Abstract

Abstract 3336

Introduction:

Heparin Induced thrombocytopenia (HIT) is a clinicopathological entity in which thrombocytopenia occurs in temporal relation to the initiation of heparin therapy. The diagnosis is made using clinical criteria and a scoring system (4T) can be applied to assess the probability of the diagnosis. A variety of sensitive tests are available but the most widely applied is an enzyme immunoassay (EIA), which detects and semi-quantifies antibodies of any class to the heparin-PF4 complex. The role of testing is largely supplementary, but recently focus has been placed on the epidemic of HIT overdiagnosis due to overreliance on laboratory tests irrespective of the clinical scenario. A newer EIA can measure the pathogenic IgG antibody only. This study examines the number of patients started on direct thrombin inhibitor (DTI) therapy for a presumptive diagnosis of HIT prior to the implementation of the IgG antibody and after its introduction at one large academic tertiary care center.

Methods:

All patients placed on the DTIs argatroban and lepirudin between October 2006-May 2009 in the pre IgG subtype antibody period and May 2009-February 2012 in the post IgG subtype period for a presumptive diagnosis of HIT were identified. Demographic data including age, sex, and primary service were recorded. All HIT antibody (Ab) immunoglobulin class EIA and IgG specific EIA optical density were recorded, as available. 4T criteria and rates of thrombosis were assessed retrospectively. Incidence of WHO Grade III (requiring transfusion) or IV (life threatening) bleeding was documented. Chi Square, Mann Whitney U, and Fisher's exact tests were used as appropriate for statistical analysis.

Results:

89 patients pre availability of the IgG EIA assay and 100 patients post availability of the IgG EIA assay met inclusion criteria and were evaluated. Groups were matched in terms of sex and 4T pretest probability distribution as well as rates of thrombosis. Patients post IgG EIA availability were older and had lower mean total HIT Ab optical densities. Post IgG EIA patients were treated with DTI therapy 5 days less, which was statistically significant. The incidence of Grade III and IV bleeding episodes, however, was statistically similar between groups. In the pre IgG EIA group, 7 bleeds (4 Grade III, 3 Grade IV) occurred in patients with low pretest probability for HIT based on 4T criteria. In the post IgG EIA group, 8 bleeds (5 Grade III, 3 Grade IV) occurred in patients with low pretest probability for HIT based on 4T criteria.

Table 1.

Comparison between demographic and clinical outcome data derived from patients treated with DTI therapy for presumed HIT prior to IgG EIA availability and post IgG EIA availability

Pre IgG EIA (N=89)Post IgG EIA (N=100)P value
Median Age (Range) 60.5 (18–91) 67 (25–98) 0.03 
M:F 46:43 54:46 0.75 
4T Pretest Probability    
Low 34 46 0.28 
Intermediate 44 40 0.19 
High 11 14 0.74 
Median Total Antibody Optical Density 0.62 0.49 0.02 
Median Days on Direct Thrombin Inhibitors (DTIs) <0.0001 
Grade III/IV Episodes of Bleeding 20 22 0.92 
Grade III 12 17 0.50 
Grade IV 0.28 
Episodes of Thrombosis 16 17 
Pre IgG EIA (N=89)Post IgG EIA (N=100)P value
Median Age (Range) 60.5 (18–91) 67 (25–98) 0.03 
M:F 46:43 54:46 0.75 
4T Pretest Probability    
Low 34 46 0.28 
Intermediate 44 40 0.19 
High 11 14 0.74 
Median Total Antibody Optical Density 0.62 0.49 0.02 
Median Days on Direct Thrombin Inhibitors (DTIs) <0.0001 
Grade III/IV Episodes of Bleeding 20 22 0.92 
Grade III 12 17 0.50 
Grade IV 0.28 
Episodes of Thrombosis 16 17 
Conclusion:

Implementation of the IgG HIT EIA resulted in a decrease in the number of days on a DTI without an observed change in serious bleeding events, indicating that such bleeding occurs early after initiation of DTI therapy. Further, patients pre and post availability of the IgG EIA were started on DTI therapy despite a low pretest clinical risk for HIT. The use of a test with a shorter turn-around time to exclude HIT or more rigorous enforcement of clinical guidelines will be required to minimize misdiagnosis and avoid therapy related morbidity.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.