Clinical evaluation of acute systemic reaction and detection of IgG antibodies against PF4/heparin complexes in hemodialysis patients

Abstract

Heparin-induced thrombocytopenia (HIT) is a pathophysiological syndrome caused by platelet-activating antibodies that recognize PF4/heparin complexes. The abrupt onset of HIT following intravenous bolus heparin is known as an acute systemic reaction. Clinical features of this type of HIT may be similar to those of common complications during hemodialysis. The aim of the study was to identify whether the clinical features of the acute systemic reaction are caused by HIT or dialytic complications. Twenty-seven dialytic patients who had thrombocytopenia and clinical features of an acute systemic reaction were enrolled out of 202 HIT-suspected patients. Thirteen patients had HIT confirmed due to the presence of positive functional and immunoassays. Eight of the thirteen patients presented with acute systemic reactions due to HIT. The most common symptom of acute systemic reaction was dyspnea. The other nineteen patients, involving both HIT and non-HIT patients, had dialysis-complicated ASR. The major feature of the acute systemic reaction in hemodialysis was hypotension and its relevant symptoms. An immunoassay for the detection of IgG antibodies against PF4/heparin complexes (HIT-IgG) showed the wide-range linearity of the calibration curve by employing three concentrations of recombinant mouse monoclonal antibodies for PF4/heparin complexes. The results are expressed as micrograms of IgG in one milliliter. Significantly high levels in thirteen HIT patients were compared with levels in fourteen non-HIT patients. The highest median of 1,530μg/ml (IQR: 3,267-813) was obtained in the presence of HIT associated with an acute systemic reaction. In HIT patients who did not show characteristics of an HIT-derived acute systemic reaction, the median was 339μg/ml (1,178-834). Despite showing a positive ELISA, nine non-HIT patients without any platelet-activating antibodies showed a value of 97μg/ml (166–56). The lowest median of 8.3μg/ml (11–6) was in non-HIT patients with a negative ELISA. In conclusion, measurements of HIT-IgG -specific antibodies can facilitate an appropriate estimation in hemodialysis patients of whether the clinical features of an acute systemic reaction are caused by HIT or dialytic complications.