The Impact of Human Platelet Antigen Allele on Antiplatelet Antibodies and Cryoglobulins in Patients With Primary Immune Thrombocytopenia and Hepatitis C Virus-Associated Immune Thrombocytopenia

Abstract

Background
 Human platelet antigens (HPAs) are alloantigens for antiplatelet alloantibodies and associated with the risk of immune thrombocytopenia (ITP). However, few studies have investigated associations among HPAs, antiplatelet autoantibodies, and cryoglobulins.
 Methods
 We enrolled 43 patients with primary ITP, 47 with hepatitis C virus-associated ITP (HCV-ITP), 21 with hepatitis B virus-associated ITP (HBV-ITP), 25 controls with HCV, and 1013 normal controls including HPA data of 998 Taiwanese blood donors. We analyzed HPA allele frequencies including HPA1-6 and 15, antiplatelet antibodies binding to platelet glycoprotein (GP) IIb/IIIa, Ia/IIa, Ib/IX, IV, human leukocyte antigen class I, cryoglobulin IgG/A/M, and their associations with thrombocytopenia.
 Results
 In the whole ITP cohort, HPA2ab predicted a low platelet count. HPA2b was associated with the risk of developing ITP, but not with anti-GPIb/IX antibodies. HPA15b was correlated with multiple antiplatelet antibodies. In the primary ITP patients, HPA3b was correlated with cryoglobulin IgG/A/M. In contrast, in the HCV-ITP patients, HPA3b was correlated with anti-GPIIb/IIIa antibodies, HCV-ITP patients with anti-GPIIb/IIIa antibodies had a higher positive rate of cryoglobulin IgG and IgA caomparred with those without anti-GPIIb/IIIa antibodies. Similar to the antiplatelet antibodies, cryoglobulins were associated with clinical thrombocytopenia, especially cryoglobulin IgA. Furthermore, cryoglobulins in the HCV-ITP patients showed characteristics to antiplatelet antibodies. 
 Conclusion
 HPA alleles were associated with antiplatelet autoantibodies but had different impacts in the patients with primary ITP and HCV-ITP. The pathophysiology and characteristics of antiplatelet antibodies were different between these two groups. HCV-ITP was considered to be a symptom of mixed cryoglobulinemia in the HCV patients.

Pattern and burden of thrombocytopenia in chronic hepatitis C virus patients at a tertiary care hospital

“…Antiviral therapy aimed at eradicating HCV can improve liver function and potentially lead to an improvement in platelet counts. Additionally, in cases where thrombocytopenia is severe, healthcare providers might consider interventions to increase platelet counts, such as platelet transfusions or medications that stimulate platelet production [15].…”