Protein S Deficiency Medication

  • Author: John E Godwin, MD, MS; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Jan 10, 2012
 

Medication Summary

Heparin is used for patients with acute thrombotic events or for the prevention of thrombosis. Heparin treatment currently is available in 2 forms—unfractionated (standard) heparin or LMWH.

Unfractionated heparin for treatment of thrombosis is administered properly by a weight-based dosing protocol, with a target heparin therapeutic range as monitored by the activated partial thromboplastin time (aPTT) test and for a minimum of 5 days. A heparin dosing protocol includes the specified weight-dosing regimen, the target therapeutic aPTT range, the time for measuring aPTT tests after bolus or adjustment in dose (4-6 h), and a standard means of adjusting the unfractionated heparin infusion based on the aPTT test result (eg, subtherapeutic, therapeutic, supratherapeutic). A commonly used weight-adjusted unfractionated heparin regimen is termed 80/18: 80 U/kg IV bolus followed by 18 U/kg continuous IV (CIV) infusion. The target therapeutic heparin range is ideally individualized to the institution's laboratory aPTT test instrument and reagent.

To obtain an institutional heparin therapeutic range, employ a method such as that described by Brill-Edwards or any other similar comparison of in vitro and ex vivo heparin levels with aPTT test results in multiple individuals. In the absence of an established institutional therapeutic range, an aPTT ratio of 1.5-2.0 is commonly used; however, aPTT reagents and patient responses to unfractionated heparin vary, and the ratio can be 1.8-3.0 for some reagents.

The pharmacodynamics of LMWHs are different from the parent unfractionated heparin. LMWHs are administered subcutaneously. The aPTT test is not affected significantly by LMWH and is not used to monitor LMWH therapy. Several different LMWHs are available in the United States, but they have different pharmacodynamic properties and are not considered interchangeable. Weight-based dosing regimens for each LMWH and for treatment or prophylaxis indications are available from each manufacturer. LMWHs are approved for treatment of DVT with or without pulmonary embolism in the inpatient hospital setting. LMWHs are approved for treatment of DVT without pulmonary embolism in the outpatient setting.

Warfarin is used for long-term oral anticoagulant management of patients with protein S deficiency after first or subsequent thrombosis.

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Anticoagulants

Class Summary

Unfractionated IV heparin and fractionated low molecular weight SC heparins are the 2 choices for initial anticoagulation therapy. Warfarin therapy may be initiated after 1-3 days of effective heparinization.

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Heparin

 

Usually administered as CIV infusion for the treatment of acute thrombosis. For prevention of thrombosis, unfractionated heparin is administered SC.

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Enoxaparin (Lovenox)

 

Enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, preferentially increases inhibition of factor Xa.

Average duration of treatment is 7-14 d.

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Dalteparin (Fragmin)

 

Enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, preferentially increases inhibition of factor Xa.

Average duration of treatment is 7-14 d.

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Fondaparinux sodium (Arixtra)

 

Only synthetic compound in this class of LMW heparins. This compound is a novel pentasaccharide capable of inhibiting factor Xa via the action of antithrombin (AT) but devoid of anti-factor IIa (thrombin) activity. Interestingly, this compound does not appear to cross-react with HIT antibodies.

Approved for use in hip fracture surgery, knee replacement surgery, and hip replacement surgery. Only FDA-approved anticoagulant drug for hip fracture surgery. Also used and approved for extended prophylactic dosing for 21 d following hip fracture surgery.

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Tinzaparin (Innohep)

 

Enhances inhibition of factor Xa and thrombin by increasing antithrombin III activity. In addition, preferentially increases inhibition of factor Xa.

Average duration of treatment is 7-14 d.

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Warfarin (Coumadin)

 

Oral anticoagulant that antagonizes action of vitamin K in normal synthesis of clotting factors II, VII, IX, and X. Safe and effective for long-term oral management of thrombotic disorders. See articles on Deep Venous Thrombosis or Pulmonary Embolism (discussed in Treatment section) for additional details on dosing and monitoring of warfarin. Therapy is initiated without a loading dose at a dose range of 5-10 mg qd for 70-kg adult. Monitor PT/INR daily during initiation of therapy to measure anticoagulation effect. After initial 5-10 d and stabilization of warfarin dose, measure PT/INR 2-3 times qwk for 2-4 wk, then monthly thereafter.

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Contributor Information and Disclosures
Author

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.

Specialty Editor Board

Rodger L Bick†, MD, PhD, FACP  Former Clinical Professor of Medicine, University of Texas Southwestern Medical Center; Former Director, Dallas and Pacific Thrombosis Hemostasis and Vascular Medicine Clinical Center

Rodger L Bick†, MD, PhD, FACP is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Blood Banks, American Cancer Society, American College of Angiology, American College of Physicians, American Geriatrics Society, American Heart Association, American Medical Association, American Society for Clinical Pathology, American Society of Hematology, Association of Clinical Scientists, California Medical Association, California Thoracic Society, International College of Angiology, International Society of Hematology, International Society on Thrombosis and Haemostasis, New York Academy of Sciences, and Southwest Oncology Group

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

Troy H Guthrie, Jr, MD  Director of Cancer Institute, Baptist Medical Center

Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

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A simplified outline of the protein C system.
 
 
 
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