Investigations
1st investigations to order
FBC
Test
The timing of the fall in platelet count (beginning from the first day of heparin exposure [day 0]) is key. An example would be a patient who experiences a 50% drop in platelet count with a nadir ≥20 × 10⁹/L (>20 × 10³/microlitre) between days 5 and 10 of heparin exposure.
The platelet count does not have to fall below 150 × 10⁹/L (150 × 10³/microlitre) for HIT to be considered (e.g., 50% or more decrease from baseline during the correct time frame is still suspicious for HIT, even if the absolute platelet nadir is >150 × 10⁹/L [>150 × 10³/microlitre]).
It is not uncommon for the platelet count to initially fall after surgery and then rise to a level higher than the preoperative count (rebound thrombocytosis). In such cases, the postoperative rebound platelet count should be considered the new baseline count in these patients when determining the clinical probability of HIT. Thrombocytopenia in the context of pancytopenia reduces the likelihood of HIT.
Result
falling platelet count
Investigations to consider
4Ts score
Test
The 4Ts score is commonly used to predict the clinical probability of HIT.[36][37]
The 4Ts score has been subject to greater evaluation than other tools, and is recommended by the American Society of Hematology:[36][37][38][39][40]
Points from 0-2 are given for 4 categories: magnitude of Thrombocytopenia, Timing of onset of platelet fall (or other sequelae of HIT), Thrombosis, and oTher explanation for the platelet fall.
Pre-test probability of HIT: a low score (0-3) indicates <1% probability of HIT; an intermediate score (4-5) indicates approximately 10% probability of HIT; and a high score (6-8) indicates approximately 50% probability of HIT.
The HIT expert probability (HEP) score is an alternative scale.[41]
Result
score of 6-8 indicates high clinical suspicion for HIT; score of 4-5 indicates intermediate clinical suspicion for HIT; score of 0-3 indicates low clinical suspicion for HIT
HIT antigen assay
Test
Antigen assays (e.g., anti-platelet factor 4 [PF4]/H enzyme-linked immunosorbent assay [ELISA], H/PF4-PaGIA) are available at most clinical centres. Antigen assays are highly sensitive (>99%), but they have a high false-positive rate. False positives result from detection of all types of HIT antibodies, regardless of their ability to activate platelets.[46] For example, up to 50% of cardiovascular surgery patients will develop HIT antibodies, but only 2% of those patients will develop HIT.[11] ELISAs that detect IgG antibodies only are more specific for HIT and the higher the titre of the antigen assay, the higher the likelihood the patient has platelet-activating antibodies (i.e., the greater the likelihood the patient has HIT or improved specificity).[36] Some rapid immunoassays that can provide results in less than 30 minutes appear to have similar diagnostic properties to the ELISAs.[45][47]
Patients with at least an intermediate clinical suspicion for HIT (i.e., 4Ts score ≥4) should undergo laboratory testing for HIT antibodies.[38] A low 4Ts score (i.e., ≤3) alone has high negative predictive value; guidelines recommend against laboratory testing in these patients.[38][43][44] If, however, there is uncertainty about the score (e.g., multiple missing platelet counts, history of recent heparin exposure is unclear, concurrent potential causes of thrombocytopenia), testing for HIT should be considered.[38][45]
Result
positive for HIT antibodies (with high titre value)
HIT functional assay
Test
Functional assays (e.g., serotonin release assay, heparin-induced platelet activation) are limited to a small number of clinical centres, but have better specificity than the antigen assays. Functional assays detect antibodies based on their platelet‐activating properties (i.e., antibodies that are more likely to be clinically significant).[48] These assays have high sensitivity (>95%) and specificity (>95%) for HIT; therefore, in the context of a compatible clinical picture, a positive result confirms HIT and a negative result excludes HIT.[10][49]
As many centres do not have access to functional assays, diagnosis is often based on clinical suspicion for HIT (based on the 4Ts score) combined with antigen assay results.[50]
Result
positive result confirms HIT; negative result excludes HIT (in the context of a compatible clinical picture)
coagulation studies
Test
INR and aPTT should be ordered in patients with suspected HIT to exclude coagulopathy.
HIT may induce disseminated intravascular coagulation in 10% to 20% of patients; therefore, coagulopathy and low fibrinogen levels do not exclude HIT if the clinical scenario is otherwise consistent.[42]
Result
may be normal or abnormal
venous Doppler ultrasound
Test
Should be ordered in all patients with suspected deep vein thrombosis (DVT).
New DVT (incompressible venous segment) or extension of a recent DVT (incompressible venous segment previously fully compressible) increases the likelihood of HIT.[51]
Thrombosis has been reported in up to 50% of patients with untreated HIT.[55]
In the context of confirmed HIT, the presence of a DVT may lengthen the duration of treatment.
Other tests may be appropriate depending on the thrombosis.
Result
inability to fully compress lumen of vein using ultrasound transducer
computed tomography pulmonary angiogram (CTPA)
Test
Should be performed in patients with suspected pulmonary embolism.[51]
Result
intraluminal filling defect seen on at least 2 views
ventilation-perfusion scan (V/Q scan)
Test
Should be performed in patients with suspected pulmonary embolism.[51]
An alternative to computed tomography pulmonary angiogram (CTPA). V/Q scan is a radiation- and medium-sparing procedure and may be appropriate for patients with contraindications or relative contraindications to CT (e.g., contrast allergy, moderate to severe renal failure, pregnancy, young patients).[56]
Result
multiple segmental defects seen with normal ventilation (high probability)
cerebral computed tomography venogram
Test
Should be performed in patients with suspected cerebral venous thrombosis.[51]
Result
intraluminal filling defect seen on at least 2 views
magnetic resonance venography (head)
Test
Should be performed in patients with suspected cerebral venous thrombosis.[51]
Result
flow defect and/or intense signal within cerebral veins or dural sinuses
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