HIPA Test in HIT Diagnosis
The heparin-induced platelet activation (HIPA) test is a gold standard functional assay for confirming heparin-induced thrombocytopenia (HIT), offering high specificity when used in patients with intermediate-to-high clinical probability and positive immunoassays. 1, 2
Role and Position in Diagnostic Algorithm
HIPA serves as a confirmatory functional assay that distinguishes pathogenic from non-pathogenic anti-PF4/heparin antibodies, addressing the high false-positive rate of immunoassays. 1 The test works by detecting platelet-activating HIT antibodies using washed platelets from healthy donors, making it technically demanding but highly specific. 1
Diagnostic Workflow
First, calculate the 4Ts score to establish pre-test probability (0-3 points = low, 4-5 = intermediate, 6-8 = high probability). 2
Second, perform immunoassays (ELISA, CLIA, or LIA) as first-line screening tests due to their high sensitivity—a negative result effectively rules out HIT. 3, 2
Third, confirm positive immunoassays with functional testing like HIPA or serotonin release assay (SRA), particularly when clinical probability is intermediate or high. 3, 2
Performance Characteristics
HIPA demonstrates excellent specificity (approaching 100%) but requires careful interpretation. 4 The test is considered positive when 2 out of 4 donor platelets show activation within 30 minutes. 4, 5
HIPA shows 83.8% positive agreement and 66.7% negative agreement with SRA, the traditional gold standard. 5
The test performs particularly well in cardiac surgery patients who underwent cardiopulmonary bypass. 5
Using a minimum of 2 platelet donors establishes positive HIT diagnosis, while 4 donors are needed to reliably exclude HIT. 5
Advantages Over Other Functional Assays
HIPA offers practical advantages compared to SRA while maintaining comparable diagnostic accuracy. 5
Does not require radioactive materials (unlike SRA with ¹⁴C-serotonin), making it more accessible for widespread laboratory implementation. 5
Less technically complex than SRA, though still demanding compared to immunoassays. 1
Can be performed without specialized radiation safety protocols. 3, 5
Critical Limitations and Pitfalls
The major limitation is that HIPA, like all functional assays, is time-consuming, technically demanding, and unavailable in most hospital coagulation laboratories. 1
Requires fresh platelets from multiple healthy donors with known reactivity. 3
Results are not available in real-time, limiting immediate clinical utility. 3
The test cannot be used to rule out HIT when negative—it confirms HIT when positive but lacks sufficient sensitivity for exclusion. 4
Clinical Context for Use
HIPA should be reserved for confirming HIT in patients with positive immunoassays and intermediate-to-high clinical probability. 2
In low probability patients (4Ts score 0-3), 85% have negative functional tests, making HIPA unnecessary. 6
In high probability patients (4Ts score 6-8), 22.2% are truly HIT-positive by functional testing. 6
The specificity of HIPA is high only when used in clinically suggestive contexts—it should complement, not replace, clinical assessment. 6
Emerging Alternatives
Flow cytometry-based assays detecting antibody-induced procoagulant platelet formation represent an emerging alternative that may become more accessible in clinical laboratories, though standardized protocols are still being developed. 1