Thromboembolische Erkrankungen in der Schwangerschaft

Zusammenfassung

In der Schwangerschaft treten thromboembolische Komplikationen sechsmal häufiger auf als bei nichtschwangeren Frauen. Die wesentlichen Faktoren für ein erhöhtes Thrombose- und Lungenembolie-Risiko sind Alter, idiopathische wie sekundäre Thrombosen in der Anamnese, Entbindungsmodus, Immobilisierung und / oder Fettleibigkeit sowie die thrombophilen Hämostasestörungen. Als Thromboseprophylaxe sind die niedermolekularen Heparine (NMHs) gegenüber den unfraktionierten Heparinen (UFHs) Mittel der ersten Wahl. Orale Antikoagulantien wie die Cumarinderivate und die Thrombozytenaggregationshemmer sind angesichts einer ganzen Reihe von Kontraindikationen von untergeordneter Bedeutung. Der Ausschluss einer tiefen Beinvenenthrombose (TVT) und / oder einer Lungenembolie in der Schwangerschaft folgt den üblichen Diagnosealgorithmen unter Berücksichtigung einer möglichst geringen Strahlenbelastung durch eventuell erforderliche apparative Diagnostik. Bei der Therapie nachgewiesener TVTs sind die UFHs zu favorisieren, es bestehen mittlerweile aber auch zunehmend gute Erfahrungen bei der Anwendung der NMHs. Erweist sich eine Heparintherapie als nicht ausreichend oder droht die Gefahr eines postthrombotischen Syndroms, so ist in bestimmten Fällen der zusätzliche Einsatz einer Lysetherapie und / oder einer operativen Thrombektomie zu erwägen.

Abstract

In pregnancy, thromboembolic complications are six times more frequent than in nonpregnant women. Maternal age, idiopathic or secondary thrombosis in the patients history, the mode of delivery, bed rest and / or obesity as well as the thrombophilic defects are considerable factors for an increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE). Compared to unfractionated heparins (UFHs) prophylactic treatment relies mainly on low molecular weight heparins (LMWHs) which safety is now well established in pregnant women. In view of their multiple side effects oral anticoagulants such as cumarine or aspirine are contraindicated or of subordinate importance. The procedures to exclude DVT follow the usual diagnostic algorithms considering maximum radiation protection in case of further apparative diagnostics. Although there are reported good experiences with LMWHs in the treatment of DVT, UFHs are still the prefered drugs in this clinical condition. Insufficient heparin treatment or impending postthrombotic complications may be reasons for additional therapies like thrombolysis or operative thrombectomy.

Schlüsselwörter

Schwangerschaft - thrombophile Hämostasestörungen - Thromboseprophylaxe - Thromboembolie - Heparin

Key words

pregnancy - thrombophilic defects - thromboprophylaxis - thromboembolia - heparin

Literatur

• 1 A Working group on behalf the Obstetric Medicine Group of Australasia . Anticoagulation in pregnancy and the puerperium.  MJA. 2001;  175 258
• 2 Thromboembolism in pregnancy. ACOG Practice Bulletin 2000 19
• 3 Anticoagulation in pregnancy and the puerperium.  Med J Aust. 2001;  175 258-263
• 4 Armour R, Schwedler M, Kerstein M D. Current assessment of thromboembolic disease and pregnancy.  Am Surg. 2001;  67 641-644
• 5 Backos M, Chilcott I, Rai R. Pregnancy complications in women with recurrent miscarriage and antiphospholipide-antibodies treated with low dose aspirin and heparin.  Br J Obstet Gynaecol.. 1999;  106 102-107
• 6 Bates S M, Ginsberg J S. How we manage venous thromboembolism during pregnancy.  Blood. 2002;  100 3470-3478
• 7 Bauduer F, Lacombe D. Factor V Leiden, prothrombin 20210A, methylenetetrahydrofolate reductase 677 T, and population genetics.  Mol Genet Metab. 2005;  86 91-99
• 8 Bechtel J J, Mountford M C, Ellinwood W E. Massive Pulmonary Embolism in Pregnancy Treated With Catheter Fragmentation and Local Thrombolysis.  Obstet Gynecol. 2005;  106 1158-1160
• 9 Bergqvist D, Hedner U. Pregnancy and venous thromboembolism.  Acta Obstet Gynecol Scand. 1983;  62 449-453
• 10 Brill-Edwards P, Ginsberg J S, Gent M. et al . Safety of withholding heparin in pregnant women with a history of venous thromboembolism. Recurrence of Clot in This Pregnancy Study Group.  N Engl J Med. 2000;  343 1439-1444
• 11 Carr M H, Towers C V, Eastenson A R, Pircon R A, Iriye B K, Adashek J A. Prolonged bedrest during pregnancy: does the risk of deep vein thrombosis warrant the use of routine heparin prophylaxis?.  J Matern Fetal Med. 1997;  6 264-267
• 12 Chan W S, Ray J G, Murray S, Coady G E, Coates G, Ginsberg J S. Suspected pulmonary embolism in pregnancy: clinical presentation, results of lung scanning, and subsequent maternal and pediatric outcomes.  Arch Intern Med. 2002;  162 1170-1175
• 13 Colvin B T, Barrowcliffe T W. The British Society for Haematology Guidelines on the use and monitoring of heparin 1992: second revision. BCSH Haemostasis and Thrombosis Task Force.  J Clin Pathol. 1992;  46 97-103
• 14 Crowther M A, Kelton J G. Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system.  Ann Intern Med. 2003;  138 128-134
• 15 Dahlbäck B, Villoutreix B O. The anticoagulant protein C pathway.  FEBS Letters. 2005;  579 3310-3316
• 16 Dahlmann T C. Osteoporotic fractures and the recurrence of thromboembolism during pregnancy and the puerperium in 184 women undergoing thromboprophylaxis with heparin.  Am J Obstet Gynecol. 1993;  168 1265-1270
• 17 De Stefano V, Rossi E, Paciaroni K, Leone G. Screening for inherited Thrombophilia: indications and therapeutic impklications.  Haematologica. 2002;  87 1095-1108
• 18 De Swiet M. Maternal mortality: Confidential enquiries into maternal deaths in the United Kingdom.  Am J Obstet Gynecol. 2000;  182 760-766
• 19 Dilley A, Austin H, El-Jamil M, Hooper W C, Barnhart E, Evatt B L, Sullivan P S, Ellingsen D, Patterson-Barnett A, Eller D, Randall H, Philipp C. Genetic factors associated with thrombosis in pregnancy in a United States population.  Am J Obstet Gynecol. 2000;  183 1271-1277
• 20 Dizon-Townson D S, Nelson L M, Jang H, Varner M W, Ward K. The incidence of the factor V Leiden mutation in an obstetric population and its relationship to deep vein thrombosis.  Am J Obstet Gynecol. 1997;  176 883-886
• 21 Eldor A. Thrombophilia, thrombosis and pregnancy.  Thromb Haemost. 2001;  86 104-111
• 22 Ensom M H, Stephenson M D. Low-molecular-weight heparins in pregnancy.  Pharmacotherapy. 1999;  19 1013-1025
• 23 Gates S. Thromboembolic disease in pregnancy.  Curr Opin Obstet Gynecol. 2000;  12 117-122
• 24 Gerhardt A, Scharf R E, Beckmann M W, Struve S, Bender H G, Pillny M, Sandmann W, Zotz R B. Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium.  N Engl J Med. 2000;  342 374-380
• 25 Gerhardt A, Scharf R E, Zotz R B. Effect of hemostatic risk factors on the individual probability of thrombosis during pregnancy and the puerperium.  Thromb Haemost. 2003;  90 77-85
• 26 Gherman R B, Goodwin T M, Leung B, Byrne J D, Hethumumi R, Montoro M. Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy.  Obstet Gynecol. 1999;  94 730-734
• 27 Ginsberg J S, Brill-Edwards P, Burrows R F, Bona R, Prandoni P, Buller H R, Lensing A. Venous thrombosis during pregnancy: leg and trimester of presentation.  Thromb Haemostat. 1992;  67 519-520
• 28 Ginsberg J S, Bates S M. Management of venous thromboembolism during pregnancy.  J Thromb Haemost. 2003;  1 1435-1442
• 29 Girardi G. Heparin treatment in pregnancy loss: Potential therapeutic benefits beyond anticoagulation.  J Reprod Immunol. 2005;  66 45-51
• 30 Greer I A, De Swiet M. Thrombosis prophylaxis in obstetrics and gynecology.  Br J Obstet Gynaecol. 1993;  100 37-40
• 31 Greer I A, 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;  106 401-407
• 32 Heilmann L, Rath W, Tempelhoff  v G F. et al . The use of low molecular weight heparin (LMWH) in pregnancy.  Geburtsh Frauenheilk. 2001;  61 355-360
• 33 Heilmann L, Rath W. Thrombophilia in pregnancy. Unimed, Bremen, London, New York 2002
• 34 Juhan C, Alimi Y, Di Mauro P, Hartung O. Surgical venous thrombectomy.  Cardiovasc Surg. 1999;  7 586-590
• 35 Kovacevich G J, Gaich S A, Lavin J P, Hopkins M P, Crane S S, Stewart J, Nelson D, Lavin L M. The prevalence of thromboembolic events among women with extended bed rest prescribed as part of the treatment for premature labor or preterm premature rupture of membranes.  Am J Obstet Gynecol. 2000;  182 1089-1092
• 36 Kupferminc M J, Eldor A, Steinman N, Many A, Bar-Am A, Jaffa A, Fait G, Lessing J B. Increased frequency of genetic thrombophilia in women with complications of pregnancy.  N Engl J Med. 1999;  340 9-13
• 37 Kyrle P A, Minar E, Hirschl M, Bialonczyk C, Stain M, Schneider B, Weltermann A, Speiser W, Lechner K, Eichinger S. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism.  N Engl J Med. 2000;  343 457-462
• 38 Aa A. Leitlinien zur Diagnostik und Therapie der Venenthrombose und Lungenembolie der Deutschen Gesellschaft für Angiologie, Gesellschaft für Gefäßmedizin.  VASA. 2002;  31 (Suppl 60) 1-19
• 39 Lepercq J, Conard J, Burel-Derlon A. et al . Venous thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies.  Br J Obstet Gynaecol. 2001;  108 1134-1140
• 40 Lindqvist P, Dahlback B, Marsal K. Thrombotic risk during pregnancy: A population study.  Obstet Gynecol. 1999;  94 595-599
• 41 Lissalde-Lavigne G, Cochery-Nouvellon E, Mercier E, Quere I, Dauzat M, Mares P, Gris J C. The association between hereditary thrombophilias and pregnancy loss.  Haematologica. 2005;  90 1223-1230
• 42 Macklon N S, Greer I A. Venous thromboembolic disease in obstetrics and gynaecology.  Scott Med J. 1996;  41 83-86
• 43 McColl M D, Ramsey J, Tait R, Walker I D, McCall F, Conkie J A, Carty M J, Greer I A. Risk factors for pregnancy associated venous thromboembolism.  Thromb Haemost. 1997;  78 1183-1188
• 44 McColl M D, Walker I D, Greer I A. The role of inherited thrombophilia in venous thromboembolism associated with pregnancy.  Br J Obstet Gynaecol. 1999;  106 756-766
• 45 McColl M D, Ellison J, Reid F, Tait R C, Walker I D, Greer I A. Prothrombin 20210 G → A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy.  Br J Obstet Gynaecol. 2000;  107 565-569
• 46 Meroni P L, Moia M, Derksen R H, Tincani A, McIntyre J A, Arnout J M, Koike T, Piette J C, Khamashta M A, Shoenfeld Y. Venous thromboembolism in the antiphospholipid syndrome: management guidelines for secondary prophylaxis.  Lupus. 2003;  12 504-507
• 47 Nassar A H, Abdallah M E, Moukarbel G V, Uste I M, Gharzuddine W S. Sequential use of thrombolytic agents for thrombosed mitral valve prosthesis during pregnancy.  J Perinat Med. 2003;  31 257-260
• 48 Nelson-Piercy C. Prevention of thromboembolism in pregnancy.  Scand J Rheumatol. 1998;  27 92-96
• 49 Pabinger I, Grafenhofer A, Kyrle P A, Quehenberger P, Mannhalter C, Lechner K, Kaider A. Temporary increase in the risk for recurrence during pregnancy in women with a history of venous thromboembolism.  Blood. 2002;  100 1060-1062
• 50 Pierangeli S S, Vega-Ostertag M, Liu X, Girardi G. Complement activation: a novel pathogenic mechanism in the antiphospholipid syndrome.  Ann N Y Acad Sci. 2005;  1051 413-420
• 51 Rai R S, Clifford K, Cohen H, Regan L. High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies.  Hum Reprod. 1995;  10 3301-3304
• 52 Rand J H, Wu X X, Guller S, Gil J, Guha A, Scher J, Lockwood C J. Reduction of annexin V (Placvental anti-coagulant protein I) on placental villi of women with antiphospholipid antibodies and recurrent spontaneous abortion.  Am J Obstet Gynecol. 1994;  171 1566-1572
• 53 Rath W, Hölzl M, Kuhn W. Thromboembolische Erkrankungen in Schwangerschaft, Wochenbett und nach Kaiserschnitt.  Gynäkol Prax. 1982;  6 241-253
• 54 Rath W, Heilmann L. Haemostatic disorders in obstetrics and gynecology. Thieme, Stuttgart, New York 1999
• 55 Ray J G, Chan W S. 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;  54 265-271
• 56 Rocha E, Panizo C, Lecumberri R. Treatment of venous thromboembolism.  Med Clin (Barc). 2000;  115 224-235
• 57 Rosendaal F R. Risk factors for venous thrombotic disease.  Thromb Haemost. 1999;  82 610-619
• 58 Rowan J A, McLintock C, Taylor R S, North R A. Prophylactic and therapeutic enoxaparin during pregnancy: indications, outcomes and monitoring.  Aust N Z J Obstet Gynaecol. 2003;  43 123-128
• 59 Rutherford S W, Montero M, Mcschee W. et al . Thromboembolic disease associated with pregnancy: An 11 year review.  Am J Obstet Gynecol. 1991;  164 286-294
• 60 Salonen R H, Lichtenstein P, Bellocco R, Petersson G, Cnattingius S. Increased risks of circulatory diseases in late pregnancy and puerperium.  Epidemiology. 2001;  12 456-460
• 61 Sanson B J, Lensing A WA, Prin M H. Safety of low molecular weight heparin in pregnancy: a systemic review.  Thromb Haemost. 1999;  81 668-672
• 62 Simpson E L, Lawrenson R A, Nightingale A L, Farmer R D. Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database.  Br J Obstet Gynaecol. 2001;  108 56-60
• 63 Toglia M R, Weg J D. Venous thromboembolism during pregnancy.  N Engl J Med. 1996;  335 108-114
• 64 Tormene D, Simioni P, Prandoni P, Luni S, Zerbinati P, Sartor D, Franz F, Girolami A. Factor V Leiden mutation and the risk of venous thromboembolism in pregnant women.  Haematologica. 2001;  86 1305-1309
• 65 Wells P S, Anderson D R, Rodger M. et al . Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis.  N Engl J Med. 2003;  349 1227-1235
• 66 Winkler U H, Schindler A E. Zur Prophylaxe und Behandlung der Thrombose in der Schwangerschaft.  Geburtsh Frauenheilk. 1996;  56 301-312
• 67 Zotz R B, Gerhardt A, Scharf R E. Prediction, prevention, and treatment of venous thromboembolic disease in pregnancy.  Seminars in Thromb and Haemost. 2003;  29 143-154