Diana Aguiar de Sousa1,2, Michele Romoli3,4, Mayte Sánchez Van Kammen5, Mirjam R Heldner6, Andrea Zini7, Jonathan M Coutinho5, Marcel Arnold6, José M Ferro1,2. 1. Department of Neurology, Centro Hospitalar Universitário de Lisboa Norte - Hospital de Santa Maria, Lisbon, Portugal (D.A.d.S., J.M.F.). 2. Faculdade de Medicina, Universidade de Lisboa, Portugal (D.A.d.S., J.M.F.). 3. Neurology and Stroke Unit, "Maurizio Bufalini" Hospital, Cesena, Italy (M.R.). 4. Neurology Clinic, University of Perugia - S. Maria della Misericordia Hospital, Italy (M.R.). 5. Department of Neurology, Amsterdam University Medical Center, the Netherlands (M.S.V.K., J.M.C.). 6. Department of Neurology, University hospital and University of Bern, Switzerland (M.R.H., M.A.). 7. IRCCS Istituto delle Scienze Neurologiche di Bologna, Neurologia e Rete Stroke Metropolitana, Ospedale Maggiore, Bologna, Italy (A.Z.).
Abstract
BACKGROUND: Cerebral venous thrombosis (CVT) has recently been reported as a common thrombotic manifestation in association with vaccine-induced thrombotic thrombocytopenia, a syndrome that mimics heparin-induced thrombocytopenia (HIT) and occurs after vaccination with adenovirus-based SARS-CoV-2 vaccines. We aimed to systematically review the incidence, clinical features, and prognosis of CVT occurring in patients with HIT. METHODS: The study protocol was registered with PROSPERO (CRD42021249652). MEDLINE, EMBASE and Cochrane CENTRAL were searched up to June 1, 2021 for HIT case series including >20 patients, or any report of HIT-related CVT. Demographic, neuroradiological, clinical, and mortality data were retrieved. Meta-analysis of proportions with random-effect modeling was used to derive rate of CVT in HIT and in-hospital mortality. Pooled estimates were compared with those for CVT without HIT and HIT without CVT, to determine differences in mortality. RESULTS: From 19073 results, we selected 23 case series of HIT (n=1220) and 27 cases of HIT-related CVT (n=27, 71% female). CVT developed in 1.6% of 1220 patients with HIT (95% CI,1.0%-2.5%, I2=0%). Hemorrhagic brain lesions occurred in 81.8% of cases of HIT-related CVT and other concomitant thrombosis affecting other vascular territory was reported in 47.8% of cases. In-hospital mortality was 33.3%. HIT-related CVT carried a 29% absolute increase in mortality rate compared with historical CVT controls (33.3% versus 4.3%, P<0.001) and a 17.4% excess mortality compared with HIT without CVT (33.3% versus 15.9%, P=0.046). CONCLUSIONS: CVT is a rare thrombotic manifestation in patients with HIT. HIT-related CVT has higher rates of intracerebral hemorrhage and a higher mortality risk, when compared with CVT in historical controls. The recently reported high frequency of CVT in patients with vaccine-induced thrombotic thrombocytopenia was not observed in HIT, suggesting that additional pathophysiological mechanisms besides anti-platelet factor-4 antibodies might be involved in vaccine-induced thrombotic thrombocytopenia-related CVT.
BACKGROUND: Cerebral venous thrombosis (CVT) has recently been reported as a common thrombotic manifestation in association with vaccine-induced thrombotic thrombocytopenia, a syndrome that mimics heparin-induced thrombocytopenia (HIT) and occurs after vaccination with adenovirus-based SARS-CoV-2 vaccines. We aimed to systematically review the incidence, clinical features, and prognosis of CVT occurring in patients with HIT. METHODS: The study protocol was registered with PROSPERO (CRD42021249652). MEDLINE, EMBASE and Cochrane CENTRAL were searched up to June 1, 2021 for HIT case series including >20 patients, or any report of HIT-related CVT. Demographic, neuroradiological, clinical, and mortality data were retrieved. Meta-analysis of proportions with random-effect modeling was used to derive rate of CVT in HIT and in-hospital mortality. Pooled estimates were compared with those for CVT without HIT and HIT without CVT, to determine differences in mortality. RESULTS: From 19073 results, we selected 23 case series of HIT (n=1220) and 27 cases of HIT-related CVT (n=27, 71% female). CVT developed in 1.6% of 1220 patients with HIT (95% CI,1.0%-2.5%, I2=0%). Hemorrhagic brain lesions occurred in 81.8% of cases of HIT-related CVT and other concomitant thrombosis affecting other vascular territory was reported in 47.8% of cases. In-hospital mortality was 33.3%. HIT-related CVT carried a 29% absolute increase in mortality rate compared with historical CVT controls (33.3% versus 4.3%, P<0.001) and a 17.4% excess mortality compared with HIT without CVT (33.3% versus 15.9%, P=0.046). CONCLUSIONS: CVT is a rare thrombotic manifestation in patients with HIT. HIT-related CVT has higher rates of intracerebral hemorrhage and a higher mortality risk, when compared with CVT in historical controls. The recently reported high frequency of CVT in patients with vaccine-induced thrombotic thrombocytopenia was not observed in HIT, suggesting that additional pathophysiological mechanisms besides anti-platelet factor-4 antibodies might be involved in vaccine-induced thrombotic thrombocytopenia-related CVT.
Authors: Anita van de Munckhof; Erik Lindgren; Timothy J Kleinig; Thalia S Field; Charlotte Cordonnier; Katarzyna Krzywicka; Sven Poli; Mayte Sánchez van Kammen; Afshin Borhani-Haghighi; Robin Lemmens; Adrian Scutelnic; Alfonso Ciccone; Thomas Gattringer; Matthias Wittstock; Vanessa Dizonno; Annemie Devroye; Ahmed Elkady; Albrecht Günther; Alvaro Cervera; Annerose Mengel; Beng Lim Alvin Chew; Brian Buck; Carla Zanferrari; Carlos Garcia-Esperon; Christian Jacobi; Cristina Soriano; Dominik Michalski; Zohreh Zamani; Dylan Blacquiere; Elias Johansson; Elisa Cuadrado-Godia; Fabrice Vuillier; Felix J Bode; François Caparros; Frank Maier; Georgios Tsivgoulis; Hans D Katzberg; Jiangang Duan; Jim Burrow; Johann Pelz; Joshua Mbroh; Joyce Oen; Judith Schouten; Julian Zimmermann; Karl Ng; Katia Garambois; Marco Petruzzellis; Mariana Carvalho Dias; Masoud Ghiasian; Michele Romoli; Miguel Miranda; Miriam Wronski; Mona Skjelland; Mostafa Almasi-Dooghaee; Pauline Cuisenier; Seán Murphy; Serge Timsit; Shelagh B Coutts; Silvia Schönenberger; Simon Nagel; Sini Hiltunen; Sophie Chatterton; Thomas Cox; Thorsten Bartsch; Vahid Shaygannejad; Zahra Mirzaasgari; Saskia Middeldorp; Marcel M Levi; Johanna A Kremer Hovinga; Katarina Jood; Turgut Tatlisumak; Jukka Putaala; Mirjam R Heldner; Marcel Arnold; Diana Aguiar de Sousa; José M Ferro; Jonathan M Coutinho Journal: Stroke Date: 2022-09-09 Impact factor: 10.170