Utility of ELISA optical density values and clinical scores for the diagnosis of and thrombosis prediction in heparin-induced thrombocytopenia

Abstract

Background: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction caused by antibodies to the heparin/platelet factor 4 (PF4) complex, resulting in thrombocytopenia and prothrombotic state. HIT diagnosis is challenging and depends on clinical presentation and laboratory tests. We investigated the usefulness of clinical scores and heparin/PF4 ELISA optical density (OD) as a diagnostic marker and thrombosis predictor in HIT.

Methods: We analyzed 92 patients with suspected HIT. The heparin/PF4 antibody was measured using a commercial ELISA kit (GTI, USA). For each patient, the 4 T's score and Chong's score were calculated.

Results: Of the 92 patients, 28 were anti-heparin/PF4-seropositive. The 4 T's score and Chong's score showed good correlation (r=0.874). The 4 T's score and OD values showed good performance for diagnosis of the definite and unlikely HIT groups; however, OD levels showed better sensitivity (93.8%) than the 4 T's score used alone (62.5%). Of the 92 patients, 26 developed thrombosis. The OD values were significantly higher in patients with thrombosis than in those without thrombosis (0.52 vs. 0.22, P<0.001). Patients with high OD values (OD>0.4) had an increased risk of thrombosis (adjusted odds ratio 9.44 [3.35-26.6], P<0.001) and a shorter 250-day thrombosis-free survival (32.1% vs. 54.7%, P=0.012).

Conclusions: ELISA OD values in combination with clinical scoring can improve the diagnosis of and thrombosis prediction in HIT. More attention should be paid to the use of clinical scores and OD values as thrombosis predictors in HIT.

Fig. 1

Optical density (OD) values according to (A) the 4 T's and (B) Chong's scoring system. Bars represent median OD level. Uppermost P values were calculated using the Kruskal-Wallis test, and pairwise comparisons were performed using the Dunn test.

Fig. 2

Frequency of thromboembolic complications according to heparin/PF4 ELISA optical density (OD) level increment. The numbers on each bar indicate the number of patients.

Fig. 3

ROC curve relating heparin/PF4 ELISA (A) optical density (OD) value and (B) 4 T's scores to occurrence of thromboembolic complication. (A) When the OD cut-off is 0.427, the sensitivity is 65.4%, and the specificity is 88.4%. (B) When the 4 T's score is greater than or equal to 4, the sensitivity is 69.2%, and the specificity is 84.8%. Abbreviation: AUC, area under curve.

Fig. 4

Thrombosis-free survival for patients who underwent heparin/PF4 ELISA for detecting the presence of the heparin/PF4 antibody based on the optical density (OD) cut-off of 0.4 (A) and 1.0 (B).