Effect of ketorolac, ketoprofen and nefopam on platelet function.

Ketorolac, ketoprofen and nefopam are often used in the treatment of postoperative pain. While nefopam is a non-narcotic, non-opioid central analgesic agent, ketorolac and ketoprofen are non-steroidal anti-inflammatory drugs, which, due to their prostaglandin-synthetase inhibiting activity, have antiplatelet effects. In this study we investigated the effect of ketorolac, ketoprofen and nefopam on platelet function by performing bleeding time and in vitro platelet aggregation in 30 healthy volunteers (10 for each treatment) before and 3 h after drug administration. Nefopam did not affect bleeding time and platelet aggregation, while ketorolac and ketoprofen significantly prolonged bleeding time without significantly inhibiting platelet aggregation in response to adenosine diphosphate. The prolongation of bleeding time observed after ketorolac and ketoprofen may have clinical relevance and suggests that nefopam could be more safely administered for the treatment of postoperative pain, especially in patients with haemostatic defects or after high bleeding risk surgery.

Effect of oral anticoagulant treatment on plasma and serum antithrombin III: a study on 172 patients at different levels of anticoagulation.

Antithrombin III (AT III) functional levels are much lower in serum than in plasma; during oral anticoagulation this difference is reduced. Plasma and serum of 172 patients taking vitamin K antagonists were tested for AT III antigen and both AT III heparin cofactor and anti-Xa heparin cofactor. Crossed immunoelectrophoresis of AT III on heparin-agarose was also carried out in plasma and serum. The patients were divided into four groups: (1) international normalized ratio (INR) 9.3-4.1, n = 25; (2) INR 4.0-2.5, n = 73; (3) INR 2.4-2.0, n = 40, and (4) INR 1.9-1.5, n = 34. 66 healthy subjects were used as controls. Plasma levels of AT III antigen, AT III heparin cofactor, and anti-Xa heparin cofactor were the same in all groups. In all groups all serum AT III parameters were higher than in controls; crossed immunoelectrophoresis of AT III on heparin-agarose indicated that this finding was due to a lower formation of complexed AT III in serum. AT III heparin cofactor serum values were the same whatever the INR over a large range (9.3-1.5); the highest anti-Xa heparin cofactor serum levels were noted in the groups treated more intensely (groups 1 and 2).

Beta-thromboglobulin in patients with acute and chronic coronary artery disease.

Beta-thromboglobulin (beta TG) plasma levels were measured by radioimmunoassay in 14 patients with acute myocardial infarction (MI), in 13 with myocardial ischemia and recurrent episodes of angina and in 14 subjects with a past history of MI. Increased beta TG plasma values were observed in patients with acute MI and with myocardial ischemia whereas subjects with a past history of MI showed results not significantly different from normal subjects. Daily measurements in acute MI showed in five cases a second peak of beta TG values which suggests the occurrence of a deep vein thrombosis. The increased platelet consumption in MI was not related with the extent of the necrosis. We suggest, therefore, that platelet activation is associated with myocardial ischemia rather than necrosis.

Platelet antibody determination by platelet factor 3 assay (comparison with radiolabelled serotonin release and platelet aggregometry).

Platelet antibody determination by the PF3 test was carried out in 96 thrombocytopenic patients with various disorders, 31 repeatedly transfused patients with or without thrombocytopenia and 24 patients with autoimmune disease (SLE and myasthenia gravis) without thrombocytopenia. The frequency of a positive test was greatest in the patients with ITP (61%), SLE (50%) or a history of numerous blood transfusions (60%). The patients with myasthenia gravis also showed a considerable frequency (20%) of platelet antibodies detectable by the PF3 test. The PF3 test is less sensitive than the serotonin release test in detecting autoantibodies, but it is more sensitive than aggregometry in detecting isoantibodies and drug-related antibodies.

Circulating anticoagulant against factor XI and thrombocytopenia with platelet aggregation inhibition in systemic lupus erythematosus.

In a patient with systemic lupus erythematosus, anticoagulant activity directed against factor XI was found together with thrombocytopenia. In the serum globulin fraction, antiplatelet antibodies and an activity-inhibiting platelet aggregation could also be found. A possible correlation between the inhibition of platelet aggregation and the anticoagulant activity directed against factor XI is discussed.

Pretreatment with heparin in thrombolytic therapy with Urokinase. Heparin-urokinase therapy.

Initially, we administered urokinase to five patients according to the following schedule: 500,000 CTA U during the first 10 min, then 250,000 CTA U/h for 12 h. Using this modality, we noted the appearance, during the first hours of treatment, of hypercoagulability. We then choose to modify the schedule by pretreatment with 7,500 U. i.v. of heparin, followed promptly by 250,000 CTA U/h of urokinase (without a loading dose). This obviate the appearance of hypercoagulability without reducing the fibrinolytic effect of treatment and without producing hemorrhagic complications.