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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Original Effective Date: 12/15/13

Reviewed: 04/08/15

Revised: 11/01/15

Subject: Protein C Concentrate, human (Ceprotin) Injection

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates

DESCRIPTION:

Congenital protein C deficiency is a rare genetic disorder caused by mutations in the PROC gene that result in changes in protein C. Protein C is a vitamin K dependent plasma protein that is a precursor to activated protein C (APC), a potent anticoagulant reduces the production of thrombin by inactivating coagulation factors V and VIII. Protein C deficiency is inherited in an autosomal dominant pattern and can be categorized as either type I or type II depending on how mutations affect protein C; type I is caused by PROC gene mutations that result in reduced levels of protein C and type II is caused by PROC gene mutations that result in the production of an altered protein C with reduced activity. Both types of mutations can be associated with mild or severe protein C deficiency as the severity is determined by the number of inherited PROC gene mutations.

While heterozygous protein C deficiency is often asymptomatic, homozygous or double heterozygous protein C deficiency results in a hypercoagulable state that typically presents at birth with purpura fulminans or disseminated intravascular coagulation (DIC). A diagnosis of severe congenital protein C deficiency is based on the appropriate clinical picture, a very-low or undetectable protein C level, heterozygous deficiency of the same protein in the parents, and, ideally, identification of the molecular defect.

Current treatment options for congenital protein C deficiency are limited to protein C concentrate, fresh frozen plasma, unfractionated heparin, low molecular weight heparin, and warfarin. Purpura fulminans, DIC, and acute thrombosis can only be managed with protein C concentrate or fresh frozen plasma. Outside of these acute conditions, most individuals with severe congenital protein C deficiency are managed for long-term secondary prophylaxis using protein C concentrate or therapeutic anticoagulation.

Protein C concentrate (Ceprotin) was approved by the U.S. Food and Drug Administration in 2007 for the prevention and treatment of venous thrombosis and purpura fulminans in children and adults with severe congenital protein C deficiency. Prior to FDA approval, protein C concentrate was designated an orphan drug for this same indication.

POSITION STATEMENT:

Protein C concentrate meets the definition of medical necessity when ALL of the following criteria are met:

1. Member is diagnosed with severe congenital protein C deficiency

2. Protein C deficiency has been confirmed by one of the following:

a. Functional protein C testing

b. Antigenic protein C testing

c. Genetic testing

3. Protein C deficiency is documented to be homozygous or double (or mixed) heterozygous

Duration of approval: 1 year

Protein C concentrate is not considered a medical necessity for members with heterozygous protein C deficiency.

DOSAGE/ADMINISTRATION:

FDA-approved:

Acute Episode/Short-term Prophylaxis

Long-term Prophylaxis

Dose Adjustments

Drug Availability

PRECAUTIONS:

Boxed Warning

None

Contraindications

None

Precautions/Warnings

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding:

J2724

Injection, protein c concentrate, intravenous, human, 10 iu

ICD-10 Diagnoses Codes That Support Medical Necessity: (Effective 10/01/15)

D68.51

Activated protein C resistance

D68.52

Prothrombin gene mutation

D68.59

Other primary thrombophilia

D68.61

Antiphospholipid syndrome

D68.62

Lupus anticoagulant syndrome

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date.

DEFINITIONS:

None

RELATED GUIDELINES:

None

OTHER:

None

REFERENCES:

  1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2015 [cited 2015-03-23]. In: STAT!Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.
  2. Bates SM, Greer IA, Middeldorp S, Veenstra DL, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e691S-736S.
  3. Baxter Healthcare Corporation. Ceprotin (protein c concentrate human) kit. 2010 [cited 2013 Oct 8]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=926914a9-78b2-40ea-b37d-2a55c09bf275 /.
  4. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2015 [cited 2015-03-23]. Available from: http://www.clinicalpharmacology.com/.
  5. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2015 [cited 2015-03-23]. Available from: http://clinicaltrials.gov/.
  6. Cooper PC, Hill M, Maclean RM. The phenotypic and genetic assessment of protein C deficiency. Int J Lab Hematol. 2012 Aug;34(4):336-46.
  7. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; 2015 [cited 2015-03-23]. Available from: http://www.thomsonhc.com/.
  8. Goldenberg NA, Manco-Johnson MJ. Protein C deficiency. Haemophilia. 2008 Nov;14(6):1214-21.
  9. Knoebl PN. Severe congenital protein C deficiency: the use of protein C concentrates (human) as replacement therapy for life-threatening blood-clotting complications. Biologics. 2008 Jun;2(2):285-96.
  10. Monagle P, Chan AKC, Goldenberg NA, Ichord RN, et al. Antithrombotic therapy in neonates and children. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e737S-801S.
  11. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2015 [cited 2015-03-23]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  12. Protein C Deficiency. 2015 [cited 2015-03-23]. In Genetic Home Reference [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://ghr.nlm.nih.gov/condition/protein-c-deficiency/.
  13. Tcheng WY, Dovat S, Gurel Z, Donkin J, Wong WY. Severe congenital protein C deficiency: description of a new mutation and prophylactic protein C therapy and in vivo pharmacokinetics. J Pediatr Hematol Oncol. 2008 Feb;30(2):166-71.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Coverage Committee on 04/08/15.

GUIDELINE UPDATE INFORMATION:

12/15/13

New Medical Coverage Guideline.

05/15/15

Revision to guideline; updated references.

11/01/15

Revision: ICD-9 Codes deleted.

Date Printed: August 22, 2017: 07:13 AM