Download PDF
Frauenheilkunde up2date 2018; 12(03): 231-249
DOI: 10.1055/s-0043-121869
Allgemeine Gynäkologie
Georg Thieme Verlag KG Stuttgart · New York

Gerinnungsstörungen der Frau

Cordula Franz
,
Vadim Tchaikovski
,
Svetlana N. Tchaikovski
Further Information

Publication History

Publication Date:
19 July 2018 (online)

Also available at
    Permissions and Reprints All articles of this category

Gerinnungsstörungen sind im klinischen Alltag unabhängig von der Fachrichtung ein immer wiederkehrender Begleiter. Bei Frauen müssen durch Schwangerschaften oder exogene Hormonzufuhr zusätzliche Einflussfaktoren berücksichtigt werden. Dieser Artikel gibt einen Überblick über die wichtigsten Thrombo-/Hämophilien und den Umgang mit ihnen in der medizinischen Praxis.
Kernaussagen

  • Ein Thrombophiliescreening kann als Einzelfallentscheidung bei idiopathischen, rezidivierenden Thrombosen, atypischen Thromboselokalisationen, Erstereignis im jungen Alter oder starker positiver Familienanamnese erwogen werden.

  • Das Thromboserisiko steigt in der folgenden Reihenfolge an: Frauen ohne hormonelle Verhütung = Levonorgestrel-freisetzende Spirale = orale Gestagen-Monopräparate < Gestagen-Implantate < 2. Generation KOK < 3. Generation KOK = Drospirenon-haltige KOK = CPA- und CMA-haltige KOK = vaginaler Verhütungsring = Verhütungspflaster.

  • Beim absoluten Thromboserisiko in der Schwangerschaft und postpartal von ≥ 3% sollte eine medikamentöse Thromboseprophylaxe empfohlen werden.

  • Eine Empfehlung zur Prophylaxe von Schwangerschaftskomplikationen mit NMH kann aktuell bei Frauen weder mit noch ohne Thrombophilie gegeben werden.

  • Bei der Verordnung der NMH-Therapie in der Schwangerschaft sollten der Nutzen, die Nachteile und die persönlichen Präferenzen der Patientin berücksichtigt werden.

  • Eine Verlängerung der postoperativen Thromboseprophylaxe bis 4 Wochen nach onkologischen Eingriffen wird empfohlen.

  • Bei onkologischen Patientinnen sollte eine laufende therapeutische Antikoagulation unabhängig von der Indikation mindestens für die Dauer der spezifischen onkologischen Therapie bzw. des Fortbestehens der aktiven onkologischen Erkrankung fortgeführt werden.

  • Kombinierte hormonelle Kontrazeptiva und eine Levonorgestrel-haltige Spirale sind die Therapie der Wahl für Blutungsstörungen aufgrund einer Hämophilie.

  • Bei bekannter Hämophilie sind die Gerinnungskontrollen bei Feststellung der Schwangerschaft, in der 28. und 34. SSW sowie eine Betreuung sinnvoll.

Schlüsselwörter

Thrombophilie - Blutungsneigung - Thrombose - Schwangerschaft - Onkologie
 

  • Literatur

  • 1 Gale AJ. Continuing education course #2: current understanding of hemostasis. Toxicol Pathol 2011; 39: 273-280
    PubMedGoogle Scholar
  • 2 Martinelli I, Mannucci PM, De Stefano V. et al. Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families. Blood 1998; 92: 2353-2358
    CrossrefPubMedGoogle Scholar
  • 3 Sanson BJ, Simioni P, Tormene D. et al. The incidence of venous thromboembolism in asymptomatic carriers of a deficiency of antithrombin, protein C, or protein S: a prospective cohort study. Blood 1999; 94: 3702-3706
    PubMedGoogle Scholar
  • 4 Meinardi JR, Middeldorp S, de Kam PJ. et al. Risk of venous thromboembolism in carriers of factor V Leiden with a concomitant inherited thrombophilic defect: a retrospective analysis. Blood Coagul Fibrinolysis 2001; 12: 713-720
    CrossrefPubMedGoogle Scholar
  • 5 Trenor 3rd CC, Chung RJ, Michelson AD. et al. Hormonal contraception and thrombotic risk: a multidisciplinary approach. Pediatrics 2011; 127: 347-357
    CrossrefPubMedGoogle Scholar
  • 6 Bank I, Libourel EJ, Middeldorp S. et al. Prothrombin 20210A mutation: a mild risk factor for venous thromboembolism but not for arterial thrombotic disease and pregnancy-related complications in a family study. Arch Intern Med 2004; 164: 1932-1937
    CrossrefPubMedGoogle Scholar
  • 7 Lijfering WM, Coppens M, van de Poel MH. et al. The risk of venous and arterial thrombosis in hyperhomocysteinaemia is low and mainly depends on concomitant thrombophilic defects. Thromb Haemost 2007; 98: 457-463
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Gris JC, Bouvier S, Molinari N. et al. Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study. Blood 2012; 119: 2624-2632
    CrossrefPubMedGoogle Scholar
  • 9 Erkan D, Merrill JT, Yazici Y. et al. High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin. Arthritis Rheum 2001; 44: 1466-1467
    CrossrefPubMedGoogle Scholar
  • 10 Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol 2007; 44: 62-69
    CrossrefPubMedGoogle Scholar
  • 11 Findeklee S, Costa SD, Tchaikovski SN. [Thrombophilia and HELLP syndrome in pregnancy – case report and overview of the literature]. Z Geburtshilfe Neonatol 2015; 219: 45-51
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Robertson L, Wu O, Langhorne P. et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol 2006; 132: 171-196
    CrossrefPubMedGoogle Scholar
  • 13 Bates SM, Greer IA, Middeldorp S. et al. 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: e691S-e736S
    CrossrefPubMedGoogle Scholar
  • 14 Koster T, Rosendaal FR, de Ronde H. et al. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet 1993; 342: 1503-1506
    CrossrefPubMedGoogle Scholar
  • 15 Rosendaal FR, Koster T, Vandenbroucke JP. et al. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 1995; 85: 1504-1508
    CrossrefPubMedGoogle Scholar
  • 16 Simone B, De Stefano V, Leoncini E. et al. Risk of venous thromboembolism associated with single and combined effects of Factor V Leiden, Prothrombin 20210A and Methylenetethraydrofolate reductase C677 T: a meta-analysis involving over 11,000 cases and 21,000 controls. Eur J Epidemiol 2013; 28: 621-647
    CrossrefPubMedGoogle Scholar
  • 17 Wu O, Robertson L, Twaddle S. et al. Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study. Health Technol Assess 2006; 10: 1-110
    PubMedGoogle Scholar
  • 18 Poort SR, Rosendaal FR, Reitsma PH. et al. A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88: 3698-3703
    CrossrefPubMedGoogle Scholar
  • 19 Pabinger I, Schneider B. Thrombotic risk in hereditary antithrombin III, protein C, or protein S deficiency. A cooperative, retrospective study. Gesellschaft fur Thrombose- und Hamostaseforschung (GTH) Study Group on Natural Inhibitors. Arterioscler Thromb Vasc Biol 1996; 16: 742-748
    CrossrefPubMedGoogle Scholar
  • 20 Ruiz-Delgado GJ, Cantero-Fortiz Y, Mendez-Huerta MA. et al. Primary thrombophilia in Mexico XII: miscarriages are more frequent in people with Sticky Platelet Syndrome. Turk J Haematol 2017; 34: 239-243
    PubMedGoogle Scholar
  • 21 Mak A, Cheung MW, Cheak AA. et al. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology (Oxford) 2010; 49: 281-288
    CrossrefPubMedGoogle Scholar
  • 22 Fachgesellschaft: Fh. Gefäßmedizin DGfrAGfr. Diagnostik und Therapie der Venenthrombose und der Lungenembolie. AWMF Leitlinien-Register Nr 065/002. 2015
    PubMedGoogle Scholar
  • 23 Connors JM. Thrombophilia Testing and Venous Thrombosis. N Engl J Med 2017; 377: 2298
    PubMedGoogle Scholar
  • 24 Tchaikovski S, Tans G, Rosing J. Venous thrombosis and oral contraceptives: current status. Womenʼs Health (Lond Engl) 2006; 2: 761-772
    PubMedGoogle Scholar
  • 25 Bremme KA. Haemostatic changes in pregnancy. Best Pract Res Clin Haematol 2003; 16: 153-168
    CrossrefPubMedGoogle Scholar
  • 26 Curvers J, Thomassen MC, Rimmer J. et al. Effects of hereditary and acquired risk factors of venous thrombosis on a thrombin generation-based APC resistance test. Thromb Haemost 2002; 88: 5-11
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Mousa HA, Downey C, Alfirevic Z. et al. Thrombin activatable fibrinolysis inhibitor and its fibrinolytic effect in normal pregnancy. Thromb Haemost 2004; 92: 1025-1031
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Johnson JV, Lowell J, Badger GJ. et al. Effects of oral and transdermal hormonal contraception on vascular risk markers: a randomized controlled trial. Obstet Gynecol 2008; 111: 278-284
    CrossrefPubMedGoogle Scholar
  • 29 Scarabin PY, Alhenc-Gelas M, Plu-Bureau G. et al. Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. Arterioscler Thromb Vasc Biol 1997; 17: 3071-3078
    CrossrefPubMedGoogle Scholar
  • 30 Bladbjerg EM, Madsen JS, Kristensen SR. et al. Effect of long-term hormone replacement therapy on tissue factor pathway inhibitor and thrombin activatable fibrinolysis inhibitor in healthy postmenopausal women: a randomized controlled study. J Thromb Haemost 2003; 1: 1208-1214
    CrossrefPubMedGoogle Scholar
  • 31 Post MS, Christella M, Thomassen LG. et al. Effect of oral and transdermal estrogen replacement therapy on hemostatic variables associated with venous thrombosis: a randomized, placebo-controlled study in postmenopausal women. Arterioscler Thromb Vasc Biol 2003; 23: 1116-1121
    CrossrefPubMedGoogle Scholar
  • 32 Folsom AR, Cushman M, Tsai MY. et al. A prospective study of venous thromboembolism in relation to factor V Leiden and related factors. Blood 2002; 99: 2720-2725
    CrossrefPubMedGoogle Scholar
  • 33 Koh KK, Shin MS, Sakuma I. et al. Effects of conventional or lower doses of hormone replacement therapy in postmenopausal women. Arterioscler Thromb Vasc Biol 2004; 24: 1516-1521
    CrossrefPubMedGoogle Scholar
  • 34 Cushman M, Legault C, Barrett-Connor E. et al. Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Circulation 1999; 100: 717-722
    CrossrefPubMedGoogle Scholar
  • 35 Callejon DR, Franceschini SA, Montes MB. et al. Hormone replacement therapy and hemostasis: effects in Brazilian postmenopausal women. Maturitas 2005; 52: 249-255
    CrossrefPubMedGoogle Scholar
  • 36 van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP. et al. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ 2009; 339: b2921
    CrossrefPubMedGoogle Scholar
  • 37 Lidegaard O, Nielsen LH, Skovlund CW. et al. Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001–10. BMJ 2012; 344: e2990
    CrossrefPubMedGoogle Scholar
  • 38 Lidegaard O, Lokkegaard E, Svendsen AL. et al. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ 2009; 339: b2890
    CrossrefPubMedGoogle Scholar
  • 39 Jick H, Jick SS, Gurewich V. et al. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet 1995; 346: 1589-1593
    CrossrefPubMedGoogle Scholar
  • 40 Kujovich JL. Factor V Leiden thrombophilia. Genet Med 2011; 13: 1-16
    CrossrefPubMedGoogle Scholar
  • 41 [Anonym] A multinational case-control study of cardiovascular disease and steroid hormone contraceptives. Description and validation of methods. World Health Organization Collaborative Study of Cardiovascular and Steroid Hormone Contraception. J Clin Epidemiol 1995; 48: 1513-1547
    CrossrefPubMedGoogle Scholar
  • 42 Sweetland S, Beral V, Balkwill A. et al. Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study. J Thromb Haemost 2012; 10: 2277-2286
    CrossrefPubMedGoogle Scholar
  • 43 James AH. Venous thromboembolism in pregnancy. Arterioscler Thromb Vasc Biol 2009; 29: 326-331
    CrossrefPubMedGoogle Scholar
  • 44 Greer IA. Thrombosis in pregnancy: updates in diagnosis and management. Hematology Am Soc Hematol Educ Program 2012; 2012: 203-207
    Google Scholar
  • 45 Knight M. UKOSS. Antenatal pulmonary embolism: risk factors, management and outcomes. BJOG 2008; 115: 453-461
    CrossrefPubMedGoogle Scholar
  • 46 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: 233 e231–e237
    CrossrefPubMedGoogle Scholar
  • 47 James AH, Jamison MG, Brancazio LR. et al. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol 2006; 194: 1311-1315
    CrossrefPubMedGoogle Scholar
  • 48 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: 3953-3961
    CrossrefPubMedGoogle Scholar
  • 49 Abdul Sultan A, West J, Tata LJ. et al. Risk of first venous thromboembolism in pregnant women in hospital: population based cohort study from England. BMJ 2013; 347: f6099
    CrossrefPubMedGoogle Scholar
  • 50 Bates SM, Middeldorp S, Rodger M. et al. Guidance for the treatment and prevention of obstetric-associated venous thromboembolism. J Thromb Thrombolysis 2016; 41: 92-128
    CrossrefPubMedGoogle Scholar
  • 51 Rodger MA, Betancourt MT, Clark P. et al. The association of factor V leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies. PLoS Med 2010; 7: e1000292
    CrossrefPubMedGoogle Scholar
  • 52 Rodger MA, Walker MC, Smith GN. et al. Is thrombophilia associated with placenta-mediated pregnancy complications? A prospective cohort study. J Thromb Haemost 2014; 12: 469-478
    CrossrefPubMedGoogle Scholar
  • 53 Martinelli I, Ruggenenti P, Cetin I. et al. Heparin in pregnant women with previous placenta-mediated pregnancy complications: a prospective, randomized, multicenter, controlled clinical trial. Blood 2012; 119: 3269-3275
    CrossrefPubMedGoogle Scholar
  • 54 Rodger MA, Hague WM, Kingdom J. et al. Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial. Lancet 2014; 384: 1673-1683
    CrossrefPubMedGoogle Scholar
  • 55 Shahbazi S, Moghaddam-Banaem L, Ekhtesari F. et al. Impact of inherited bleeding disorders on pregnancy and postpartum hemorrhage. Blood Coagul Fibrinolysis 2012; 23: 603-607
    CrossrefPubMedGoogle Scholar
  • 56 Pike GN, Bolton-Maggs PH. Factor deficiencies in pregnancy. Hematol Oncol Clin North Am 2011; 25: 359-378 viii–ix
    CrossrefPubMedGoogle Scholar
  • 57 Phillips LE, McLintock C, Pollock W. et al. Recombinant activated factor VII in obstetric hemorrhage: experiences from the Australian and New Zealand Haemostasis Registry. Anesth Analg 2009; 109: 1908-1915
    CrossrefPubMedGoogle Scholar