A 26-year-old female presented with severe headache for 5 days. She had been previously healthy without comorbidities eight days earlier when she had been scheduled for the first dose of ChAdOx1 nCoV-19 vaccine (AstraZeneca) vaccination. She had no adverse event following immunization until three days later when she developed a severe headache. She did not report any fever, myalgia, blurred vision, nausea, or vomiting. Her headache was not improved by acetaminophen and mefenamic acid. One day prior to admission, she noticed multiple discrete reddish spots at both lower legs without bleeding gums or epistaxis. On examination, mildly pale conjunctiva and petechiae at both legs were noted while other examinations were unremarkable. The initial complete blood count showed a hemoglobin of 9.7 g/dL, mean corpuscular volume of 71.5 fL, white blood cell count of 3.66 x 109/L (neutrophil 75%, lymphocyte 18%, monocyte 4.7%, eosinophil 2% basophil 0.3%), and platelet count of 22 x 109/L. Prothrombin time was 11.9 seconds (normal range, 9.8–12.9 seconds), activated partial thromboplastin time was 25.8 seconds (normal range, 21.8–30.2 seconds), and fibrinogen was 173.8 mg/dL. D-dimer was 9452 ng/mL (normal d-dimer, < 500 ng/mL). NS-1 antigen, dengue IgM, and IgG serologic testing were negative. SARS-CoV2 RNA test was negative. Lupus anticoagulants, anticardiolipin IgM, IgG, as well as anti-β2 glycoprotein I IgM and IgG were negative. Magnetic resonance imaging, angiography, and venography of brain were normal without evidence of thrombosis. Computed tomography angiography of the pulmonary arteries showed no pulmonary embolism, and computed tomography of abdomen was unremarkable.
Due to the high degree of suspicious of VITT, we performed a test for antibody against platelet factor 4 (PF4) by enzyme-linked immunosorbent assay-based assay (Zymutest HIA IgG, HYPHEN BioMed, Neuville-sur-Oise, France), and the result was positive with an optical density (OD) of 2.10 (normal OD, < 0.4) (Fig. 1). After we added heparin at a concentration of 100 units/mL, the OD was lower at 0.09 (Fig. 1). We then demonstrated a functional test of antibody by a heparin-induced platelet aggregation (HIPA) test. Platelet rich plasma from healthy volunteer with blood group O was incubated with the patient’s serum for one hour. Low doses (0.1 and 0.5 unit/mL) and a high dose (100 units/mL) of heparin and normal saline were added into the mixture mentioned above. Platelet aggregation was assessed by light transmission (AggRAM Analyzer®, Helena Laboratories, Beaumont, Texas). Platelet aggregation of > 25% was detected after adding the low concentrations of 0.1 and 0.5 unit/mL of heparin, but it was absent at 100 unit/mL (Table 1). Without adding heparin, spontaneous platelet aggregation was also detected.
Table 1
Heparin-induce platelet aggregation results of the patient
Heparin for final concentration, units/mL | Platelet aggregation, % |
D0 | D1 | D4 |
0.1 | 31.8 | 18.7 | 16.8 |
0.5 | 46.0 | 20.4 | 15.3 |
100 | 15.9 | 19.2 | 18.7 |
Saline | 30.0 | 16.0 | 6.9 |
Notes:- Abbreviations: D#, day after admission |
After discussion with the patient, we promptly started treatment with 2 days of 1 g/kg of intravenous immunoglobulin (IVIG) infusion and dexamethasone 40 mg per day for severe thrombocytopenia, and we administered 2.5 mg of apixaban every 12 hours for thromboprophylaxis. We opted to monitor thrombus formation by d-dimer level because we did not find evidence of thrombosis by imaging studies, and d-dimer level gradually decreased during the hospital course after treatment (Fig. 2). After 6 days of IVIG and dexamethasone treatment, the platelet count had slowly increased to 97 x 109/L (Fig. 2). Her symptoms were improved, and she was discharged from the hospital by day 6. At three weeks follow-up, the number of platelet counts was 134 x 109/L (Fig. 2) and no clinical thrombosis was detected.