Protein S Deficiency Follow-up

Updated: Sep 20, 2018
  • Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: Perumal Thiagarajan, MD  more...
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Follow-up

Deterrence/Prevention

In patients with heterozygous protein S deficiency and no history of thrombosis, physicians may administer prophylactic heparin during situations that present high risk for thrombosis. Such situations include surgery, orthopedic trauma (especially with a cast), pregnancy, and prolonged bed rest. Heparin may be administered subcutaneously in standard protocols for venous thromboembolism (VTE) prevention.

The risk of VTE during pregnancy and for the first 6 weeks postpartum varies among the hereditary thrombophilic states. Protein S and protein C deficiencies significantly elevate the risks for thrombosis when compared with the modest increase in thrombosis seen with factor V Leiden mutation. Protein S deficiency was also associated with a seven-fold increase in fetal loss. Many experts recommend that women with protein S deficiency and a history of fetal loss, and severe or recurrent eclampsia, receive low-dose aspirin and prophylactic-dose low molecular weight heparin (LMWH) therapy during pregnancy, with the LMWH prophylaxis extending for 6 weeks postpartum.

For women with heterozygous protein S deficiency and no prior VTE history of fetal loss, treatment choices vary. Some recommend VTE prophylaxis only during the 6 weeks postpartum (the highest risk period for VTE) unless the pregnancy is complicated. Others recommend prophylaxis for the entire pregnancy and 6 weeks postpartum. Recommendations for other scenarios include the following:

  • For women with no prior history of VTE and protein S deficiency plus any other thrombophilic defect, active prophylaxis with LMWH should be given during pregnancy and for 6 weeks postpartum.

  • For women with a prior VTE history and confirmed protein S deficiency, experts recommend prophylactic or intermediate dosing of LMWH during pregnancy and for 6 weeks postpartum.

  • For women with a prior history of VTE who are already receiving oral anticoagulants at the time of pregnancy, full anticoagulant dosing of LMWH is recommended with transition back to oral anticoagulant postpartum.

  • Patients with recurrent thrombosis should remain on lifelong warfarin.

Interruption of anticoagulation

In patients with a history of thrombosis who are taking warfarin, no standard exists for "bridging" (ie, on and off use of warfarin for surgery or other procedures that require cessation of warfarin). Some institutions cover with subcutaneous heparin while holding warfarin for 3-4 days. In other situations, this temporary interruption of warfarin is not covered by heparin. Each clinician should weigh the thrombosis risk with the bleeding risk in the individual patient because no data in controlled trials are available to answer this difficult question.