Recent studies suggest that thrombotic complications are a common phenomenon in the novel SARS-CoV-2 infection. The main objective of our study is to assess cumulative incidence of pulmonary embolism (PE) in non critically ill COVID-19 patients and to identify its predicting factors associated to the diagnosis of pulmonary embolism. We retrospectevely reviewed 452 electronic medical records of patients admitted to Internal Medicine Department of a secondary hospital in Madrid during Covid 19 pandemic outbreak. We included 91 patients who underwent a multidetector Computed Tomography pulmonary angiography(CTPA) during conventional hospitalization. The cumulative incidence of PE was assessed ant the clinical, analytical and radiological characteristics were compared between patients with and without PE. PE incidence was 6.4% (29/452 patients). Most patients with a confirmed diagnosed with PE recieved low molecular weight heparin (LMWH): 79.3% (23/29). D-dimer peak was significatly elevated in PE vs non PE patients (14,480 vs 7230 mcg/dL, p = 0.03). In multivariate analysis of patients who underwent a CTPA we found that plasma D-dimer peak was an independen predictor of PE with a best cut off point of > 5000 µg/dl (OR 3.77; IC95% (1.18-12.16), p = 0.03). We found ninefold increased risk of PE patients not suffering from dyslipidemia (OR 9.06; IC95% (1.88-43.60). Predictive value of AUC for ROC is 75.5%. We found a high incidence of PE in non critically ill hospitalized COVID 19 patients despite standard thromboprophylaxis. An increase in D-dimer levels is an independent predictor for PE, with a best cutoff point of > 5000 µg/ dl.

Introduction Some local protocols suggest using intermediate or therapeutic doses of anticoagulants for thromboprophylaxis in hospitalized patients with coronavirus disease 2019 (COVID‐19). However, the incidence of bleeding, predictors of major bleeding, or the association between bleeding and mortality remain largely unknown. Methods We performed a cohort study of patients hospitalized for COVID‐19 that received intermediate or therapeutic doses of anticoagulants from March 25 to July 22, 2020, to identify those at increased risk for major bleeding. We used bivariate and multivariable logistic regression to explore the risk factors associated with major bleeding. Results During the study period, 1965 patients were enrolled. Of them, 1347 (69%) received intermediate‐ and 618 (31%) therapeutic‐dose anticoagulation, with a median duration of 12 days in both groups. During the hospital stay, 112 patients (5.7%) developed major bleeding and 132 (6.7%) had non‐major bleeding. The 30‐day all‐cause mortality rate for major bleeding was 45% (95% confidence interval [CI]: 36%‐54%) and for non‐major bleeding 32% (95% CI: 24%‐40%). Multivariable analysis showed increased risk for in‐hospital major bleeding associated with D‐dimer levels >10 times the upper normal range (hazard ratio [HR], 2.23; 95% CI, 1.38–3.59), ferritin levels >500 ng/ml (HR, 2.01; 95% CI, 1.02–3.95), critical illness (HR, 1.91; 95% CI, 1.14–3.18), and therapeutic‐intensity anticoagulation (HR, 1.43; 95% CI, 1.01–1.97). Conclusions Among patients hospitalized with COVID‐19 receiving intermediate‐ or therapeutic‐intensity anticoagulation, a major bleeding event occurred in 5.7%. Use of therapeutic‐intensity anticoagulation, critical illness, and elevated D‐dimer or ferritin levels at admission were associated with increased risk for major bleeding.

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BackgroundType 2 Diabetes (T2DM) is the most rapidly increasing risk factor for ischemic stroke. We aimed to compare trends in outcomes for ischemic stroke in people with or without diabetes in Spain between 2003 and 2012.MethodsWe selected all patients hospitalized for ischemic stroke using national hospital discharge data. We evaluated annual incident rates stratified by T2DM status. We analyzed trends in the use of diagnostic and therapeutic procedures, patient comorbidities, and in-hospital outcomes. We calculated in-hospital mortality (IHM), length of hospital stay (LOHS) and readmission rate in one month after discharge. Time trend on the incidence of hospitalization was estimated fitting Poisson regression models by sex and diabetes variables. In-hospital mortality was analyzed using logistic regression models separate for men and women. LOHS were compared with ANOVA or Kruskal-Wallis when necessary.ResultsWe identified a total of 423,475 discharges of patients (221,418 men and 202,057 women) admitted with ischemic stroke as primary diagnosis. Patients with T2DM accounted for 30.9% of total. The estimated incidence rates of discharges increased significantly in all groups. The incidence of hospitalization due to stroke (with ICD9 codes for stroke as main diagnosis at discharge) was higher among those with than those without diabetes in all the years studied. T2DM was positively associated with ischemic stroke with an adjusted incidence rate ratio (IRR) of 2.27 (95% CI 2.24–2.29) for men and 2.15 (95%CI 2.13–2.17) for women. Over the 10 year period LOHS decreased significantly in men and women with and without diabetes. Readmission rate remained stable in diabetic and non diabetic men (around 5%) while slightly increased in women with and without diabetes. We observed a significant increase in the use of fibrinolysis from 2002–2013. IHM was positively associated with older age in all groups, with Charlson Comorbidity Index > 3 and atrial fibrillation as risk factors. The IHM did not change significantly over time among T2DM men and women ranging from 9.25% to 10.56% and from 13.21% to 14.86%, respectively; neither did among non-diabetic women. However, in men without T2DM IHM decreased significantly over time. Diabetes was associated to higher IHM only in women (OR 1.07; 95% CI, 1.05–1.11).ConclusionsOur national data show that incidence rate of ischemic stroke hospitalization increased significantly during the period of study (2003–2012). People with T2DM have more than double the risk of ischemic stroke after adjusting for other risk factors. Women with T2DM had poorer outcomes- IHM and readmission rates- than diabetic men. Diabetes was an independent factor for IHM only in women.

BackgroundThe main aims of this study were to describe trends and outcomes during admission for infective endocarditis (IE) in people ≥ 40 years old with or without type 2 diabetes distributed in five time-periods (2001–2003; 2004–2006; 2007–2009; 2010–2012 and 2013–2015), using Spanish national hospital discharge data.MethodsWe estimated admission rates by diabetes status. We analyzed comorbidity, therapeutic procedures, and outcomes. We built Poisson regression models to compare the adjusted time-trends in admission rates. Type 2 diabetes cases were matched with controls using propensity score matching (PSM). We tested in-hospital mortality (IHM) in logistic regression analyses.ResultsWe identified 16,626 hospitalizations in patients aged ≥ 40 years for IE in Spain, 2001–2015. The incidence of IE increased significantly from 6.0/100,000 per year to 13.1/100,000 per year (p < 0.001) in the population with type 2 diabetes, and from 3.9/100,000 per year to 5.5/100,000 per year (p < 0.001) in the population without diabetes, over the study period. The adjusted incidence of IE was 2.2-times higher among patients with diabetes than among those without diabetes (IRR = 2.2; 95% CI 2.1–2.3). People with type 2 diabetes less often underwent heart valve surgery than people without diabetes (13.9% vs. 17.3%; p < 0.001). Although IHM decreased significantly in both groups over time, it represented 20.8% of IE cases among diabetes patients and 19.9% among PSM matched controls (p = 0.337). Type 2 diabetes was not associated with a higher IHM in people admitted to the hospital for IE (OR = 1.1; 95% CI 0.9–1.2).ConclusionIncidence rates of IE in Spain, among those with and without T2DM, have increased during the period 2001–2015 with significantly higher incidence rates in the T2DM population. In our population based study and after PSM we found that T2DM was not a predictor of IHM in IE.

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Background: Incidence of thrombotic events associated to Coronavirus disease-2019 (COVID-19) is difficult to assess and reported rates differ significantly. Optimal thromboprophylaxis is unclear.Objectives: We aimed to analyze the characteristics of patients with a confirmed thrombotic complication including inflammatory and hemostatic parameters, compare patients affected by arterial vs venous events and examine differences between survivors and non-survivors. We reviewed compliance with thromboprophylaxis and explored how the implementation of a severity-adjusted protocol could have influenced outcome. Methods: Single-cohort retrospective study of COVID-19 patients admitted, from March 3 to May 3 2020, to the Infanta Leonor University Hospital in Madrid, epicenter of the Spanish outbreak. Results: Among 1127 patients, 80 thrombotic events were diagnosed in 69 patients (6.1% of the entire cohort). Forty-three patients (62%) suffered venous thromboembolism, 18 (26%) arterial episodes and 6 (9%) concurrent venous and arterial thrombosis. Most patients (90%) with a confirmed thrombotic complication where under low-molecular-weight heparin treatment. Overt disseminated intravascular coagulation (DIC) was rare. Initial ISTH DIC score and pre-event CRP were significantly higher among non-survivors. In multivariate analysis, arterial localization was an independent predictor of mortality (OR = 18, 95% CI: 2.4-142, p < .05). Conclusions: Despite quasi-universal thromboprophylaxis, COVID-19 lead to a myriad of arterial and venous thrombotic events. Considering the subgroup of patients with thrombotic episodes, arterial events appeared earlier in the course of disease and conferred very poor prognosis, and an ISTH DIC score ≥ 3 at presentation was identified as a potential predictor of mortality. Severity-adjusted thromboprophylaxis seemed to decrease the number of events and could have influenced mortality. Randomized controlled trials are eagerly awaited.

Background : Hospitalized patients with COVID-19 are at increased risk for thrombosis, acute respiratory distress syndrome and death. The optimal dosage of thromboprophylaxis is unknown. Objective: To evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate, and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia. Design, setting, and participants : Randomized controlled, multicenter trial (PROTHROMCOVID) enrolling non-critical, hospitalized adult patients with COVID-19 pneumonia. Interventions: Patients were randomized to prophylactic (4500 IU), intermediate (100 IU/kg), or therapeutic (175 IU/kg) doses of tinzaparin during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. Measurements: 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. Results : Of the 311 subjects randomized, 300 were included in the 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.   Conclusions: In non-critically ill COVID-19 patients, intermediate or full-dose tinzaparin compared to standard prophylactic doses did not appear to increase benefit regarding the likelihood of thrombotic event, non-invasive ventilation or high-flow oxygen, or death. Trial Registration  ClinicalTrials.gov Identifier (NCT04730856). Funding: This independent research initiative was supported by Leo-Pharma; Tinzaparin was provided by Leo Pharma.