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Toxins Jan 2022Snakebite is a significant and under-resourced global public health issue. Snake venoms cause a variety of potentially fatal clinical toxin syndromes, including... (Review)
Review
Snakebite is a significant and under-resourced global public health issue. Snake venoms cause a variety of potentially fatal clinical toxin syndromes, including venom-induced consumption coagulopathy (VICC) which is associated with major haemorrhage. A subset of patients with VICC develop a thrombotic microangiopathy (TMA). This article reviews recent evidence regarding snakebite-associated TMA and its epidemiology, diagnosis, outcomes, and effectiveness of interventions including antivenom and therapeutic plasma-exchange. Snakebite-associated TMA presents with microangiopathic haemolytic anaemia (evidenced by schistocytes on the blood film), thrombocytopenia in almost all cases, and a spectrum of acute kidney injury (AKI). A proportion of patients require dialysis, most survive and achieve dialysis free survival. There is no evidence that antivenom prevents TMA specifically, but early antivenom remains the mainstay of treatment for snake envenoming. There is no evidence for therapeutic plasma-exchange being effective. We propose diagnostic criteria for snakebite-associated TMA as anaemia with >1.0% schistocytes on blood film examination, together with absolute thrombocytopenia (<150 × 10/L) or a relative decrease in platelet count of >25% from baseline. Patients are at risk of long-term chronic kidney disease and long term follow up is recommended.
Topics: Humans; Snake Bites; Thrombotic Microangiopathies
PubMed: 35051033
DOI: 10.3390/toxins14010057 -
CMAJ : Canadian Medical Association... Jul 2021
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Thrombosis; Vaccines
PubMed: 34226274
DOI: 10.1503/cmaj.210882-f -
Transfusion Medicine Reviews Oct 2015MicroRNAs (miRNAs) are short ~22-nucleotide noncoding RNA that have been found to influence the expression of many genes and cellular processes by either repressing... (Review)
Review
MicroRNAs (miRNAs) are short ~22-nucleotide noncoding RNA that have been found to influence the expression of many genes and cellular processes by either repressing translation or degrading messenger RNA transcripts. Platelet miRNA expression has been shown to be perturbed during ex vivo storage of platelets and in platelet-associated disorders. Although bioinformatics-based miRNA target predictions have been established, direct experimental validation of the role of miRNAs in platelet biology has been rather slow. Target prediction studies are, nonetheless, valuable in directing the design of appropriate experiments to test specific miRNA:messenger RNA interactions relevant to the underlying mechanisms of platelet function in general and in disease as well as in ex vivo storage-associated "storage lesions," a collective term used to include physiologic, biochemical, and morphologic changes that occur in stored platelets. This brief review will focus on emerging human platelet miRNA studies to emphasize their potential role relevant to transfusion medicine field in terms of regulating platelet signaling pathways, markers of platelet associated disorders, and remote impactors of gene expression (intercellular biomodulators) as well as potential platelet quality markers of storage and pathogen reduction treatments.
Topics: Animals; Blood Platelet Disorders; Blood Platelets; Blood Preservation; Gene Expression Regulation; Genetic Markers; Humans; MicroRNAs; Signal Transduction
PubMed: 26341586
DOI: 10.1016/j.tmrv.2015.08.002 -
Journal of Thrombosis and Haemostasis :... Jun 2015Our understanding of platelets, anucleate cells with a traditional role in hemostasis and inflammation, has developed greatly over the last decade. Platelets' role in... (Review)
Review
Our understanding of platelets, anucleate cells with a traditional role in hemostasis and inflammation, has developed greatly over the last decade. Platelets' role in the systemic response of the body to vascular injury, inflammation, and infection has expanded as has our understanding of their importance to the body's regulation of these processes. One recently explored mechanism by which platelets regulate the body's inflammatory and immune response is through its endogenous RNA. Platelets' messenger RNA (mRNAs) and microRNA (miRNAs) profiles have been shown to reflect disease and disease risk factors and have been correlated with select human clinical phenotypes. Developing an understanding of platelet transcripts in the circulation elucidates how platelets function in both their traditional thrombotic role and non-traditional functions and may have widespread implications in several fields including thrombosis, infection, cancer, and systemic inflammation.
Topics: Animals; Blood Platelet Disorders; Blood Platelets; Gene Expression Regulation; Genetic Predisposition to Disease; Hemostasis; Humans; MicroRNAs; Phenotype; RNA, Messenger; Thrombosis; Transcription, Genetic; Transcriptome
PubMed: 26149043
DOI: 10.1111/jth.12922 -
Haematologica Aug 2020Over the last 100 years the role of platelets in hemostatic events and their production by megakaryocytes have gradually been defined. Progressively, thrombocytopenia... (Review)
Review
Over the last 100 years the role of platelets in hemostatic events and their production by megakaryocytes have gradually been defined. Progressively, thrombocytopenia was recognized as a cause of bleeding, first through an acquired immune disorder; then, since 1948, when Bernard-Soulier syndrome was first described, inherited thrombocytopenia became a fascinating example of Mendelian disease. The platelet count is often severely decreased and platelet size variable; associated platelet function defects frequently aggravate bleeding. Macrothrombocytopenia with variable proportions of enlarged platelets is common. The number of circulating platelets will depend on platelet production, consumption and lifespan. The bulk of macrothrombocytopenias arise from defects in megakaryopoiesis with causal variants in transcription factor genes giving rise to altered stem cell differentiation and changes in early megakaryocyte development and maturation. Genes encoding surface receptors, cytoskeletal and signaling proteins also feature prominently and Sanger sequencing associated with careful phenotyping has allowed their early classification. It quickly became apparent that many inherited thrombocytopenias are syndromic while others are linked to an increased risk of hematologic malignancies. In the last decade, the application of next-generation sequencing, including whole exome sequencing, and the use of gene platforms for rapid testing have greatly accelerated the discovery of causal genes and extended the list of variants in more common disorders. Genes linked to an increased platelet turnover and apoptosis have also been identified. The current challenges are now to use next-generation sequencing in first-step screening and to define bleeding risk and treatment better.
Topics: Bernard-Soulier Syndrome; Blood Platelets; Humans; Megakaryocytes; Thrombocytopenia; Thrombopoiesis
PubMed: 32527953
DOI: 10.3324/haematol.2019.233197 -
Hematology. American Society of... Dec 2020Women with bleeding disorders suffer from multiple bleeding symptoms, including easy bruising, epistaxis, bleeding from minor wounds and the oral cavity, and bleeding... (Review)
Review
Women with bleeding disorders suffer from multiple bleeding symptoms, including easy bruising, epistaxis, bleeding from minor wounds and the oral cavity, and bleeding after dental work or surgery. However, women with bleeding disorders especially suffer from gynecologic and obstetrical bleeding. These symptoms often are not recognized as abnormal, and many women are left undiagnosed and without access to appropriate medical care. Additional challenges to diagnosing women with bleeding disorders include lack of access to appropriate laboratory testing and issues around disease classification and nomenclature. Efforts have been undertaken to address these challenges, including the development and validation of bleeding assessment tools and strategies to clarify diagnostic thresholds and algorithms for von Willebrand disease (VWD) and platelet function disorders. Efforts to improve communication with the nomenclature used for hemophilia carriers are also underway.
Topics: Adolescent; Algorithms; Female; Health Services Accessibility; Hemorrhage; Humans; Women's Health Services; von Willebrand Diseases
PubMed: 33275722
DOI: 10.1182/hematology.2020000140 -
Clinics in Laboratory Medicine Mar 2021Transfusion of red blood cells, platelets, and fresh frozen plasma in neonatal patients has not been well characterized in the literature, with guidelines varying... (Review)
Review
Transfusion of red blood cells, platelets, and fresh frozen plasma in neonatal patients has not been well characterized in the literature, with guidelines varying greatly between institutions. However, anemia and thrombocytopenia are highly prevalent, especially in preterm neonates. When transfusing a neonatal patient, clinicians must take into consideration physiologic differences, gestational and postnatal age, congenital disorders, and maternal factors while weighing the risks and benefits of transfusion. This review of existing literature summarizes current evidence-based neonatal transfusion guidelines and highlights areas of current ongoing research and those in need of future studies.
Topics: Blood Transfusion; Humans; Platelet Transfusion; Thrombocytopenia
PubMed: 33494882
DOI: 10.1016/j.cll.2020.10.002 -
Bioscience Reports Oct 2018Platelets respond to vascular injury via surface receptor stimulation and signaling events to trigger aggregation, procoagulant activation, and granule secretion during... (Review)
Review
Platelets respond to vascular injury via surface receptor stimulation and signaling events to trigger aggregation, procoagulant activation, and granule secretion during hemostasis, thrombosis, and vascular remodeling. Platelets contain three major types of secretory granules including dense granules (or δ-granules, DGs), α-granules (AGs), and lysosomes. The contents of platelet granules are specific. Platelet DGs store polyphosphate and small molecules such as ADP, ATP, Ca, and serotonin, while AGs package most of the proteins that platelets release. The platelet DGs and AGs are regarded as being budded from the endosomes and the -Golgi network (TGN), respectively, and then matured from multivesicular bodies (MVBs). However, the sorting machineries between DGs and AGs are different. Inherited platelet disorders are associated with deficiency of DGs and AGs, leading to bleeding diathesis in patients with Hermansky-Pudlak syndrome (HPS), gray platelet syndrome (GPS), and arthrogryposis, renal dysfunction, and cholestasis syndrome (ARC). Here, we reviewed the current understanding about how DGs differ from AGs in structure, biogenesis, and function. In particular, we focus on the sorting machineries that are involved in the formation of these two types of granules to provide insights into their diverse biological functions.
Topics: Arthrogryposis; Blood Platelets; Cholestasis; Cytoplasmic Granules; Endosomes; Gray Platelet Syndrome; Hermanski-Pudlak Syndrome; Humans; Lysosomes; Multivesicular Bodies; Renal Insufficiency; Secretory Vesicles; trans-Golgi Network
PubMed: 30104399
DOI: 10.1042/BSR20180458 -
International Journal of Molecular... Sep 2022Coronavirus disease 2019 (COVID-19) can lead to clinically significant multisystem disorders that also affect the kidney. According to recent data, renal injury in the... (Review)
Review
Coronavirus disease 2019 (COVID-19) can lead to clinically significant multisystem disorders that also affect the kidney. According to recent data, renal injury in the form of thrombotic microangiopathy (TMA) in native kidneys ranks third in frequency. Our review of global literature revealed 46 cases of TMA in association with COVID-19. Among identified cases, 18 patients presented as thrombotic thrombocytopenic purpura (TTP) and 28 cases presented as atypical hemolytic uremic syndrome (aHUS). Altogether, seven patients with aHUS had previously proven pathogenic or likely pathogenic genetic complement abnormalities. TMA occurred at the time of viremia or even after viral clearance. Infection with COVID-19 resulted in almost no or only mild respiratory symptoms in the majority of patients, while digestive symptoms occurred in almost one-third of patients. Regarding the clinical presentation of COVID-19-associated TMA, the cases showed no major deviations from the known presentation. Patients with TTP were treated with plasma exchange (88.9%) or fresh frozen plasma (11.1%), corticosteroids (88.9%), rituximab (38.9%), and caplacizumab (11.1%). Furthermore, 53.6% of patients with aHUS underwent plasma exchange with or without steroid as initial therapy, and 57.1% of patients received a C5 complement inhibitor. Mortality in the studied cohort was 16.7% for patients with TTP and 10.7% for patients with aHUS. The exact role of COVID-19 in the setting of COVID-19-associated TMA remains unclear. COVID-19 likely represents a second hit of aHUS or TTP that manifests in genetically predisposed individuals. Early identification of the TMA subtype and appropriate prompt and specific treatment could lead to good outcomes comparable to survival and recovery statistics for TMA of all causes.
Topics: Atypical Hemolytic Uremic Syndrome; COVID-19; Complement Inactivating Agents; Humans; Purpura, Thrombotic Thrombocytopenic; Rituximab; Steroids; Thrombotic Microangiopathies
PubMed: 36232608
DOI: 10.3390/ijms231911307 -
The New England Journal of Medicine Jul 2018Platelet counts of less than 150,000 per cubic millimeter during uncomplicated pregnancies are described as gestational thrombocytopenia if no alternative cause is...
BACKGROUND
Platelet counts of less than 150,000 per cubic millimeter during uncomplicated pregnancies are described as gestational thrombocytopenia if no alternative cause is identified. Platelet counts may be even lower in women with pregnancy-related complications. However, the occurrence and severity of thrombocytopenia throughout pregnancy are not defined.
METHODS
We evaluated platelet counts throughout pregnancy in women who delivered at Oklahoma University Medical Center between 2011 and 2014. These platelet counts were compared with those of nonpregnant women who were included in the National Health and Nutrition Examination Survey from 1999 through 2012.
RESULTS
Among the 15,723 deliveries that occurred during the study period, 7351 women had sufficient data for our analyses. Of these women, 4568 had uncomplicated pregnancies, 2586 had pregnancy-related complications, and 197 had preexisting disorders associated with thrombocytopenia. Among the women who had uncomplicated pregnancies, the mean platelet count in the first trimester (mean gestation, 8.7 weeks) was 251,000 per cubic millimeter, which was lower than the mean platelet count in the 8885 nonpregnant women (273,000 per cubic millimeter) (P<0.001). At the time of delivery, 9.9% of the women with uncomplicated pregnancies had a platelet count below 150,000 per cubic millimeter. During the course of the uncomplicated pregnancies and deliveries, only 45 women (1.0%) had a platelet count below 100,000 per cubic millimeter. Among the 12 women with uncomplicated pregnancies who had a platelet count below 80,000 per cubic millimeter, only 5 (0.1%, among whom the range of platelet counts was 62,000 to 78,000 per cubic millimeter; median, 65,000) were identified by medical record review as having no alternative cause for the thrombocytopenia. Platelet counts of less than 150,000 per cubic millimeter at the time of delivery were more common among women who had pregnancy-related complications than among women who had uncomplicated pregnancies (11.9% vs. 9.9%, P=0.01). Throughout their pregnancies and deliveries, 59 women (2.3%) with pregnancy-related complications had a platelet count below 100,000 per cubic millimeter, and 31 (1.2%) had a platelet count below 80,000 per cubic millimeter.
CONCLUSIONS
Mean platelet counts decreased during pregnancy in all the women, beginning in the first trimester. In women who have a platelet count of less than 100,000 per cubic millimeter, a cause other than pregnancy or its complications should be considered. (Funded by the National Heart, Lung, and Blood Institute.).
Topics: Adolescent; Adult; Female; Humans; Platelet Count; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Reference Values; Thrombocytopenia; Young Adult
PubMed: 29972751
DOI: 10.1056/NEJMoa1802897