Fabris f, ahmad s, cella g, jeske wp, walenga jm, fareed j. The 4ts for the diagnosis of heparininduced thrombocytopenia hit is a tool developed to help clinicians rule out hit in patients who develop thrombocytopenia in the clinical setting. Heparininduced thrombocytopenia ii has an immunologic origin4,5 and is characterized by a significant reduction in platelets 30%, generally after the fifth day of therapy. 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. Hit predisposes to thrombosis the abnormal formation of blood clots inside a blood vessel because platelets release microparticles that activate thrombin, thereby leading to thrombosis. Heparininduced thrombocytopenia type i is harmless, causing a mild and transient reduction in platelet count. Riia on platelets and monocytes to propagate a hypercoagulable state culminating in lifethreatening thrombosis. Hit usually occurs after you are treated with heparin. Laboratory testing reveals a platelet count of 86,000 per cubic millimeter, as compar.
A 63yearold man with coronary artery disease who has recently undergone bypass surgery presents with dyspnea. Hit results from an autoantibody directed against platelet factor 4. Heparininduced thrombocytopenia hit is a clinicalpathologic syndrome diagnosed based on clinical findings and laboratory evidence of antibodies directed to the heparin and platelet factor 4 complex hpf4. Onset of hit usually occurs 514 days after the start of heparin therapy. Heparininduced thrombocytopenia hit is a complication of heparin therapy and is characterized by two types. Heparininduced thrombocytopaenia following abdominal. The pathophysiological basis of hit results from the formation of an immunocomplex consisting of an autoantibody against platelet. Heparininduced thrombocytopenia clinical presentation. Welcome to, the heparin induced thrombocytopenia information source, an internet site designed for physicians and other health care personnel who want information about topics related to the pathophysiology, pharmacology, and clinical aspects of heparin induced thrombocytopenia. Risk of heparininduced thrombocytopenia in vascular.
Hit ii may also be defined as a transitory, autoimmune, and heparininduced thrombocytopenia. Pathophysiology of heparininduced thrombocytopenia. Pathogenic antibodies to pf4heparin bind and activate cellular fc. Heparin induced thrombocytopaenia hit is a rare lifethreatening complication following exposure to heparin. Heparininduced thrombocytopenia is a clinicopathologic syndrome that can be associated with severe complications and significant mortality. Heparininduced thrombocytopenia is an adverse drug reaction to heparin therapy leading to devastating clinical outcomes including venous thromboembolism, myocardial infarction, stroke, and limb amputation. Thrombocytopenia is defined as a platelet count below the lower limit of. Heparininduced thrombocytopenia hit is the most important druginduced immunemediated cytopenia for several reasons.
Heparininduced thrombocytopenia deranged physiology. 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. Hit is usually an immune response which typically occurs 410 days after exposure to heparin. The mechanism underlying heparininduced thrombocytopenia is an immune response 18, 19. Heparininduced thrombocytopenia hit is a clinicopathologic syndrome that occurs when heparindependent, igg antibodies bind to heparinplatelet factor 4 pf4 complexes to activate platelets and produce a hypercoagulable state. Heparininduced thrombocytopenia hit is a prothrombotic disorder caused by antibodies to complexes of platelet factor 4 pf4 and heparin. Heparininduced thrombocytopenia type ii occurs in 15% of patients started on heparin. The onset of clinical symptoms and laboratory changes is usually delayed 12 weeks after exposure to heparin. Thrombocytopenia which means low platelets is associated with a variety of conditions. First, heparin is a widely used anticoagulant see chapter 149. Platelet factor 4 is a small positively charged molecule of uncertain biological function normally found in. Heparininduced thrombocytopenia may occur even when verylowdose heparin eg, used in flushes to keep iv or arterial lines open is used. Discuss the historical context of using the aptt for therapeutic drug monitoring.
Heparininduced thrombocytopenia type ii hit is a more serious autoimmune disease causing a low platelet count and paradoxical blood clotting. Heparin cessation alone is not sufficient for the management of heparininduced thrombocytopenia. James zehnder, md, professor of pathology and hematology at stanford university discusses the pathophysiology, clinical features, diagnosis and management of heparininduced thrombocytopenia, and the limitations of aptt and xabased assays for monitoring heparin. An iv or central line that is flushed with heparin or coated with heparin. Clinical features that help distinguish hit from other forms of thrombocytopenia include the timing of onset and the presence of thrombosis eg, venous thromboembolism or other sequelae. Heparininduced thrombocytopenia hit occurs in up to 1% of patients receiving unfractionated heparin. The pathophysiology of hitts remains controversial. It is mediated by immunemediated thrombocytopaenia due to antibody against heparin pl. The principal antigen is a complex of heparin and platelet factor 4 pf4. Heparininduced thrombocytopenia and thrombosis syndrome hitts is an immunemediated response to the administration of heparin that results in lifethreatening thrombosis. Heparininduced thrombocytopenia symptoms, diagnosis and.
In 1973, rhodes et al5 described thrombocytopenia as a component of the syndrome. Rauova and colleagues reported that heparin and pf4 form stable, ultralarge 670 kda complexes ulcs composed of multiple pf4 tetramers arrayed in a lattice with several molecules of unfractionated heparin. In view of this, it has been apportioned its own revision chapter. Heparininduced thrombocytopenia hit is the most important and most frequent druginduced, immunemediated type of thrombocytopenia. 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. It occurs in approximately 5% of all patients receiving heparin therapy. The pathophysiology of heparininduced thrombocytopenia. It is considered the most severe nonbleeding adverse reaction of heparin treatment and one of the most important adverse drug reactions. The pathophysiology of heparininduced thrombocytopenia includes an immunemediated reaction to heparin that activates platelets and results in an acquired hypercoagulability. Increased destruction can happen in some autoimmune diseases like lupus, and medications like heparin can induce a severe thrombocytopenia in patients. Heparininduced thrombocytopenia hit is an adverse reaction to the drug heparin resulting in an abnormally low amount of platelets thrombocytopenia. Heparininduced thrombocytopenia and thrombosis hitt disseminated intravascular coagulation dic of a prothrombotic type e. Heparininduced thrombocytopenia hit is the development of thrombocytopenia a low platelet count, due to the administration of various forms of heparin, an anticoagulant. Heparininduced thrombocytopenia has appeared several times in the cicm fellowship exam, both in the written paper question 9.
The pathogenic role of heparin was confirmed by the recurrence of thrombocytopenia when a patient was reexposed to heparin. Second, hit is relatively common, occurring in approximately 1% to 3% of postoperative patients, and 0. Heparininduced thrombocytopenia hit is a condition that causes a decrease of platelets in the blood. Heparininduced thrombocytopenia is a profoundly dangerous, potentially lethal, immunologically mediated adverse drug reaction to unfractionated heparin or, less commonly, to lowmolecular weight heparin. The use of heparin to flush some vascular access devices makes hit a concern for infusion nurses. Arch pathol lab medvol 124, november 2000 pathophysiology of heparininduced thrombocytopeniafabris et al 1659 pathophysiology of the heparininduced thrombocytopenia hit syndrome. Because the platelet count normalizes even with continued heparin therapy, it is not associated with increased thrombotic risk. Heparininduced thrombocytopenia hit, even rare, is a lifethreatening, immunemediated complication of heparin exposure. Heparininduced thrombocytopenia hit is a life and limbthreatening thrombotic complication of heparin, which is the result of platelet activation by antipf4heparin antibodies. The development of thrombocytopenia or a new thrombus in a patient receiving heparin or a lowmolecular weight heparin lmwh necessitates careful assessment for heparininduced thrombocytopenia hit, an antibodymediated complication of heparin therapy. Epidemiology of heparininduced thrombocytopenia hit general consensus of incidence 80 years ago,1 and within a short interval it was used as an anticoagulant. Pathophysiology, abstract hit is a procoagulant disorder that is associated with significant morbidity and mortality if undetected and untreated.
Heparininduced thrombocytopenia hit is an immunemediated complication of heparin therapy. Heparininduced thrombocytopenia and thrombosis syndrome. Bleeding complications are a primary safety concern with the use of heparin therapy. Like i said, less than 100,000, but usually we dont start treating until less than 40,000 or so. Heparininduced thrombocytopenia what you need to know. Ultralarge complexes of pf4 and heparin are central to the pathogenesis of heparininduced thrombocytopenia. Shock liver causes depletion of protein c and antithrombin, with subsequent microvascular thrombosis of extremities. Heparininduced thrombocytopenia hit is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 pf4 and heparin. Stop the heparin treatment is the withdrawal of heparin and use of alternative anticoagulants.