Thrombodynamics—A new global hemostasis assay for heparin monitoring in patients under the anticoagulant treatment

<div><p>Background</p><p>Heparin therapy and prophylaxis may be accompanied by bleeding and thrombotic complications due to individual responses to treatment. Dosage control based on standard laboratory assays poorly reflects the effect of the therapy. The aim of our work was to compare the heparin sensitivity of new thrombodynamics (TD) assay with sensitivity of other standard and global coagulation tests available to date.</p><p>Study population and methods</p><p>A total of 296 patients with high risk of venous thromboembolism (deep vein thrombosis (DVT), early postoperative period, hemoblastosis) were enrolled in the study. We used a case-crossover design to evaluate the sensitivity of new thrombodynamics assay (TD) to the hemostatic state before and after unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) therapy/prophylaxis and to compare it with the activated partial thromboplastin time (APTT), anti-Xa activity test, thrombin generation test (TGT) and thromboelastography (TEG). A receiver operating characteristic (ROC) curve analysis was used to evaluate changes before and after heparin prophylaxis and therapy. Blood was sampled before heparin injection, at the time of maximal blood heparin concentration and before the next injection.</p><p>Results</p><p>Hypercoagulation before the start of heparin treatment was detected by TD, TGT and TEG but not by APTT. The area under the ROC curve (AUC) was maximal for TD and anti-Xa, intermediate for TGT and TEG and minimal for APTT.</p><p>Conclusions</p><p>These results indicate that TD has a high sensitivity to the effects of UFH and LMWH after both prophylactic and therapeutic regimes and may be used for heparin monitoring.</p></div

APTT vs TD parameters before heparin treatment.

<p>(A) APTT and (B) V in TD before heparin treatment in groups: healthy volunteers (control group), group 1, group 2 and group 3. The box plots indicate the following parameters: the mean value (the dot inside the box), the median (the horizontal line inside the box), the 25th and 75th percentiles (the bottom and top of the box, respectively) and the 5th and 95th percentiles (the ends of the whiskers). * indicates a significant difference from healthy volunteers group (p<0.01, Mann-Whitney test).</p

The thrombodynamics method principle.

<p>(A) The photos of fibrin clot growth are shown for normal plasma and in LMWH presence (0.08 IU/ml). The edge of the activator on the top of the pictures is covered with immobilized tissue factor. Clot starts growing from the edge of the activator to the bulk of the plasma. The process of fibrin clot formation is recorded in a time-lapse video microscopy mode by means of dark-field light scattering method. The obtained series of photos shows how the size of fibrin clot changes over time. (B) Plot of clot size versus time in normal plasma (black line) and in LMWH presence (0.1 IU/ml) representing the principle of the parameter V calculation. (C) The in vitro heparin dose dependency for V in the presence of UFH or LMWH in plasma of healthy volunteers. Means and SEM were shown (n = 10).</p

Heparin effect on APTT vs TD.

<p>ROC curves for APTT (gray lines) and V in TD (black lines) for treatment with LMWH (group 1) at the Point 1 (A) and Point 2 (B) or UFH (group 1) at the Point 1 (C) and Point 2 (D) and prophylactics with LMWH (group 2) at the Point 1 (E) and Point 2 (F) or UFH (group 3) at Point 1 (G). Data of the same patients before the first heparin injection were used as controls.</p