Despite administration of a total of 8 g fibrinogen, the fibrinogen level remained <1.0 g/l and the aPTT was still more than 100 seconds. Therefore, after careful consideration, the decision was made to switch to fondaparinux.

In addition to the above, targeted temperature management was started for 24 hours, with a target temperature of 36 °C in light of the patient’s coagulopathy. Within 24 hours after admission, the obstructive shock gradually resolved. The platelet count normalised, as did the renal function. No bleeding complications occurred. However, after cessation of the sedation, the patient developed a post-anoxic status epilepticus. This was thought to be due to the prolonged shock state, since CPR had been started without delay. In the next few days, she was treated with four antiepileptic drugs and three sedatives. At day seven of admission, distributive shock occurred concurrent with a rise in inflammatory parameters. No specific site of infection could be identified, but ceftriaxone, vancomycin and hydrocortisone were started based on a positive sputum culture (Klebsiella pneumoniae) and the possibility of a catheter-related infection. A component of obstructive shock was excluded with POCUS at day eight, which showed no signs of elevated right ventricular pressures. Although her haemodynamic status improved over the next few days, the status epilepticus persisted. At day 11 of admission, the prognosis was deemed infaust. The treatment was discontinued and the patient died 12 days after her initial presentation at the emergency department.

Discussion
VITT is a relatively new and rare vaccine-associated adverse event, characterised by thrombocytopenia and thrombosis occurring 4-28 days after vaccination with the ChAdOx1-S/nCoV-19 (AstraZeneca) or Ad26.COV2.S (Janssen) SARS-CoV-2 vaccines. Thrombosis is often seen at unusual sites, including the cerebral venous sinus and splanchnic veins. In addition to venous thrombi, arterial thromboembolisms, including aortoiliac thrombosis and stroke, have been described.[9,10] VITT closely resembles HIT, which is characterised by antibodies against the multimolecular complexes of heparin and platelet factor 4 (PF4, a protein stored in platelet α granules and released during platelet activation). These antibodies induce the release of procoagulant platelet microparticles including PF4 itself, thus creating a cascade of further platelet activation and thrombin generation. This cycle causes widespread thrombosis and a consumptive coagulopathy with thrombocytopenia, hypofibrinogenaemia and elevated D-dimer concentrations. In VITT, antibodies against PF4 are found in the absence of heparin as a trigger. It is currently unclear whether these are autoantibodies induced by the strong inflammatory stimulus of vaccination or antibodies induced by the vaccine that cross-react with PF4 and platelets. HIT-ELISA tests have the most appropriate sensitivity for anti-PF4 antibodies in VITT, but positive results must be confirmed by a functional HIPAA.[11] Its incidence has been estimated at 0.73 per 100,000 persons receiving a first dose of the ChAdOx1-S/nCoV-19 vaccine.[12] A higher risk of VITT is seen in patients with younger age and female sex.[11] With her age of 63, our patient belongs to the 15% of patients aged >60 years at the time of diagnosis of VITT. In the Netherlands, 40 cases of thrombosis with thrombocytopenia after vaccination with a COVID-19 vaccine (AstraZeneca and Janssen) were reported to the Netherlands Pharmacovigilance Centre Lareb until 1 August 2021. VITT was confirmed in 22 of these cases based on a positive HIT-ELISA and/or HIPAA or based on clinically severe thrombosis. Of these patients, 18 had received the AstraZeneca vaccine. Of the 40 patients with thrombocytopenia and thrombosis, six died, three of whom were presumed to have developed VITT following the AstraZeneca vaccine, according to Lareb.[13] In this article we have described one of these cases. Given the massive scale on which vaccinations are still taking place worldwide, it seems likely that some of our colleagues will encounter the same therapeutic challenges as we did.

The first and most difficult problem we encountered was the combination of pulmonary embolism and obstructive shock with severe thrombocytopenia. Although there are several published guidelines for the treatment of venous thromboembolism, recommendations on the management of pulmonary embolism in patients with severe thrombocytopenia are lacking. In this particular case we treated our patient with a full dose of alteplase despite the severe thrombocytopenia, given the lack of readily-available alternative options in our hospital. Our treatment was successful: the patient became haemodynamically stable and did not develop any bleeding. Alternatives to systemic thrombolysis include embolectomy by aspiration, catheter-directed fragmentation with local fibrinolytic therapy and surgical embolectomy. The last two procedures have been successfully performed in a few patients with HIT or thrombocytopenia due to another cause,[5,14,15] and current guidelines list embolectomy and catheter-directed treatment as reasonable alternatives in patients with contraindications to systemic thrombolysis if expertise and resources are available on-site.[1] Currently, several centres in the Netherlands provide these treatment options. In our case, we chose not to transfer the patient to an intervention centre, since this would have caused a significant delay in reperfusion treatment.