Platelet to Lymphocyte Ratio and Neutrophil to Lymphocyte Ratio as Risk Factors for Venous Thrombosis

High platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) are associated with an increased risk of arterial thrombosis, but their role in venous thromboembolism (VTE) has not been fully investigated. A case\ue2\u80\u93control study, of 486 patients with VTE, 100 with cerebral vein thrombosis (CVT), and 299 healthy individuals, was carried out to investigate whether high PLR or NLR values are associated with an increased risk of VTE. Patients with high PLR or NLR did not have an increased risk of VTE (odds ratio [OR] 0.89, 95% confidence interval [CI]: 0.46-1.76; OR: 0.69, 95% CI: 0.34-1.39, respectively) or CVT (OR: 1.65, 95% CI: 0.68-4.00; OR: 0.39, 95% CI: 0.09-1.72, respectively). Subgroups analysis showed that high PLR values were associated with the risk of provoked CVT (OR: 2.65, 95% CI: 1.02-6.92), and there was an interaction with thrombophilia abnormalities (OR: 7.67, 95% CI: 1.67-35.27) in patients with CVT. In conclusion, high PLR and NLR values are not associated with an overall increased risk of VTE or CVT. High PLR values increase the risk of provoked CVT and interact with thrombophilia abnormalities in patients with CVT

How the direct oral anticoagulant apixaban affects thrombin generation parameters

BACKGROUND AND OBJECTIVES: Apixaban is a direct oral anticoagulant (DOAC) targeting factor Xa and thus quenching thrombin generation and clot formation. However, little information is available on the influence that apixaban may have on the parameters of thrombin generation. METHODS: Aliquots of a pooled normal plasma have been added with increased concentrations of purified apixaban and were used to assess the degree of modification brought about by the drug on the basic tests of coagulation prothrombin and activated partial thromboplastin time (PT and APTT) and on thrombin generation parameters. RESULTS: The study shows that while apixaban has little effect on PT or APTT it does affect all the parameters of thrombin generation, including the lag-time (which is increased), the endogenous thrombin potential (ETP) and thrombin-peak (both decreased although to a different extent), and the velocity index (decreased). Interestingly, the above effects were more pronounced when the measurements were recorded in the presence of thrombomodulin, thus making the ratio (with/without thrombomodulin) to decrease consistently as a function of the apixaban concentrations. CONCLUSIONS: These findings support the antithrombotic properties of apixaban and can help to understand the mechanism(s) of action of this drug. Thrombin generation could be used as a convenient laboratory tool to assess the anticoagulant activity of other drugs and to make between-DOAC compariso

The thrombin generation assay distinguishes inhibitor from non-inhibitor patients with severe haemophilia A

Introduction Patients with haemophilia A (HA) have impaired thrombin generation (TG) capacity and TG assay (TGA) values are linearly related to plasma factor VIII (FVIII) levels. Aim This study carried out in patients with unmeasurable FVIII (<1 IU dL 121) was aimed at unravelling any difference in TG capacity in patients with or without inhibitors. Methods Blood samples were collected from patients in a non-bleeding state, after a 5-day wash-out period from last treatment. Results TGA was performed in 102 patients with severe HA (15% with high-responding inhibitors; 51% with null F8 mutations, that as expected were more prevalent in inhibitor than in non-inhibitor patients). TG capacity was significantly lower in inhibitor than non-inhibitor patients and in those with null mutations than in those with non-null mutations. When the TG capacity was evaluated only in patients with null mutations with and without inhibitors it was lower in the presence of inhibitors. Conclusions This study shows a greater TG impairment in inhibitor patients irrespective of FVIII levels, inhibitor titre and F8 mutation type, suggesting a role for the TGA in unravelling functional interferences of anti-FVIII inhibitors on coagulation system activation

Low thrombin generation during major orthopaedic surgery fails to predict the bleeding risk in inhibitor patients treated with bypassing agents

Introduction: In the presence of high-titre inhibitors, haemostatic bypassing agents are used to control bleeding and perform surgery. In this setting, no specific laboratory test is yet available to guide drug choice, monitor treatment efficacy and predict the risk of bleeding. Aim: The aims of this study, carried out in patients candidate to orthopaedic surgery, were to assess the dose-dependent increase in thrombin generation (TG) after infusion of bypassing agents and to evaluate whether or not a correlation existed between the haemostatic efficacy of bypassing therapies and perioperative TG values. Methods and Results: TG was measured in 16 inhibitor patients, 10 of whom underwent 11 major orthopaedic procedures. In the non-bleeding state, TG significantly improved 30 min after whichever dose (P < 0.01), with no dose\u2013response relationship when values obtained after different rFVIIa doses were compared. TG significantly improved 30 min after the preoperative bolus (P < 0.05), while during the postoperative period TG values measured before and after dosing did not differ. Moreover, postoperative TG values were similar or even more impaired (P 64 0.05) than those measured before preoperative dosing. No difference was found by comparing procedures with and without bleeding complications and yet no bleeding occurred in spite of persistently low TG values in one-third of procedures. Conclusion: This study fails to support a definite role for the TG assay as a reliable laboratory tool to monitor the haemostatic efficacy of bypassing therapies and as a predictor of the risk of bleeding in inhibitor patients using these agents during orthopaedic surgery

How the direct oral anticoagulant apixaban affects hemostatic parameters : results of a multicenter multiplatform study

Abstract Background: Apixaban is a newly developed direct oral anticoagulant targeting activated factor X (FXa). The degree of interference of apixaban with coagulation parameters has not been thoroughly investigated. Methods: Increasing amounts of apixaban were added to aliquots of a pooled normal plasma (PNP) to mimic a large range of concentrations (n=8) that are observed in treated patients. Upon preparation, samples were stored frozen and tested for a vast array of coagulation parameters (including procoagulant and anticoagulant factors) in three laboratories, using three widely used coagulation platforms (reagent/coagulometer combinations). Results: Results for each parameter were expressed as ratios of the value corresponding to each apixaban concentration to the value corresponding to the PNP without apixaban. By definition, ratios higher or lower than the unity define overestimation or underestimation, respectively. Prothrombin and activated partial thromboplastin times were barely prolonged by apixaban 200 ng/mL (ratios <1.29 or <1.19, respectively). Conversely, antithrombin was considerably overestimated when the measurement was made with FXa as target enzyme (ratios up to 1.43). Protein C and protein S were overestimated when measured as anticoagulant activities (ratios up to 1.20 or 1.95, respectively), and most measurements for individual coagulation factors (except fibrinogen) were considerably underestimated (ratios from 0.62 to 1.01). Conclusions: This large multicenter multiplatform study investigating a common set of test plasmas shows that apixaban interferes with the measurement of most coagulation parameters requested for investigation of hemostasis and highlights the need for a careful interpretation of results obtained in patients under treatment

Thrombin Generation in Preterm Newborns With Intestinal Failure-Associated Liver Disease

Background and Aim: Intestinal failure-associated liver disease (IFALD) affects one-fifth of neonates receiving parenteral nutrition (PN) for more than 2 weeks. We aimed to define the effect of IFALD on hemostasis of preterm infants. Methods: This is an ancillary analysis of a prospective study aimed at defining coagulation in preterm infants. We included neonates exposed to PN (at least 14 days), in full-enteral feeding. We compared thrombin generation in the presence of thrombomodulin, defined as endogenous thrombin potential-ETP, PT, aPTT between infants with IFALD vs. those without (controls), at birth, and after 30 days. IFALD was defined as conjugated bilirubin 651 mg/dl. Results: We enrolled 92 preterm infants (32 IFALD; 60 controls). Cholestatic patients had a lower birthweight, longer exposure to PN, and longer hospitalization. Infants with IFALD showed longer median PT (12.8-vs.-12 sec; p = 0.02) and aPTT (39.2-vs.-36.5 sec; p = 0.04) than controls, with no difference in ETP. Conclusions: Despite prolonged PTs and aPTTs infants with IFALD had similar ETP than those without

Evaluation of procoagulant imbalance in Cushing’s syndrome after short- and long-term remission of disease

Objective: Patients with Cushing’s syndrome (CS) are at high risk of venous thromboembolism related to a hypercoagulability due to procoagulant imbalance. However, whether these alterations are reversible after disease remission is still unclear. The endogenous thrombin potential (ETP) measured with and without the addition of thrombomodulin provides a global representation of coagulation and previous data confirmed hypercoagulable profile in patients with active hypercortisolism. Aim of this study was to assess the short- and long-term modification of ETP in patients with CS after disease remission. Design and methods: Nineteen patients with CS for whom surgical remission was achieved, were prospectively evaluated for clinical characteristics, cortisol secretion profile and ETP at different time points: (i) before surgical intervention; (ii) after 6&nbsp;months and (iii) 5&nbsp;years from the time of persistent remission. Nineteen healthy subjects matched for age and gender were also evaluated as control group. Results: Before surgery, patients showed higher ETP-ratio (with/without thrombomodulin) than controls (0.62 ± 0.09-vs-0.56 ± 0.09, p = 0.034). No significant correlation between ETP-ratio and cortisol secretion was found. 6 months after remission, ETP-ratio was still significantly increased compared to controls (0.64 ± 0.09-vs-0.56 ± 0.09, p = 0.01), but was similar to baseline (0.64 ± 0.09-vs-0.62 ± 0.09, p = 0.87). At 5&nbsp;years, ETP-ratio showed a significant decrease (0.55 ± 0.14-vs-0.62 ± 0.09, p = 0.02) and was comparable to controls (0.55 ± 0.14-vs-0.56 ± 0.09, p = 0.7). Conclusions: Plasma hypercoagulability detected in patients with active hypercortisolism persists at short-term evaluation and seems to be completely reversible after long-term remission of disease. These data, as part of a whole evaluation of thrombotic risk, can contribute to make appropriate therapeutic choice in these patients