Jørn Dalsgaard Nielsen

Quality of reinfused drainage blood after total knee arthroplasty

Reinfusion of postoperative wound drainage blood has become an attractive alternative in primary total knee and hip arthroplasty. Quality of the drainage blood was studied with respect to content of extracellular bioactive substances and coagulation split products. Using the HandyVac ATS autotransfusion system, drainage blood was collected and reinfused within 6 hours postoperatively from 10 patients undergoing primary total knee arthroplasty. Blood samples were collected from the patients immediately after and 1 hour after opening of the tourniquet and after reinfusion of drainage blood. Samples were also collected from the drainage blood immediately before and at the end of reinfusion. The leukocyte-derived and platelet-derived bioactive substances histamine, eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase (MPO), plasminogen activator inhibitor type 1 (PAI-1), and activated complement factor C3(C3a) and various coagulation factors and split products were analyzed in patient and drainage blood samples. None of the patients received additional predonated autologous blood or allogeneic blood components during the study period. Within 6 hours postoperatively, 250 to 1,000 mL drainage blood was collected and reinfused. Histamine, ECP, EPX, MPO, PAI-1, and C3a content was significantly increased in drainage blood immediately before and at the end of reinfusion. Reinfusion did not change the concentration of these substances in samples from the patients. Coagulation factors and various split products showed that drainage blood was defibrinated. Reinfusion of drainage blood did not change the coagulative capacity of the patients. Drainage blood appears to be defibrinated and contains various extracellular leukocyte-derived and platelet-derived bioactive substances. Reinfusion does not change the coagulative capacity or the concentration of bioactive substances of patients.

Application of basic and composite thrombelastography parameters in monitoring of the antithrombotic effect of the low molecular weight heparin dalteparin: an in vivo study

BackgroundLow molecular weight heparin (LMWH) is in vast usage for treatment of thromboembolic diseases such as deep venous thrombosis and acute coronary syndromes. There are certain clinical situations where a quick point of care testing of the effect of LMWH would be useful. At this point there are no point of care devices available in the market for monitoring the effect of LMWH. Thrombelastography (TEG) evaluates the viscoelastic properties of blood during coagulation. The clinical application of TEG in monitoring LMWH treatment is not yet well defined. The purpose of this in vivo study was to systematically evaluate the most suitable TEG parameters for evaluation of the antithrombotic effect of LMWH. We furthermore evaluated for the first time the usefulness of the composite TEG parameter the Thrombodynamic Ratio (TDR) in monitoring LMWH treatment.MethodsHealthy male volunteers (n = 7) were injected subcutaneously with the LMWH dalteparin 120 IU/kg. TEG parameters and antifactor Xa levels were measures at baseline, 2, 4, 5 and 24 hours after the injection. Correlation between TEG parameters and antiXa were calculated. The sensitivity and specificity of the TEG parameters for plasma levels of antiXa in the therapeutic range of 0.5 - 1.0 U/ml were calculated.ResultsAll basic TEG parameters correlated significantly with antiXa levels. Among the basic parameters, the TEG reaction time R had the best correlation with antiXa levels with the most favorable combination of sensitivity and specificity for the therapeutic range of antiXa levels (r = 0.82, p < 0.0001, sensitivity 68%, specificity 100%). The composite TEG parameter TDR demonstrated the best correlation with antiXa levels, and an even more favorable combination of sensitivity and specificity compared to any of the basic parameters (r = - 0.87, p < 0.0001, sensitivity 95%, specificity 79%).ConclusionThe TEG reaction time R and TDR are the most suitable TEG parameters for evaluation of the antithrombotic effect of dalteparin with a highly significant correlation with antiXa levels in healthy male volunteers. Measures for uniform clinical use of these parameters are proposed. Larger clinical trials are needed to correlate R and TDR with clinical outcomes.

Intra-arterial thrombin activity produced by percutaneous transluminal angioplasty eliminated by segmentally enclosed thrombolysis

We determined the specific marker of thrombin activity, fibrinopeptide A (FPA), in the vicinity of dilated sites during percutaneous transluminal angioplasty (PTA) for femoro-popliteal obstructions in 24 patients. Blood samples were drawn proximal to dilated segments from a 4F catheter inserted retrogradely in the common femoral artery and distal to dilated segments from the balloon catheter tip. Median +/- S.E. FPA concentration was 21.5 +/- 4.4ng ml-1 before PTA. Immediately after dilatation, FPA concentrations were increased to 970.0 +/- 836.9 ng ml-1 distal to dilated segments (p less than 0.00005) and to 48.5 +/- 11.4 ng ml-1 proximally (p less than 0.003). Segmentally enclosed thrombolysis (SET) was undertaken immediately after PTA, when a double balloon catheter was positioned with a balloon at each end of dilated segments. Both balloons were inflated and 5 mg recombinant tissue plasminogen activator (rt-PA) and 1000 IU heparin were enclosed in the segments for 30 min. Immediately after SET, FPA concentration distal to dilated segments was 34.0 +/- 14.2 ng ml-1 and not different from proximal concentrations found after PTA (p = 0.57). Intense fibrinolysis was indicated by significantly increased levels of cross-linked fibrin degradation products (D-dimer) for hours after SET, but FPA concentrations in peripheral blood remained near baseline values. This finding differed from increased thrombin activity found by others during systemic thrombolytic therapy. Early rethrombosis did not occur after PTA in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombosis and Intrinsic Fibrinolysis in Percutaneous Transluminal Angioplasty

Coagulation and fibrinolysis were investigated in 14 claudicants undergoing percutaneous transluminal angioplasty (PTA) for femoropopliteal artery lesions. Cross-linked fibrin degradation products (XL-FDP), tissue plasminogen activator (t-PA) antigen, fibrinopeptide A (FPA), and plasminogen activator inhibitor-1 (PAI-1) activity were measured in peripheral blood. XL-FDP and t-PA increased, and FPA and PAI-1 decreased significantly after angioplasty. XL-FDP increased from baseline 266 +/- 72 ng/ml to 481 +/- 239 ng/ml (p < 0.0005) 30 min after PTA, indicating mural thrombus formation in spite of the significant fall in FPA influenced by heparin. A groin haematoma developed after PTA in 4/6 patients, who received more than 5600 IU heparin and in 1/8 patients receiving smaller dosages. The alterations in PAI-1 showed no correlation with those of t-PA, whereas heparin had a sparing effect on PAI-1 consumption. These findings may indicate that PAI-1 acts as a thrombin inhibitor following deep vessel wall injury by angioplasty. In two patients, who had signs of rethrombosis on the next day, residual FPA was relatively high, XL-FDP peaked at 3530 +/- 1170 ng/ml, and t-PA increased by 2.6 +/- 1.0 ng/ml. The corresponding values in patients with an uncomplicated course were 406 +/- 89 ng/ml (p < 0.0001) and 0.1 +/- 0.5 ng/ml (p < 0.02). We conclude that thrombin promotes activation of coagulation and fibrinolysis in femoropopliteal PTA. Instability between these counteracting systems resulting in thrombosis is not prevented by conventional heparin administration at dosages causing bleeding complications.

Assessment of the effect of direct oral anticoagulants dabigatran, rivaroxaban, and apixaban in healthy male volunteers using a thrombin generation assay

Essentials The value of thrombin generation assay (TGA) in monitoring direct oral anticoagulants (DOAC) is not well defined. TGA parameters were measured and correlated to DOAC levels in 10 healthy volunteers after oral intake of DOACs. Lag time is the only sensitive TGA parameter across different DOACs, dabigatran, rivaroxaban and apixaban. Endogenous thrombin potential had weak correlation with DOAC levels and not suitable as stand‐alone parameter.