M. Pazzagli

Prolonged Prophylaxis with Unfractioned Heparin Is Effective to Reduce Delayed Deep Vein Thrombosis in Total Hip Replacement

The aim of this study was to assess the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) until 45 days after elective total hip replacement (THR) and the efficacy of prolonged unfractioned heparin (UH) prophylaxis up to postoperative day 30. To this end 79 of 96 patients admitted consecutively to the University Hospital of Pisa for THR were randomly assigned to short- or long-term UH prophylaxis. Sixty-one patients completed the study: 28 of them received short-term prophylaxis (subcutaneous UH 15,000 IU/24 h for 15 days) and 33 prolonged prophylaxis (subcutaneous UH 15,000 IU/24 h for 30 days). Lower limb phlebography was performed in all patients on day 45 after THR. DVT was demonstrated in 10 (16.3%) cases after hospital discharge. Among them, 2 patients also had symptomatic PE. The incidence of DVT was 21.4% in short- and 12.1% in long-term UH-treated patients. The incidence of only proximal DVT was 17.8% in short- and 3.0% in long-term UH-treated patients; although the difference was only close to significance (p = 0.085), the relative risk of developing proximal DVT was about six times greater in the former group of patients. We concluded that the risk for thromboembolism persists at least until 45 days after surgery in patients subjected to THR. Prophylaxis with UH given up to postoperative day 30 appears more effective and safer in reducing the delayed thromboembolic risk compared to prophylaxis with UH given up to discharge only.

Resolution of Pulmonary Embolism: Effect of Therapy and Putative Age of Emboli

The purpose of this study was to evaluate functional and scintigraphic improvement in patients with pulmonary embolism (PE) according to the kind of treatment and the putative age of the emboli. The study includes 20 patients with both scintigraphic and angiographic diagnosis of PE enrolled in Pisa as a part of two previous multicenter trials: PAIMS 2 and BAPE. All patients were admitted to the Pulmonary Unit of the University of Pisa and treated with recombinant tissue-type plasminogen activator (rt-PA) plus heparin (H) (n = 10) or with H alone (n = 10). Results confirmed previous data, namely that perfusion damage decreases significantly from embolization to 7 days later in both patients treated with rt-PA + H and H alone (p < 0.001), although patients treated with rt-PA + H have a significantly higher perfusion restoration (p < 0.001) and a standard PaO2 increase (p < 0.01). Interestingly, our data also showed that the putative age of the emboli does not influence the efficacy of rt-PA + H treatment, while it does influence that of H treatment alone; in other words, rt-PA + H therapy may act efficaciously not only in fresh, but also in old pulmonary emboli.

Clinical, Anamnestic and Coagulation Data in Patients with Suspected or Confirmed Pulmonary Embolism

We studied 84 consecutive patients referred with the suspicion of pulmonary embolism (PE) to investigate the influence of clinical and hematological profiles on the diagnosis and severity of this disease and recovery. Diagnosis of PE was confirmed in 48 out of 84 patients by perfusion scintigraphy and/or pulmonary arteriography. Severity of PE and entity of recovery were investigated by measuring standard PaO2 on blood gas analysis and the number of unperfused lung segments ULS on perfusion scintigraphy. Most common clinical predisposing conditions were more frequent, though not significantly so, in embolic patients and a very low prevalence of PE was appreciable in patients without clear predisposing conditions. Among coagulation factors, only thrombin-antithrombin (TAT) complexes were twice as high in embolic as in nonembolic patients (14.0 +/- 13.6 vs. 7.0 +/- 4.2 ng/ml; p < 0.02), while there was no statistically significant difference between embolic and nonembolic patients for activated partial thromboplastin time, prothrombin time, antithrombin III, protein C, fibrinogen, plasminogen, alpha 2-plasmin inhibitor, and plasminogen activator inhibitor-1. Sensitivity and specificity of TAT complexes in diagnosis of PE were 95.8% and 30.5%, respectively. Therefore, normal values of TAT complexes may help exclude the diagnosis of PE, while abnormal values allow to reinforce the clinical suspicion of PE. No relation was found between coagulation parameters and the severity of PE. The follow-up of 48 patients with confirmed PE was favorable on the average; however, neither the presence of predisposing conditions nor abnormal coagulation parameters allow to predict the degree of functional and scintigraphic improvement during follow-up.

Value of Thrombin-Antithrombin III Complexes in Major Orthopedic Surgery: Relation to the Onset of Venous Thromboembolism

This study evaluated (a) the possible changes of plasma levels of thrombin-antithrombin III complexes during hospitalization to predict venous thromboembolism in patients undergoing elective total hip replacement and (b) the sensitivity and specificity of thrombin-antithrombin III complexes in the late incidence of deep vein thrombosis when these patients are discharged from the hospital. In 50 consecutive patients (18 men, mean age = 63 ± 8 years) a venous blood sample was obtained from each patient before surgery and postsurgery on days 5 ± 2, 9 ± 2, and 45 to evaluate the thrombin-antithrombin III complexes by the enzyme-linked immunosorbent assay as a part of a larger surveillance program. Six of 50 patients devel oped deep vein thrombosis, diagnosed by phlebography on the 45th day postsurgery. From the day before until the ninth day after surgery, mean values of the thrombin-antithrombin III complexes increased to a greater extent in patients with deep vein thrombosis than in those without, although the differences were not significant (from 14.8 ± 11.2 ng/mL to 36.2 ± 19.1 ng/mL in the former group and from 13.6 ± 3.3 ng/mL to 22.4 ± 5.1 ng/mL in the latter, p = NS). On the 45th day after surgery the mean value of the thrombin-antithrombin III com plexes reduced less in patients with deep vein thrombosis (up to 9.9 ± 1.9 ng/mL and to 25.2 ± 17.2 ng/mL, respectively, p = NS). In addition, thrombin-antithrombin III complexes re mained over the level reached on the fifth day only in the patients who developed deep vein thrombosis. On the 45th day after surgery, thrombin-antithrombin III complexes exhibited a sensitivity of 17%, a specificity of 86%, and an accuracy of 78% in differentiating the presence and absence of deep vein thrombosis as compared with phlebography. We conclude that after total hip replacement (a) serial measurement of the throm bin-antithrombin III complexes does not appear helpful in pre dicting venous thromboembolism during hospitalization, and (b) measurement of thrombin-antithrombin III complexes has a low diagnostic accuracy in diagnosing delayed deep vein thrombosis. However, the greater and persistent increase of thrombin-antithrombin III complexes level in patients who de veloped deep vein thrombosis may deserve further investiga tions.

Thrombin-Antithrombin III Complexes as an Additional Diagnostic Aid in Pulmonary Embolism

Plasma levels of selected coagulation and fibrinolytic parameters (activated partial thromboplastin time, prothrombin time, fibrinogen, antithrombin III, protein C, thrombin-anti-thrombin III complexes (TAT), plasminogen activator inhibitor-1 (PAI-1), plasminogen, alpha 2-plasmin inhibitor) were evaluated in 90 patients with clinical suspicion of pulmonary embolism (PE). Plasma levels of fibrinogen, PAI-1 and TAT were significantly higher in patients than in controls (p < 0.01): evaluation of TAT displayed a sensitivity of 96.1% and specificity of 30.8%, and positive and negative predictive values of 64.5 and 85.7%, respectively. The number of nonperfused lung segments correlated directly with TAT levels (p < 0.01) and inversely with arterial pO2 values (p < 0.01). No significant difference was found in the other parameters between patients and controls. Our results suggest that the finding of normal TAT plasma levels can help to exclude PE in patients with clinically suspected PE.