Twelve days earlier, she had received the 1st vaccination with ChAdOx1 nCov-19 (AstraZeneca)

Twelve days earlier, she had received the 1st vaccination with ChAdOx1 nCov-19 (AstraZeneca). need to be elucidatedespecially in case of cerebral sinus venous thrombosis (CSVT) with connected mind haemorrhage as the underlying thrombotic event. We here report our medical encounter with two young women diagnosed with VITT-associated CSVT, treated with high-dose intravenous immunoglobulins (IVIGs), corticosteroids and argatroban in the hyperacute phase, followed by dabigatran resulting in excellent outcome. Patient 1 A 39-year-old female with an unremarkable medical history was admitted with severe holocephalic headache since 2?days. Eight days earlier, she experienced received the 1st Carteolol HCl vaccination with ChAdOx1 nCov-19 (AstraZeneca). Physical and neurological exam was normal. Laboratory investigations exposed moderate thrombocytopenia (84109/L) and significantly elevated D-dimer (14.2?mg/L; normal 0.5?mg/L). Fibrinogen and additional routine parameters were normal (table 1). Mind CT including venography was unremarkable as were CT pulmonary angiography and compression ultrasound of both legs. Coincidentally, the patient had contact with a COVID-19-positive Carteolol HCl person a few days after vaccination and SARS-CoV-2 reverse transcription PCR (RT-PCR) on admission was positive with cycle threshold value 26 on a nasopharyngeal swab. Prophylactic treatment with danaparoid 750?IU two times per day subcutaneously and intravenous dexamethasone 40?mg were started. While the patient remained clinically stable, platelets further decreased (36109/L) on day 4 after hospital admission, and fibrinogen depleted 150?mg/dL (table 1). Remarkably, during the next night, she developed a new left-sided dull occipital headache and D-dimer again increased to 14.41?mg/dL (table 1). Brain MRI now showed left sigmoid/transverse sinus thrombosis without brain parenchymal involvement. Therefore, we initiated high-dose IVIG 1?g/kg bodyweight (for 2?days) and switched danaparoid to intravenous argatroban (starting with 2?g/kg bodyweight/min with dose adjustments for target activated partial thromboplastin time (aPTT) 1.5 above baseline). From then on, her clinical condition improved; platelets and fibrinogen increased, while D-dimer levels markedly decreased (table 1). Four days later, anticoagulation was changed to oral dabigatran 150?mg two times per day. During the entire hospital stay, she did not develop any symptoms related to her COVID-19 contamination. Moreover, COVID-19-specific laboratory markers (ferritin, C reactive protein or interleukin 6) remained normal. The patient was discharged 10 days after admission free of any symptoms. A follow-up examination 1?month after discharge was unremarkable. SARS-CoV-2 spike protein antibodies were 86.20?U/mL, while SARS-CoV-2 nucleocapsid antibodies were negative. Table 1 Laboratory parameters over the course of time in both Carteolol HCl patients thead Variable (reference units)d1*d2*d3*d4*d5*d6*d7*d8*d9*d10*d18? /thead Patient 1 br / (39?years, first ChAdOx1 nCov-19 vaccination 8?days before hospital admission)CSVT?Platelets (140C440109/L)84615136476710410498121126?D-dimer (0.5?mg/L)14.211.411.811.914.49.368.637.17.654.140.91?Fibrinogen (210C400?mg/dL)23623417314383626490201292285?Coagulation factor 13 ( 70%)119117C947767C6865C99?CRP ( 5.0?mg/L) 0.6 0.6 0.6 0.6 0.6C6.2C?Ferritin (9C140?ng/mL)83C100786863CCCCC?Interleukin 6 (0C7.0?pg/mL)12C43.63.64.2CCCCCPatient 2 br / (24?years, first ChAdOx1 nCov-19 vaccination 12 days before hospital admission)CSVT?Platelets (140C440109/L)294178135166188258304337254183?D-dimer (0.5?mg/L) 3323.614.62.811.811.532.912.813.312.251.35?Fibrinogen (210C400?mg/dL)9555 50 50 50 50152169208232254?Coagulation factor 13 ( 70%)C25C3622CCC465898?CRP ( 5.0?mg/L)16.714. (9C140?ng/mL)80CC6147CCCCCC?Interleukin 6 (0C7.0?pg/mL)11CC2.72.5CCCCCC Open in a separate window *Hospital treatment ?Follow-up visit 1?week after hospital discharge CRP, C reactive protein; CSVT, cerebral sinus venous thrombosis (diagnosis); d, day. Patient 2 A 24-year-old woman was admitted with a severe persisting headache in the past 4?days. Twelve days earlier, she had received the first vaccination with ChAdOx1 nCov-19 (AstraZeneca). She had an unremarkable medical history, Carteolol HCl and her physical as well as neurological examination was normal. Initial laboratory investigations revealed severe thrombocytopenia Carteolol HCl (29109/L), massively elevated D-dimer ( 33?mg/L) and fibrinogen depletion (95?mg/dL). SARS-CoV-2 RT-PCR on admission was negative. Brain MRI showed thrombosis of two cortical veins with related small frontal right juxtacortical haemorrhage. We immediately started IVIG 1?g/kg bodyweight, dexamethasone 40?mg and argatroban (target aPTT 1.5 baseline) intravenously. Apart from a short-lasting epileptic seizure on day 1, the patient remained clinically stable and her headache rapidly resolved. Thrombocytes increased and D-dimer decreased after treatment initiation (table 1). Fibrinogen initially decreased but recovered on day 7, and dabigatran 150?mg was started two times per day. The patient was discharged free of any symptoms and remained asymptomatic in a follow-up examination 2?weeks later. SARS-CoV-2 spike protein antibodies were 41.80?U/mL, while SARS-CoV-2 nucleocapsid antibodies were negative. Notably, initial testing for platelet factor-4 antibodies was unfavorable in a HemosIL HIT IgG test in both patients but they were later on tested positive in a confirmatory ELISA assay. Both patients had neither a positive prior or family history of thromboembolic events nor another genetic or acquired thrombophilia in extensive laboratory evaluations (eg, factor V Leiden or prothrombin mutation, protein C or S deficiency, antiphospholipid antibodies). CSVT has been reported as one main thrombotic complication in VITT. Although it has also been associated with COVID-19 contamination, such Rabbit polyclonal to SR B1 a link seems less likely in our SARS-CoV-2 PCR-positive patient 1.