Heparin induced thrombocytopenia hit is an immunemediated complication of heparin therapy. Diagnosis requires the combination of a compatible clinical picture and laboratory confirmation of the presence of heparin dependent plateletactivating hit antibodies. Heparininduced thrombocytopenia hit is a prothrombotic complication mediated by auto antibodies against heparinplatelet complexes. Riia on the platelet surface, platelets become activated, microparticles are released, and the coagulation cascade is triggered. Heparininduced thrombocytopenia type ii hit is a more serious autoimmune disease causing a low platelet count and paradoxical blood clotting. The common, coincidental, and the complicated sanofi genzyme. Heparininduced thrombocytopenia hit is an immunemediated adverse drug reaction that is caused by heparin dependent, plateletactivating igg antibodies that recognize complexes of platelet factor 4 pf4 bound to heparin.
A 63yearold man with coronary artery disease who has recently undergone bypass surgery presents with dyspnea. Heparininduced thrombocytopenia is defined as a decrease in platelet count during or shortly following exposure to heparin 8. Older terminology distinguishes between two forms of heparin induced thrombocytopenia. We present an exemplifying case of severe heparin induced thrombocytopenia hit in an effort to solidify its high priority in the differential diagnosis of thrombocytopenia. Thrombocytopenia commonly occurs in hospitalized patients, particularly critically ill patients. Diagnosis and management of heparininduced thrombocytopenia. Dailymed heparin sodium in sodium chloride injection. Laboratory testing reveals a platelet count of 86,000 per cubic millimeter, as compar. Heparin induced thrombocytopenia is defined as a decrease in platelet count during or shortly following exposure to heparin 8. Delayedonset heparininduced thrombocytopenia is increasingly being recognized. Heparininduced thrombocytopenia hit is a wellknown complication of heparin therapy. This exclusive resource is available only to nejm community members and is made up of the clinical care articles your peers viewed the most on.
While the treatment of hitt hit with thrombosis with anticoagulation is well established, the risks and treatment of isolated hit are unclear. Lepirudin is approved for use in heparininduced thrombocytopenia. Heparininduced thrombocytopenia type i is harmless, causing a mild and transient reduction in platelet count. Heparin induced thrombocytopenia is an antibodymediated drug reaction that may be complicated not by just low platelets but arterial or venous thrombosis heparin induced thrombocytopenia heparin induced thrombocytopenia occurs in up to 5 % of patients receiving unfractionated heparin and in 0. Apr 30, 2007 thrombocytopenia commonly occurs in hospitalized patients, particularly critically ill patients. The new england journal of medicine downloaded from nejm. Heparininduced thrombocytopenia is defined as a decrease in platelet count during or shortly following exposure to heparin.
Heparininduced thrombocytopenia, fifthedition although first reported in 1973, immune heparininduced thrombocytopenia hit remains one of the most frequent and devastating adverse drug reactions encountered by physicians. Laboratory testing reveals a platelet count of 86,000 per cubic millimeter, as compared with 225,000 per cubic millimeter at the time of discharge nine days earlier. One of these is heparininduced thrombocytopenia hit, a common, serious and potentially lifethreatening condition 1,2, and one for which diagnosis can be dif. Hit results from an interaction between negatively charged heparin and a. May 03, 2012 heparin induced thrombocytopenia hit is an adverse reaction to the drug heparin resulting in an abnormally low amount of platelets thrombocytopenia. See the letter heparininduced thrombocytopenia on page 81a. Heparininduced thrombocytopenia investigations bmj best. Feb 03, 2020 heparin induced thrombocytopenia hit is a condition that causes a decrease of platelets in the blood. These collated data on patterns are based on descriptive studies small case seriescase reports reported across the world and are not based on large, prospectively. A severe drug reaction to heparin that can lead to life and limbthreatening venous andor arterial thromboembolism. Heparin induced thrombocytopenia hit is an unusual immunemediated adverse drug reaction with the central paradox being its strong association with thrombosis, despite the role of an anticoagulant heparin in causing a fall in platelet count thrombocytopenia. Heparin is used to treat and prevent abnormal blood clotting.
Aug 10, 2010 isolated heparin induced thrombocytopenia is defined as a fall in platelet count associated with a positive heparin pf4 antibody test, in the absence of clinically overt thrombosis. We present an exemplifying case of severe heparininduced thrombocytopenia hit in an effort to solidify its high priority in the differential diagnosis of thrombocytopenia. Increased heparin tolerance and recurrent thromboembolism which included myocardial infarction 3 patients, pulmonary embolism 2 patients and complete aortoiliac occlusion 2 patients, heralded the development of thrombocytopenia between the eighth and twelfth day of heparin therapy. Heparin induced thrombocytopenia hit treatment page 1. Consequently, heparin induced thrombocytopenia hit, an immune complication of heparin therapy, remains a highly relevant complication for the hematology practitioner to diagnose. Heparin induced thrombocytopenia hit is a lifethreatening immune response to heparin and its derivatives that is associated with a high risk of thromboembolic complications. Hit is an antibodymediated disorder of coagulation caused by exposure to heparin and associated with significant risk of thromboembolic complications and death 1,2,3. Rodgers, md, phd professor of medicine and pathology, medical director, arup hemostasisthrombosis laboratory, university of utah. Cutaneous findings reported in covid19 nebraska medicine. It causes prolonged morbidity, is fatal in 5%10% of cases and causes lifelong disability in another 10% of cases 1. Full text get a printable copy pdf file of the complete article 329k, or click on a page image below to browse page by page. Key clinical pointsheparin induced thrombocytopenia heparininduced thrombocytopenia hit is characterized by a decrease in the platelet count of more than 50% from the highest platelet count valu. Heparininduced thrombocytopenia what you need to know. Heparininduced thrombocytopenia and optimal management of.
Heparin induced thrombocytopenia hit is a notuncommon adverse effect of heparin exposure, with potentially serious andor fatal thrombotic consequences. Vancomycin drug induced thrombocytopeniaend stage renal disease. The first, hit type i also called heparin associated thrombocytopenia in the past, is a benign form not associated with an increased risk of thrombosis. Pdf heparin induced thrombocytopenia hit is an antibody mediated adverse effect of heparin therapy which is classified into two. Heparin induced thrombocytopenia mild to moderate thrombocytopenia or a 50 percent reduction after exposure to heparin or lowmolecularweight heparin arterial and venous. This algorithm has been developed for md anderson using a multidisciplinary approach considering circumstances particular to md andersons specific patient population, services and structure, and clinical information. American college of chest physicians evidencebased clinical practice guidelines 8th edition. Smock, md associate professor of pathology, medical director, arup hemostasisthrombosis laboratory, university of utah and george m. The use of heparin to flush some vascular access devices makes hit a concern for infusion nurses. The new england journal of medicine 812 n engl j med 355.
Delayedonset heparininduced thrombocytopenia annals of. To avoid disastrous outcomes, physicians must consider heparin induced thrombocytopenia whenever a recently hospitalized patient returns with thromboembolism. Antithrombotic therapy is required to manage heparin induced thrombocytopenia hitbut currently approved agents such as argatroban must be given parenterally and closely monitored. Incidence and outcomes of heparininduced thrombocytopenia in. Heparininduced thrombocytopenia in patients treated with lowmolecularweight heparin or unfractionated heparin. New guidelines for heparininduced thrombocytopenia. Hit is a transient, immunemediated adverse drug reaction in patients recently exposed to heparin that generally produces thrombocytopenia and often results in venous andor arterial thrombosis. Heparin induced thrombocytopenia hit is a serious adverse reaction that is caused by plateletactivating antiplatelet factor 4 pf4 heparin antibodies and leads to an.
Heparin induced thrombocytopenia hit low blood platelet count as a result of the medication heparin. Plex was discontinued in all patients and did not have to be resumed 2. Heparininduced thrombocytopenia genetic and rare diseases. Hospital acquired thrombocytopenia drug induced acute illness related. This is a pdf file of an unedited manuscript that has. Heparininduced thrombocytopenia hit is an adverse reaction to the drug heparin resulting in an abnormally low amount of platelets thrombocytopenia. Nonheparin anticoagulants for heparininduced thrombocytopenia. Protamine heparin induced thrombocytopenia pit protamine argininerich, positivelycharged protein an additive to certain preparations of insulin nph and a rapidlyacting antidote to heparin particularly to neutralize the effects of high heparin. Heparininduced thrombocytopenia prevention bmj best practice. Hit ii which is an autoimmunemediated adverse effect of heparin. Clinical picture of heparin induced thrombocytopenia hit and its differentiation from nonhit thrombocytopenia. Heparin induced thrombocytopenia hit is a lifethreatening complication of exposure to heparin ie, unfractionated heparin, low molecular weight lmw heparin that occurs in up to 5 percent of patients exposed, regardless of the dose, schedule, or route of administration. Target population adult patients with suspicion or diagnosis of heparin induced thrombocytopenia key practice recommendations screening for hit 1.
Correspondence from the new england journal of medicine heparin induced thrombocytopenia. Heparin induced thrombocytopenia hit treatment page 1 of 7 disclaimer. Heparininduced thrombocytopenia hit is an immunemediated response to heparin that curiously causes thrombi. Hit type i is a shortlived nonimmune, mild thrombocytopenia usually occurring within the first few hours to days of heparin. An iv or central line that is flushed with heparin or coated with heparin. Heparininduced thrombocytopenia differential diagnoses.
N engl j med dec at 23 years of followup, life expectancy was nearly 3 years longer with prostatectomy than with watchful waiting. The first, hit type i also called heparinassociated thrombocytopenia in the past, is a benign form not associated with an increased risk of thrombosis. Pf4 antibodies and thus has a very low likelihood of causing, or exacerbating, hit. Key clinical pointsheparin induced thrombocytopenia heparin induced thrombocytopenia hit is characterized by a decrease in the platelet count of more than 50% from the highest platelet count valu. These canadian researchers describe the time course of serologically confirmed heparininduced thrombocytopenia. Heparin is used in more than 12 million patients per year, 1 and can cause two forms of thrombocytopenia. Heparin induced thrombocytopenia nejm pdf antiplatelet factor 4 heparin antibodies present a major risk of heparin induced thrombocytopenia hit. Some heparin recipients develop thrombocytopenia, which is caused by igg antibodies against complexes of platelet factor 4 and heparin.
Correspondence from the new england journal of medicine heparin induced thrombocytopenia nejm. Antithrombotic therapy is required to manage heparin induced thrombocytopenia. New guidelines for heparin induced thrombocytopenia on september 3, 20 uwmedicine laboratory services released a new reflexive panel for hit antibody testing. Hit usually occurs after you are treated with heparin. Vancomycin induced thrombocytopenia protracted course in a. Heparininduced thrombocytopenia hit is an immunemediated hypercoagulable disorder caused by antibodies to platelet factor 4 pf4 and heparin. Heparininduced thrombocytopenia retrospective analysis of. Heparin induced thrombocytopenia hit is a lifethreatening complication of exposure to heparin eg, unfractionated heparin, low molecular weight lmw heparin that occurs in a small percentage of patients exposed, regardless of the dose, schedule, or route of administration. Clinical presentation and diagnosis of heparininduced.
Prevention and treatment of vte in patients with cancer. Currently, the term hit is used without a modifier to describe the immunemediated severe form. Heparin induced thrombocytopenia adult inpatient clinical. Heparin induced thrombocytopenia hit is an antibodymediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke. Heparininduced thrombocytopenia is a profoundly dangerous, potentially lethal, immunologically mediated adverse drug reaction to unfractionated heparin or, less commonly, to lowmolecular weight heparin. Management of heparininduced thrombocytopenia article pdf available in bmj clinical research 3076897. The adverse drug effect known as heparininduced thrombocytopenia hit shows many similarities to a bacterial. Ticagrelor causes falsenegative functional tests for. Desirudin is not approved for use in heparininduced throm bocytopenia, but it is approved for prevention of deepvein thrombosis after hipfracture surgery.
Heparininduced thrombocytopenia hit, formerly hit type ii, is a prothrombotic and potentially lethal disorder caused by platelet, endothelial, and monocyteactivating antibodies that target multimolecular complexes of platelet factor 4 pf4 and heparin. Heparin induced thrombocytopenia hit is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 pf4 and heparin. Approach to thrombocytopenia conditions that need to be considered. A 75yearold female underwent cardiac surgery with intraaortic balloon pump iabp placement. Heparininduced thrombocytopenia type ii occurs in 15% of patients started on heparin. This algorithm has been developed for md anderson using a multidisciplinary approach considering. Heparin induced thrombocytopenia panel was sent and was negative. Neutrophil activation and netosis are the major drivers of. Clinical presentation and laboratory diagnosis of heparin. Hit occurs in up to 5% of patients receiving unfractionated heparin.
Mar 21, 2019 the pathogenesis of heparin induced thrombocytopenia and thrombosis hit is mediated by heparin reactive autoantibodies binding to platelets thrombocytes. Laboratory testing for the antibodies that cause heparin induced thrombocytopenia. To assist clinicians with the diagnosis and initial management of heparin. Heparin induced thrombocytopenia is a prothrombotic iatrogenic disorder induced by plateletactivating antibodies that target multimolecular complexes of platelet factor 4 and heparin. Hit is usually an immune response which typically occurs 410 days after exposure to heparin. Treatment and prevention of heparininduced thrombocytopenia. Heparininduced thrombocytopenia with thromboembolic. Key clinical pointsheparininduced thrombocytopenia heparininduced thrombocytopenia hit is characterized by a decrease in the platelet count of more than 50% from the highest platelet count valu. Hit is caused by formation of immunoglobulin g antibodies that recognize complexes of platelet factor 4 pf4 and heparin and activate platelets resulting in mild to moderate thrombocytopenia.
In conjunction with this change, new guidelines for management of suspected hit and management of confirmed hit have also been developed. Heparin induced thrombocytopenia hit is a serious disorder caused by the development of antibodies against complexes formed by heparin and platelet factor 4. Monitoring fondaparinux in the setting of antithrombin. Heparin induced thrombocytopenia hit treatment page 1 of 7. The following guideline is intended to guide the management of heparin induced thrombocytopenia and includes recommendations for diagnosis and treatment agents. Heparininduced thrombocytopenia hit is a lifethreatening complication of exposure to heparin eg, unfractionated heparin, low molecular weight lmw heparin that occurs in a. The cardinal manifestations of hit are declining platelet counts. Plex was discontinued in all patients and did not have to be resumed.
This chapter about the recognition, treatment, and prevention of heparininduced thrombocytopenia hit is part of the antithrombotic and thrombolytic therapy. Heparin induced thrombocytopenia hit is an antibodymediated adverse drug reac tion that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke. Hit develops in temporal association with heparin therapy and manifests either as an unexplained thrombocytopenia or thrombocytopenia. Smock, md associate professor of pathology, medical director, arup hemostasisthrombosis.
Prophylaxis for hospitalized and nonhospitalized medical patients. Thrombocytopenia differential diagnosis falsely low platelet count in vitro platelet clumping caused by edtadependent agglutinins giant platelets common causes of thrombocytopenia pregnancy gestational thrombocytopenia, preeclampsia drug induced thrombocytopenia i. The objective of this report is to present the impact of different. However, there have been three reported isolated cases of fondaparinux.
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