The 4Ts scoring system for heparin-induced thrombocytopenia in medical-surgical intensive care unit patients

Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Journal of critical care (Impact Factor: 2.19). 02/2010; 25(2):287-93. DOI: 10.1016/j.jcrc.2009.12.006
Source: PubMed

ABSTRACT Heparin-induced thrombocytopenia (HIT) is commonly considered but rarely confirmed in critically ill patients. The 4Ts score (Thrombocytopenia, Timing of thrombocytopenia, Thrombosis, and oTher reason) might identify individual patients at risk of having this disorder.
The aim of the study was to evaluate the value of the 4Ts HIT score in comparison with the serotonin-release assay (SRA) in critically ill patients.
This study describes the combined results of 3 prospective studies enrolling critically ill patients who were investigated for HIT if platelets fell to less than 50 x 10(9)/L or if platelet counts decreased to less than 50% of the value upon intensive care unit admission. We confirmed HIT by a positive platelet SRA. We assigned a 4Ts score blinded to SRA results to all 50 patients investigated for HIT; those with positive SRA results were scored in duplicate.
Of 528 patients, 50 (9.5%) were investigated for HIT; 39 (78%) of 50 (64%-88%) of these patients were scored as "low probability" by 4Ts score and none had a positive SRA. Of 49 patients who underwent SRA testing because of thrombocytopenia, only 2 (4.1%; 0.5-14.0) had a positive SRA (1 with a moderate 4Ts score and 1 with a high 4Ts score). Therefore, the overall incidence of HIT confirmed by SRA was 2 (0.4%) of 528 (0.04%-1.4%).
Significant thrombocytopenia during heparin administration occurred in 9.5% of critically ill patients, but HIT was confirmed in only 4.1% of those undergoing testing, for an overall incidence of 0.4%. A low 4Ts score occurred in 78% of patients investigated for HIT; none of these patients had a positive SRA. We conclude that HIT is uncommon in critically ill patients and that the 4Ts score is worthy of further evaluation in this patient population.

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    • "This substitution is expensive and could be associated with an increased risk of bleeding (10-20% of major haemorrhage) without effective antidote [3] [4]. While early diagnosis of HIT is essential to improve clinical management of patients, it remains challenging, especially in critically ill patients, in intensive care [5]. The current diagnostic relies on the use of a clinical scoring algorithm ( " 4T's rule " ) together with immunological and platelet activation assays [1] [2] [6]. "
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    ABSTRACT: Early diagnosis of immune heparin-induced thrombocytopenia (HIT) is challenging. HemosIL® AcuStar HIT and heparin-induced multiple electrode aggregometry (HIMEA) were recently proposed as rapid diagnostic methods. We conducted a study to assess performances of AcuStar HIT-IgG (PF4-H) and AcuStar HIT-Ab (PF4-H). The secondary objective was to compare the performances of the combination of Acustar HIT and HIMEA with standardised clinical diagnosis. Sera of 104 suspected HIT patients were retrospectively tested with AcuStar HIT. HIMEA was performed on available sera (n=81). The clinical diagnosis was established by analysing in a standardized manner the patient's medical records. These tests were also compared with PF4-Enhanced®, LTA, and SRA in subsets of patients. Thresholds were determined using ROC curve analysis with clinical outcome as reference. Using the recommended thresholds (1.00AU), the negative predictive value (NPV) of HIT-IgG and HIT-Ab were 100.0% (95% CI: 95.9%-100.0% and 95.7%-100.0%). The positive predictive value (PPV) were 64.3% (95% CI: 35.1%-87.2.2%) and 45.0% (95% CI: 23.2%-68.6%), respectively. Using our thresholds (HIT-IgG: 2.89AU, HIT-Ab: 9.41AU), NPV of HIT-IgG and HIT-Ab were 100.0% (95% CI: 96.0%-100.0% and 96.1%-100.0%). PPV were 75.0% (95% CI: 42.7%-94.5%) and 81.8% (95% CI: 48.3%-97.7%), respectively. Of the 79 patients with a medium-high pretest probability score, 67 were negative using HIT-IgG (PF4-H) test at our thresholds. HIMEA was performed on HIT-IgG positive patients. Using this combination, only one patient on 79 was incorrectly diagnosed. Acustar HIT showed good performances to exclude the diagnosis of HIT. Combination with HIMEA improves PPV.
    Thrombosis Research 06/2013; 132(3). DOI:10.1016/j.thromres.2013.06.004 · 2.43 Impact Factor
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    • "Sensitive assays for HIT are available, but limitations remain [8] [11] [33]. Functional assays are technically demanding and time-consuming, and are mostly used for research proposes [11] [34]. Commercial immunological assays, known to identify nonplatelet-activating antibodies, may not be routinely available to many institutions [9]. "
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    ABSTRACT: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction associated with thrombosis, and its paradoxical nature is a challenging issue for the diagnosis. The '4Ts' scoring system represents a simple and efficient way to improve clinical diagnoses of the syndrome. This system classifies patients as having high, intermediate, and low clinical probability for HIT. However, uncertainty remains concerning its clinical meaning, thus weakening the diagnostic value of this screening instrument. We analyzed the diagnostic test accuracy based on individual patient data extracted from published primary scientific studies. This study focused on 186 cases of treatment with heparin, which later evolved into a clinical suspicion of HIT. Upon choosing the most appropriate reference laboratory, the accuracy of the 4Ts was analyzed using the receiver operator characteristic curve analysis. Half of the positive cases (57.1%) were classified as having a high score, while 25.5% of the negative cases were classified as a having low score for HIT. Slightly more than half of all patients (53.2%) were classified as having an intermediate score. As such, the pre-test instrument would most likely fail to distinguish between diseased and nondiseased patients in a relevant number of cases. The calculated accuracy of the summary indicates that the 4Ts can be considered a good, but not a defining, test. Further studies are warranted regarding clinical score systems, either alone or in combination with laboratory tests, in an attempt to improve the early diagnosis of this adverse drug reaction and to provide better care for at-risk patients.
    Clinica chimica acta; international journal of clinical chemistry 08/2011; 412(17-18):1521-6. DOI:10.1016/j.cca.2011.04.026 · 2.76 Impact Factor
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    • "According to the well-established 4 T scoring model, the probability of HIT can be classified into low, intermediate, and high according to the clinical manifestations [8]. However, the differential diagnosis of HIT is usually difficult, especially in critical care patients [9] [10] [11]. Thus, the clinical diagnosis must be confirmed by in vitro demonstration of PF4/heparin (hep) antibodies. "
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    ABSTRACT: The in vitro demonstration of antibodies against platelet factor-4/heparin (PF4/hep) complexes is an important contribution to the diagnosis of heparin-induced thrombocytopenia (HIT). The use of PF4/hep IgG-specific immunoassays enhances the specificity of HIT-investigations without any impairment of the sensitivity. Several IgG-specific immunoassays with different origin and structure of the target antigen-complex are commercially available. Using a retrospective cohort consisting of 459 patients suspected to have HIT, we compared the performance characteristics of two commercially available IgG-specific immunoassays, GTI- (Genetic Testing Institute) and HIA-IgG-ELISA (Hyphen Biomed Research). PF4/hep antibodies were detected in 85 and 81 sera using GTI- and HIA-IgG-ELISA, respectively. OD values and clinical likelihood of patients who tested positive in one assay only were significantly lower than in those who tested positive in both immunoassays. Both IgG-specific assays showed high negative predictive values (100%) and similar but unsatisfactory positive predictive values, determined by a minimum clinical score of 5 and a positive HIPA result (41% and 43%, respectively). The implementation of a confirmatory step using excessive heparin increased the PPV of both assays, but results in a reduction of NPV in HIA-IgG-ELISA. The detection of IgG antibodies alone improves the clinical usefulness of immunoassays. However, functional assays remain indispensable to avoid the overdiagnosis of HIT caused by the detection of IgG non-platelet activating antibodies. The OD value in IgG immunoassays appears to correlate with the clinical relevance of the antibodies and might be used as a predictive parameter in the assessment of HIT.
    Thrombosis Research 04/2011; 127(4):345-8. DOI:10.1016/j.thromres.2010.12.001 · 2.43 Impact Factor
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