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LCD Title

MolDX: Genetic Testing for Hypercoagulability / Thrombophilia (Factor V Leiden, Factor II Prothrombin, and MTHFR)

AMA CPT / ADA CDT / AHA NUBC Copyright Statement

CPT codes, descriptions and other data only are copyright 2022 American Medical Association. All Rights Reserved. Applicable FARS/HHSARS apply.

Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not
recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data
contained or not contained herein.

Current Dental Terminology © 2022 American Dental Association. All rights reserved.

Copyright © 2023, the American Hospital Association, Chicago, Illinois. Reproduced with permission. No portion of the American Hospital Association
(AHA) copyrighted materials contained within this publication may be copied without the express written consent of the AHA. AHA copyrighted
materials including the UB‐04 codes and descriptions may not be removed, copied, or utilized within any software, product, service, solution or derivative
work without the written consent of the AHA. If an entity wishes to utilize any AHA materials, please contact the AHA at 312‐893‐6816.

Making copies or utilizing the content of the UB‐04 Manual, including the codes and/or descriptions, for internal purposes, resale and/or to be used in any
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information contained in this material, nor was the AHA or any of its affiliates, involved in the preparation of this material, or the analysis of information
provided in the material. The views and/or positions presented in the material do not necessarily represent the views of the AHA. CMS and its products
and services are not endorsed by the AHA or any of its affiliates.

1
Issue
Issue Description

This LCD outlines noncoverage for this service with specific details under Coverage Indications, Limitations and/or Medical Necessity.

CMS National Coverage Policy

Title XVIII of the Social Security Act (SSA), §1862(a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable
and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

42 CFR §410.32(a) Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: Conditions

CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, §80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory,
and Other Diagnostic Tests, §80.1.1 Certification Changes

Coverage Guidance
Coverage Indications, Limitations, and/or Medical Necessity

Indications

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This is a non-coverage policy for genetic testing for thrombophilia testing for the Factor V Leiden (FVL) variant in the F5 gene, the G20210G>A
(G20210A) variant in the F2 gene, and the MTHFR gene which encodes the 5,10-methylenetetrahydrofolate reductase enzyme. Genetic testing for these
genes for all risk factors, signs, symptoms, diseases, or conditions, including cardiovascular risk assessment, are non-covered except for pregnant patients.

Testing for FVL and F2 G20210A mutations is indicated for pregnant patients who have a history of personal venous thromboembolism (VTE) associated
with a non-recurrent (transient) risk factor who are not otherwise receiving anticoagulant prophylaxis. The results of genetic testing can inform risk
stratification for VTE recurrence and subsequent need for antenatal prophylaxis. However, Medicare will not add coverage of thrombophilia testing for
pregnant women because they likely represent a very small group of potential Medicare (disabled) patients. Claims submitted on this limited Medicare
population will deny per the policy, but should be appealed for coverage with submission of medical records supporting the necessity for testing, and
specify how testing changed anticoagulant prophylaxis management for the patient.

Background

Thrombophilia (or hypercoagulability) is the propensity to develop thrombosis due to either an acquired or inherited defect in the coagulation system. The
major clinical manifestation of thrombophilia is VTE. Acquired thrombophilia risk factors include but are not limited to advancing age (> 50), trauma,
malignancy, chemotherapy, major surgery, immobilization, pregnancy, estrogen, inflammation, antiphospholipid antibody syndrome, myeloproliferative
disorders, heparin-induced thrombocytopenia, liver disease, nephrotic syndrome and prolonged air travel. Inherited thrombophilia risk factors include
deficiencies in antithrombin, Protein C, Protein S, mutations in FVL and F2, and dysfibrinogenemias. Mixed or unknown risk factors include
hyperhomocysteinemia, elevated levels of Factor VIII, acquired Protein C resistance in the absence of Factor V Leiden, and elevated levels of Factors IX
and XI.

Testing for thrombophilia may consist of functional testing, antigenic testing, and genetic testing. Functional testing for thrombophilia may include tests
such as:

• Anti-phospholipid antibody (lupus anticoagulant)

• Protein C
• Protein S
• Activated Protein C resistance (a surrogate for Factor V Leiden mutation)

span style='font-size:15.0pt;font-family:"Muli",serif; color:#323A45;font-weight:normal'Coverage Guidanceo:p 3

 • Factor VIII
• Fibrinogen
• C-reactive protein
• Homocysteine levels

Antigenic testing may be performed to identify specific glycoprotein antibodies associated with abnormal functional anti-phospholipid antibody studies, or
to subtype deficiencies detected by decreased Protein S, Protein C and Antithrombin functional activity.

VTE is characteristically seen in deficiencies in Protein C, Protein S and antithrombin, as well as with FVL and F2 mutations. This is unlike the
combination of arterial and venous thrombosis associated with hyperhomocysteinemia and lupus anticoagulant.

Genetic Testing for Thrombophilia

Genetic testing is available for a number of types of inherited thrombophilia, including mutations in the FVL, F2 and MTHFR genes. However, the clinical
utility of testing is uncertain. The clinical utility of genetic testing depends on the ability of testing results to change management that results in improved
clinical outcomes. The clinical utility of genetic testing for thrombophilia is based on the overall risk of thromboembolism and the risk/benefit ratio of
treatment, primarily with anticoagulants.

During the previous 5 years, a number of guidelines and/or position statements on testing for thrombophilia have been published. In 2011, The Evaluation
of Genomic Applications in Practice and Prevention Working Groups (EGAPP) addressed genetic testing for FVL and F2 mutations. The expert consensus
recommended:

• There is no evidence that knowledge of FVL/F2 mutation status in patients with VTE affects anticoagulation treatment to avoid
recurrence;
• There is convincing evidence that anticoagulation beyond three months reduces recurrence of VTE, regardless of mutation status;

span style='font-size:15.0pt;font-family:"Muli",serif; color:#323A45;font-weight:normal'Coverage Guidanceo:p 4

 • There is no evidence that knowledge of FVL/F2 mutation status among symptomatic family members of patients with VTE leads to
anticoagulation aimed at avoiding initial episodes of VTE (See note).

Note: The Medicare benefit applies only to individuals with signs and symptoms of disease. There is no Medicare benefit for assessment of thrombosis
risk in asymptomatic patients (aka screening for inherited thrombophilia) or in asymptomatic individuals whose relatives have documented inherited
thrombophilia.

In 2008, the American College of Chest Physician’s (ACCP) published guidelines for the treatment of thromboembolic disease stated the following
concerning genetic testing for thrombophilia:

• The presence of hereditary thrombophilia has not been used as a major factor to guide duration of anticoagulation for VTE in these guidelines
because evidence from prospective studies suggests that these factors are not major determinates of the risk of recurrence.

In the 2012 ACCP Clinical Practice Guidelines, Guyatt10 and Bates3 make the following recommendations for treatment and management of VTE:

• In persons with asymptomatic thrombophilia (i.e., without a previous history of VTE), we recommend against the long −term daily use of
mechanical or pharmacologic thromboprophylaxis to prevent VTE;
• For pregnant women with no prior history of VTE who are known to be homozygous for factor V Leiden or the prothrombin 20210A mutation and
have a positive family history for VTE, we suggest antepartum prophylaxis with prophylactic− or intermediate− dose low− molecular− weight
heparin (LMWH) and postpartum prophylaxis for 6 weeks with prophylactic− or intermediate− dose LMWH or vitamin K antagonists (VKAs)
targeted at INR 2.0 to 3.0 rather than no prophylaxis;
• For all pregnant women with prior VTE, we suggest postpartum prophylaxis for 6 weeks with prophylactic− or intermediate −dose LMWH or
VKAs targeted at INR 2.0 to 3.0 rather than no prophylaxis;
• For pregnant women at low risk of recurrent VTE (single episode of VTE associated with a transient risk factor not related to pregnancy or use of
estrogen), we suggest clinical vigilance antepartum rather than antepartum prophylaxis;
• For pregnant women at moderate to high risk of recurrent VTE (single unprovoked VTE, pregnancy− or estrogen −related VTE, or multiple prior
unprovoked VTE not receiving long− term anticoagulation), we suggest antepartum prophylaxis with prophylactic− or intermediate− dose LMWH
rather than clinical vigilance or routine care.

In the 2013 American Congress of Obstetricians and Gynecologists (ACOG) clinical management guidelines for inherited thrombophilia in pregnancy,
ACOG experts note that the following guidelines are based on limited or inconsistent scientific evidence:

span style='font-size:15.0pt;font-family:"Muli",serif; color:#323A45;font-weight:normal'Coverage Guidanceo:p 5

 • “Screening for thrombophilia is controversial. It is useful only when results will affect management decisions, and it is not useful in
situations where treatment is indicated for other risk factors.
• Screening may be considered in the following clinical settings:

♦ A personal history of VTE that was associated with a non-recurrent risk factor (e.g., fractures, surgery, and prolonged
immobilizations).

• A first-degree relative (e.g., parent or sibling) with a history of high-risk thrombophilia.” (See note below)

ACOG also stated that testing for inherited thrombophilia in women who have experienced recurrent fetal loss or placental abruption is not recommended
because it is unclear if anticoagulation therapy reduces recurrence. They indicate that there is insufficient clinical evidence that antepartum prophylaxis
with unfractionated heparin or LMWH prevents recurrence in these patients, and note insufficient evidence to either screen for or treat women with
inherited thrombophilia including complications such as fetal growth restriction or preeclampsia.

On behalf of the American College of Medical Genetics (ACMG), Grody7 recommended testing for FVL for the following indications:

• Age under 50, any venous thrombosis;

• Venous thrombosis in unusual sites (such as hepatic, mesenteric, and cerebral veins;
• Recurrent venous thrombosis;
• Venous thrombosis and a strong family history of thrombotic disease;
• Venous thrombosis in pregnant women or women taking oral contraceptives;
• Relatives of individuals with venous thrombosis under age 50;
• Myocardial infarction in female smokers under age 50.

ACMG suggested that FVL testing may also be considered in the following situations:

• Venous thrombosis, age over 50, except when active malignancy is present;
• Relatives of individuals known to have FVL. Knowledge that they have the FVL mutation may influence management of pregnancy and
may be a factor in decision −making regarding oral contraceptive use;
• Women with recurrent pregnancy loss or unexplained severe preeclampsia, placental abruption, intrauterine fetal growth retardation, or
stillbirth. Knowledge of FVL carrier status may influence management of future pregnancies.

span style='font-size:15.0pt;font-family:"Muli",serif; color:#323A45;font-weight:normal'Coverage Guidanceo:p 6

FVL testing is not recommended for the following:

• A general population screen;

• A routine initial test during pregnancy or prior to the use of oral contraceptives, hormone replacement therapy (HRT) or selective estrogen
receptor modulators (SERMs);
• A prenatal or newborn test, or as a routine test in asymptomatic children;
• A routine initial test in individuals with arterial thrombosis (testing may be considered, however, in selected young individuals [under age
50] with unexplained arterial thrombosis in the absence of other risk factors for atherosclerotic vascular disease).

In 2013, (ACMG) published a practice guideline on the lack of evidence for MTHFR polymorphism testing. Among a number of recommendations,
ACMG experts concluded:

• MTHFR polymorphism genotyping should not be ordered as part of the clinical evaluation for thrombophilia or recurrent pregnancy loss;
• MTHFR polymorphism genotyping should not be ordered for at-risk family members.

Non-coverage Summary

Genetic testing for inherited thrombophilias is controversial. While the association between FVL and F2 mutations and increased risk for VTE is apparent,
the actual impact of this increased risk on clinical management is less certain. Older professional society guidelines recommend genetic testing for
thrombophilia for a wide range of indications, while more recent consensus statements and recommendations suggest much more limited clinical utility of
testing.

The population for which genetic testing results have direct implications for treatment is pregnant women with a previous history of VTE associated with a
transient risk factor (e.g., surgery, trauma). These women would typically not be treated with antepartum anticoagulant prophylaxis unless they were found
to have a genotype associated with a high risk of VTE recurrence (FVL homozygosity, F2 G20210A homozygosity, or compound heterozygosity for FVL
and F2 G20210A). Genetic testing for these patients is indicated.

span style='font-size:15.0pt;font-family:"Muli",serif; color:#323A45;font-weight:normal'Coverage Guidanceo:p 7

There may also be benefit to screening pregnant women with a family history of known thrombophilia, as those women found to have a high risk genotype
would be offered antenatal prophylactic anticoagulant therapy even in the absence of a personal history of VTE. However, the Medicare benefit applies
only to patients with signs and symptoms of disease and does not include screening in asymptomatic patients.

Finally, despite many earlier publications suggesting a link between MTHFR polymorphisms and a risk for a wide spectrum of obstetric and
cardiovascular complications, it is now accepted that MTHFR genotype alone is not associated with VTE. There is no clinical indication for MTHFR
genotyping in any population.

There is insufficient evidence in the published peer-reviewed scientific literature to support coverage for genetic testing for inherited thrombophilias
outside the pregnant women as described above. Genetic testing for FVL and F2 G20210A is considered investigational for all other indications. However,
Medicare may consider coverage for FVL and/or F2 genetic testing in unusual circumstances where testing will change clinical management of the patient.
Denied claims can be appealed with supporting evidence of specific medical necessity. Only providers with evidence of formal training with board
eligibility or certification in hematology/oncology, hematopathology or coagulation disorders at an accredited program satisfy reasonable and necessary
criteria for these tests . There is broad consensus in the medical literature that MTHFR genotyping has no clinical utility in any clinical scenario. This
testing is considered investigational and is NOT a Medicare benefit.

Summary of Evidence

N/A

Analysis of Evidence (Rationale for Determination)

N/A

Associated Information

General Informationo:p 8
Documentation Requirements

The patient's medical record must contain documentation that fully supports the medical necessity for services included within this LCD. (See “Coverage
Indications, Limitations, and/or Medical Necessity"). This documentation includes, but is not limited to, relevant medical history, physical examination,
and results of pertinent diagnostic tests or procedures.

Documentation supporting the medical necessity should be legible, maintained in the patient's medical record, and must be made available to the MAC
upon request.

Sources of Information

N/A

Bibliography

1. American College of Obstetricians and Gynecologists Women's Health Care ACOG Practice Bulletin No. 138: inherited thrombophilias in
pregnancy. Obstet Gynecol. 2013;122(3):706-717.
2. Baglin T, Gray E, Greaves M, et Clinical guidelines for testing for heritable thrombophilia. Br J Haematol. 2010;149(2):209-220.
3. Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. 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;141(2 Suppl):e691S-e736S.
4. Bauer KA, Lip Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors. In: Leung LLK,
ed. UptoDate. UptoDate; 2011. Accessed June 1, 2023. www.uptodate.com

General Informationo:p 9
 5. Bradley LA, Palomaki GE, Bienstock J, Varga E, Scott JA. Can Factor V Leiden and prothrombin G20210A testing in women with recurrent
pregnancy loss result in improved pregnancy outcomes?: Results from a targeted evidence-based review. Genet Med. 2012;14:39-50.
6. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based
Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):381S-
7. Grody WW, Griffin JH, Taylor AK, Korf BR, Heit JA; ACMG Factor Leiden Working Group. American College of Medical Genetics consensus
statement on factor V Leiden mutation testing. Genet Med. 2001;3(2):139- 148.
8. Gohil R, Peck G, Sharma The genetics of venous thromboembolism. A meta-analysis involving approximately 120,000 cases and 180,000
controls. Thromb Haemost. 2009;102(2):360-370.
9. Grandone E, Villani M, Tiscia GL, et Clinical pregnancies and live births in women approaching ART: a follow-up analysis of 157 women after
thrombophilia screening. Thromb Res. 2014;133(2):168-172.
10. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ; American College of Chest Physicians Antithrombotic Therapy and
Prevention of Thrombosis Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest
Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):7S-47S.
11. Hickey SE, Curry CJ, Toriello ACMG Practice Guideline: lack of evidence for MTHFR. Genet Med. 2013;15(2):153-156.
12. Kearon C, Julian JA, Kovacs MJ, et al. Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a
randomized Blood. 2008;112(12):4432-4436.
13. Lijfering WM, Brouwer JL, Veeger NJ, et al. Selective testing for thrombophilia in patients with first venous thrombosis: results from a
retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479
relatives. Blood. 2009;113(21):5314-5322.

Revision History Information

Revision Revision
History History
Date Number Revision History Explanation Reasons for Change
07/20/2023R5 Under CMS National Coverage Policy updated section heading for 2nd regulation, and
revised the following regulation CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit • Provider
Policy Manual, Chapter 15, §80 Requirements for Diagnostic X-Ray, Diagnostic Laboratory, Education/Guidance
and Other Diagnostic Tests to include section 80.1.1. Under Bibliography changes were made
to citations to reflect AMA citation guidelines. Formatting, punctuation, and typographical
errors were corrected throughout the LCD.
08/12/2021R4 Under Coverage Indications, Limitations and/or Medical
Necessity subheading Background revised verbiage in first paragraph, third sentence to read • Provider
“Acquired thrombophilia risk factors include but are not limited to advancing age (> 50), Education/Guidance
trauma, malignancy, chemotherapy, major surgery, immobilization, pregnancy, estrogen,

span style='font-family:"Arial",sans-serif;color:#323A45'Revision History Informationo:p 10

 inflammation, antiphospholipid antibody syndrome, myeloproliferative disorders,
heparin-induced thrombocytopenia, liver disease, nephrotic syndrome, and prolonged air
travel”.

Under Bibliography changes were made to citations to reflect AMA citation guidelines.
Formatting, punctuation, and typographical errors were corrected throughout the LCD.
11/01/2019R3 The LCD is revised to remove CPT/HCPCS codes in the Keyword Section of the LCD.
• Other (The LCD is revised
At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage to remove CPT/HCPCS
which requires comment and notice. This revision is not a restriction to the coverage codes in the Keyword
determination; and, therefore not all the fields included on the LCD are applicable as noted in Section of the LCD.)
this policy.
11/01/2019R2 CMS references are revised.
• Creation of Uniform LCDs
At this time 21st Century Cures Act will apply to new and revised LCDs that restrict coverage With Other MAC
which requires comment and notice. This revision is not a restriction to the coverage Jurisdiction
determination; and, therefore not all the fields included on the LCD are applicable as noted in
this policy
11/01/2019R1 As required by CR 10901, all billing and coding information has been moved to the
companion article, this article is linked to the LCD. • Revisions Due To Code
Removal

Attachments

N/A

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Articles

A57424 - Billing and Coding: MolDX: Genetic Testing for Hypercoagulability / Thrombophilia (Factor V Leiden, Factor II Prothrombin, and MTHFR)

A54894 - Response to Comments: MolDX: Genetic Testing for Hypercoagulability / Thrombophilia

LCDs

Associated Documentso:p 11
DL36157 - (MCD Archive Site)

DL36159 - (MCD Archive Site)

Related National Coverage Documents

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Public Versions

Updated On Effective Dates Status

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Article Title

Billing and Coding: MolDX: Genetic Testing for Hypercoagulability / Thrombophilia (Factor V Leiden, Factor II Prothrombin, and MTHFR)

Article Type

Billing and Coding

AMA CPT / ADA CDT / AHA NUBC Copyright Statement

Associated Documentso:p 12
CPT codes, descriptions and other data only are copyright 2022 American Medical Association. All Rights Reserved. Applicable FARS/HHSARS apply.

Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not
recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data
contained or not contained herein.

Current Dental Terminology © 2022 American Dental Association. All rights reserved.

Copyright © 2023, the American Hospital Association, Chicago, Illinois. Reproduced with permission. No portion of the American Hospital Association
(AHA) copyrighted materials contained within this publication may be copied without the express written consent of the AHA. AHA copyrighted
materials including the UB‐04 codes and descriptions may not be removed, copied, or utilized within any software, product, service, solution or derivative
work without the written consent of the AHA. If an entity wishes to utilize any AHA materials, please contact the AHA at 312‐893‐6816.

Making copies or utilizing the content of the UB‐04 Manual, including the codes and/or descriptions, for internal purposes, resale and/or to be used in any
product or publication; creating any modified or derivative work of the UB‐04 Manual and/or codes and descriptions; and/or making any commercial use
of UB‐04 Manual or any portion thereof, including the codes and/or descriptions, is only authorized with an express license from the American Hospital
Association. The American Hospital Association (the "AHA") has not reviewed, and is not responsible for, the completeness or accuracy of any
information contained in this material, nor was the AHA or any of its affiliates, involved in the preparation of this material, or the analysis of information
provided in the material. The views and/or positions presented in the material do not necessarily represent the views of the AHA. CMS and its products
and services are not endorsed by the AHA or any of its affiliates.

CMS National Coverage Policy

Title XVIII of the Social Security Act, §1833(e) prohibits Medicare payment for any claim lacking the necessary documentation to process the claim.

CMS Internet-Only Manual, Pub. 100-04, Medicare Claims Processing Manual, Chapter 16, §50.5 Jurisdiction of Laboratory Claims, 60.1.2 Independent
Laboratory Specimen Drawing, 60.2 Travel Allowance.

CMS Internet-Only Manual, Pub. 100-04, Medicare Claims Processing Manual, Chapter 23, §10 Reporting ICD Diagnosis and Procedure Codes

Article Text

span style='font-size:15.0pt;font-family: "Muli",serif;color:#323A45;font-weight:normal'CMS National Coverage Policyo:p 13

The following coding and billing guidance is to be used with its associated Local coverage determination.

To report a Genetic Testing for Hypercoagulability / Thrombophilia (Factor V Leiden, Factor II Prothrombin, and MTHFR) service, please submit the
following claim information:

• Select appropriate CPT® code

• Enter 1 unit of service (UOS)
• Enter the appropriate DEX Z-Code™ identifier adjacent to the CPT® code in the comment/narrative field for the following Part B claim field/types:
• Loop 2400 or SV101-7 for the 5010A1 837P
• Item 19 for paper claim
• Enter the appropriate DEX Z-Code™ identifier adjacent to the CPT® code in the comment/narrative field for the following Part A claim field/types:
• Line SV202-7 for 837I electronic claim
• Block 80 for the UB04 claim form
• Select the appropriate ICD-10-CM code

Coding Information

(3 Codes)

Group 1 Paragraph

N/A

Group 1 Codes

Code Description
81240F2 (PROTHROMBIN, COAGULATION FACTOR II) (EG, HEREDITARY HYPERCOAGULABILITY) GENE ANALYSIS, 20210G>A
VARIANT
81241F5 (COAGULATION FACTOR V) (EG, HEREDITARY HYPERCOAGULABILITY) GENE ANALYSIS, LEIDEN VARIANT
81291MTHFR (5,10-METHYLENETETRAHYDROFOLATE REDUCTASE) (EG, HEREDITARY HYPERCOAGULABILITY) GENE ANALYSIS,
COMMON VARIANTS (EG, 677T, 1298C)

Article Guidanceo:p 14
N/A

(1 Code)

Group 1 Paragraph

N/A

Group 1 Codes

Code Description
XX000 Not Applicable

N/A

N/A

N/A

Contractors may specify Bill Types to help providers identify those Bill Types typically used to report this service. Absence of a Bill Type does not
guarantee that the article does not apply to that Bill Type. Complete absence of all Bill Types indicates that coverage is not influenced by Bill Type and the
article should be assumed to apply equally to all claims.

Code Description
0x TBD

Contractors may specify Revenue Codes to help providers identify those Revenue Codes typically used to report this service. In most instances Revenue
Codes are purely advisory. Unless specified in the article, services reported under other Revenue Codes are equally subject to this coverage determination.
Complete absence of all Revenue Codes indicates that coverage is not influenced by Revenue Code and the article should be assumed to apply equally to
all Revenue Codes.

CPT/HCPCS Modifierso:p 15
N/A

N/A

Revision History Revision History

Date Number Revision History Explanation
08/12/2021 R2 Formatting, punctuation, and typographical errors were corrected throughout the Article.
11/01/2019 R1 CMS references are revised.

Related Local Coverage Documents

Articles

A54894 - Response to Comments: MolDX: Genetic Testing for Hypercoagulability / Thrombophilia

LCDs

DL36157 - (MCD Archive Site)

DL36159 - (MCD Archive Site)

L36159 - MolDX: Genetic Testing for Hypercoagulability / Thrombophilia (Factor V Leiden, Factor II Prothrombin, and MTHFR)

Related National Coverage Documents

N/A

Statutory Requirements URLs

N/A

Rules and Regulations URLs

Revenue Codeso:p 16
N/A

CMS Manual Explanations URLs

N/A

Other URLs

N/A

Public Versions

Updated On Effective Dates Status

08/03/2021 08/12/2021 - N/A Currently in Effect You are here

URL for source document:

https://www.cms.gov/medicare-coverage-database/view/article.aspx?articleId=54894&ver=4

Article Title

Response to Comments: MolDX: Genetic Testing for Hypercoagulability / Thrombophilia

AMA CPT / ADA CDT / AHA NUBC Copyright Statement

CPT codes, descriptions and other data only are copyright 2022 American Medical Association. All Rights Reserved. Applicable FARS/HHSARS apply.

Associated Documentso:p 17
Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT, and the AMA is not
recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data
contained or not contained herein.

Current Dental Terminology © 2022 American Dental Association. All rights reserved.

Copyright © 2023, the American Hospital Association, Chicago, Illinois. Reproduced with permission. No portion of the American Hospital Association
(AHA) copyrighted materials contained within this publication may be copied without the express written consent of the AHA. AHA copyrighted
materials including the UB‐04 codes and descriptions may not be removed, copied, or utilized within any software, product, service, solution or derivative
work without the written consent of the AHA. If an entity wishes to utilize any AHA materials, please contact the AHA at 312‐893‐6816.

Making copies or utilizing the content of the UB‐04 Manual, including the codes and/or descriptions, for internal purposes, resale and/or to be used in any
product or publication; creating any modified or derivative work of the UB‐04 Manual and/or codes and descriptions; and/or making any commercial use
of UB‐04 Manual or any portion thereof, including the codes and/or descriptions, is only authorized with an express license from the American Hospital
Association. The American Hospital Association (the "AHA") has not reviewed, and is not responsible for, the completeness or accuracy of any
information contained in this material, nor was the AHA or any of its affiliates, involved in the preparation of this material, or the analysis of information
provided in the material. The views and/or positions presented in the material do not necessarily represent the views of the AHA. CMS and its products
and services are not endorsed by the AHA or any of its affiliates.

Article Guidance
Article Text

Noridian’s Response to Provider Recommendations (for comment period ending 08/10/2015).

Number Comment Response

1 1. LCD ignores fact that MTHFR is associated with homocysteinuria. Agreement acknowledged.
The commenter notes that it is rare that a typical Medicare beneficiary
would be tested for homocystinuria, the commenter notes young
children may be qualify for Medicare, and the appropriate diagnosis and
treatment makes a huge difference in the prognosis of homocystinuria.
The commenter notes that MTHFR sequencing should not be done in the
evaluation of thrombophilia.
2 2. Factor V Leiden (FVL) - Long-term anticoagulation. Commenter It must be emphasized that there currently no data from prospective,
notes that Long-term anticoagulation should be considered in individualsrandomized, controlled trials specifically designed to address the

span style='font-size:15.0pt;font-family:"Muli",serif; color:#323A45;font-weight:normal'Article Guidanceo:p 18

 homozygous for FVL or with multiple thrombophilic disorders; optimal duration of anticoagulation therapy in patients with specific
“potential benefits from long-term warfarin may outweigh the bleeding hypercoagulable states. Any decision regarding the ideal duration of
risks”, and cites Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob therapy must take into account the estimates of VTE recurrence for a
GE, Comerota AJ. American College of Chest Physicians; given disorder, the nature of the index VTE, and the risk of bleeding
Antithrombotic therapy for venous thromboembolic disease: American associated with prolonged oral anticoagulation.
College of Chest Physicians Evidence-Based Clinical Practice
Guidelines (8th Edition). Chest. 2008b;133:454S–545S. [PubMed]
3 3. Prophylactic anticoagulation Because the initial thrombosis in factor This policy does not address the need for or against prophylactic
V Leiden heterozygotes occurs in association with other circumstantial anticoagulation therapy. The policy addresses the appropriateness of
risk factors in 50% of cases, a short course of prophylactic FVL, F2 and MTHFR genetic testing.
anticoagulation during exposure to hemostatic stresses may prevent
some of these episodes. Prophylactic anticoagulation should be
considered in high-risk clinical settings such as surgery, pregnancy, or
prolonged immobilization, although currently no evidence confirms the
benefit of primary prophylaxis for all asymptomatic carriers. Decisions
regarding prophylactic anticoagulation should be based on a risk/benefit
assessment in each individual case. Factors that may influence decisions
about the indication for and duration of anticoagulation include age,
family history, and other coexisting risk factors. Recommendations for
prophylaxis at the time of surgery and other high-risk situations are
available in consensus guidelines [Geerts et al 2008].” Geerts WH,
Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, Colwell
CW. American College of Chest Physicians; Prevention of venous
thromboembolism: American College of Chest Physicians
Evidence-Based Clinical Practice Guidelines (8th Edition). Chest.
2008;133:381S–453S. [PubMed].
4 4. Genetic Testing for Thrombophilia Commenter states that EGAPP The policy specifically addresses the “other” risk factors such as
statement included “the recommendations do not extend to patients with contraceptive use. However, initiation of oral anticoagulation for
other risk factors for thrombosis, such as contraceptive use, as the primary VTE prophylaxis in asymptomatic carriers of any
evidence review that serves as the basis for the recommendations hypercoagulable state has not been advised, mainly because the annual
focused primarily on idiopathic VTE.” absolute risk of idiopathic VTE is low or not high enough to be
favorably balanced against the annual risk of oral anticoagulation-related
major and fatal hemorrhage. However, because most VTEs (50-70%) in
patients with a predisposition to hypercoagulability occur following a
situational risk factor, such as major or orthopedic surgery, aggressive
VTE prophylaxis should be prescribed to asymptomatic carriers of

Response To Commentso:p 19
 hypercoagulable states during high-risk situations. Many physicians
justify hypercoagulability state testing because, if an abnormality is
found, prescription of long-term oral anticoagulation is believed to be
more appropriate than the recommended 3- to 6-month course.
However, there are no data from prospective, randomized, controlled
trials specifically designed to address the optimal duration of
anticoagulation in patients with specific hypercoagulable states.
5 5. ACOG Clinical Management Guidelines The commenter agrees with Testing for hypercoagulable states is best performed in stages by
the ACOG guidelines, but states that ACOG includes screening for individuals with specific training in hematology/oncology,
thrombophilia when the results will affect pregnancy/postpartum hematopathology or coagulation disorders. Highest yielding assays
management and suggest avoiding screening when treatment is indicated (screening tests) should be performed first, and if positive, should be
because of patient-specific risk factors. followed by appropriate confirmatory tests. If screening test results are
negative and sufficient suspicion exists, less common disorders can be
tested for. Specific testing for FVL is not necessary if the test result for
APC-R is negative. Prothrombin G20210A mutation detection by PCR
is preferred over prothrombin activity level quantification because the
latter does not sufficiently differentiate carriers from non-carriers of the
mutation. Activity assays for antithrombin, protein C, and protein S are
initially preferred because they will be abnormal in both type I
(quantitative) and type II (qualitative) deficiencies. If activity assay
results are normal, there is no benefit to pursuing antigenic testing.
6 6. Testing is reasonable in asymptomatic women planning a pregnancy A Medicare benefit applies only to patients with signs or symptoms of
The commenter specifies that genetic testing is reasonable in an disease. An asymptomatic individual is not eligible for testing under
asymptomatic woman planning a pregnancy who have a first degree Medicare.
relative with a history of a high-risk thrombophilia.

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