Efficacy and Safety of Tinzaparin in Prophylactic, Intermediate and Therapeutic Doses in Non-Critically Ill Patients Hospitalized with COVID-19: The PROTHROMCOVID Randomized Controlled Trial.

Hospitalized patients with COVID-19 are at increased risk of thrombosis, acute respiratory distress syndrome and death. The optimal dosage of thromboprophylaxis is unknown. The aim was to evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate, and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia. PROTHROMCOVID is a randomized, unblinded, controlled, multicenter trial enrolling non-critical, hospitalized adult patients with COVID-19 pneumonia. Patients were randomized to prophylactic (4500 IU), intermediate (100 IU/kg), or therapeutic (175 IU/kg) groups. All tinzaparin doses were administered once daily during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non-invasive mechanical ventilation, or death within 30 days. The main safety outcome was major bleeding at 30 days. Of the 311 subjects randomized, 300 were included in the prespecified interim analysis (mean [SD] age, 56.7 [14.6] years; males, 182 [60.7%]). The composite endpoint at 30 days from randomization occurred in 58 patients (19.3%) of the total population; 19 (17.1 %) in the prophylactic group, 20 (22.1%) in the intermediate group, and 19 (18.5%) in the therapeutic dose group (p = 0.72). No major bleeding event was reported; non-major bleeding was observed in 3.7% of patients, with no intergroup differences. Due to these results and the futility analysis, the trial was stopped. In non-critically ill COVID-19 patients, intermediate or full-dose tinzaparin compared to standard prophylactic doses did not appear to affect the risk of thrombotic event, non-invasive ventilation, or mechanical ventilation or death. Trial RegistrationClinicalTrials.gov Identifier (NCT04730856). Edura-CT registration number: 2020-004279-42.

Manejo de las complicaciones vasculares gestacionales y trombosis en la mujer / Management of gestational vascular complications and thrombosis in women

Objetivo: conocer la prevalencia de trombofilia en trombosis gestacional y complicaciones vasulares gestacionales en nuestro entorno y el manejo de las mismas. Material y métodos: estudio prospectivo y observacional en el que se incluyeron cuatro cohortes: trombosis, profilaxis de trombosis, complicaciones vasulares gestacionales, profilaxis de complicaciones vasulares gestacionales. Se registraron 1.032 episodios, de los cuales se incluyeron 994 en el análisis final. Resultados: la distribución de episodios fue: 5,5% trombosis, 30,2% profilaxis de trombosis, 35,7% complicaciones vasulares gestacionales y 24,9% profilaxis de complicaciones vasulares gestacionales. Las pérdidas gestacionales fueron la complicación más frecuente. Se realizó estudio de trombofilia en 82,6% de complicaciones vasulares gestacionales y 70,2% de trombosis. Los resultados fueron positivos en el 47% de trombosis y en 21% de complicaciones vasulares gestacionales. Los defectos más comunes en complicaciones vasulares gestacionales fueron la elevación del factor VIII, la presencia de anticuerpos antifosfolípidos y la mutación F12C46T en homocigosis. Se empleó tratamiento antitrombótico en el 85% de profilaxis de trombosis y en el 77% de profilaxis de complicaciones vasulares gestacionales. La tromboprofilaxis de complicaciones vasulares gestacionales no se relacionó con una mejora en el resultado de la gestación. Conclusiones: se realizaron estudios de trombofilia a la mayoría de las pacientes, con resultados diferentes en trombosis y complicaciones vasulares gestacionales. Se empleó tromboprofilaxis en más del 70% de las pacientes. La profilaxis farmacológica de complicaciones vasulares gestacionales no aportó beneficio significativo. Serían necesarios estudios futuros para confirmar nuestros resultados (AU)

Objective: The main objectives were to establish the prevalence of thrombophilia in pregnancy-related thrombosis and vascular placental complications and to evaluate the clinical management of these complications. Materials and methods: Multicenter, prospective and observational study. We analysed 4 patient cohorts: thrombosis, thrombosis prophylaxis, vascular placental complications, vascular placental complications prophylaxis. A total of 1032 episodes were registeredand 994 were included in the final analysis. Results: The distribution of the episodes was: 5.5% thrombosis, 30.2% thrombosis prophylaxis, 35.7% vascular placental complications and 24.9% vascular placental complications prophylaxis. Pregnancy loss was the most frequent complication registered. Thrombophilia studies were made in 82.6% patients in vascular placental complications cohort and in 70.2% of thrombosis patients. Positive results were obtained in 47% of patients in thrombosis group and in 21% of patients with vascular placental complications. In this group the most common defects found were high levels of FVIII, positive antiphospholipid antibodies and homocigosity for F12C46T polymorphism. Antithrombotic treatment was used in 85% of thrombosis prophylaxis episodes and in 77% of vascular placental complications prophylaxis episodes. Pharmacologic prophylaxis was not related with a better pregnancy outcome in vascular placental complications prophylaxis group. Conclusions: Thrombophilia studies were made to most patients in this registry. Results were different in patients with thrombosis and vascular placental complications. Most patients in vascular placental complications prophylaxis group with or without thrombophilia recieved LMWH +/- aspirin, but we did not find a benefit of these treatments. Further studies with more patients will be needed to confirm our findings (AU)