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Blood Advances Nov 2019Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This...
Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This article is an update of the International Consensus Report published in 2010. A critical review was performed to identify all relevant articles published between 2009 and 2018. An expert panel screened, reviewed, and graded the studies and formulated the updated consensus recommendations based on the new data. The final document provides consensus recommendations on the diagnosis and management of ITP in adults, during pregnancy, and in children, as well as quality-of-life considerations.
Topics: Clinical Decision-Making; Combined Modality Therapy; Decision Trees; Disease Management; Humans; Purpura, Thrombocytopenic, Idiopathic; Severity of Illness Index; Treatment Outcome
PubMed: 31770441
DOI: 10.1182/bloodadvances.2019000812 -
International Journal of Laboratory... Sep 2022Thrombotic microangiopathy (TMA) is characterized by thrombocytopenia, microangiopathic haemolytic anaemia and end organ damage. TMAs have varying underlying... (Review)
Review
Thrombotic microangiopathy (TMA) is characterized by thrombocytopenia, microangiopathic haemolytic anaemia and end organ damage. TMAs have varying underlying pathophysiology and can therefore present with an array of clinical presentations. Renal involvement is common as the kidney is particularly susceptible to the endothelial damage and microvascular occlusion. TMAs require rapid assessment, diagnosis, and commencement of appropriate treatment due to the high morbidity and mortality associated with them. Ground-breaking research into the pathogenesis of TMAs over the past 20 years has driven the successful development of targeted therapeutics revolutionizing patient outcomes. This review outlines the clinical presentations, pathogenesis, diagnostic tests and treatments for TMAs.
Topics: Humans; Thrombotic Microangiopathies
PubMed: 36074708
DOI: 10.1111/ijlh.13954 -
Pediatric Nephrology (Berlin, Germany) Sep 2022The syndrome of thrombotic microangiopathy (TMA) is a clinical-pathological entity characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ... (Review)
Review
The syndrome of thrombotic microangiopathy (TMA) is a clinical-pathological entity characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ involvement. It comprises a spectrum of underlying etiologies that may differ in children and adults. In children, apart from ruling out shigatoxin-associated hemolytic uremic syndrome (HUS) and other infection-associated TMA like Streptococcus pneumoniae-HUS, rare inherited causes including complement-associated HUS, cobalamin defects, and mutations in diacylglycerol kinase epsilon gene must be investigated. TMA should also be considered in the setting of solid organ or hematopoietic stem cell transplantation. In this review, acquired and inherited causes of TMA are described with a focus on particularities of the main causes of TMA in children. A pragmatic approach that may help the clinician tailor evaluation and management is provided. The described approach will allow for early initiation of treatment while waiting for the definitive diagnosis of the underlying TMA.
Topics: Child; Complement System Proteins; Hematopoietic Stem Cell Transplantation; Hemolytic-Uremic Syndrome; Humans; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies
PubMed: 35041041
DOI: 10.1007/s00467-021-05370-8 -
The New England Journal of Medicine Aug 2014This review article covers the diverse pathophysiological pathways that can lead to microangiopathic hemolytic anemia and a procoagulant state with or without damage to... (Review)
Review
This review article covers the diverse pathophysiological pathways that can lead to microangiopathic hemolytic anemia and a procoagulant state with or without damage to the kidneys and other organs.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies
PubMed: 25119611
DOI: 10.1056/NEJMra1312353 -
Hematology/oncology Clinics of North... Dec 2021Von Willebrand disease (VWD) is a common bleeding disorder, affecting male and female individuals equally, that often manifests in mucosal bleeding. VWD can be secondary... (Review)
Review
Von Willebrand disease (VWD) is a common bleeding disorder, affecting male and female individuals equally, that often manifests in mucosal bleeding. VWD can be secondary to a quantitative (Type 1 and Type 3) or qualitative (Type 2) defects in Von Willebrand factor (VWF). Initial testing includes VWF antigen, as well as a platelet binding assay to differentiate between qualitative and quantitative defects. Further subtyping requires additional testing and is needed to ensure appropriate treatment. Desmopressin, antifibrinolytics, hormonal treatments for heavy menstrual bleeding, and VWF concentrates are commonly used in the treatment of VWD.
Topics: Blood Platelets; Female; Humans; Male; von Willebrand Diseases; von Willebrand Factor
PubMed: 34400042
DOI: 10.1016/j.hoc.2021.07.004 -
Archivos Argentinos de Pediatria Jun 2021Thrombocytopenia, defined as a platelet count below 100 x 109/L, is a very common finding in the neonatal period, especially in critically ill infants and preterm... (Review)
Review
Thrombocytopenia, defined as a platelet count below 100 x 109/L, is a very common finding in the neonatal period, especially in critically ill infants and preterm newborns. Its causes are multiple: it may be due both to pediatric conditions and to other factors involved in the fetal-placental-maternal interface. This initial article describes the causes of thrombocytopenia, proposes a diagnostic approach to manage a thrombocytopenic newborn infant, and provides a detailed description of the different conditions corresponding to thrombocytopenia of immune etiology. It also describes the different causative mechanisms and reviews the varying characteristics of thrombocytopenia secondary to maternal immune thrombocytopenia and neonatal alloimmune thrombocytopenia. The different treatment approaches to each of the different conditions are described both for their pre- as well as their postnatal management. The severity of thrombocytopenia and the serious complications and sequelae associated with the neonatal alloimmune thrombocytopenia are highlighted.
Topics: Diagnosis, Differential; Female; Humans; Infant; Infant, Newborn; Placenta; Platelet Count; Pregnancy; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia, Neonatal Alloimmune
PubMed: 34033425
DOI: 10.5546/aap.2021.eng.e202 -
F1000Research 2019The thrombotic microangiopathies (TMAs) are a group of diseases characterised by microangiopathic haemolysis, thrombocytopenia, and thrombus formation leading to tissue... (Review)
Review
The thrombotic microangiopathies (TMAs) are a group of diseases characterised by microangiopathic haemolysis, thrombocytopenia, and thrombus formation leading to tissue injury. Traditionally, TMAs have been classified as either thrombotic thrombocytopenic purpura (TTP) or haemolytic uremic syndrome (HUS) based on the clinical presentation, with neurological involvement predominating in the former and acute kidney injury in the latter. However, as our understanding of the pathogenesis of these conditions has increased, it has become clear that this is an over-simplification; there is significant overlap in the clinical presentation of TTP and HUS, there are different forms of HUS, and TMAs can occur in other, diverse clinical scenarios. This review will discuss recent developments in the diagnosis of HUS, focusing on the different forms of HUS and how to diagnose and manage these potentially life-threatening diseases.
Topics: Acute Kidney Injury; Hemolysis; Hemolytic-Uremic Syndrome; Humans; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies
PubMed: 31598213
DOI: 10.12688/f1000research.19957.1 -
Translational Research : the Journal of... Nov 2020There are currently no effective substitutes for high intensity therapy with unfractionated heparin (UFH) for cardiovascular procedures based on its rapid onset of... (Review)
Review
There are currently no effective substitutes for high intensity therapy with unfractionated heparin (UFH) for cardiovascular procedures based on its rapid onset of action, ease of monitoring and reversibility. The continued use of UFH in these and other settings requires vigilance for its most serious nonhemorrhagic complication, heparin induced thrombocytopenia (HIT). HIT is an immune prothrombotic disorder caused by antibodies that recognize complexes between platelet factor 4 (PF4) and polyanions such as heparin (H).The pathogenicity of anti-PF4/H antibodies is likely due to the formation of immune complexes that initiate intense procoagulant responses by vascular and hematopoietic cells that lead to the generation of platelet microparticles, monocyte and endothelial cell procoagulant activity, and neutrophil extracellular traps, among other outcomes. The development of anti-PF4/H antibodies after exposure to UFH greatly exceeds the incidence of clinical disease, but the biochemical features that distinguish pathogenic from nonpathogenic antibodies have not been identified. Diagnosis relies on pretest clinical probability, screening for anti-PF4/H antibodies and documentation of their platelet activating capacity. However, both clinical algorithms and test modalities have limited predictive values making diagnosis and management challenging. Given the unacceptable rates of recurrent thromboembolism and bleeding associated with current therapies, there is an unmet need for novel rational nonanticoagulant therapeutics based on the pathogenesis of HIT. We will review recent developments in our understanding of the pathogenesis of HIT and its implications for future approaches to diagnosis and management.
Topics: Anticoagulants; Heparin; Humans; Thrombocytopenia
PubMed: 32417430
DOI: 10.1016/j.trsl.2020.04.014 -
Haematologica Jun 2022Several therapeutic agents can cause thrombocytopenia by either immune-mediated or non-immune-mediated mechanisms. Non-immune-mediated thrombocytopenia is due to direct... (Review)
Review
Several therapeutic agents can cause thrombocytopenia by either immune-mediated or non-immune-mediated mechanisms. Non-immune-mediated thrombocytopenia is due to direct toxicity of drug molecules to platelets or megakaryocytes. Immune-mediated thrombocytopenia, on the other hand, involves the formation of antibodies that react to platelet-specific glycoprotein complexes, as in classic drug-induced immune thrombocytopenia (DITP), or to platelet factor 4, as in heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT). Clinical signs include a rapid drop in platelet count, bleeding or thrombosis. Since the patient's condition can deteriorate rapidly, prompt diagnosis and management are critical. However, the necessary diagnostic tests are only available in specialized laboratories. Therefore, the most demanding step in treatment is to identify the agent responsible for thrombocytopenia, which often proves difficult because many patients are taking multiple medications and have comorbidities that can themselves also cause thrombocytopenia. While DITP is commonly associated with an increased risk of bleeding, HIT and VITT have a high mortality rate due to the high incidence of thromboembolic complications. A structured approach to drug-associated thrombocytopenia/thrombosis can lead to successful treatment and a lower mortality rate. In addition to describing the treatment of DITP, HIT, VITT, and vaccine-associated immune thrombocytopenia, this review also provides the pathophysiological and clinical information necessary for correct patient management.
Topics: Hemorrhage; Heparin; Humans; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Thrombosis
PubMed: 35642486
DOI: 10.3324/haematol.2021.279484 -
Blood Apr 2023Within the first months of the COVID-19 vaccination campaign, previously healthy recipients who developed severe thrombosis (often cerebral and/or splanchnic...
Within the first months of the COVID-19 vaccination campaign, previously healthy recipients who developed severe thrombosis (often cerebral and/or splanchnic vasculature) and thrombocytopenia typically after adenoviral vector-based vaccination were identified. Similarities between this syndrome, vaccine-induced immune thrombotic thrombocytopenia (VITT), and heparin-induced thrombocytopenia prompted recognition of the role of antiplatelet factor 4 (PF4) antibodies and management strategies based on IV immunoglobulin and nonheparin anticoagulants, which improved outcome. We update current understanding of VITT and potential involvement of anti-PF4 antibodies in thrombotic disorders.
Topics: Humans; COVID-19 Vaccines; COVID-19; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Thrombosis; Vaccines; Platelet Factor 4
PubMed: 36669155
DOI: 10.1182/blood.2022017696