Current evidence does not support genetic testing in several settings outside the specific covered indications listed in this policy. F5/F2 variant analysis (Factor V Leiden and Prothrombin 20210G>A) is not supported to confirm an inherited thrombophilia for indications such as fetal loss or adverse pregnancy outcomes; see the policy’s exclusions for full details. Similarly, VWF variant analysis is not supported to establish a diagnosis of von Willebrand disease for routine indications because standard laboratory and biochemical testing can achieve diagnosis. Providers should order genetic testing only when the member meets the defined clinical and laboratory criteria in the covered indications sections and should document the supporting clinical rationale and results of prior testing.

CDC guidance for diagnosis and management of von Willebrand disease recommends specific laboratory tests to aid diagnosis and does not include genetic testing as part of routine recommended laboratory testing. Genetic testing therefore is not considered a routine diagnostic step for VWD and should be reserved for situations consistent with the policy’s covered indications or when guided by specialist evaluation.

The following tests or test uses are considered not supported by current evidence for indications outside the policy’s defined criteria: F5/F2 variant analysis for non-specified indications including fetal loss or adverse pregnancy outcomes; F8/F9 variant analysis when clinical and laboratory criteria for hemophilia are not met; and VWF variant analysis for routine diagnosis of von Willebrand disease, since diagnosis can be achieved with standard laboratory and biochemical testing. Additionally, multigene panel analysis for Fanconi anemia is not supported for indications other than those tied to a positive or inconclusive chromosome breakage test with compatible clinical features.

Policy language previously labeled as 'Investigational' has been revised to state that 'current evidence does not support…' genetic testing for certain indications that fall outside the specific medical necessity criteria. This wording change clarifies that the tests are not routinely supported by available evidence rather than being judged investigational, and highlights the importance of applying the policy’s defined clinical and laboratory thresholds when ordering testing.

VWF variant analysis to confirm or establish a diagnosis of von Willebrand disease is not supported by current evidence for routine diagnostic purposes. Diagnosis of VWD can be achieved through standard laboratory and biochemical testing, and genetic sequencing of VWF should not be used as the primary diagnostic approach in typical cases.

Routine genetic testing is not included among the CDC-recommended laboratory tests for diagnosis of von Willebrand disease. As noted in CDC guidance, genetic testing is not part of the standard diagnostic panel for VWD and therefore may not be indicated in routine evaluation absent specific clinical justification.

Eligibility for testing is determined by the specific clinical and laboratory criteria listed for each condition. For F5/F2 variant analysis, eligibility requires a qualifying venous thromboembolism (VTE) presentation (e.g., VTE provoked by nonsurgical major transient risk factor, pregnancy/postpartum, or combined oral contraceptive use) and additional situational requirements such as planning to discontinue anticoagulation or specified personal or family VTE history. Documentation of the provoking factor, plans for anticoagulation management, and relevant family history is required.

For HBA1/HBA2 and/or HBB variant analysis, eligibility requires prior hematologic screening that is either positive for a hemoglobinopathy (examples: MCV, MCH, CBC, hemoglobin electrophoresis, DCIP) or is inconclusive such that molecular testing is needed to establish diagnosis or inform reproductive planning. Providers must document the hematologic screening results and any relevant family history, using the policy definition of close relatives when reporting familial findings.

Eligibility for F8/F9 variant analysis requires the presence of a compatible bleeding phenotype (examples include hemarthrosis, deep muscle hematomas, intracranial bleeding without major trauma, prolonged bleeding after procedures, heavy menstrual bleeding, recurrent significant epistaxis, excessive bruising) together with laboratory features such as normal platelet count, prolonged aPTT, and normal PT. These clinical and laboratory findings must be documented to support testing.

Eligibility for a Fanconi anemia multigene panel requires a positive or inconclusive chromosome breakage analysis in addition to at least one supportive clinical feature (for example: short stature, abnormal skin pigmentation, skeletal malformations such as hypoplastic thumb, microcephaly, genitourinary anomalies, macrocytosis, cytopenias, progressive bone marrow failure, early-onset malignancy, or unusual toxicities from chemo/radiation). Per FA guidance, genetic testing to identify causative variants should follow a positive chromosome breakage test to confirm diagnosis and support familial risk counseling.

This policy addresses genetic testing to diagnose or confirm benign hematologic disorders, including inherited thrombophilias (F5/F2), hemoglobinopathies (HBA1/HBA2, HBB), hemophilia A and B (F8/F9), von Willebrand disease (VWF), and Fanconi anemia. The policy defines condition-specific medical necessity criteria, clarifies prior testing requirements (such as hematologic screening or chromosome breakage testing), and notes that standard laboratory/biochemical testing can establish certain diagnoses without variant analysis. Providers should follow the condition-specific eligibility and documentation requirements when ordering genetic testing.