Case Presentation: The patient is a 66-year-old female with a past medical history of asthma-COPD overlap (ACO) with recent exacerbation who presented with sudden-onset severe dyspnea. Patient was intubated for ACO exacerbation three weeks prior to admission and was started on heparin for deep vein thrombosis prophylaxis with platelet at 293, 000/microliter. At the rehabilitation facility, her platelet was steadily decreasing to a nadir of 38, 000/microliter with associated lower limb extremity swelling. Heparin was then discontinued. On the day of admission, she suddenly developed dyspnea, shortness of breath, and desaturation to 80% on ambient air. She was brought to the emergency department, and the patient was tachycardic at 117 beats per minute, tachypneic at 21 cycles per minute, and hypoxemic at 80’s on room air but 96% on 5 liters oxygen via nasal cannula. Electrocardiogram demonstrated S1Q3T3 pattern. Computed Tomography Scan of the chest with contrast revealed saddle pulmonary embolism with right ventricle enlargement. Bedside ultrasound demonstrated right heart strain. Patient’s 4T score was eight, consistent with a high probability of HIT. She was started on argatroban drip. She had a thrombectomy. Further workup revealed positive heparin-induced antibodies (1.270 Optical Density) and negative serotonin-release assay (< 1%). Argatroban was continued, and platelets steadily increased to > 150, 000/microliter. She was then started on Eliquis upon discharge.
Discussion: Serotonin Release assay (SRA) is a test commonly used in North America in confirming Heparin-Induced Thrombocytopenia. Platelets when activated releases serotonin. The SRA test detects the serotonin release in the test platelets with heparin and presence of the patient’s serum. It has a sensitivity and specificity of >95%. Recently, the concept of SRA-negative HIT has been proposed. IIt is defined by negative SRA and meeting three clinical criteria: 4Ts ≥ 4 points, EIA-positive (≥1.00 units), and PF4-SRA-positive. The patient in the case report met the 2 out of 3 criteria. A PF4-SRA test was not done due to strong suspicion for HIT. The PF4 testing and the 4Ts scoring were used by the clinical team to confirm diagnosis and treat the patient despite negative SRA.The incidence of SRA-negative HIT is still unknown and its occurrence is very rare. A factor to be considered for this event is the quality of the assay performed which can lead to false negative results. There are differences among institutions in the techniques used which can affect performance characteristics.
Conclusions: Further studies are needed to document the incidence of SRA-negative HIT. Since there are varying techniques among laboratories, this opens the idea of the need to standardize the high technical demands of the test. It is also important to determine the cost-effectivity and necessity of SRA to diagnose HIT considering its high cost and its use of radioactive materials.