CPT® Code 81108

Official Description

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)

Common Language Description

The CPT® Code 81108 refers to the gene analysis for Human Platelet Antigen 4 (HPA-4) genotyping, specifically targeting the ITGB3 gene, which encodes the integrin beta 3 protein, also known as platelet glycoprotein IIIa (CD61). This analysis is particularly relevant in the context of conditions such as neonatal alloimmune thrombocytopenia (NAIT) and post-transfusion purpura, both of which are associated with platelet alloantigens. The test focuses on identifying common variants of the HPA-4 allele, specifically the HPA-4a/b variant characterized by the R143Q single nucleotide polymorphism (SNP). Gene analysis is crucial for diagnosing and managing these conditions, as it helps in identifying specific HPA-4 variants that may lead to complications in neonates or during transfusions. NAIT occurs when maternal antibodies, specifically IgG, cross the placenta and target paternal alloantigens present on the fetal platelets, leading to severe thrombocytopenia and potential hemorrhagic complications. Symptoms of NAIT can manifest as severe low platelet counts, intracranial hemorrhage, and skin manifestations such as petechiae or purpura. On the other hand, post-transfusion purpura arises when a woman receives a platelet transfusion that contains incompatible HPA or platelet-specific antigens, resulting in a severe bleeding episode typically occurring 5 to 10 days post-transfusion. The identification of HPA-4 a/b allele variants is particularly significant, as studies indicate that these variants are present in approximately 80% of NAIT cases within the Asian population. The samples for this analysis can be obtained from blood, amniotic fluid, or cultured amniocytes, and the testing is performed using multiplex polymerase chain reaction (PCR) techniques, which involve allele-specific primer extensions and fluorescence detection to accurately identify the genetic variants present.

1. Indications

The Human Platelet Antigen 4 genotyping (HPA-4) test is indicated for several specific clinical scenarios, particularly related to conditions that affect platelet function and immune response. The following indications are explicitly provided:

Neonatal Alloimmune Thrombocytopenia (NAIT) - This condition occurs when maternal IgG antibodies cross the placenta and attack paternally derived alloantigens on fetal platelets, leading to severe thrombocytopenia and potential complications such as intracranial hemorrhage.
Post-Transfusion Purpura - This condition is characterized by severe bleeding that occurs 5 to 10 days after a platelet transfusion containing incompatible HPA or platelet-specific antigens, necessitating the identification of HPA-4 variants to assess risk.
Fetal Alloimmunization Screening - The test may be used to screen for fetal alloimmunization during pregnancy, helping to identify at-risk pregnancies where maternal antibodies may affect fetal platelet levels.
Maternal Risk Assessment - The analysis can assist in assessing the risk for NAIT in future pregnancies or the likelihood of post-transfusion purpura in women who have previously experienced these conditions.

2. Procedure

The procedure for Human Platelet Antigen 4 genotyping involves several key steps to ensure accurate identification of the HPA-4a/b allele variants. The following procedural steps are outlined:

Sample Collection - Blood, amniotic fluid, or cultured amniocytes are collected as the source material for genetic analysis. Each sample type is obtained through a separate reportable procedure, ensuring that the correct specimen is used for testing.
DNA Extraction - Once the samples are collected, DNA is extracted from the cells present in the blood, amniotic fluid, or cultured amniocytes. This step is crucial for isolating the genetic material needed for analysis.
Multiplex Polymerase Chain Reaction (PCR) - The extracted DNA undergoes multiplex PCR, a technique that allows for the simultaneous amplification of multiple target DNA sequences. This method utilizes allele-specific primer extensions to selectively amplify the regions of interest related to the HPA-4 gene.
Fluorescence Observation - Following amplification, fluorescence detection is employed to observe the results of the PCR. This step enables the identification of specific allele variants present in the sample, confirming the presence of HPA-4a/b variants.

3. Post-Procedure

After the completion of the HPA-4 genotyping procedure, the following post-procedure considerations are important:

Results from the gene analysis will be interpreted by qualified healthcare professionals, who will assess the presence of HPA-4 variants and their implications for the patient. In cases where HPA-4 variants are identified, further clinical management may be necessary, particularly for pregnant women or those with a history of NAIT or post-transfusion purpura. Patients may require additional monitoring or interventions based on the findings of the test. It is also essential to provide appropriate counseling to patients regarding the implications of the results for future pregnancies or transfusion needs. Overall, the post-procedure phase is critical for ensuring that the results are utilized effectively in clinical decision-making and patient care.

Short Descr	HPA-4 GENOTYPING
Medium Descr	HPA-4 GENOTYPING GENE ANALYSIS COMMON VARIANT
Long Descr	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)
Status Code	Statutory Exclusion (from MPFS, may be paid under other methodologies)
Global Days	XXX - Global Concept Does Not Apply
PC/TC Indicator (26, TC)	9 - Not Applicable
Multiple Procedures (51)	9 - Concept does not apply.
Bilateral Surgery (50)	9 - Concept does not apply.
Physician Supervisions	09 - Concept does not apply.
Assistant Surgeon (80, 82)	9 - Concept does not apply.
Co-Surgeons (62)	9 - Concept does not apply.
Team Surgery (66)	9 - Concept does not apply.
Diagnostic Imaging Family	99 - Concept Does Not Apply
CLIA Waived (QW)	No
APC Status Indicator	Service Paid under Fee Schedule or Payment System other than OPPS
Type of Service (TOS)	5 - Diagnostic Laboratory
Berenson-Eggers TOS (BETOS)	none
MUE	1

90	Reference (outside) laboratory: when laboratory procedures are performed by a party other than the treating or reporting physician or other qualified health care professional, the procedure may be identified by adding modifier 90 to the usual procedure number.
GW	Service not related to the hospice patient's terminal condition