Heparin-PF4 Antibodies in Heparin Induced Thrombocytopenia: Its Relationship with FcgRIIa Polymorphism

Abstract

Abstract:We did the pilot study, in an attempt to determine the prevalence of HIT in Indians and determine its relationship, if any, to FcγRIIa polymorphism, the occurrence of heparin-induced thrombocytopenia (HIT) was investigated in 33 Indian patients undergoing cardiovascular surgery (CVS) who received unfractionated heparin (UFH). Platelet counts were performed prior to the initiation of UFH therapy and 5-16 days, post-therapy. The fall in patients' platelet count >35% of the baseline value or <100,000 µL 1 was considered to be suggestive of HIT syndrome. Heparin-induced platelet aggregation (HIPA), Enzyme Linked Immunosorbant assay (ELISA) and Serotonin Release Assay (SRA) tests were performed in all the patients to detect the antibodies formed against the heparin and platelet factor 4 complex (H-PF4). DNA analysis for FcγRIIa polymorphism was done by allele specific PCR. Thrombocytopenia was found to be present in 10 (30%) patients. Of these, 5 patients were found to be positive by HIPA, ELISA and SRA tests. These 5 patients were considered to have classic HIT syndrome. One of these patients had bleeding while the others were asymptomatic. One of the HIT positive patients was found to be homozygous for FcγRIIa His/ His polymorphism and others were heterozygous, had one defective allele with single amino acid change (Arg 131 His) at FcγRIIa platelet receptor. Frequency of occurrence of homozygous (FcγRIIa His/ His) and heterozygous (FcγRIIa Arg/ His ) polymorphism was higher in patients with HIT (100%) than in the normal population (68%). The prevalence of HIT in the pilot study (15%) was higher than that in the west (5%) but comparable to that from Japan (12%) (14). However, the Occurance of FcγRIIa polymorphism in Indian (68%) was higher than in the east (51%) and comparable to that in the west (78%). Thus it appears that the FcγRIIa polymorphism may have some relation to occurrence of HIT. Higher prevalence of FcγRIIa polymorphism in Indian may predispose to higher prevalence of HIT in India. Thus, it is recommended that, heparin-treated patients should be routinely tested for not only aPTT but also for platelet count, HPF4 antibodies and FcγRIIa polymorphism analysis. From the pilot study, it shows that absence of FcγRIIa receptor polymorphism may suggest low or negligible risk of development of HIT antibodies. However, further studies required with more patients using the same protocol.

An Update on the Prevalence and Characterization of H-PF4 Antibodies in Asian-Indian Patients

“…In our experience, of the 33 patients who underwent heparin therapy for cardiovascular surgery at our institution, 10 showed a drastic reduction in platelet count (thrombocytopenia), and all of them carried at least one defective allele with a single amino acid change (Arg 131 His) on the FcgRIIa platelet receptor. The occurrence of this polymorphism in Indians was observed to be higher than that observed in the East, for example, Japan (51%), but comparable with that observed in the West (78%) 17 (Fig. 1).…”

“…1 AIIMS, All India Institute of Medical Sciences. Data from Kannan et al 17 patients had at least one defective allele, it appears that the occurrence of FcgRIIa polymorphism may predispose cardiovascular surgery patients to develop immune-mediated HIT on heparin therapy.…”

“…Moreover, it is expected that the introduction of newer anti-Xa and anti-IIa Figure 4 Global prevalence of HIT. Data from Kannan et al, 17 King and Kelton, 36 Warkentin et al, 37 and Chua et al 38 H-PF4 ANTIBODIES IN ASIAN-INDIAN PATIENTS/KANNAN ET AL drugs in the near future might result in a reduction of the use of heparin for some indications. 30,31 As the newer anticoagulants are of synthetic origin, it is likely that these will generate H-PF4 antibodies.…”