1. THROMBOEMBOLIC DISEASE IN PREGNANCY AND PUERPERIUM DR ASHRAF ATIA DEWIDAR MD MRCOG

2. Background Epidemiology Pulmonary embolism remains one of the leading direct causes of maternal death in the UK (1.56/100 000 maternities) Second most common cause of maternal death overall (11% of maternal deaths) Many antenatal VTE events occur in the first trimester and therefore, prophylaxis, if given, should begin early in pregnancy Pulmonary embolism remains one of the leading direct causes of maternal death in the UK (1.56/100 000 maternities) Second most common cause of maternal death overall (11% of maternal deaths) Many antenatal VTE events occur in the first trimester and therefore, prophylaxis, if given, should begin early in pregnancy DR ASHRAF ATIA DEWIDAR MD MRCOG

3. The highest risk period for VTE, and pulmonary embolism in particular, is during the postpartum period. Caesarean section is a significant risk factor but women having vaginal deliveries are also at risk and 55% (25/45) of the postpartum maternal deaths from VTE in the UK between 1997 and 2005 occurred in women who had delivered vaginally. Overall incidence of VTE in pregnancy and the puerperium of 1–2/1000. The highest risk period for VTE, and pulmonary embolism in particular, is during the postpartum period. Caesarean section is a significant risk factor but women having vaginal deliveries are also at risk and 55% (25/45) of the postpartum maternal deaths from VTE in the UK between 1997 and 2005 occurred in women who had delivered vaginally. Overall incidence of VTE in pregnancy and the puerperium of 1–2/1000. DR ASHRAF ATIA DEWIDAR MD MRCOG

5. NICE estimates that LMWH reduces VTE risk in medical and surgical patients by 60% and 70%, respectively. DR ASHRAF ATIA DEWIDAR MD MRCOG

6. THROMBOEMBOLIC DISEASE deep venous thrombosis (DVT) PULMONARY thromboembolism (PTE ) DR ASHRAF ATIA DEWIDAR MD MRCOG

7. The subjective, clinical assessment is particularly unreliable in pregnancy and a minority of women with clinically suspected VTE have the diagnosis confirmed when objective testing is employed. DR ASHRAF ATIA DEWIDAR MD MRCOG

8. Symptoms and Signs Consistent with Possible VTE Leg pain and swelling Lower abdominal pain Low-grade pyrexia Dyspnoea, chest pain, haemoptysis DR ASHRAF ATIA DEWIDAR MD MRCOG Collapse

9. LMW Heparin is polysaccharide chain with MW of 4-6 kDa DR ASHRAF ATIA DEWIDAR MD MRCOG

10. Unfractionated heparin is a polysaccharide chain with MW of 12-14 kDa DR ASHRAF ATIA DEWIDAR MD MRCOG

13. Diagnosis of Acute VTE in Pregnancy DR ASHRAF ATIA DEWIDAR MD MRCOG

14. Any woman with signs and symptoms suggestive of VTE should have objective testing performed expeditiously and treatment with low-molecular- weight heparin (LMWH) (until the diagnosis is excluded by objective testing), unless treatment is strongly contraindicated Individual hospitals should have an agreed protocol for the objective diagnosis of suspected VTE during pregnancy. This may recommend the involvement of obstetricians, physicians and haematologists and radiologists DR ASHRAF ATIA DEWIDAR MD MRCOG

15. What Investigations are Needed for the Diagnosis of an Acute DVT? DR ASHRAF ATIA DEWIDAR MD MRCOG

17.  Duplex ultrasound combines Doppler and conventional ultrasound to allow physicians to see the structure of your blood vessels.  Duplex ultrasound shows how blood is flowing through your vessels and measures the speed of the flow of blood.  It can also be useful to estimate the diameter of a blood vessel as well as the amount of obstruction, if any, in the blood vessel.  Duplex ultrasound combines Doppler and conventional ultrasound to allow physicians to see the structure of your blood vessels.  Duplex ultrasound shows how blood is flowing through your vessels and measures the speed of the flow of blood.  It can also be useful to estimate the diameter of a blood vessel as well as the amount of obstruction, if any, in the blood vessel. DR ASHRAF ATIA DEWIDAR MD MRCOG

18. When iliac vein thrombosis is suspected (back pain and swelling of the entire limb), magnetic resonance venography or conventional contrast venography may be considered. DR ASHRAF ATIA DEWIDAR MD MRCOG

19. What Investigations are Needed for the Diagnosis of an Acute PTE? DR ASHRAF ATIA DEWIDAR MD MRCOG

20. clinical suspicion of acute PTE chest X-ray Compression duplex DOPLLER LMW NORMA +CLINICAL SUSP CTPA V/Q LMW OR + DR ASHRAF ATIA DEWIDAR MD MRCOG

21. CHEST X’RAY? yes NO DR ASHRAF ATIA DEWIDAR MD MRCOG

22. Alternative or repeat testing should be carried out where V/Q scan or CTPA and duplex Doppler are normal but the clinical suspicion of PTE is high. Anticoagulant treatment should be continued until PTE is definitively excluded. Alternative or repeat testing should be carried out where V/Q scan or CTPA and duplex Doppler are normal but the clinical suspicion of PTE is high. Anticoagulant treatment should be continued until PTE is definitively excluded. DR ASHRAF ATIA DEWIDAR MD MRCOG

23. A pulmonary ventilation/perfusion scan is a pair of nuclear scan tests. These tests use inhaled and injected radioactive material (radioisotopes) to measure breathing (ventilation) and circulation (perfusion) in all areas of the lungs nuclear scan A pulmonary ventilation/perfusion scan is a pair of nuclear scan tests. These tests use inhaled and injected radioactive material (radioisotopes) to measure breathing (ventilation) and circulation (perfusion) in all areas of the lungs nuclear scan DR ASHRAF ATIA DEWIDAR MD MRCOG

24. Alternative Diagnoses from CT Pulmonary Angiography Pneumothorax Pneumonia Pleural effusion Pericarditis Aortic dissection Congestive heart failure Rib fracture Lung Cancer Alternative Diagnoses from CT Pulmonary Angiography Pneumothorax Pneumonia Pleural effusion Pericarditis Aortic dissection Congestive heart failure Rib fracture Lung Cancer DR ASHRAF ATIA DEWIDAR MD MRCOG

25. Women with suspected PTE should be advised that V/Q scanning carries a slightly increased risk of childhood cancer compared with CTPA (1/280,000 versus less than 1/1,000,000) but carries a lower risk of maternal breast cancer (lifetime risk increased by up to 13.6% with CTPA, background risk of 1/200 for study population DR ASHRAF ATIA DEWIDAR MD MRCOG

26. Where feasible, women should be involved in the decision to undergo CTPA or V/Q scanning. Ideally, informed consent should be obtained before these tests are undertaken. Where feasible, women should be involved in the decision to undergo CTPA or V/Q scanning. Ideally, informed consent should be obtained before these tests are undertaken. DR ASHRAF ATIA DEWIDAR MD MRCOG

27. Should D-dimer testing be performed prior to objective diagnosis? D-dimer testing should not be performed to diagnose acute VTE in pregnancy. DR ASHRAF ATIA DEWIDAR MD MRCOG

28. Baseline Blood Investigations Before anticoagulant therapy is commenced, blood should be taken for a full blood count, coagulation screen, urea, electrolytes and liver function tests. Performing a thrombophilia screen prior to therapy is not routinely recommended. Before anticoagulant therapy is commenced, blood should be taken for a full blood count, coagulation screen, urea, electrolytes and liver function tests. Performing a thrombophilia screen prior to therapy is not routinely recommended. Thrombophilia screens should be interpreted by clinicians (usually haematologists) with specific expertise in the area. DR ASHRAF ATIA DEWIDAR MD MRCOG

29. Initial Anticoagulant Treatment of VTE in Pregnancy In clinically suspected DVT or PTE, treatment with LMWH should be given until the diagnosis is excluded by objective testing, unless treatment is strongly contraindicated DR ASHRAF ATIA DEWIDAR MD MRCOG

30. LMWH should be given daily in two subcutaneous divided doses with dosage titrated against the woman’s booking or most recent weight. There should be clear local guidelines for the dosage of LMWH to be used. DR ASHRAF ATIA DEWIDAR MD MRCOG

31. A twice-daily dosage regimen is recommended for these LMWHs in the treatment of VTE in pregnancy (Enoxaparin) 1 mg/kg twice daily; (Dalteparin)100 units/kg twice daily (Tinzaparin) 175 units/kg daily DR ASHRAF ATIA DEWIDAR MD MRCOG

33. Should blood tests be performed to monitor LMWH therapy in pregnancy? DR ASHRAF ATIA DEWIDAR MD MRCOG

34. Routine measurement of peak anti-Xa activity for patients on LMWH for treatment of acute VTE in pregnancy or postpartum is not recommended except in women at extremes of body weight (less than 50 kg and 90 kg or more) or with other complicating factors (for example with renal impairment or recurrent VTE) putting them at high risk. Routine platelet count monitoring should not be carried out (unless unfractionated heparin has been given). DR ASHRAF ATIA DEWIDAR MD MRCOG

35. How should massive life- threatening PTE in pregnancy be managed? DR ASHRAF ATIA DEWIDAR MD MRCOG

36. Collapsed, shocked patients need to be assessed by a team of experienced clinicians, including the on call consultant obstetrician, who should decide on an individual basis whether a woman receives intravenous unfractionated heparin, thrombolytic therapy or thoracotomy and surgical embolectomy. DR ASHRAF ATIA DEWIDAR MD MRCOG

37. Intravenous unfractionated heparin is the preferred treatment in massive PTE with cardiovascular compromise. DR ASHRAF ATIA DEWIDAR MD MRCOG

38. The on-call medical team should be contacted immediately. An urgent portable echocardiogram or CTPA within 1 hour of presentation should be arranged. If massive PTE is confirmed or, in extreme circumstances prior to confirmation, immediate thrombolysis should be considered. DR ASHRAF ATIA DEWIDAR MD MRCOG

39. Maternity units should develop guidelines for the administration of intravenous unfractionated heparin. Management should involve a multidisciplinary resuscitation team including senior physicians, obstetricians and radiologists. DR ASHRAF ATIA DEWIDAR MD MRCOG

41. What additional therapies should be employed in the management of VTE in pregnancy? DR ASHRAF ATIA DEWIDAR MD MRCOG

42. In the initial management of DVT, the leg should be elevated and a graduated elastic compression stocking applied to reduce oedema. Mobilisation with graduated elastic compression stockings should be encouraged. DR ASHRAF ATIA DEWIDAR MD MRCOG

43. Consideration should be given to the use of a temporary inferior vena caval filter in the perinatal period for women with iliac vein VTE, to reduce the risk of PTE or in women with proven DVT and who have continuing PTE despite adequate anticoagulation. DR ASHRAF ATIA DEWIDAR MD MRCOG

45. Treatment with therapeutic doses of subcutaneous LMWH should be employed during the remainder of the pregnancy. DR ASHRAF ATIA DEWIDAR MD MRCOG

46. Arrangements should be made to allow safe disposal of needles and syringes. Outpatient follow-up should include clinical assessment and advice with assessment of blood platelets and peak anti-Xa levels if appropriate. DR ASHRAF ATIA DEWIDAR MD MRCOG

47. Women receiving therapeutic-dose unfractionated heparin should have their platelet count monitored at least every other day until day 14 or until the unfractionated heparin is stopped, whichever occurs first. DR ASHRAF ATIA DEWIDAR MD MRCOG

48. Pregnant women who develop heparin-induced thrombocytopenia (HIT) or have heparin allergy and require continuing anticoagulant therapy should be managed with the heparinoid, danaparoid sodium or fondaparinux, under specialist advice. DR ASHRAF ATIA DEWIDAR MD MRCOG

49. HIT EARLY BENIGN MILD DEALYED 6-6 DAYSS IMMUNEMEDIATED SEVERE A.&V. THROMBOSIS MORBIDITY MORTALITY DR ASHRAF ATIA DEWIDAR MD MRCOG

50. Because of their adverse effects on the fetus, oral anticoagulants should not be used for antenatal VTE treatment. DR ASHRAF ATIA DEWIDAR MD MRCOG

51. Anticoagulant Therapy During Labour and Delivery DR ASHRAF ATIA DEWIDAR MD MRCOG

52. The woman taking LMWH for maintenance therapy should be advised that once she is established in labour or thinks that she is in labour, she should not inject any further heparin. DR ASHRAF ATIA DEWIDAR MD MRCOG

53. Where delivery is planned, LMWH maintenance therapy should be discontinued 24 hours before planned delivery DR ASHRAF ATIA DEWIDAR MD MRCOG

54. Regional anaesthetic or analgesic techniques should not be undertaken until at least 24 hours after the last dose of therapeutic LMWH. A thromboprophylactic dose of LMWH should be given by 3 hours after a caesarean section (more than 4 hours after removal of the epidural catheter, if appropriate. The epidural catheter should not be removed within 12 hours of the most recent injection. DR ASHRAF ATIA DEWIDAR MD MRCOG

55. LMWH should not be given for at least 4 hours after the epidural catheter has been removed. DR ASHRAF ATIA DEWIDAR MD MRCOG

56. In women receiving therapeutic doses of LMWH, wound drains (abdominal and rectus sheath) should be considered at the time of caesarean section and the skin incision should be closed with staples or interrupted sutures to allow drainage of any haematoma. DR ASHRAF ATIA DEWIDAR MD MRCOG

57. Any woman who is considered to be at high-risk of haemorrhage and in whom continued heparin treatment is considered essential should be managed with intravenous, unfractionated heparin until the risk factors for hemorrhage have resolved. DR ASHRAF ATIA DEWIDAR MD MRCOG

58. Postnatal Anticoagulation Therapeutic anticoagulant therapy should be continued for the duration of the pregnancy and for at least 6 weeks post natal and at least 3 months of treatment has been given in total. DR ASHRAF ATIA DEWIDAR MD MRCOG

59. Women should be offered a choice of LMWH or oral anticoagulant for postnatal therapy after discussion about the need for regular blood tests for monitoring of warfarin, particularly during the first 10 days of treatment DR ASHRAF ATIA DEWIDAR MD MRCOG

60. Recommendations for Thromboprophylaxis During Pregnancy All women should undergo a documented assessment of risk factors for venous thromboembolism (VTE). This assessment should be repeated if the woman is admitted to hospital for any reason or develops other inter current problems. DR ASHRAF ATIA DEWIDAR MD MRCOG

62. Women at high risk of VTE in pregnancy, such as those with previous VTE, should be offered pre pregnancy counseling and a prospective management plan for thromboprophylaxis in pregnancy. Those who become pregnant before receiving such counseling should be referred to a consultant obstetrician or trust-nominated expert in thrombosis in pregnancy early in pregnancy. DR ASHRAF ATIA DEWIDAR MD MRCOG

63. Women with a previous non- estrogen-related VTE provoked by a minor risk factor should undergo testing for thrombophilia, as this will influence management and decisions regarding thromboprophylaxis antenatally. DR ASHRAF ATIA DEWIDAR MD MRCOG

64. Antenatal thromboprophylaxi s should begin as early in pregnancy as practical.

65. Low molecular weight heparins (LMWH) are the agents of choice for antenatal thromboprophylaxis. These are at least as effective as and safer than unfractionated heparin. DR ASHRAF ATIA DEWIDAR MD MRCOG

66. Any woman with three or more current or persisting risk factors listed in table 1 should be considered for prophylactic LMWH antenatally DR ASHRAF ATIA DEWIDAR MD MRCOG

68. Women with a previous single provoked (excluding estrogen-related) VTE and no other risk factors require close surveillance; antenatal LMWH is not routinely recommended. DR ASHRAF ATIA DEWIDAR MD MRCOG

69. Women with previous recurrent VTE or a previous unprovoked or estrogen or pregnancy-related VTE or a previous VTE and a history of VTE in a first-degree relative (or a documented thrombophilia) or other risk factors should be offered antenatal thromboprophylaxis with LMWH. DR ASHRAF ATIA DEWIDAR MD MRCOG

70. Women with asymptomatic inherited or acquired thrombophilia may be managed with close surveillance antenatally. Exceptions are women with antithrombin deficiency, those with more than one thrombophilic defect (including homozygosity for factor V Leiden) or those with additional risk factors: where advice of a local expert should be sought and antenatal prophylaxis considered. Women with asymptomatic inherited or acquired thrombophilia may be managed with close surveillance antenatally. Exceptions are women with antithrombin deficiency, those with more than one thrombophilic defect (including homozygosity for factor V Leiden) or those with additional risk factors: where advice of a local expert should be sought and antenatal prophylaxis considered. DR ASHRAF ATIA DEWIDAR MD MRCOG

71. Women receiving antenatal LMWH should be advised that, if they have any vaginal bleeding or once labour begins, they should not inject any further LMWH. They should be reassessed on admission to hospital and further doses should be prescribed by medical staff. DR ASHRAF ATIA DEWIDAR MD MRCOG

73. Recommendations for thromboprophylaxis following delivery All women should be assessed after delivery for the risk factors listed in Figure1, Table1 and Appendix lll. DR ASHRAF ATIA DEWIDAR MD MRCOG

74. All women should be encouraged to mobilize both during labour and postpartum. Dehydration should be avoided. DR ASHRAF ATIA DEWIDAR MD MRCOG

75. 1.Women with two or more persisting risk factors listed in Table 1 should be considered for LMWH for 7 days after delivery. 2.Women with three or more persisting risk factors listed in Table 1 should be given graduated compression stockings in addition to LMWH. DR ASHRAF ATIA DEWIDAR MD MRCOG

76. All women with class-three obesity: body mass index (BMI) > 40kg/m2, should be considered for thromboprophylaxis with LMWH for 7 days after delivery. DR ASHRAF ATIA DEWIDAR MD MRCOG

77. All women who have had an emergency caesarean section (category 1, 2 or 3) should be considered for thromboprophylaxis with LMWH for 7 days after delivery. DR ASHRAF ATIA DEWIDAR MD MRCOG

78. All women who have had an elective caesarean section (category 4) who have one or more additional risk factors (such as age over 35 years, BMI greater than 30) should be considered for thromboprophylaxis with LMWH for 7 days after delivery. DR ASHRAF ATIA DEWIDAR MD MRCOG

80. All women with asymptomatic heritable or acquired thrombophilia should be considered for LMWH for at least 7 days following delivery, even if they were not receiving antenatal thromboprophylaxis. This could be extended to 6 weeks if there is a family history or other risk factors present. DR ASHRAF ATIA DEWIDAR MD MRCOG

81. Women with VTE before the current pregnancy should be offered LMWH for 6 weeks following delivery. DR ASHRAF ATIA DEWIDAR MD MRCOG

82. Women receiving LMWH antenatally should usually continue prophylactic doses of LMWH until 6 weeks postpartum but a postnatal risk assessment should be made. If they are receiving long- term anticoagulation with warfarin, this can be started when the risk of hemorrhage is low. Women receiving LMWH antenatally should usually continue prophylactic doses of LMWH until 6 weeks postpartum but a postnatal risk assessment should be made. If they are receiving long- term anticoagulation with warfarin, this can be started when the risk of hemorrhage is low. DR ASHRAF ATIA DEWIDAR MD MRCOG

83. Both warfarin and LMWH are safe when breastfeeding. DR ASHRAF ATIA DEWIDAR MD MRCOG

84. Women should be repeatedly assessed for risk factors for VTE if they develop intercurrent problems or require surgery or readmission in the puerperium. DR ASHRAF ATIA DEWIDAR MD MRCOG

85. In women who have additional persistent risk factors (lasting more than 7 days postpartum), such as prolonged admission or wound infection, thrombo- prophylaxis should be extended for up to 6 weeks or until the additional risk factors are no longer present. DR ASHRAF ATIA DEWIDAR MD MRCOG