Biomedical subjects
Publications and source records attributed to G Agnelli.
In a randomized double-blind crossover study in 16 patients with enhanced in vitro spontaneous platelet aggregation, sulfinpyrazone proved to be effective in normalizing platelet aggregability within 4 days after initiation of therapy.
Quantitation of the thrombocytopathy of uraemics may be one useful way of evaluating forms of therapy. 24 patients treated by haemodialysis and peritoneal dialysis at two different times had platelet aggregation studies whose parameters were compared with those of 24 normal persons, 5 successful transplants or 13 untreated uraemics. Renal transplantation and peritoneal dialysis improved platelet function. The haemodialysis procedure itself impaired platelet function: this was not due to heparin.
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BACKGROUND: Venous thromboembolism is a common, life-threatening complication in neurosurgery, but prophylaxis with anticoagulant agents has not gained wide acceptance because of concern about intracranial bleeding. We performed a meta-analysis of controlled randomized trials on the efficacy and safety of heparin in the prophylaxis of venous thromboembolism in neurosurgery. OBJECTIVE: To review the clinical benefit of prophylaxis of venous thromboembolism with heparin in the controversial setting of neurosurgery. METHODS: Relevant trials evaluating heparin for prophylaxis of venous thromboembolism in neurosurgery were identified by a MEDLINE search, scan of meeting abstracts, and scrutiny of the references of original articles and reviews. Four controlled randomized studies, 3 of which involved low-molecular-weight heparin, were included in the analysis, and 4 uncontrolled studies are commented on in the article. The outcome measure (observed minus expected number of events) and its variance were calculated for each single trial and then summed. Two-tailed P values and 95% confidence intervals (CIs) were calculated. Efficacy was assessed per protocol and safety by intention-to-treat analysis. The homogeneity of the studies was tested with the chi(2) statistic. The results were also expressed as number needed for 1 extra event. RESULTS: A total of 187 thromboembolic events were recorded in 827 patients (22.6%). Heparin prophylaxis resulted in a 45% relative risk reduction of venous thromboembolic events (odds ratio [OR], 0.48; 95% CI, 0.35-0.66; P<. 001). Nineteen major bleedings were recorded in 1022 patients. None were fatal. Heparin treatment resulted in a 71% relative risk increase of major bleeding (OR, 1.72; 95% CI, 0.69-4.27; P =.24). The number needed to treat was 7.7 for venous thromboembolism and 16 for proximal deep vein thrombosis. The number needed to harm was 102 (115 for low-molecular-weight heparin). CONCLUSIONS: Low-molecular-weight and unfractionated heparin have been shown to be effective for prophylaxis of venous thromboembolism in elective neurosurgery without excessive bleeding risk.
Postoperative deep vein thrombosis is usually asymptomatic so that pulmonary embolism is often the first clinical manifestation of venous thromboembolism. The diagnostic accuracy of impedance plethysmography, 125I-fibrinogen leg scanning and real-time B-mode ultrasonography has been extensively evaluated in patients with asymptomatic deep vein thrombosis. Impedance plethysmography has been evaluated in a number of studies and its sensitivity has been invariably found to be approximately 20% or less. These results seem to be due to the high prevalence in asymptomatic patients of distal, small and nonocclusive thrombi, unable to produce a critical obstruction of the venous flow. The accuracy of 125I-fibrinogen leg scanning has been assessed in a number of studies and found to be significantly different in the initial and more recent studies. This difference has been found to be due to the quality of the study design: the better the methodology, the lower the diagnostic accuracy of 125I-fibrinogen leg scanning. The association of impedance plethysmography and 125I-fibrinogen leg scanning do not result in an improvement of the results obtained by the single diagnostic method. Study methodology strongly influenced the results obtained with real-time B-mode ultrasonography with a reported sensitivity of approximately 50% in the studies performed adopting an appropriate methodology. In conclusion, noninvasive diagnostic methods are inaccurate in the diagnosis of asymptomatic deep vein thrombosis. Thus, venography remains the only accurate diagnostic method for the diagnosis of asymptomatic deep vein thrombosis.
The aim of this double-blind, placebo-controlled crossover study was to investigate the effect of 1-deamino-8-D-arginine vasopressin (dDAVP) on hemostasis in patients with chronic liver disease. Nine consecutive patients with biopsy-proven liver cirrhosis and related coagulation abnormalities received in a random order dDAVP, 0.5 microgram/kg, or saline intravenously. Blood samples were taken before dDAVP infusion and 30, 60 and 180 min after its end. dDAVP infusion induced a statistically significant shortening of the bleeding time from 9 min (range 6.5-15.5) to 6 min (range 4.5-9.5) at 1 h after the infusion. The activated partial thromboplastin time was significantly shortened at 30 and 60 min after dDAVP infusion. Plasma levels of factor VIII, XI and XII coagulant activities were significantly increased at all sampling times after dDAVP infusion. The maximum increase over basal values in plasma levels of factor VIII, XI and XII was 63, 22 and 40%, respectively. dDAVP did not induce any significant changes of prothrombin time, thrombin clotting time, fibrinogen, plasma levels of factor II, V, VII, IX, X, factor XII antigen, protein C (activity and antigen), antithrombin III, plasminogen and alpha 2-antiplasmin. Placebo infusion did not produce any significant changes in the evaluated parameters. We conclude that dDAVP can positively influence the hemostatic system in patients with liver cirrhosis. The clinical relevance of this hemostatic improvement deserves further evaluation.
Five widely used activated partial thromboplastin time (APTT) reagents (Actin-FS, Actin-FSL, Hemolab Silimat, IL-Test APTT Ellagic Acid and Thrombofax Activated) were compared for their sensitivity and precision in measuring the effect of dermatan sulphate on blood coagulation. On each of 4 days, aliquots of the same normal human plasma pool were mixed with dermatan sulphate (MF701) at concentrations ranging from 10 to 100 micrograms/ml, and APTT was measured in duplicate with all reagents by a photo-optical coagulometer. The order of testing between and within reagents was changed every day. The relationship of APTT ratio to dermatan sulphate concentration was linear with all the reagents. There were statistically significant differences between reagents in their sensitivity to DS, as reflected by linear regression slopes. IL-Test was the most sensitive reagent. At dermatan sulphate concentrations of 20, 50, and 80 micrograms/ml APTT ratio ranged from 1.5 to 1.7, 1.9 to 2.3 and 2.3 to 2.9, respectively, according to the reagent. The lambda coefficient and coefficient of variation derived from regression analysis, both reflecting assay precision, ranged from 0.57 to 0.71 and from 4.6 to 5.1%, respectively, with all but the least precise reagent. The best sensitivity/precision balance was displayed by IL-Test. The APTT reagent should therefore be standardized, with special regard to sensitivity to DS, when testing the relationship of dermatan sulphate clinical effects to APTT response.
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Low molecular weight heparins (LMWHs) have been prepared from unfractionated heparin by means of different fragmentation or fractional procedures with the aim of obtaining a more effective and/or safer antithrombotic agent than standard heparin (SH). LMWHs resulting from different production procedures are structurally heterogeneous; this could account for the different efficacy and safety observed clinically. Many clinical trials have been carried out on the prevention of deep-vein thrombosis (DVT) and pulmonary embolism in patients undergoing major abdominal or orthopedic surgery, hemodialysis or affected by non-hemorrhagic stroke. Moreover, experience is accumulating on the use of LMWHs in the treatment of DVT. LMWHs have been shown to be an effective antithrombotic agent in preventing DVT in general surgery when compared to placebo. Furthermore, CY 216, given once daily, is at least as effective as standard heparin given twice or three times daily. In two studies CY 216 was more effective than standard heparin. However, the promising experimental findings that LMWHs produce less bleeding than standard heparin have not been proved yet. There is convincing evidence that PK 10169 is effective in preventing DVT in patients undergoing hip surgery. In one study PK 10169 was more effective than standard heparin. Both ORG 10172 and KABI 2165 were effective in the prevention of DVT in patients with stroke but the safety in terms of bleeding remains to be established. The role of LMWHs in DVT treatment has yet to be established. The dose of LMWHs which offers the best risk-benefit ratio must be established for each compound before LMWHs are accepted as standard prophylaxis or treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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BACKGROUND AND OBJECTIVE: Venous thromboembolism includes two closely related clinical manifestations: deep vein thrombosis (DVT), more commonly of the lower limbs, and pulmonary embolism. Pulmonary embolism is the most common cause of preventable death in hospitalized patients. The definition of the risk factors for venous thromboembolism should allow to adopt the most suitable prophylactic regimen. Determinants for the risk of venous thromboembolism are patient risk factors, both clinical and molecular, and the clinical setting. In this article the prophylactic regimens most widely employed in the prevention of venous thromboembolism in high-risk clinical settings with be reviewed. Then, the available guidelines for the management of thrombophilic patients will be given. INFORMATION SOURCES: The authors have been working in this field contributing original papers. In addition, the material examined in this review article includes papers published in the journals covered by the Science Citation Index and Medline. STATE OF ART AND PERSPECTIVES: Pharmacological prophylaxis is an effective approach for reducing morbidity and mortality from venous thromboembolism. Nevertheless, prophylaxis for venous thromboembolism is under employed because the incidence of venous thromboembolism is underestimated and there is fear of bleeding side effects. Adopting the proper prophylactic strategy for venous thromboembolism requires defining the patient risk factor. Determinants for the risk of venous thromboembolism are patient risk factors, both clinical and molecular, and the clinical setting. The risk connected with the clinical setting is the only risk defined by properly performed epidemiological studies. High-risk clinical settings are major orthopedic surgery, elective neurosurgery, spinal cord injury, cancer surgery and multiple trauma. The most effective anticoagulant regimens in the prevention of venous thromboembolism in high-risk patients are adjusted-dose unfractionated heparin, low molecular weight heparins (LMWHs) and oral anticoagulants. LMWHs are as effective and safe as the other two agents, but they do not require laboratory monitoring. On the other hand, LMWHs are more expensive than unfractionated heparin and warfarin. The use of effective agents still leaves the patients with a high prevalence of venous thromboembolism. Hence the search for more effective agents such as selective thrombin inhibitors like hirudin and its analogues. In patients undergoing elective hip surgery, hirudin has been recently shown to be more effective than low-dose unfractionated heparin and the LMWH enoxaparin.