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Case Report
Fatal exacerbation of ChadOx1-nCoV-19-induced thrombotic thrombocytopenia syndrome after initial successful therapy with intravenous immunoglobulins - a rational for monitoring immunoglobulin G levels
The present report describes a vaccine-induced throm- botic thrombocytopenia (VITT) case with fatal exacerba- tion after initial improvement following initial intra- venous immunoglobulin (IVIg) administration and anti- coagulation. An 83-year-old woman presented at the emergency room with an alteration of her general condi- tion. She presented with symptoms of weakness, nausea, vomiting, weight loss and spontaneous bruises without any obvious reason, 14 days after having received her first dose of ChadOx1 nCov-19. According to our med- ical records, she did not receive heparin or derivative dur- ing the previous 4 months. Clinical examination unrav- eled bruising on the upper limbs. Computer tomography (CT) of thorax and abdomen was normal. Oxygen satu- ration was 98% at admission and the patient was tested negative for SARS-CoV-2 infection as assessed by reverse-transcriptase polymerase chain reaction (RT-PCR). The initial laboratory investigations on the day of admission revealed that the patient was suffering from marked thrombocytopenia (i.e., platelet count of 10,000 per mm3), dramatically increased D-dimers plasma levels (i.e., > 20,000 ng/mL) and slightly low plasma fibrinogen (i.e., 179 mg/dL) (Figure 1). She was transfused with a platelet concentrate (roughly 3.5x1011 platelets) on the day of admission.
During the night, she suffered from dyspnea grade NYHA 4. Pulmonary ventilation and perfusion (V/Q) scan was performed and disclosed bilateral pulmonary
embolism. Anti-PF4 immunoglobulin G (IgG) antibodies (i.e. 1.80 AU/mL, Figure 1) were detected on day 1 post- admission using a PF4/polyvinylsulfonate rapid assay (HemosIL® AcuStar HIT IgG assay, Instrumentation Laboratory Belgium NV, Zaventem, Belgium). The diag- nosis of VITT was confirmed using a heparin-induced multi-electrode aggregometry method.1 In face of the clinical picture, i.e., thrombocytopenia and thrombosis, with the presence of anti-PF4 antibodies and positive platelet activation tests within 30 days after vaccination with ChadOx1 nCov-19, VITT was diagnosed.2 The patient therefore promptly received 15 grams of IVIg (Privigen®, CSL Behring Gmbh, Marburg, Germany) and methylprednisolone 1 mg/kg. A second platelet concen- trate (roughly 4.5x1011 platelets) was administered to allow initiation of anticoagulation as the platelet count was still below 30,000 per mm3. The platelet count rap- idly improved, i.e., 53,000 per mm3, and anticoagulation was started with fondaparinux 5 mg once a day (od) sub- cutaneously from day 1 to day 3 (taking into account renal failure, i.e., Cockcroft-Gault creatinine clearance <50 mL/min). She received additional IVIg on day 2 and 3, at the dose of 60 grams per day for a total IVIg dose of 135 grams corresponding to 1.7 grams of IVIg per kg administered over a period of 48 hours. Fondaparinux dose was increased to 7.5 mg od from day 4 to day 11 since renal function improved. On day 6, the patient was stabilized, and her global health status was improved as witnessed by normalized platelet count, decrease in D- dimers (i.e., from > 20,000 ng/mL at admission to 14,380 ng/mL) and C-reactive protein (CRP) (from 145 mg/dL at admission to 23 mg/dL). Later that day, however, oxygen saturation dropped below 80%. Cough with sputum pro- duction was noted and exacerbation of COPD with Moraxella catarrhalis infection was diagnosed. Oxygen
Figure 1. Clinical and laboratory data of the case. CRP: C-reactive protein; CODP: chronic obstructive pulmonary disease; HIT: heparin-induced thrombocytope- nia; od: once daily.
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