Protein S Deficiency Treatment & Management

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

Management of protein S deficiency takes place in the event of acute venous thromboembolism (VTE). Prophylaxis may be used in selected patients with asymptomatic carrier states without a thrombotic event. Following an acute thrombosis, administer heparin therapy and then transition to warfarin oral anticoagulation.


Heparin is administered as follows:

  • Initial heparin treatment may be with intravenous unfractionated heparin or subcutaneous low molecular weight heparin (LMWH)

  • Heparin should be given for a minimum of 5 days

  • Manage heparin with standard protocols; see Deep Venous Thrombosis or Pulmonary Embolism for additional details


Warfarin administration can start on day 1 or 2 of heparin therapy. After two consecutive therapeutic International Normalized Ratio (INR) clotting tests and a minimum of 5 days of heparin therapy, the patient can continue on warfarin alone. In most patients, specialists recommend 6-9 months of initial treatment with warfarin.

The question of whether to continue lifelong warfarin in patients with identified protein S deficiency after their first thrombotic event is controversial. If the first thrombotic event was life threatening or occurred in multiple or unusual sites (eg, cerebral veins, mesenteric veins), most experts recommend lifelong therapy initially. If precipitated by a strong event (eg, trauma, surgery) and the thrombosis did not meet the criteria of life threatening or multiple or unusual sites, some experts argue that these patients may have a lower risk of recurrence and deserve a trial without warfarin after 9 months.

Direct Factor Xa Inhibitors

These agents bind to factor Xa and prevent it from cleaving prothrombin to thrombin. Although there are no direct trials to support use of these drugs in protein S deficiency, these drugs are widely being used in multiple hypercoagulable states, including protein S deficiency. Currently the oral agents that are available are rivaroxaban, apixaban, and edoxaban. [30]

Direct Thrombin Inhibitors

Dabigatran is another option for treatment of hypercoagulable states, however there are no direct trials to support its use in protein S deficiency. Specific reversal agents for non–vitamin K antagonist oral anticoagulants are lacking, but idarucizumab, an antibody fragment, is available for reversing the anticoagulant effects of dabigatran.


In patients who are asymptomatic carriers of protein S deficiency, the goal of therapy is prevention of the first thrombosis. In such patients, avoid drugs that predispose to thrombosis, including oral contraceptives. In these patients, if surgery or orthopedic injury occurs, prophylaxis with heparin is mandatory.

In pregnancy, experts recommend prophylaxis with heparin; however, the timing is controversial. Most experts would treat from the second trimester through 4-6 weeks postpartum.

The patient's bleeding risks must be assessed on an individual basis for any of these prophylactic recommendations. No single prescription fits all cases.


Diet and Activity

Dietary issues relate to patients with protein S deficiency who are on oral anticoagulation with warfarin. Avoid foods that are rich in vitamin K.

Restrictions apply to activity shortly after acute venous thrombosis (ie, DVT, pulmonary embolism). See Deep Venous Thrombosis or Pulmonary Embolism for additional details concerning such restrictions. While on anticoagulation therapy, patients should avoid vigorous contact activities.