Unlike other drug induced thrombocytopenia, hit does not usually. A 63yearold man with coronary artery disease who has recently undergone bypass surgery presents with dyspnea. Platelet factor 4heparin antibody tests, plate letactivation assays. Isolated heparininduced thrombocytopenia is defined as a fall in platelet count associated with a positive heparin pf4 antibody test, in the absence of clinically overt thrombosis.
Heparin induced thrombocytopenia nejm pdf antiplatelet factor 4heparin antibodies present a major risk of heparininduced thrombocytopenia hit. Heparin sodium is routinely used in the prophylaxis against deep venous thrombosis in medical and surgical patients. Argatroban suggested guidelines for use university of. Bleeding complications are a primary safety concern with the use of heparin therapy. Drug induced thrombocytopenia dit is a relatively common clinical disorder. Heparininduced thrombocytopenia hit is an immunemediated hypercoagulable disorder caused by antibodies to platelet factor 4 pf4 and heparin. Heparin induced thrombocytopenia hit can be defined as any clinical event best explained by platelet factor 4 pf4. Delayedonset heparininduced thrombocytopenia, a newly described syndrome of immunemediated thrombocytopenia that. 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 compar. 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. 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 an immunemediated response to heparin administration that causes thrombocytopenia and a prothrombotic state.
Highdose intravenous immunoglobulin for the treatment and. Heparininduced thrombocytopenia type i is harmless, causing a mild and transient reduction in platelet count. Heparininduced thrombocytopenia hit is the most important and most frequent druginduced, immunemediated type of thrombocytopenia. Heparin induced thrombocytopenia hit is an immunemediated hypercoagulable disorder caused by antibodies to platelet factor 4 pf4 and heparin. Antithrombotic therapy is required to manage heparin induced thrombocytopenia hitbut currently approved agents such as argatroban must be given parenterally and closely monitored. The propensity for thrombosis distinguishes hit from other common drug induced. It has a relatively short half life of 4050 minutes and is eliminated by hepatic metabolism and biliary secretion. Jan 04, 2020 heparin induced thrombocytopenia nejm pdf antiplatelet factor 4heparin antibodies present a major risk of heparininduced thrombocytopenia hit. It is associated with significant morbidity and mortality if unrecognized. Heparininduced thrombocytopenia hit is a prothrombotic complication mediated by auto antibodies against heparinplatelet complexes. 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.
Hit predisposes to thrombosis the abnormal formation of blood clots inside a blood vessel because platelets release microparticles that activate thrombin, thereby. Hit usually occurs after you are treated with heparin. Platelet factor 4 pf4 that is released from platelet. To determine whether fondaparinux is safe and effective for the treatment of hit. Thrombocytopenia is the most common event in hit and occurs in at least 90% of patients, depending. It causes prolonged morbidity, is fatal in 5%10% of cases and causes lifelong disability in another 10% of cases 1. Increased platelet consumption continued heparininduced thrombocytopenia immune thrombocytopenic purpura infection. 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. Watanabe j, nishimura k, miyasaka s, morimoto k, hamasaki t, ishiguro s. Hit is associated with 50fold increase in thrombosis risk. Treatment and prevention of heparininduced thrombocytopenia. May 03, 2012 heparin induced thrombocytopenia hit is an adverse reaction to the drug heparin resulting in an abnormally low amount of platelets thrombocytopenia. Heparininduced thrombocytopenia has been listed as one of the natural sciences good articles under the good article criteria. Heparin induced thrombocytopenia hit is the development of thrombocytopenia a low platelet count, due to the administration of various forms of heparin, an anticoagulant.
A new clinical practice article provides an overview of heparin induced thrombocytopenia. Hit results from an autoantibody directed against endogenous. Thrombocytopenia is defined as a platelet count below the 2. Heparininduced hyperkalemia jama internal medicine jama.
New guidelines for heparininduced thrombocytopenia on september 3, 20 uwmedicine laboratory services released a new reflexive panel for hit antibody testing. While the treatment of hitt hit with thrombosis with anticoagulation is well established, the risks and treatment of isolated hit are unclear. Heparininduced thrombocytopenia and optimal management of. Advertisers institutions editorial policies archive of pdf issues rss. Target population adult patients with suspicion or diagnosis of heparin induced thrombocytopenia key practice recommendations screening for hit 1. Heparininduced thrombocytopenia hit refers to a distinct group of clinical pathological disorders characterized by thrombocytopenia, greatly. Heparin binds to antithrombin iii to form a heparinantithrombin iii complex.
Heparininduced thrombocytopenia hit is a condition that causes a decrease of platelets in the blood. Pdf heparin induced thrombocytopenia hit is an antibody mediated adverse effect of heparin therapy which is classified into two subtypes, hiti. Hit develops in temporal association with heparin therapy and manifests either as an unexplained thrombocytopenia or thrombocytopenia complicated by thrombosis. Hit results from an autoantibody directed against platelet factor 4. Clinical picture of heparininduced thrombocytopenia hit and its differentiation from nonhit thrombocytopenia. Platelet factor 4 heparin antibody testing has a high negative, but low positive, predictive value. Heparin induced 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.
Heparininduced 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 heparininduced platelet activation test was carried out using washed platelets of four healthy blood donors. Fondaparinux is safe for heparininduced thrombocytopenia. Heparin induced thrombocytopenia hit, a well known side effect of heparin therapy, occurs in 15% of adults exposed to heparin. Heparin induced thrombocytopenia hit is the most important and most frequent drug induced, immunemediated type of thrombocytopenia.
Heparininduced thrombocytopenia retrospective analysis of. An iv or central line that is flushed with heparin or coated with heparin. 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. While most physicians are aware of heparininduced thrombocytopenia and skin necrosis, the association of heparin and hyperkalemia is less well recognized. How to approach thrombocytopenia hematology american. In conjunction with this change, new guidelines for management of suspected hit and management of. Heparininduced thrombocytopenia prevention bmj best practice. 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.
Heparininduced thrombocytopenia what you need to know. Hit is characterized by a platelet count fall of more than 50% at 5 to 10 days after the start of heparin and hypercoagulability. The complex binds to and irreversibly inactivates thrombin and other activated clotting factors, such as factors ix, x, xi, and xii, thereby preventing the polymerization of fibrinogen to fibrin and the subsequent formation of clots. A case of heparininduced thrombocytopenia type 2 after repair of juxtarenal abdominal aortic aneurysm. Patients with heparininduced thrombocytopenia hit require alternative. Apr 30, 2007 thrombocytopenia commonly occurs in hospitalized patients, particularly critically ill patients. Feb 03, 2020 heparin induced thrombocytopenia hit is a condition that causes a decrease of platelets in the blood. Heparininduced 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. There are no specific guidelines for dosing in hepatic impairment and therefore argatroban should be avoided in patients with any degree of hepatic impairment. Pathogenic antibodies to pf4heparin bind and activate cellular fc.
N engl j med dec at 23 years of followup, life expectancy was nearly 3 years longer with prostatectomy than with watchful waiting. Heparininduced thrombocytopenia type ii occurs in 15% of patients started on heparin. Increased platelet consumption continued heparininduced thrombocytopenia immune thrombocytopenic purpura infection e. Heparininduced thrombocytopenia new england journal. Jun 08, 2019 heparin induced thrombocytopenia nejm pdf antiplatelet factor 4heparin antibodies present a major risk of heparininduced thrombocytopenia hit. Druginduced thrombocytopenia dit is a relatively common clinical disorder. While most physicians are aware of heparininduced thrombocytopenia and skin necrosis, the association of heparin and hyperkalemia is less well. Heparin induced thrombocytopenia hit is a clinicopathological syndrome that occurs when heparin dependent igg antibodies bind to heparinplatelet factor 4 complexes to activate platelets and produce a hypercoagulable state.
Heparin induced thrombocytopenia mild to moderate thrombocytopenia or a 50 percent reduction after exposure to heparin or lowmolecularweight heparin arterial and venous thrombosis. Heparin induced 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 the development of thrombocytopenia a low platelet count, due to the administration of various forms of heparin, an anticoagulant. 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. Delayedonset heparininduced thrombocytopenia and cerebral. Heparininduced thrombocytopenia hit is an immunemediated adverse drug reaction that is caused by heparindependent, plateletactivating igg antibodies that recognize complexes of platelet factor 4 pf4 bound to heparin. Thrombocytopenia commonly occurs in hospitalized patients, particularly critically ill patients. Neutrophil activation and netosis are the major drivers of. The propensity for thrombosis distinguishes hit from other common druginduced. The risk of heparin induced thrombocytopenia is believed to be even lower perhaps negligible with fondaparinux arixtra, 2 a factor xa inhibitor modeled after a critical heparin. Heparininduced thrombocytopenia clinical presentation. Heparininduced thrombocytopenia hit is a lifethreatening immune response to heparin and its derivatives that is associated with a high risk of thromboembolic complications. A severe drug reaction to heparin that can lead to life and limbthreatening venous andor arterial thromboembolism. Heparininduced thrombocytopenia investigations bmj best.
Heparininduced thrombocytopenia type ii hit is a more serious autoimmune disease causing a low platelet count and paradoxical blood clotting. 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. Although first reported in 1973, immune heparin induced thrombocytopenia hit remains one of the most frequent and devastating adverse drug reactions encountered by physicians. Heparin induced thrombocytopenia hit is an immunemediated response to heparin administration that causes thrombocytopenia and a prothrombotic state. Target population adult patients with suspicion or diagnosis of heparin induced thrombocytopenia key practice recommendations screening for. Heparininduced thrombocytopenia hit is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 pf4 and heparin.
Diagnosis requires the combination of a compatible clinical picture and laboratory confirmation of the presence of heparin dependent plateletactivating hit antibodies. Heparin is a sulfurrich glycosaminoglycan with anticoagulant property. Hit is usually an immune response which typically occurs 410 days after exposure to heparin. A 75yearold female underwent cardiac surgery with intraaortic balloon pump iabp placement.
New guidelines for heparininduced thrombocytopenia. Diagnosis requires the combination of a compatible clinical picture and laboratory confirmation of the presence of heparindependent plateletactivating hit antibodies. Laboratory testing for the antibodies that cause heparin induced thrombocytopenia. Laboratory testing for the antibodies that cause heparininduced thrombocytopenia. Heparininduced thrombocytopenia hit syndrome that occurs in 15% of all heparinexposed patients immunemediated formation of igg antibodies to heparinplatelet factor 4 pf4 complexes pf4 is released from platelet granules and is positively charged heparin is negatively charged. Heparin induced thrombocytopenia is a prothrombotic disorder caused by plateletactivating antibodies that recognize platelet factor 4 pf4 heparin complexes. Clinical picture of heparin induced thrombocytopenia hit and its differentiation from nonhit thrombocytopenia. Heparin induced thrombocytopenia hit treatment page 1 of 7.
This thoroughly updated fifth edition from international experts professors warkentin and greinacher is the gold standard for accurate diagnosis and management of this. Heparininduced 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. Heparin induced thrombocytopenia adult inpatient clinical. Heparininduced thrombocytopenia hit is an adverse reaction to the drug heparin resulting in an abnormally low amount of platelets thrombocytopenia. Although first reported in 1973, immune heparininduced thrombocytopenia hit remains one of the most frequent and devastating adverse drug reactions encountered by physicians. 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.
This results in thrombocytopenia or thrombosis in temporal relation to a preceding heparin exposure. Heparin induced thrombocytopenia hit is a prothrombotic iatrogenic disorder induced by plateletactivating antibodies that target multimolecular complexes of platelet factor 4 and heparin. It is imperative to provide rapid identification and removal of the offending agent before clinically significant bleeding or, in the case of heparin, thrombosis occurs. Heparininduced thrombocytopenia genetic and rare diseases. Heparininduced thrombocytopenia hit is a prothrombotic iatrogenic disorder induced by plateletactivating antibodies that target multimolecular complexes of platelet factor 4 and heparin. A case of heparin induced thrombocytopenia type 2 after repair of juxtarenal abdominal aortic aneurysm. Heparininduced thrombocytopenia blood american society. Heparininduced thrombocytopenia is a profoundly dangerous, potentially lethal, immunologically mediated adverse drug reaction to unfractionated heparin or, less commonly, to lowmolecular weight heparin. Results of the third us national health and nutrition examination survey nhanes iii support the traditional value of 150.