The hemostatic system. 1st Part

The hemostatic system is a complex ancestral pathway physiologically dedicated to protect the individual from bleeding. It starts immediately after an endothelial injury. Platelets and blood coagulation act synergically to provide a strength clot able to stop bleeding. In healthy subjects, the hemostatic system is able to work to avoid an excess of fibrin formation and deposition within the blood vessels on the one hand but is ready to stop bleeding on the other. To reach this crucial objective, a fine regulation of its activity is required. In other words, all actions of the hemostatic system are under control to assure a perfect balance to maintain people distant from both Scylla (bleeding) and Charybdis (thrombosis). Fibrinolysis is a complementary defensive system essential to regulate fibrin deposition via its dissolution. It is, in turn, well controlled to avoid bleeding and thrombosis by a fine control of its inducers and inhibitors. The aim of this review is to provide a picture of global haemostasis for helping in understanding this complex topic

Living on Oral Anticoagulants: Duke Anticoagulation Satisfaction Scale Results

Background: Direct oral anticoagulants (DOACs) are widely used in patients with atrial fibrillation and venous thromboembolism. The lack of the need for laboratory monitoring and a better safety than vitamin K antagonists (VKAs) has probably changed the quality of life of patients on these oral anticoagulants. This was a real-life prospective observational cohort study. The aim was to evaluate if a long-term treatment with DOACs could offer a better quality of life than VKAs. Moreover, age, gender, education level, time in therapeutic range for VKAs, taking medication once or twice a day for DOACs, the total daily number of medications and thrombotic and bleeding complications were considered as variables probably associated with the quality of life of these patients. Methods: Between January and December 2021, the Duke Anticoagulation Satisfaction Scale (DASS) 25-items was administered as an interview to patients on either VKAs or DOACs therapy. During the follow-up period, all of the patients were closely monitored to evaluate possible bleeding and thrombotic events. Results: The analysis included 300 outpatients treated with VKAs and 254 treated with DOACs. In general, the quality of life was better in patients taking DOACs (DASS total score: DOACs = 44.7, 42.9-46.5 vs. VKAs = 51, 49.2-52.8, p < 0.0001) as the daily-life limitations, hassles and burdens and the psychological impact were less important than in patients on VKAs therapy. Conclusions: VKAs negatively influence the daily-life of the patients in terms of both less satisfaction and time-consuming tasks. DOACs confer a better quality of life even if some concerns emerge from not knowing how their therapy is working

Heparins and 2019-nCoV infection: a narrative review

Abstract. – OBJECTIVE: Patients with 2019-nCoV infection have a high risk to develop venous thrombotic events. Several guidelines recommend the use of either unfractionated heparin or low molecular weight heparins in preventing thrombotic events in these patients. However, results from clinical studies, so far published, reached controversial conclusions on heparin efficacy in this kind of patients since the incidence of venous thromboembolism remains high despite prophylaxis. This narrative review aims to provide an overview of the antiviral and anti-inflammatory properties of heparins and their efficacy and safety in SARSCoV-2 medical ward-patients. Moreover, anatomical findings and ongoing trials are also reported. Finally, this narrative review tries to explain why heparins fail to prevent venous thrombosis. MATERIALS AND METHODS: We searched for the most relevant published studies on heparins and 2019-nCoV infected patients using the MEDLINE electronic database in the period between January and December 2020. Articles were preliminarily defined as eligible if they: a) were in English language, b) enrolled 250 or more medical ward-patients and 100 or more ICU-patients, c) reported results on patients treated with heparins in a percentage of at least 70% and d) performed an objectively confirmed diagnosis of VTE. RESULTS: Data from medium to large scientific studies show that the incidence of venous thrombotic events in medical ward-patients with SARS-CoV-2 vary between 0% and 8.3%, while this rate is higher, from 6.2% to 49%, in Intensive Care Unit-patients. However, heparins reduce the mortality rate in these patients of about 50%. Histological findings show that thrombosis could affect capillaries, main and small-midsized vessels, and it is associated with diffuse alveolar damage. CONCLUSIONS: Heparins have anti-inflammatory and anti-viral properties, which may be of help in reducing mortality in SARS-CoV-2 patients. Failure of heparins at prophylactic dosages in preventing VTE, especially in ICU-patients, could be due to the severity of the disease. Data on the use of heparins in an early phase of the 2019-nCoV infection are still lacking

Practical Suggestions for an Optimal Management of Vitamin K Antagonists: Italian Federation of Centers for the Diagnosis of Thrombotic Disorders and the Surveillance of the Antithrombotic Therapies (FCSA) Position Paper

In the era of direct oral anticoagulants, vitamin K antagonists retain a clinically relevant role in thrombotic disorders. In Italy, approximately 20% of the patients on anticoagulant therapies receives a VKA, in most cases warfarin. The optimal management of this drug is challenging and cannot disregard its intricate and unpredictable pharmacokinetic properties and patient's thrombotic and bleeding risk. Several clinical issues encountered during warfarin treatment are still unanswered and are tentatively addressed by physicians. In this regard, the Italian Federation of Centers for the diagnosis of thrombotic disorders and the Surveillance of the Antithrombotic therapies (FCSA) provides some experience-based good clinical practice's suggestions on the following topics: (1) how to start the anticoagulant treatment with warfarin and warfarin induction regimen; (2) how to manage a subtherapeutic INR value; (3) how to manage a supratherapeutic INR value in asymptomatic patients; and (4) how to manage the association of warfarin with interfering drugs

Heterogeneity of Antiphospholipid Syndrome (APS) as Characterized by Brain Perfusion Techniques. Towards New Ways of Syndrome Characterization

Antiphospholipid Syndrome (APS) syndrome is an autoimmune condition that affects the way that blood cells in humans bind together. Though the cause of APS is unclear, researchers believe that many factors have an impact on developing this pathological condition. Phospholipids (PLs) play numerous central roles in biological systems, and processes of biological systems regulation act through the liberation of a vast amount of different signalling molecules, which are also involved in the modulation of cell proliferation, inflammation, oxidative stress, neurotransmission and many other processes.A global landmark, holistic, is required to evaluate different phenotypes in APS. All thecriteria validated for the APS diagnosislead to an extremely heterogeneous landmark of the pathology and related to several manifestations in different systems. Heterogeneity also characterizes the SPECT acquisition of the patients and it is connected to several neurological and underestimates symptoms of the pathology. We present some examples to highlight the connection between heterogeneity in SPECT and APS markers of pathology indicating the needs to approach to the Syndrome in a holistic way. At the end of the paper we suggested the multidisciplinary approach that we are tuning for our analysis, approach based on Imaging, Metabolomic and Clinical evaluation, including mental health test for a neuropsychiatric characterization of the pathology

Molecular pathways triggered by COVID-19 in different organs: ACE2 receptor-expressing cells under attack? A review

OBJECTIVE: In human pathology, SARS-CoV-2 utilizes multiple molecular pathways to determine structural and biochemical changes within the different organs and cell types. The clinical picture of patients with COVID-19 is characterized by a very large spectrum. The reason for this variability has not been clarified yet, causing the inability to make a prognosis on the evolution of the disease. MATERIALS AND METHODS: PubMed search was performed focusing on the role of ACE 2 receptors in allowing the viral entry into cells, the role of ACE 2 downregulation in triggering the tissue pathology or in accelerating previous disease states, the role of increased levels of Angiotensin II in determining endothelial dysfunction and the enhanced vascular permeability, the role of the dysregulation of the renin angiotensin system in COVID-19 and the role of cytokine storm. RESULTS: The pathological changes induced by SARS-CoV-2 infection in the different organs, the correlations between the single cell types targeted by the virus in the different human organs and the clinical consequences, COVID-19 chronic pathologies in liver fibrosis, cardiac fibrosis and atrial arrhythmias, glomerulosclerosis and pulmonary fibrosis, due to the systemic fibroblast activation induced by angiotensin II are discussed. CONCLUSIONS: The main pathways involved showed different pathological changes in multiple tissues and the different clinical presentations. Even if ACE2 is the main receptor of SARS-CoV-2 and the main entry point into cells for the virus, ACE2 expression does not always explain the observed marked inter-individual variability in clinical presentation and outcome, evidencing the complexity of this disorder. The proper interpretation of the growing data available might allow to better classifying COVID-19 in human pathology

Clot characterization by multidisciplinary approach: biochemical and imaging parameters in a hypocoagulative setting. A pilot study.

Background: Clot characterization is, to the present days, a multimodal approach: scanning the clot by electron microscopy (SEM) is helpful for the visualization of fibrin structure along with laboratory parameters such as the clot waveform analysis (CWA) and thrombin generation in different settings of clot abnormalities. This study aimed to assess whether the coagulative parameters were consistent with the clot images texture acquired by SEM, and therefore to propose a more generalist and integrative approach to clots classification.Design and Methods: In this pilot study, the examined population consists of eight healthy subjects, seven patients affected by Acquired Hemophilia A (AHA) and seven patients treated with Vitamin K Antagonists (VKAs), similar for age and gender. We studied the velocity and acceleration (1st and 2nd derivative of the aPTT) of clot formation (CWA), the thrombin generation, and the clots' scanning by SEM. Images acquired with SEM were then analyzed with the MATLAB software with the "Texture Analysis" methods to perform classification. Among the various texture parameters, we reported Contrast and Energy.Results: Significant differences among healthy subjects, patients with AHA and those treated with VKAs were detected for the coagulative parameters. We found no differences between VKAs and AHA patients. Contrast and energy highlighted a significant difference among the three groups in agreement with the laboratory's parameters. We found no significant differences between VKAs and AHA patients.Conclusions: The use of SEM, CWA and thrombin generation parameters may be a starting point for studies aimed to demonstrate the general characteristics of clot formation in different clinical conditions with a multiparametric approach