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Human Platelet Antigens
Platelet-specific antigens associated with the formation of alloantibodies in exposed patients are the basis for human platelet antigen (HPA) categorization. Over the years, these antigenic determinants have been mapped to a relatively short list of platelet-expressed adhesion/aggregation molecules, namely GPIa, GPIb, and GPIIb/IIIa.
Antigens
Table 31.1 lists current nomenclature for the various HPA groups with their associated other names, the major protein within which the antigenic epitope resides, and relative frequencies in the white population. HLA Class I and A/B/H group antigens are also found on the platelet surface. For the latest allelic frequency information, the Immuno Polymorphism Database section on HPA can be queried at http://www.ebi.ac.uk/ipd/hpa/ .
Table 31.1
Human Platelet Antigen Table
Modified from Metcalfe, P, Watkins, N. A, Ouwehand, W. H., Kaplan, C., Newman, P., Kekomaki, R., et al. (2003). Nomenclature of human platelet antigens. Vox Sang, 85 (3), 240–245; Allen et al., 2005; https://www.ebi.ac.uk/ipd/hpa/table1.html .
| System | Antigen | Other Names | Glycoprotein | Antigen Frequency (%) |
|---|---|---|---|---|
| HPA-1 | HPA-1a HPA-1b |
Zw a , Pl A1 Zw b , Pl A2 |
GPIIIa (CD61) | 97.9 28.8 |
| HPA-2 | HPA-2a HPA-2b |
Ko b Ko a , Sib a |
GPIbα (CD42b) | >99.9 13.2 |
| HPA-3 | HPA-3a HPA-3b |
Bak a , Lek a Bak b |
GPIIb (CD41) | 80.95 69.8 |
| HPA-4 | HPA-4a HPA-4b |
Yuk b , Pen a Yuk a , Pen b |
GPIIIa (CD61) | >99.9 <0.1 |
| HPA-5 | HPA-5a HPA-5b HPA-6bw HPA-7bw HPA-8bw HPA-9bw HPA-10bw HPA-11bw HPA-12bw HPA-13bw HPA-14bw |
Br b , Zav b Br a , Zav a , Hc a Ca a , Tu a Mo a Sr a Max a La a Gro a ly a Sit a Oe a |
GPIa (CD49b)
GPIIIa (CD61) |
99.0 19.7 0.7 0.2 <0.01 0.6 <1.6 <0.25 0.4 0.25 <0.17 |
| HPA-15 | HPA-15a HPA-15b HPA-16bw HPA-17bw HPA-18bw HPA-19bw HPA-20bw HPA-21bw HPA-22bw HPA-23bw HPA-24bw HPA-25bw HPA-26bw HPA-27bw HPA-28bw HPA-29bw |
Gov b Gov a Duv a Va a Cab a Sta Kno Nos Sey Hug Cab2 a+ Swi a Sec a Cab3 a+ War Kha b |
CD109 (CD109)
GPIIIa (CD61) |
74 81 <1 <0.4 Case report Case report Case report Case report Case report Case report Case report (<1) Case report Case report Case report (<1) Case report Case report |
| Pl T Vis Pe a Dy a Mou a Lap a |
GPV GPIV GPIbα (CD42b) 38 kDa GP Unknown GPIIb (CD41) |
>99.9
26 |
Mode of Inheritance
Of the 35 HPAs, 12 have been categorized into six biallelic groups (HPA-1, 2, 3, 4, 5, 15). Designated “a” antigen of the pair is typically the high-frequency antigen, whereas “b” antigen is the low-frequency antigen. The remaining 23 HPAs do not appear to correspond to a pair of alleles and are all designated as “b” antigens due to their low population frequency. It is hypothesized that due to the very low frequency of the “b” antigen that the probability of having a “bb” homozygote would be exceedingly rare and therefore no antibodies against a hypothetical corresponding “a” antigen have been clinically documented.
Molecular Basis of Type
The majority of HPAs reside on platelet-specific adhesion/aggregation molecules, which include GPIIb, GPIIIa, GPIa, GPIbα, GPIbβ, GPIV, GPV, and CD109. Originally, typing was performed with patient-derived antisera; however, an important limitation is that patients often have additional antibodies against Class I HLA antigens and therefore the sera was not monospecific and contaminated with anti-HLA antibodies. Once the molecular determinants for HPA type were discovered to be due to amino acid substitutions at specific points, the application of molecular methods to perform typing using DNA-based techniques became the “gold standard.”
Disease Associations
Alloantibody formation against HPA antigens is associated with several forms of thrombocytopenia, specifically neonatal alloimmune thrombocytopenia (NAIT), posttransfusion purpura (PTP), and platelet transfusion refractoriness (see Chapter 94, Chapter 69, Chapter 57 , respectively).
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