A previously healthy 43-year-old male patient of Sephardic-Jewish descent presented to a local medical facility with chest pain and exertional dyspnoea that began earlier that day, following a week-long course that included loss of appetite and diarrhoea that resolved 1 day prior to presentation. He underwent a standard initial emergency department workup and was diagnosed with acute pulmonary embolism (PE), with a saddle-embolus and large bilateral thrombotic burden, RV systolic dysfunction, and mildly increased serum troponin levels. He was admitted to the local intensive cardiac care unit and therapeutic unfractionated heparin was started. Over the next few days, RV function further deteriorated despite therapy on serial echocardiographic studies, and the patient was transferred to our tertiary medical centre where several further treatment lines are available. Upon arrival, the patient was asymptomatic and had stable vital signs. His routine laboratory panel showed normal renal function, high-sensitivity troponin-I, and lactate levels. His physical examination was positive for jugular venous distention but was otherwise non-remarkable. The patients’ electrocardiogram showed a normal sinus rhythm with a normal QRS axis and T-wave inversion in leads V1–4 (). The echocardiogram demonstrated a dilated RV with moderately reduced systolic function, and moderate estimated systolic pulmonary pressure (eSPAP) of 50 mmHg. The next day, CDT was performed using the EkoSonic Endovascular System, placed bilaterally. During 9.5 h, he received a total of 19 mg of alteplase. During therapy, D-dimer levels rose from a baseline level of 7000 ng/mL to a 121 000 ng/mL, while fibrinogen levels decreased from 560 mg/dL to 398 mg/dL. Unfortunately, a follow-up echocardiogram performed the next day did not show any significant changes. At Day 2 after CDT, the patient suffered an episode of exertional syncope, with no associated arrhythmia, convulsions, or secondary trauma. At Day 3 after CDT, computed tomographic angiography showed a mixed picture composed of both worsening central thrombus burden, and partial improvement in some bilateral segmental and sub-segmental vessels (). Compression Doppler sonography revealed a small right popliteal vein thrombus. Brain-natriuretic peptide (BNP) levels were elevated at 244 pg/mL, and troponin levels, that were previously normal, rose to a peak level of 88 ng/L. At this point in time, we knew that the patient was negative for anti-phospholipid antibodies, but further laboratory studies for hypercoagulability were still pending. The case was presented at a multidisciplinary PE response team (PERT), and it was hypothesized that the patient, who at the time of clinical deterioration signified by the syncopal episode was treated with unfractionated heparin for a total of 10 days, might suffer from heparin-induced thrombocytopenia (HIT). A review of his previous platelet levels, which were mostly overlooked as they were well within normal range, showed a gradual downward trend, from initial levels at the range of 260 k/mcl to a nadir around the range of 180 k/mcl (). This meant that the patient met the more minor platelet-level criteria for HIT of having a 30–50% decrease in platelet levels, as well as fulfilling the other three criteria of the 4 t’s score for HIT for a total of 6 points, which is classified as high probability (). The patient was tested for heparin immune antibodies, that were strongly positive at 6.8 U/mL, establishing the diagnosis of HIT. Other differential diagnoses were deemed as having a low probability due to a lack of supporting findings. These included, among others, disseminated intravascular coagulation, sepsis, microangiopathic haemolysis, systemic lupus erythematosus, antiphospholipid syndrome, and drug-induced thrombocytopenia. The patient was switched from continuous intravenous heparin to bivalirudin therapy following the PERT meeting, and this was continued once the diagnosis of HIT was established. An echocardiogram performed the next day showed a normal sized and functioning RV, with moderately estimated eSPAP. Subsequent studies over the next few days also showed normal RV size and function, with a gradual decrease in eSPAP. Serum biomarkers such as troponin-I and BNP rapidly normalized, and platelet levels stabilized around 340 k/mcl. Previously drawn laboratory studies for hypercoagulability were positive for methylenetetrahydrofolate reductase heterozygosity, and antithrombin levels were low (58%), although this test was taken after several days of unfractionated heparin therapy. The patient began mobilizing and was asymptomatic. After 6 days of bivalirudin treatment, doses ranging 0.4–2.0 mg/kg/h and titrating according to partial thromboplastin time, the patient was switched to oral rivaroxaban therapy. Initial rivaroxaban dose was 15 mg b.i.d., for 3 weeks, followed by a maintenance dose of 15 mg o.d. continued permanently during subsequent follow-up. The rest of the patients’ stay was unremarkable, and he was later discharged to his home in good clinical condition. At the 6-month follow-up visit, the patient was well and resumed his previous lifestyle without limitations. A small persistent asymptomatic thrombus was still present in his right popliteal vein. The complete clinical timeline is summarized in.