scholarly journals Heparin-induced thrombocytopenia: research and clinical updates

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 262-268 ◽  
Author(s):  
Oluwatoyosi Onwuemene ◽  
Gowthami M. Arepally
Keyword(s):  
Limited Data ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Diagnostic Strategies ◽  
Immune Mediated ◽  
Emerging Therapies ◽  
Current Perspective ◽  
Clinical Advances ◽  
A Current

Abstract Heparin-induced thrombocytopenia (HIT) remains an important diagnosis to consider in hospitalized patients developing thrombocytopenia. HIT is an immune-mediated prothrombotic disorder caused by antibodies to platelet factor 4 (PF4) and heparin. Recent basic scientific studies have advanced our understanding of disease pathogenesis through studies of the PF4/heparin structure, immune mechanisms, and cellular basis of thrombosis. Clinical advances have also occurred in areas of HIT prevention, description of disease variants, and diagnostic strategies. Emerging anticoagulants with the potential to change HIT treatment are evolving, although with limited data. This review will provide a current perspective on HIT pathogenesis, disease features, diagnostic strategies, and role of emerging therapies for the management of HIT.

Heparin-induced thrombocytopenia: when a low platelet count is a mandate for anticoagulation

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Thomas L. Ortel
Keyword(s):  
Platelet Count ◽  
Heparin Therapy ◽  
Severe Thrombocytopenia ◽  
Drug Induced ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Immune Mediated ◽  
Number Of Patients ◽  
Increased Risk ◽  
Antibody Levels

Abstract Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of ~50 to 60 × 109 platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.

Management of Heparin-Induced Thrombocytopenia and Heparin-Induced Thrombocytopenia and Thrombosis Syndrome

1997 ◽  
Vol 3 (1_suppl) ◽  
pp. S53-S63 ◽  
Author(s):  
Jeanine M. Walenga ◽  
Bruce E. Lewis ◽  
Debra A. Hoppensteadt ◽  
Jawed Fareed ◽  
Mamdouh Bakbos
Keyword(s):  
Antibody Titer ◽  
Platelet Factor 4 ◽  
Positive Patient ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Comprehensive Account ◽  
Immune Mediated ◽  
Life Threatening ◽  
Pros And Cons ◽  
Sensitivity Specificity

Summary: Heparin-induced thrombocytopenia (HIT) is an immune mediated response to heparin in which antibody driven thrombosis can have a dramatic life-threatening expression. There is much interest on this subject including studies on the pathophysiologic mechanism, the clinical managements of the initial stages of HIT versus the HIT-positive patient requiring continued anticoagulation versus the HIT patient with thrombosis, the pros and cons of available alterr~aci~~ anticoagulants, and the laboratory assays to aid in the diagnosis of HIT with particular reference to the sensitivity/specificity of the new heparin-platelet factor 4 antibody titer assay. A comprehensive account of these timely issues is given in this article.

The Journey of Thiazolidinediones as Modulators of PPARs for the Management of Diabetes: A Current Perspective

2019 ◽  
Vol 25 (23) ◽  
pp. 2540-2554 ◽  
Author(s):  
Waquar Ahsan
Keyword(s):  
Peroxisome Proliferator ◽  
Expression Of Genes ◽  
Current Perspective ◽  
Drug Designing ◽  
Peroxisome Proliferator Activated Receptors ◽  
To Come ◽  
Ppar Ligands ◽  
A Current

Peroxisome Proliferator-Activated Receptors (PPARs) also known as glitazone receptors are a family of receptors that regulate the expression of genes and have an essential role in carbohydrate, lipid and protein metabolism apart from other functions. PPARs come in 3 sub-types: PPAR-α, PPAR-β/δ and PPAR-γ - with PPAR-γ having 2 isoforms - γ1 and γ2. Upon activation, the PPARs regulate the transcription of various genes involved in lipid and glucose metabolism, adipocyte differentiation, increasing insulin sensitivity, prevention of oxidative stress and to a certain extent, modulation of immune responses via macrophages that have been implicated in the pathogenesis of insulin resistance. Hence, PPARs are an attractive molecular target for designing new anti-diabetic drugs. This has led to a boost in the research efforts directed towards designing of PPAR ligands - particularly ones that can selectively and specifically activate one or more of the PPAR subtypes. Though, PPAR- γ full agonists such as Thiazolidinediones (TZDs) are well established agents for dyslipidemia and type 2 diabetes mellitus (T2D), the side effect profile associated with TZDs has potentiated an imminent need to come up with newer agents that act through this pathway. Several newer derivatives having TZD scaffold have been designed using structure based drug designing technique and computational tools and tested for their PPAR binding affinity and efficacy in combating T2D and some have shown promising activities. This review would focus on the role of PPARs in the management of T2D; recently reported TZD derivatives which acted as agonists of PPAR- γ and its subtypes and are potentially useful in the new drug discovery for the disease.

Risk factors for heparin-induced thrombocytopenia: Focus on Fcγ receptors

2016 ◽  
Vol 116 (11) ◽  
pp. 799-805 ◽  
Author(s):  
Jérôme Rollin ◽  
Claire Pouplard ◽  
Yves Gruel
Keyword(s):  
Risk Factors ◽  
Tyrosine Phosphatase ◽  
Inhibitory Effect ◽  
Igg Antibodies ◽  
Fcγ Receptors ◽  
Heparin Induced Thrombocytopenia ◽  
Thrombosis Risk ◽  
Immune Mediated ◽  
Healthy Donors

SummaryFcγ receptors have critical roles in the pathophysiology of heparin-induced thrombocytopenia (HIT), a severe immune-mediated complication of heparin treatment. Activation of platelets, monocytes and neutrophils by platelet-activating anti-PF4/heparin IgG antibodies results in thrombocytopenia, hypercoagulability and thrombosis in susceptible patients, effects that depend on FcγRIIA. In addition, FcγRIIIA receptors probably contribute to clearance of platelets sensitised by HIT immune complexes. FcγRI has also been reported to be involved in monocyte activation by HIT IgG antibodies and synthesis of tissue factor. This review focuses on the role of these FcγRs in HIT pathophysiology, including the potential influence of several gene variations associated with variable risk of HIT and related thrombosis. In particular, the 276P and 326Q alleles of CD148, a protein tyrosine phosphatase that regulates FcγRIIA signalling, are associated with a lower risk of HIT, and platelets from healthy donors expressing these alleles are hyporesponsive to anti-PF4/H antibodies. It was also recently demonstrated that the risk of thrombosis is higher in HIT patients expressing the R isoform of the FcγRIIA H131R polymorphism, with HIT antibodies shown to activate RR platelets more efficiently, mainly explained by an inhibitory effect of normal IgG2, which bound to the FcγRIIA 131H isoform more efficiently. Environmental risk factors probably interact with these gene polymorphisms affecting FcγRs, thereby increasing thrombosis risk in HIT.

scholarly journals Heparin-Induced Thrombocytopenia

2020 ◽  
Author(s):  
Gowthami M. Arepally ◽  
Anand Padmanabhan
Keyword(s):  
Risk Factors ◽  
Immune Complexes ◽  
Optimal Management ◽  
Cellular Mechanisms ◽  
Platelet Factor ◽  
Thrombotic Risk ◽  
Heparin Induced Thrombocytopenia ◽  
Factors Associated ◽  
Clinical Complications ◽  
Immune Mediated

Heparin-induced thrombocytopenia is an immune-mediated disorder caused by antibodies that recognize complexes of platelet factor 4 and heparin. Thrombosis is a central and unpredictable feature of this syndrome. Despite optimal management, disease morbidity and mortality from thrombosis remain high. The hypercoagulable state in heparin-induced thrombocytopenia is biologically distinct from other thrombophilic disorders in that clinical complications are directly attributable to circulating ultra-large immune complexes. In some individuals, ultra-large immune complexes elicit unchecked cellular procoagulant responses that culminate in thrombosis. To date, the clinical and biologic risk factors associated with thrombotic risk in heparin-induced thrombocytopenia remain elusive. This review will summarize our current understanding of thrombosis in heparin-induced thrombocytopenia with attention to its clinical features, cellular mechanisms, and its management.

A Current Perspective of Imagery in Psychoanalysis

1986 ◽  
Vol 5 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Erma Dosamantes-Alperson
Keyword(s):  
Object Relations ◽  
Forward Movement ◽  
Psychoanalytic Treatment ◽  
Current Perspective ◽  
Transference And Countertransference ◽  
Different Types ◽  
A Current

Two schools of thought concerning the value of imagery in psychoanalysis are contrasted. Discussion centers on the kinds of object relations manifested in the images of different types of patients, the role of imagery in internalizing particular analyst functions, and the value of attending to transference and countertransference images in promoting the forward movement of psychoanalytic treatment.

The role of platelet factor 4 in platelet aggregation induced by the antibodies implicated in heparin-induced thrombocytopenia

2001 ◽  
Vol 12 (7) ◽  
pp. 511-520 ◽  
Author(s):  
G. T. Gerotziafas ◽  
I. Elalamy ◽  
C. Lecrubier ◽  
J. Lebrazi ◽  
M. Mirshahi ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia

Genetics of Stuttering

1996 ◽  
Vol 39 (4) ◽  
pp. 771-784 ◽  
Author(s):  
Ehud Yairi ◽  
Nicoline Ambrose ◽  
Nancy Cox
Keyword(s):  
Familial Aggregation ◽  
Twin Studies ◽  
Clinical Work ◽  
Genetic Component ◽  
Future Research ◽  
Epidemiologic Factors ◽  
Current Perspective ◽  
Genetic And Environmental Factors ◽  
A Current

The fact that stuttering runs in families has been documented over a long period and has led to speculations and research about the role of a genetic component to this disorder. Although the genetic factor cannot be proved by familial aggregation and twin studies alone, such research has continued to provide support for a relationship between stuttering and genetics. The purposes of this article are to review and critique the research in this area. The article first assesses research methodologies that have been employed in familial studies of stuttering. It proceeds to review and critique incidence, twin, and aggregation studies. In addition, it includes sections on subgroups, genetic models of stuttering, and implications for future research as well as for clinical work. With a focus on improved methodology and recent findings, a current perspective on our knowledge of the genetic component to stuttering is provided. Among other conclusions, the article emphasizes that failure to consider epidemiologic factors has probably biased previous results regarding the genetics of stuttering. New preliminary data also appear to provide evidence that spontaneous recovery and chronicity are influenced by genetic factors. Generally, however, the review of incidence and twin studies, as well as of evidence for the various inheritance models, confirms previous conclusions about the interaction between genetic and environmental factors in stuttering.

scholarly journals To Clot or Not to Clot? Ad is the Question - Insights on Mechanisms Related to Vaccine Induced Thrombotic Thrombocytopenia

2021 ◽  
Author(s):  
Maha Othman ◽  
Alexander T. Baker ◽  
Elena Gupalo ◽  
Abdelrahman Elsebaie ◽  
Carly M. Bliss ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Severe Thrombocytopenia ◽  
Host Proteins ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Autoimmune Condition ◽  
Global Concern ◽  
Mechanistic Basis ◽  
The Uk

Vaccine-induced immune thrombotic thrombocytopenia (VITT), or thrombotic thrombocytopenic syndrome (TTS), has caused global concern. VITT is characterized by thrombosis and thrombocytopenia following COVID-19 vaccinations with the AstraZeneca ChAdOx1 nCov-19 and the Janssen Ad26.COV2.S vaccines. The clinical features of VITT include thrombosis, typically cerebral venous thrombosis, and severe thrombocytopenia developing 5 to 24 days following first dose of vaccine, with elevated D-dimer, and antibodies specific to platelet factor 4 (PF4), signifying platelet activation. As of June 1, 2021, over 1.93 billion COVID-19 vaccine doses had been administered worldwide. Currently, 467 VITT cases (0.000024%) have been reported across the UK, Europe, Canada and Australia. Clinically, VITT presents similarly to a rare autoimmune condition called “spontaneous/autoimmune heparin Induced Thrombocytopenia” (HIT) without prior heparin exposure. Guidance on diagnosis and management of VITT has been reported but the pathogenic mechanism of VITT is not fully elucidated. A definite causal relationship with the vaccine material is yet to be confirmed. To date, it is established that IgG antibodies recognizing PF4 activate platelets through FcγRIIA, however it remains unclear what triggers production of these antibodies. The fact that VITT, has only been described in association with adenoviral vector-based DNA virus vaccines, but not mRNA/lipid-based vaccines, raises the likelihood that the syndrome is somehow linked to the vector or other constituents in the vaccine preparation. Here, we propose and discuss potential mechanisms in relation to adenovirus induction of VITT. We discuss adenovirus immunogenicity and interactions with platelets and other host proteins, the role of PF4 and platelet activation. Whilst confirming a single mechanism underpinning VITT is challenging, we provide insights and clues into areas warranting investigation into the mechanistic basis of VITT, highlighting the unanswered questions. Further research is required to help solidify a pathogenic model for this condition.

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