Protein C Deficiency Medication

  • Author: Adam Cuker; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Oct 26, 2011
 

Anticoagulant Agents

Class Summary

Anticoagulation is the mainstay of therapy for the treatment and prevention of VTE in patients with protein C deficiency.

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Heparin

 

Primarily used during the treatment of an acute thrombotic event or before initiating oral anticoagulant therapy.

Heparin mediates anticoagulant effects by augmenting the effect of the anticoagulant protein antithrombin.

Higher doses are needed in infants and children due to their low antithrombin levels.

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Enoxaparin (Lovenox)

 

Produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). Binds to antithrombin, enhancing its therapeutic effect. The heparin-antithrombin complex binds to and inactivates activated factor X (Xa) and factor II (thrombin).

Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.

Advantages include intermittent dosing and decreased requirement for monitoring. Heparin anti–factor Xa levels may be obtained if needed to establish adequate dosing.

LMWH differs from UFH by having a higher ratio of antifactor Xa to antifactor IIa compared with UFH.

Prevents DVT, which may lead to pulmonary embolism in patients undergoing surgery who are at risk for thromboembolic complications. Used for prevention in hip replacement surgery (during and following hospitalization), knee replacement surgery, or abdominal surgery in those at risk of thromboembolic complications, or in nonsurgical patients at risk of thromboembolic complications secondary to severely restricted mobility during acute illness.

Used to treat DVT or PE in conjunction with warfarin for inpatient treatment of acute DVT with or without PE or for outpatient treatment of acute DVT without PE.

No utility in checking aPTT (drug has wide therapeutic window and aPTT does not correlate with anticoagulant effect).

May be used during the treatment of an acute thrombotic event, before initiating PO anticoagulant therapy, or SC as an outpatient medication.

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Dalteparin (Fragmin)

 

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

Except in overdoses, no utility exists in checking PT or aPTT because aPTT does not correlate with anticoagulant effect of fractionated LMWH.

Average duration of treatment is 7-14 d.

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Tinzaparin (Innohep)

 

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

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Fondaparinux (Arixtra)

 

Synthetic anticoagulant, which works by inhibiting factor Xa, a key component involved in blood clotting. Provides highly predictable response. Bioavailability is 100%, has a rapid onset of action, and a half-life of 14-16 h, allowing for sustained antithrombotic activity over 24-h period. Does not affect prothrombin time or activated partial thromboplastin time, nor does it affect platelet function or aggregation.

Prevents DVT, which may lead to pulmonary embolism, in patients undergoing orthopedic surgery who are at risk for thromboembolic complications.

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Warfarin (Coumadin)

 

Acts by preventing proper functional synthesis of the vitamin K–dependent procoagulant proteins prothrombin; factors VII, IX, and X; and anticoagulant proteins C and S.

Tailor dose to maintain an INR in the range of 2 to 3.

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Sources of Exogenous Protein C

Class Summary

A source of exogenous protein C in the form of either fresh frozen plasma or the protein C concentrate Ceprotin is used in the management of NPF and may also be employed in the treatment of WISN.

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Protein C concentrate (Ceprotin)

 

A decision to administer protein C concentrate should take into consideration the protein C activity concentration, the severity of symptomatology, the cost, and the clinical scenario.

Although the concentrate is intended for IV use, reports of effective management with SC protein C concentrate have been documented in several cases of homozygous deficiency.

Ceprotin is indicated for prevention and treatment of life-threatening venous thrombosis and purpura fulminans caused by severe congenital protein C deficiency. Off-label use in the treatment of warfarin-induced skin necrosis in patients with heterozygous protein C deficiency has also been reported.

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Fresh frozen plasma

 

Contains plasma components of whole blood.

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Contributor Information and Disclosures
Author

Adam Cuker  MD, MS, Assistant Professor of Medicine, Assistant Professor of Pathology and Laboratory Medicine, University of Pennsylvania

Adam Cuker is a member of the following medical societies: American College of Physicians, American Society of Hematology, Hemophilia and Thrombosis Research Society, International Society on Thrombosis and Haemostasis, and National Hemophilia Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Eleanor S Pollak, MD  Associate Director of Special Coagulation, Associate Professor, Department of Pathology and Laboratory Medicine, Section of Hematology and Coagulation, University of Pennsylvania

Eleanor S Pollak, MD is a member of the following medical societies: American Society of Hematology, College of American Pathologists, and National Multiple Sclerosis Society

Disclosure: Nothing to disclose.

Specialty Editor Board

David Aboulafia, MD  Medical Director, Bailey-Boushay House, Clinical Professor, Department of Medicine, Division of Hematology, Attending Physician, Section of Hematology/Oncology, Virginia Mason Clinic; Investigator, Virginia Mason Community Clinic Oncology Program/SWOG

David Aboulafia, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Directors Association, American Society of Hematology, Infectious Diseases Society of America, and Phi Beta Kappa

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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The protein C pathway. APC = activated protein C; PC = protein C; S= protein S; T = thrombin; TM = thrombomodulin; Va = factor Va; VIII = factor VIIIa.
A patient with warfarin-induced skin necrosis.
A patient with neonatal purpura fulminans.
 
 
 
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