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Nature Reviews. Cardiology Mar 2021The core pathology of coronavirus disease 2019 (COVID-19) is infection of airway cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in... (Review)
Review
The core pathology of coronavirus disease 2019 (COVID-19) is infection of airway cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in excessive inflammation and respiratory disease, with cytokine storm and acute respiratory distress syndrome implicated in the most severe cases. Thrombotic complications are a major cause of morbidity and mortality in patients with COVID-19. Patients with pre-existing cardiovascular disease and/or traditional cardiovascular risk factors, including obesity, diabetes mellitus, hypertension and advanced age, are at the highest risk of death from COVID-19. In this Review, we summarize new lines of evidence that point to both platelet and endothelial dysfunction as essential components of COVID-19 pathology and describe the mechanisms that might account for the contribution of cardiovascular risk factors to the most severe outcomes in COVID-19. We highlight the distinct contributions of coagulopathy, thrombocytopathy and endotheliopathy to the pathogenesis of COVID-19 and discuss potential therapeutic strategies in the management of patients with COVD-19. Harnessing the expertise of the biomedical and clinical communities is imperative to expand the available therapeutics beyond anticoagulants and to target both thrombocytopathy and endotheliopathy. Only with such collaborative efforts can we better prepare for further waves and for future coronavirus-related pandemics.
Topics: Administration, Inhalation; Anticoagulants; Blood Coagulation Disorders; Blood Platelet Disorders; COVID-19; Endothelium, Vascular; Endothelium-Dependent Relaxing Factors; Epoprostenol; Heart Disease Risk Factors; Humans; Iloprost; Inflammation; Nitric Oxide; Platelet Aggregation Inhibitors; SARS-CoV-2; Systemic Inflammatory Response Syndrome; Thrombosis; Thrombotic Microangiopathies; Vascular Diseases; Vasodilator Agents; Venous Thromboembolism; COVID-19 Drug Treatment
PubMed: 33214651
DOI: 10.1038/s41569-020-00469-1 -
Orthopedic Nursing 2008The serotonergic effects on platelet dysfunction (thrombocytopathy) can cause deficient hemostasis during orthopaedic surgery. Peripheral serotonin located within the... (Review)
Review
The serotonergic effects on platelet dysfunction (thrombocytopathy) can cause deficient hemostasis during orthopaedic surgery. Peripheral serotonin located within the granules of platelets assists in initial platelet aggregation. Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs) are drugs used to treat a myriad psychological-related, mental-related, and psychosocial-related disorders. A correlation exists between low levels of peripheral serotonin and a bleeding diathesis during orthopaedic surgery. The relationship of excessive bleeding during orthopaedic surgery secondary to thrombocytopathy and low levels of serotonin caused by drugs that inhibit the reuptake of serotonin is presented.
Topics: Blood Flow Velocity; Blood Platelet Disorders; Drug Monitoring; Humans; Monitoring, Intraoperative; Nurse's Role; Orthopedic Nursing; Orthopedic Procedures; Platelet Aggregation; Risk Factors; Serotonin; Serotonin Agents; Serotonin Syndrome
PubMed: 18300689
DOI: 10.1097/01.NOR.0000310612.93118.ec -
Pediatrics in Review May 2020After vascular injury and exposure of subendothelial matrix proteins to the intravascular space, mediators of hemostasis are triggered and allow for clot formation and... (Review)
Review
After vascular injury and exposure of subendothelial matrix proteins to the intravascular space, mediators of hemostasis are triggered and allow for clot formation and restoration of vascular integrity. Platelets are the mediators of primary hemostasis, creating a platelet plug and allowing for initial cessation of bleeding. Platelet disorders, qualitative and quantitative, may result in bleeding signs and symptoms, particularly mucocutaneous bleeding such as epistaxis, bruising, petechiae, and heavy menstrual bleeding. Increasing evidence suggests that platelets have functional capabilities beyond hemostasis, but this review focuses solely on platelet hemostatic properties. Herein, normal platelet function as well as the effects of abnormal function and thrombocytopenia are reviewed.
Topics: Blood Platelet Disorders; Child; Diagnosis, Differential; Humans; Pediatrics; Referral and Consultation
PubMed: 32358028
DOI: 10.1542/pir.2018-0359 -
Platelets Sep 2016
Topics: Blood Platelet Disorders; Blood Platelets; Humans; Research
PubMed: 27540958
DOI: 10.1080/09537104.2016.1213058 -
Journal of the American Society of... May 2010Platelet dysfunction in renal failure is attributable to high levels of small, partly dialyzable molecules known as uremic toxins, hence the term "uremic...
Platelet dysfunction in renal failure is attributable to high levels of small, partly dialyzable molecules known as uremic toxins, hence the term "uremic thrombocytopathy." Although a variety of moieties contribute to platelet dysfunction or abnormal interactions between platelets and the vascular wall, urea remains a potential factor. Here, we studied three family members with familial azotemia, a rare autosomal dominant syndrome characterized by high plasma urea resulting from impaired urinary excretion but normal renal function otherwise. Platelet function, assessed in vitro and by traditional bleeding time, was normal in all individuals. Abnormal platelet function in patients with renal failure is not caused by high concentrations of urea.
Topics: Adult; Azotemia; Blood Platelet Disorders; Child, Preschool; Female; Humans; Male; Middle Aged; Urea
PubMed: 20360312
DOI: 10.1681/ASN.2009111181 -
Hematology/oncology Clinics of North... Dec 2021Bleeding disorders due to platelet dysfunction are a common hematologic complication affecting patients, and typically present with mucocutaneous bleeding or hemorrhage.... (Review)
Review
Bleeding disorders due to platelet dysfunction are a common hematologic complication affecting patients, and typically present with mucocutaneous bleeding or hemorrhage. An inherited platelet disorder should be suspected in individuals with a suggestive family history and no identified secondary causes of bleeding. Genetic defects have been described at all levels of platelet activation, including receptor binding, signaling, granule release, cytoskeletal remodeling, and platelet hematopoiesis. Management of these disorders is typically supportive, with an emphasis on awareness, patient education, and anticipatory guidance to prevent future episodes of bleeding.
Topics: Blood Coagulation Disorders; Blood Platelet Disorders; Blood Platelets; Hemorrhage; Humans; Platelet Activation
PubMed: 34391603
DOI: 10.1016/j.hoc.2021.07.003 -
Ugeskrift For Laeger Oct 2021Inherited platelet disorders (IPD) cover a heterogenous group of disorders with large differences in severity, disease mechanisms and prevalence. Pathogenic variants in... (Review)
Review
Inherited platelet disorders (IPD) cover a heterogenous group of disorders with large differences in severity, disease mechanisms and prevalence. Pathogenic variants in more than 60 different genes, associated with megakaryocyte or platelet number and/or function, are causal of IPD. Due to disease heterogeneity IPDs are often difficult to diagnose, problematic to manage and underestimated. In the past decade, genetic diagnostics using whole-genome sequencing has revolutionised the field by identifying numerous novel genes involved in IPD aetiology as described in this review.
Topics: Blood Platelet Disorders; Blood Platelets; Humans; Whole Genome Sequencing
PubMed: 34709163
DOI: No ID Found -
British Journal of Haematology Mar 1967
Topics: Adult; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Clot Retraction; Genes; Humans; Lipids; Male; Middle Aged; Phospholipids; Thrombocytopenia
PubMed: 6019024
DOI: 10.1111/j.1365-2141.1967.tb08725.x -
Seminars in Thrombosis and Hemostasis Sep 2013Sticky platelet syndrome (SPS) is a thrombophilic thrombocytopathy with familial occurrence and autosomal dominant trait, characterized by an increased in vitro platelet... (Review)
Review
Sticky platelet syndrome (SPS) is a thrombophilic thrombocytopathy with familial occurrence and autosomal dominant trait, characterized by an increased in vitro platelet aggregation in response to low concentrations of adenosine diphosphate (ADP) and/or epinephrine (EPI). According to aggregation pattern, three types of the syndrome can be identified (hyperresponse after both reagents, Type I; EPI alone, Type II; ADP alone, Type III). Clinically, the syndrome is associated with both venous and arterial thrombosis. In pregnant women, complications such as fetal growth retardation and fetal loss have been reported. The first thrombotic event usually occurs before 40 years of age and without prominent acquired risk factors. Antiplatelet drugs generally represent adequate treatment. The use of other antithrombotics is usually ineffective and may result in the recurrence of thrombosis. In most patients, low doses of antiplatelet drugs (acetylsalicylic acid, 80-100 mg/d) lead to normalization of hyperaggregability. Combination of SPS with other thrombophilic disorders has been described. Despite several studies investigating platelet glycoproteins' role in platelets' activation and aggregation, the precise defect responsible for the syndrome remains unknown. The aim of this review is to summarize authors' own experience about SPS and the clinical data indexed in selected databases of medical literature (PubMed and Scopus).
Topics: Blood Platelet Disorders; Female; Fetal Growth Retardation; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications, Hematologic; Syndrome; Thrombophilia
PubMed: 23934738
DOI: 10.1055/s-0033-1353394 -
Thrombosis and Haemostasis Feb 2017Platelet defects due to hyper-responsive GPIbα causing enhanced VWF interaction, counter-intuitively result in bleeding rather than thrombosis. The historical...
Platelet defects due to hyper-responsive GPIbα causing enhanced VWF interaction, counter-intuitively result in bleeding rather than thrombosis. The historical explanation of platelet/VWF clearance fails to explain mechanisms of impaired haemostasis particularly in light of reported poor platelet binding to fibrinogen. This study aimed to evaluate the defects of platelets with hyper-responsive GPIbα and their contribution to impaired in vivo thrombosis. Using the PT-VWD mouse model, platelets from the hTg were compared to control hTg mice. Platelets' pro-coagulant capacity was evaluated using flowcytometry assessment of P-selectin and annexin V. Whole blood platelet aggregation in response to ADP, collagen and thrombin was tested. Clot kinetics using laser injury thrombosis model and the effect of GPIbα inhibition in vivo using 6B4; a monoclonal antibody, were evaluated. Thrombin-induced platelet P-selectin and PS exposure were significantly reduced in hTg compared to hTg and not significantly different when compared to unstimulated platelets. The hTg platelets aggregated normally in response to collagen, and had a delayed response to ADP and thrombin, when compared to hTg platelets. Laser injury showed significant impairment of in vivo thrombus formation in hTg compared to hTg mice. There was a significant lag in in vitro clot formation in turbidity assay but no impairment in thrombin generation was observed using thromboelastography. The in vivo inhibition of GPIbα facilitated new - unstable - clot formation but did not improve the lag. We conclude platelets with hyper-responsive GPIbα have complex intrinsic defects beyond the previously described mechanisms. Abnormal signalling through GPIbα and potential therapy using inhibitors require further investigations.
Topics: Adenosine Diphosphate; Animals; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Collagen; Disease Models, Animal; Genetic Predisposition to Disease; Hemostasis; Humans; Kinetics; Mice, Transgenic; Mutation; Phenotype; Platelet Activation; Platelet Glycoprotein GPIb-IX Complex; Signal Transduction; Thrombin; Thrombosis; von Willebrand Diseases
PubMed: 28004055
DOI: 10.1160/TH16-04-0317