Hemostatic Profile and Serological Response of Patients with Immune Thrombotic Thrombocytopenic Purpura after Receiving BNT162b2 Vaccine: A Prospective Study.

INTRODUCTION: Coronavirus disease is a clinical challenge for patients with autoimmune conditions. Patients affected by immune thrombotic thrombocytopenic purpura (iTTP) are particularly vulnerable to SARS-CoV-2 infection. Protecting these patients with vaccination is therefore mandatory, although concerns may exist on a possible increased thrombotic risk or risk of disease relapse after vaccine exposure. So far, there is no information on serological response and hemostatic activation in iTTP patients after SARS-CoV-2 vaccination. MATERIALS AND METHODS: In this study, in April 2021, we enrolled iTTP patients in clinical remission and on regular outpatient follow-up to receive the first and second dose BNT162b2 vaccine as a part of a prospective trial aimed at monitoring for 6 months after vaccination the occurrence of subclinical laboratory signs of clotting activation, as well as overt thrombotic complications or disease relapse. The seroconversion response was monitored in parallel. The results were compared with those of control non-iTTP subjects. RESULTS: A moderate decrease of ADAMTS-13 activity was recorded at 3 and 6 months in five patients with normal values at baseline, while an ADAMTS-13 relapse occurred at 6 months in one patient. Abnormalities in the endothelium activation biomarkers postvaccination were observed in iTTP patients compared with controls. The immunological response to vaccine was overall positive. No clinical iTTP relapses or thrombotic events manifested in the 6 month-follow-up after vaccination. CONCLUSION: The results of this study are in favor of efficacy and safety of mRNA vaccines in patients with iTTP, and highlight the importance of long-term monitoring of iTTP patients.

Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients.

Introduction: In a prospective cohort of hospitalized COVID-19 patients, an extensive characterization of hemostatic alterations by both global and specific assays was performed to clarify mechanisms underlying the coagulopathy and identify predictive factors for thrombotic and hemorrhagic events during hospitalization. Materials and Methods: Intensive care unit (ICU; n = 46) and non-ICU (n = 55) patients were enrolled, and the occurrence of thrombotic and hemorrhagic events was prospectively monitored. At study inclusion, thromboelastometry together with the measurement of specific coagulation proteins and hypercoagulation markers was performed. Results: Patients (median age 67 years) showed significantly shorter clot formation time together with greater maximum clot firmness by thromboelastometry, increased levels of F1 + 2 and D-dimer, as biomarkers of hypercoagulability, and of procoagulant factors V, VIII, IX, XI, and fibrinogen, while FXIII was significantly reduced. The concentration of fibrinolytic proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were elevated in the overall cohort of patients. Many of these hemostatic alterations were significantly greater in ICU compared to non-ICU subjects and, furthermore, they were associated with inflammatory biomarker elevation [i.e., interleukin 6 (IL-6), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and procalcitonin]. After enrollment, 7 thrombosis and 14 major bleedings occurred. Analysis of clinical and biological data identified increased t-PA, PAI-1, and NLR values as independent predictive factors for thrombosis, while lower FXIII levels were associated with bleeding. Conclusion: This study demonstrates alterations in all different hemostatic compartments analyzed, particularly in severe COVID-19 conditions, that strongly correlated with the inflammatory status. A potential role of fibrinolytic proteins together with NLR and of FXIII as predictors of thrombotic and hemorrhagic complications, respectively, is highlighted.

Endothelium Activation Markers in Severe Hospitalized COVID-19 Patients: Role in Mortality Risk Prediction.

Introduction Endothelial damage and hypercoagulability are major players behind the hemostatic derangement of SARS-CoV-2 infection. Aim In this prospective study we assessed endothelial and inflammatory biomarkers in a cohort of COVID-19 patients, aiming to identify predictive factors of in-hospital mortality. Methods COVID-19 patients hospitalized in intensive care (ICU) and non-ICU units at 2 Bergamo (Italy) hospitals from March 23 to May 30, 2020, were enrolled. Markers of endothelium activation including von-Willebrand factor (vWF), soluble thrombomodulin (sTM), and fibrinolytic proteins (t-PA and PAI-1) were measured. Additionally, D-dimer, Fibrinogen, FVIII, nucleosomes, C reactive protein (CRP) and procalcitonin were assessed. Results Sixty-three (45 ICU, and 18 non-ICU) patients, with a median age of 62 years were analyzed. Increased plasma levels of D-dimer, FVIII, fibrinogen, nucleosomes, CRP, and procalcitonin were observed in the whole cohort. Extremely elevated vWF levels characterized all patients (highest values in ICU-subjects). After a median time of 30 days, death occurred in 13 (21%) patients. By multivariable analysis, vWF-activity, neutrophil-count and PaO2/FiO2 were significantly associated with death. Using these variables, a linear score with 3-risk groups was generated that provided a cumulative incidence of death of 0% in the low-, 32% in the intermediate-, and 78% in the high-risk group. Conclusions COVID-19-induced hemostatic abnormalities are exacerbated by the severity of the disease and strongly correlate with the inflammatory status, underlying the link between coagulation, endothelial activation, and inflammation. Our study provides evidence for a role of vWF, together with neutrophils and PaO2/FiO2, as a significant predictor of in-hospital mortality by SARSCoV-2 infection.