提示: 手机请竖屏浏览!

妊娠并发静脉血栓形成
Pregnancy Complicated by Venous Thrombosis


Ian A. Greer ... 心脑血管疾病 妇产科和儿科 • 2015.08.06

本刊的这一栏目首先提供一份强调某一常见临床问题的病历摘要,然后提出支持各种策略的证据。如果有正式指南,作者接下来会对其进行综述。文章以作者的临床建议结尾。

 

一名37岁的初产女性在孕12周时出现左腿肿胀、疼痛、气急、下腹部疼痛。数周前开始出现妊娠剧吐。患者无静脉血栓形成病史,但据她报告,她的母亲和姨妈均有血栓形成病史。在检查时,她的体质指数(BMI,体重[kg]除以身高[m]的平方)为36,整条腿部肤色发暗、肿胀。肺部检查未发现异常,血氧饱和度正常。对她如何评估和治疗?

 

临床问题


静脉血栓栓塞是发达国家孕产妇死亡和发病的主要原因。治疗和预防的改善可以消除或减少死亡或发病的风险1-3。妊娠女性与未妊娠者相比,深静脉血栓形成更常见于左腿(85% vs. 55%),更多出现在近端(髂股静脉,72% vs.9%)4,栓塞并发症和血栓后综合征风险更高2

尽管妊娠期静脉血栓栓塞的绝对发生率低(每1,000例妊娠中有1或2例)3,但这一风险约为未妊娠女性的5倍5。这些风险反映出静脉淤滞及在凝血和纤维蛋白溶解方面出现的促凝血改变,而这两者被认为是身体为了应对分娩时的止血难题而做出的生理准备的一部分。整个妊娠期间均会出现血栓事件,超过一半出现在孕20周之前6,7。产褥期(分娩后的6周)的血栓事件风险进一步升高,很可能是因为分娩期间出现的盆腔血管内皮损伤。最新的数据表明,相对风险升高(但绝对风险低)一直持续至分娩后12周8。然而,约80%的产后血栓栓塞事件发生在分娩后3周内9

静脉血栓形成是一种“多重打击”所致疾病。最强危险因素之一是既往发生过妊娠相关的静脉血栓形成(后续妊娠中静脉血栓形成的复发风险约为6%~9%)10,但妊娠期间发生静脉血栓栓塞的女性常有多种危险因素并存。

已经确定的妊娠期内的危险因素包括妊娠剧吐(由于相关的脱水和不活动)、高BMI、不活动11-13和血栓形成倾向(包括纯合的凝血因子Ⅴ Leiden突变)10。与静脉血栓形成风险升高有关的产后因素包括接受过剖宫产(特别是在产程中紧急剖宫产或者与产后出血等其他因素有关的剖宫产)、先兆子痫伴胎儿生长受限、血栓形成倾向和产后感染10。预防血栓形成的详细讨论不在本文的范围内,血栓形成的预防在其他文章中有详细讨论10

 

临床要点





作者信息

Ian A. Greer, M.D.
From the Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom. Address reprint requests to Dr. Greer at the Faculty of Medical and Human Sciences, University of Manchester, 46 Grafton St., Manchester M13 9NT, United Kingdom, or at ian.greer@manchester.ac.uk.

 

参考文献

1. Centre for Maternal and Child Enquiries (CMACE). Saving mothers’ lives: reviewing maternal deaths to make motherhood safer: 2006–08 — the Eighth Report of the Confidential Enquiries into Maternal Deaths in the United Kingdom. BJOG 2011;118:Suppl 1:57-64

2. Wik HS, Jacobsen AF, Sandvik L, Sandset PM. Prevalence and predictors for post-thrombotic syndrome 3 to 16 years after pregnancy-related venous thrombosis: a population-based, cross-sectional, case-control study. J Thromb Haemost 2012;10:840-847

3. Kane EV, Calderwood C, Dobbie R, Morris CA, Roman E. Greer IA. A population-based study of venous thrombosis in pregnancy in Scotland 1980-2005 Eur J Obstet Gynecol Reprod Biol 2013;169:223-229

4. Greer IA. Thrombosis in pregnancy: updates in diagnosis and management. Hematology Am Soc Hematol Educ Program 2012;2012:203-207

5. Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ III. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 2005;143:697-706

6. Gherman RB, Goodwin TM, Leung B, Byrne JD, Hethumumi R, Montoro M. Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstet Gynecol 1999;94:730-734

7. James AH, Tapson VF, Goldhaber SZ. Thrombosis during pregnancy and the postpartum period. Am J Obstet Gynecol 2005;193:216-219

8. 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;370:1307-1315

9. 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:e1-e7

10. 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

11. Robertson L, Wu O, Langhorne P, et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol 2006;132:171-196

12. 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;194:1311-1315

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;6:905-912

14. Chan WS, Ray JG, Murray S, Coady GE, Coates G, Ginsberg JS. Suspected pulmonary embolism in pregnancy: clinical presentation, results of lung scanning, and subsequent maternal and pediatric outcomes. Arch Intern Med 2002;162:1170-1175

15. Shahir K, Goodman LR, Tali A, Thorsen KM, Hellman RS. Pulmonary embolism in pregnancy: CT pulmonary angiography versus perfusion scanning. AJR Am J Roentgenol 2010;195:W214-W120

16. Hull RD, Raskob GE, Carter CJ. Serial impedance plethysmography in pregnant patients with clinically suspected deep-vein thrombosis: clinical validity of negative findings. Ann Intern Med 1990;112:663-667

17. Bates SM, Jaeschke R, Stevens SM, et al. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:2 Suppl:e351S-e418S.

18. Le Gal G, Kercret G, Ben Yahmed K, et al. Diagnostic value of single complete compression ultrasonography in pregnant and postpartum women with suspected deep vein thrombosis: prospective study. BMJ 2012;344:e2635-e2635

19. Chan WS, Spencer FA, Lee AY, et al. Safety of withholding anticoagulation in pregnant women with suspected deep vein thrombosis following negative serial compression ultrasound and iliac vein imaging. CMAJ 2013;185:E194-E200

20. Green-top Guideline No. 37b — thromboembolic disease in pregnancy and the puerperium: acute management. London: Royal College of Obstetricians and Gynaecologists, April 2015 (https://www.rcog.org.uk/globalassets/documents/guidelines/gtg-37b.pdf).

21. Scarsbrook AF, Evans AL, Owen AR, Gleeson FV. Diagnosis of suspected venous thromboembolic disease in pregnancy. Clin Radiol 2006;61:1-12

22. Ridge CA, McDermott S, Freyne BJ, Brennan DJ, Collins CD, Skehan SJ. Pulmonary embolism in pregnancy: comparison of pulmonary CT angiography and lung scintigraphy. AJR Am J Roentgenol 2009;193:1223-1227

23. Remy-Jardin M, Remy J. Spiral CT angiography of the pulmonary circulation. Radiology 1999;212:615-636

24. Allen C, Demetriades T. Radiation risk overestimated. Radiology 2006;240:613-614

25. Hurwitz LM, Yoshizumi TT, Goodman PC, et al. Radiation dose savings for adult pulmonary embolus 64-MDCT using bismuth breast shields, lower peak kilovoltage, and automatic tube current modulation. AJR Am J Roentgenol 2009;192:244-253

26. Cutts BA, Dasgupta D, Hunt BJ. New directions in the diagnosis and treatment of pulmonary embolism in pregnancy. Am J Obstet Gynecol 2013;208:102-108

27. Groves AM, Yates SJ, Win T, et al. CT pulmonary angiography versus ventilation-perfusion scintigraphy in pregnancy: implications from a UK survey of doctors’ knowledge of radiation exposure. Radiology 2006;240:765-770

28. Nguyen CP, Goodman LH. Fetal risk in diagnostic radiology. Semin Ultrasound CT MR 2012;33:4-10

29. Bourjeily G, Paidas M, Khalil H, Rosene-Montella K, Rodger M. Pulmonary embolism in pregnancy. Lancet 2010;375:500-512

30. Schembri GP, Miller AE, Smart R. Radiation dosimetry and safety issues in the investigation of pulmonary embolism. Semin Nucl Med 2010;40:442-454

31. Khalafallah AA, Morse M, Al-Barzan AM, et al. D-Dimer levels at different stages of pregnancy in Australian women: a single centre study using two different immunoturbidimetric assays. Thromb Res 2012;130:e171-e177

32. Chan WS, Lee A, Spencer FA, et al. Predicting deep venous thrombosis in pregnancy: out in “LEFt” field? Ann Intern Med 2009;151:85-92

33. Righini M, Jobic C, Boehlen F, et al. Predicting deep venous thrombosis in pregnancy: external validation of the LEFT clinical prediction rule. Haematologica 2013;98:545-548

34. O’Connor C, Moriarty J, Walsh J, Murray J, Coulter-Smith S, Boyd W. The application of a clinical risk stratification score may reduce unnecessary investigations for pulmonary embolism in pregnancy. J Matern Fetal Neonatal Med 2011;24:1461-1464

35. 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;106:401-407

36. 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;11:270-281

37. 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;159:293-299

38. Knol HM, Schultinge L, Veeger NJGM, Kluin-Nelemans HC, Erwich JJHM, Meijer K. The risk of postpartum hemorrhage in women using high dose of low-molecular-weight heparins during pregnancy. Thromb Res 2012;130:334-338

39. Patel JP, Green B, Patel RK, Marsh MS, Davies JG, Arya R. Population pharmacokinetics of enoxaparin during the antenatal period. Circulation 2013;128:1462-1469

40. Tang AW, Greer IA. A systematic review on the use of new anticoagulants in pregnancy. Obstet Med 2013;6:64-71

41. Kahn SR, Shapiro S, Wells PS, et al. Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial. Lancet 2014;383:880-888

42. te Raa GD, Ribbert LSM, Snijder RJ, Biesma DH. Treatment options in massive pulmonary embolism during pregnancy; a case-report and review of literature. Thromb Res 2009;124:1-5

43. Milford W, Chadha Y, Lust K. Use of a retrievable inferior vena cava filter in term pregnancy: case report and review of literature. Aust N Z J Obstet Gynaecol 2009;49:331-333

44. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141:2 Suppl:e419S-e494S.

45. James A. Practice bulletin no. 123: thromboembolism in pregnancy. Obstet Gynecol 2011;118:718-729

46. Chan WS, Rey E, Kent NE, et al. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can 2014;36:527-553

47. Green-top Guideline No. 37a — reducing the risk of thrombosis and embolism during pregnancy and the puerperium. London: Royal College of Obstetricians and Gynaecologists, April 2015 (https://www.rcog.org.uk/globalassets/documents/guidelines/gtg-37a.pdf).

48. McLintock C, Brighton T, Chunilal S, et al. Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period. Aust N Z J Obstet Gynaecol 2012;52:14-22

服务条款 | 隐私政策 | 联系我们