The Sysmex CS-5100 coagulation analyzer offers comparable analytical performance and excellent throughput capabilities

Objectives: This study compared the new high-volume blood coagulation analyzer Sysmex CS-5100 System™ (Siemens Healthcare Diagnostics, Erlangen, Germany) to the mid-volume blood coagulation analyzer Sysmex CS-2000i System™ (Siemens) for analytical performance. Additionally, the operational performance of the Sysmex CS-5100 System was compared with the blood coagulation analyzer ACL TOP 700 (Instrumentation Laboratory, Werfen Group, Kirchheim bei Munchen, Germany). Materials and methods: We compared the Sysmex CS-5100 to the Sysmex CS-2000i and the ACL TOP analyzer for routine coagulation, chromogenic and immunological assays. Imprecision studies were performed for the Sysmex CS-5100 and Sysmex CS-2000i systems. A throughput and STAT analysis comparison of the CS-5100 and the ACL TOP was performed. A stress test was performed to characterize the robustness and the error rate of the CS-5100. We also performed correlation analysis between the CS-5100 and the CS-2000i or the ACL TOP in the measurement of patients’ samples. Results: The inter-assay precision using the CS systems was impressive (inter-assay CV generally <3.5%) and the correlation between the two Sysmex analyzers was excellent. In the throughput study, the CS-5100 completed the measurement of 100 samples (210 results) in less than 49 min. Conclusions: Our results demonstrated that the CS-5100 is a robust high-throughput analyzer, well-suited for coagulation laboratories. Keywords: Coagulation analyzer, CS-5100, Evaluation, Automatio

How would we treat our own heparin-induced thrombocytopenia during cardiac surgery?

The aim of this article is to provide a comprehensive review of the current state of knowledge on heparin-induced thrombocytopenia (HIT) in cardiac surgery. The management of HIT patients undergoing cardiac surgery with cardiopulmonary bypass is complex and requires an interdisciplinary and patient-tailored approach because available evidence is limited and current anticoagulation strategies have potential risks. An index case is used to discuss both the established and new perioperative therapeutic options in HIT patients undergoing urgent cardiac surgery with cardiopulmonary bypass

Emergency coagulation assessment during treatment with direct oral anticoagulants: Limitations and solutions.

BACKGROUND AND PURPOSE: In patients receiving direct oral anticoagulants (DOACs), emergency treatment like thrombolysis for acute ischemic stroke is complicated by insufficient availability of DOAC-specific coagulation tests. Conflicting recommendations have been published concerning the use of global coagulation assays for ruling out relevant DOAC-induced anticoagulation. METHODS: Four hundred eighty-one samples from 96 DOAC-treated patients were tested using prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), DOAC-specific assays (anti-Xa activity, diluted TT), and liquid chromatography-tandem mass spectrometry. Sensitivity and specificity of test results to identify DOAC concentrations &lt;30 ng/mL were calculated. Receiver operating characteristic analyses were used to define reagent-specific cutoff values. RESULTS: Normal PT and aPTT provide insufficient specificity to safely identify DOAC concentrations &lt;30 ng/mL (rivaroxaban/PT: specificity, 77%/sensitivity, 94%; apixaban/PT: specificity, 13%/sensitivity, 94%, dabigatran/aPTT: specificity, 49%/sensitivity, 91%). Normal TT was 100% specific for dabigatran, but sensitivity was 26%. In contrast, reagent-specific PT and aPTT cutoffs provided &gt;95% specificity and a specific TT cutoff enhanced sensitivity for dabigatran to 84%. For apixaban, no cutoffs could be established. CONCLUSIONS: Even if highly DOAC-reactive reagents are used, normal results of global coagulation tests are not suited to guide emergency treatment: whereas normal PT and aPTT lack specificity to rule out DOAC-induced anticoagulation, the low sensitivity of normal TT excludes the majority of eligible patients from treatment. However, reagent-specific cutoffs for global coagulation tests ensure high specificity and optimize sensitivity for safe emergency decision making in rivaroxaban- and dabigatran-treated patients

Monitoring of low dabigatran concentrations: Diagnostic performance at clinically relevant decision thresholds.

The direct oral anticoagulant dabigatran does not require therapeutic drug monitoring, however emergency measurements are gaining importance. Current assays feature good performance at intermediate and high dabigatran concentrations but show limited accuracy at low concentrations. This area requires more attention as clinical decision threshold values currently lie at 30 and 50 ng/ml. The objective of the study was to evaluate and compare diagnostic performance of dabigatran assays at these thresholds. Dabigatran concentrations of 293 plasma samples taken from 50 patients were measured with the INNOVANCE direct thrombin inhibitor assay (DTI) from Siemens, the Biophen direct thrombin inhibitor assay (BDTI), the BDTI using a low range calibrator (BDTI-low), the Hemoclot direct thrombin inhibitor assay (HTI) and an ecarin clotting time assay (ECT). Assay results were compared to ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and test characteristics were calculated for thresholds of 30 and 50 ng/ml. DTI, BDTI-low and ECT showed very strong correlation and high agreement with UPLC-MS/MS and an improved determination of low dabigatran concentrations. ROC curve analyses revealed very high accuracy at the 30/50 ng/ml thresholds for DTI (AUC = 0.989/0.995), BDTI-low (AUC = 0.980/0.991) and ECT (AUC = 0.990/0.996) measurements. Sensitivity and specificity in detecting were calculated for DTI (98/92%), BDTI-low (87/95%), ECT (97/96%), BDTI (99/82%) and HTI (86/89%) measurements. Compared to the previously available HTI and BDTI, both novel assays, DTI and BDTI-low, reliably determine low dabigatran plasma concentrations around the clinical decision thresholds with very high sensitivity and specificity

Limitations of specific coagulation rests for direct oral anticoagulants: A critical analysis.

Background-During treatment with direct oral anticoagulants (DOAC), coagulation assessment is required before thrombolysis, surgery, and if anticoagulation reversal is evaluated. Limited data support the accuracy of DOAC-specific coagulation assays around the current safe-for-treatment threshold of 30 ng/mL.Methods and Results-In 481 samples obtained from 96 patients enrolled at a single center, DOAC concentrations were measured using Hemoclot direct thrombin inhibitor assay, Biophen direct thrombin inhibitor assay or ecarin clotting time for dabigatran, chromogenic anti-Xa assay (AXA) for factor Xa inhibitors (rivaroxaban, apixaban) and ultraperformance liquid chromatography-tandem mass spectrometry as reference. All dabigatran-specific assays had high sensitivity to concentrations &gt; 30 ng/mL, but specificity was lower for Hemoclot direct thrombin inhibitor assay (78.2%) than for Biophen direct thrombin inhibitor assay (98.9%) and ecarin clotting time (94.6%). AXA provided high sensitivity and specificity for rivaroxaban, but low sensitivity for apixaban (73.8%; concentrations up to 82 ng/mL were misclassified as &lt; 30 ng/mL). If no DOAC-specific calibration for AXA is available, results 2-fold above the upper limit of normal indicate relevant rivaroxaban concentrations. For apixaban, all elevated results should raise suspicion of relevant anticoagulation.Conclusions-DOAC-specific tests differ considerably in diagnostic performance for concentrations close to the currently accepted safe-for-treatment threshold. Compared with Biophen direct thrombin inhibitor assay and ecarin clotting time, limited specificity of Hemoclot direct thrombin inhibitor assay poses a high risk of unnecessary anticoagulation reversal or treatment delays in patients on dabigatran. While AXA accurately detected rivaroxaban, the impact of low apixaban levels on the assay was weak. Hence, AXA results need to be interpreted with extreme caution when used to assess hemostatic function in patients on apixaban

Diagnostic accuracy of a novel chromogenic direct thrombin inhibitor assay: Clinical experiences for dabigatran monitoring.

Background Direct oral anticoagulants (DOACs) are increasingly replacing vitamin K antagonists (VKA) for clinical indications requiring long-term oral anticoagulation. In contrast to VKA, treatment with DOAC including dabigatran-the only direct thrombin inhibitor amongst them-does not require therapeutic drug monitoring. However, in case of treatment complications (e.g., major haemorrhage) and conditions requiring urgent surgery or thrombolytic therapy, information about actual DOAC plasma levels is needed to guide treatment decisions. Due to short reagent stability, limited accuracy at low dabigatran levels and high heparin sensitivity, the applicability of the widely used Hemoclot thrombin inhibitor (HTI) coagulation assay is limited in the emergency setting. Methods Dabigatran concentrations of 288 citrated plasma samples taken from 48 dabigatran-treated patients with drug concentrations of up to 300 ng/mL were measured with the chromogenic anti-IIa Biophen direct thrombin inhibitor (BDTI) assay and results compared with HTI using ultra performance liquid chromatography-tandem mass spectrometry as the reference method for measuring dabigatran plasma concentrations. Results BDTI results showed a very strong correlation with dabigatran concentrations (r = 0.965, p &lt; 0.0001) as well as a low intra-and inter-assay variation of &lt;5%. Compared with HTI, BDTI provides an improved on-board reagent stability of 72 hours, rapid turnaround times comparable to routine coagulation assays, high accuracy at low drug levels and reduced heparin sensitivity. Conclusion The BDTI is an ideal coagulation assay for the around-the-clock determination of dabigatran plasma levels in clinical routine including emergency situations