Guidelines on preparation, certification, and use of certified plasmas for ISI calibration and INR determination--a rebuttal.
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Calibration↗
Biomedical subjects
N Egberg
Publications and source records attributed to N Egberg.
Haemostatic complications in haemodialysis patients: effect of type of vascular access and dialysis filter.
Impaired haemostasis is common in patients with end-stage renal disease, and may cause either thrombotic or bleeding complications. The purpose of this study was to assess whether plasma markers of coagulation activation in patients undergoing chronic haemodialysis (HD) can identify high-risk individuals, and to test the relevancy of type of vascular access or dialysis filter. We measured plasma levels of prothrombin fragment 1+2, fibrin D-dimers and tissue factor in 82 HD patients before and after dialysis. Clinical endpoints during the year following blood sampling were thrombosis in blood access, changes in blood access, other thromboembolic events, bleeding complications, ischaemic vascular disease, or death. We found elevated baseline levels of all three parameters in HD patients, compared to normal reference ranges. Plasma levels of all parameters (particularly fibrin D-dimers) were significantly higher in patients with prosthetic grafts and central venous dialysis catheters than in patients with native vessels. Patients with AV-fistulas or grafts who had bleeding complications (n=7) had significantly higher plasma levels of fibrin D-dimer and prothrombin fragment 1+2. Bleeding complications also occurred more frequently among the patients with prosthetic grafts (3/18) or central venous dialysis catheters (3/11) compared with those with grafts from native vessels (1/53). Other than a bleeding tendency, our data do no show any correlation between coagulation parameters and other clinical complications during haemodialysis. In conclusion, we found elevated plasma levels of markers of coagulation activation among HD patients. High levels of D-dimers and prothrombin fragment 1+2 correlated to bleeding diathesis instead of thromboembolism, and this tendency was most pronounced in patients with prosthetic grafts.
Aged↗
European Concerted Action on Anticoagulation (ECAA): multicentre international sensitivity index calibration of two types of point-of-care prothrombin time monitor systems.
A multicentre modified World Health Organization (WHO)-type international sensitivity index (ISI) calibration has been performed at 10 European Concerted Action on Anticoagulation (ECAA) national laboratories using non-citrated whole-blood on two point-of-care test (POCT) prothrombin time (PT) monitor systems, CoaguChek Mini and TAS PT-NC, using single lots of test cards/strips. The relevant species (human and rabbit) WHO international reference preparations (IRPs) were tested with the manual PT technique on citrated plasma from the same blood donations. The ISI was calculated from the slope of the orthogonal regression line relating log PT (POCT) to log PT (IRP). The mean ISI of the CoaguChek Mini system was 1.75 and 1.13 with the prothrombin time non-citrated Thrombolytic Assessment System (TAS PT-NC). With the CoaguChek Mini system, seven out of 10 calibrations exceeded the current 3% WHO recommended limit for the coefficient of variation (CV) of the slope with conventional PT testing, whereas with the TAS PT-NC system, it was eight out of 10. All the POCT calibrations had a CV of the slope <5%. It is suggested that this level of precision be adopted as the limit of acceptability of calibration of these monitor systems. In these circumstances, the modified WHO-type ISI calibration appeared to be satisfactory for the POCT whole-blood monitors.
Animals↗
Increases in circulating levels of monocyte-platelet and neutrophil-platelet complexes following hip arthroplasty.
Platelets and leucocytes are important effector cells of the haemostatic and inflammatory responses to tissue injury. To investigate the effects of surgical trauma on platelet activation (assessed by measuring levels of P-selectin and beta-thromboglobulin), leucocyte activation (CD11b expression) and leucocyte-platelet interactions (leucocyte-platelet complexes), 30 patients undergoing primary hip arthroplasty were studied before and at the end of surgery, and on days 1 and 10 post-operatively, using a whole-blood flow cytometry assay. The inflammatory response was followed by measurement of the levels of C-reactive protein and interleukin-6 in plasma, and the activation of coagulation was monitored by determination of prothrombin fragment 1+2 levels. On day 1 post-operatively a significantly increased expression of CD11b on monocytes was noted, but no direct correlation was found between monocyte activation and interleukin-6 production or C-reactive protein at this time point. The percentage of monocyte-platelet and neutrophil-platelet complexes was markedly increased on day 10 post-operatively compared with pre-operative levels, and levels of these complexes were significantly positively correlated with beta-thromboglobulin levels. Activation of coagulation (prothrombin fragment 1+2) on day 10 post-operatively was positively correlated with the extent of surgical trauma (duration of surgery, amount of blood loss) and with the increase in platelet activation (beta-thromboglobulin). In conclusion, hip arthroplasty induces platelet and coagulation activation, and also an inflammatory response that is maintained for more than 10 days post-operatively. This indicates an interaction between the immune and the haemostatic systems in the post-operative phase after hip arthroplasty.
Aged↗
[New in vitro analysis tested: bleeding time is still the best method for evaluation of primary hemostasis].
The need is great for a simple, cheap and readily accessible method for the evaluation of primary hemostasis in work-ups at both out-patient clinics and units caring for surgical or intensive care patients. PFA-100 is a recently introduced instrument for in vitro testing of platelet function. We report experiences from Stockholm, Gothenburg and Malmo of PFA-100 measurements performed on samples from healthy controls and from patients with von Willebrand disease or platelet disorders. It is shown that the PFA-100 system has a high sensitivity for von Willebrands disease, while the sensitivity for hereditary platelet dysfunction is low. In its present design this new device could not replace the template bleeding time as a screening test for primary hemostasis.
Bleeding Time↗
Platelet storage in PAS-2 or autologous plasma: impact on functional parameters.
Currently, several platelet additive solutions for long-term platelet storage have been introduced. The aim of this study was to compare the deterioration of functional status of platelets stored for up to 5 days in autologous plasma (AP) only, with platelet stored in PAS-2, a salt solution containing acetate, citrate and sodium chloride. Change in platelet adhesion, aggregation and activation was measured by flow cytometric technique. In addition, beta-Thromboglobulin (beta-TG), lactate and glucose were determined. After 5 days of storage, the expression of P-Selectin was significantly higher, the production of lactate and the consumption of glucose were significantly lower, in platelets stored in PAS-2 than in autologous plasma. No significant differences were detected on day 5 between the two groups with regard to fibrinogen, von Willebrand factor binding capacity, or to beta-TG release. It can be concluded that neither storage medium was consistently better for the parameters tested. However, it must be emphasized that platelets stored in autologous plasma exhibited less lesion, in terms of P-Selectin expression compared with platelets stored in PAS-2.
Acetates↗
Coagulation system activity before coronary artery bypass surgery for unstable angina.
OBJECTIVE: To measure coagulation activity immediately prior to coronary artery bypass surgery. Previous reports have shown that a hypercoagulable state and reduced fibrinolytic activity increase the risk of postoperative graft failure. DESIGN: Fifty patients with unstable angina and ongoing low-molecular-weight heparin antithrombotic treatment for a median of 4 days and 25 stable patients undergoing elective surgery were included. RESULTS: Antithrombin levels were significantly lower whereas fibrinogen and plasminogen activator inhibitor-1 levels were higher in the unstable patients than in the stable patients. Median preoperative levels of thrombin-antithrombin complex (TAT), prothrombin fragment1+2 (F1+2), fibrin D-dimers and beta-thromboglobulin did not differ significantly in unstable and stable patients. There were signs of activated coagulation with elevated levels of TAT and F1+2 before the operation in half of the unstable patients, who had had chest pain at rest within 48 h preceding the operation and also in one-third of patients undergoing elective surgery. CONCLUSION: A hypercoagulable state may be present in unstable as well as in stable angina pectoris patients accepted for coronary artery bypass surgery.
Adult↗
Thrombin inhibitors suppress the thrombin-thrombomodulin-mediated generation of activated protein C.
In the treatment of unstable coronary artery disease, direct thrombin inhibitors have shown no or only limited benefit as compared with heparin, despite theoretical advantages. One explanation may be that the direct thrombin inhibitors to a greater extent than heparin have an inhibiting effect on the generation and activity of activated protein C. In the present study, this hypothesis was tested in an in vitro, "purified" system, where human protein C underwent activation to activated protein C by the thrombin-thrombomodulin complex. Direct thrombin inhibitors, inogatran and hirudin, unfractionated heparin+antithrombin, or dalteparin+antithrombin, were added to the system before activation to evaluate their inhibitory effect on the generation of activated protein C. At inhibitor concentrations well below the achieved plasma levels in major clinical trials, the thrombin-thrombomodulin-mediated activation of protein C was inhibited by all the studied inhibitors in a dose-dependent manner, but, contrary to our hypothesis, to a greater extent by unfractionated heparin+antithrombin and dalteparin+antithrombin than by the direct thrombin inhibitors, hirudin and inogatran. Despite difficulties to draw conclusions for the in vivo situation, the in vitro inhibition, by all studied inhibitors, of the generation of activated protein C, found in this study may be a possible explanation for ongoing cardiovascular events despite adequate treatment with thrombin inhibitors, in patients with unstable coronary artery disease. This inhibition of the generation of activated protein C may also contribute to the rebound in cardiovascular events after withdrawal of effective antithrombotic treatment.
Antithrombins↗
[Coordinated Swedish transfer is recommended during 1999. Prothrombin complex measurement should be indicated as a quota, not percent].
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Anticoagulants↗
The effect of a low molecular mass thrombin inhibitor, inogatran, and heparin on thrombin generation and fibrin turnover in patients with unstable coronary artery disease.
AIM: This study evaluated a novel specific thrombin inhibitor, inogatran, in comparison with unfractionated heparin, with regard to markers for coagulation activity in patients with unstable coronary artery disease. METHODS AND RESULTS: In the Thrombin Inhibition In Myocardial Ischaemia (TRIM) study patients were randomized to one of three different doses of inogatran or to unfractionated heparin, given intravenously over 72 h. In a subpopulation of 320 patients, markers for coagulation activity were measured at baseline, during and after the study infusion. Prothrombin fragment 1 + 2, indicating thrombin generation, decreased in the low, medium and high dose inogatran groups and in the heparin group during the first 6 h of treatment by 12%, 15%, 21% and 26%, respectively. From 6 h to 72 h after the start of infusion the levels changed by -7%, -6%, -4% and +34%, respectively. The increase in the heparin group continued after the infusion was stopped. Thrombin-antithrombin complex, also indicating thrombin generation, decreased by 0%, 2%, 18% and 22%, respectively, during the first 6 h of treatment. During the same period soluble fibrin, an intermediate in fibrin formation, increased both in the low and medium inogatran group by 9%, while a decrease by 4% and 18%, respectively, was seen in the high dose inogatran group and in the heparin group. Fibrin dissolution, as measured by fibrin D-dimer, decreased during the first 24 h of treatment by 20%, 18%, 18% and 20%, respectively. The first 24 h after discontinuation of infusion, fibrin D-dimer increased by 6%, 23%, 25% and 44%, respectively. After 72 h, at the end of infusion, patients treated with inogatran, to a larger extent than those given heparin, had suffered from death, myocardial infarction or refractory angina pectoris. After 7 days this trend was less marked. CONCLUSION: The more pronounced decrease in thrombin generation and fibrin turnover during the first 6 h of infusion, and the later increase in thrombin generation and fibrin turnover, in the heparin group, as compared to the inogatran groups, may be related to the lower clinical event rate during infusion with heparin compared with inogatran and the recurrence of ischaemic events, early after cessation of heparin infusion.
Aged↗
Relationship between plasma fibrinogen and coronary heart disease in women.
Plasma fibrinogen is an independent risk factor for coronary heart disease (CHD) in men; however, its role in women is less clear. We examined the ability of plasma fibrinogen to predict CHD in a community-based, case-control study of women aged 65 years or younger living in the greater Stockholm area. Cases were all patients hospitalized for an acute coronary event between February 1991 and February 1994. Controls were randomly selected from the city census and were matched to cases by age and catchment area. Plasma fibrinogen was measured 3 to 6 months after hospitalization by using a fibrinogen assay based on fibrinogen polymerization time measurement. Of the 292 consecutive cases, 110 (37%) were hospitalized for an acute myocardial infarction and 182 (63%) for angina pectoris. The mean age+/-SD in both patients and controls was 56+/-7 years. Mean levels of plasma fibrinogen in patients and controls were 3.66+/-0.81 and 3.25+/-0.64 g/L (P<0.0001), respectively. The age-adjusted odds ratio (OR) for CHD in the highest versus the lowest quartile of plasma fibrinogen was 6.0 (95% confidence interval [CI], 3.5 to 10.4). After adjustment for age, cigarette smoking, body mass index, systolic blood pressure, total cholesterol, high density lipoprotein cholesterol, triglycerides, and educational level, the OR was 3.0 (95% CI, 1.6 to 5.5). Further adjustment for C-reactive protein yielded the same result. In both premenopausal and postmenopausal women, the multivariate-adjusted ORs were 7.0 (95% CI, 1.8 to 28.3) and 2.1 (95% CI, 1.0 to 4.4), respectively. These results provide evidence that plasma fibrinogen is associated with an excess risk of CHD in women.
Adult↗
Genetic effects for plasma factor VII levels independent of and in common with triglycerides.
BACKGROUND: Coagulation factor VII has been demonstrated as a potential risk factor for cardiovascular disease. Both genes and non-genetic factors are related to plasma levels of factor VII. However, the extent to which genetic effects influence variability in plasma factor VII levels is unknown. Further, increased levels of plasma factor VII are associated with serum triglycerides, yet the reason for this association is not fully understood. METHODS AND RESULTS: Quantitative genetic analyses were applied to evaluate the relative importance of genetic and different environmental influences on plasma factor VII levels and to test the significance of genetic and environmental factors in common to factor VII and triglycerides in 215 pairs of middle-aged and elderly twins, of whom 104 were reared apart and 120 were women. Genetic influences were found to account for 57% of the individual differences in plasma factor VII levels, whereas shared-rearing and residual-familial environmental factors were not significant. Furthermore, a significant genetic correlation of 0.38 was found between factor VII and triglycerides, but the environmental correlation between these two measures was not significant. Genetic factors in common to factor VII and triglycerides explain about 7% of the total variance for factor VII. CONCLUSION: The present study suggests that there are substantial genetic influences on plasma factor VII levels. Furthermore, genetic effects explain the phenotypic association between factor VII and triglycerides.
Aged↗
The risk of recurrent venous thromboembolism in carriers and non-carriers of the G1691A allele in the coagulation factor V gene and the G20210A allele in the prothrombin gene. DURAC Trial Study Group. Duration of Anticoagulation.
The results concerning the risk of recurrent venous thromboembolism (VTE) in carriers of the G1691A mutation in the coagulation factor V gene are not consistent and this risk in carriers of the G20210A polymorphism in the prothrombin gene has hitherto not been reported. We followed 534 patients for 48 months after their first episode of objectively documented VTE. The prevalence of the G1691A allele in 467 (87.5%) of the patients and in 207 controls was 25.3% and 8.2%, respectively, in heterozygote form and 2.4% and 0.5%, respectively, in homozygote form. The adjusted odds ratio (OR) for the first VTE was 4.4 (95% CI 2.6-7.8). The risk of recurrent VTE in heterozygotes was not statistically different from non-carriers (17.8% vs 17.6%), with 85% power to detect a hazard ratio of 2.35. Homozygotes had a significantly increased risk (p = 0.036) of recurrent VTE. The prevalence of the G20210A allele in 456 patients and 207 controls was 6.1% and 1.4%, respectively. The adjusted OR was 4.6 (95% CI 1.6-19.3) for the first VTE in 28 carriers of this polymorphism. The risk of recurrent VTE for these was not statistically different from non-carriers with an OR of 0.9 (95% CI 0.2-2.9).
Adolescent↗
Effects on the hemostatic system and liver function in relation to Implanon and Norplant. A prospective randomized clinical trial.
In this prospective randomized clinical trial, two long-term contraceptive implants were studied with respect to hemostasis and liver function in 86 healthy young women. The two implants used were Implanon, containing the progestagen etonogestrel (the biologically active metabolite of desogestrel) and Norplant, the implant containing the progestagen levonorgestrel. The results of the trial showed that both implants had similar small effects on the hemostatic system that are not suggestive of a tendency towards thrombosis. The effect on liver function was characterized by increases in total bilirubin and gamma-glutamyl transferase and decreases in alanine aminotransferase and aspartate aminotransferase.
Adult↗
Kinetics of bradykinin levels during and after leucocyte filtration of platelet concentrates.
OBJECTIVE: To measure bradykinin levels in platelet concentrates during and after leucocyte filtration. METHODS: Platelet concentrates were leukocyte depleted using three different leucocyte-depletion filters selected to represent filters with negative, positive or neutral charge, respectively. Bradykinin levels were analysed before, during and up to 90 min post-filtration. RESULTS: Significant levels of bradykinin were generated when negatively charged leucocyte depletion filters were used. However, we found a high variation between platelet concentrates prepared from different donors as well as within the same concentrate when this was divided into three aliquots. Generated bradykinin was rapidly degraded in the collection bag and no bradykinin was detectable 60 min post-filtration. CONCLUSION: Bradykinin generation is more pronounced when negatively charged leucocyte removal filters are used. Due to a rapid degradation of bradykinin in the storage bag, pre-storage filtration should minimise the risk of bradykinin related adverse reactions during transfusion with some filters.
Adolescent↗
Antithrombin III supplementation for patients undergoing PTCA for unstable angina pectoris. A controlled randomized double-blind pilot study.
BACKGROUND: Thrombin activation may be a higher risk for complications and restenosis after percutaneous transluminal coronary angioplasty in unstable patients than in patients with stable angina pectoris. The effects of heparin may be partly counteracted by a decrease in antithrombin (III). The primary objectives of this study were to evaluate whether a subnormal antithrombin level was associated with a hypercoagulable state and to evaluate the effects of antithrombin supplementation, before and after percutaneous transluminal coronary angioplasty, on biochemical signs of coagulation activation. Secondary objectives were to evaluate acute complications and restenosis rate at 3 months. METHODS: In a double-blind pilot study, 50 patients with unstable angina, with ongoing heparin infusion and with subnormal antithrombin levels (< 85%) were randomized to receive antithrombin supplementation or placebo. Treatment targeted to an antithrombin level of 120% was started with a 2h intravenous infusion before the percutaneous transluminal coronary angioplasty and was repeated, if there were further subnormal values, every 12th hour for 48 h. RESULTS: Angiographic success was 20/25 in the antithrombin group and 21/25 in the placebo group (ns). Abrupt closure occurred in two and one patients in the two groups, respectively. Activation of coagulation measured as elevations of prothrombin fragment 1+2, thrombin-antithrombin complexes and fibrin D-dimer was seen 2 days after the procedure. Baseline levels of fibrin D-dimer were 68 +/- 69 micrograms.l-1 in the antithrombin group vs 71 +/- 46 micrograms.l-1 in the placebo group (ns). Two days after percutaneous transluminal coronary angioplasty the levels increased to 135 +/- 103 vs 242 +/- 150 micrograms.l-1, respectively (P < 0.05 between the groups). Restenosis at 3 months occurred in 4/20 antithrombin patients and in 8/21 placebo patients (ns). CONCLUSIONS: In unstable angina patients with heparin treatment and subnormal antithrombin levels, anti-thrombin supplementation resulted in less activation of coagulation and a tendency towards less restenosis.
Angina, Unstable↗
Moderate genetic influences on plasma levels of plasminogen activator inhibitor-1 and evidence of genetic and environmental influences shared by plasminogen activator inhibitor-1, triglycerides, and body mass index.
Both genes and environmental factors have been reported to influence plasma levels of plasminogen activator inhibitor-1 (PAI-1). However, the relative importance of genetic influences (i.e., heritability) on plasma PAI-1 levels has not yet been investigated. Furthermore, PAI-1 levels are correlated with body mass index (BMI) and triglycerides. These correlations could reflect genetic and/or environmental factors in common to PAI-1, triglycerides, and BMI. We applied multivariate genetic analysis methods to assess the relative importance of genetic and environmental influences on plasma PAI-1 levels and to test the significance of genetic and/or environmental influences shared by PAI-1, triglycerides, and BMI in 217 pairs of middle-aged and elderly twins, of whom 113 pairs were reared apart and 121 pairs were women. The heritability estimate for PAI-1 levels was 42%. Individual-specific environmental factors explained 36% of the variance for PAI-1 levels. The remaining variance of PAI-1 was explained by rearing and residual-familial environmental factors. Furthermore, a genetic correlation of 1.00 between PAI-1 and triglycerides, a rearing environmental correlation of 1.00 between PAI-1 and BMI, a residual-familial environmental correlation of 1.00 between PAI-1 and triglycerides, and a genetic correlation of 0.63 between PAI-1 and BMI, were found. In conclusion, the present results suggest that genetic influences on plasma PAI-1 are moderate. Genetic and shared rearing or residual-familial environmental factors shared by PAI-1, BMI, and triglycerides explain the phenotypic association between these measures. It appears that all the genetic influences for PAI-1 are more or less shared with those for triglycerides and BMI.
Adoption↗
Nicotinic acid treatment shifts the fibrinolytic balance favourably and decreases plasma fibrinogen in hypertriglyceridaemic men.
BACKGROUND: Nicotinic acid in gram doses decreases cholesterol and triglyceride concentrations in plasma, but the effect on haemostatic function is not known. METHODS: Twenty-three men with hypertriglyceridaemia were treated with 4 g nicotinic acid daily for 6 weeks. Tests for haemostatic function and serum lipoproteins were performed before and at the end of the period of treatment. RESULTS: Treatment with nicotinic acid had the expected effect on lipoprotein concentrations: it reduced the serum concentrations of triglyceride and the three major density fractions of triglyceride (very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL)). The VLDL cholesterol concentration was reduced, but that of HDL cholesterol was increased (all P<0.0001). The lipoprotein(a) (Lp(a)) concentration decreased significantly (P<0.01). The total fibrinolytic activity was increased by nicotinic acid treatment as indicated by decreases in plasminogen activator inhibitor-1 activity from 34.3 to 23.8 U/ml (P<0.01) and in alpha2-antiplasmin activity from 1.10 to 0.97 U/ml (P<0.01). The plasma fibrinogen concentration decreased from 3.55 to 3.01 U/ml (P<0.01). Multvariate analysis showed that the changes in alpha2-antiplasmin and Lp(a) concentrations could explain 53% of the change in plasma fibrinogen, suggesting that increased plasmin mobilization could be responsible for the decrease in plasma fibrinogen. CONCLUSION: This study of hypertriglyceridaemic men has shown that long-term treatment with nicotinic acid not only corrects serum lipoprotein abnormalities, but also reduces the fibrinogen concentration in plasma and stimulates fibrinolysis.
Administration, Oral↗