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Protein S Deficiency Treatment & Management

  • Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: Perumal Thiagarajan, MD  more...
Updated: Jan 27, 2016

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.


See the list below:

  • Initial heparin treatment may be administered as intravenous unfractionated heparin or as subcutaneous low molecular weight heparin (LMWH)
  • Heparin should be administered 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, however 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. 

Direct Thrombin Inhibitors

Dabigatran  is another option available these days used for hypercoagulable states, however there are no direct trials to support the use in Protein S deficiency. Since specific reversal agents for non–vitamin K antagonist oral anticoagulants are lacking,  Idarucizumab, an antibody fragment, is available in the market which can reverse 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.

Patient 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.

Contributor Information and Disclosures

Mohammad Muhsin Chisti, MD, FACP Assistant Professor of Hematology and Oncology, Karmanos Cancer Institute, Michigan State University College of Human Medicine

Mohammad Muhsin Chisti, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, Medical Society of the State of New York

Disclosure: Nothing to disclose.


Suma Chinta, MD, MBBS Resident Physician, Department of Internal Medicine, St Joseph Mercy Oakland Hospital

Suma Chinta, MD, MBBS is a member of the following medical societies: American College of Physicians, Medical Council of India

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Perumal Thiagarajan, MD Professor, Department of Pathology and Medicine, Baylor College of Medicine; Director, Transfusion Medicine and Hematology Laboratory, Michael E DeBakey Veterans Affairs Medical Center

Perumal Thiagarajan, MD is a member of the following medical societies: American College of Physicians, American Society for Clinical Investigation, Association of American Physicians, American Society for Biochemistry and Molecular Biology, American Heart Association, American Society of Hematology, Royal College of Physicians

Disclosure: Nothing to disclose.


John E Godwin, MD, MS Professor of Medicine, Chief Division of Hematology/Oncology, Associate Director, Simmons Cooper Cancer Institute, Southern Illinois University School of Medicine

John E Godwin, MD, MS is a member of the following medical societies: American Association for the Advancement of Science, American Heart Association, and American Society of Hematology

Disclosure: Nothing to disclose.

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A simplified outline of the protein C system.
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