Vitamin K2 (Menaquinone-7) supplementation does not affect vitamin K-dependent coagulation factors activity in healthy individuals.

BACKGROUND: Vitamin K has long been regarded as a procoagulant drug by physicians, and concerns have been raised with regard to its effects on hemostasis. Although many studies have shown that vitamin K supplementation is safe for thrombotic events, the effect of vitamin K supplementation on the activities of vitamin K dependent procoagulation factors in healthy individuals is not available. OBJECTIVES: This study aimed to investigate whether vitamin K2 supplementation at recommended doses affects the activity of vitamin K dependent procoagulation factors in healthy individuals without any anticoagulation treatment. DESIGN: Forty healthy volunteers between 25 and 40 years of age were recruited. Menaquinone-7 (MK-7) was administrated at 90 µg for 30 days. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and blood coagulation factors II, VII, IX, and X activities and Protein induced by vitamin K absence or antagonist-II (PIVKA-II) were measured on days 0 and 30 after MK-7 administration. RESULTS: PT, APTT, and TT showed no significant differences on day 30 when compared with baseline. The activities of coagulation factors II, VII, IX, and X on day 30 showed no significant differences with those at baseline. PIVKA-II levels were unchanged after 30 days of MK-7 supplementation. CONCLUSIONS: MK-7 supplementation at recommended dosage does not affect vitamin K-dependent coagulation factors' coagulation activity, and does not enhance the carboxylation of prothrombin in healthy individuals. This indicated that MK-7 administration does not alter hemostatic balance in healthy populations without anticoagulation treatment.

Thrombin generation is increased in patients with Clostridium difficile colitis - a pilot study.

Background: There are only limited data in the literature on the thrombotic risk of patients with Clostridium difficile (CD) colitis, although this disease is widespread throughout the world. Objective: The aim of this study was to explore thrombin generation in these patients - the best way to evaluate their coagulation. Methods: A prospective observational study was conducted during 15 months on hospitalized patients with CD colitis. Thrombin generation was performed in platelet-poor plasma using a Ceveron® alpha analyzer and was compared with a group of volunteer control subjects. Results: Thirty-three patients and 51 control subjects were enrolled in the study. Two biomarkers - mean velocity index and peak thrombin - were significantly higher in patient group, compared to the control subjects (p = 0.010, respectively, p = 0.0395). This pattern of thrombin generation suggests that patients with CD colitis without septic shock have a potential thrombotic risk. The mean velocity index significantly correlated with the estimated related risk of death according to the Charlson age-comorbidity index. Conclusions: The higher values of thrombin generation suggest that CD colitis increases the thromboembolic risk. The pattern of thrombin generation could identify patients with particularly higher thromboembolic risk. They are potential candidates for thromboprophylaxis strategies and monitorization.

Diagnostic and predictive performance of biomarkers in patients with sepsis in an intensive care unit.

OBJECTIVE: This study was performed to compare the predictive performance of serum procalcitonin (PCT), N-terminal brain natriuretic propeptide (NT-proBNP), interleukin-6 (IL-6), prothrombin time (PT), thrombin time (TT), and Sequential Organ Failure Assessment (SOFA) score in the intensive care unit (ICU). METHODS: This retrospective cohort study enrolled 150 patients with sepsis and septic shock and 30 control patients without sepsis. Each patient was followed until death or 28 days. Correlations between variables were assessed with Spearman's rho test. The Kruskal-Wallis and Mann-Whitney U tests were used for between-group comparisons. RESULTS: Receiver operating characteristic curve analysis of the SOFA score, PCT, NT-proBNP, IL-6, PT, and TT showed an area under the curve of 0.872, 0.732, 0.711, 0.706, 0.806, and 0.691, respectively, for diagnosing sepsis. Binary logistic regression demonstrated that the SOFA score was an independent predictor of 28-day mortality and septic shock. The correlation coefficient (r) between SOFA and PCT, NT-proBNP and SOFA, IL-6 and SOFA, PT and SOFA, and TT and SOFA was 0.79, 0.52, 0.57, 0.56, and 0.58, respectively. CONCLUSION: While the SOFA score is the gold standard, analysis of multiple biomarkers could increase the performance capacity for diagnosis and prognosis in patients with sepsis in the ICU.

Comparison of the ecarin chromogenic assay and diluted thrombin time for quantification of dabigatran concentrations.

Essentials Routine monitoring is unnecessary but measuring dabigatran levels is helpful in certain situations. We compared ecarin chromogenic assay (STA-ECA-II) and dilute thrombin time (dTT) in patient samples. Both tests provided accurate measurements over a wide range of dabigatran concentrations. Adoption of STA-ECA-II and dTT into routine clinical practice will improve patient care. SUMMARY: Background Although routine coagulation monitoring is unnecessary, measuring plasma dabigatran concentrations can be useful for detecting drug accumulation in renal failure or overdose, assessing the contribution of dabigatran to serious bleeding, planning the timing of urgent surgery or intervention, or determining the suitability for thrombolytic therapy for acute ischemic stroke. Dabigatran concentrations can be quantified using chromogenic or clot-based tests, such as the ecarin chromogenic assay (ECA) and the diluted thrombin time (dTT), respectively. Objective The purpose of this study was to compare the results of these assays with dabigatran concentrations measured by the reference standard of mass spectrometry in samples from 50 dabigatran-treated patients collected at peak and trough after at least 4 months of drug intake. Methods Drug levels measured with either the STA Ecarin Chromogenic Assay-II (STA-ECA-II) or dTT were linearly correlated with those determined by mass spectrometry over a wide range of concentrations. Results and Conclusions For detection of levels below 50 ng mL-1 both tests have specificities of at least 96%, suggesting that they accurately detect even low levels of drug. Therefore, regardless of whether a chromogenic or clot-based platform is preferred, the STA-ECA-II and dTT are useful tests for measuring dabigatran concentrations. Unfortunately, neither test is licensed by the United States Food and Drug Administration. Although approved in other jurisdictions, the dTT and STA-ECA-II are not widely or rapidly available in most hospitals. Therefore, cooperation between regulators and hospitals is urgently needed to render these tests readily available to inform patient care.

[THE COMPARATIVE CHARACTERISTIC OF KAOLIN-ACTIVATED THROMBOELASTOGRAPHY IN HEALTHY NEWBORNS AND NEWBORNS WITH HEART AILMENTS].

The study was carried out to diferentiate reference values for kaolin-activated thromboelastography in newborns with congenital heart disease. The study included two groups ofpatients. The first one consisted of 62 newborns with congenital heart disease and the second one consisted of 35 healthy newborns. The results of kaolin-activated thromboelastography implemented in groups are evaluated as condition of normal coagulation. The valuable diferences of homeostasis system in healthy newborns and newborns with congenital heart disease (without severe concomitant pathology) are not established. They have similar indicators of kaolin-activated thromboelastography. The derived results can be applied as standards in full-term newborns with congenital heart disease.

The effect of dabigatran on the activated partial thromboplastin time and thrombin time as determined by the Hemoclot thrombin inhibitor assay in patient plasma samples.

Dabigatran is an oral direct thrombin inhibitor that does not require routine laboratory monitoring. However, an assessment of its anticoagulant effect in certain clinical settings is desirable. We examined the relationship between dabigatran levels, as determined by the Hemoclot thrombin inhibitor assay (HTI), the thrombin time (TT) and the activated partial thromboplastin time (aPTT) using different reagents. We describe these parameters with the clinical outcomes of patients receiving dabigatran. Seventy-five plasma samples from 47 patients were analysed. The HTI assay was established to measure dabigatran level. aPTTs were performed using TriniCLOT aPTT S reagent (TC) and three additional aPTT reagents. From linear regression lines, we established the aPTT ranges corresponding to the therapeutic drug levels for dabigatran (90-180 ng/ml). The aPTT demonstrated a modest correlation with the dabigatran level (r= 0.80) but the correlation became less reliable at higher dabigatran levels. The therapeutic aPTT ranges for reagents were clinically and statistically different compared with our reference reagent (46-54 s (TC) vs 51-60 s (SP), 54-64 s (SS) and 61-71 s (Actin FS) (p<0.05)). The TT was sensitive to the presence of dabigatran with a level of 60 ng/ml resulting in a TT > 300 s. In conclusion, the aPTT demonstrated a modest correlation with the dabigatran level and was less responsive with supra-therapeutic levels. aPTT reagents differed in their responsiveness, suggesting individual laboratories must determine their own therapeutic range for their aPTT reagent. The TT is too sensitive to quantify dabigatran levels, but a normal TT suggests minimal or no plasma dabigatran.

Reducing the use of coagulation test panels.

Use of a coagulation panel [prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT) and fibrinogen], intended for evaluation of bleeding, tripled over 6 years, out of proportion to admissions, surgery, or transfusions. To determine whether the panels were ordered appropriately, we classified 28,737 sets of panel results into groups followed by chart reviews to determine typical patient histories. In 39% of panels, PT/PTT was normal. Prolonged PT occurred in 33% of results, due to liver failure (8%), warfarin (23%), and presumed vitamin K deficiency (69%). Prolonged PTT occurred in 34% of results and was primarily associated with long PT or lupus inhibitors. Prolonged PTT and TT (15% of panels) indicated heparin therapy. Fibrinogen was normal in 98% and low in 1.4%. Critical fibrinogen (below 100 mg/dl, 0.6% of panels) was associated with bleeding in 90% of patients. Only 8% of panel orders were clinically indicated based on patient history. Clinician interviews indicated many were unaware the panel included fibrinogen and TT. Interventions included an education program and an order form change. The education program had no effect on overall order volume or test selection. A later order form change made TT and fibrinogen a separate order. This reduced TT and fibrinogen testing by 90% without complaints or changes in blood transfusion statistics. We conclude that many coagulation test panel orders were not clinically indicated, that PT more often diagnosed vitamin K deficiency than bleeding risk, and that order-based restriction of testing was more effective than educational programs at introducing change in clinical test utilization.

The measurement of low levels of factor VIII or factor IX in hemophilia A and hemophilia B plasma by clot waveform analysis and thrombin generation assay.

BACKGROUND: Precise assessment of clotting function is essential for monitoring of hemostatic treatment for hemophilias A and B. MATERIALS AND METHODS: Clot waveform analysis and thrombin generation assays were performed on factor (F) VIII- and FIX-deficient plasmas, which had been reconstituted with known amounts of recombinant FVIII (rFVIII) and affinity-purified FIX respectively. Clot waveforms were assessed qualitatively and quantitatively by measuring the parameters clotting time, maximum coagulation velocity (Min1), and maximum coagulation acceleration (Min2). The thrombin generation assay was also assessed qualitatively and measurements made of time to peak and peak height. RESULTS: Overall results obtained with both assays showed good correlation for both clotting factors confirming that the changes in clotting waveform reflected changes in thrombin generation. Both assays demonstrated a predictable dose response to the addition of FVIII or IX. However, clot waveform analysis was more sensitive than the thrombin generation assay, particularly in detecting very low levels (0-0.1 IU dL(-1)) of both factors. CONCLUSIONS: These data suggest that the application of clot waveform analysis to the routine management of the hemophiliacs could increase our understanding of the clinical significance of low levels of FVIII and FIX that cannot be measured by assays in current use. This may be particularly useful in the management of hemophiliacs with inhibitors or undergoing gene therapy.