Michael R. Lassen

Efficacy and Safety of Prolonged Thromboprophylaxis with a Low Molecular Weight Heparin (Dalteparin) after Total Hip Arthroplasty— The Danish Prolonged Prophylaxis (DaPP) Study☆☆☆★

The aim of this study was to compare the efficacy and safety of prolonged (35 days) thromboprophylaxis with a standard length (7 days) regimen of a low molecular weight heparin in patients undergoing total hip arthroplasty. The study was multicentre, randomised, double-blind, and prospective with two groups. Following seven days on a standard length regimen of dalteparin (5000 antifactor Xa units subcutaneously once daily starting 12 h before surgery), patients were randomized to continue the prophylaxis with either subcutaneous injections of dalteparin or placebo injections for a further 28 days. Efficacy was evaluated at the end of the study (day 35) in all patients with bilateral ascending phlebography to detect deep vein thrombosis. Bleeding complications and other adverse events were registered throughout the study period. Three hundred consecutive patients agreed to participate before the operation: 281 were finally randomised and 215 completed the study; two patients died before randomisation; 17 developed deep vein thrombosis; none developed pulmonary embolism; and five of 113 patients (4.4%, 95% CI 1-10%) developed deep vein thrombosis in the dalteparin group, compared with 12 of 102 (11.8%; 95% CI 6-20%) in the placebo group (p=0.039). Deep vein thrombosis in the proximal veins was diagnosed in one patient (0.9%; 95% CI 0-5%) in the dalteparin group, and in five (5.0%; 95% CI 2-11%) in the placebo group (p=0.076). Major bleeding was observed in one patient in the placebo group; minor bleeding complications and adverse events were equally distributed between the groups. We concluded that prolonged (35 days) thrombo prophylaxis with dalteparin is more effective than a standard length (7 days) regimen without increased risk of bleeding complications or other adverse events.

Elbow dislocation in children and adults: A long-term follow-up of conservatively treated patients

Sixty-three elbow dislocations in 28 children and 34 adults were followed for a median time of 7 years. Fifty-seven dislocations were posterior or posterolateral. All the cases were treated with closed reduction and immobilization. Although function became satisfactory in both age groups, it was better in children than in adults.

Real-time B-mode ultrasonography in the diagnosis of postoperative deep vein thrombosis in non-symptomatic high-risk patients

In a prospective study of 61 patients who were undergoing elective total hip replacement, the accuracy of real-time B-mode ultrasonography (B-US) in the diagnosis of postoperative deep vein thrombosis (DVT) was compared with blindly assessed bilateral ascending phlebography. The overall sensitivity and specificity of ultrasound was 71 and 94%, and the positive and negative predictive values were 77 and 92%, respectively. The sensitivity and specificity for diagnosis of proximal DVT was 73 and 96%, respectively. Thrombi smaller than 1 cm were not detected. It is concluded that B-US may be used as a screening test for postoperative DVT after elective hip surgery.

Haemostatic activation in patients with head injury with and without simultaneous multiple trauma.

In a prospective study including 16 patients with multiple trauma and head injury and 14 patients with isolated head injury we measured plasma levels of prothrombin fragment 1 and 2 (F1 + 2) and thrombin/antithrombin III complex (TAT) on admission and on days 1, 2, 3, and 7 after the incident. On admission, all patients had values of F1 + 2 and TAT above the reference range. Admission levels of both F1 + 2 and TAT were significantly higher compared with levels on the following days. Admission levels of F1 + 2 was significantly correlated to the Injury Severity Score. TAT was higher in patients with multiple trauma than in patients with isolated head injury and were significantly correlated to the Injury Severity Score on admission and on day 3. Levels of F1 + 2 were significantly lower on day 1 in four patients with post-traumatic pulmonary dysfunction compared with patients without pulmonary dysfunction. With respect to levels of TAT, no differences were detected between patients with and without pulmonary dysfunction.

PHLEBOGRAPHY AS THE GOLD STANDARD IN THROMBOPROPHYLACTIC STUDIES? A multicenter interobserver variation study

In 241 patients with total hip arthroplasty and entering a study on thrombosis prophylaxis, phlebography was adequately performed in 451 legs 7 to 11 days after surgery. The phlebograms were primary evaluated by 4 independent observers, and finally a consensus of the images in which disagreement primarily occurred was obtained. The diagnosis of thrombosis in the 4 primary observations varied between 65% and 83% (mean 70%) and the agreement on a negative diagnosis between 97% and 99% (mean 98%). Taking into account agreement by chance, kappa-values varied from 0.60 to 0.83 when the 6 different pairs of observations were compared. When comparing the primary evaluations with the final consensus, agreements on positive diagnosis varied between 70% and 90% (mean 80%) and on negative diagnosis between 97% and 99% (mean 98%). Kappa-values varied from 0.68 to 0.90. The factor of uncertainty in evaluation of phlebography may have to be considered when studies on postsurgical thromboprophylaxis are planned.

Association between plasma levels of tissue plasminogen activator and postoperative deep vein thrombosis-influence of prophylaxis with a low molecular weight heparin

Abstract In a prospective, randomized controlled study, tissue plasminogen activator (t-PA) and tissue plasminogen activator antigen (t-PA:ag) were measured pre-and postoperatively in 40 consecutive patients undergoing total hip replacement. Patients received either a subcutaneous injection of low molecular weight heparin or placebo once daily. Deep vein thrombosis was diagnosed by bilateral phlebography. Patients who developed postoperative thromboembolic complications had significantly lower preoperative t-PA activity levels than patients who did not develop such complications. No difference was observed between the two groups with respect to t-PA:ag. Thromboprophylaxis with low molecular weight heparin did not cause any significant changes in t-PA activity and t-PA:ag. This study in high risk patients indicates that impaired fibrinolysis may be associated with development of thromboembolic complications after operation.

Markers of coagulation and fibrinolysis after fractures of the lower extremities.

The study was performed to detect activation of coagulation and fibrinolysis in terms of prothrombin fragment 1 and 2 (F1 + 2), thrombin-antithrombin III complex (TAT), fibrin degradation products (FbDP), fibrinogen degradation products (FgDP), and soluble fibrin monomers (FM) in plasma from 39 patients with fractures of the lower extremities. We found substantially elevated levels of the molecular markers at admission and on the day after admission (Day 1) compared with control levels. Admission levels of F1 + 2, TAT, FbDP and FgDP were significantly higher compared with levels on day 1, whereas levels of FM were not significantly different between the two days. Generally there were good correlations between all markers of coagulation and fibrinolysis at admission whereas correlations were weaker or absent on day 1. In conclusion we found substantial haemostatic activation as a immediate response to trauma. Increased levels of F1 + 2, TAT, FM, FbDP and FgDP appear to be a normal physiological reaction after fractures of the lower extremities.

Components of coagulation and fibrinolysis during thrombosis prophylaxis with a low molecular weight heparin (enoxaparin) versus dextran 70 in HIP arthroplasty

In a prospective randomized study heptest, thrombin-antithrombin complexes (TAT), D-dimer, and t-PA:ag were analysed pre- and postoperatively in 206 consecutive patients undergoing hip arthroplasty during thromboprophylaxis with either a LMW heparin (Enoxaparin) or Dextran 70. Deep vein thrombosis (DVT) developed in 6 of 102 (6%) Enoxaparin and in 21 of 104 (20%) Dextran patients diagnosed by bilateral phelobography. In the Enoxaparin group heptest showed a significant increase from the pre- to the postoperative level opposed to a significant decrease in the Dextran group. Postoperative levels of TAT, D-dimer, and t-PA:ag were significantly increased in both groups, however, TAT was significantly higher in patients in the Dextran group than in the Enoxaparin patients. D-dimer was significantly higher in Dextran patients with DVT postoperatively compared with patients without DVT. No differences concerning TAT or t-PA:ag were observed between patients with and without DVT in any of the groups.

Dose relation in the prevention of proximal vein thrombosis with a low molecular weight heparin (tinzaparin) in elective hip arthroplasty.

This is a review of a double-blind, prospective study comparing the thromboprophylactic efficacy and safety of two different prophylactic regimens of a low molecular weight heparin (tinzaparin) in 250 consecutive patients (aged < or 18) undergoing primary elective hip arthroplasty. Regimen 1: 75 U anti-Xa/kg BW (actual range 63 to 91) once daily started 12 hours before operation; and regimen 2: 50 U anti-Xa/kg BW (actual range 41 to 71) once daily started 2 hours before operation. Both regimens were administered in a weight-adjusted fashion and were continued for 7 days after operation or until full mobilization. Efficacy was evaluated by occurrence of postoperative deep vein thrombosis (DVT) diagnosed by bilateral ascending phlebography on day 7 +/- 2 after operation, and the venograms were evaluated in an assessor blind fashion by a panel of three expert radiologists. Safety was evaluated by the amount of blood lost and transfusion requirements during and after the operation; all bleeding complications, reoperations, adverse events and deaths were observed during the study. A 3-month follow-up on survival and occurrence of thromboembolism was performed on all randomized patients. The result was a significantly better protective effect against proximal DVT by regimen 1 compared with regimen 2. This was achieved with improved safety in terms of a significantly decreased need for blood transfusions during operation and fewer wound complications in the postoperative period in favor of regimen 1. Therefore, tinzaparin administered in a dosage of 75 U anti-Xa/kg BW 12 hours before surgery is significantly more protective against proximal DVT and safer than the standard regimen of 50 U anti-Xa/kg BW started 2 hours before surgery in patients undergoing primary elective hip arthroplasty.

Phlebography as the Gold Standard in Thromboprophylactic Studies

In 241 patients with total hip arthroplasty and entering a study on thrombosis prophylaxis, phlebography was adequately performed in 451 legs 7 to 11 days after surgery. The phlebograms were primary evaluated by 4 independent observers, and finally a consensus of the images in which disagreement primarily occurred was obtained. The diagnosis of thrombosis in the 4 primary observations varied between 65% and 83% (mean 70%) and the agreement on a negative diagnosis between 97% and 99% (mean 98%). Taking into account agreement by chance, kappa-values varied from 0.60 to 0.83 when the 6 different pairs of observations were compared. When comparing the primary evaluations with the final consensus, agreements on positive diagnosis varied between 70% and 90% (mean 80%) and on negative diagnosis between 97% and 99% (mean 98%). Kappa-values varied from 0.68 to 0.90. The factor of uncertainty in evaluation of phlebography may have to be considered when studies on postsurgical thromboprophylaxis are planned.