Infectious agents including COVID-19 and the involvement of blood coagulation and fibrinolysis. A narrative review

Platelets, blood coagulation along with fibrinolysis are greatly involved in the pathophysiology of infectious diseases induced by bacteria, parasites and virus. This phenomenon is not surprising since both the innate immunity and the hemostatic systems are two ancestral mechanisms which closely cooperate favoring host's defense against foreign invaders. However, the excessive response of these systems may be dangerous for the host itself

Position paper on the safety/efficacy profile of Direct Oral Anticoagulants in patients with Chronic Kidney Disease: Consensus document of Società Italiana di Nefrologia (SIN), Federazione Centri per la diagnosi della trombosi e la Sorveglianza delle terapie Antitrombotiche (FCSA) and Società Italiana per lo Studio dell’Emostasi e della Trombosi (SISET)

Direct oral anticoagulants (DOAC) are mostly prescribed to prevent cardioembolic stroke in patients with non-valvular atrial fibrillation (AF). An increasing number of guidelines recommend DOAC in AF patients with preserved renal function for the prevention of thromboembolism and an increased use of DOAC in daily practice is recorded also in elderly patients. Aging is associated with a reduction of glomerular filtration rate and impaired renal function, regardless of the cause, increases the risk of bleeding. Multiple medication use (polypharmacy) for treating superimposed co-morbidities is common in both elderly and chronic kidney disease (CKD) patients and drug-drug interaction may cause accumulation of DOAC, thereby increasing the risk of bleeding. There is uncertainty on the safety profile of DOAC in patients with CKD, particularly in those with severely impaired renal function or end stage renal disease, due to the heterogeneity of studies and the relative paucity of data. This document reports the position of three Italian scientific societies engaged in the management of patients with atrial fibrillation who are treated with DOAC and present with CKD

Central precocious puberty during COVID-19 pandemic and sleep disturbance: an exploratory study

Background: Increased incidence of central precocious puberty (CPP) after coronavirus infectious disease-19 lockdown has been reported. Our study aims in investigating changes in CPP rates and in sleep patterns in CPP and healthy controls. Methods: CPP were retrospectively evaluated from April 2020 to April 2021. Parents of girls diagnosed with CPP during lockdown and of matched healthy controls filled out a questionnaire about sleep disturbances (SDSC questionnaire) and sleep schedules. Results: Thirty-five CPP and 37 controls completed the survey. Incidence of new CPP cases significantly increased in 2020–2021 compared to 2017–2020 (5:100 vs 2:100, p = 0.02). Sleep disturbance rates did not differ between CPP and healthy controls before lockdown. During lockdown, CPP reported higher rates of sleep disturbs for total score (p = 0.005), excessive somnolence (p = 0.049), sleep breathing disorders (p = 0.049), and sleep–wake transition disorders (p = 0.005). Moreover, CPP group more frequently shifted toward later bedtime (p = 0.03) during lockdown compared to controls. Hours of sleep and smartphone exposure around bedtime did not differ between groups. Conclusions: Our study confirms the observation of increased incidence of CPP after lockdown measures. Additionally, CPP showed higher rates of sleep disturbances and later bedtime compared to controls. The causality link between sleep disturbances and CPP should be further investigated to gain knowledge in this association

Association between hepatic steatosis and obstructive sleep apnea in children and adolescents with obesity

Background: Owing to the increasing rate of pediatric obesity, its complications such as non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) have become prevalent already in childhood. We aimed to assess the relationship between these two diseases in a cohort of children with obesity. Methods: We enrolled 153 children with obesity (mean age 10.5 ± 2.66, mean BMI 30.9 ± 5.1) showing OSA. Subjects underwent a laboratory evaluation, a cardio-respiratory polysomnography (PSG), and a liver ultrasound. Results: All subjects had a clinical diagnosis of OSA based on the AHI > 1/h (mean AHI 8.0 ± 5.9; range 2.21–19.0). Of these, 69 showed hepatic steatosis (62.3% as mild, 20.3% as moderate, and 17.4% as severe degree). A strong association between ALT and apnea/hypopnea index (AHI) was observed (p = 0.0003). This association was not confirmed after adjusting for hepatic steatosis (p = 0.53). By subdividing our population according to the presence/absence of steatosis, this association was found only in the steatosis group (p = 0.009). As the severity of steatosis increased, the significance of its association with AHI compared to the absence of steatosis became progressively stronger (all p < 0.0001). Conclusions: Hepatic steatosis seems to drive the association between OSA and ALT levels, suggesting a potential pathogenic role of OSA in NAFLD

Obstetric outcomes in pregnant COVID-19 women: the imbalance of von Willebrand factor and ADAMTS13 axis

Background: Thrombotic microangiopathy has been invoked as one of the most important mechanisms of damage in COVID-19 patients. Protease ADAMTS13 is a marker of microangiopathy responsible for controlling von Willebrand multimers size. Von Willebrand factor/ADAMTS13 ratio has been found impaired in COVID-19 patients outside pregnancy. Methods: We prospectively investigated 90 pregnant women admitted to two tertiary academic hospitals in Italy with a laboratory-confirmed diagnosis of SARS-CoV-2 infection. Demographic, clinical information and routine laboratory data were collected at the hospital admission and until discharge. We investigated whether vonWillebrand /ADAMTS13 axis imbalance is a predictor of adverse outcomes. Logistic regression analysis, which controlled for potential confounders, was performed to evaluate the association between laboratory parameters and clinical outcomes. Results: Most women (55.6%) were parae, with median gestational age at admission of 39 weeks. At hospital admission, 63.3% were asymptomatic for COVID-19 and 24.4% showed more than one sign or symptom of infection. Nulliparae with group O showed Willebrand / ADA MTS-13 ratios significantly lower than non-O, whereas in multiparae this difference was not observed. Logistic regression showed that ratio von Willebrand to ADAMTS13 was significantly and independently associated with preterm delivery (OR 1.9, 95%CI 1.1–3.5). Conclusion: This study shows an imbalance of vonWillebrand /ADAMTS13 axis in pregnant women with COVID-19, leading to a significantly higher and independent risk of preterm delivery. Monitoring these biomarkers might support decision making process to manage and follow-up pregnancies in this setting

Identification of FVIII gene mutations in patients with hemophilia A using new combinatorial sequencing by hybridization

Background: Standard methods of mutation detection are time consuming in Hemophilia A (HA) rendering their application unavailable in some analysis such as prenatal diagnosis. Objectives: To evaluate the feasibility of combinatorial sequencing-by-hybridization (cSBH) as an alternative and reliable tool for mutation detection in FVIII gene. Patients/Methods: We have applied a new method of cSBH that uses two different colors for detection of multiple point mutations in the FVIII gene. The 26 exons encompassing the HA gene were analyzed in 7 newly diagnosed Italian patients and in 19 previously characterized individuals with FVIII deficiency. Results: Data show that, when solution-phase TAMRA and QUASAR labeled 5-mer oligonucleotide sets mixed with unlabeled target PCR templates are co-hybridized in the presence of DNA ligase to universal 6-mer oligonucleotide probe-based arrays, a number of mutations can be successfully detected. The technique was reliable also in identifying a mutant FVIII allele in an obligate heterozygote. A novel missense mutation (Leu1843Thr) in exon 16 and three novel neutral polymorphisms are presented with an updated protocol for 2-color cSBH. Conclusions: cSBH is a reliable tool for mutation detection in FVIII gene and may represent a complementary method for the genetic screening of HA patients