division of Angiology, University Center of Vascular Medicine, University Hospital Regensburg, Regensburg, Germany

› Author Affiliations

Abstract

Venous thromboembolism (VTE) is a major cause of maternal morbidity during pregnancy and the postpartum period. Because there is a lack of adequate study data, management strategies for the prevention of VTE during pregnancy have mainly been deduced from case–control and observational studies and extrapolated from recommendations for non-pregnant patients. The decision for or against pharmacologic thromboprophylaxis must be made on an individual basis weighing the risk of VTE against the risk of adverse side effects such as severe bleeding complications. A comprehensive, multidisciplinary approach is often essential as the clinical scenario is made more complex by the specific obstetric context, especially in the peripartum period. As members of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH), we summarize the evidence from the available literature and aim to establish a more uniform strategy for VTE risk assessment and thromboprophylaxis in pregnancy and the puerperium. In this document, we focus on women with hereditary thrombophilia, prior VTE and the use of anticoagulants that can safely be applied during pregnancy and the lactation period.

Keywords

venous thromboembolism - thromboprophylaxis - pregnancy - postpartum - risk assessment - heparin

Full Text

References

References
1 Say L, Chou D, Gemmill A. et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health 2014; 2 (06) e323-e333
2 Pomp ER, Lenselink AM, Rosendaal FR, Doggen CJ. Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study. J Thromb Haemost 2008; 6 (04) 632-637
3 James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol 2006; 194 (05) 1311-1315
4 Ray JG, Chan WS. Deep vein thrombosis during pregnancy and the puerperium: a meta-analysis of the period of risk and the leg of presentation. Obstet Gynecol Surv 1999; 54 (04) 265-271
5 Jacobsen AF, Skjeldestad FE, Sandset PM. Incidence and risk patterns of venous thromboembolism in pregnancy and puerperium–a register-based case-control study. Am J Obstet Gynecol 2008; 198 (02) 233.e1-233.e7
6 Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton III LJ. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 2005; 143 (10) 697-706
7 Kane EV, Calderwood C, Dobbie R, Morris C, Roman E, Greer IA. A population-based study of venous thrombosis in pregnancy in Scotland 1980-2005. Eur J Obstet Gynecol Reprod Biol 2013; 169 (02) 223-229
8 Chan WS, Spencer FA, Ginsberg JS. Anatomic distribution of deep vein thrombosis in pregnancy. CMAJ 2010; 182 (07) 657-660
9 James AH. Venous thromboembolism in pregnancy. Arterioscler Thromb Vasc Biol 2009; 29 (03) 326-331
10 Jackson E, Curtis KM, Gaffield ME. Risk of venous thromboembolism during the postpartum period: a systematic review. Obstet Gynecol 2011; 117 (03) 691-703
11 Kamel H, Navi BB, Sriram N, Hovsepian DA, Devereux RB, Elkind MS. Risk of a thrombotic event after the 6-week postpartum period. N Engl J Med 2014; 370 (14) 1307-1315
12 Rova K, Passmark H, Lindqvist PG. Venous thromboembolism in relation to in vitro fertilization: an approach to determining the incidence and increase in risk in successful cycles. Fertil Steril 2012; 97 (01) 95-100
13 Jacobsen AF, Skjeldestad FE, Sandset PM. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. J Thromb Haemost 2008; 6 (06) 905-912
14 Sultan AA, Tata LJ, West J. et al. Risk factors for first venous thromboembolism around pregnancy: a population-based cohort study from the United Kingdom. Blood 2013; 121 (19) 3953-3961
15 Linnemann B, Bauersachs R, Rott H. et al; Working Group in Women's Health of the Society of Thrombosis and Haemostasis. Diagnosis of pregnancy-associated venous thromboembolism - position paper of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH). Vasa 2016; 45 (02) 87-101
16 Linnemann B, Scholz U, Rott H. et al; Working Group in Women's Health of the Society of Thrombosis and Hemostasis. Treatment of pregnancy-associated venous thromboembolism - position paper from the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH). Vasa 2016; 45 (02) 103-118
17 Cumming AM, Tait RC, Fildes S, Yoong A, Keeney S, Hay CR. Development of resistance to activated protein C during pregnancy. Br J Haematol 1995; 90 (03) 725-727
18 Kadauke S, Khor B, Van Cott EM. Activated protein C resistance testing for factor V Leiden. Am J Hematol 2014; 89 (12) 1147-1150
19 Bremme KA. Haemostatic changes in pregnancy. Best Pract Res Clin Haematol 2003; 16 (02) 153-168
20 Franchini M. Haemostasis and pregnancy. Thromb Haemost 2006; 95 (03) 401-413
21 Pabinger I, Grafenhofer H, Kyrle PA. et al. Temporary increase in the risk for recurrence during pregnancy in women with a history of venous thromboembolism. Blood 2002; 100 (03) 1060-1062
22 Brill-Edwards P, Ginsberg JS, Gent M. et al; Recurrence of Clot in This Pregnancy Study Group. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. N Engl J Med 2000; 343 (20) 1439-1444
23 De Stefano V, Martinelli I, Rossi E. et al. The risk of recurrent venous thromboembolism in pregnancy and puerperium without antithrombotic prophylaxis. Br J Haematol 2006; 135 (03) 386-391
24 White RH, Chan WS, Zhou H, Ginsberg JS. Recurrent venous thromboembolism after pregnancy-associated versus unprovoked thromboembolism. Thromb Haemost 2008; 100 (02) 246-252
25 Folkeringa N, Brouwer JL, Korteweg FJ, Veeger NJ, Erwich JJ, van der Meer J. High risk of pregnancy-related venous thromboembolism in women with multiple thrombophilic defects. Br J Haematol 2007; 138 (01) 110-116
26 Gerhardt A, Scharf RE, Greer IA, Zotz RB. Hereditary risk factors for thrombophilia and probability of venous thromboembolism during pregnancy and the puerperium. Blood 2016; 128 (19) 2343-2349
27 Middeldorp S. Thrombosis in women: what are the knowledge gaps in 2013?. J Thromb Haemost 2013; 11 (Suppl. 01) 180-191
28 Stevens SM, Woller SC, Bauer KA. et al. Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. J Thromb Thrombolysis 2016; 41 (01) 154-164
29 Jacobsen AF, Dahm A, Bergrem A, Jacobsen EM, Sandset PM. Risk of venous thrombosis in pregnancy among carriers of the factor V Leiden and the prothrombin gene G20210A polymorphisms. J Thromb Haemost 2010; 8 (11) 2443-2449
30 Robertson L, Wu O, Langhorne P. et al; Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thrombophilia in pregnancy: a systematic review. Br J Haematol 2006; 132 (02) 171-196
31 Skeith L. Preventing venous thromboembolism during pregnancy and postpartum: crossing the threshold. Hematology (Am Soc Hematol Educ Program) 2017; 2017 (01) 160-167
32 Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ. The value of family history as a risk indicator for venous thrombosis. Arch Intern Med 2009; 169 (06) 610-615
33 Yelnik CM, Urbanski G, Drumez E. et al. Persistent triple antiphospholipid antibody positivity as a strong risk factor of first thrombosis, in a long-term follow-up study of patients without history of thrombosis or obstetrical morbidity. Lupus 2017; 26 (02) 163-169
34 Bergrem A, Jacobsen EM, Skjeldestad FE, Jacobsen AF, Skogstad M, Sandset PM. The association of antiphospholipid antibodies with pregnancy-related first time venous thrombosis–a population-based case-control study. Thromb Res 2010; 125 (05) e222-e227
35 Garcia D, Erkan D. Diagnosis and management of the antiphospholipid syndrome. N Engl J Med 2018; 379 (13) 1290
36 Larsen TB, Sørensen HT, Gislum M, Johnsen SP. Maternal smoking, obesity, and risk of venous thromboembolism during pregnancy and the puerperium: a population-based nested case-control study. Thromb Res 2007; 120 (04) 505-509
37 Robinson HE, O'Connell CM, Joseph KS, McLeod NL. Maternal outcomes in pregnancies complicated by obesity. Obstet Gynecol 2005; 106 (06) 1357-1364
38 Blondon M, Harrington LB, Boehlen F, Robert-Ebadi H, Righini M, Smith NL. Pre-pregnancy BMI, delivery BMI, gestational weight gain and the risk of postpartum venous thrombosis. Thromb Res 2016; 145: 151-156
39 Abdul Sultan A, West J, Tata LJ, Fleming KM, Nelson-Piercy C, Grainge MJ. Risk of first venous thromboembolism in pregnant women in hospital: population based cohort study from England. BMJ 2013; 347: f6099
40 Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e691S-e736S
41 Chan WS, Rey E, Kent NE. et al; VTE in Pregnancy Guideline Working Group; Society of Obstetricians and Gynecologists of Canada. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can 2014; 36 (06) 527-553
42 Chan WS, Ginsberg JS. A review of upper extremity deep vein thrombosis in pregnancy: unmasking the ‘ART’ behind the clot. J Thromb Haemost 2006; 4 (08) 1673-1677
43 Bauersachs RM, Manolopoulos K, Hoppe I, Arin MJ, Schleussner E. More on: the ‘ART’ behind the clot: solving the mystery. J Thromb Haemost 2007; 5 (02) 438-439
44 Lindqvist P, Dahlbäck B, Marŝál K. Thrombotic risk during pregnancy: a population study. Obstet Gynecol 1999; 94 (04) 595-599
45 Simpson EL, Lawrenson RA, Nightingale AL, Farmer RD. Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database. BJOG 2001; 108 (01) 56-60
46 Blondon M, Casini A, Hoppe KK, Boehlen F, Righini M, Smith NL. Risks of venous thromboembolism after cesarean sections: a meta-analysis. Chest 2016; 150 (03) 572-596
47 Ducloy-Bouthors AS, Baldini A, Abdul-Kadir R, Nizard J. ESA VTE Guidelines Task Force. European guidelines on perioperative venous thromboembolism prophylaxis: surgery during pregnancy and the immediate postpartum period. Eur J Anaesthesiol 2018; 35 (02) 130-133
48 Okoroh EM, Azonobi IC, Grosse SD, Grant AM, Atrash HK, James AH. Prevention of venous thromboembolism in pregnancy: a review of guidelines, 2000-2011. J Womens Health (Larchmt) 2012; 21 (06) 611-615
49 Said JM, Ignjatovic V, Monagle PT, Walker SP, Higgins JR, Brennecke SP. Altered reference ranges for protein C and protein S during early pregnancy: Implications for the diagnosis of protein C and protein S deficiency during pregnancy. Thromb Haemost 2010; 103 (05) 984-988
50 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
51 Nelson-Piercy CMP, Mackillop L. et al, for the Royal College of Obstetricians and Gynaecologists. Reducing the risk of venous thromboembolism in pregnancy and the puerperium. Green-top Guideline No. 37a. London: RCOG; 2015
52 ACOG Practice Bulletin No. 196: thromboembolism in pregnancy. Obstet Gynecol 2018; 132 (01) e1-e17
53 Bain E, Wilson A, Tooher R, Gates S, Davis LJ, Middleton P. Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period. Cochrane Database Syst Rev 2014; (02) CD001689
54 Lazo-Langner A, Rodger MA, Barrowman NJ, Ramsay T, Wells PS, Coyle DA. Comparing multiple competing interventions in the absence of randomized trials using clinical risk-benefit analysis. BMC Med Res Methodol 2012; 12: 3
55 Carrier M, Le Gal G, Wells PS, Rodger MA. Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med 2010; 152 (09) 578-589
56 Kourlaba G, Relakis J, Kontodimas S, Holm MV, Maniadakis N. A systematic review and meta-analysis of the epidemiology and burden of venous thromboembolism among pregnant women. Int J Gynaecol Obstet 2016; 132 (01) 4-10
57 Greer IA, Nelson-Piercy C. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood 2005; 106 (02) 401-407
58 Romualdi E, Dentali F, Rancan E. et al. Anticoagulant therapy for venous thromboembolism during pregnancy: a systematic review and a meta-analysis of the literature. J Thromb Haemost 2013; 11 (02) 270-281
59 Bates SM, Middeldorp S, Rodger M, James AH, Greer I. Guidance for the treatment and prevention of obstetric-associated venous thromboembolism. J Thromb Thrombolysis 2016; 41 (01) 92-128
60 Eckman MH, Alonso-Coello P, Guyatt GH. et al. Women's values and preferences for thromboprophylaxis during pregnancy: a comparison of direct-choice and decision analysis using patient specific utilities. Thromb Res 2015; 136 (02) 341-347
61 Bates SM, Alonso-Coello P, Tikkinen KA. et al. Women's values and preferences and health state valuations for thromboprophylaxis during pregnancy: a cross-sectional interview. Thromb Res 2016; 140: 22-29
62 Caspers M, Pavlova A, Driesen J. et al. Deficiencies of antithrombin, protein C and protein S - practical experience in genetic analysis of a large patient cohort. Thromb Haemost 2012; 108 (02) 247-257
63 Alhenc-Gelas M, Plu-Bureau G, Hugon-Rodin J, Picard V, Horellou MH. GFHT Study Group on Genetic Thrombophilia. Thrombotic risk according to SERPINC1 genotype in a large cohort of subjects with antithrombin inherited deficiency. Thromb Haemost 2017; 117 (06) 1040-1051
64 Bauer KA, Nguyen-Cao TM, Spears JB. Issues in the diagnosis and management of hereditary antithrombin deficiency. Ann Pharmacother 2016; 50 (09) 758-767
65 Bucciarelli P, Passamonti SM, Biguzzi E. et al. Low borderline plasma levels of antithrombin, protein C and protein S are risk factors for venous thromboembolism. J Thromb Haemost 2012; 10 (09) 1783-1791
66 Di Minno MN, Dentali F, Veglia F, Russolillo A, Tremoli E, Ageno W. Antithrombin levels and the risk of a first episode of venous thromboembolism: a case-control study. Thromb Haemost 2013; 109 (01) 167-169
67 Linnemann B, Hart C. Laboratory diagnostics in thrombophilia. Hamostaseologie 2019; 39 (01) 49-61
68 Pearson-Stuttard B, Bagot C, Ciantar E. et al. Severe antithrombin deficiency in pregnancy: achieving adequate anticoagulation. Obstet Med 2019; 12 (01) 45-51
69 James AH, Bates SM, Bauer KA. et al. Management of hereditary antithrombin deficiency in pregnancy. Thromb Res 2017; 157: 41-45
70 Bauersachs RM, Dudenhausen J, Faridi A. et al; EThIG Investigators. Risk stratification and heparin prophylaxis to prevent venous thromboembolism in pregnant women. Thromb Haemost 2007; 98 (06) 1237-1245
71 Cohen H, Arachchillage DR, Middeldorp S, Beyer-Westendorf J, Abdul-Kadir R. Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH: reply. J Thromb Haemost 2017; 15 (01) 195-197
72 Bapat P, Pinto LS, Lubetsky A. et al. Examining the transplacental passage of apixaban using the dually perfused human placenta. J Thromb Haemost 2016; 14 (07) 1436-1441
73 Bapat P, Pinto LS, Lubetsky A, Berger H, Koren G. Rivaroxaban transfer across the dually perfused isolated human placental cotyledon. Am J Obstet Gynecol 2015; 213 (05) 710.e1-710.e6
74 Bapat P, Kedar R, Lubetsky A. et al. Transfer of dabigatran and dabigatran etexilate mesylate across the dually perfused human placenta. Obstet Gynecol 2014; 123 (06) 1256-1261
75 Lameijer H, Aalberts JJJ, van Veldhuisen DJ, Meijer K, Pieper PG. Efficacy and safety of direct oral anticoagulants during pregnancy; a systematic literature review. Thromb Res 2018; 169: 123-127
76 Cohen H, Arachchillage DR, Middeldorp S, Beyer-Westendorf J, Abdul-Kadir R. Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH. J Thromb Haemost 2016; 14 (08) 1673-1676
77 Beyer-Westendorf J, Michalski F, Tittl L. et al. Pregnancy outcome in patients exposed to direct oral anticoagulants - and the challenge of event reporting. Thromb Haemost 2016; 116 (04) 651-658
78 Moore KL, Persaud TVN, Torchia MG. eds. Human birth defects. In: The Developing Human: Clinically Oriented Embryology. 9th ed. Philadelphia, PA: Saunders/Elsevier; 2013: 471-501
79 Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch Intern Med 2000; 160 (02) 191-196
80 Schaefer C, Hannemann D, Meister R. et al. Vitamin K antagonists and pregnancy outcome. A multi-centre prospective study. Thromb Haemost 2006; 95 (06) 949-957
81 Hüttel E, Padberg S, Meister R, Beck E, Schaefer C. Pregnancy outcome of first trimester exposure to the vitamin K antagonist phenprocoumon depends on duration of treatment. Thromb Haemost 2017; 117 (05) 870-879
82 Hall JG, Pauli RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med 1980; 68 (01) 122-140
83 Ginsberg JS, Hirsh J, Turner DC, Levine MN, Burrows R. Risks to the fetus of anticoagulant therapy during pregnancy. Thromb Haemost 1989; 61 (02) 197-203
84 Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J. et al; ESC Scientific Document Group. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J 2018; 39 (34) 3165-3241
85 Nishimura RA, Otto CM, Bonow RO. et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63 (22) e57-e185
86 Xu Z, Fan J, Luo X. et al. Anticoagulation regimens during pregnancy in patients with mechanical heart valves: a systematic review and meta-analysis. Can J Cardiol 2016; 32 (10) 1248.e1-1248.e9
87 Beinema M, Brouwers JR, Schalekamp T, Wilffert B. Pharmacogenetic differences between warfarin, acenocoumarol and phenprocoumon. Thromb Haemost 2008; 100 (06) 1052-1057
88 te Velde ER, Eijkemans R, Habbema HD. Variation in couple fecundity and time to pregnancy, an essential concept in human reproduction. Lancet 2000; 355 (9219): 1928-1929
89 Casele HL, Laifer SA. Prospective evaluation of bone density in pregnant women receiving the low molecular weight heparin enoxaparin sodium. J Matern Fetal Med 2000; 9 (02) 122-125
90 Wawrzyńska L, Tomkowski WZ, Przedlacki J, Hajduk B, Torbicki A. Changes in bone density during long-term administration of low-molecular-weight heparins or acenocoumarol for secondary prophylaxis of venous thromboembolism. Pathophysiol Haemost Thromb 2003; 33 (02) 64-67
91 Haas S, Encke A, Kopp I. German S3 guideline for the prevention of venous thromboembolism updated Comment on Vasa Supplement 92. Vasa 2016; 45 (05) 347-348
92 Galambosi PJ, Kaaja RJ, Stefanovic V, Ulander VM. Safety of low-molecular-weight heparin during pregnancy: a retrospective controlled cohort study. Eur J Obstet Gynecol Reprod Biol 2012; 163 (02) 154-159
93 Ferres MA, Olivarez SA, Trinh V, Davidson C, Sangi-Haghpeykar H, Aagaard-Tillery KM. Rate of wound complications with enoxaparin use among women at high risk for postpartum thrombosis. Obstet Gynecol 2011; 117 (01) 119-124
94 Andersen AS, Berthelsen JG, Bergholt T. Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin. Acta Obstet Gynecol Scand 2010; 89 (01) 15-21
95 Nelson-Piercy C, Powrie R, Borg JY. et al. Tinzaparin use in pregnancy: an international, retrospective study of the safety and efficacy profile. Eur J Obstet Gynecol Reprod Biol 2011; 159 (02) 293-299
96 Gould MK, Dembitzer AD, Doyle RL, Hastie TJ, Garber AM. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials. Ann Intern Med 1999; 130 (10) 800-809
97 Quinlan DJ, McQuillan A, Eikelboom JW. Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials. Ann Intern Med 2004; 140 (03) 175-183
98 Pettilä V, Kaaja R, Leinonen P, Ekblad U, Kataja M, Ikkala E. Thromboprophylaxis with low molecular weight heparin (dalteparin) in pregnancy. Thromb Res 1999; 96 (04) 275-282
99 Linkins LA, Dans AL, Moores LK. et al. Treatment and prevention of heparin-induced thrombocytopenia: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e495S-e530S
100 Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e24S-e43S
101 Bates SM, Ginsberg JS. How we manage venous thromboembolism during pregnancy. Blood 2002; 100 (10) 3470-3478
102 Uprichard J, Manning RA, Laffan MA. Monitoring heparin anticoagulation in the acute phase response. Br J Haematol 2010; 149 (04) 613-619
103 Greinacher A. Heparin-induced thrombocytopenia. N Engl J Med 2015; 373 (19) 1883-1884
104 Linkins LA, Dans AL, Moores LK. et al. Treatment and prevention of heparin-induced thrombocytopenia: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e495S-e530S
105 Watson H, Davidson S, Keeling D. Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. Br J Haematol 2012; 159 (05) 528-540
106 Cines DB, Levine LD. Thrombocytopenia in pregnancy. Blood 2017; 130 (21) 2271-2277
107 Bergmann F, Rath W. The differential diagnosis of thrombocytopenia in pregnancy. Dtsch Arztebl Int 2015; 112 (47) 795-802
108 Schindewolf M, Lindhoff-Last E, Ludwig RJ, Boehncke WH. Heparin-induced skin lesions. Lancet 2012; 380 (9856): 1867-1879
109 Schindewolf M, Gobst C, Kroll H. et al. High incidence of heparin-induced allergic delayed-type hypersensitivity reactions in pregnancy. J Allergy Clin Immunol 2013; 132 (01) 131-139
110 Ludwig RJ, Schindewolf M, Alban S, Kaufmann R, Lindhoff-Last E, Boehncke WH. Molecular weight determines the frequency of delayed type hypersensitivity reactions to heparin and synthetic oligosaccharides. Thromb Haemost 2005; 94 (06) 1265-1269
111 Le Templier G, Rodger MA. Heparin-induced osteoporosis and pregnancy. Curr Opin Pulm Med 2008; 14 (05) 403-407
112 Lefkou E, Khamashta M, Hampson G, Hunt BJ. Review: low-molecular-weight heparin-induced osteoporosis and osteoporotic fractures: a myth or an existing entity?. Lupus 2010; 19 (01) 3-12
113 Gerhardt A, Zotz RB, Stockschlaeder M, Scharf RE. Fondaparinux is an effective alternative anticoagulant in pregnant women with high risk of venous thromboembolism and intolerance to low-molecular-weight heparins and heparinoids. Thromb Haemost 2007; 97 (03) 496-497
114 Knol HM, Schultinge L, Erwich JJ, Meijer K. Fondaparinux as an alternative anticoagulant therapy during pregnancy. J Thromb Haemost 2010; 8 (08) 1876-1879
115 Magnani HN. An analysis of clinical outcomes of 91 pregnancies in 83 women treated with danaparoid (Orgaran). Thromb Res 2010; 125 (04) 297-302
116 Harenberg J. Treatment of a woman with lupus and thromboembolism and cutaneous intolerance to heparins using fondaparinux during pregnancy. Thromb Res 2007; 119 (03) 385-388
117 Dempfle CE. Minor transplacental passage of fondaparinux in vivo. N Engl J Med 2004; 350 (18) 1914-1915
118 De Carolis S, di Pasquo E, Rossi E. et al. Fondaparinux in pregnancy: could it be a safe option? A review of the literature. Thromb Res 2015; 135 (06) 1049-1051
119 Elsaigh E, Thachil J, Nash MJ. et al. The use of fondaparinux in pregnancy. Br J Haematol 2015; 168 (05) 762-764
120 Chaudhary RK, Nepal C, Khanal N, Pathak R, Giri S, Bhatt VR. Management and outcome of heparin-induced thrombocytopenia in pregnancy: a systematic review. Cardiovasc Hematol Agents Med Chem 2015; 13 (02) 92-97
121 Mauermann E, Vökt C, Tsakiris DA, Tobler D, Girard T. Heparin-induced thrombocytopenia in pregnancy: an interdisciplinary challenge-a case report and literature review. Int J Obstet Anesth 2016; 26: 79-82
122 Ciurzyński M, Jankowski K, Pietrzak B. et al. Use of fondaparinux in a pregnant woman with pulmonary embolism and heparin-induced thrombocytopenia. Med Sci Monit 2011; 17 (05) CS56-CS59
123 Limmer JS, Grotegut CA, Thames E, Dotters-Katz SK, Brancazio LR, James AH. Postpartum wound and bleeding complications in women who received peripartum anticoagulation. Thromb Res 2013; 132 (01) e19-e23
124 Gogarten W, Vandermeulen E, Van Aken H, Kozek S, Llau JV, Samama CM. European Scoeity of Anaesthesiology. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol 2010; 27 (12) 999-1015
125 Waurick K, Riess H, van Aken H. et al. Rückenmarksnahe Regionalanästhesien und Thromboembolieprophylaxe/ antithrombotische Medikation. 3. Überarbeitete Empfehlung der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin. Anaesth Intensivmed 2014; 55: 464-492
126 Ito S. Drug therapy for breast-feeding women. N Engl J Med 2000; 343 (02) 118-126
127 Schaefer C, Spielmann H, Vetter K, Weber-Schöndorfer C. Arzneimittel in Schwangerschaft und Stillzeit, 8thed. München: Urban und Fischer (Elsevier); 2012
128 Charite. Accessed March 23, 2020 at: www.embryotox.de