Risk of thromboembolism in the general population with SCD

• SCD is a hypercoagulable state involving alterations in platelet function, activation of the coagulation cascade, impaired fibrinolysis, and venous stasis from vaso-occlusion. Consequently, thrombotic events are a common complication in the general population with SCD. Compared to people without SCD, people with SCD have ~3.5-fold increased risk of all-cause thromboembolism (104) and a 50- to 100-fold increased risk of pulmonary embolism (105). Risk of thromboembolism during pregnancy
• Pregnancy is also a hypercoagulable state. Overall, pregnancy carries a four- to five-fold higher rate of thromboembolism. Thromboembolism is still a rare event, however, occurring in approximately 1/1000 pregnancies (106, 107). Pregnant women are at risk of thromboembolism throughout pregnancy, including the first and second trimesters, with a substantial increase in risk in the third trimester and in the postnatal period (108). Thromboembolism is responsible for 3.2% of maternal mortality globally (109).
• Pregnant women with SCD are at increased risk of pulmonary thromboembolism (RR 7.74; 95% CI 4.65 to

• 12.89) (110), and all-cause VTE (RR 32.2; 95% CI 9.70 to 107.00) (111). The risk is even higher for women with complicated SCD. The prevalence of VTE was 3.5-fold greater in women with complications such as vaso-occlusive crisis, acute chest syndrome and pneumonia compared to women without these complications (112).

• Significant risk factors for VTE include previous VTE or thrombophilia (113, 114). Other risk factors include obesity (107, 115, 116, 117, 118), age over 35 years 114,117, 119), immobility and long-distance travel (120), admission to hospital (121), and comorbidities — including inflammatory bowel disease (122, 123), urinary tract infection (122), systemic lupus erythematosus, heart disease (114), and pregnancy-induced hypertension/pre-eclampsia (113, 124). SCD (alone) has been identified as conferring an intermediate risk of VTE (odds ratio [OR] 6.70; 95% CI 4.40 to 10.10) (107).
• Women with multiple risk factors may be at greatly increased risk of VTE in pregnancy, especially in the third trimester and postnatally (125). Considerations in thromboprophylaxis use during pregnancy
• Thromboprophylaxis with direct oral anticoagulants, low molecular weight heparin (LMWH), unfractionated heparin, and warfarin can reduce the risk of thromboembolism, however the antithrombotic benefits need to be weighed against the risk of postpartum haemorrhage (PPH) which may be exacerbated by anticoagulation.
• The use of direct oral anticoagulants such as warfarin) is generally avoided in pregnancy due to their association with adverse pregnancy outcomes, including fetal loss and fetal anomalies (126, 127) 6 .
• Unfractionated heparin (UFH), LMWH and danaparoid (a heparinoid) do not cross the placenta and are safe for the fetus (128, 129, 130, 131, 132, 133, 134, 135, 136). LMWH is considered to have a better safety profile than UFH (137, 138).
• LMWHs are eliminated primarily by renal excretion and may accumulate in people with significant renal dysfunction. In the non-pregnant population, it has been suggested that therapeutic dose LMWH not be used in patients with significant renal impairment (e.g. a glomerular filtration rate [GFR] of less than 30 mL/ min), although it is recognized that accumulation in people with renal impairment may differ between the various LMWHs (139, 140).
• LMWH is the most frequently used drug for treatment and prevention of VTE in pregnancy, except in people with heparin-induced thrombocytopaenia (HIT), a history of HIT, or significant renal dysfunction. UFH is generally used in people with significant renal dysfunction (140).
• As LMWHs are expensive, especially in LMICs, UFH might be an alternative.
• Thromboprophylaxis late in pregnancy may preclude the use of epidural or spinal anaesthesia at the time of delivery, so discontinuation of any preventative treatment is a consideration, in line with local practice on the use of anticoagulants in pregnancy (141).