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.
"To assist in the diagnosis of HIT, a scoring system called the 4Ts has been developed that incorporates a combination of clinical criteria associated with HIT . Retrospective studies in ICU patients found that a low probability score was unlikely to be associated with clinical HIT [8,9]. "
[Show abstract][Hide abstract] ABSTRACT: Heparin-induced thrombocytopenia (HIT) results from antibodies to PF4/heparin complexes and clinical diagnosis is difficult. We evaluated the particle immunofiltration anti-platelet factor 4 (PIFA) rapid assay, in conjunction with a clinical risk score, in the diagnosis of HIT.
We performed a prospective observational study in all patients admitted to the medical intensive care unit (MICU) in a large academic medical center. Patients were screened daily for thrombocytopenia defined as either a platelet count that decreased by at least 33% or an absolute platelet count less than 150,000/uL. Patients with suspected HIT underwent PIFA and ELISA testing for anti-PF4/heparin antibodies. Available residual frozen sera were sent to a reference laboratory in batches for serotonin release assay (SRA) testing.
During the study period, 340 patients were admitted to the MICU, of which 143 patients met criteria for thrombocytopenia. Forty three patients had no evidence of recent heparin exposure. PIFA and ELISA testing was performed on 100 patients, of which 92 had samples available for SRA analysis. PIFA results were negative in 62, positive in 28 and inconclusive in 2 patients. The 4Ts score was low to intermediate risk in 57 of the PIFA negative patients. The ELISA results were negative in 86 and positive in 6 patients. SRA testing identified 3 patients with a positive SRA test and 89 patients with a negative result. All patients with a negative PIFA result also had a negative SRA result. In the one patient deemed to have clinical HIT the pretest probability was high (4Ts score of 6) and the anti-PF4/heparin antibody testing revealed a positive SRA, inconclusive PIFA and a negative ELISA result.
While thrombocytopenia in our population is common, the prevalence of HIT is low. The combination of a low to intermediate pretest probability with a negative PIFA test can rapidly exclude the presence of platelet activating anti-PF4/heparin antibodies and therefore HIT as the cause of the thrombocytopenia. Since a positive PIFA result has a very low positive predictive value, a positive PIFA is not diagnostic of HIT and additional evaluation is warranted.
"This substitution is expensive and could be associated with an increased risk of bleeding (10-20% of major haemorrhage) without effective antidote  . While early diagnosis of HIT is essential to improve clinical management of patients, it remains challenging, especially in critically ill patients, in intensive care . The current diagnostic relies on the use of a clinical scoring algorithm ( " 4T's rule " ) together with immunological and platelet activation assays   . "
[Show abstract][Hide abstract] 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 · 2.45 Impact Factor
"Our results are in agreement with the literature data (Table 5) which show that the negative predictive value of the 4TS score is high and may therefore be useful to exclude HIT in case of low probability of the pretest. [12, 14, 16, 17]. Unlikely, the positive predictive value of the test is generally low and sometimes differs considerably from one center to another. "
[Show abstract][Hide abstract] ABSTRACT: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction caused by antibodies to the heparin/platelet factor 4 (PF4) complexes. HIT diagnosis is challenging and depends on clinical presentation and laboratory tests. We investigated the interest of the combined use of 4 Ts score and the functional and immunological tests for the diagnosis of HIT.
We analyzed 178 patients with suspected HIT, for which the 4 Ts score was calculated. Heparin-PF4 antibodies were detected by both Heparin-induced platelet activation test (HIPA) and Heparin platelet induced antibodies enzyme immunoassay.
Our results shown that in low probability group, 85% of plasmas were found negative versus 55.5% in the high probability group. On the other hand, 22.2% of patients were HIT positive in high probability group versus 0% in the low probability group.
These results confirmed that the negative predictive value of the HIT score was high. The 4T's model has demonstrated excellent sensitivity but its specificity was limited. The specificity of the functional and immunological test is high only in a context suggestive of HIT. Both methods should be considered complementary in the diagnostic strategy.
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