title: Functional characterization of antibodies against heparin-platelet factor 4 complex in heparin-induced thrombocytopenia patients in Asian-Indians: relevance to inflammatory markers.
abstract: Occurrence of heparin-induced thrombocytopenia (HIT) was investigated for 33 Indian patients undergoing cardiovascular surgery who received unfractionated heparin (UFH). Platelet counts were performed prior to the initiation of UFH therapy and 5-16 days post therapy. Heparin-induced platelet aggregation, C-serotonin release assay, and enzyme-linked immmunosorbent assay (ELISA) tests were performed in all the patients to detect the antibodies formed against the complex of heparin and platelet factor 4 (HPF4). Levels of inflammatory markers/mediators such as CD40 ligand (CD40L) and C-reactive protein (CRP) were also measured in the patient plasmas utilizing ELISA tests. Based on clinical observations and laboratory diagnoses, five patients (15%) were considered to have confirmed HIT. Despite wide variations in the titers of inflammatory markers, patients who tested ELISA-positive for HPF4 antibodies showed markedly elevated levels of both soluble CD40L and C-reactive protein. Most strikingly, the C-serotonin release assay-positive patients showed up to a 10-fold increase in the level of CD40L. It is concluded that approximately 15% Asian-Indian patients receiving UFH during cardiovascular surgery develop functional HPF4 antibodies, which are associated with the increased levels of inflammatory markers/mediators in this catastrophic HIT syndrome.
authors.affiliation: All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
authors.forename: Meganathan
authors.initials: M
authors.lastname: Kannan
authors.forename: Sarfraz
authors.initials: S
authors.lastname: Ahmad
authors.forename: Firdos
authors.initials: F
authors.lastname: Ahmad
authors.forename: Shailaja
authors.initials: S
authors.lastname: Kale
authors.forename: Debra A
authors.initials: DA
authors.lastname: Hoppensteadt
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
authors.forename: Renu
authors.initials: R
authors.lastname: Saxena
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood* / Q000276:immunology; D000925:Anticoagulants / Q000009:adverse effects / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000276:immunology*; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology*
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D015415:Biomarkers; D023201:CD40 Ligand; D010978:Platelet Factor 4; D006493:Heparin; D002097:C-Reactive Protein