Clinical and economic implications of false-positive heparin-induced thrombocytopenia immunoassays: utility of the 4T score.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition induced by platelet-activating IgG antibodies that recognize PF4/heparin complexes. Diagnosis of HIT relies on enzyme immunologic assays (EIAs) and functional assays [serotonin release assay (SRA)]. Our institution uses a latex immunoturbidimetric assay (LIA), which has shown a positive-predictive value (PPV) of 55.6%, and a negative-predictive value (NPV) of 99.7%. The low PPV of EIAs/LIAs, in combination with the clinical delay in obtaining results of a SRA, commonly leads to a false-positive diagnosis of HIT and inappropriate treatment. We performed a single-institution retrospective study at a large tertiary center to assess patient management decisions and economic costs following a false-positive HIT (LIA) test. This study found an 89.5% incidence of false-positive HIT (LIA) tests. 97.4% of patients underwent anticoagulation changes. 69.6% of patients were switched to argatroban. Of patients with a false-positive HIT immunoassay (LIA), 42 (40.7%) patients were on a prophylactic dose of anticoagulation at the time of HIT (LIA) positivity, of which 22 (52.4%) were switched to full anticoagulation with either argatroban or fondaparinux. Of the 22 patients switched to full anticoagulation, 15 (68%) had low-probability 4T scores. Seven (8.8%) of patients had bleeding events after HIT (LIA) positivity. All seven patients were switched to argatroban from a full-dose heparin anticoagulation. Five of the seven patients were considered major bleeds. Utilization of argatroban incurred substantial costs, estimated at approximately $73 000 for false-positive HIT cases. False-positive HIT (LIA) tests contribute to unwarranted anticoagulation changes, increased bleeding risks, and substantial healthcare costs. Incorporating the 4T score into diagnostic algorithms may help mitigate these risks by guiding appropriate clinical decisions. Future research should focus on refining diagnostic approaches and standardizing management strategies to improve patient outcomes and cost-effectiveness in HIT diagnosis and management.

[Heparin-induced thrombocytopenia type II (HIT II) : A medical-economic view]. / Die heparininduzierte Thrombozytopenie (HIT II) : Eine medizinökonomische Betrachtung.

BACKGROUND: In the context of inpatient and increasingly ambulatory thrombosis prophylaxis, heparins have been recognised as standard therapy for decades. In addition to the therapeutic benefit, therapy with heparins also entails the risk of undesirable side effects, such as bleeding and thrombocytopenia. Heparin-induced thrombocytopenia (HIT II) is deemed a serious side effect. AIM: In the following work, HIT II is subjected to a medico-economic consideration (treatment, pharmaceuticals, subsequent costs due to possible complications) and, with regard to a possible HIT II prophylaxis, aspects of increasingly respected patient safety are also considered. METHODS: In the context of a literature search the active ingredients argatroban and danaparoid, which are approved for HIT II treatment, were evaluated. RESULTS: HIT II - especially in combination with thromboembolic complications - represents a medical-economic burden for the hospital. Although this is only an orientation guide, it shows that HIT II syndrome is not adequately cost-covered by the G­DRG system. An early thrombosis prophylaxis with argatroban/danaparoid for HIT II risk patients should therefore be taken into account for medical-related as well as patient safety-relevant aspects. According to experience, the pharmaceutical supply for these medically needed products (anticoagulants) should be ensured for reasons of patient safety. CONCLUSION: The risk of an immunological response to heparin therapy is known. Within the context of increased patient safety, thrombosis prophylaxis should be issued with a risk-adjusted prophylaxis.

A randomized, open-label pilot study comparing desirudin and argatroban in patients with suspected heparin-induced thrombocytopenia with or without thrombosis: PREVENT-HIT Study.

Because of an extreme risk for thromboemboli, patients with suspected heparin-induced thrombocytopenia (HIT) require immediate initiation of an alternative anticoagulant. The only therapies approved by the Food and Drug Administration require intravenous infusion of expensive direct thrombin inhibitors. This prospective, randomized, open-label, exploratory study compared the clinical and economic utility of subcutaneous desirudin vs argatroban, the most frequently used agent for suspected or immunologically confirmed HIT, with or without thrombosis. Sixteen patients were randomized to treatment with fixed-dose desirudin (15 or 30 mg) every 12 hours or activated partial thromboplastin time-adjusted argatroban by intravenous infusion. Arm A included 8 patients naive to direct thrombin inhibitor therapy, whereas Arm B included 8 patients on argatroban for at least 24 hours before randomization. The primary efficacy measure was the composite of new or worsening thrombosis (objectively documented), amputation, or death. Other end points included major and minor bleeding while on drug therapy, time to platelet count recovery, and pharmacoeconomics. No amputations or deaths occurred. One patient randomized to argatroban had worsening of an existing thrombosis. Major bleeding occurred in 2 patients on argatroban and in none during desirudin treatment. There was 1 minor bleed in each treatment group. The average medication cost per course of treatment was $1688 for desirudin and $8250 for argatroban. Desirudin warrants further study as a potentially cost-effective alternative to argatroban in patients with suspected HIT.

The use of alternative anti-coagulation strategies for a nocturnal home hemodialysis patient with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a potentially catastrophic hyercoagulable state. The prevalence of HIT in individuals doing nocturnal home hemodialysis (NHD) is unknown and the appropriate treatment protocol has yet to be determined. The objective is to describe the clinical course and treatment plan ofa patient who developed HIT while undergoing NHD. A 49-year-old man with a past history of end stage renal disease (ESRD) of unknown etiology was initiated on NHD in February 2005. His clinical and biochemical parameters improved after conversion to NHD. However, excessive bleeding at the vascular access sites complicated his treatments. Clinical investigations revealed development of HIT Alternative therapeutic strategies were attempted to enable our patient to continue NHD: unfractionated heparin, citrated regional anticoagulation, Danaparoid, and Argatroban. In conclusion, NHD patients with HIT pose a specific clinical challenge. We speculate that the augmented exposure of heparin coupled with a primed autoimmune response may be responsible for the development of HIT in our patient. Further research is required to elucidate the appropriate clinical monitoring and treatment strategy for this patient.

Direct thrombin inhibition during percutaneous coronary intervention in patients with heparin-induced thrombocytopenia.

Patients with or at risk of heparin-induced thrombocytopenia (HIT) who are undergoing percutaneous coronary intervention (PCI) are at particular risk of thrombosis due to the prothrombotic nature of HIT and the endovascular disruption from PCI. Patients require aggressive anticoagulation during PCI, and alternative, nonheparin anticoagulation is recommended over heparin in patients with acute or previous HIT. Argatroban, bivalirudin, and lepirudin are nonheparin, fast-acting, parenteral direct thrombin inhibitors (DTIs). Multicenter, prospective studies have demonstrated that argatroban and lepirudin each reduce thrombosis in HIT and that argatroban and bivalirudin each provide adequate anticoagulation during PCI in patients with or at risk of HIT. We review current therapeutic practices with direct thrombin inhibitors in patients with or at risk of HIT during PCI, including individuals requiring periprocedural anticoagulation, and the factors influencing the choice of DTI in this setting.

The cost-effectiveness of argatroban treatment in heparin-induced thrombocytopenia: the effect of early versus delayed treatment.

A decision-tree analysis was used to estimate the average cost per patient using the direct thrombin inhibitor argatroban for early treatment (<48 hours after thrombocytopenia onset) compared with delayed treatment (> or =48 hours after thrombocytopenia onset) of immune-mediated heparin-induced thrombocytopenia (HIT) with or without thrombosis. Clinical probability data used to populate the model were obtained from argatroban clinical trials and from published clinical literature. Resource utilization data and cost data were also obtained from available literature, the 2003 Physician's Fee Reference, the Healthcare Cost and Utilization Project 2000, the 2003 Drug Topics RedBook, and a modified Delphi panel. The total per-patient cost included hospital days, diagnostic tests, heparin, argatroban, major hemorrhagic events, and patient outcomes (ie, amputation, new thrombosis, stroke, or death), multiplied by the probability of each event. The incremental cost-effectiveness ratio was calculated by dividing the incremental cost between patients with and without argatroban treatment by the incremental effectiveness, or the cost per new thrombosis event avoided. The mean cost per HIT patient without thrombosis who did not receive argatroban was $38,046. The mean cost decreased by 6.85% for patients who were treated earlier with argatroban therapy (average cost, $35,441), representing a $2605 saving per patient compared with those not treated with argatroban. For those receiving delayed argatroban therapy, the mean cost increased by $9024 per patient compared with those receiving early treatment with argatroban. The mean cost for HIT patients with thrombosis who did not receive argatroban was $48,101, which was 9.0% higher than for those receiving early argatroban therapy, representing a $3957 savings per patient. For HIT with thrombosis, mean costs increased by 18.2% in patients whose argatroban was delayed, representing a cost increase of $8020 per patient compared with early treatment (mean cost $44,144 for early treatment and $52,164 for delayed treatment). The results of this analysis support the recommendation to initiate early argatroban treatment upon suspicion of HIT to reduce the thrombotic consequences of HIT and associated healthcare costs. Argatroban therapy should not be delayed pending the results of HIT diagnostic tests.

Argatroban: a direct thrombin inhibitor for heparin-induced thrombocytopenia and other clinical applications.

Argatroban, a direct thrombin inhibitor derived from arginine, is an effective anticoagulant indicated for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT). Argatroban has been used as an alternative anticoagulant in patients with HIT in various clinical conditions including interventional cardiovascular procedures that require anticoagulation. Satisfactory clinical outcomes with acceptable complications have been reported in these patients. Whether argatroban offers additional clinical advantage over conventional heparin therapy in patients without HIT remains unclear. Argatroban has been evaluated as an alternative anticoagulant to replace heparin in various clinical studies, especially in patients with coronary artery disease or cerebral vascular disease. To date, it remains unclear if argatroban is more effective than heparin, although the agent seems to cause less bleeding complications. This article reviews the pharmacology of argatroban and its clinical application beyond the management of HIT, with particular emphasis on interventional cardiology procedure, acute myocardial infarction, unstable angina pectoris, cerebral thrombosis or ischemic stroke, peripheral obstructive arterial disease, and extracorporeal circulation.