J. S. Biedermann

Agreement between Coaguchek XS and STA-R Evolution (Hepato Quick) INR results depends on the level of INR.

INTRODUCTION Introducing point-of-care (POC) INR measurement to monitor anticoagulant therapy may be beneficial for both patients and anticoagulation clinics. However, agreement between POC and laboratory INR results is still unclear, especially at sub- and supratherapeutic levels. Therefore we investigated the analytical and clinical agreement between POC INR results of the Coaguchek XS and laboratory INR results of the STA-R Evolution. MATERIALS AND METHODS Paired POC and laboratory INR results were obtained and analyzed in 3257 patients aged 18-104 years between August 2008 and March 2014. RESULTS Mean difference between POC and laboratory results ranged from -0.18 (95%CI -0.20;-0.16) INR point for POC results 2.0-3.0, up to 1.14 (95%CI 0.87;1.42) INR point for POC results 7.1-8.0. In the therapeutic range (POC INR 2.0-4.0), mean difference between POC and laboratory results was -0.13 (95%CI -0.15;-0.12) INR point. At subtherapeutic (POC INR <2.0) and supratherapeutic (POC INR >4.0) INR levels, mean differences were -0.13 (95%CI -0.15;-0.11) and 0.72 (95%CI 0.63;0.80) INR point, respectively. Clinical agreement regarding therapeutic range was present in 92.0% (POC within range), 67.7% (POC below range) and 87.6% (POC above range) of the paired measurements. We observed ≥15% INR difference between the POC and laboratory result in 14.8% (POC INR 2.0-4.0), 17.0% (POC INR<2.0) and 47.8% (POC INR >4.0) of the paired measurements. CONCLUSIONS POC and laboratory INR results were strongly correlated within the therapeutic range and differences between results become larger with increasing INR. Clinical disagreement between laboratory and POC results occurs often at both sub- and supratherapeutic INR levels.

Can we prevent venous thrombosis with statins: an epidemiologic review into mechanism and clinical utility

ABSTRACT Introduction: Statins may be causally associated with a decreased risk of venous thrombosis. If so, this could be a substantive breakthrough since statins do not increase the risk of bleeding and could therefore be used as a safer antithrombotic drug. However, scepticism exists on the observed reduction of venous thrombosis by statins, as it may have been confounded by healthy user effects or other biases. Areas covered: The main focus of this review will be the biases that may have arisen in clinical studies that investigated the relationship between statin use and risk of venous thrombosis. We also discuss the suggested causal association from a pathophysiological perspective. Furthermore, we integrate the knowledge from clinical and pathophysiological studies into a proposal for new study designs that are needed to sufficiently answer the question whether we can, and should, prevent recurrent venous thrombosis with statins. Expert commentary: A drug to prevent recurrent venous thrombosis in patients at risk of bleeding that does not induce bleeding and in which the number needed to treat for the prevention of venous thrombosis is sufficiently high, is a remedy that we should continue to look for, and for which statin therapy might be a suitable candidate.

Rosuvastatin use improves measures of coagulation in patients with venous thrombosis

Aims Observational studies indicate that statins reduce the risk of recurrent venous thrombosis (VT). However, trials have not been performed and the mechanism is unknown. We aimed to determine whether statin therapy improves the coagulation profile in patients with prior VT. Methods and results Randomized clinical trial (NCT01613794). Patients were randomized to rosuvastatin 20 mg/day for 4 weeks or no intervention. Blood was drawn at baseline and at end of study. The primary outcome was factor (F) VIII:C. In total, five coagulation factors were measured: FVIII:C, von Willebrand factor:Ag, FVII:C, FXI:C, and D‐dimer. Among 247 randomized participants, mean age was 58 years, 62% were women and 49% had unprovoked VT. For all tested coagulation factors, mean levels were clearly decreased at end of study in rosuvastatin users, whereas they hardly differed in non‐statin users. Results were most consistent for FVIII:C where mean FVIII:C levels were 7.2 IU/dL [95% CI (confidence interval) 2.9‐11.5] lower in rosuvastatin users, while among non‐users, no change in FVIII:C was observed (mean difference −0.1; 95% CI −3.0 to 2.9). The mean age and sex adjusted difference in FVIII:C change was −6.7 IU/dL (95% CI −12.0 to −1.4) in rosuvastatin users vs. non‐users. Subgroup analyses revealed that the decrease in coagulation factors by rosuvastatin was more pronounced in participants with unprovoked VT and in those with cardiovascular risk factors. Conclusion Rosuvastatin 20 mg/day substantially improved the coagulation profile among patients with prior VT. These results suggest that statin therapy might be beneficial in patients at risk of recurrent VT. Figure. No Caption available.

Major bleeding risks of different low-molecular-weight heparin agents: a cohort study in 12 934 patients treated for acute venous thrombosis

Essentials Low‐molecular‐weight‐heparins (LMWH) kinetics differ which may result in different bleeding risks. A cohort of 12 934 venous thrombosis patients on LMWH was followed until major bleeding. The absolute major bleeding risk was low among patients registered at the anticoagulation clinic. Once‐daily dosing was associated with a lower bleeding risk as compared with twice‐daily.

Predictors of oral cavity bleeding and clinical outcome after dental procedures in patients on vitamin K antagonists

Patients on vitamin K antagonists (VKA) often undergo invasive dental procedures. International guidelines consider all dental procedures as low-risk procedures, while bleeding risk may differ between standard low-risk (e. g. extraction 1-3 elements) and extensive high-risk (e. g. extraction of >3 elements) procedures. Therefore current guidelines may need refinement. In this cohort study, we identified predictors of oral cavity bleeding (OCB) and evaluated clinical outcome after low-risk and high-risk dental procedures in patients on VKA. Perioperative management strategy, procedure risk, and 30-day outcomes were assessed for each procedure. We identified 1845 patients undergoing 2004 low-risk and 325 high-risk procedures between 2013 and 2015. OCB occurred after 67/2004 (3.3 %) low-risk and 21/325 (6.5 %) high-risk procedures (p=0.006). In low-risk procedures, VKA continuation with tranexamic acid mouthwash was associated with a lower OCB risk compared to continuation without mouthwash [OR=0.41, 95 %CI 0.23-0.73] or interruption with bridging [OR=0.49, 95 %CI 0.24-1.00], and a similar risk as interruption without bridging [OR=1.44, 95 %CI 0.62-3.64]. In high-risk procedures, VKA continuation was associated with an increased OCB risk compared to interruption [OR=3.08, 95 %CI 1.05-9.04]. Multivariate analyses revealed bridging, antiplatelet therapy, and a supratherapeutic or unobjectified INR before the procedure as strongest predictors of OCB. Non-oral cavity bleeding (NOCB) and thromboembolic event (TE) rates were 2.1 % and 0.2 %. Bridging therapy was associated with a two-fold increased risk of NOCB [OR=1.93, 95 %CI 1.03-3.60], but not with lower TE rates. In conclusion, predictors of OCB were mostly related to perioperative management and differed between low-risk and high-risk procedures. Perioperative management should be differentiated accordingly.

Platelet reactivity in patients with venous thrombosis who use rosuvastatin: a randomized controlled clinical trial

Essentials Statins, especially rosuvastatin, may reduce venous thrombosis risk, but the mechanism is unclear. We performed a randomized trial investigating the effect of rosuvastatin on platelet reactivity. Thromboxane‐A2 mediated platelet aggregation was measured before and after rosuvastatin therapy. Rosuvastatin did not inhibit thromboxane‐mediated platelet aggregation in venous thrombosis patients.

Clinical outcome of patients with a vitamin K antagonist-associated bleeding treated with prothrombin complex concentrate

Essentials Data on clinical outcome of vitamin K antagonist (VKA)‐associated bleeding is scarce. Cohort study of patients with VKA bleeds treated with prothrombin complex concentrate (PCC). Effective haemostasis was achieved in 68% of patients with a VKA‐associated bleeding. Thromboembolism rates were low and mortality rates high at 30 days after PCC administration.

Clinical effects of antiplatelet drugs and statins on D-dimer levels

Acute pulmonary embolism may be ruled out by combining nonhigh clinical probability and a normal D‐dimer level. Both antiplatelet drugs and HMG‐CoA reductase inhibitors (statins) have been associated with effects on thrombus formation, potentially influencing D‐dimer levels in this setting, leading to a higher rate of false‐negative tests. Therefore, we determined whether D‐dimer levels in patients with suspected pulmonary embolism are affected by concomitant use of antiplatelet drugs and/or statins and evaluated whether the effect of antiplatelet drugs or statins might affect diagnostic accuracy.

Reply to: Effect of statins on measures of coagulation—potential role of low-density lipoprotein receptors

We would like to thank Francesco Paciullo and Paolo Gresele for their interest in the STAtins Reduce Thrombophilia (START) clinical trial which was recently published in European Heart Journal. They formulate a number of interesting hypotheses that relate to findings of this trial. First, authors point out that of all tested coagulation factors in START [i.e. factor (F)VII, FVIII, FXI, and von Willebrand factor], rosuvastatin was most able to lower circulating FVIII levels. Although this finding suggests that rosuvastatin may be able to reduce the risk of first and recurrent venous thrombosis through downregulation of FVIII, this result does not answer the ultimate question that is how rosuvastatin reduces FVIII. The authors suggest that statin-mediated FVIII reduction could be explained by up-regulation of lipoprotein receptor-related protein 1 (LRP1), with the contribution of the low-density lipoprotein receptor (LDLR). We agree that this could explain our findings, as circulating FVIII is cleared by LRP1. We believe that this mechanism deserves further exploration in upcoming statin studies. Second, authors point out that if the mechanism is explained through LRP1 and LDLR, the use of PCSK9 inhibitors might be interesting to study and to see if they are also able to reduce FVIII levels. We agree, and would like to add that studies that look into the association between PCSK9 inhibitors and reduced venous thrombosis risk could be of additional benefit to establish a pathophysiological link. Third, the authors point out that although the relatively small reductions in FVIII are not likely to increase bleeding risk in the general population, this may not be applicable to haemophilia patients. We agree, but consider the potential bleeding effect of statins in haemophilia (i.e. patients with a very low/negligible risk to develop venous thrombosis) of lesser concern for the purpose for which the START trial was designed, that is to find a pathophysiological substrate behind the supposed causal association between statin use and a reduced risk of recurrent venous thrombosis. The aetiologic questions raised by Paciullo and Gresele do merit consideration and could, when finally answered, lead to whole new treatment avenues in the prevention and treatment of venous thrombosis. This should however not deviate from another question that is also still unanswered, that is whether rosuvastatin should be used for the prevention of recurrent venous thrombosis. For this an adequately powered randomized clinical trial, with recurrent venous thrombosis as primary endpoint, should be conducted. The results of the START trial support the conduction of such a trial from a pathophysiological perspective.

Control of anticoagulation with VKAs: overestimation of median TTR when assessed by linear interpolation: Reply

Control of anticoagulation with VKAs: overestimation of median TTR when assessed by linear interpolation: Reply -