Heparininduced thrombocytopenia hit is a lifethreatening immune response to heparin and its derivatives that is associated with a high risk of thromboembolic complications. 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 severe drug reaction to heparin that can lead to life and limbthreatening venous andor arterial thromboembolism. Heparininduced thrombocytopenia deranged physiology. An enzymelinked immunosorbent assay elisa is usually performed to assist in the diagnosis of hit. Target population adult patients with suspicion or diagnosis of heparin induced thrombocytopenia key practice recommendations screening for. Heparin induced thrombocytopenia mild to moderate thrombocytopenia or a 50 percent reduction after exposure to heparin or lowmolecularweight heparin arterial and venous thrombosis. The propensity for thrombosis distinguishes hit from other common drug induced. Heparin induced thrombocytopenia hit is considered the most common form of drug induced thrombocytopenia as well as one of the common causes of thrombocytopenia in hospitalized patients. Heparin induced thrombocytopenia hit is an immunemediated adverse drug reaction associated with a decrease of platelet counts that usually begins after at least 5 days of heparin treatment. Rates of mortality and morbidity have decreased from 20% to 610% with improvements in early. Heparininduced thrombocytopenia hit is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 pf4 and heparin. Heparininduced thrombocytopenia genetic and rare diseases.
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. 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. It is associated with significant morbidity and mortality if unrecognized. N engl j med dec 1 forty percent of patients with relapsed or refractory disease achieved complete remission. Platelets aggregate thrombocytopenia and release of thrombogenic microparticles from platelet. Furthermore, thrombocytopenia is commonly associated with bleeding complications. Heparin induced thrombocytopenia nejm pdf antiplatelet factor 4 heparin antibodies present a major risk of heparin induced thrombocytopenia hit. A snapshot of these guidelines is also available as a pdf.
Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. 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. Heparininduced thrombocytopenia hit is a potentially lifethreatening immune complication which occurs after exposure to unfractionated heparin ufh or less commonly, to lowmolecular weight heparins lmwhs. Heparin induced thrombocytopenia hit is an antibody mediated adverse effect of heparin therapy which is classified into two subtypes, hit i which is nonimmune, spontaneously reversible thrombocytopenia and. An iv or central line that is flushed with heparin or coated with heparin.
Hit usually occurs after you are treated with heparin. Hit often leads to thrombosis in large veins and arteries. Thrombotic thrombocytopenic purpura and heparininduced. Studies of the immune response in heparin induced thrombocytopenia. Heparininduced thrombocytopenia hit is a serious complication of heparin utilization. Uncertainty exists about the risk of early onset of hit ie, heparin induced thrombocytopenia thrombotic thrombocytopenic purpura. Heparin induced thrombocytopenia hit is an immunemediated hypercoagulable disorder caused by antibodies to platelet factor 4 pf4 and heparin.
Although first reported in 1973, immune heparin induced thrombocytopenia hit remains one of the most frequent and devastating adverse drug reactions encountered by physicians. Hit is a strong risk factor for venous and arterial thrombosis odds ratio, 20 to 40. The adverse drug effect known as heparininduced thrombocytopenia hit shows many similarities to a bacterial. Heparininduced thrombocytopenia hit is estimated to occur in up to 5% of patients receiving unfractionated heparin. Although heparin is highly successful in reducing morbidity and mortality associated with. Heparin induced thrombocytopenia hit treatment page 3 of 7 disclaimer. Heparininduced thrombocytopenia type ii occurs in 15% of patients started on heparin. The following guideline is intended to guide the management of heparin induced thrombocytopenia and includes recommendations for diagnosis and treatment agents. 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 a dangerous, potentially lethal, immunologicallymediated adverse drug reaction to unfractionated heparin ufh or, less commonly, low. Understanding the misunderstood disease of heparin induced. May 03, 2012 heparin induced thrombocytopenia hit is an adverse reaction to the drug heparin resulting in an abnormally low amount of platelets thrombocytopenia. Immunemediated heparin induced thrombocytopenia hit, which is caused by plateletactivating igg antibodies that recognize platelet factor 4 bound to heparin antipf4 heparin abs, is a relatively common side effect of heparin therapy and presents a strong risk factor for thromboembolic events associated with high mortality and morbidity warkentin, 2007a. American college of chest physicians evidencebased clinical practice guidelines 8th edition. Clinically, see drop in plts by 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. The first, hit type i also called heparinassociated thrombocytopenia in the past, is a benign form not associated with an increased risk of thrombosis.
The rapid production of igg antibodies median of 4 days without initial igm antibody production suggests a secondary immune response, despite the absence of previous exposure to heparin in the majority of patients who develop hit. Blood 2016 oct 28 compared with argatroban or bivalirudin, fondaparinux is considerably more costeffective and is associated with a higher probability of averting adverse events. In this case report, we described a 65year old male patient with hit ii after coronary artery bypass grafting. Riia on the platelet surface, platelets become activated, microparticles are released, and the coagulation cascade is triggered. Stanworth et al, nejm 20 multicenter, noninferiority rct n600. These antibodies are present in nearly all pa tients who receive a clinical diagnosis of the disorder 5,6 and cause disease in animals. Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin induced thrombocytopenia. Risk for heparin induced thrombocytopenia with unfractionated and lowmolecularweight heparin thromboprophylaxis. Pathogenic antibodies to pf4 heparin bind and activate cellular fc. Heparininduced thrombocytopenia is a syndrome of antibodymediated thrombocytopenia that paradoxically is often associated with thrombosis. 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. In 170 patients, platelet counts began to fall 4 or more days after heparin therapy was started most commonly between days 4 and 10 typicalonset thrombocytopenia. The goal was to determine the incidence of hit within our 1,061bed tertiary.
Arnold md msc director, mcmaster centre for transfusion research. Heparin induced thrombocytopenia hit heparin induced thrombocytopenia hit is a potentially lethal, immunologically induced complication to unfractionated heparin therapy and to a smaller degree, low molecular weight heparin salter, 2016. Argatroban and lepirudin are fdaapproved for the treatment of hit. Alarcon perez l, rodriguez huerta am, duque gonzalez p. Heparininduced thrombocytopenia hit is a prothrombotic adverse drug reaction. Heparininduced thrombocytopenia type ii hit is a more serious autoimmune disease causing a low platelet count and paradoxical blood clotting.
Thrombocytopenia associated with heparin due to heparin pf4 antibodies is referred to as heparin induced thrombocytopenia hit. Heparin induced thrombocytopenia hit is an immunemediated response to heparin administration that causes thrombocytopenia and a prothrombotic state. The pocket guides are available as a mobile application for ios and android devices, as a mobilefriendly website, and as pdf downloads. Heparininduced thrombocytopenia hit is considered the most common form of druginduced thrombocytopenia as well as one of the common causes of thrombocytopenia in hospitalized patients. Laboratory testing reveals a platelet count of 86,000 per cubic millimeter, as compar. Target population adult patients with suspicion or diagnosis of heparin induced thrombocytopenia key practice recommendations screening for hit 1. Heparininduced thrombocytopenia hit occurs in two major forms type i, which is non immunologic and associated with mild transient thrombocytopenia, and type ii, caused by an immunologic reaction that induces a declining platelet count and an intense prothrombotic state. There are three main reasons of thrombocytopenia, adecreasing of making platelet bincreasing of destruc. Diagnosis of hit is based on both clinical and serological features. Hit may affect up to 5% of the patients receiving unfractionated heparin ufh, but an accurate estimate is complicated by diagnostic difficulty. This chapter about the recognition, treatment, and prevention of heparin induced thrombocytopenia hit is part of the antithrombotic and thrombolytic therapy. Heparin induced thrombocytopenia hit is the development of thrombocytopenia a low platelet count, due to the administration of various forms of heparin, an anticoagulant.
Treatment and prevention of heparininduced thrombocytopenia. Heparin induced thrombocytopenia adult inpatient clinical. Heparininduced thrombocytopenia clinical presentation. Diagnosis requires the combination of a compatible clinical picture and laboratory confirmation of the presence of heparin dependent plateletactivating hit antibodies. Heparininduced thrombocytopenia aetiology bmj best. Heparin induced thrombocytopenia hit is the most important and most frequent drug induced, immunemediated type of thrombocytopenia. Heparininduced thrombocytopenia in aortoiliac thrombosis treated with argatroban. Heparin induced thrombocytopenia hit can be defined as any clinical event best explained by platelet factor 4 pf4. Platelet factor 4 pf4 that is released from platelet. A 63yearold man with coronary artery disease who has recently undergone bypass surgery presents with dyspnea.
Antithrombotic therapy is required to manage heparininduced thrombocytopenia hitbut currently approved agents such as argatroban must be given parenterally and closely monitored. This thoroughly updated fifth edition from international experts professors warkentin and greinacher is the gold standard for accurate diagnosis and management of this. These canadian researchers describe the time course of serologically confirmed heparininduced thrombocytopenia in 243 patients. Heparininduced thrombocytopenia hit immune complexes heparinpf4igg cause platelet activation via the platelet fc. A 75yearold female underwent cardiac surgery with intraaortic balloon pump iabp placement. Report from the 61st american society of hematology annual. Antiplatelet factor 4 heparin antibodies present a major risk of heparin induced thrombocytopenia hit. No matter where you are in your career, we would welcome you and encourage you to consider joining our community. The exact mechanism of heparin induced thrombocytopenia is not clearly understood, but an immunemediated response to heparin result ing in platelet consumption is the most widely accepted theory. Thrombocytopenia is the result of falling the number of platelet from 150,000microl. Heparininduced thrombocytopenia what you need to know. Heparininduced thrombocytopenia retrospective analysis of. Thrombocytopenia commonly occurs in hospitalized patients, particularly critically ill patients.
Heparininduced thrombocytopenia is caused by antibodies against complexes of platelet factor 4 pf4 and heparin. Heparininduced thrombocytopenia prevention bmj best practice. How we manage patients with heparin induced thrombocytopenia. Combining heparin with aspirin reduces the risk of thrombosis by 75%2. Hit ii which is an autoimmunemediated adverse effect of heparin therapy. Vs hat caused by nonimmunologic mechanisms mild direct platelet activation by heparin onset within 4 days.
Riia on platelets and monocytes to propagate a hypercoagulable state culminating in lifethreatening thrombosis. Feb 03, 2020 heparin induced thrombocytopenia hit is a condition that causes a decrease of platelets in the blood. Hit predisposes to thrombosis the abnormal formation of blood clots inside a blood vessel because platelets release microparticles that activate thrombin, thereby. Heparin induced thrombocytopenia is a prothrombotic disorder caused by plateletactivating antibodies that recognize platelet factor 4 pf4 heparin complexes. While the treatment of hitt hit with thrombosis with anticoagulation is well established, the risks and treatment of isolated hit are unclear. 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. The main treatment is discontinuation of heparin therapy. Prospective multicentre cohort study of heparininduced.
Temporal aspects of heparininduced thrombocytopenia nejm. The use of heparin is associated with a risk for hit regardless of the route of administration or dose. Heparin induced thrombocytopenia hit is a type of drug induced immune thrombocytopenia ditp. Hit results from an autoantibody directed against platelet factor 4. Hitt is then a flavour of hit type ii, which has both antibodymediated thrombocytopenia and thrombosis. Heparininduced thrombocytopenia and optimal management of. Heparininduced thrombocytopenia hit global cardiology.
Heparininduced thrombocytopenia hit is an immunemediated response to heparin administration that causes thrombocytopenia and a prothrombotic state. Heparin induced thrombocytopenia hit syndrome that occurs in 15% of all heparin exposed patients immunemediated formation of igg antibodies to heparin platelet factor 4 pf4 complexes pf4 is released from platelet granules and is positively charged heparin is negatively charged. Heparininduced thrombocytopenia is defined as a decrease in platelet count during or shortly following exposure to heparin. 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. Heparin induced thrombocytopenia hit treatment page 1 of 7.
A new clinical practice article provides an overview of heparin induced thrombocytopenia. Thrombocytopenia is the most common event in hit and occurs in at least 90% of patients, depending. Two clinical forms of hit are generally recognized. Heparininduced thrombocytopenia type i is harmless, causing a mild and transient reduction in platelet count. Timing of the thrombocytopenia is also helpful, because patients who have not received heparin in the previous 100 days will develop thrombocytopenia and detectable hit antibodies only after about day 4 of heparin exposure, at a median time of 6. Heparininduced thrombocytopenia is a profoundly dangerous, potentially lethal, immunologically mediated adverse drug reaction to unfractionated heparin or, less commonly, to lowmolecular weight heparin.
Heparin induced anaphylactoid reaction associated with heparin induced thrombocytopenia in the ed. In contrast to other pathological conditions which lead to thrombocytopenia and bleeding complications, hit results in a paradoxical prothrombotic state. Hit is usually an immune response which typically occurs 410 days after exposure to heparin. Heparin induced thrombocytopenia hit is a transient, antibodymediated thrombocytopenia syndrome that usually follows exposure to unfractioned heparin ufh or lowmolecularweight heparin lmwh. 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.
Ditp is a rare and challenging clinical issue, especially when it is associated with thrombosis. Hit is characterized by a platelet count fall of more. The new engl and journal of medicine 582 n engl j med 357. Overview of heparininduced thrombocytopenia medscape. 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.
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