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Veterinary Clinical Pathology Oct 2019Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. The understanding of ITP pathogenesis is rapidly evolving. We now recognize ITP as a complex and... (Review)
Review
Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. The understanding of ITP pathogenesis is rapidly evolving. We now recognize ITP as a complex and heterogeneous syndrome that results from a combination of humoral and cell-mediated attacks on platelets peripherally and megakaryocytes in the bone marrow. Autoantibody-mediated ITP also varies in the pathway used to clear platelets, which depends on the platelet glycoprotein being targeted. Moreover, ITP patients present with variable bleeding severities and treatment responses that do not closely correlate with platelet count. A gold standard diagnostic test for ITP is lacking, and biomarkers to assess disease severity are in their infancy. This review provides an update on the immunopathogenesis of ITP and summarizes currently available tests for ITP diagnosis, prediction of disease severity, and treatment responses. Given the heterogeneous pathogenesis and clinical presentation of ITP, we highlight the need for the development of diagnostic and prognostic tests that would allow for the individualized management of a complex disease.
Topics: Animals; Autoantibodies; Biomarkers; Blood Platelets; Bone Marrow; Hemorrhage; Megakaryocytes; Platelet Count; Prognosis; Purpura, Thrombocytopenic, Idiopathic
PubMed: 31538353
DOI: 10.1111/vcp.12774 -
European Journal of Anaesthesiology Feb 2022Bleeding is a potential complication after neuraxial and peripheral nerve blocks. The risk is increased in patients on antiplatelet and anticoagulant drugs. This joint...
BACKGROUND
Bleeding is a potential complication after neuraxial and peripheral nerve blocks. The risk is increased in patients on antiplatelet and anticoagulant drugs. This joint guideline from the European Society of Anaesthesiology and Intensive Care and the European Society of Regional Anaesthesia aims to provide an evidence-based set of recommendations and suggestions on how to reduce the risk of antithrombotic drug-induced haematoma formation related to the practice of regional anaesthesia and analgesia.
DESIGN
A systematic literature search was performed, examining seven drug comparators and 10 types of clinical intervention with the outcome being peripheral and neuraxial haematoma. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for assessing the methodological quality of the included studies and for formulating recommendations. A Delphi process was used to prepare a clinical practice guideline.
RESULTS
Clinical studies were limited in number and quality and the certainty of evidence was assessed to be GRADE C throughout. Forty clinical practice statements were formulated. Using the Delphi-process, strong consensus (>90% agreement) was achieved in 57.5% of recommendations and consensus (75 to 90% agreement) in 42.5%.
DISCUSSION
Specific time intervals should be observed concerning the adminstration of antithrombotic drugs both prior to, and after, neuraxial procedures or those peripheral nerve blocks with higher bleeding risk (deep, noncompressible). These time intervals vary according to the type and dose of anticoagulant drugs, renal function and whether a traumatic puncture has occured. Drug measurements may be used to guide certain time intervals, whilst specific reversal for vitamin K antagonists and dabigatran may also influence these. Ultrasound guidance, drug combinations and bleeding risk scores do not modify the time intervals. In peripheral nerve blocks with low bleeding risk (superficial, compressible), these time intervals do not apply.
CONCLUSION
In patients taking antiplatelet or anticoagulant medications, practitioners must consider the bleeding risk both before and after nerve blockade and during insertion or removal of a catheter. Healthcare teams managing such patients must be aware of the risk and be competent in detecting and managing any possible haematomas.
Topics: Anesthesia, Conduction; Anticoagulants; Fibrinolytic Agents; Hemorrhage; Humans; Pharmaceutical Preparations
PubMed: 34980845
DOI: 10.1097/EJA.0000000000001600 -
Cardiovascular Therapeutics 2020Antiplatelet therapy is the mainstay of treatment and secondary prevention of cardiovascular disease (CVD), including acute coronary syndrome (ACS), transient ischemic... (Review)
Review
Antiplatelet therapy is the mainstay of treatment and secondary prevention of cardiovascular disease (CVD), including acute coronary syndrome (ACS), transient ischemic attack (TIA) or minor stroke, and peripheral artery disease (PAD). The P2Y inhibitors, of which clopidogrel was the first, play an integral role in antiplatelet therapy and therefore in the treatment and secondary prevention of CVD. This review discusses the available evidence concerning antiplatelet therapy in patients with CVD, with a focus on the role of clopidogrel. In combination with aspirin, clopidogrel is often used as part of dual antiplatelet therapy (DAPT) for the secondary prevention of ACS. Although newer, more potent P2Y inhibitors (prasugrel and ticagrelor) show a greater reduction in ischemic risk compared with clopidogrel in randomized trials of ACS patients, these newer P2Y inhibitors are often associated with an increased risk of bleeding. Deescalation of DAPT by switching from prasugrel or ticagrelor to clopidogrel may be required in some patients with ACS. Furthermore, real-world studies of ACS patients have not confirmed the benefits of the newer P2Y inhibitors over clopidogrel. In patients with very high-risk TIA or stroke, short-term DAPT with clopidogrel plus aspirin for 21-28 days, followed by clopidogrel monotherapy for up to 90 days, is recommended. Clopidogrel monotherapy may also be used in patients with symptomatic PAD. In conclusion, there is strong evidence supporting the use of clopidogrel antiplatelet therapy in several clinical settings, which emphasizes the importance of this medication in clinical practice.
Topics: Blood Platelets; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Secondary Prevention; Treatment Outcome
PubMed: 32284734
DOI: 10.1155/2020/8703627 -
Current Opinion in Hematology Nov 2020: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder mediated by antiplatelet autoantibodies and antigen-specific T cells that either destroy platelets... (Review)
Review
UNLABELLED
: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder mediated by antiplatelet autoantibodies and antigen-specific T cells that either destroy platelets peripherally in the spleen or impair platelet production in the bone marrow. There have been a plethora of publications relating to the pathophysiology of ITP and since January of 2019, at least 50 papers have been published on ITP pathophysiology.
PURPOSE OF REVIEW
To summarize the literature relating to the pathophysiology of ITP including the working mechanisms of therapies, T-cell and B-cell physiology, protein/RNA/DNA biochemistry, and animal models in an attempt to unify the perceived abnormal immune processes.
RECENT FINDINGS
The most recent pathophysiologic irregularities associated with ITP relate to abnormal T-cell responses, particularly, defective T regulatory cell activity and how therapeutics can restore these responses. The robust literature on T cells in ITP points to the notion that ITP is a disease initiated by faulty self-tolerance mechanisms very much like that of other organ-specific autoimmune diseases. There is also a large literature on new and existing animal models of ITP and these will be discussed. It appears that understanding how to specifically modulate T cells in patients with ITP will undoubtedly lead to effective antigen-specific therapeutics.
CONCLUSIONS
ITP is predominately a T cell disorder which leads to a breakdown in self tolerance mechanisms and allows for the generation of anti-platelet autoantibodies and T cells. Novel therapeutics that target T cells may be the most effective way to perhaps cure this disorder.
Topics: Animals; B-Lymphocytes; Disease Models, Animal; Humans; Immunity, Cellular; Purpura, Thrombocytopenic, Idiopathic; T-Lymphocytes
PubMed: 32868673
DOI: 10.1097/MOH.0000000000000612 -
Deutsche Medizinische Wochenschrift... Nov 2017Reasons for leukopenia can be numerous. To get close to the diagnosis it's always useful to check previous blood counts of the patient to get a feeling for the dynamic...
Reasons for leukopenia can be numerous. To get close to the diagnosis it's always useful to check previous blood counts of the patient to get a feeling for the dynamic development of the leukopenia. Furthermore, it's important to check the red blood cell count and platelet count as well; a bi- or a pancytopenia usually implies an insufficient production in the bone marrow. Nevertheless, a manual counted peripheral blood smear is an essential step towards the right diagnosis in leukopenia: Beside cell counts of the single subgroups of leucocytes it also provides information on potential causes such as dysplasia.Leukopenia can be life-threatening for the patient especially if the patient presents with an agranulocytosis and fever: In this case admission is mandatory and the patient has to be treated immediately with broad-spectrum antibiotics to reduce mortality.
Topics: Blood Cell Count; Diagnosis, Differential; Germany; Hematology; Leukopenia; Practice Guidelines as Topic
PubMed: 29145679
DOI: 10.1055/s-0043-113123 -
Journal of Cerebral Blood Flow and... Feb 2023Stroke is a sudden and rapidly progressing ischemic or hemorrhagic cerebrovascular disease. When stroke damages the brain, the immune system becomes hyperactive, leading... (Review)
Review
Stroke is a sudden and rapidly progressing ischemic or hemorrhagic cerebrovascular disease. When stroke damages the brain, the immune system becomes hyperactive, leading to systemic inflammatory response and immunomodulatory disorders, which could significantly impact brain damage, recovery, and prognosis of stroke. Emerging researches suggest that ischemic stroke-induced spleen contraction could activate a peripheral immune response, which may further aggravate brain injury. This review focuses on hemorrhagic strokes including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) and discusses the central nervous system-peripheral immune interactions after hemorrhagic stroke induction. First, inflammatory progression after ICH and SAH is investigated. As a part of this review, we summarize the various kinds of inflammatory cell infiltration to aggravate brain injury after blood-brain barrier interruption induced by hemorrhagic stroke. Then, we explore hemorrhagic stroke-induced systemic inflammatory response syndrome (SIRS) and discuss the interactions of CNS and peripheral inflammatory response. In addition, potential targets related to inflammatory response for ICH and SAH are discussed in this review, which may lead to novel therapeutic strategies for hemorrhagic stroke.
Topics: Humans; Hemorrhagic Stroke; Cerebral Hemorrhage; Stroke; Subarachnoid Hemorrhage; Blood-Brain Barrier; Brain Injuries
PubMed: 36476130
DOI: 10.1177/0271678X221145089 -
Cardiovascular & Hematological... 2020Prevention is essential for avoiding the complications of muscle hematomas (compartment syndrome, pseudotumors and peripheral nerve lesions) in hemophilic patients. This... (Review)
Review
Prevention is essential for avoiding the complications of muscle hematomas (compartment syndrome, pseudotumors and peripheral nerve lesions) in hemophilic patients. This is achieved through early diagnosis of muscle hematomas and proper long-term hematological treatment until they have resolved (confirmed by image studies). Ultrasound-guided percutaneous drainage could be beneficial in terms of achieving better and faster symptom relief. Acute compartment syndrome (ACS) requires emergency surgical treatment (decompression fasciotomy). As for pseudotumors, the biopsy will help us confirm the diagnosis and rule out true tumors (chondrosarcoma, liposarcoma, synovial sarcoma) that sometimes mimic hemophilic pseudotumors. Surgical removal of hemophilic pseudotumors is the best solution. As alternatives, there are curettage and filling with cancellous bone and radiotherapy (when surgery is contraindicated). Preoperative arterial embolization (ideally 2 weeks before surgery) helps control intraoperative bleeding during surgery for giant pelvic pseudotumors. Peripheral nerve injuries, which are rare, almost always occur due to compression of hematomas in the vicinity. In most cases, they usually resolve with hematological treatment only. If such treatment fails, surgery would be indicated.
Topics: Animals; Compartment Syndromes; Disease Management; Hematoma; Hemophilia A; Humans; Muscles; Peripheral Nerve Injuries
PubMed: 32294050
DOI: 10.2174/1871529X20666200415121409 -
Journal of Nephrology Jun 2017Patients affected by cardiovascular disease (CVD) are treated with antiplatelet agents (AA) and/or anticoagulant drugs, which are fundamental in the management of... (Review)
Review
Patients affected by cardiovascular disease (CVD) are treated with antiplatelet agents (AA) and/or anticoagulant drugs, which are fundamental in the management of stroke, coronary atherosclerotic disease, peripheral vascular disease and atrial fibrillation. CVD is the most important cause of death in chronic renal failure (CRF). Death rates from myocardial infarction (MI) and from all other cardiac causes exceed those for the general population. Incidence of MI in CRF is triple that in the general population. Moreover, mortality is seven- to eight-fold higher in patients requiring chronic hemodialysis compared to the general population, and approximately 40% of deaths in this population are attributable to coronary artery disease (CAD). For these reasons, AA are widely used in patients affected by CRF. Current data do not support a protective effect of antiplatelet administration in hemodialytic patients as primary prevention of cardiovascular mortality. Different results have been obtained concerning secondary prevention of CVD. The Cooperative Cardiovascular Project demonstrated that dialysis patients treated with aspirin following MI had a 43% lower mortality. Another study reported that the use of aspirin and beta-blockers following MI was associated with lower mortality in CRF patients. However, aspirin plus clopidogrel seems to increase the hemorrhagic risk without a significant reduction in cardiovascular mortality and there are insufficient data to support the use of new AA drugs in hemodialytic patients. In conclusion, since CRF patients are one of the groups at highest risk for atherosclerotic events, it could be reasonable to use aspirin in HD patients. However, the bleeding risk in HD patients needs to be strongly evaluated, especially before starting dual AA treatment.
Topics: Blood Coagulation; Blood Platelets; Cardiovascular Diseases; Clinical Decision-Making; Hemorrhage; Humans; Kidney Diseases; Patient Selection; Platelet Aggregation Inhibitors; Renal Dialysis; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 27928736
DOI: 10.1007/s40620-016-0367-5 -
International Journal of Laboratory... Jun 2023The diagnosis of benign and neoplastic hematologic disorders relies on analysis of peripheral blood and bone marrow aspirate smears. As demonstrated by the widespread... (Review)
Review
The diagnosis of benign and neoplastic hematologic disorders relies on analysis of peripheral blood and bone marrow aspirate smears. As demonstrated by the widespread laboratory adoption of hematology analyzers for automated assessment of peripheral blood, digital analysis of these samples provides many significant benefits compared to relying solely on manual review. Nonetheless, analogous instruments for digital bone marrow aspirate smear assessment have yet to be clinically implemented. In this review, we first provide a historical overview detailing the implementation of hematology analyzers for digital peripheral blood assessment in the clinical laboratory, including the improvements in accuracy, scope, and throughput of current instruments over prior generations. We also describe recent research in digital peripheral blood assessment, particularly in the development of advanced machine learning models that may soon be incorporated into commercial instruments. Next, we provide an overview of recent research in digital assessment of bone marrow aspirate smears and how these approaches could soon lead to development and clinical adoption of instrumentation for automated bone marrow aspirate smear analysis. Finally, we describe the relative advantages and provide our vision for the future of digital assessment of peripheral blood and bone marrow aspirate smears, including what improvements we can soon expect in the hematology laboratory.
Topics: Humans; Bone Marrow; Hematologic Tests; Bone Marrow Examination; Hematology; Neoplasms
PubMed: 37211430
DOI: 10.1111/ijlh.14082 -
Transfusion Medicine Reviews Jan 2020Multiple mathematical equations inform the practice of transfusion medicine. These equations apply to a wide range of topics: dosage of blood products, calculation of... (Review)
Review
Multiple mathematical equations inform the practice of transfusion medicine. These equations apply to a wide range of topics: dosage of blood products, calculation of fluid volumes, and even specific treatment decisions (e.g. corrected count increment for determination of platelet refractoriness). The calculation of these equations can be complicated, prone to error, and time-consuming. A trusted source is needed to accurately perform these calculations 24 hours a day without error and without monetary cost. We sought to build internet-enabled calculators relevant to the practice of transfusion medicine. We partnered with MDCalc, an online host of medical calculators with 1 million monthly users in 196 countries, to design and host the calculators. The calculators guide users in the application of transfusion medicine equations by providing indications for use, inputs for the equations variables, error-checking, warnings for bad inputs, and interpretive guidance of the result. The following calculators were built: blood volume, corrected count increment (CCI), plasma dosage, cryoprecipitated antihemophilic factor dosage, approximate number of units for compatibility testing, maternal-fetal hemorrhage Rh(D) immune globulin dosage, intrauterine RBC transfusion dosage, neonatal polycythemia partial exchange, theoretical removal of a substance by plasmapheresis, sickle cell RBC exchange volume, peripheral blood stem cell collection, and a calculator relevant to donor lymphocyte infusion. Clinicians can now utilize this reputable and highly visible online source to access these common transfusion medicine equations at any time with an internet-enabled device (https://www.mdcalc.com/search?filter=transfusion+medicine).
Topics: Costs and Cost Analysis; Decision Making, Computer-Assisted; Erythrocyte Transfusion; Humans; Internet; Models, Theoretical; Plasma Exchange; Platelet Transfusion; Practice Patterns, Physicians'; Transfusion Medicine
PubMed: 31785949
DOI: 10.1016/j.tmrv.2019.10.003