Review

Authors: Gemma L Thompson, David Kavanagh

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

Review

Authors: James N George, Carla M Nester

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

Review

Authors: David C Dale

PURPOSE OF REVIEW

Neutropenia absolute neutrophil count (ANC) less than 1.5 × 10(9)/l is a common hematological finding, and severe neutropenia, that is, ANC less than 0.5 × 10(9)/l is a well known risk factor for susceptibility to bacterial infections. This review provides a succinct clinical approach to the diagnosis and treatment of neutropenia with specific recommendations on the treatment of severe chronic neutropenia with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF).

RECENT FINDINGS

Experts agree that patients with acute febrile neutropenia should be treated with antibiotics and that patients at high risk of severe neutropenia (>20% risk) after myelosuppressive chemotherapy should be treated prophylactically with a myeloid growth factor, usually G-CSF. The diversity of causes and consequences of chronic neutropenia make the diagnosis and management of these patients more complicated.

SUMMARY

The review provides a stepwise approach to neutropenia focusing first on reaching a provisional diagnosis and treatment plan then steps to a final diagnosis. It also provides specific recommendations on the treatment of severe chronic neutropenia with G-CSF.

Topics: Humans; Neutropenia

PubMed: 26554885
DOI: 10.1097/MOH.0000000000000208

Review

Authors: Fiona Swain, Robert Bird

Thrombocytopenia is a common reason for referral to hematologists in community and hospital practice. A broad differential diagnosis, combined with the potentially life-threatening nature of some presentations necessitates a rapid evaluation of the situation and potential need for emergency intervention; followed by further comprehensive investigation to confirm the diagnosis and institution of longer term management. This review offers an approach to the initial assessment, diagnosis, and referral. We then highlight aspects of the clinical history, examination and laboratory investigations which may provide critical insights into the most likely diagnosis. ITP is the commonest cause of severe isolated thrombocytopenia in the general community and is the most common cause of thrombocytopenia in patients referred to our hematology service. It remains a diagnosis of exclusion and a high degree of vigilance for alternative diagnoses should be maintained, particularly if presentations are atypical or expected response to treatment is not seen. Adult presentation of hereditary thrombocytopenia syndromes can mimic new onset thrombocytopenia, however, improving access to genetic testing will facilitate accurate diagnosis and avoid unnecessary treatment.

Topics: Diagnosis, Differential; Disease Management; Disease Susceptibility; Humans; Thrombocytopenia

PubMed: 31269407
DOI: 10.1080/09537104.2019.1637835

Review

Authors: Annemarie E Fogerty, David J Kuter

Thrombocytopenia is a common hematologic abnormality in pregnancy, encountered in ∼10% of pregnancies. There are many possible causes, ranging from benign conditions that do not require intervention to life-threatening disorders necessitating urgent recognition and treatment. Although thrombocytopenia may be an inherited condition or predate pregnancy, most commonly it is a new diagnosis. Identifying the responsible mechanism and predicting its course is made challenging by the tremendous overlap of clinical features and laboratory data between normal pregnancy and the many potential causes of thrombocytopenia. Multidisciplinary collaboration between hematology, obstetrics, and anesthesia and shared decision-making with the involved patient is encouraged to enhance diagnostic clarity and develop an optimized treatment regimen, with careful consideration of management of labor and delivery and the potential fetal impact of maternal thrombocytopenia and any proposed therapeutic intervention. In this review, we outline a diagnostic approach to pregnant patients with thrombocytopenia, highlighting the subtle differences in presentation, physical examination, clinical course, and laboratory abnormalities that can be applied to focus the differential. Four clinical scenarios are presented to highlight the pathophysiology and treatment of the most common causes of thrombocytopenia in pregnancy: gestational thrombocytopenia, preeclampsia, and immune thrombocytopenia.

Topics: Pregnancy; Female; Humans; Thrombocytopenia; Anemia; Purpura, Thrombocytopenic, Idiopathic; Pre-Eclampsia; Pregnancy Complications, Hematologic

PubMed: 37992219
DOI: 10.1182/blood.2023020726

Authors: Peter L Greenberg, Heinz Tuechler, Julie Schanz...

The International Prognostic Scoring System (IPSS) is an important standard for assessing prognosis of primary untreated adult patients with myelodysplastic syndromes (MDS). To refine the IPSS, MDS patient databases from international institutions were coalesced to assemble a much larger combined database (Revised-IPSS [IPSS-R], n = 7012, IPSS, n = 816) for analysis. Multiple statistically weighted clinical features were used to generate a prognostic categorization model. Bone marrow cytogenetics, marrow blast percentage, and cytopenias remained the basis of the new system. Novel components of the current analysis included: 5 rather than 3 cytogenetic prognostic subgroups with specific and new classifications of a number of less common cytogenetic subsets, splitting the low marrow blast percentage value, and depth of cytopenias. This model defined 5 rather than the 4 major prognostic categories that are present in the IPSS. Patient age, performance status, serum ferritin, and lactate dehydrogenase were significant additive features for survival but not for acute myeloid leukemia transformation. This system comprehensively integrated the numerous known clinical features into a method analyzing MDS patient prognosis more precisely than the initial IPSS. As such, this IPSS-R should prove beneficial for predicting the clinical outcomes of untreated MDS patients and aiding design and analysis of clinical trials in this disease.

Topics: Adult; Aged; Aged, 80 and over; Bone Marrow; Chromosome Aberrations; Cytogenetic Analysis; Female; Humans; International Agencies; Karyotyping; Male; Middle Aged; Myelodysplastic Syndromes; Pancytopenia; Prognosis; Risk Assessment; Risk Factors; Survival Rate

PubMed: 22740453
DOI: 10.1182/blood-2012-03-420489

Review

Authors: Lilian Monteiro P Palma, Maria Helena Vaisbich-Guimarães, Meera Sridharan...

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

Review

Authors: Hugo Donato

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

Review

Authors: Neil S Sheerin, Emily Glover

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

Review

Authors: Gowthami M Arepally, Douglas B Cines

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