Testing for Heparin Induced Thrombocytopenia: Comparison of Practice at an Academic Center with Choosing Wisely Guidelines

Background: The American Society of Hematology Choosing Wisely Guidelines 2014 recommend against testing for treatment of Heparin Induced Thrombocytopenia (HIT) in individuals at low risk, defined by a 4T score ≤ 3.  Diagnosis of HIT relies on a combination of clinical characteristics and laboratory testing. The 4T score is a pretest probability score that defines clinical characteristics of HIT with reported negative predictive value of 99.8%.  A new scoring model, the HIT Expert Probability (HEP) score, was introduced in 2010 and postulated to reduce inter-observer variability.  The primary objective of this study was to examine compliance with guidelines at our institution; a 456 bed university hospital. Secondary objectives were to compare the performance of the 4T and HEP score in regards to inter-observer variability and the predictive value of low risk scores.

Methods: Local practice is initial testing with anti-PF4 antibody enzyme immunoassay (EIA), and subsequent reflex serotonin release assay (SRA) if the EIA is positive or indeterminate.  Consecutive patients with requests for HIT testing were identified from laboratory records.  With Research Ethics Board approval, retrospective chart review was conducted by 3 reviewers who independently applied 4T and HEP scores; discrepancies were resolved by consensus.  Adverse events including thrombosis, skin necrosis, heparin infusion reactions, bleeding (classified as major by ISTH criteria) and mortality were recorded. Inter-observer variability was assessed using the intraclass correlation (ICC).

Results: Between 2013 January 1 and 2015 Feb 21, 76 patients were referred for EIA testing.  Excluded from this analysis were 7 patients with prior history of HIT or with testing requested from an outside institution.  Of the remaining 69, median age was 67 years (range 24-90),  36 (56%) were male, 49 (71%) admitted with a medical diagnosis and 20 (29%) under a surgical service.  Hematology service was consulted at some point during admission in 25 (36%). Pretest probability was documented in 16 (23%). A greater percentage of patients with documented pre-test probability had a hematology consult 11 (69%) than patients without 5 (31%). Also, 36 (86%) patients without a documented pre-test probability were considered low risk by the 4T score.

Scoring system	Pre-test probability	Total N=69 (%)	EIA positive	SRA positive*
4T	Low (≤3)	42 (61)	9 (13)	1* (1)
	Intermediate (4-5)	25 (36)	10 (14)	4 (6)
	High (6-8)	2 (3)	2 (3)	1 (1)
HEP	Low (≤2)	35 (51)	7 (10)	1* (1)
	Intermediate (2-5)	20 (29)	17 (25)	1 (1)
	High (≥6)	14 (20)	7 (10)	4 (6)
* If SRA inconclusive, result confirmed with anti-PF4 IgG ** Admitted with ischemic leg requiring catheter directed thrombolysis.  Rapid onset thrombocytopenia within 24 hours of heparin exposure.  Prior heparin exposure 150 days prior.  Heparin stopped.  No alternative anti-coagulation.  No sequelae of HIT.

The ICC for the pre-test probability scores was 0.796 (95% CI  0.714- 0.860) for 4T and 0.742 (95% CI- 0.645-0.821) for HEP score.  By risk category, ICC for 4T score was 0.667 (95% CI  0.553 - 0.765) and HEP score was 0.702 (95% CI  0.553 - 0.765).  HIT testing was performed in patients classified as low risk; 42 (61%) according to 4T and 35 (45%) according to HEP score.  Among the 42 classified as low risk by 4T score, heparin was held in 26 (55) % pending results of testing and alternative anticoagulation commenced in 14 (33%) (fondaparinux 13, argatroban 1), at prophylactic dose in 12 and at therapeutic dose in 1 without a separate indication for anticoagulation.  One low risk patient suffered major bleeding and 2 had thrombotic events.  Overall, bleeding occurred in 10 (14%), major in 6 (9%), and thrombotic events occurred in 9 (13%).  One patient presenting with septic shock, who developed thrombocytopenia with 4T score of 4, received argatroban and died on the same day from intracranial hemorrhage.   All cause mortality during admission was 23 (33%).

Conclusion: Compliance with Choosing Wisely Guidelines at our institution is low, and potentially associated with unnecessary financial expenditure and patient harm due to over-testing and over-treatment. We did not observe benefit of the more complex HEP score over the 4T score.  Efforts are underway to increase awareness and align practice with recommendations.