The effect of ticlopidine on platelet function in normal volunteers and in patients with platelet hyperaggregability in vitro.
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Biomedical subjects
Publications and source records attributed to J Gormsen.
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Fibrinolytic activity and capacity were studied in a group of 18 patients with sudden sensorineural hearing loss of unknown etiology. The fibrinolytic activity and capacity were found reduced in 12 patients. No distinct changes in platelet aggregation in vitro could be demonstrated. Further, repeated studies in this category of patients should be performed.
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Thirty-eight patients with juvenile diabetes mellitus, aged 21-77, were tested for platelet aggregation in vitro. Vascular complications were found in 20 patients with diabetic retinopathy in 16 of these. All patients received their usual dose of insulin in the morning on the day of the examinations, where were carried out shortly before a 2--3 hours after lunch. Ninety normal controls were tested at the same time of day. The aggregation was estimated turbidometrically and defined by the threshold concentration of adenosine diphosphate or adrenaline that produced a secondary aggregation with a light transmission not less than 80% of that given by the platelet-poor plasma. No significant differences could be demonstrated in platelet aggregation between the normal controls and the patients with diabetes mellitus or any subgroup of these. No correlation was found between the threshold concentrations and the plasma levels of glucose or beta-hydroxybutyric acid.
Forty-two patients, mean age 68 years, with severe leg ischaemia were randomly treated with placebo or by controlled defibrination with ancrod for 3 weeks. Plasma fibrinogen concentration was kept at about 20% of normal in the ancrod treated group. The two groups proved to be well matched regarding factors which could affect the degree of ischaemia. Objective measurements showed a significant rise in ankle and toe systolic blood pressure in the ancrod group lasting for 3 months. There was no rise in distal blood pressure in the control group. In the ancrod treated group the toe and ankle systolic pressures rose about 8 mmHg, but this was not accompanied by an improvement in the clinical course.
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ADP-induced platelet aggregation in vitro has been studied in 90 normal controls and in 30 patients with ischemic heart disease (IHD) and 22 with peripheral thromboatherosclerosis (PTA). The sensitivity to ADP was defined by the threshold concentration which produced secondary aggregation with an amplitude corresponding to not less than 80% of the transmission obtained by platelet-poor plasma. In the normal controls the threshold concentration was significantly lower in women aged 50 or more than in women under that age. The geometric means were lower in the patients than in the controls. Significantly lower threshold concentrations than in the corresponding age groups of controls were found in the following age groups of patients: Men and women greater than or equal to 50 years with IHD (p less than 0.005 and p less than 0.001, respectively), men and women under 50 with IHD (p less than 0.05). Men and women greater than or equal to 50 years with PTA (p less than 0.002 and p less than 0.01, respectively), men and women under 50 with PTA (p less than 0.005).
In a consecutive series of 11 young patients with clinical evidence of cerebral infarction, platelet function and plasma lipid levels were examined. The results show that increased platelet aggregability characterizes the patient group as a whole. Hyperlipidemia was frequently found, and the number of heavy smokers was high. It is suggested that all younger patients with cerebrovascular disease are examined with regard to these presumed risk factors.
The present study was performed in 34 patients with transient cerebral ischemia, TCI. Twenty-four of the patients were examined angiographically. Atherosclerotic abnormalities were demonstrated in 13 and a total occlusion of the interior carotid artery was found in one patient. The angiograms were normal in 10 patients. One patient suffered from hyperlipoproteinemia, type IV, and one from diabetes mellitus. The platelet aggregation in vitro was increased significantly, as more patients than normal controls showed secondary aggregation with low ADP-concentration: less than or equal to 1 mumol (p less than 0.001). The fibrinolytic capacity was significantly reduced (p less than 0.01) but not particularly in the patients with increased tendency for platelet aggregation. No correlation found between changes in platelet aggregation, the fibrinolytic activity and the angiographic findings. The results described may favor the concept that a prophylactic use of drug excerting an antiaggregation effect on platelets might be useful in patients suffering from TCI.
56 patients undergoing elective major surgery received low dose heparin prophylaxis, 5,000 IU 2 h before surgery and every 8 h for 7 days. The patients were tested by the 125I-fibrinogen uptake test, which, if positive, was controlled by venography. The heparin concentrations were measured by the method of DENSON and BONNAR and by the chromogenic method of TEIEN et al. in blood samples drained immediately before and after surgery and on the 1st and 5th postoperative day 2 and 4h after the injection of heparin. The values were found higher when estimated by the method of DENSON and BONNAR than by the chromogenic method. Deep vein thrombosis (DVT) developed in 11 patients, and in 10 of them within the first 48 after the operative procedure, in 1 after 4 days. The preoperative values were not lower in the patients who developed DVT, and the heparin concentrations found on the 1st and 5th postoperative day were at the same level as in those who did not develop DVT.