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Clinics in Chest Medicine Sep 2016Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is associated with oculocutaneous albinism, bleeding diatheses, granulomatous colitis, and highly... (Review)
Review
Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is associated with oculocutaneous albinism, bleeding diatheses, granulomatous colitis, and highly penetrant pulmonary fibrosis in some subtypes, including HPS-1, HPS-2, and HPS-4. HPS pulmonary fibrosis shows many of the clinical, radiologic, and histologic features found in idiopathic pulmonary fibrosis, but occurs at a younger age. Despite knowledge of the underlying genetic defects, there are currently no definitive therapeutic or preventive approaches for HPS pulmonary fibrosis other than lung transplant.
Topics: Albinism; Albinism, Oculocutaneous; Arteriovenous Malformations; Blood Coagulation Disorders; Crohn Disease; Epistaxis; Gastrointestinal Diseases; Hemorrhagic Disorders; Hermanski-Pudlak Syndrome; Humans; Hypertension, Pulmonary; Intracranial Arteriovenous Malformations; Liver Diseases; Pulmonary Artery; Pulmonary Fibrosis; Pulmonary Veins; Telangiectasis
PubMed: 27514596
DOI: 10.1016/j.ccm.2016.04.012 -
Current Opinion in Anaesthesiology Apr 2015Sepsis, defined by the presence of infection and host inflammation, is a lethal clinical syndrome with an increasing mortality rate worldwide. In severe disease, the... (Review)
Review
PURPOSE OF REVIEW
Sepsis, defined by the presence of infection and host inflammation, is a lethal clinical syndrome with an increasing mortality rate worldwide. In severe disease, the coagulation system becomes diffusely activated, with consumption of multiple clotting factors resulting in disseminated intravascular coagulation (DIC). When present, DIC portends a higher mortality rate. Understanding the mechanisms that tie inflammation and diffuse thrombosis will allow therapeutic interventions to be developed. The coagulopathy of acute sepsis is a dynamic process that is time and disease burden specific. Whole-blood testing of coagulation may provide more clinically useful information than the classical tests. Natural anticoagulants that regulate thrombosis are downregulated in sepsis. Patients may benefit from the modulation of the coagulation system when systemic inflammation and hypercoagulopathy exist. Proper timing of anticoagulant therapy may ultimately lead to decreased incidence of multisystem organ dysfunction.
RECENT FINDINGS
The pathogenesis of coagulopathy in sepsis is driven by an upregulation of procoagulant mechanisms and simultaneous downregulation of natural anticoagulants. Inflammation caused by the invading organism is a natural host defense that cannot be eliminated during treatment. Successful strategies to prevent multisystem organ dysfunction center on stratifying patients at high risk for DIC and restoring the balance of inflammation and coagulation.
SUMMARY
The prevention of DIC in septic patients is a key therapeutic target in preventing death from multisystem organ failure. Stratifying patients for therapy using thromboelastometry, specific markers for DIC, and composite scoring systems is an area of growing research.
Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Humans; Multiple Organ Failure; Sepsis; Thrombosis
PubMed: 25590467
DOI: 10.1097/ACO.0000000000000163 -
Life Sciences Nov 2020Coronavirus disease 2019 (COVID-19) is a prominent pandemic disease that emerged in China and hurriedly stretched worldwide. There are many reports on COVID-19... (Review)
Review
Coronavirus disease 2019 (COVID-19) is a prominent pandemic disease that emerged in China and hurriedly stretched worldwide. There are many reports on COVID-19 associated with the amplified incidence of thrombotic events. In this review, we focused on COVID-19 coupled with the coagulopathy contributes to severe outcome inclusive of comorbidities such as venous thromboembolism, stroke, diabetes, lung, heart attack, AKI, and liver injury. Initially, the COVID-19 patient associated coagulation disorders show an elevated level of the D-dimer, fibrinogen, and less lymphocyte count such as lymphopenia. COVID-19 associated with the Kawasaki disease has acute vasculitis in childhood which further affects the vessels found all over the body. COVID-19 linked with the thrombotic microangiopathy triggers the multiple vasculitis along with the arterioles thrombosis, medium, large venous and arterial vessels mediates the disseminated intravascular coagulation (DIC). SARS-Co-V-2 patients have reduced primary platelet production, increased destruction of the platelet, decreased circulating platelet leads to the condition of increased thrombocytopenia which contributes to the coagulation disorder. Endothelial dysfunction plays an important role in the coagulation disorders via increased generation of the thrombin and stops fibrinolysis further leads to hypercoagulopathy. Along with that endothelial dysfunction activates the complement system pathways and contributes to the acute and chronic inflammation via cytokine storm with the production of the cytokines and chemokines, coagulation in different organs such as lung, brain, liver, heart, kidney and further leads to multi-organ failure.
Topics: Betacoronavirus; Blood Coagulation Disorders; COVID-19; Coronavirus Infections; Humans; Multiple Organ Failure; Pandemics; Pneumonia, Viral; Prognosis; SARS-CoV-2
PubMed: 32946915
DOI: 10.1016/j.lfs.2020.118431 -
The Lancet. Haematology Sep 2020
Topics: Betacoronavirus; Blood Coagulation Disorders; COVID-19; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; Prognosis; Retrospective Studies; Risk Factors; SARS-CoV-2
PubMed: 32659213
DOI: 10.1016/S2352-3026(20)30218-0 -
CMAJ : Canadian Medical Association... Nov 2020
Topics: Betacoronavirus; Blood Coagulation Disorders; COVID-19; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; Prognosis; SARS-CoV-2
PubMed: 33168770
DOI: 10.1503/cmaj.200685-f -
Journal of Thrombosis and Haemostasis :... May 2018
Topics: Animals; Blood Coagulation Disorders; Cardiovascular Diseases; Female; Genetic Predisposition to Disease; Health Status Disparities; Healthcare Disparities; Humans; Male; Phenotype; Prognosis; Risk Assessment; Risk Factors; Sex Factors
PubMed: 29675977
DOI: 10.1111/jth.14019 -
Journal of Thrombosis and Haemostasis :... Jun 2015We have proposed that modified platelets could potentially be used to correct intrinsic platelet defects as well as for targeted delivery of therapeutic molecules to... (Review)
Review
We have proposed that modified platelets could potentially be used to correct intrinsic platelet defects as well as for targeted delivery of therapeutic molecules to sights of vascular injury. Ectopic expression of proteins within α-granules prior to platelet activation has been achieved for several proteins, including urokinase, factor (F) VIII, and partially for FIX. Potential uses of platelet-directed therapeutics will be discussed, focusing on targeted delivery of urokinase as a thromboprophylactic agent and FVIII for the treatment of hemophilia A patients with intractable inhibitors. This presentation will discuss new strategies that may be useful in the care of patients with vascular injury as well as remaining challenges and limitations of these approaches.
Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Factor V Deficiency; Gene Transfer Techniques; Genetic Predisposition to Disease; Genetic Therapy; Hemophilia A; Humans; Platelet Transfusion; Treatment Outcome; Urokinase-Type Plasminogen Activator
PubMed: 26149015
DOI: 10.1111/jth.12938 -
Anaesthesia Jan 2015Over the last 10 years, the management of major haemorrhage in trauma patients has changed radically. This is mainly due to the recognition that many patients who are... (Review)
Review
Over the last 10 years, the management of major haemorrhage in trauma patients has changed radically. This is mainly due to the recognition that many patients who are bleeding when they come in to the emergency department have an established coagulopathy before the haemodilution effects of fluid resuscitation. This has led to the use of new terminology: acute traumatic coagulopathy, acute coagulopathy of trauma shock or trauma-induced coagulopathy. The recognition of acute traumatic coagulopathy is important, because we now understand that its presence is a prognostic indicator, as it is associated with poor clinical outcome. This has driven a change in clinical management, so that the previous approach of maintaining an adequate circulating volume and oxygen carrying capacity before, as a secondary event, dealing with coagulopathy, has changed to haemostatic resuscitation as early as possible. While there is as yet no universally accepted assay or definition, many experts use prolongation of the prothrombin time to indicate that there is, indeed, a coagulopathy. Hypoxia, acidosis and hypothermia and hormonal, immunological and cytokine production, alongside consumption and blood loss, and the dilutional effects of resuscitation may occur to varying extents depending on the type of tissue damaged, the type and extent of injury, predisposing to, or amplifying, activation of coagulation, platelets, fibrinolysis. These are discussed in detail within the article.
Topics: Acute Disease; Blood Coagulation Disorders; Humans; Resuscitation; Thrombelastography; Wounds and Injuries
PubMed: 25440402
DOI: 10.1111/anae.12914 -
International Journal of Molecular... Mar 2022Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by thrombosis. In some cases... (Review)
Review
Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by thrombosis. In some cases of severe COVID-19, fibrinolysis may be markedly enhanced within a few days, resulting in fatal bleeding. In the treatment of COVID-19, attention should be paid to both coagulation activation and fibrinolytic activation. Various thromboses are known to occur after vaccination with SARS-CoV-2 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can occur after adenovirus-vectored vaccination, and is characterized by the detection of anti-platelet factor 4 antibodies by enzyme-linked immunosorbent assay and thrombosis in unusual locations such as cerebral venous sinuses and visceral veins. Treatment comprises high-dose immunoglobulin, argatroban, and fondaparinux. Some VITT cases show marked decreases in fibrinogen and platelets and marked increases in D-dimer, suggesting the presence of enhanced-fibrinolytic-type disseminated intravascular coagulation with a high risk of bleeding. In the treatment of VITT, evaluation of both coagulation activation and fibrinolytic activation is important, adjusting treatments accordingly to improve outcomes.
Topics: Biomarkers; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; COVID-19; COVID-19 Vaccines; Combined Modality Therapy; Disease Management; Disease Susceptibility; Fibrinolysis; Humans; Prognosis; SARS-CoV-2; Treatment Outcome
PubMed: 35328761
DOI: 10.3390/ijms23063338 -
World Journal of Gastroenterology Jun 2021Hemostasis is a complex physiological process based on the balance between pro-coagulant and anticoagulant systems to avoid pathological bleeding or thrombosis. The... (Review)
Review
Hemostasis is a complex physiological process based on the balance between pro-coagulant and anticoagulant systems to avoid pathological bleeding or thrombosis. The changes in standard coagulation tests in liver disease were assumed to reflect an acquired bleeding disorder, and cirrhotic patients were considered naturally anticoagulated. In the light of the new evidence, the theory of rebalanced hemostasis replaced the old concept. According to this model, the hemostatic alteration leads to a unique balance between pro-coagulant, anticoagulant, and fibrinolytic systems. But the balance is fragile and may prone to bleeding or thrombosis depending on various risk factors. The standard coagulation tests [INR (international normalized ratio), platelet count and fibrinogen] only explore parts of the hemostasis, not offering an entire image of the process. Rotational thromboelastometry (ROTEM) and thromboelastography (TEG) are both point of care viscoelastic tests (VET) that provide real-time and dynamic information about the entire hemostasis process, including clot initiation (thrombin generation), clot kinetics, clot strength, and clot stability (lysis). Despite prolonged PT/INR (international normalized ratio of prothrombin time) and low platelet counts, VET is within the normal range in many patients with both acute and chronic liver disease. However, bleeding remains the dominant clinical issue in patients with liver diseases, especially when invasive interventions are required. VET has been shown to asses more appropriately the risk of bleeding than conventional laboratory tests, leading to decrial use of blood products transfusion. Inappropriate clotting is common but often subtle and may be challenging to predict even with the help of VET. Although VET has shown its benefit, more studies are needed to establish cut-off values for TEG and ROTEM in these populations and standardization of transfusion guidelines before invasive interventions in cirrhotic patients/orthotopic liver transplantation.
Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Hemostasis; Humans; Liver Diseases; Thrombelastography
PubMed: 34163112
DOI: 10.3748/wjg.v27.i23.3290