Direct oral anticoagulants in point-of-care monitoring: an ex-vivo study.

BACKGROUND: Anticoagulatory activity of direct oral anticoagulants (DOACs) is not routinely measurable by point-of-care monitoring. Thus, the aim of this study was to evaluate the influence of dabigatran/rivaroxaban on point-of-care testing. METHODS: Samples from 34 participants under DOAC therapy were drawn at two time points. Before ingestion and two-to-three hours afterwards. Thrombelastometric (ROTEM) and aggregometric (Multiplate) measurements were performed. Dabigatran and rivaroxaban plasma levels were determined. RESULTS: Dabigatran and rivaroxaban plasma levels showed significant correlations with clotting time (CT) in EXTEM (r=0.765, P<0.0001; r=0.689, P<0.0001) and INTEM (r=0.792, P<0.0001; r=0.595, P<0.001). A positive correlation was identified between dabigatran ingestion and maximum-clot-firmness (MCF) (r=0.354, P<0.05) in the EXTEM test, pronounced in the absence of concomitant antiplatelet therapy (r=0.709, P<0.05). EXTEM-MCF positively correlated with the TRAP test in aggregometry (0.662, P<0.05), an effect not observed in patients treated with antiplatelet therapy. CONCLUSIONS: Prolongation of CT-EXTEM and CT-INTEM indicates delayed initiation of clot formation. The CT-EXTEM seems to facilitate qualitative monitoring of dabigatran. In contrast, qualitative monitoring of rivaroxaban by CT-EXTEM may be limited as rivaroxaban may affect the measurement at therapeutic plasma levels. It seems that clot formation is faster/firmer in the presence of increased dabigatran plasma levels. This can be attributed to a non-dose-dependent effect via increased fibrin polymerization and second to a dose-dependent effect via increased platelet sensitivity to thrombin.

IgM-Enriched Immunoglobulin Attenuates Systemic Endotoxin Activity in Early Severe Sepsis: A Before-After Cohort Study.

INTRODUCTION: Sepsis remains associated with a high mortality rate. Endotoxin has been shown to influence viscoelastic coagulation parameters, thus suggesting a link between endotoxin levels and the altered coagulation phenotype in septic patients. This study evaluated the effects of systemic polyspecific IgM-enriched immunoglobulin (IgM-IVIg) (Pentaglobin® [Biotest, Dreieich, Germany]) on endotoxin activity (EA), inflammatory markers, viscoelastic and conventional coagulation parameters. METHODS: Patients with severe sepsis were identified by daily screening in a tertiary, academic, surgical ICU. After the inclusion of 15 patients, the application of IgM-IVIg (5 mg/kg/d over three days) was integrated into the unit's standard operation procedure (SOP) to treat patients with severe sepsis, thereby generating "control" and "IgM-IVIg" groups. EA assays, thrombelastometry (ROTEM®) and impedance aggregometry (Multiplate®) were performed on whole blood. Furthermore, routine laboratory parameters were determined according to unit's standards. RESULTS: Data from 26 patients were included. On day 1, EA was significantly decreased in the IgM-IVIg group following 6 and 12 hours of treatment (0.51 ±0.06 vs. 0.26 ±0.07, p<0.05 and 0.51 ±0.06 vs. 0.25 ±0.04, p<0.05) and differed significantly compared with the control group following 6 hours of treatment (0.26 ±0.07 vs. 0.43 ±0.07, p<0.05). The platelet count was significantly higher in the IgM-IVIg group following four days of IgM-IVIg treatment (200/nl ±43 vs. 87/nl ±20, p<0.05). The fibrinogen concentration was significantly lower in the control group on day 2 (311 mg/dl ±37 vs. 475 mg/dl ±47 (p = 0.015)) and day 4 (307 mg/dl ±35 vs. 420 mg/dl ±16 (p = 0.017)). No differences in thrombelastometric or aggregometric measurements, or inflammatory markers (interleukin-6 (IL-6), leukocyte, lipopolysaccharide binding protein (LBP)) were observed. CONCLUSION: Treatment with IgM-enriched immunoglobulin attenuates the EA levels in patients with severe sepsis and might have an effect on septic thrombocytopenia and fibrinogen depletion. Viscoelastic, aggregometric or inflammatory parameters were not influenced. TRIAL REGISTRATION: clinicaltrials.gov NCT02444871.

Coagulation management in trauma-associated coagulopathy: allogenic blood products versus coagulation factor concentrates in trauma care.

PURPOSE OF REVIEW: Coagulation management by transfusion of allogenic blood products and coagulation factors are competing concepts in current trauma care. RECENT FINDINGS: Rapid and adequate therapy of trauma-associated coagulopathy is crucial to survival of severely injured patients. Standard coagulation tests such as prothrombin time and activated partial thromboplastin time are commonly used, but these tests are inappropriate for monitoring and guiding therapy in trauma patients. Coagulation factor-based treatment showed promising results, but randomized trials have not yet been performed. In addition, viscoelastic tests are needed to guide therapy, although there is in fact limited evidence for these in tests in trauma care. Regarding transfusion therapy with allogenic blood products, plasma transfusion has been associated with improved survival in trauma patients following massive transfusion. In contrast, patients not requiring massive transfusion seem to be at risk for suffering complications with increasing volumes of plasma transfused. SUMMARY: The collective of trauma patients is heterogeneous. Despite the lack of evidence, there are strong arguments for individualized patient treatment with coagulation factors for some indications and to abstain from the use of fresh frozen plasma. In patients with severe trauma and major bleeding, plasma, platelets, and red blood cells should be considered to be administered at a ratio of 1 : 1 : 1.

Perioperative coagulation management during cardiac surgery.

PURPOSE OF REVIEW: Cardiac surgery patients commonly present bleeding complications that negatively influence patient's clinical outcome. Therefore, fast and detailed diagnoses as well as early and specific therapy of perioperative coagulopathy are of high clinical relevance. The so-called point-of-care (POC) methods for coagulation analyses are increasingly used in perioperative care. It is the purpose of this review to present modern aspects of coagulation management, discuss the effect of the implementation of POC methods in perioperative care, and present substantial components of hemotherapy algorithms to manage coagulopathy in cardiac surgery patients. RECENT FINDINGS: Recent studies suggest that implementation of point-of-care testing in hemotherapy algorithms which inclose stepwise therapeutic escalation may reduce perioperative blood loss and the transfusion rate of allogenic blood products. This should improve patient's clinical outcome and reduce costs. SUMMARY: Prospective randomized multicenter studies are needed to confirm the hypothesis that algorithm-based specific hemotherapy in conjunction with POC testing minimizes patient's exposure to blood products and improves clinical outcome.