Impact of allele-selective silencing of von Willebrand factor in mice based on a single nucleotide allelic difference in von Willebrand factor.

INTRODUCTION: Von Willebrand factor (VWF) plays a pathophysiological role in hemostatic disorders. Partial inhibition of the VWF gene through small interfering RNA (siRNA)-mediated allele-selective silencing could be a promising therapeutic strategy. For von Willebrand disease, allele-selectively inhibiting dominant-negative VWF-alleles might ameliorate the phenotype. For thrombotic disorders, partial VWF reduction can lower thrombotic risk, while avoiding bleeding. Previously, we demonstrated the feasibility of Vwf-silencing in homozygous C57BL/6J (B6) or 129S1/SvImJ (129S) mice. The present study investigated allele-selective Vwf-silencing in a complex heterozygous setting of crossed B6 and 129S mice and its subsequent hemostatic impact. MATERIALS AND METHODS: Heterozygous B6.129S mice were treated with siRNAs targeting Vwf expressed from either B6- (siVwf.B6) or 129S-alleles (siVwf.129S). Plasma VWF and lung Vwf mRNA were determined. siVwf.B6-treated B6.129S mice were subjected to ferric chloride-induced mesenteric vessel thrombosis and tail-bleeding. RESULTS: In B6.129S mice, siVwf.B6 reduced Vwf mRNA of the targeted B6-allele by 72% vs. only 12% of the non-targeted 129S-allele (41% total mRNA reduction), lowering plasma VWF by 46%. Oppositely, siVwf.129S reduced Vwf mRNA by 45%, now selectively inhibiting the 129S-allele over the B6-allele (58% vs. 9%), decreasing plasma VWF by 43%. The allele-selective VWF reduction by siVwf.B6 coincided with decreased thrombus formation in mesenteric arterioles, without prolonging tail-bleeding times. CONCLUSIONS: This study demonstrates the feasibility of allele-selective Vwf-silencing in a heterozygous setting, achieving a controlled close to 50% reduction of plasma VWF. The observed thromboprotection and absence of prolonged bleeding times underline the potential of allele-selective Vwf-silencing as a therapeutic strategy in hemostatic disorders.

Bleeding disorders in Saudi Arabia, causes and prevalence: a review.

As bleeding disorders are a worldwide health concern, Saudi Arabia is experiencing a notable prevalence of such disorders. Studying the frequency and cause of hemostatic disorders is the key to successful clinical interventions and instigating effective public policies that limit the spread of such disorders. The current review aims to highlight the major findings of the body of literature that has investigated the causes, prevalence, and major challenges associated with bleeding disorders in the country. The current review summarizes the major findings of different studies that have been conducted in Saudi Arabia regarding different bleeding disorders. Multiple causes and symptoms of bleeding disorders have been reported by different studies. Some studies investigated the genetic aspect of bleeding disorders and revealed specific mutations in coagulation factor genes influencing the symptoms of different bleeding disorders. Moreover, rare bleeding disorders such as Glanzmann thrombasthenia and Henoch-Schönlein purpura, have been reported in different regions of Saudi Arabia. Combining clinical presentations, genetic factors, and epidemiological data, the current review of the literature provides a comprehensive insight into bleeding disorders in the kingdom. This will help in advancing the diagnostic capabilities and genetic counseling enhancing management strategies and therapeutic interventions benefiting bleeding disorder patients and the kingdom.

Point-of-care, goal-directed management of bleeding in trauma patients.

PURPOSE OF REVIEW: The purpose of this review is to consider the clinical value of point-of-care (POC) testing in coagulopathic trauma patients with traumatic brain injury (TBI) and trauma-induced coagulopathy (TIC). RECENT FINDINGS: Patients suffering from severe TBI or TIC are at risk of developing pronounced haemostatic disorders. Standard coagulation tests (SCTs) are insufficient to reflect the complexity of these coagulopathies. Recent evidence has shown that viscoelastic tests (VETs) identify haemostatic disorders more rapidly and in more detail than SCTs. Moreover, VET results can guide coagulation therapy, allowing individualised treatment, which decreases transfusion requirements. However, the impact of VET on mortality remains uncertain. In contrast to VETs, the clinical impact of POC platelet function testing is still unproven. SUMMARY: POC SCTs are not able to characterise the complexity of trauma-associated coagulopathy. VETs provide a rapid estimation of underlying haemostatic disorders, thereby providing guidance for haemostatic therapy, which impacts allogenic blood transfusion requirements. The value of POC platelet function testing to identify platelet dysfunction and guide platelet transfusion is still uncertain.

Hemostatic disorders in patients with infective endocarditis undergoing urgent surgical valve replacement - Rethinking current beliefs.

BACKGROUND: Although infective endocarditis (IE) represents a unique model of thrombo-inflammatory disease, the most frequent early complications of surgical valve replacement (SVR) in IE population are coagulopathy and bleeding. The hemostatic capacity and procedure-related coagulation disorders of IE patients undergoing SVR are unknown. The aims of this study were to test periprocedural hemostasis in IE patients undergoing urgent SVR, and to assess the association between disorders of hemostasis and early bleeding as well as with thromboembolic events. METHODS: A prospective, two-center, hypothesis generating, observational study was performed between Dec 2017 and Jan 2020. Periprocedural hemostasis of IE patients was assessed using Total Thrombus-formation Analysis System (T-TAS Plus) within 24 h before and 72 h post SVR. RESULTS: Overall, 25 patients with active IE undergoing urgent SVR were tested. Hemostatic capacity of IE patients was significantly impaired pre-SVR as well as post-SVR compared to normal values, in most aspects of T-TAS assays under high and low shear forces, including prolonged activation of coagulation (T10), final clot formation (OT) and clot strength (AUC30). Post-SVR T-TAS results were significantly associated with early bleeding and with red blood cell, platelet, and fresh frozen plasma administration. No association with thrombo-embolic events was found. CONCLUSIONS: Patients with active IE undergoing urgent SVR have significantly reduced hemostatic capacity before and after SVR. Hemostatic insufficiency post-SVR is related to bleeding and blood products transfusion. T-TAS may be helpful in assessment of periprocedural hemostasis in patients with IE undergoing SVR.

[Hemostatic disorders in neurosurgical patients: diagnostics and correction]. / Narusheniya sistemy gemostaza u neirokhirurgicheskikh bol'nykh: diagnostika i korrektsiya.

The authors analyzed the main causes of perioperative hemostatic disorders in neurosurgical patients. The problem of preoperative hemostatic screening, intraoperative and postoperative factors contributing to hemostatic disorders are considered. The authors also discuss the methods for correction of hemostatic disorders.

Recent advances in therapeutic options for rare hemostatic disorders: selected poster extracts of recent research in hemophilia A, congenital hemophilia with inhibitors, von Willebrand disease, and thrombotic thrombocytopenic purpura presented at the 29th congress of the International Society on Thrombosis and Haemostasis (ISTH 2021, Jul 17-21; virtual congress).

Hemophilia, von Willebrand disease (VWD), and thrombotic thrombocytopenic purpura (TTP) are rare diseases affecting normal hemostasis. Although they differ in their pathogenesis and clinical manifestation, if left undiagnosed and untreated, all these conditions can result in severe long-term consequences and can be potentially life-threatening. This article summarizes a poster series funded by Takeda and presented virtually at the 29th annual congress of the International Society on Thrombosis and Haemostasis (ISTH) in 2021: Data from real-world evidence highlight the importance of joint health and personalized prophylaxis to prevent bleeding for patients with hemophilia, the need to further raise disease awareness in support of timely diagnosis and access to treatment in general practice settings for patients with VWD, and describe the clinical burden for patients with TTP and the importance to advance treatment options for these patients.

Thrombodynamics as a tool for monitoring hemostatic disorders in patients with chronic glomerulonephritis complicated by nephrotic syndrome.

Nephrotic syndrome (NS) is associated with a high risk for venous and arterial thrombosis due to hypercoagulability. Integral tests designed to assess hemostasis can become an alternative for measuring hypercoagulability in patients with NS. STUDY OBJECTIVE: To assess hemostatic disorders in CGN patients complicated by NS using the thrombodynamics test. MATERIALS AND METHODS: The study included 60 adult patients with chronic glomerulonephritis (CGN), mean age 37 years, 31 (52%) women, and 29 (48%) men. Among all patients, 53 % of patients had NS, 47 % had no sign of NS. Hemostasis was assessed using the thrombodynamics test. The results were compared with biochemical parameters, which are usually associated with NS and renal dysfunction. RESULTS: According to the thrombodynamics test, CGN patients with NS demonstrated a tendency to hypercoagulability: increased rates of V (rate of clot growth), increased D (clot density), and increased CS (clot size) after 30 minutes. A positive correlation of these parameters with the serum albumin, creatinine levels, and glomerular filtration rate (GFR) indicates the influence of severe NS and renal dysfunction on the hemostasis activation in CGN patients with NS. CONCLUSION: According to the thrombodynamics test, CGN patients with NS demonstrate increased rates of clot formation, increased clot size after 30 minutes, and increased clot density due to secondary hemostasis activation. These changes positively correlate with the severity of hypoalbuminemia, hypercholesterolemia, and renal dysfunction in NS patients.

Emergency Department Evaluation of Abnormal Uterine Bleeding in US Children's Hospitals.

STUDY OBJECTIVE: To assess initial evaluation patterns of patients presenting to the Emergency Department (ED) with abnormal uterine bleeding (AUB) including differences by race DESIGN: Retrospective multicenter cohort study from October 2015 through September 2020 SETTING: Forty-seven children's hospitals submitting data to the Pediatric Health Information System PARTICIPANTS: Female patients aged 8-21 with an ED encounter with AUB as the primary diagnosis code INTERVENTIONS AND MAIN OUTCOME MEASURES: Proportion of visits with at least 1 laboratory assessment for the evaluation of anemia, iron deficiency, and/or hemostatic disorders RESULTS: We identified 17,759 unique patients with AUB seen in the ED who met inclusion criteria. Median age was 16.3 years (IQR, 14.1-17.8 years). Most encounters (n = 11,576, 65.2%) included evaluation for anemia, but only 6.8% (n = 1,215) included assessment for iron deficiency and 26.2% (n = 4,654) for hemostatic disorders. Black patients accounted for 34.7% (n = 6,155) of AUB encounters yet constituted only 25% of all ED encounters (n = 198,192). Black patients with AUB were less likely to undergo bleeding disorder evaluation (OR = 0.76; 95% CI, 0.69-0.83) but more likely to receive evaluation for sexually transmitted infections (OR = 1.63; 95% CI, 1.48-1.80) compared with White patients, despite controlling for age and concomitant pain. CONCLUSIONS: In a national cohort of adolescents presenting to the ED with AUB, evaluations for anemia and hemostatic disorders were infrequently performed, and racial differences existed regarding initial assessment. Further studies are needed to understand the factors underlying racial differences in hematologic testing and the impact of this disparity on health outcomes for females with AUB.

Generation of neutrophil extracellular traps in patients with acute liver failure is associated with poor outcome.

BACKGROUND AND AIMS: Acute liver failure (ALF) is characterized by significant changes in the hemostatic system and by systemic inflammation. The formation of neutrophil extracellular traps (NETs), in which an activated neutrophil expels its DNA, histones, and granular enzymes, such as myeloperoxidase (MPO), has been associated with immune-mediated and thrombotic diseases. We hypothesized that formation of NETs in patients with ALF contributes to progression of disease. APPROACH AND RESULTS: A total of 676 patients with ALF (international normalized ratio [INR], ≥1.5) or severe acute liver injury (ALI; INR, ≥2.0) were recruited from the U.S. ALF Study Group Registry between 2011 and 2018, of whom 308 patients (45.6%) had acetaminophen-induced ALF. Up to 21 days after admission, 483 patients (71.5%) survived without liver transplantation (LT). Levels of cell-free DNA (cfDNA) and the specific NET marker MPO-DNA complexes were measured in plasma samples obtained on admission and compared to levels in healthy controls. In addition, liver tissue obtained at transplantation of 20 ALF patients was stained for NETs. Levels of cfDNA were 7.1-fold, and MPO-DNA complexes 2.5-fold, higher in patients with ALF compared to healthy controls. cfDNA levels were not associated with 21-day transplant-free survival, but were higher in those patients with more-severe disease on admission, as reflected by various laboratory and clinical parameters. MPO-DNA levels were 30% higher in patients with ALF who died or required urgent LT. Liver tissue of ALF patients stained positive for NETs in 12 of 18 evaluable patients. CONCLUSIONS: Here, we provide evidence for NET formation in patients with ALF. Elevated plasma levels of MPO-DNA complexes in patients with ALF were associated with poor outcome, which suggests that NET formation contributes to disease progression.

Laboratory Methods in the Assessment of Hereditary Hemostatic Disorders.

In patients presenting with a suspect hereditary bleeding disorder a detailed bleeding history is first obtained. Testing proceeds in a tiered manner with platelet count, platelet morphology, platelet histogram, PFA-100, fibrinogen, prothrombin time, and activated partial thromboplastin time. More detailed testing includes von Willebrand factor, individual clotting factor assays, and platelet function testing. Next, testing for a dysfibrinogenemia, FXIII, or a fibrinolytic defect is considered. Hemostatic abnormality is not demonstrated in a fraction of patients. An approach to management in these patients, such as desmopressin or antifibrinolytic therapy, may be required and empiric use of blood component therapy is discouraged.

Hemostatic Disorders: Physiology, Diagnostics, and Management.

A defect in any step of hemostasis can lead to potentially catastrophic results. The purpose of this article is to review hemostatic physiology, laboratory studies, and management of platelet and coagulation disorders to familiarize the advanced practice RN (APRN) with this often overlooked but critical system. Learning the underlying mechanisms allows for better understanding of the various disease states that can occur in the hematology and oncology settings.

Clinical screening for menorrhagia and other bleeding symptoms in Nigerian women.

Objective: The objective of the study was to evaluate the prevalence of perceived bleeding symptoms in Nigerian women and the usefulness of a simple clinical screening tool for bleeding symptoms. Materials and Methods: A population-based cross-sectional survey of 1524 women of 16-50 years in Southeast Nigeria using a structured, prevalidated, pretested questionnaire was conducted. Results: A total of 1524 (85%) women responded with the mean age of 26 (10.6) years. Prevalence of bleeding symptoms was 24.6% and 11% of the women reported a positive family history of bleeding symptoms. There was a significant association between having a positive family history of bleeding disorder and experiencing bleeding symptoms (adjusted odds ratio: 0.12, 95% confidence interval: 0.06-0.22 P < 0.0001). Two hundred and six women experienced at least one bleeding symptom, 125 (8.2%) experienced at least two, whereas 43 (2.8%) experienced >3 bleeding symptoms. The most common perceived bleeding symptom was heavy menstrual bleeding (HMB) present in 83 women (22.2%), 141 (9.3%) reported a past history of HMB, 202 (13.3%) had heavy bleeds during most of their monthly cycle, and 351 (23%) requiring resuscitation with blood support. Conclusion: The prevalence of perceived bleeding symptoms among women is high, and HMB is the most common bleeding symptom. This clinical screening tool is easy and cost-effective in routinely identifying women with bleeding symptoms needing further hemostatic and obstetrics evaluation.

RésuméObjectif: L'objectif de l'étude était d'évaluer la prévalence des symptômes hémorragiques perçus chez les femmes nigérianes et l'utilité d'un outil de dépistage clinique simple des symptômes hémorragiques. Matériel et méthodes: enquête transversale auprès de la population auprès de 1 524 femmes de 16 à 50 ans dans le sud-est du Nigéria à l'aide d'un questionnaire structuré, prévalidé et prétesté. Résultats: Un total de 1524 (85%) les femmes ont répondu avec l'âge moyen de 26 (10,6) ans. La prévalence des symptômes hémorragiques était de 24,6% et 11% des femmes ont signalé un antécédents familiaux positifs de symptômes hémorragiques. Il y avait une association significative entre avoir des antécédents familiaux de saignement positifs trouble et présentant des symptômes hémorragiques (rapport de cotes ajusté: 0,12, intervalle de confiance à 95%: 0,06­0,22 P <0,0001). Deux cent et six femmes ont présenté au moins un symptôme de saignement, 125 (8,2%) en ont eu au moins deux, tandis que 43 (2,8%) ont eu> 3 saignements symptômes. Le symptôme de saignement perçu le plus courant était le saignement menstruel abondant (HMB) présent chez 83 femmes (22,2%), 141 (9,3%) ont signalé des antécédents de HMB, 202 (13,3%) ont eu des saignements abondants pendant la majeure partie de leur cycle mensuel et 351 (23%) ont dû être réanimés avec support sanguin. Conclusion: la prévalence des symptômes hémorragiques perçus chez les femmes est élevée et le HMB est le plus courant symptôme de saignement. Cet outil de dépistage clinique est simple et économique pour identifier systématiquement les femmes présentant des symptômes hémorragiques nécessitant évaluation hémostatique et obstétrique plus poussée.

Pharmacological Correction of Cisplatin-Induced Hemostatic Disorders.

A single intraperitoneal administration of cisplatin in the MTD to outbred female mice disturbed hemostasis and formed the procoagulant phenotype of hemostatic potential on days 7-10 culminating in a pronounced hypocoagulation on day 15. Hemostasis was corrected with warfarin and an extract containing furocoumarins composed of isopimpinellin (42.97%), bergapten (35.18%), and xanthotoxin (15.41%). The extract was standardized with gas chromatography-mass spectrometry, thin-layer chromatography, and HPLC. Furocoumarins and reference drug warfarin were administered intragastrically during 4 days starting on day 6 after the administration of cisplatin. Both furocoumarins and warfarin corrected hypercoagulation on days 7-10. On day 10, furocoumarins normalized coagulation, whereas warfarin resulted in hypocoagulation. On days 15-30, no effects of warfarin were observed. furocoumarins corrected hypocoagulation on days 15-20 with prolongation of this effect up to experimental day 30.

Therapeutic Potential of Resveratrol in COVID-19-Associated Hemostatic Disorders.

Coagulation disorders, endotheliopathy and inflammation are the most common hallmarks in SARS-CoV-2 infection, largely determining COVID-19's outcome and severity. Dysfunctions of endothelial cells and platelets are tightly linked in contributing to the systemic inflammatory response that appears to be both a cause and a consequence of COVID-19-associated coagulation disorders and thrombotic events. Indeed, elevated levels of circulating inflammatory cytokines are often associated with abnormal coagulation parameters in COVID-19 patients. Although treatments with low molecular weight heparin (LMWH) have shown beneficial effects in decreasing patient mortality with severe COVID-19, additional therapeutic strategies are urgently needed. Utilizing the anti-inflammatory and anti-thrombotic properties of natural compounds may provide alternative therapeutic approaches to prevent or reduce the risk factors associated with pre-existing conditions and comorbidities that can worsen COVID-19 patients' outcomes. In this regard, resveratrol, a natural compound found in several plants and fruits such as grapes, blueberries and cranberries, may represent a promising coadjuvant for the prevention and treatment of COVID-19. By virtue of its anti-thrombotic and anti-inflammatory properties, resveratrol would be expected to lower COVID-19-associated mortality, which is well known to be increased by thrombosis and inflammation. This review analyzes and discusses resveratrol's ability to modulate vascular hemostasis at different levels targeting both primary hemostasis (interfering with platelet activation and aggregation) and secondary hemostasis (modulating factors involved in coagulation cascade).

Rationale for the Role of Heparin and Related GAG Antithrombotics in COVID-19 Infection.

The SARS-CoV-2 pandemic has focused attention on prevention, restriction and treatment methods that are acceptable worldwide. This means that they should be simple and inexpensive. This review examines the possible role of glycosaminoglycan (GAG) antithrombotics in the treatment of COVID-19. The pathophysiology of this disease reveals a complex interplay between the hemostatic and immune systems that can be readily disrupted by SARS-CoV-2. Some of the GAG antithrombotics also possess immune-modulatory actions and since they are relatively inexpensive they could play an important role in the management of COVID-19 and its complications.

Device-Induced Hemostatic Disorders in Mechanically Assisted Circulation.

Mechanically assisted circulation (MAC) sustains the blood circulation in the body of a patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) or on ventricular assistance with a ventricular assist device (VAD) or on extracorporeal membrane oxygenation (ECMO) with a pump-oxygenator system. While MAC provides short-term (days to weeks) support and long-term (months to years) for the heart and/or lungs, the blood is inevitably exposed to non-physiological shear stress (NPSS) due to mechanical pumping action and in contact with artificial surfaces. NPSS is well known to cause blood damage and functional alterations of blood cells. In this review, we discussed shear-induced platelet adhesion, platelet aggregation, platelet receptor shedding, and platelet apoptosis, shear-induced acquired von Willebrand syndrome (AVWS), shear-induced hemolysis and microparticle formation during MAC. These alterations are associated with perioperative bleeding and thrombotic events, morbidity and mortality, and quality of life in MCS patients. Understanding the mechanism of shear-induce hemostatic disorders will help us develop low-shear-stress devices and select more effective treatments for better clinical outcomes.

Inflammation and thrombosis in patients with COVID-19: A prothrombotic and inflammatory disease caused by SARS coronavirus-2.

Coronavirus disease 2019 (COVID-19) caused by 'Severe Acute Respiratory Syndrome Coronavirus-2' (SARS-CoV-2) infection emerged in Wuhan, a city of China, and spread to the entire planet in early 2020. The virus enters the respiratory tract cells and other tissues via ACE2 receptors. Approximately 20% of infected subjects develop severe or critical disease. A cytokine storm leads to over inflammation and thrombotic events. The most common clinical presentation in COVID-19 is pneumonia, typically characterized by bilateral, peripheral, and patchy infiltrations in the lungs. However multi-systemic involvement including peripheral thromboembolic skin lesions, central nervous, gastrointestinal, circulatory, and urinary systems are reported. The disease has a higher mortality compared to other viral agents causing pneumonia and unfortunately, no approved specific therapy, nor vaccine has yet been discovered. Several clinical trials are ongoing with hydroxychloroquine, remdesivir, favipiravir, and low molecular weight heparins. This comprehensive review aimed to summarize coagulation abnormalities reported in COVID-19, discuss the thrombosis, and inflammation-driven background of the disease, emphasize the impact of thrombotic and inflammatory processes on the progression and prognosis of COVID-19, and to provide evidence-based therapeutic guidance, especially from antithrombotic and anti-inflammatory perspectives.

Correlating Fibrinogen Consumption and Profiles of Inflammatory Molecules in Human Envenomation's by Bothrops atrox in the Brazilian Amazon.

Snakebites are considered a major public health problem worldwide. In the Amazon region of Brazil, the snake Bothrops atrox (B. atrox) is responsible for 90% of the bites. These bites may cause local and systemic signs from acute inflammatory reaction and hemostatic changes, and present common hemorrhagic disorders. These alterations occur due the action of hemostatically active and immunogenic toxins which are capable of triggering a wide range of hemostatic and inflammatory events. However, the crosstalk between coagulation disorders and inflammatory reaction still has gaps in snakebites. Thus, the goal of this study was to describe the relationship between the consumption of fibrinogen and the profile of inflammatory molecules (chemokines and cytokines) in evenomations by B. atrox snakebites. A prospective study was carried out with individuals who had suffered B. atrox snakebites and presented different levels of fibrinogen consumption (normal fibrinogen [NF] and hypofibrinogenemia [HF]). Seventeen patients with NF and 55 patients with HF were eligible for the study, in addition to 50 healthy controls (CG). The molecules CXCL-8, CCL-5, CXCL-9, CCL-2, CXCL-10, IL-6, TNF, IL-2, IL-10, IFN-γ, IL-4, and IL-17A were quantified in plasma using the CBA technique at three different times (pre-antivenom therapy [T0], 24 h [T1], and 48 h [T2] after antivenom therapy). The profile of the circulating inflammatory response is different between the groups studied, with HF patients having higher concentrations of CCL-5 and lower IFN-γ. In addition, antivenom therapy seems to have a positive effect, leading to a profile of circulating inflammatory response similar in quantification of T1 and T2 on both groups. Furthermore, these results suggest that a number of interactions of CXCL-8, CXCL-9, CCL-2, IL-6, and IFN-γ in HF patients are directly affected by fibrinogen levels, which may be related to the inflammatory response and coagulation mutual relationship induced by B. atrox venom. The present study is the first report on inflammation-coagulation crosstalk involving snakebite patients and supports the better understanding of envenomation's pathophysiology mechanisms and guides in the search for novel biomarkers and prospective therapies.

Recomendaciones de consenso SEDAR-SEMICYUC sobre el manejo de las alteraciones de la hemostasia en los pacientes graves con infección por COVID-19 / SEDAR-SEMICYUC consensus recommendations on the management of haemostasis disorders in severely ill patients with COVID-19 infection

La infección por el coronavirus SARS-CoV-2, causante de la enfermedad denominada COVID-19, provoca alteraciones fundamentalmente en el sistema respiratorio. En los pacientes graves, con frecuencia la enfermedad evoluciona a un síndrome de distrés respiratorio agudo que puede predisponer a los pacientes a un estado de hipercoagulabilidad, con trombosis tanto a nivel venoso como arterial. Esta predisposición presenta una fisiopatología multifactorial, relacionada tanto con la hipoxia como con el grave proceso inflamatorio ligado a esta patología, además de los factores trombóticos adicionales presentes en muchos de los pacientes.Ante la necesidad de optimizar el manejo de la hipercoagulabilidad, los grupos de trabajo de las sociedades científicas de Anestesiología-Reanimación y Terapéutica del Dolor (SEDAR) y de Medicina Intensiva, Crítica y de Unidades Coronarias (SEMICYUC) han desarrollado un consenso para establecer unas pautas de actuación frente a las alteraciones de la hemostasia observadas en los pacientes graves COVID-19. Estas recomendaciones incluyen la profilaxis de la enfermedad tromboembólica venosa en pacientes graves y en el periparto, el manejo de los pacientes en tratamiento crónico con fármacos antiagregantes o anticoagulantes, de las complicaciones hemorrágicas en la evolución de la enfermedad y de la interpretación de las alteraciones generales de la hemostasia

The infection by the coronavirus SARS-CoV-2, which causes the disease called COVID-19, mainly causes alterations in the respiratory system. In severely ill patients, the disease often evolves into an acute respiratory distress syndrome that can predispose patients to a state of hypercoagulability, with thrombosis at both venous and arterial levels. This predisposition presents a multifactorial physiopathology, related to hypoxia as well as to the severe inflammatory process linked to this pathology, including the additional thrombotic factors present in many of the patients. In view of the need to optimise the management of hypercoagulability, the working groups of the Scientific Societies of Anaesthesiology-Resuscitation and Pain Therapy (SEDAR) and of Intensive, Critical Care Medicine and Coronary Units (SEMICYUC) have developed a consensus to establish guidelines for actions to be taken against alterations in haemostasis observed in severely ill patients with COVID-19. These recommendations include prophylaxis of venous thromboembolic disease in these patients, and in the peripartum, management of patients on long-term antiplatelet or anticoagulant treatment, bleeding complications in the course of the disease, and the interpretation of general alterations in haemostasis