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Protein S Deficiency Follow-up

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


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.

  • The risk of VTE during pregnancy and for the 6 weeks postpartum varies among the hereditary thrombophilic states. Protein S and protein C deficiencies have significantly elevated 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 LMWH during pregnancy, and the LMWH prophylaxis should extend 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.
  • 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.
  • Physicians can administer heparin SC in standard protocols for VTE prevention.
  • 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 SC 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.

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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