blue cross blue shield - tennessee thrombosis testing Coverage

Coverage Criteria for Thrombophilia and Related Testing

inv-01: Covered Indications for Genetic and Plasma Testing

Genetic and plasma testing meet coverage criteria when ALL conditions per the listed clinical scenarios are met as specified below.

Covered genetic testing (Factor V Leiden and Prothrombin G20210A)

Clinical scenarios: a) Age <50 with any deep venous thrombosis; b) Deep venous thrombosis in unusual sites (such as hepatic, mesenteric, and cerebral veins); c) Deep venous thrombosis with a strong family history of thrombotic disease; d) Deep venous thrombosis in pregnant women or women taking oral contraceptives; e) First- and second-degree relatives of individuals with DVT under age 50; f) Myocardial infarction in female smokers under age 50; g) Targeted testing before administration of oral contraceptives in women with a personal or family history of DVT; h) Pediatric arterial ischemic stroke.
From policy indications list

Covered plasma testing (Protein C, Protein S, Antithrombin III)

Clinical scenarios: a) Age <50 with any deep venous thrombosis; b) Deep venous thrombosis in unusual sites (such as hepatic, mesenteric, and cerebral veins); c) Deep venous thrombosis with a strong family history of thrombotic disease; d) Deep venous thrombosis in pregnant women or women taking oral contraceptives; e) Relatives of individuals with DVT under age 50; f) Myocardial infarction in female smokers under age 50; g) Targeted testing before administration of oral contraceptives in women with a personal or family history of DVT; h) Individuals with warfarin-induced skin necrosis; i) Infants with Neonatal Purpura Fulminans; j) Pediatric arterial ischemic stroke.timing: >=6 weeks after acute event and off anticoagulants
From reimbursement policy

inv-03: Appropriate Indications, Timing, and Populations

Guidance-aligned indications where thrombophilia/genetic testing is reasonable or should be considered; includes timing and population considerations.

Primary indications: Testing for Factor V Leiden and Prothrombin G20210A is recommended or reasonable in these circumstances: first unprovoked VTE (especially age <50), VTE at unusual sites, recurrent VTE, personal history of VTE with multiple affected family members or early-onset VTE in a first-degree relative, and patients with low activated protein C (APC) resistance activity.

Supported by specialty guidance

Timing and pre-test considerations: Do not perform testing during an acute clot or while the patient is anticoagulated; defer plasma testing (protein C, protein S, antithrombin) until at least 4–6 weeks after an acute event (factor VIII may require up to 6 months) and commonly after completion of initial anticoagulation (often >=3 months); when testing after VTE consider two-stage testing or waiting until at least 3 months after anticoagulation per guidance.

Anticoagulation Forum, ACC/Connors guidance, ACMG

Patient populations to avoid routine testing: Avoid routine testing in asymptomatic minors, routine population or prenatal screening, and asymptomatic family members unless test results would change clinical management; generally do not test patients after provoked VTE because results rarely change treatment decisions.

inv-04: Society-guided coverage criteria

Coverage guidance reflected from specialty society recommendations:

Avoid testing during active clot or on DOAC/DTI: Do not perform Protein C, Protein S, or Antithrombin testing during an active clotting event because results are not analytically accurate; do not perform a hypercoagulable workup while patients are taking direct factor Xa or direct thrombin inhibitors because results may be uninterpretable.

ASCP Choosing Wisely statements

D-dimer use: Use plasma D-dimer measurement with a highly sensitive assay (or an age-adjusted or clinical-probability–adapted cut-off) to exclude PE/DVT in outpatients/emergency patients with low or intermediate clinical probability; do not use D-dimer to exclude PE in patients with high clinical probability.age-adjusted or clinical-probability-adapted cut-off

ESC and ESC Working Group guidance

Routine laboratory screening discouraged: Routine laboratory screening for heritable thrombophilias is not recommended.

The policy explicitly excludes a range of routine and population-based testing from coverage. Genetic testing for inherited thrombophilia does not meet coverage criteria for routine population screening, prenatal or preimplantation testing, routine newborn screening, and for repeat testing more than once per lifetime. Specific variant tests and multi-gene panels (for example, factor V HR2, prothrombin G1199A, factor VII R353Q, factor 13B V34L, PAI-1) and DVT risk testing as part of pre-transplant evaluation are also listed as not meeting coverage criteria.

Testing for MTHFR variants is specifically discouraged: the ACMG does not support MTHFR variant testing in thrombophilia assessment due to lack of clinical correlation. The policy therefore states that MTHFR genetic testing does not meet coverage criteria for hypercoagulable evaluation or evaluation of 'at risk' family members. The ACMG guidance also advises against routine prenatal or population screening and recommends careful evaluation of personal and family history before testing in women considering estrogen-containing therapies.

Multiple society statements and the policy discourage routine laboratory screening for heritable thrombophilias. SIGN and other guideline bodies state that routine laboratory screening for heritable thrombophilias is not recommended, and the policy lists routine population-level testing and screening of asymptomatic individuals as not meeting coverage criteria.

The policy declares that MTHFR genetic testing for hypercoagulable evaluation or for 'at risk' family members does not meet coverage criteria. It further enumerates multiple clinical situations where genetic testing for inherited thrombophilia is not covered, including evaluation of recurrent fetal loss, arterial thrombosis not attributable to paradoxical emboli, routine screening of asymptomatic women considering oral contraceptives or hormone replacement therapy, prenatal/preimplantation testing, routine newborn screening, and testing more than once per lifetime.

The policy aligns with external guidance that routine testing for Factor V Leiden and prothrombin G20210A in many situations is not beneficial. EGAPP recommends against routine FVL/PT testing in adults with idiopathic VTE and in asymptomatic adult family members when used to consider primary prophylaxis. The Anticoagulation Forum similarly discourages thrombophilia testing in provoked VTE and routine testing of asymptomatic family members, noting testing should be reserved for cases where results would alter management.

The policy discourages certain components of routine thrombophilia panels and inappropriate timing of testing. The American Society for Clinical Laboratory Science recommends against ordering a homocysteine assay as part of a thrombophilia workup. The American Society for Clinical Pathology advises that Protein C, Protein S, and Antithrombin testing should not be performed during an active clotting event or while patients are taking direct factor Xa or direct thrombin inhibitors because results may be inaccurate or uninterpretable.

Covered Indications and Diagnostic Uses

inv-29: See covered indications for Factor V Leiden and Prothrombin G20210A genetic testing and plasma testing for protein C/S and antithrombin III (listed patient groups under criteria_sets).

See covered indications above for Factor V Leiden and Prothrombin G20210A genetic testing and plasma testing for protein C/S and antithrombin III; the following summarizes related covered indications and constraints.

See covered indications: Refer to covered indications for Factor V Leiden and Prothrombin G20210A genetic testing and plasma testing for protein C, protein S, and antithrombin III (patient groups and timing requirements listed in the covered indications and reimbursement policy).

Cross-reference to covered indications

inv-30: First unprovoked VTE (especially <50), VTE at unusual sites, recurrent VTE, strong personal/family history where results would alter management — Includes genetic testing for factor V Leiden and prothrombin G20210A and targeted testing when clinically actionable

Genetic and targeted testing may be appropriate when results would alter clinical management in these high-yield scenarios.

High-yield clinical scenarios:

Not Medically Necessary / Not Covered

inv-02: Not Medically Necessary / Not Covered

The following tests and situations are considered not medically necessary or do not meet coverage criteria.

Not medically necessary / Not covered: MTHFR genetic testing for hypercoagulable evaluation or for 'at risk' family members; genetic testing for Factor V Leiden and Prothrombin G20210A in patients receiving lifelong anticoagulation for recurrent events; venous thrombosis risk testing for superficial venous thrombosis (including superficial thrombophlebitis and varicosities); genetic testing for inherited thrombophilia for evaluation of recurrent fetal loss, placental abruption, preeclampsia, or fetal growth restriction; evaluation of arterial thrombosis not attributable to paradoxical emboli; routine population screening; routine screening of asymptomatic women considering oral contraceptives or HRT; routine screening of asymptomatic pregnant women; prenatal or preimplantation testing; routine newborn screening; testing more than once per lifetime; testing for listed additional variants (factor V HR2, prothrombin G1199A, factor VII R353Q, factor 13B V34L, PAI-1) or multi-gene panel testing; DVT risk testing as part of pre-transplant evaluation; and Factor V Leiden and Prothrombin G20210A testing to determine arterial thrombosis risk.

Explicit 'does not meet coverage criteria' list

MTHFR testing for thrombophilia evaluation and numerous other listed tests and indications are explicitly identified as not covered. The policy text lists MTHFR testing, testing to determine arterial thrombosis risk with Factor V Leiden or Prothrombin mutations, superficial venous thrombosis testing, and multiple other scenarios and variant tests as not meeting coverage criteria.

Frequency Limits and Repeat Testing

inv-32: genetic testing for inherited thrombophilia — Testing more than once per lifetime does not meet coverage criteria

Frequency limitGenetic testing for inherited thrombophilia: testing more than once per lifetime does not meet coverage criteria.

Examples of non-covered repeat situationsRepeat genetic testing for the same inherited thrombophilia variants (e.g., Factor V Leiden, Prothrombin G20210A) is not covered.

Related exclusionsRepeat or lifetime re-testing is listed alongside other non-covered items such as prenatal/preimplantation testing and routine newborn screening.

inv-33: Protein C, Protein S, Antithrombin, Factor VIII, homocysteine — Repeat testing of protein levels

Recommended timingPerform protein C, protein S, and antithrombin testing at least 4-6 weeks after an acute thrombotic event (factor VIII may require up to 6 months); avoid testing during the acute phase.

Provider Actions, Prior Authorization, and Documentation

Documentation Required

Ordering requirements and timing

Coverage is contingent on verification of individual member benefits at time of request. Order plasma assays for protein C, protein S, and antithrombin III at least six weeks after an acute thrombotic event and only when the patient is not anticoagulated. Assays for clotting inhibitor amount and function should be performed prior to any molecular/genetic testing.

Perform testing only when results would change clinical management.
Document that testing timing is >6 weeks post-event and off anticoagulation, or justify why testing while anticoagulated is required.

Prior Authorization

Prior Authorization May Be Required

Prior authorization may be required for thrombophilia testing in settings identified as often inappropriate (for example, testing during provoked VTE, routine population screening, prenatal screening, or repeat lifetime testing). Verify PA requirements before ordering.

Coding and Test Identifiers

inv-11: D-dimer age-adjusted cut-off — referenced as alternative to fixed cut-off (exact numeric threshold not provided in this segment)

ReferenceD-dimer age-adjusted cut-off is cited as an alternative to a fixed cut-off for excluding PE/DVT in appropriate outpatients.

Context of usePrefer highly sensitive assays and consider age-adjusted or clinical-probability–adapted cut-offs in low or intermediate clinical probability patients.

LimitationD-dimer is not recommended to rule out PE in patients with high clinical probability even when using highly sensitive assays.

Ordering Requirements and Preconditions

Billing Rule

Benefit verification required and timing conditions for plasma assays

Coverage is contingent on individual benefit verification at time of request; timing requirements include performing plasma assays at least six weeks after an acute event and while the patient is not on anticoagulants.

Confirm member coverage before submitting claims or prior authorization requests.
Adhere to the policy’s timing conditions for plasma assays to avoid claim denials.

Documentation Required

Limit orders to clinically actionable testing and avoid acute/anticoagulated state

Order testing only when results will change clinical management; avoid testing during acute thrombosis or while the patient is receiving anticoagulation, and consider specialist‑guided timing or post‑therapy testing strategies.

Many guidelines recommend waiting until after completion of initial therapy (commonly ≥3 months) before testing when indicated.

Background and Clinical Context

Thrombosis encompasses venous and arterial events including deep vein thrombosis (DVT) and pulmonary embolism (PE). Inherited thrombophilias—such as Factor V Leiden, prothrombin G20210A, and deficiencies of protein C, protein S, and antithrombin—contribute to VTE risk. The policy notes that VTE incidence is substantial and that the risk of recurrence is best predicted by whether an index event was provoked or unprovoked. It also emphasizes that thrombophilia testing performed during an acute clot or while on anticoagulation can produce spurious results because natural anticoagulants are consumed during acute events or affected by therapy.

Definitions and Terminology

inv-25: Selected terminology — VTE = Venous thromboembolism; DVT = Deep vein thrombosis; PE = Pulmonary embolism; FVL = Factor V Leiden; OC = Oral contraceptives; APS =...

VTEVenous thromboembolism

DVTDeep vein thrombosis

PEPulmonary embolism

FVLFactor V Leiden

OCOral contraceptives

APSAntiphospholipid syndrome

inv-26: Unprovoked VTE — Venous thromboembolism occurring without major transient risk factors such as surgery, trauma, immobility, or cancer; carries higher recu...

Policy Revision History

2023-07-01policy_effectiveLatest

Policy adopted effective date per Avalon policy recommendation.

OpenPayer

Venous and Arterial Thrombosis Risk Testing