scholarly journals Obstacles in the diagnostics and therapy of heparin-induced thrombocytopenia

2010 ◽  
Vol 138 (suppl. 1) ◽  
pp. 69-73 ◽  
Author(s):  
Nebojsa Antonijevic ◽  
Nebojsa Radovanovic ◽  
Slobodan Obradovic ◽  
Dragica Vucelic ◽  
Bojan Stojanovic ◽  
...  
Keyword(s):  
Clinical Problem ◽  
Laboratory Diagnostics ◽  
Low Molecular Weight Heparins ◽  
Laboratory Findings ◽  
Heparin Induced Thrombocytopenia ◽  
Vte Prophylaxis ◽  
Clinical Probability ◽  
Immune Mediated ◽  
Number Of Patients ◽  
Immunologic Assays

An immune-mediated, severe, acquired prothrombotic disorder, heparin-induced thrombocytopenia type II (HIT II) occurs in 0.5-5% of patients exposed to unfractionated heparin longer than 5-7 days. Arterial and venous thromboses are induced by HIT II in about 35-50% of patients. Typical death rate for HIT is about 29%, while 21% of HIT patients result in amputation of a limb. The trend towards the occurrence of HIT due to the administration of low molecular weight heparins (LMWH) taking ever conspicuous place in the standard venous thromboembolism (VTE) prophylaxis has been more frequently observed recently. It is considered that LMWH may cause HIT II in about 0.25-1%. The need for further modification of HIPA assays with LMWH has been imposed in the HIT laboratory diagnostics, heretofore overburdened with complexity. There are several constantly opposing problems arising in HIT laboratory diagnostics, one of which is that in a certain number of patients immunologic assays detect nonpathogenic antibodies (mainly IgM or IgA heparin-PF4 antibodies) while, on the other hand, the occurrence of HIT pathogenetically mediated by minor antigens (neutrophil-activating peptide 2 or interleukin 8) may be neglected in certain cases. The following factors play an important role in the interpretation of each laboratory HIT assays performed: 1. correlation with HIT clinical probability test, the best known of which is 4T?score, 2. the interpretation of the laboratory findings dependent on the time of the thrombocytopenia onset, as well as 3. the sensitivity and specificity of each test respectively. The HIT diagnostics in the presence of other comorbid states which may also induce thrombocytopenia, more precisely known as pseudo HIT (cancer, sepsis, disseminated intravascular coagulation, pulmonary embolism, antiphospholipid syndrome, etc), represents a specific clinical problem.

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.

Heparin-induced thrombocytopenia in children: 12 new cases and review of the literature

2004 ◽  
Vol 91 (04) ◽  
pp. 719-724 ◽  
Author(s):  
Anne Klenner ◽  
Norbert Lubenow ◽  
Ricarda Raschke ◽  
Andreas Greinacher
Keyword(s):  
Risk Groups ◽  
Heparin Therapy ◽  
Severe Adverse Effect ◽  
Low Molecular Weight Heparins ◽  
Double Blind ◽  
Heparin Induced Thrombocytopenia ◽  
Medline Search ◽  
Immune Mediated ◽  
Few Data ◽  
Surgery Incidence

SummaryImmune-mediated heparin-induced thrombocytopenia (HIT) is a rare but severe adverse effect of heparin therapy. Only few data are available on clinical presentation, diagnosis and management of HIT in children. Records of all patients sent to our laboratory between 1995 and November 2003 were reviewed. To identify literature reports a Medline search was performed, the reference lists of those publications were screened and the abstracts of meetings on thrombosis and hemostasis between 2000 and 2003 were assessed. We identified 12 new HIT patients between 13 months and 18 years of age from our laboratory and 71 reports on HIT in children in the literature. For the assessment of frequency of HIT all studies enrolling > 100 patients were analyzed. HIT is rare in children. In pediatric patients, there seem to be two risk groups: newborns and infants under 4 years of age undergoing cardiac surgery (incidence ∼ 1-2%), and teenagers treated with heparin for thrombosis. For confirmation of HIT in children, antigen assays are most important. There are conflicting data on the optimal cut-off, with one randomized, double-blind trial indicating that the cut-off established in adults is appropriate.There are no systematic studies on alternative anticoagulants in children affected by HIT. Most data are available for lepirudin and danaparoid. Substitution of unfractionated heparin by low-molecular-weight heparins for regular anticoagulation may reduce the incidence of HIT.

Drug-Induced Immune Thrombocytopenia

2014 ◽  
Vol 27 (5) ◽  
pp. 430-439 ◽  
Author(s):  
Teresa Kam ◽  
Maurice Alexander
Keyword(s):  
Data Collection ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Immune Thrombocytopenia ◽  
Treatment Options ◽  
Diagnosis And Treatment ◽  
Drug Induced ◽  
Laboratory Findings ◽  
Heparin Induced Thrombocytopenia ◽  
Immune Mediated

Thrombocytopenia is commonly seen in laboratory findings, especially in critically ill patients. Although the incidence is rare, drug-induced immune thrombocytopenia (DITP) is a serious complication that is often overlooked as a cause of thrombocytopenia. Over the last century, extensive research and data collection have been done in an attempt to better characterize DITP. Heparin-induced thrombocytopenia is the most common DITP and has distinct pathogenesis, diagnosis, and treatment options. However, other offending medications are less well known and have triggered many questions and constant search for answers. This review will discuss both drug-induced immune-mediated and nonimmune-mediated thrombocytopenias, with a focus on immune-mediated processes. Thrombocytopenia caused by chemotherapy will not be discussed in this article.

Treatment of Heparin-Induced Thrombocytopenia

2002 ◽  
Vol 36 (3) ◽  
pp. 489-503 ◽  
Author(s):  
William E Dager ◽  
Richard H White
Keyword(s):  
Adverse Reaction ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Low Molecular Weight ◽  
National Library ◽  
Severe Adverse Reaction ◽  
Heparin Induced Thrombocytopenia ◽  
Immune Mediated ◽  
Study Selection ◽  
Clinical Conditions

OBJECTIVE: To describe heparin-induced thrombocytopenia (HIT or HIT-2), an immune-mediated adverse reaction to heparin or low-molecular-weight heparin. Available treatment options and considerations in developing a therapy approach are discussed. DATA SOURCES: A search of the National Library of Medicine (1992–June 2001) was done to identify pertinent literature. Additional references were reviewed from selected articles. STUDY SELECTION: Articles related to laboratory recognition and treatment options of HIT, including the use of agents in selected clinical conditions, were reviewed and included. CONCLUSIONS: HIT is a rare but potentially severe adverse reaction to heparin that was, until recently, poorly understood and had limited treatment options. Recent advances describing the recognition and clinical manifestations of immune-mediated HIT, including recently available antithrombotic treatment options, have dramatically changed outcomes for patients having this syndrome.

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.

Platelet count recovery and seroreversion in immune HIT despite continuation of heparin: further observations and literature review

2017 ◽  
Vol 117 (10) ◽  
pp. 1868-1874 ◽  
Author(s):  
Jo-Ann Sheppard ◽  
Theodore Warkentin ◽  
Andrew Shih
Keyword(s):  
Platelet Count ◽  
Additional Patient ◽  
Heparin Induced Thrombocytopenia ◽  
Prophylactic Dose ◽  
Heparin Administration ◽  
Immune Mediated ◽  
Antibody Levels ◽  
Count Recovery

SummaryOne of the standard distinctions between type 1 (non-immune) and type 2 (immune-mediated) heparin-induced thrombocytopenia (HIT) is the transience of thrombocytopenia: type 1 HIT is viewed as early-onset and transient thrombocytopenia, with platelet count recovery despite continuing heparin administration. In contrast, type 2 HIT is viewed as later-onset (i. e., 5 days or later) thrombocytopenia in which it is generally believed that platelet count recovery will not occur unless heparin is discontinued. However, older reports of type 2 HIT sometimes did include the unexpected observation that platelet counts could recover despite continued heparin administration, although without information provided regarding changes in HIT antibody levels in association with platelet count recovery. In recent years, some reports of type 2 HIT have confirmed the observation that platelet count recovery can occur despite continuing heparin administration, with serological evidence of waning levels of HIT antibodies (“seroreversion”). We now report two additional patient cases of type 2 HIT with platelet count recovery despite ongoing therapeutic-dose (1 case) or prophylactic-dose (1 case) heparin administration, in which we demonstrate concomitant waning of HIT antibody levels. We further review the literature describing this phenomenon of HIT antibody seroreversion and platelet count recovery despite continuing heparin administration. Our observations add to the concept that HIT represents a remarkably transient immune response, including sometimes even when heparin is continued.

Evaluation of a new nanoparticle-based lateral-flow immunoassay for the exclusion of heparin-induced thrombocytopenia (HIT)

2011 ◽  
Vol 106 (12) ◽  
pp. 1197-1202 ◽  
Author(s):  
Jakob Hesberg ◽  
Sentot Santoso ◽  
Gregor Bein ◽  
Tamam Bakchoul ◽  
Ulrich Sachs
Keyword(s):  
Lateral Flow ◽  
Lateral Flow Immunoassay ◽  
Medical Patients ◽  
High Potency ◽  
Platelet Factor ◽  
Predictive Values ◽  
Heparin Induced Thrombocytopenia ◽  
Clinical Probability ◽  
Short Period ◽  
Test Probability

SummaryHeparin-induced thrombocytopenia (HIT) is an adverse complication of heparin caused by HIT antibodies (abs) that recognise platelet factor 4-heparin (PF4/hep) complexes. Several laboratory tests are available for the confirmation and/or refutation of HIT. A reliable and rapid singlesample test is still pending. It was the objective of this study to evaluate a new lateral-flow immunoassay based on nanoparticle technology. A cohort of 452 surgical and medical patients suspected of having HIT was evaluated. All samples were tested in two IgG-specific ELISAs, in a particle gel immunoassay (PaGIA) and in a newly developed lateral-flow immunoassay (LFI-HIT) as well as in a functional test (HIPA). Clinical pre-test probability was determined using 4T's score. Platelet-activating antibodies were present in 34/452 patients, all of whom had intermediate to high clinical probability. PF4/hep abs were detected in 79, 87, 86, and 63 sera using the four different immunoassays. The negative predictive values (NPV) were 100% for both ELISA tests and LFI-HIT but only 99.2% for PaGIA. There were less false positives (n=29) in the LFI-HIT compared to any other test. Additionally, significantly less time was required to perform LFI-HIT than to perform the other immunoassays. In conclusion, a newly developed lateral-flow assay, LFI-HIT, was capable of identifying all HIT patients in a cohort in a short period of time. Beside an NPV of 100%, the rate of false-positive signals is significantly lower with LFI-HIT than with other immunoassay(s). These performance characteristics suggest a high potency in reducing the risk and costs in patients suspected of having HIT.

scholarly journals An Unusual Case of “Conjugal” Polymyalgia Rheumatica after SARS-CoV-2 Vaccination

Rheumato ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 17-21
Author(s):  
Elena Vanni ◽  
Jacopo Ciaffi ◽  
Luana Mancarella ◽  
Francesco Ursini
Keyword(s):  
Environmental Factors ◽  
Polymyalgia Rheumatica ◽  
Temporal Correlation ◽  
Married Couples ◽  
Laboratory Findings ◽  
Immune Mediated ◽  
Asia Syndrome ◽  
Causative Effect ◽  
Genetic And Environmental Factors

The rare occurrence of polymyalgia rheumatica (PMR) in married couples has been reported in the literature. Susceptibility to PMR is contributed by genetic and environmental factors and cases of PMR developing after influenza vaccine have also been described, in a debated phenomenon known as ‘ASIA’ syndrome. We report the case of two cohabitating married patients developing PMR few weeks after the first dose of ChAdOx1-S SARS-CoV-2 vaccine. Both patients presented with typical symptoms suggestive of PMR. Laboratory findings and ultrasound examination confirmed the diagnosis. Glucocorticoid therapy led to rapid improvment of symptoms. Anti-receptor-binding domain IgG titre was tested and, eight weeks after vaccination, both patients showed no antibody response. It has been suggested that vaccines might trigger autoimmune or inflammatory states in predisposed individuals and various hypotheses have been made regarding the pathogenesis of PMR. Although the causative effect of vaccines cannot be determined, the close temporal correlation observed in our case supports the potential role of environmental factors in triggering the onset of PMR. However, the literature indicates that post-COVID19 vaccination immune-mediated or inflammatory adverse events are extremely rare and vaccination should be encouraged since the benefit largely outweighs possible risks.

scholarly journals Membranoproliferative Glomerulonephritis Type 1 Secondary to an Infected Ventriculoperitoneal Shunt: a Case Report

2014 ◽  
Vol 12 (2) ◽  
pp. 119-121
Author(s):  
Christos Paliouras ◽  
Foteini Lamprianou ◽  
Georgios Ntetskas ◽  
Georgios Mattas ◽  
Nikolaos Karvouniaris ◽  
...  
Keyword(s):  
Ventriculoperitoneal Shunt ◽  
Membranoproliferative Glomerulonephritis ◽  
Classical Pathway ◽  
Glomerular Injury ◽  
Laboratory Findings ◽  
Immune Mediated ◽  
Histologic Pattern ◽  
Life Threatening ◽  
Subsequent Activation

AbstractVentricular shunting is the usual method for treatment of congenital or acquired hydrocephalus. Immune-mediated glomerulonephritis (shunt nephritis) is a rare but life-threatening complication of this neurosurgical technique. Intraglomerular deposition of circulating immune complexes and the subsequent activation of the classical pathway of serum complement’s cascade result in glomerular inflammation. Membranoproliferative gomerulonephritis is the most common histologic pattern observed in renal biopsy. The diagnosis needs high suspicion and is based on clinical and laboratory findings. Deterioration of renal function in association with signs of infection and low levels of serum complement’s proteins C3 and C4 make the diagnosis possible. The prognosis is variable and depends on the time of diagnosis after the onset of glomerular injury. The optimal treatment includes timely removal of the infected shunt in combination with aggressive antibiotic therapy. In this paper we present the case of a membranoproliferative glomerulonephritis type 1 in a patient with a ventriculoperitoneal shunt. Although this type of shunting is considered safer than the ventriculoatrial one, the risk of complications such as an immune-mediated glomerulonephritis still exists.

scholarly journals Effectiveness and safety of inpatient versus extended venous thromboembolism (VTE) prophylaxis with heparin following major pelvic surgery for malignancy: protocol for a systematic review

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Bridget Heijkoop ◽  
Natalie Parker ◽  
George Kiroff ◽  
Daniel Spernat
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Systematic Reviews ◽  
Pelvic Surgery ◽  
Current Evidence ◽  
Cochrane Library ◽  
Vte Prophylaxis ◽  
Optimum Duration ◽  
Number Of Patients ◽  
Increased Risk

Abstract Background Venous thromboembolism (VTE) is a common postoperative complication associated with significant morbidity and mortality. The use of prophylactic heparin postoperatively reduces this risk, and the use of extended duration prophylaxis is becoming increasingly common. Malignancy and pelvic surgery both independently further increase the risk of postoperative VTE and patients undergoing major pelvic surgery for malignancy are at particularly high risk of VTE. However, the optimum duration of prophylaxis specifically in this population currently remains unclear. Methods We will conduct a systematic review of literature in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0.,2011) to evaluate current evidence of the effectiveness and safety of inpatient versus extended VTE prophylaxis with heparin (all forms) following major pelvic surgery for malignancy. We will search PubMed, EMBASE, and the Cochrane Library. Regarding safety, Food and Drug Administration (FDA), and Therapeutic Goods Administration (TGA) websites will be searched, including all levels of evidence. Results will be the postoperative timeframe in which a VTE event can be considered to have been provoked by the surgery, and the number of patients needed to treat with both inpatient and extended prophylaxis to prevent a VTE event in this timeframe, comparing these to determine if there is a significant benefit from extended prophylaxis. Discussion This systematic review will aim to identify the postoperative period in which patients undergoing major pelvic surgery for malignancy are at further increased risk of VTE as a result of their surgery and the optimum duration of heparin VTE prophylaxis with heparin to reduce this risk. Determining this will allow evidence-based recommendations to be made for the optimum duration of heparin VTE prophylaxis post major pelvic surgery for malignancy, leading to improved standards of care that are consistent between different providers and institutions. Systematic review registration In accordance with guidelines, our systematic review was submitted to PROSPERO for consideration of registration on 16/12/17 and was registered on 12/1/18 with the registration number CRD42018068961, and it was last updated on December 1, 2018.

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