[Still unnecessary dosage errors in the administration of insulin].
Explore the source record for details and available documents.
Drug Information Services↗
Biomedical subjects
L Tengborn
Publications and source records attributed to L Tengborn.
Regional fibrinolysis following total hip replacement.
The local effect of operative trauma on the fibrinolytic system was studied in ten patients undergoing total hip replacement. Catheters were inserted in the femoral veins on both sides and blood was sampled from these catheters perioperatively. The following fibrinolytic variables were analysed in plasma and related to the different steps of surgery: tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor (PAI-1) activity. During surgery PAI-1 activity and t-PA antigen in the operated limb were significantly increased compared with preoperative values. There was a significant difference in PAI-1 activity and t-PA antigen between the operated and the non-operated limbs during surgery and within one hour postoperatively. During fixation of the femoral implant there was a significant difference between the operated and the non-operated limbs in t-PA activity. Thus the regional fibrinolytic response to trauma was dissociated from the response in the non-operated limb. The clinical relevance of the observed alterations in regional fibrinolysis, as related to thrombogenic mechanisms after hip surgery, remains to be elucidated.
Aged↗
The acute effect of insulin on tissue plasminogen activator and plasminogen activator inhibitor in man.
The present study was performed to elucidate the acute effect of insulin on levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor of endothelial cell type (PAI-1). Nine middle-aged, non-obese and non-smoking men were studied during a hyperinsulinemic, euglycemic glucose clamp for 2 h. Plasma insulin level during the clamp averaged 84 +/- 12 mU/l and euglycemia was maintained at 4.9 +/- 0.6 mmol/l. The t-PA activity gradually increased (75% mean increase after 2 h, p less than 0.001) and the PAI-1 activity decreased (49% mean decrease after 2 h, p less than 0.001) during the clamp. t-PA activity decreased and PAI-1 activity increased after the insulin infusion was ceased, but they were still 48% higher and 38% lower, respectively, after 60 min. PAI-1 and t-PA activities were not affected by saline infusion for 2 h. Thus, acute changes in the insulin levels lead to rapid alterations in the fibrinolytic system even when euglycemia is maintained. These effects may be induced by insulin itself or by the concomitant activation of the sympatho-adrenal system during the euglycemic clamp.
Blood Glucose↗
Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors.
Insulin resistance and hyperinsulinaemia may play an important role in both the development of hypertension and its accompanying metabolic aberrations. In order to investigate this possibility, nine non-obese, non-diabetic, non-smoking, middle-aged men with untreated hypertension were treated with metformin 850 mg b.i.d. for 6 weeks as a pilot study and within-patient comparison. Metformin decreased total and LDL-cholesterol (P less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P less than 0.001). Tissue plasminogen activator (t-PA) activity increased (P less than 0.02), and t-PA antigen decreased (P less than 0.01), whereas plasminogen activator inhibitor (PAI-1) and fibrinogen were unaffected by metformin treatment. Body weight remained unchanged. Withdrawal of metformin was associated with the return of both blood pressure and metabolism towards the initial levels. In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects. These results support the view that insulin resistance plays a role in hypertension, and may open up a new field for the alleviation of abnormalities associated with cardiovascular disease.
Blood Glucose↗
von Willebrand factor antigen and plasminogen activator inhibitor in giant cell arteritis.
Sixty three patients (51 women, 12 men) with giant cell arteritis were studied by serial analyses of von Willebrand factor antigen (vWF: Ag) concentration and plasminogen activator inhibitor activity. Their mean age at the time of diagnosis was 71 years. Two hundred and one randomly selected subjects from the general population, aged 75 years, served as controls. The mean concentration of vWF:Ag in the patients with giant cell arteritis before the start of corticosteroid treatment was 2.63 (SD 1.35) IU/ml compared with 1.71 (0.69) IU/ml in the general population. The vWF:Ag concentration slowly decreased and reached the control range about 18 months after the diagnosis. The vWF:Ag did not correlate with the clinical group of giant cell arteritis nor with the results of temporal artery biopsy. Flare ups and vascular complications were not indicated by the vWF:Ag. Plasminogen activator inhibitor activity in the patients was not significantly different from that of the general population at any time. It was concluded that the determination of vWF:Ag and plasminogen activator inhibitor activity is of limited clinical value in the diagnosis, prognosis, and monitoring of steroid treatment in patients with giant cell arteritis.
Aged↗
Plasma homocysteine in venous thromboembolism.
Severe hyperhomocysteinemia due to inborn errors of methionine metabolism results in precocious development of arteriosclerosis and predisposition to venous and arterial thromboembolism. Although the findings of several studies have indicated that mild hyperhomocysteinemia is common in occlusive arterial disease, no similar studies have been made on venous thromboembolism. In this study of subjects under 50 years of age, we found no significant differences in the plasma homocysteine concentrations, either in the fasting state or after methionine loading, between 42 patients with venous thromboembolism and 42 healthy controls. Nonetheless, male patients manifested a tendency toward higher homocysteine concentrations than male controls; 6 patients (14%) versus 2 controls (5%) responded abnormally to methionine loading which might indicate heterozygosity for cystathionine synthase deficiency. Thus, further studies on plasma homocysteine in venous thromboembolism are warranted.
Adult↗
Prevention of deep-vein thrombosis and pulmonary embolism after total hip replacement. Comparison of low-molecular-weight heparin and unfractionated heparin.
In a prospective, randomized, double-blind study, the efficacy and safety of a low-molecular-weight heparin were compared with those of unfractionated sodium heparin (standard heparin) in 136 patients who had elective total hip replacement. The patients received subcutaneous injection of either 5000 international units of low-molecular-weight heparin once daily or 5000 international units of standard heparin three times a day. Treatment with low-molecular-weight heparin began twelve hours before the operation, and treatment with standard heparin began two hours preoperatively; both regimens were continued for ten days. Twelve days postoperatively, bilateral ascending phlebography was performed in 122 patients, sixty-three in the treatment group that received low-molecular-weight heparin and fifty-nine in the treatment group that received standard heparin. Pulmonary scintigraphy was performed in 127 patients. Deep-vein thrombosis was diagnosed in forty-four patients: nineteen (30 per cent) of the sixty-three who received low-molecular-weight heparin and twenty-five (42 per cent) of the fifty-nine who received standard heparin. All but four patients, two from each treatment group, were asymptomatic. The difference in the total rate of thrombosis in the two groups was not significant (p = 0.189). However, thrombosis occurred in the thigh in only six (10 per cent) of the patients who received low-molecular-weight heparin but in eighteen (31 per cent) of those who received standard heparin, a significant difference (p = 0.011). Pulmonary embolism was detected in twenty-seven patients: eight (12.3 per cent) of those who received low-molecular-weight heparin and nineteen (30.6 per cent) of those who received standard heparin. Only three patients had clinical signs of embolism. Pulmonary embolism was significantly more frequent in the group that received standard heparin (p = 0.016). Total loss of blood and the total amount of blood that was transfused were significantly reduced in the patients who received low-molecular-weight heparin compared with those who received standard heparin. Prophylaxis was not discontinued because of hemorrhage in any patient. The efficacy of low-molecular-weight heparin was superior to that of standard heparin in the prevention of femoral thrombosis and pulmonary embolism, although the over-all incidence of deep-vein thrombosis was not statistically different.(ABSTRACT TRUNCATED AT 400 WORDS)
Aged↗
Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-1.
Recent epidemiologic studies have shown that abdominal obesity, characterized by a high waist to hip circumference ratio (WHR), is associated with increased cardiovascular morbidity and mortality. The present study examines components of the fibrinolytic system in obese and lean middle-aged women with a high and low WHR. Ten women in each group were carefully matched with respect to age, body weight, lean body mass, and body fat. Fibrinogen and endothelial type of plasminogen activator inhibitor -1 (PAI-1) were significantly elevated in the obese women with a high WHR compared with the obese women with a low WHR or with both groups of lean women. In addition, obese women with a high WHR exhibited a greater metabolic risk profile (elevated glucose, insulin, and triglyceride levels). When all subjects were pooled for the analyses, both fibrinogen and PAI-1 levels correlated positively with glucose and insulin levels. PAI-1 was also negatively related to degree of insulin sensitivity measured with the euglycemic clamp technique. In the obese groups, WHR but not body mass index (BMI), correlated with PAI-1 levels. No such correlations were seen in the lean groups. In conclusion, the data show that a high WHR in obese, but not lean middle-aged women, is associated with an impaired fibrinolytic activity. This perturbation becomes enhanced when it is associated with hyperinsulinemia and insulin resistance, which is a typical feature of abdominal obesity.
Cardiovascular Diseases↗
Elevated fibrinogen and plasminogen activator inhibitor (PAI-1) in hypertension are related to metabolic risk factors for cardiovascular disease.
The relationship between hypertension, glucose metabolism, fibrinogen and plasminogen activator inhibitor of endothelial cell type (PAI-1) was studied under conditions in which the influence of obesity and adipose tissue distribution (waist/hip ratio) were controlled. Twenty-two non-obese, middle-aged men with normal blood pressure (n = 11) and untreated mild hypertension (n = 11), respectively, participated in the study. Cholesterol, triglyceride and insulin levels were higher in hypertensive men than in the control group. Glucose disposal was studied as an indicator of insulin sensitivity using the euglycaemic clamp technique. The insulin effect tended to be less marked in men with hypertension. PAI-1 was higher in hypertensive men compared to the controls. A strong positive correlation was observed between PAI-1 and insulin levels as well as blood pressure. PAI-1 and fibrinogen levels correlated negatively with the rate of glucose disposal. Thus, even in these non-obese and mildly hypertensive individuals, an enhanced metabolic risk factor profile for cardiovascular disease was found. The metabolic aberrations were related to elevated fibrinogen and PAI-1 levels which, in turn, increase the risk of thrombus formation.
Anthropometry↗
Effects of desmopressin acetate on platelet aggregation, von Willebrand factor, and blood loss after cardiac surgery with extracorporeal circulation.
The effects of desmopressin acetate (DDAVP) on platelet aggregation and the von Willebrand factor antigen (vWF:Ag) were studied in 19 patients undergoing cardiac surgery with extracorporeal circulation. The patients represented one of five blocks in a randomized double-blind placebo-controlled parallel group trial on the effects of DDAVP on postoperative bleeding after uncomplicated coronary artery bypass operations. After termination of extra-corporeal circulation, DDAVP (0.3 microgram/kg body wt) or its vehicle was infused into a peripheral vein throughout 15 minutes. The increase in factor VIII coagulant activity after infusion did not differ between the groups but there was a significantly larger increase in vWF:Ag levels in DDAVP-treated patients. The aggregatory response to adenosine-diphosphate (ADP) and ristocetin showed a normal pattern and was not significantly different between the two groups. As compared with placebo, DDAVP did not decrease the bleeding time or the postoperative blood loss. We conclude that DDAVP causes an increase in vWF:Ag levels but does not alter platelet aggregation, bleeding time, or blood loss in uncomplicated coronary artery bypass patients.
Coronary Artery Bypass↗
Intraoperative collection of shed blood with citrated compresses for autotransfusion. An experimental study in pigs.
Six pigs were used to study whether the collection of shed blood by means of surgical compresses instead of suction traumatizes such blood. In an in vivo part of the study, the whole blood volume of the pigs was retransfused after treatment with citrated compresses, and in an in vitro part the blood was treated extensively with compresses and analyzed. All animals survived, with a minor fall in hemoglobin after 48 hours and a rise in serum citrate concentration at the end of the experiment. A study of the coagulation system revealed no important change after retransfusion of compress-treated blood. In the in vitro part of the study, repeatedly squeezing blood from the compresses increased the concentration of free hemoglobin to a maximum of 5 g/l after ten squeezes, whereas platelets were numerically unchanged. The study indicates that collecting shed blood by means of surgical compresses may be a safe and efficient method.
Animals↗
Changes of plasma coagulation and fibrinolysis in response to mental stress.
To study the effects of standardized mental stress (arithmetic and the Stroop color word test) on plasma coagulation and fibrinolysis, blood samples were obtained before, during, and after 20 minutes of mental stress from 10 healthy, non-smoking young males aged 22 to 30 years. Reactions were compared with those observed during physical exercise and infusion of adrenaline. Both von Willebrand factor antigen and factor VIII coagulant activity increased significantly in response to mental stress (95 +/- 28 vs 123 +/- 56%; p less than 0.05 and 125 +/- 54 vs 217 +/- 170%; p less than 0.05, respectively). There was also a significant increase of factor VII coagulant activity (86 +/- 31 vs 108 +/- 51%; p less than 0.05). Furthermore, mental stress caused an activation of the fibrinolytic system with an elevation of tissue plasminogen activator activity and tissue plasminogen activator antigen (0.80 +/- 0.48 vs 1.23 +/- 0.96 IU/ml; p = 0.076 and 4.38 +/- 1.87 vs 5.78 +/- 2.58 IU/ml; p less than 0.01). Fibrinogen concentration increased during stress (1.95 +/- 0.29 vs 2.11 +/- 0.27 g/l; p less than 0.05). Similar but more pronounced responses were observed during exercise and adrenaline infusion. Parallel to the increases in coagulation and fibrinolytic factors there were significant increases in heart rate, and systolic and diastolic blood pressure. It is concluded that mental stress has significant effects on plasma coagulation and fibrinolysis, and that it could thus affect important risk factors for cardiovascular disease.
Adult↗
The effect of various anticoagulant/antiplatelet mixtures on determination of plasminogen activator inhibitor, platelet proteins and hemostasis parameters.
Blood collected in different anticoagulant/antiplatelet agents (ETP, EDTA, citrate, citrate/citric acid pH 4.5 and CTAD) was compared with respect to determination of PAI-1 activity and PAI-1 antigen. beta TG and PF4 were analysed as markers of platelet release. Both the middle layer and the remaining layer of the plasma were studied. Moreover vWF:Ag, FVII:Ag, ECLT, t-PA:Ag, t-PA activity, APTT, VIII:C and VII:C were assayed in blood collected in citrate and CTAD. PAI-1 activity showed the same level in all citrate based anticoagulants and ETP and no increase was found in blood standing for 2 hours at room temperature. On the contrary quick handling was most important for determination of PAI-1 antigen. In tubes anticoagulated with citrate no significant increase was found if the sample was prepared within 1 hour. EDTA was not suitable as anticoagulant mixture. Tubes containing the antiplatelet mixture CTAD could be used for determination of PAI activity, PAI antigen, vWF:Ag, FVII:Ag, t-PA activity and APTT. For measurement of PAI-1 antigen quick handling of blood anticoagulated with antiplatelet mixtures are preferable, and plasma treated in that manner could also be used to assay some hemostasis parameters.
Anticoagulants↗
Homocysteine, factor VII and antithrombin III in subjects with different gene dosage for cystathionine beta-synthase.
Cystathionine beta-synthase deficiency results in severe homocysteinaemia, precocious arteriosclerosis and frequent thromboembolism. In addition, antithrombin III activity and factor VII are low. Arteriosclerosis seems to be increased in heterozygotes as well (cystathionine beta-synthase gene dosage 50%) but rare in Down syndrome (cystathionine beta-synthase gene dosage 150%). In the present study total plasma homocysteine was high in three homozygotes, slightly increased in 20 obligate heterozygotes but not reduced in nine subjects with Down syndrome when compared to controls. After methionine loading, increases of homocysteine were pathologically high in 14 of 20 heterozygotes but was not, as expected, low in subjects with Down syndrome. Antithrombin III activity and factor VII antigen tended to be low in homozygotes but were normal in heterozygotes. In Down syndrome antithrombin III activity was reduced and factor VII antigen normal. There were no correlations between levels of homocysteine, antithrombin III activity and factor VII antigen. Thus, subjects with Down syndrome seem not to exhibit the expected gene dosage effect on homocysteine metabolism which could explain their reduced proneness to develop arteriosclerosis, nor do antithrombin III activity or factor VII antigen seem to be related to homocysteine metabolism.
Antithrombin III↗
Recurrent thromboembolism in pregnancy and puerperium. Is there a need for thromboprophylaxis?
By sending a questionnaire (response rate 93%) to 321 women with a history of venous thromboembolism and previous coagulation tests, 72 patients were identified who had a total of 87 pregnancies after the thromboembolic episode. The main aim of the study was to analyze the influence of prophylaxis during pregnancy and delivery on the development of further thromboembolic complications. During pregnancy there was no difference in frequency of thromboses between the group given prophylaxis (n = 20) and the group not receiving it (n = 67). At delivery the frequency of thrombosis was 5.3% among the 57 women given prophylaxis and 11.1% among the 30 without prophylaxis, a difference that is not significant. The implication of these findings is discussed both concerning the indications for giving prophylaxis and concerning the problem of designing relevant prophylactic trials.
Female↗
Clinical experience with human plasma-derived factor VIIa in patients with hemophilia A and high titer inhibitors.
FVIIa purified from human plasma and spontaneously activated during the purification procedure was given to 4 patients with hemophilia A and inhibitors against FVIII:C in association with joint bleeds. A dose of 9-20 micrograms/kg b.w. (700-1,000 U/kg b.w.) seemed to be hemostatically active in moderate to severe joint bleeds. Plasma levels of FVII of 5-7 U/ml were achieved and recoveries varied between 17 and 66%. The lower recovery rates of 17-39% were all found in 1 of the patients. No immediate side effects were seen. Neither were any signs of a systemic activation of the coagulation system observed. It is concluded that highly purified FVIIa may be useful in the treatment of hemophilia A patients with inhibitors against FVIII:C.
Adult↗
Antithrombin III molecular variants with defective binding to heparin or to serine proteases: evidence of two different abnormal patterns identified by crossed immunoelectrofocusing.
Molecular heterogeneity of antithrombin III (AT III) was investigated by a technique of crossed immunoelectrofocusing (CIEF) in plasma samples of patients from 16 families with AT III congenital defect, including 8 AT III molecular variants. The AT III CIEF pattern was normal in all the patients with AT III quantitative deficiency, showing a balanced decrease of all the peaks. Out of the 8 AT III variants investigated, 6 had an abnormal pattern: the three variants with defective binding to heparin (AT III Roma, AT III Barcelona, AT III Malmö) shared a similar abnormal pattern; three variants with defective binding to serine proteases (AT III Pescara, AT III Milano, AT III Tampere) had a common abnormal pattern clearly different from the first one, whereas the other two variants deficient in the inactivation of the serine proteases (AT III Chicago, AT III Milano 2) showed a normal pattern. The first type of pathological pattern (type Roma) was characterized by the presence of an abnormal peak overlapping the normal isoforms present at pH 4.8-4.6 and by an additional peak at pH 4.5. The second type of pattern (type Pescara) showed an additional peak at pH 4.5 and an abnormal quantitative distribution of the isoantithrombins all throughout the pH range (5.2-4.6). In order to separate the abnormal AT III fraction from the normal one, plasma of a patient with Roma defect and serum of a patient with Pescara defect were passed throughout an heparin-ultrogel column.(ABSTRACT TRUNCATED AT 250 WORDS)
Antithrombin III↗
[Examination of blood coagulation and fibrinolysis in patients with increased tendency to thrombosis].
Explore the source record for details and available documents.
Blood Coagulation Tests↗