Clinical evaluation of the safety and efficacy of enoxaparin in patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), increases thrombotic risk in hospitalised patients. The rate of thrombosis in patients with COVID-19 is unclear. The role of heparin, frequently used in the management of hospitalised patients, also needs to be clarified. In this study, we investigated the efficacy and safety of enoxaparin given at prophylactic or therapeutic dose in hospitalised patients with COVID-19, and evaluated its role in the development of disease in terms of mortality, and incidence of thrombotic and bleeding events. MATERIAL AND METHODS: We included 141 patients with SARS-CoV-2 infection, admitted to five different wards (one intensive care unit, 2 sub-intensive care units, and 2 general infectious disease units) of Cotugno Hospital, a tertiary care hospital in Naples, Italy, between March and May 2020. RESULTS: Over a median time of 17 days (IQR 11-25), enoxaparin was given to 90/141 patients (63.8%) of whom 65 took a prophylactic and 25 a therapeutic dose. We documented 14 episodes of thrombosis (9.9%); almost all were cases of pulmonary embolism. No significant difference in terms of thromboembolic prevention was found between those patients not receiving anticoagulants and those on prophylactic or therapeutic dose of enoxaparin. Five episodes of major bleeding occurred (3.5%); therapeutic dose of enoxaparin was associated with a greater bleeding risk than prophylactic dose (p=0.002). During follow-up, 31 patients (22%) died; these were mostly elderly men with two or more comorbidities at admission. No advantages of enoxaparin, either as prophylaxis or at high doses, in terms of mortality were observed. At multivariate analysis, low estimated glomerular filtration rate, and high total bilirubin and fasting hyperglycemia were independently associated with a higher mortality. DISCUSSION: We did not observe advantages in terms of either thromboembolic prevention or mortality of enoxaparin, which however was more frequently used in patients with more severe disease. Prophylactic enoxaparin was not seen to be associated with bleeding risk.

Clinical evaluation of the safety and efficacy of enoxaparin in patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), increases thrombotic risk in hospitalised patients. The rate of thrombosis in patients with COVID-19 is unclear. The role of heparin, frequently used in the management of hospitalised patients, also needs to be clarified. In this study, we investigated the efficacy and safety of enoxaparin given at prophylactic or therapeutic dose in hospitalised patients with COVID-19, and evaluated its role in the development of disease in terms of mortality, and incidence of thrombotic and bleeding events. MATERIAL AND METHODS: We included 141 patients with SARS-CoV-2 infection, admitted to five different wards (one intensive care unit, 2 sub-intensive care units, and 2 general infectious disease units) of Cotugno Hospital, a tertiary care hospital in Naples, Italy, between March and May 2020. RESULTS: Over a median time of 17 days (IQR 11-25), enoxaparin was given to 90/141 patients (63.8%) of whom 65 took a prophylactic and 25 a therapeutic dose. We documented 14 episodes of thrombosis (9.9%); almost all were cases of pulmonary embolism. No significant difference in terms of thromboembolic prevention was found between those patients not receiving anticoagulants and those on prophylactic or therapeutic dose of enoxaparin. Five episodes of major bleeding occurred (3.5%); therapeutic dose of enoxaparin was associated with a greater bleeding risk than prophylactic dose (p=0.002). During follow-up, 31 patients (22%) died; these were mostly elderly men with two or more comorbidities at admission. No advantages of enoxaparin, either as prophylaxis or at high doses, in terms of mortality were observed. At multivariate analysis, low estimated glomerular filtration rate, and high total bilirubin and fasting hyperglycaemia were independently associated with a higher mortality. DISCUSSION: We did not observe advantages in terms of either thromboembolic prevention or mortality of enoxaparin, which however was more frequently used in patients with more severe disease. Prophylactic enoxaparin was not seen to be associated with bleeding risk.

Clinical Significance and Prognostic Value of Hemostasis Parameters in 337 Patients with Acute Infective Endocarditis.

(1) Background: The aim of this study was to assess the clinical significance and prognostic role of the main hemostasis parameters in infective endocarditis (IE): prothrombin time as international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT), fibrinogen, D-dimers, platelet count, homocysteine. (2) Methods: We studied 337 patients with IE. Clinical, hemato-chemical and echocardiography parameters were analyzed. Coagulation parameters were measured on admission. (3) Results: D-dimers levels (p = 0.012) and a prolonged PT-INR (p = 0.013) were associated with higher in-hospital mortality, while prolonged aPTT (p = 0.021) was associated with increased 1-year mortality. Staphylococcus aureus (S. aureus) infection (p = 0.003), prosthetic valve endocarditis (PVE) (p = 0.001), surgical indication (p = 0.002) and higher D-dimer levels (p = 0.005) were independent predictors of in-hospital mortality. PVE (p = 0.001), a higher Charlson Comorbidity Index (p = 0.049), surgical indication (p = 0.001) and prolonged aPTT (p = 0.012) were independent predictors of 1-year mortality. Higher levels of D-dimers (p < 0.001) and a shorter aPTT (p < 0.001) were associated with embolic complications of IE. S. aureus etiology was bound to higher D-dimers levels (p < 0.001) and a shorter aPTT (p = 0.006). (4) Conclusions: Elevated D-dimers are associated with a higher risk for in-hospital mortality in IE patients. High D-dimers and a short aPTT are associated with a higher risk for embolic events in IE. A longer aPTT is associated with 1-year mortality.

Predictors of long-term mortality in left-sided infective endocarditis: an historical cohort study in 414 patients.

INTRODUCTION: Very limited data are available on the long-term outcome of infective endocarditis (IE) and its determinants. The aim of this study was to identify the predictors of long-term mortality in patients affected by left sided IE (LSIE). METHODS: This was an historical retrospective observational study on prospectively collected data from patients with LSIE hospitalized in our Unit (January 2000-December 2017). Multiple variables relevant to history, physical examination, laboratory tests, echocardiography, comorbidities, complications and outcome were analysed by Cox regression to identify predictors of long-term mortality. RESULTS: 414 patients were included, and followed up for a median of 39 months [IQR 11-74]. Median age was 59 years [range 3-89], and most patients were male. Over 50% showed at least one comorbidity. Hyperglycaemia, increased creatinine and an indication for surgery predicted in-hospital mortality, while a prior myocardial infarction, chronic kidney disease (CKD) on hemodialysis and a larger vegetation were independent predictors of 1-year mortality. At multivariate analysis, peripheral arterial disease (p= 0.017), hyperglycemia on admission (p=0.013) and a higher BMI (p=0.009) were independent predictors of long-term mortality in 1-year survivors. At multivariable Cox proportional hazard regression, peripheral arterial disease (p=0.002), hyperglycemia (p=0.041) and CKD on hemodialysis (p=0.025) confirmed to be independently associated with an increased risk of long-term mortality in the overall 414 patient cohort. CONCLUSIONS: Cardiovascular and metabolic risk signals, specifically peripheral arterial disease and hyperglicemia, affect long-term mortality of LSIE. An active and long-term follow up seems warranted in IE survivors showing these conditions at outset.

Dynamics and management of oral anticoagulant treatment in chronic hepatitis C patients undergoing therapy with direct antiviral agents.

Current regimens of direct-acting antiviral agents (DAA) are effective and safe for chronic hepatitis C (CHC). However, DAA often interfere with concomitant medications. We treated seven CHC patients with DAA who were on chronic anticoagulant treatment with warfarin, and describe the dynamics of prothrombin time, providing novel data, useful for the clinician.

Prevalence and significance of two major inherited thrombophilias in infective endocarditis.

The pathogenesis of infective endocarditis (IE) involves activation of the haemostasis system at the site of endocardial defects. Whether prothrombotic conditions are associated with IE by enhancing early vegetation formation is unknown. In this study, we assess the prevalence and clinical significance of two major conditions associated with thrombophilia in patients with IE. Mutations G20210A of the prothrombin (PTH) gene and G1691A of factor V (FV Leiden) gene were studied by means of allele-specific polymerase chain reaction in 203 IE patients, 175 valvular heart disease (VHD) patients and 200 blood donors (BD). IE patients show higher cumulative frequencies of mutated alleles of PTH and FV Leiden [6.4 vs 3.25 %; OR 2.03 (95 % CI 0.97-3.66); p = 0.047] compared to BD, but not VHD. Device-related IE is enriched with FV Leiden, and prosthetic valve IE with PTH mutations (allele frequency 8.3 vs 2.2 % in native valve IE; p = 0.021). Vegetation size and embolic complications are not influenced by the examined thrombophilias. A trend for a higher mortality was observed in IE patients with any of the two thrombophilias studied. Our data do not support a role for factor V Leiden and G20210A prothrombin gene mutations in the susceptibility to IE. Whether any of these genetic polymorphisms play a role in a specific subtype of IE needs to be re-examined in larger studies.

High-dose daptomycin for cardiac implantable electronic device-related infective endocarditis.

BACKGROUND: Cardiac implantable electronic device (CIED)-related endocarditis is a growing challenge because of increasing incidence and significant mortality. Current treatment is based on complete hardware removal coupled with long-term administration of effective and safe antimicrobials. Daptomycin at the dose of 6 mg/kg/day has been found to be effective in staphylococcal endocarditis, but limited data exist on CIED endocarditis. Moreover, whether higher doses could be more effective but equally safe in this setting is currently unknown. METHODS: We report here our experience with high-dose daptomycin in the treatment of 25 cases of CIED endocarditis due to staphylococci. RESULTS: Patients were mostly elderly and male, with large lead vegetations and severe comorbidities. Pathogens were Staphylococcus epidermidis (56%), Staphylococcus aureus (28%), and other coagulase-negative staphylococci (16%). Only 4 patients (16%) had a normal pretreatment renal function. The median daptomycin daily dose was 8.3 mg/kg (range, 6.4-10.7). Daptomycin was administered for a median of 20 days (range, 8-52). Percutaneous lead extraction was performed in 88% of patients. Two patients (8%) failed to clear bacteremia. The overall clinical success of treatment was 80%, whereas a complete microbiological success was observed in 92% of patients. Creatine phosphokinase values were monitored and increased above normal in 5 cases (20%). No serious adverse event related to high-dose daptomycin was observed and no patient required discontinuation because of muscle toxicity. CONCLUSIONS: Our experience suggests that high-dose daptomycin may be a safe therapeutic option in staphylococcal CIED endocarditis and may be associated with high microbiological responses and clinical success.

Management of Gram-negative and fungal endocarditis.

Infective endocarditis is infrequently caused by Gram-negative bacteria or fungi. Gram-negative organisms are responsible for <4% of cases, whilst fungal endocarditis accounts for <1.5% of culture-positive cases worldwide. Endocarditis due to Gram-negative organisms or fungi is a rare but severe disease. It often has a nosocomial origin, is caused by virulent and often resistant organisms and presents a high rate of complications and high mortality. In this article we present the most recent literature data and address the current management of Gram-negative and fungal infective endocarditis. We also discuss the major challenges of antimicrobial treatment and discuss some issues related to surgical decision-making in difficult-to-manage cases. We finally present our centre's experience with Gram-negative infective endocarditis, with a special focus on the demanding issues that the management of these complex and severely ill patients raise.

Cardiovascular risk factors and outcome in patients with retinal vein occlusion.

The pathogenesis and treatment of retinal vein occlusions (RVO) are largely unclear. Prevalence of cardiovascular risk factors and of thrombophilic abnormalities was evaluated in 117 patients (61 M, 56 F; mean age 51 +/- 13 years) with a history of RVO (62 central, CRVO; 48 branch, BRVO; 7 both) and in 202 age- and sex-matched control subjects. Cardiovascular outcome after a mean 8.2 year follow-up was recorded for 90 patients. Arterial hypertension was significantly more frequent in patients than in controls (64.9 vs. 28.2%; adjusted OR 4.5 95% CI 2.4-7.9; P < 0.0001), as well diabetes mellitus (17.9 vs. 7.9%; P < 0.05). Antithrombin, Protein C, Protein S and homocysteine levels, lupus anticoagulant, anticardiolipin antibodies, FV G1691A and prothrombin G20210A polymorphisms were comparable in the two groups, nor were different according to RVO localization or to the age at event. BRVO patients were significantly older (55 +/- 9 vs. 47 +/- 15 years; P = 0.002) and had higher prevalence of diabetes, overweight and hypertension (29.2 vs. 8.1%; 83.3 vs. 58.1%, 79.2 vs. 56.5%; P always <0.05). In 58/90 (64%) patients for whom clinical follow-up was available, new vascular events were recorded (coronary/cerebral, n = 38); only 22 patients (24%) received long-term antiplatelet agents (mostly aspirin 100 mg/d), with lower, but not statistically significant, prevalence of overall vascular recurrence (45.4 vs. 70.6%, P = 0.06). High rate of vascular recurrence is shown in patients with previous RVO, in which conventional cardiovascular risk factors play a major role, especially in BRVO and in older patients.