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1.
B. H. Chong 《Journal of thrombosis and haemostasis》2003,1(7):1471-1478
Summary. Heparin-induced thrombocytopenia (HIT) is not only a common but also a potentially serious drug adverse effect. Unlike other drug-induced thrombocytopenias, HIT does not usually cause bleeding, but instead causes thrombosis. Thrombosis in HIT can lead to limb gangrene (requiring leg amputation) or even death. HIT is mediated by an antibody that recognizes an epitope on the platelet factor 4 (PF4)–heparin complex. The antibody–PF4–heparin complex binds to FcγRII receptors on the platelet surface and cross-links the receptors. This induces intense platelet activation and platelet aggregation, and simultaneously activates blood-coagulation pathways. These changes are probably the basis of the thrombotic events in HIT. Diagnosis of HIT should be made mainly on clinical criteria but should be confirmed whenever possible by laboratory tests, particularly in patients with comorbid conditions, in whom the diagnosis of HIT cannot be made with certainty without testing. The tests for HIT antibodies are either immunoassays (e.g. ELISA), or functional tests, (e.g. 14 C-serotonin release assay). Once a clinical diagnosis of HIT is made, heparin should be ceased immediately and treatment with an alternative anticoagulant (such as danaparoid, r-hirudin or argatroban) commenced. This should continue for at least 5 days unless the diagnosis of HIT is subsequently proven to be incorrect. Warfarin should also be commenced when the patient is clinically stable and thrombosis is under control. There should be an overlap of a few days between warfarin and the alternative anticoagulant therapy. 相似文献
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Cines DB Rauova L Arepally G Reilly MP McKenzie SE Sachais BS Poncz M 《Journal of clinical apheresis》2007,22(1):31-36
Heparin‐induced thrombocytopenia (HIT) is the most common drug‐induced, antibody‐mediated cause of thrombocytopenia and thrombosis. HIT is caused by IgG antibodies that bind to epitopes on platelet factor 4 (PF4) released from activated platelets that develop when it forms complexes with heparin. Anti‐PF4/antibodies develop in over 50% of patients undergoing surgery involving cardiopulmonary bypass (CPB), an incidence 20‐fold higher than HIT. Why might this occur? Binding of HIT IgG occurs only over a narrow molar ratio of reactants, being optimal at 1 mol PF4 tetramer to 1 mol unfractionated heparin (UFH). At these ratios, PF4 and UFH form ultralarge (>670 kD) complexes that bind multiple IgG molecules/complex, are highly antigenic, and promote platelet activation. Low molecular weight heparin (LMWH), which is less antigenic, forms ultralarge complexes less efficiently and largely at supratherapeutic concentrations. In transgenic mice that vary in expression of human PF4 on their platelets, antigenic complexes form between PF4 and endogenous chondroitin sulfate. Binding of HIT IgG to platelets and induction of thrombocytopenia in vivo is proportional to PF4 expression. Heparin prolongs the duration and exacerbates the severity of the thrombocytopenia. High doses of heparin, as used in CPB, or protamine, which competes with PF4 for heparin, disrupts antigen formation and prevents thrombocytopenia induced by HIT antibody. These studies may help explain the disparity between the incidence of antibody formation and clinical disease and may help identify patients at risk for HIT (high platelet PF4). They also demonstrate that this autoimmune disease can be modulated at the level of autoantigen formation and point to rational means to intervene proximal to thrombin generation. J. Clin. Apheresis. 22:, 2007 © 2007 Wiley‐Liss, Inc. 相似文献
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《Expert review of cardiovascular therapy》2013,11(2):335-345
Heparin use is ubiquitous, wherein 1 to 5% of patients exposed to standard unfractionated heparin develop thrombocytopenia due to antibodies to a complex of heparin and platelet factor 4. Classic features include onset of thrombocytopenia after 5 to 10 days of ongoing heparin exposure, a 50% fall in the platelet count from baseline, resolution of the thrombocytopenia 5 to 10 days after cessation of heparin and a high risk of thrombosis noted in 30 to 75% of patients with heparin-induced thrombocytopenia (HIT) in terms of every-other-day platelet-count monitoring in patients on standard unfractionated heparin. And those patients developing thrombocytopenia necessitate an accurate, readily accessible diagnostic test for HIT. Diagnosis has been recently facilitated by the development of an enzyme-linked immunsorbent assay (ELISA) test for the heparin–P4 antibody complex, although this test carries a relatively low specificity. Widespread use of the ELISA demonstrates a relatively high prevalence of the antibody in patients exposed to heparin in certain settings, such as cardiopulmonary bypass, wherein a quarter of patients have a positive ELISA of unclear significance. Once HIT is diagnosed, the high risk of thrombosis necessitates empiric anticoagulation with an antithrombin such as argatroban or lepirudin, or the heparinoid danaparoid. Additional agents under further study include the antithrombin bivalirudin and the pentasaccharide fondaparinux. Future issues in HIT include increasing awareness for HIT, improving the specificity of HIT testing and the development of new anticoagulants for HIT that will enable out-patient management. 相似文献
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Hassan Y Awaisu A Aziz NA Aziz NH Ismail O 《Journal of clinical pharmacy and therapeutics》2007,32(6):535-544
OBJECTIVES: To highlight therapeutic controversies, and present a critical review of the most recent evidence on the management of heparin-induced thrombocytopenia (HIT). DATA SOURCES: A MEDLINE search from October 1996 until October 2006 was carried out. Pertinent literature was identified and other references identified from the bibliographic citations of the articles identified on MEDLINE. STUDY SELECTION: Articles related to the treatment of HIT including meta-analyses, systematic reviews, critical reviews, randomized and non-randomized trials, as well as case-reports, were reviewed. RESULTS AND CONCLUSION: The diagnostic and therapeutic dilemmas associated with HIT can be overwhelming and call for an evidence-based approach in the management of this frequently fatal event. HIT is associated with significant morbidity and mortality. The evidence suggests when heparin is stopped, alternative anticoagulant therapy with one of the newer agents such as lepirudin and argatroban is of benefit in avoiding deaths and morbidity. 相似文献
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Warkentin TE 《Critical Care Clinics》2011,27(4):805-23, v
Critically ill patients commonly evince thrombocytopenia, either evident on admission to the intensive care unit (ICU) or that develops during their stay. Heparin-induced thrombocytopenia (HIT) explains thrombocytopenia in only approximately 1/100 critically ill patients; also, only 1 or 2 in 10 ICU patients with a positive PF4-dependent enzyme immunoassay has “true” HIT. Thus, there is major potential for overdiagnosis of HIT in the ICU. A recent study showing that dalteparin is associated with a reduced frequency of HIT indicates that critically ill patients too can benefit from the HIT-reducing potential of this low molecular weight heparin preparation. 相似文献
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A. GREINACHER D. JUHL U. STROBEL A. WESSEL N. LUBENOW K. SELLENG P. EICHLER T. E. WARKENTIN† 《Journal of thrombosis and haemostasis》2007,5(8):1666-1673
INTRODUCTION: Platelet-activating antiplatelet factor 4/heparin (anti-PF4/heparin) antibodies are the major cause of heparin-induced thrombocytopenia (HIT). However, the relative utility of functional (platelet activation) vs. antigen [enzyme-immunoassay (EIA)] assays, and the significance of assay discrepancies remain unresolved. METHODS: Consecutive patient sera (n = 1650) referred for diagnostic HIT testing were screened prospectively by both the heparin-induced platelet activation (HIPA) test and anti-PF4/heparin EIA - including individual classes (IgG, IgA, IgM) - with clinical correlations studied. Platelet microparticle and annexin-V-binding properties of the sera were also investigated. RESULTS: Only 205 (12.4%) sera tested positive in either the HIPA and/or EIA: 95 (46.3%) were positive in both, 109 (53.1%) were only EIA-positive, and, notably, only one serum was HIPA-positive/EIA-negative. Of 185 EIA-positive sera, only 17.6% had detectable IgM and/or IgA without detectable IgG. Among sera positive for EIA IgG, optical density values were higher when the sera were HIPA-positive (1.117 vs. 0.768; P < 0.0001), with widely overlapping values. Two HIPA-positive but EIA-IgG-negative sera became HIPA-negative following IgG depletion, suggesting platelet-activating antibodies against non-PF4-dependent antigens. Clinical correlations showed that HIPA-negative/EIA-positive patients did not develop thrombosis and had reasons other than HIT to explain thrombocytopenia. IgM/A antibodies did not increase microparticle penetration, but increased annexin-V binding. CONCLUSIONS: The anti-PF4/heparin EIA has high ( approximately 99%) sensitivity for HIT. However, only about half of EIA-positive patients are likely to have HIT. Anti-PF4/heparin antibodies of IgM/A class and non-PF4-dependent antigens have only a minor role in HIT. 相似文献
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5B9, a monoclonal antiplatelet factor 4/heparin IgG with a human Fc fragment that mimics heparin‐induced thrombocytopenia antibodies 下载免费PDF全文
C. Kizlik‐Masson C. Vayne S. E. McKenzie A. Poupon Y. Zhou G. Champier C. Pouplard Y. Gruel J. Rollin 《Journal of thrombosis and haemostasis》2017,15(10):2065-2075
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A. GREINACHER 《Journal of thrombosis and haemostasis》2009,7(S1):9-12
Summary. Heparin-induced thrombocytopenia (HIT), typically occurring in the second week of heparin therapy, is an antibody-mediated adverse drug reaction associated with increased thrombotic risk. The most important antigens are located on platelet factor 4 (PF4)/heparin complexes. All HIT is caused by platelet-activating antibodies, but not all PF4/heparin-reactive antibodies cause HIT. Thus, tests have high negative, but only moderate, positive predictive value. Cessation of heparin requires substitution with an alternative anticoagulant, but as these drugs have increased bleeding risk, they should be used in therapeutic doses only if HIT is considered very likely. Avoiding/postponing coumarin is crucial in minimizing microthrombotic complications. Recent studies of HIT immunobiology suggest that HIT mimics immunity against repetitive antigens, as they are relevant in microbial defense. Thus, understanding HIT may help unravel why host defenses can trigger autoimmunity. 相似文献
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F. Lovecchio 《Clinical toxicology (Philadelphia, Pa.)》2014,52(6):579-583
A summary of heparin-induced thrombocytopenia (HIT) is presented. HIT is an adverse drug reaction characterized by thrombocytopenia and a high risk for venous or arterial thrombosis. The frequency of HIT ranges from 1 to 5% of patients receiving heparin with exact frequencies ranging between specific agents. Interestingly, this immune-mediated syndrome is ironically associated with thrombosis, not bleeding, with thrombin formation playing a major role. It is caused by heparin-dependent, platelet-activating antibodies that identifies a self-protein, PF4, bound to heparin that results in an antibody formation. The resulting platelet activation is associated with increased thrombin generation. Typically, the platelet count fall begins 5–10 days after starting heparin, although a rapid platelet count fall can occur in a patient who has antibodies from recent heparin use. Typical causes of HIT as well as the best diagnostic studies and treatment are discussed in this review. HIT was reviewed using a pubmed? search; google scholar? using key words: “Heparin-induced thrombocytopenia”; “heparin”, and “drug AND thrombocytopenia.” 相似文献
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Unkle DW 《Orthopaedic nursing / National Association of Orthopaedic Nurses》2007,26(6):383-5; quiz 386-7
Each year, 25% of all hospitalized patients are affected by venous thromboembolism, a disease comprising deep vein thrombosis and pulmonary embolism, that is responsible for up to 10% of all inpatient deaths (Alikhan, Peters, Wilmott, Cohen, 2004). Used in both the treatment and the prevention of venous thromboembolism, heparin is administered to more than 12 million patients each year in the United States, making it one of the most widely prescribed medications and the leading intravenous anticoagulant. Heparin-induced thrombocytopenia is an antibody-mediated adverse drug reaction to heparin therapy with potentially life-threatening complications. This article discusses the pathogenesis, diagnosis, and treatment of patients with heparin-induced thrombocytopenia. 相似文献
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D R Baldwin 《Journal of intravenous nursing》1989,12(6):378-382
Although adverse reactions to heparin are rare and usually quickly reversible, recent studies have reported a potentially more serious complication occurring in up to 30 percent of patients receiving heparin. This phenomenon, known as heparin-induced thrombocytopenia, is believed to be of two distinct types that differ in etiology, clinical onset, and therapeutic ramifications. The most common type is characterized by a mild, transient drop in the platelet count on the second or third day of heparin therapy that generally reverses itself with continued heparin administration. The second type is believed to be the consequence of an immune mechanism or heparin-dependent antibody and may be life-threatening because of an associated thrombosis known as white clot syndrome. This type occurs on the fourth to eighth day of heparin therapy and is signaled by declining platelet count and/or increasing resistance to heparin therapy and eventual development of a clot composed almost entirely of fibrin and platelet aggregates. Heparin-induced thrombocytopenia is significant in that it is not related to age, sex, blood type, or amount of heparin administered. Because of the absence of known risk factors, all patients receiving heparin should be considered at risk for heparin-induced thrombocytopenia. 相似文献
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Bambrah RK Pham DC Zaiden R Vu H Tai S 《Clinical advances in hematology & oncology : H&O》2011,9(8):594-599
Heparin-induced thrombocytopenia (HIT) is a growing complication of a common medication used to prevent deep vein thrombosis (DVT) in hospitalized patients. The purpose of this article is to review the mechanism that causes paradoxical thrombus formation in HIT and ways to recognize this important complication with various testing modalities and to discuss the approaches to treatment once a diagnosis has been made. HIT is a clinical diagnosis that can be further supported by utilizing the "4 Ts": thrombocytopenia, timing of platelet count fall, thrombosis or other complications, and other causes for thrombocytopenia. Diagnosis of HIT can be established using an HIT antibody test. Once a drop in platelet count is observed in a patient, it is important to rule out HIT. When HIT is first suspected, it is important to discontinue all heparin products. The gold standard in diagnosing HIT is the 14C-serotonin release assay (14C-SRA) assay, which has high sensitivity and specificity but is technically demanding and more time consuming than other antibody-detecting immunoassays. Anticoagulation in HIT patients is essential due to the increased risk of thrombosis. Treatment consists of utilizing alternative, nonheparin anticoagulants like lepirudin, argatroban, bivalirudin, or fondaparinux (although fondaparinux is not formally approved by the US Food and Drug Administration for this condition). Each of these agents should be individually formulated based on the patient and the presence/absence of liver or renal failure. Treatment duration has yet to be determined. However, in patients requiring long-term anticoagulation (pulmonary embolism, DVT, stroke), the transition to warfarin can be made once the platelet count recovers and there has been at least 5 days of overlap with a nonheparin anticoagulant. 相似文献
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Heparin is widely used for the prevention and treatment of thrombotic and particularly cardiovascular disorders. Unfortunately, 0.5 to 3.0% of patients given heparin develop an immune reaction, commonly termed Type II heparin-induced thrombocytopenia (HIT). This is characterized by a moderate thrombocytopenia and in some patients, a venous or arterial thrombosis. This frequently leads to disastrous sequelae, such as limb amputation and death. The pathophysiological basis of this serious adverse drug reaction is the production of an immunoglobulin G antibody that reacts with an antigenic complex consisting of heparin and platelet factor 4. A significant risk factor for the development of HIT is recent surgery, and the frequency of developing an antiheparin-platelet factor 4 or HIT antibody is particularly high in cardiac surgery patients, although surprisingly, only a few of these patients actually develop the clinical syndrome of HIT. This review will discuss the frequency, pathophysiology, clinical features, diagnosis and management of HIT. 相似文献
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Cellular immune responses to platelet factor 4 and heparin complexes in patients with heparin‐induced thrombocytopenia 下载免费PDF全文
I. Nazy R. Clare P. Staibano T. E. Warkentin M. Larché J. C. Moore J. W. Smith R. P. Whitlock J. G. Kelton D. M. Arnold 《Journal of thrombosis and haemostasis》2018,16(7):1402-1412
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S. SELLENG K. SELLENG H.-G. WOLLERT† B. MUELLEJANS‡ T. LIETZ T. E. WARKENTIN§ A. GREINACHER 《Journal of thrombosis and haemostasis》2008,6(3):428-435
Summary. Background: The diagnosis of heparin-induced thrombocytopenia (HIT) is problematic in postcardiac surgery (CS) intensive care unit (ICU) patients, as there are multiple potential explanations for thrombocytopenia and the presence of anti-platelet factor 4/heparin antibodies is not highly specific for HIT. Two platelet count profiles for HIT – a 40% or greater fall in platelet count beginning on or after day 5 (pattern 1) and persisting thrombocytopenia (< 100 × 109 L–1 ) beyond day 7 (pattern 2) – have been described in post-CS patients. Methods and results: We examined the platelet count profiles of 329 consecutive post-CS patients who required ICU treatment beyond 7 days. Although 70 patients (21.3%) developed thrombocytopenia (57.1% pattern 1, 42.9% pattern 2), the overall incidence of HIT was only 1.8% [6/329; 95% confidence interval (95% CI) 0.7–3.9%] in these ICU patients, with more HIT patients showing a pattern 2 than a pattern 1 platelet count decrease (four vs. two patients). Notably, pattern 2 patients with HIT also showed a new proportional fall of > 30% in platelet count between postoperative days 5 and 10. Among the remaining 2242 post-CS patients without a prolonged ICU stay, only three (0.1%; 95% CI 0.03–0.4%) developed symptomatic HIT (OR 0.07; 95% CI 0.01–0.3; P = 0.0002 vs. ICU patients), all presenting with pattern 1. Conclusions: Among post-CS ICU patients, a postoperative platelet count fall between days 5 and 10 increases diagnostic specificity for HIT, irrespective of whether this platelet count fall occurs after postoperative platelet count recovery (pattern 1) or is superimposed upon persisting postoperative thrombocytopenia (pattern 2). A prospective study is required in order to validate the findings of this retrospective analysis. 相似文献