Subject(s)
Anticoagulants/administration & dosage , Atrial Fibrillation/drug therapy , Myeloproliferative Disorders/complications , Venous Thromboembolism/drug therapy , Administration, Oral , Atrial Fibrillation/etiology , Atrial Fibrillation/pathology , Humans , International Agencies , Venous Thromboembolism/etiology , Venous Thromboembolism/pathologyABSTRACT
The recent association of cerebral venous thrombosis (CVT) with COVID-19 vaccinations prompted the current retrospective review of 74 cases of CVT (median age = 44 years, range 15-85; 61% females) associated with myeloproliferative neoplasms (MPNs), seen at the Mayo Clinic, Catholic University of Rome, and University of Florence, between 1991 and 2021. Disease-specific frequencies were 1.3% (39/2893), 1.2% (21/1811) and 0.2% (3/1888) for essential thrombocythemia, polycythemia vera and primary myelofibrosis, respectively. Cerebral venous thrombosis occurred either prior to (n = 20, 27%), at (n = 32, 44%) or after (n = 22) MPN diagnosis. A total of 72% of patients presented with headaches. Transverse (51%), sagittal (43%) and sigmoid sinuses (35%) were involved with central nervous system hemorrhage noted in 10 (14%) patients. In all, 91% of tested patients harbored JAK2V617F. An underlying thrombophilic condition was identified in 19 (31%) cases and history of thrombosis in 10 (14%). Treatment for CVT included systemic anticoagulation alone (n = 27) or in conjunction with aspirin (n = 24), cytoreductive therapy (n = 14), or both (n = 9). At a median follow-up of 5.1 years (range 0.1-28.6), recurrent CVT was documented in three (4%) patients while recurrent arterial and venous thromboses and major hemorrhage were recorded in 11%, 9% and 14%, respectively. Follow-up neurological assessment revealed headaches (n = 9), vision loss (n = 1) and cognitive impairment (n = 1). The current study lends clarity to MPN-associated CVT and highlights its close association with JAK2V617F, younger age and female gender. Clinical features that distinguish COVID vaccine-related CVT from MPN-associated CVT include, in the latter, lower likelihood of concurrent venous thromboses and intracerebral hemorrhage; as a result, MPN-associated CVT was not fatal.
Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Intracranial Thrombosis/etiology , Myeloproliferative Disorders/complications , Venous Thrombosis/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Intracranial Thrombosis/genetics , Janus Kinase 2/genetics , Male , Middle Aged , Myeloproliferative Disorders/genetics , Point Mutation , Polycythemia Vera/complications , Polycythemia Vera/genetics , Primary Myelofibrosis/complications , Primary Myelofibrosis/genetics , Retrospective Studies , Thrombocythemia, Essential/complications , Thrombocythemia, Essential/genetics , Venous Thrombosis/genetics , Young AdultSubject(s)
COVID-19 Vaccines/administration & dosage , Myeloproliferative Disorders/drug therapy , Myeloproliferative Disorders/immunology , Pyrazoles/therapeutic use , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Humans , Nitriles , Pyrimidines , SARS-CoV-2/immunologySubject(s)
Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pyrazoles/therapeutic use , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/mortality , Coronavirus Infections/virology , Cross-Sectional Studies , Disease Progression , Humans , Italy/epidemiology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/mortality , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/virology , Nitriles , Philadelphia Chromosome/drug effects , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Pyrimidines , SARS-CoV-2 , Severity of Illness Index , Survival AnalysisABSTRACT
Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.