Serum Fibrinogen Concentrations Research Articles

Serum Lipids and Apolipoproteins and Their Relationship with Macrovascular Disease in Type 1 Diabetes

In order to examine the relationship between serum lipids and apolipoproteins and macrovascular disease in patients with Type 1 diabetes mellitus, 50 patients with Type 1 diabetes mellitus attending the diabetic clinics at St Mary's and St Charles' Hospitals, London were recruited into a cross-sectional study. B-mode ultrasound was used to measure intima-media thickness and define an arterial ultrasound score for each patient as a non-invasive indicator of atherosclerotic change. Intima-medial (i-m) thickness was significantly higher in those subjects with clinical evidence of macrovascular disease compared to those without macrovascular disease (0.865 +/- 0.191 vs 0.695 +/- 0.162 mm, p = 0.0038). In the study group there were significant correlations between i-m thickness and age (r = 0.65, p < 0.01), total serum cholesterol (r = 0.32, p < 0.01), and serum fibrinogen (r = 0.43, p < 0.01) but no other lipid or apolipoprotein variable. When i-m thickness was corrected for age there were significant correlations with total cholesterol (r = 0.43, p < 0.01) and LDL-cholesterol (r = 0.42, p < 0.01). Whereas total and LDL-cholesterol and serum fibrinogen concentrations were related to the extent of atherosclerotic disease by ultrasound techniques, there was no relationship with high density lipoprotein (HDL) or subfraction cholesterol concentrations. HDL-cholesterol may not be a useful marker for cardiovascular disease in Type 1 diabetes.

Coagulopathy as a predictor of outcome in meningococcal sepsis and the systemic inflammatory response syndrome with purpura

To identify simple, contemporary predictors of both morbidity and mortality in pediatric patients with purpuric sepsis syndrome in order to provide a basis for future study of innovative interventions. Retrospective study. An 18-bed multidisciplinary intensive care unit (ICU) in a large pediatric hospital. A total of 53 patients, ranging in age from 18 days to 17 yrs (mean 4.9 yrs) with either culture-proven meningococcal sepsis or the systemic inflammatory response syndrome with purpura, who were admitted to the ICU during the period from January 1, 1982 through March 15, 1992. A computerized database was constructed containing the characteristics of these patients at presentation, during the first 24 hrs of hospitalization, and on discharge. Single variables were screened for significance between "good" (intact survival) and "poor" (mortality or survival with significant morbidity) outcome groups. Those variables found to be most significant were then tested for sensitivity, specificity, and predictive value. The best predictors identified in this manner were then compared with the two most-cited prognosticating strategies as applied to these patients. Coagulopathy (defined as a partial thromboplastin time > 50 secs or serum fibrinogen concentration < 150 mg/dL [4.4 mumol/L]) at the referral site or on ICU admission was identified as an excellent predictor of poor outcome: sensitivity, specificity, positive and negative predictive values of a low serum fibrinogen value, being 81%, 95%, 93%, and 88%, and of prolonged partial thromboplastin time, being 95%, 90%, 86%, and 97%, respectively. Classical prognosticating strategies were found to be inadequately associated with mortality, yet comparable with coagulopathy in identifying patients destined for clinically important morbidity. We conclude that: a) outcome of pediatric patients with meningococcal sepsis or the systemic inflammatory response syndrome with purpura can be predicted rapidly, more easily, and with overall accuracy superior to classical prognostication strategies by the simple presence or absence of coagulopathy; b) when applied to a contemporary population, classical prognostication strategies lack value for prediction of mortality, yet remain valid for prediction of "poor outcome" (significant morbidity + mortality); c) when evaluating treatment strategies for such patients, the presence of serious coagulopathy may potentially be useful as an index of illness severity.

Fibrinogen and lipid concentrations as risk factors for transient ischaemic attacks and minor ischaemic strokes.

To determine whether fibrinogen and lipid concentrations are risk factors for ischaemic stroke. Case-control study with a population based comparison within the overall study. Oxfordshire community stroke project and a neurology clinic. 105 patients who had a transient ischaemic attack or minor ischaemic stroke and 352 randomly chosen controls matched for age and sex from the same general practitioners as the incident cases. 52 controls were ineligible or refused interview. 104 cases and 241 controls gave blood samples for analysis. Response to structured questionnaire, height, weight, blood pressure, and serum concentrations of fibrinogen and lipids. Adjusted for other variables, odds ratios of ischaemic stroke were 1.78 (95% confidence interval 0.91 to 3.48; p = 0.09) [corrected] for fibrinogen concentrations greater than 3.6 g/l; 1.73 (0.90 to 3.29; p = 0.09) [corrected] for total cholesterol concentrations greater than 6.0 mmol/l; 1.34 (0.69 to 2.61; p greater than 0.4) for low density lipoprotein cholesterol concentrations greater than 3.5 mmol/l; and 0.32 (0.15 to 0.69; p = 0.002) for high density lipoprotein cholesterol concentration greater than 1.2 mmol/l. Similar results emerged comparing only community derived cases with transient ischaemic attacks and controls. The effects of fibrinogen, total cholesterol, and high density lipoprotein cholesterol were significant in a test of trend after adjusting for all other variables in the study (chi 2 = 4.14, p less than 0.05; chi 2 = 4.31, p less than 0.05, and chi 2 = 12.15, p greater than 0.001, respectively). History of ischaemic heart disease and hypertension were the only other variables that showed significance, though both lost significance after adjustment (2.06, p = 0.08 and 1.53, p = 0.2, respectively). Fibrinogen and lipids are important risk factors for ischaemic stroke. The pattern of changes mirrors that found in ischaemic heart disease.

The effects of experimentally induced bronchopneumonia on the pharmacokinetics and tissue depletion of gentamicin in healthy and pneumonic calves

The effects of a bovine bronchopneumonia model on the pharmacokinetics and tissue residue depletion profiles of gentamicin in calves weighing 90-140 kg was explored. Two groups of heifer calves were used. The first was a normal group, while the second group had bronchopneumonia induced. A scoring system was developed to evaluate the extent of disease in the groups. A bimodal distribution of the serum pharmacokinetic parameters in the pneumonic group was caused by the effects of dehydration. When the severely dehydrated calves were omitted from the analysis, serum clearance of gentamicin was significantly higher in the pneumonic group than in the normal group (P less than 0.05). The pharmacokinetic equations used to fit the tissue concentrations varied from tissue to tissue and between groups. Because the best equation of a particular tissue's concentrations varied between groups, withdrawal periods, which are normally determined in healthy animals, may be inappropriate in diseased animals. Addition of several parameters (serum creatinine, serum urea nitrogen, albumin, fibrinogen, and total protein concentrations, white blood cell counts, central fluid volume, volume of distribution at steady state, area under the serum concentration vs time curve, serum clearance, and elimination rate constant) to these tissue-depletion models using multiple regression improved the prediction of a concentration in a given tissue.

The Association of Different Measures of Insulinaemia with Vascular Risk Factors in Healthy Normoglycaemic Normotensive Non-obese Men and Women

Hyperinsulinaemia is said to be a risk factor for cardiovascular disease, but the extent to which different insulinaemic measures are associated with vascular risk factors in ostensibly healthy individuals, and whether they operate independently in men and women, remains uncertain. The association between risk factors and various insulinaemic measures was examined in 148 men and 118 women who were normoglycaemic, normotensive, and non-obese (body mass index in men less than 27, in women less than 25). A 75 g glucose tolerance test was administered after blood sampling for fibrinogen, lipids, lipoproteins and insulin. Insulin was also measured after 1 and 2 hours. Significant univariate correlations (p less than 0.01) were most consistently recorded between insulinaemic measures and fasting serum triglycerides in men and women, whilst systolic blood pressure only correlated with insulinaemia in women, and diastolic blood pressure correlated with fasting and 2 hour insulinaemic measures in men and women. Inconsistent associations were noted with total serum cholesterol in men and women, with high density lipoprotein cholesterol, body mass index, apoprotein B and A1 in men, and with fibrinogen in women. Age was not correlated with any insulinaemic measure in men or women. Differences in vascular risk factors between quintiles of the insulinaemic measures were examined, after correction for body mass index. The dominant association with fasting and post-glucose load insulinaemic measures was with triglycerides, especially in women, with less frequent graded differences between quintiles observed for total cholesterol, and diastolic and systolic blood pressures in men and women. The incidence of other risk factors often only differed in the lowest or highest quintile in comparison to other quintiles, suggesting a threshold rather than a graded effect. Furthermore, differences in HDL cholesterol and apoprotein B were only recorded for top quintiles of post-glucose challenge/integrated insulinaemic measures in men, whilst serum fibrinogen concentrations only differed significantly in women in the top insulinaemic area under the curve quintile. In the absence of additional risk factors such as diabetes, hypertension and obesity, insulinaemic measures are not consistently related to blood pressure and measures of lipid metabolism and coagulation, and are thus a weak predictor of other cardiovascular risk factors. The vascular risk profile associated with insulin appears somewhat different in apparently healthy men and women.

Association between necropsy evidence of disseminated intravascular coagulation and coagulation variables before death in patients in intensive care units.

The necropsy findings in 21 patients on an intensive care unit, on whom coagulation studies had been performed immediately before death, were assessed. Eleven of the patients were retrospectively studied and 10 were reviewed consecutively in a prospective study. Fifteen patients (eight retrospective and seven prospective) had evidence of disseminated intravascular coagulation. Microthrombi were most often found in the lungs and kidneys. The most common abnormal coagulation tests in patients with necropsy evidence of disseminated intravascular coagulation were raised serum concentrations of fibrinogen and fibrin degradation products, prolonged prothrombin time, and reduced platelet counts. Reduced fibrinogen concentrations and a prolonged thrombin time were the least commonly observed abnormalities. There was no difference in either the prevalence or magnitude of abnormality of any particular coagulation variable test result between those patients with evidence of disseminated intravascular coagulation at necropsy and those without.

Ascorbate status and fibrinogen concentrations after cerebrovascular accident.

Leucocyte ascorbate (LA) and serum ascorbate (SA) were measured in patients who had sustained an acute cerebrovascular accident. There was a significant fall in LA and Sa within 24 hours of the incident and this persisted for several weeks. The "stress" of the event resulted in a rise in serum cortisol concentration and depletion of both pituitary and adrenal glands of ascorbate when examined at post mortem. Serum fibrinogen concentrations also rose above normal. The role of ascorbate in pituitary and adrenal function and the relation of ascorbate to acute and chronic vascular disorders has still to be established.

Evaluation of the effectiveness of intracoronary streptokinase infusion in acute myocardial infarction: Postprocedure management and hospital course in 204 patients

A multicenter study evaluated the early management and subsequent hospital course of 204 patients with acute myocardial infarction who were receiving intracoronary infusions of streptokinase (STK). The in-hospital mortality in 37 patients with thrombotic occlusion of the infarct-related vessel, in whom recanalization could not be achieved, was 24%. However, the cardiac mortality in 129 patients who were successfully treated by percutaneous transluminal coronary recanalization (PTCR) was only 5.4%. Cardiac deaths (five patients) and nonfatal reinfarctions (20 patients) occurred in the early period in the cardiac care unit (CCU) in 21% of the latter group and, despite anticoagulation measures, could not be consistently prevented. Hemorrhagic complications, necessitating blood transfusion, occurred in 15 (7.4%) of the total 204 patients in the group, usually in the acute CCU stage, and were positively related to decline of fibrinogen serum concentrations below 100 mg/dl and to use of the Judkins technique. The later course of most of the patients on the general ward was uneventful until hospital discharge. Thus there were only two more cardiac deaths, and of 64 successfully treated STK-PTCR patients who left the CCU without clinical indications of reinfarction and agreed to repeat coronary angiography before hospital discharge, the infarct-related vessel was patent in 59 patients and reoccluded in only five (7.8%).

Platelet function, factor VIII, fibrinogen, and fibrinolysis in Nigerians and Europeans in relation to atheroma and thrombosis.

Platelet function, factor VIII, fibrinogen levels, and fibrinolysis were studied in Europeans and in two groups of Nigerians living in Zaria, northern Nigeria, in order to see whether differences could help to explain the low incidence of atheroma and thrombosis in Nigerians. We confirmed the relative thrombocytopenia and observed a rapid disaggregation after ADP-induced platelet aggregation in Nigerians. The most striking difference was a reduced or absent ristocetin-induced platelet aggregation in Nigerian platelet-rich plasma, probably due to a plasma component interacting with the von Willebrand activity (VWF), since factor VIII coagulant activity, factor VIII related antigen, and isolated VWF were normal or high by European standards. Group II (rural population), but not group I (senior university staff in Zaria) of the Nigerians, tended to have high serum fibrinogen concentrations. Spontaneous fibrinolytic activity was enhanced in most Nigerians compared to the Europeans and was normally increased after venostasis in proportion to the initial activity. Fibrinolysis and ristocetin-induced platelet aggregation values for the Nigerians in group I were intermediate between European and Nigerian in the group II values, suggesting that differences were due more to environmental than to genetic factors.Relative thrombocytopenia, disaggregation after ADP-induced aggregation, inhibition of ristocetin-induced platelet aggregation, and active fibrinolysis help to explain the infrequency of thrombotic disease in Africans. Also the low incidence of atheroma may follow from less platelet adherence and less platelet release of mitogenic factors, which cause intimal hyperplasia.

Giant hemangioma with consumption coagulopathy

Patient J. K., an 8-week-old white female, was admitted to Children's Memorial Hospital for evaluation of an enlarging right axillary mass first noted at 6 weeks of age. Physical examination showed a 6 x 7 cm mass in the right axilla (Fig. 1). Laboratory studies on admission included a hemoglobin concentration of 9.9 gm/dl and a platelet count of 101,000/mm:~; the PT was 24.5 sec, and the aPTT was 45.4 sec. Over the ensuing several hours, a massive hematoma appeared at a venipuncture site. Repeat coagulation studies showed: PT 24.5 sec, aPTT 47.5 sec, serum fibrinogen concentration 8 mg/dl, fibrinogen degradation products titer > 40 /~g/ml, platelet count 20,000/ram :~, and hemoglobin 7.0 gm/dl. The peripheral blood smear contained many fragmented erythrocytes. The child received 20 ml/kg of fresh whole blood and 2 units of platelets, with an increase in hemoglobin level to 9.2 gm/dl, but no increase in platelet count. Because of the abnormal coagulation studies and bleeding from multiple sites, treatment was begun with intravenous heparin, 50 U/kg, every 4 hours, and then increased to 75 U/kg every 4 hours. Prednisone, 2 mg/kg/ day, was given in an attempt to decrease the size of the hemangioma. The hospital course is summarized in Fig. 2. During the first 48 hours of heparin therapy, the serum fibrinogen level increased rapidly and the FDP titer fell and remained stable for approximately one week. Therefore an attempt was made to discontinue heparin; the results of coagulation studies became markedly abnormal within 12 hours, and anticoagulant therapy was