Contemporary standards for the diagnosis and treatment of heparin-induced thrombocytopenia (HIT)

BACKGROUND: Heparin binding to platelet factor 4 (PF4) generates a new antigenic epitope. In an unpredictable fashion, as many as approximately 17% of patients treated with unfractionated heparin (UFH) and approximately 8% treated with low-molecular-weight heparin (LMWH) subsequently develop the anti-heparin-PF4 antibodies that mediate heparin-induced thrombocytopenia and thrombosis (HIT). Very few of those patients with circulating anti-heparin-PF4 antibodies, however, progress to develop clinical HIT (referred to previously as Type II HIT). Only 20% of those who harbor antibodies ( approximately 3% of those exposed to heparin) will manifest the thrombocytopenia subsequently. Even fewer patients (0.03% to 0.09% of those exposed to heparin) experience the marked platelet activation and morbid thromboses characteristic of the HIT syndrome. The pathogenesis of heparin-induced thrombocytopenia (HIT) remains elusive. The pathophysiologic understanding to date has revolved around pathogenic anti-heparin-PF4 antibodies that trigger platelet activation, release of platelet procoagulant microparticles, and resultant thrombosis. The clinical diagnosis of HIT is confusing because current assays to detect anti-heparin-PF4 antibodies do not correlate well with the disease. Currently available assays lack either adequate sensitivity and interlaboratory reproducibility (ie, functional serotonin release assays) or specificity (ie, enzyme-linked immunosorbent assays or ELISAs). CONCLUSIONS: Fortunately, the treatment for HIT is not confusing. The purposes of this review are as follows: (1) to examine the relevant clinical definition of HIT, (2) to explore our current understanding as to the pathogenesis of HIT, and (3) to present an algorithm for the identification and treatment of the HIT syndrome.     

血液透析应用低分子肝素诱发Ⅱ型血小板减少症一例

血液透析常用的抗凝剂低分子肝素诱发的Ⅱ型血小板减少症（HIT）较为罕见，现报告1例。 患者，女，68岁，因多尿、多饮10余年，间断颜面水肿5年，恶心、呕吐3d入院。既往无药物过敏史。实验室检查：血小板148×10^9／L，BUN26．25mmol／L，Ser503．9μmol／L，诊断为糖尿病肾病，慢性肾衰竭。入院后行右股静脉双腔管置管血液透析，动静脉内瘘成形术。     

Heparin-induced thrombocytopenia (HIT II) in liver transplant recipients: a retrospective multivariate analysis of prognostic factors

We investigated the prevalence of HIT II in liver transplant recipients and analysed associated factors. In recipients with clinically suspected HIT II in the 4Ts pretest clinical scoring system HIPA-assay was performed. Next, 37 clinical variables were analysed retrospectively for their association with HIT II. Factors significantly correlated to our findings in univariate analysis were included in a multivariate model and binary logistic regression analysis. Among 46 recipients 21 patients were suspicious in the 4Ts pretest and 14 of them (30.4%) were diagnosed HIT-antibody positive. Patient's age (P = 0.001), postoperative dialysis (P = 0.028), and postoperative hospital stay (P = 0.035) were significantly associated with development of HIT-antibodies in univariate analysis. Postoperative dialysis and postoperative hospital stay turned out as epiphenomena of patient's age, the only independent predictor (P = 0.021). Using multiple χ(2) -testing, a cut-off could be calculated, assigning patients younger than 59 years to a low risk group and patients of 59 years and older to a high risk group. High incidence of peri-operative HIT II seroconversion in liver transplant recipients is not associated with factors known to induce thrombocyte activation, like blood products or cell-saver. Only patients' age was identified as independent predictor.     

Die Heparin-induzierte Thrombozytopenie (HIT)

For many decades, heparins have been used successfully for prophylaxis and treatment of thromboembolic complications world-wide. Although heparin-induced thrombocytopenia (HIT Type II) is a well-known adverse effect of heparin therapy, thromboembolic complications during heparin therapy are rarely diagnosed exactly to be related to HIT. At present an immunologic etiology of HIT by generation of multimodal immune complexes against a neo antigen of heparin and platelet factor 4 is equivocally accepted. The incidence of HIT seems to be related to the type of heparin (unfractioned/low molecular weight) or other underlying risks such as peripheral occlusive vessel disease. Mortality and complications resulting from HIT is reported to be about 20-30% each. For diagnosis of HIT Type II, clinical observation and simultaneous laboratory testing are essential. Discontinuation of heparin is a simple and essential manoeuvre, and anticoagulation has to be continued by alternative drugs. The heparinoid danaparoid-sodium and the thrombin inhibitor recombinant hirudin have been used successfully world-wide for treatment in many patients with HIT Type II including cardiopulmonary bypass surgery or renal replacement procedures. Furthermore, other therapeutical alternatives (e.g. immunoglobulins, prostaglandines) exist. Randomised controlled studies have to evaluate which drug has to be preferred in the future including risk/benefit ratio. The need of supplementary surgical procedures (e.g. embolectomy) depends on the individual clinical status. The patients have to be informed in detail about their underlying disease and further deleterious consequences of re-exposition with heparin. HIT should be recorded in an emergency certificate and the national Committee on Drugs should be informed about this severe side effect of heparin therapy.     

The use of lepirudin in haemodialysis complicated with heparin-induced thrombocytopenia type II (HIT II)--dosage monitoring.

Sir, Heparin-induced thrombocytopenia type II (HIT II) is an unpredictableprothrombotic, immune-mediated life-threatening complicationthat occurs following administration of unfractionated heparin(UFH) or low-molecular weight heparin (LMWH) for a variety ofprophylactic or therapeutic applications [1]. The mainstay ofHIT treatment consists of the immediate cessation of all formsof heparin therapies and the simultaneous     

Heparininduzierte Thrombozytopenie (HIT) und Thrombose

Apart from bleeding complications, heparin-induced thrombocytopenia (HIT) type II is the most severe side effect of heparin therapy. It is widely agreed that its most important clinical symptom is thrombocytopenia, with or without thrombembolism.Assuming, unlike other authors, that thrombosis is the leading clinical symptom of HIT type II, we investigated the frequency of an immunological reaction indicative of HIT type II in patients suffering from thrombosis.From January 1999 to December 2000, 77% (n=6713) of our in-patients received heparin for more than 5 days as thrombosis prophylaxis.When thrombosis was suspected on the grounds of clinical appearances, the patient concerned underwent phlebography, and two different serological tests for anti-heparin antibodies were also carried out. In such cases, patients were immediately switched to hirudin instead of heparin. In 29 out of 101 patients, the clinical suspicion of thrombosis was confirmed. Three patients developed pulmonary embolism.In 4 patients both serological tests revealed the presence of anti-heparin antibodies. Three of the remaining 72 patients with negative phlebography results were found to have antibodies on serological testing. In none of the 7 patients with a confirmed diagnosis of HIT type II was the classical sign of thrombocytopenia was present.Even with thorough clinical and phlebographic examinations, the incidence of HIT type II is only 0.13% in our institution. One of the 7 patients with thrombosis was not thrombocytopenic but did show the typical immunological reaction. Since the incidence of HIT type II is low and thrombocytopenia is not a reliable indicator for HIT II, the need for frequent thrombocyte counts (twice weekly) should be reconsidered.However,patients developing thrombosis while receiving heparin need to be treated for clinically suspected HIT type II until the final diagnosis is made.     

Use of plasma exchange and heparin during cardiopulmonary bypass for a patient with heparin induced thrombocytopenia: a case report

Patients with documented history of heparin-induced thrombocytopenia (HIT) pose a difficult problem during surgery using cardiopulmonary bypass (CPB). Several alternatives to heparin exist, but these products either are not approved for use in the United States or have more side effects than heparin. We report on a patient with documented heparin-induced antibody and left main coronary artery disease who underwent uneventful coronary artery bypass surgery and recovery by using preoperative plasmaphresis and limited use of porcine intestinal heparin during CPB.     

Heparininduzierte Thrombozytopenie Typ II (HIT II)

Heparin-induced thrombocytopenia type II (HIT II) is the most severe complication during prophylactic treatment with low doses of heparin. Five cases demonstrate the life-threatening consequences of this immune-mediated thromboembolic disease. In order to improve prognosis it is most important to start therapy just before diagnosis is assured by laboratory tests. First choice treatment is the low-molecular-weight heparinoid Orgaran®. In patients with an episode of HIT II both low-molecular-weight heparin and unfractionated heparin will be contraindicated for a life time.     

Extracorporeal circulation with danaparoid sodium for valve replacement in thrombocytopenia induced by type II heparin]

A type II heparin-induced thrombocytopenia (HIT) was diagnosed in a 64-year-old woman at day 20 of intravenous unfractionated heparin (UFH) therapy, given after myocardial infarction treated by angioplasty and intracoronary stent. The infarction was complicated by a mitral insufficiency that led to a mitral valve replacement. Cardiopulmonary bypass was successfully performed with sodium danaparoid (Orgaran), as an alternative to UFH, without thrombotic or haemorrhagic complications and the follow-up was uneventful.