key: cord-0887147-omlywmp5 authors: Thaler, Johannes; Ay, Cihan; Gleixner, Karoline V.; Hauswirth, Alexander W.; Cacioppo, Filippo; Grafeneder, Jürgen; Quehenberger, Peter; Pabinger, Ingrid; Knöbl, Paul title: Successful treatment of vaccine‐induced prothrombotic immune thrombocytopenia (VIPIT) date: 2021-06-11 journal: J Thromb Haemost DOI: 10.1111/jth.15346 sha: 7f1a5aa3a63bf972f175ac6f9fd4c927bbe8876d doc_id: 887147 cord_uid: omlywmp5 Cases of unusual thrombosis and thrombocytopenia after administration of the ChAdOx1 nCoV‐19 vaccine (AstraZeneca) have been reported. The term vaccine‐induced prothrombotic immune thrombocytopenia (VIPIT) was coined to reflect this new phenomenon. In vitro experiments with VIPIT patient sera indicated that high‐dose intravenous immunoglobulins (IVIG) competitively inhibit the platelet‐activating properties of ChAdOx1 nCoV‐19 vaccine induced antibodies. Here, we report a case of a 62‐year‐old woman who had received this vaccine and developed VIPIT. She visited the emergency ward because of petechiae and hematomas. In the laboratory work‐up, thrombocytopenia, low fibrinogen, elevated D‐dimer, and positivity in the platelet factor 4/heparin‐enzyme‐immunoassay were present. Signs and symptoms of thrombosis were absent. Upon immediate therapy with non‐heparin anticoagulation, high‐dose IVIG, and prednisolone, laboratory parameters steadily improved and the patient was discharged from hospital without thrombotic complications. We conclude that early initiation of VIPIT treatment results in a swift response without thrombotic complications. antibodies causing massive activation of platelets via the Fc receptor, resembling heparin-induced thrombocytopenia (HIT), but without previous contact with heparin (HIT mimicry). These antibodies and clinical symptoms seem to occur 4 to 16 days after vaccination. In vitro experiments with sera from VIPIT patients indicate that high-dose intravenous immunoglobulins (IVIG) competitively inhibit the platelet activating properties of ChAdOx1 nCOV-19-induced antibodies. 3 Based on these observations, recent guidance was published that recommends considering the administration of IVIG in case of severe thromboembolic complications after VIPIT confirmation by heparin induced platelet activation (HIPA) assay/modified HIPA assay or serotonin release assay (SRA). 1 Practical restrictions of this recommendation are the limited availability of HIPA/SRA assays in non-specialized coagulation laboratories and the lack of guidance on the preemptive use of IVIG for prevention of thrombosis in patients with VIPIT. Two recent studies report on VIPIT patients who had developed unusual thrombosis. 4,5 A substantial proportion of these patients died (3/5 patients and 6/11 patients, respectively). One of these studies provides information on VIPIT treatment, indicating that administration of high-dose IVIG is indeed effective. 4 Here, we describe the first clinical case of a patient with early VIPIT diagnosis and its management, resulting in swift normalization of laboratory parameters and subsequent hospital discharge without thrombotic complications. A 62-year-old woman in good health condition received the ChAdOx1 nCOV-19 vaccine (day 0). The following day she developed flu-like symptoms including aching joints, moderate headache, and moderate dizziness. She self-medicated 1 g paracetamol, was afebrile, but stayed the whole day at home, most of the time in bed (day 1). The next day, she felt significantly better but self-medicated 400 mg aspirin (day 2). On days 3 and 4, she felt completely recovered and on day 4 she drove herself 100 miles by car to the lower Austrian alpine foothills for vacation. On day 5, she was crosscountry skiing for several hours without complaints. The same evening, she developed chills and high fever (39.8°C/103.6°F) and took 400 mg aspirin. The following morning (day 6) again she took 400 mg aspirin, she was afebrile, felt much better, and drove back home by car. On days 7 and 8, she had no complaints and returned to work as a psychotherapist. The evening of day 8, she slightly bit her lip and developed an unusually large hematoma. She also noticed bleedings at the gums, which she never had before. The morning of day 9, she recognized an atraumatic hematoma at the right ankle. The CT scan showed no pathologies, especially no signs of venous or arterial thrombosis. The hemogram revealed isolated thrombocytopenia (normal differential blood count, no schistocytes). D-dimer was highly elevated and fibrinogen was low ( Figure 1 ; Table S1 in supporting information). Global coagulation tests were within the normal range. The anti-platelet factor 4 (PF4)/heparin IgG enzymeimmunoassay (Zymutest HIA IgG, HYPHEN Biomed), which has been recommended for VIPIT screening, 1 was highly positive and supported the suspected diagnosis of VIPIT. Due to the clinically obvious signs of bleeding, which could be attributed to thrombocytopenia and hypofibrinogenemia, and intake of aspirin, we substituted a low dose (1 g) of a fibrinogen concentrate patient self-medicated 1200 mg aspirin after vaccination. Inhibition of platelet aggregation due to aspirin intake may had prevented occurrence of thrombosis prior to hospitalization. Second, we immediately administered high-dose IVIG, which seem to readily inhibit platelet-activating antibodies. Third, non-heparin anticoagulation with short-acting danaparoid-sodium (monitoring anti-Xa target trough levels) may have prevented thrombosis and administration of fibrinogen concentrates at low endogenous fibrinogen levels may have prevented hemorrhage. In conclusion, our case is the first report that suggests that early non-heparin anticoagulation in conjunction with early administration of high-dose IVIG can interrupt the prothrombotic process in patients with suspected VIPIT and may be life saving. The authors have no conflicts of interest to declare. Diagnosis and mamagement of vaccine-related thrombosis following AstraZeneca COVID-19 vaccination: guidance statement from the GTH. Hämostaseologie (ahead of print New problems erode confidence in AstraZeneca's vaccine A prothrombotic thrombocytopenic disorder resembling heparin-induced thrombocytopenia following Coronavirus-19 vaccination Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination Perinatal/Pediatric Hemostasis Subcommittees Working G. 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