Utilization of the Caprini score in conjunction with thrombodynamic testing reduces the number of unpredicted postoperative venous thromboembolism events in patients with colorectal cancer.

BACKGROUND: The thrombodynamic test (TD) is a novel global test of hemostasis that allows to study the spatial-temporal characteristics of a clot formation in real time under conditions close to natural ones and demonstrates high sensitivity to detect the state of hypercoagulation. The main paraments of the test are the velocity of clot growth, clot's size, and clot density. The objective of this study was to compare the classic Caprini 2005 score and its modified version in association with the results of TD. The goal is to predict postoperative venous thromboembolism (VTE) in surgical patients undergoing surgery for colorectal cancer. METHODS: This was a prospective observational clinical study involving 80 patients (33 men and 47 women; mean age, 73.9 ± 7.2 years) who underwent major (79 cases) or minor (1 case) surgery for colorectal cancer. Patients were at high risk for postoperative VTE (ie, a mean Caprini score of 9.9 ± 2.0) and received combined prophylaxis (ie, antiembolic compression stockings and enoxaparin 40 mg once daily) until discharge. Enoxaparin was administered at a fixed time of blood sampling for the TD test. Duplex ultrasound scan was performed to detect postoperative vein thrombosis before and 5 to 7 days after surgery. RESULTS: Postoperative vein thrombosis was found in 21 of 80 patients (26.3%; 95% confidence interval, 17.9%-36.8%). Regression analysis and receiver operating characteristic (ROC) curve showed that Caprini scores significantly predicted VTE (P < .0001; area under the curve [AUC] = 0.839 ± 0.045). Analysis of ROC curve coordinates showed that a cutoff point of 11 scores had a sensitivity of 76.2% and a specificity of 74.6%. The results of the TD test showed significant hypercoagulation despite enoxaparin administration in patients with VTE. Regression analysis and ROC curves demonstrated that the following TD parameters had the greatest predictability for postoperative DVT: initial velocity of clot growth (Vin) and clot size (CS) measured at 12 hours after enoxaparin administration (AUC, 0.697 ± 0.063 and AUC, 0.790 ± 0.059, respectively), as well as Vin and CS measured 24 hours after the enoxaparin injection (S = 0.847 ± 0.059 and S = 0.803 ± 0.069, respectively). The cutoff points for VTE prediction at 12 and 24 hours seemed to be a Vin of greater than 62.5 and greater than 64.5 µm/minute (normal range, 35-56 µm/minute) as well as a CS of greater than 1351.5 and greater than 1333.5 µm (normal range, 800-1200 µm), respectively. Identified thresholds for TD parameters have been integrated into Caprini scores under the item "other congenital or acquired thrombophilia." The total Caprini scores were recalculated in patients where one or all TD parameters had exceeded the cutoff followed by reanalysis of the ROC curves. The best predictability was found for Caprini scores considering the elevation of all four TD parameters (AUC, 0.924 ± 0.029) with increased cutoff to a score of 12 with a sensitivity of 85.7% and a specificity of 81.4%. The use of cutoffs for the original and modified scores could be used to calculate the number of patients that were under cutoff but developed with VTE: 10.2% and 5.9%, respectively. CONCLUSIONS: Integrating TD parameters into the Caprini score increases the ability to predict postoperative VTE.

Epidemiology of venous thromboembolism (VTE) associated with pregnancy.

This review is focused on the epidemiology of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), associated with pregnancy. Superficial vein thrombosis, a less hazardous and less studied type of thrombosis in pregnant women, is beyond the scope of this review. This study discusses the VTE incidence rate in women from developed countries for both antepartum and postpartum periods and for subpopulations of women affected by additional risk factors, such as thrombophilias, circulatory diseases, preeclampsia of varying degrees of severity, and Caesarean section. To minimize bias due to historical changes in medical and obstetric practices, lifestyle, diet, etc., this review is generally limited to relatively recent studies, i.e., those that cover the last 35 years. The absolute risk or incidence rate was used to ascertain risk of VTE associated with pregnancy. For the studies where the direct incidence rates of VTE were not reported, we calculated an estimate of the observed but not reported absolute incidence rates using the data presented in respective articles.

Drug-drug interaction of the anti-TFPI aptamer BAX499 and factor VIII: studies of spatial dynamics of fibrin clot formation in hemophilia A.

BACKGROUND: In recent years, a number of tissue factor pathway inhibitor (TFPI) antagonists have been developed to serve as bypassing agents to improve hemostasis in hemophilia A. Since TFPI antagonists and FVIII concentrates are procoagulants, their combined effect on spatial clot formation could be potentially pro-thrombotic. OBJECTIVE: To investigate the cooperative effect of TFPI inhibition and supplementation of FVIII in hemophilia A in a spatial, reaction-diffusion experiment in vitro. METHODS: Plasma was collected at different time points from hemophilia A patients undergoing prophylaxis and was supplemented in vitro with TFPI inhibitor BAX499 (formerly ARC19499) at concentrations from 0 up to 600nM. Clotting propagation in recalcified plasma activated by a surface with immobilized tissue factor (TF) was monitored by videomicroscopy. RESULTS: Increasing concentration of BAX499 improved coagulation for all hemophilia A plasma samples activated with TF at 1.6pmole/m(2) by shortening lag time and increasing initial clot growth velocity and clot size. In contrast, plasma concentration of FVIII had little effect on lag time, but increased spatial clot growth velocity. There was a decrease in the BAX499 efficiency as FVIII concentration increased (lag time shortened by 50% if FVIII:C<5%, but the effect was only 25% if FVIII:C>30%). CONCLUSIONS: The results indicate that BAX499 has an effect on clotting in hemophilia A plasma at low FVIII concentrations, however has little effect at high FVIII concentrations.

Effect of pre-analytical conditions on the thrombodynamics assay.

INTRODUCTION: Standardization of pre-analytical conditions is the obligatory step for all potential diagnostic tests. Spatial clot growth (Thrombodynamics) is a new global hemostasis assay that considers spatial organization of coagulation. The principal parameter is rate of fibrin clot growth from the tissue-factor coated surface. In this work we studied the pre-analytical variables of Thrombodynamics assay that include conditions of blood collection, sample preparation and storage. MATERIALS AND METHODS: Blood of apparently healthy volunteers was used. Eight types of citrate blood collection tubes were tested, centrifugation conditions for plasma preparation were evaluated and impact of plasma freezing/thawing was tested. RESULTS: Among the blood collection tubes tested, BD Vacutainer glass tubes showed a significantly higher clot growth rate compared to plastic tubes. There was no difference between 3.2% and 3.8% of sodium citrate. For plasma preparation, a single 15 min centrifugation at 1,600 g shows significantly increased clot growth rate compared to plasma obtained by two sequential centrifugations (15 min 1 600 g, 5min 10,000 g). There was no significant difference between 1,600 g and 2,100 g if the second centrifugation was performed. For the second centrifugation there was no difference between 20 min at 1 600 g and 5 min at 10,000g. Frozen-thawed plasma showed increased clot growth rate compared to fresh plasma. CONCLUSION: The data represent the necessary steps for the standardization of Thrombodynamics assay and for the formulation of the operating guide.

Predicting prothrombotic tendencies in sepsis using spatial clot growth dynamics.

Inflammation in sepsis is associated with hypercoagulation that may lead to thrombosis and disseminated intravascular coagulation. Conventional diagnostic assays are poorly sensitive to procoagulant changes in sepsis. Objectives of the article is to study changes in hemostatic state of septic patients using spatial clot growth assay (currently being developed under the trademark of thrombodynamics) and to compare the sensitivity of this method with the sensitivity of conventional methods. Sixteen patients with hematological malignancies and sepsis were enrolled in the study. All patients had been surveyed for a month following the infection onset. Spatial clot growth assay monitors fibrin clot development in a nonstirred thin layer of platelet-free plasma activated by immobilized tissue factor. Clotting time tests, thromboelastography, D-dimer assays were also performed. Spatial clot growth revealed hypercoagulation in six patients. D-dimer levels increase (with vein thrombosis in one case) was subsequently observed in five of them. D-dimer levels did not increase when spatial clot growth was normal. At the next time point, after spatial clot growth assay showed hypercoagulation, the mean D-dimer concentration was significantly higher than after a normal analysis (457 versus 234 µg/l; P < 0.05); there was no such correlation for other assays. The remaining 10 patients had elevated D-dimer levels on the first day; this either decreased gradually or remained elevated. Spatial clot growth showed normalization in survivors and growing hypocoagulation in nonsurvivors. Measuring spatial clot growth dynamics has potential diagnostic utility for the evaluation of thrombotic risk.