UnitedHealthcare® Medicare Advantage Policy Guideline Blood Product Molecular Antigen Typing Guideline Number: MPG388.01 Approval Date: February 10, 2021 Terms and Conditions Table of Contents Page Related Medicare Advantage Policy Guidelines Policy Summary ............................................................................. 1 • Clinical Diagnostic Laboratory Services Applicable Codes .......................................................................... 2 • Molecular Pathology/Molecular References ..................................................................................... 7 Diagnostics/Genetic Testing Guideline History/Revision Information ....................................... 8 Purpose .......................................................................................... 9 Related Medicare Advantage Coverage Summaries Terms and Conditions ................................................................... 9 • Genetic Testing • Laboratory Tests and Services Policy Summary See Purpose Overview Based on the Centers for Medicare & Medicaid Services (CMS) Program Integrity Manual (100-08), this policy addresses the circumstances under which the item or service is reasonable and necessary under the Social Security Act, §1862(a)(1)(A). For laboratory services, a service can be reasonable and necessary if the service is safe and effective; and appropriate, including the duration and frequency that is considered appropriate for the item or service, in terms of whether it is furnished in accordance with accepted standards of medical practice for the diagnosis of the patient's condition; furnished in a setting appropriate to the patient's medical needs and condition; ordered and furnished by qualified personnel; one that meets, but does not exceed, the patient's medical need; and is at least as beneficial as an existing and available medically appropriate alternative. Compliance with the provisions in this policy is subject to monitoring by post payment data analysis and subsequent medical review. Title XVIII of the Social Security Act, Section 1862(a)(1)(A) states " ...no Medicare payment shall be made for items or services which are not reasonable and necessary for the diagnosis and treatment of illness or injury...". Furthermore, it has been longstanding CMS policy that "tests that are performed in the absence of signs, symptoms, complaints, or personal history of disease or injury are not covered unless explicitly authorized by statute". Screening services, such as pre - symptomatic genetic tests and services, are those used to detect an undiagnosed disease or disease predisposition, and as such are not a Medicare benefit and not covered by Medicare. Similarly, Medicare may not reimburse the costs of tests/examinations that assess the risk for and/or of a condition unless the risk assessment clearly and directly effects the management of the patient. Guidelines Limited coverage is provided for molecular phenotyping of blood product antigens as part of the pre-transfusion evaluation for patients who may require or are expected to require a blood product transfusion(s) (Red Blood Cells, Platelets or Leukocytes) when at least one of the following criteria is met: Long term, frequent transfusions anticipated to prevent the development of alloantibodies (e.g., sickle cell anemia, thalassemia, chronic transfusion dependent hematologic disorders or other reasons); or Autoantibodies or other serologic reactivity that impedes the exclusion of clinically significant alloantibodies (e.g., autoimmune hemolytic anemia, warm autoantibodies, patient recently transfused with a positive DAT, high-titer low avidity antibodies, patients about to receive or on daratumumab therapy, other reactivity of no apparent cause); or Blood Product Molecular Antigen Typing Page 1 of 9 UnitedHealthcare Medicare Advantage Policy Guideline Approved 02/10/2021 Proprietary Information of UnitedHealthcare. Copyright 2021 United HealthCare Services, Inc. Suspected antibody against an antigen for which typing sera is not available; or Laboratory discrepancies on serologic typing (e.g., rare Rh D antigen variants) Laboratory developed tests (LDTs) that perform molecular phenotyping of blood product antigens may be considered covered for the same indications if the test demonstrates validity and clinical utility equivalent to or better than covered tests as demonstrated in a technical assessment. Medicare does not expect molecular testing to be performed on patients undergoing surgical procedures such as bypass or other cardiac procedures, hip or knee replacements or revisions, or patients with alloantibodies identifiable by serologic testing that are not expected to require long term, frequent transfusions. The medical necessity for molecular blood product phenotyping must be documented in the patient’s medical record. Blood product molecular antigen typing tests are considered germline tests and thus must comply with relevant Medicare or Contractor policies regarding germline testing. As molecular genotyping includes a review of many genes that code for cellular antigens that must be evaluated for proper patient care, single gene tests are not reasonable and necessary. Applicable Codes The following list(s) of procedure and/or diagnosis codes is provided for reference purposes only and may not be all inclusive. Listing of a code in this guideline does not imply that the service described by the code is a covered or non-covered health service. Benefit coverage for health services is determined by the member specific benefit plan document and applicable laws that may require coverage for a specific service. The inclusion of a code does not imply any right to reimbursement or guarantee claim payment. Other Policies and Guidelines may apply. CPT Code Description 81403 Molecular pathology procedure, level 4 (eg, analysis of single exon by DNA sequence analysis, analysis of >10 amplicons using multiplex PCR in 2 or more independent reactions, mutation scanning or duplication/deletion variants of 2-5 exons) (See the Medicare Advantage Policy Guideline Titled Tier 2 Molecular Pathology Procedures) 0001U Red blood cell antigen typing, DNA, human erythrocyte antigen gene analysis of 35 antigens from 11 blood groups, utilizing whole blood, common RBC alleles reported 0084U Red blood cell antigen typing, DNA, genotyping of 10 blood groups with phenotype prediction of 37 red blood cell antigens Non-covered 81105 Human Platelet Antigen 1 genotyping (HPA-1), ITGB3 (integrin, beta 3 [platelet glycoprotein IIIa], antigen CD61 [GPIIIa]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant, HPA-1a/b (L33P) 81106 Human Platelet Antigen 2 genotyping (HPA-2), GP1BA (glycoprotein Ib [platelet], alpha polypeptide [GPIba]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant, HPA-2a/b (T145M) 81107 Human Platelet Antigen 3 genotyping (HPA-3), ITGA2B (integrin, alpha 2b [platelet glycoprotein IIb of IIb/IIIa complex], antigen CD41 [GPIIb]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post- transfusion purpura), gene analysis, common variant, HPA-3a/b (I843S) 81108 Human Platelet Antigen 4 genotyping (HPA-4), ITGB3 (integrin, beta 3 [platelet glycoprotein IIIa], antigen CD61 [GPIIIa]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant, HPA-4a/b (R143Q) 81109 Human Platelet Antigen 5 genotyping (HPA-5), ITGA2 (integrin, alpha 2 [CD49B, alpha 2 subunit of VLA- 2 receptor] [GPIa]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant (eg, HPA-5a/b (K505E)) Blood Product Molecular Antigen Typing Page 2 of 9 UnitedHealthcare Medicare Advantage Policy Guideline Approved 02/10/2021 Proprietary Information of UnitedHealthcare. Copyright 2021 United HealthCare Services, Inc. CPT Code Description Non-covered 81110 Human Platelet Antigen 6 genotyping (HPA-6w), ITGB3 (integrin, beta 3 [platelet glycoprotein IIIa, antigen CD61] [GPIIIa]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant, HPA-6a/b (R489Q) 81111 Human Platelet Antigen 9 genotyping (HPA-9w), ITGA2B (integrin, alpha 2b [platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41] [GPIIb]) (eg, neonatal alloimmune thrombocytopenia [NAIT], post- transfusion purpura), gene analysis, common variant, HPA-9a/b (V837M) 81112 Human Platelet Antigen 15 genotyping (HPA-15), CD109 (CD109 molecule) (eg, neonatal alloimmune thrombocytopenia [NAIT], post-transfusion purpura), gene analysis, common variant, HPA-15a/b (S682Y) 0180U Red cell antigen (ABO blood group) genotyping (ABO), gene analysis Sanger/chain termination/conventional sequencing, ABO (ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase) gene, including subtyping, 7 exons 0181U Red cell antigen (Colton blood group) genotyping (CO), gene analysis, AQP1 (aquaporin 1 [Colton blood group]) exon 1 0182U Red cell antigen (Cromer blood group) genotyping (CROM), gene analysis, CD55 (CD55 molecule [Cromer blood group]) exons 1-10 0183U Red cell antigen (Diego blood group) genotyping (DI), gene analysis, SLC4A1 (solute carrier family 4 member 1 [Diego blood group]) exon 19 0184U Red cell antigen (Dombrock blood group) genotyping (DO), gene analysis, ART4 (ADP-ribosyltransferase 4 [Dombrock blood group]) exon 2 0185U Red cell antigen (H blood group) genotyping (FUT1),