Mean Plasma Fibrinogen Levels Research Articles

Plasma Fibrinogen Levels and Protein C Activity in Patients with Chronic Kidney Disease in a Nigerian Tertiary Hospital

Introduction: Haemostatic abnormalities have been observed in patients with chronic kidney disease (CKD). Hypercoagulability and thrombotic complications may contribute to the increased morbidity and mortality associated with CKD. Thrombotic tendency has not been fully evaluated in CKD subjects in our environment. This research was to assess the plasma fibrinogen and protein C activity levels in patients with CKD in a Nigerian tertiary hospital, with the view of deducing their associations with thromboembolic manifestations and providing possible therapeutic interventions.
 Material and Methods: A hospital based, cross-sectional survey conducted amongst CKD patients on renal replacement therapy (RRT), who were managed in the renal unit of the University of Benin Teaching Hospital (UBTH). Participants were appropriately matched with apparently healthy control subjects and these were interviewed with a structured questionnaire to obtain data on their clinical details as well as hospital records. Citrated plasma was obtained and analysed to determine the functional protein C activity as well as the fibrinogen levels of both subjects on RRT and apparently healthy control. Haematologic and biochemical parameters were also determined including complete blood count, urea and creatinine and liver function tests. Descriptive and Inferential statistics were performed using Statistical Package for Social Sciences (SPSS) version 20. Results were presented in tables and charts
 Results: A total of 222 subjects participated in this study, comprising 74 patients with CKD on conservative management, 74 subjects with CKD on RRT, and 74 apparently healthy control subjects. The mean age across the groups including subjects on conservative management, RRT, and controls were 54.70±14.42, 49.5±15.73, and 49.3±12.5 years respectively; with the median age of 56-, 52-, and 48.5- years f across the groups respectively. The mean plasma fibrinogen levels across the groups were 240.4±57.76, 241.8±54.87, 360.9±69.5mg/dl respectively. This was statistically significant. The mean protein C activity for the respective groups was 59.6 ± 24.20, 63.6 ± 28.89, 86.7.±2.6%. Protein C activity was significantly depleted in the CKD subjects (p = 0.002).
 Conclusion: The study showed a low protein C activity amongst patients with CKD and those with cardiovascular or thromboembolic events, suggestive of thromboembolic risk in these individuals. Contrary to existing literature, plasma fibrinogen levels were not significantly elevated in patients with CKD, and there was no association with thromboembolic events.

Plasma Fibrinogen as a Predictor of Perioperative-Blood-Component Transfusion in Major-Nontraumatic-Orthopedic-Surgery Patients: A Cohort Study.

There is a trend towards increased perioperative bleeding in patients with plasma fibrinogen levels < 200 mg/dL-1. This study aimed to assess whether there is an association between preoperative fibrinogen levels and perioperative blood-product transfusion up to 48 h after major orthopedic surgery. This cohort study included 195 patients who underwent primary or revision hip arthroplasty for nontraumatic etiologies. Plasma fibrinogen, blood count, coagulation tests, and platelet count were measured preoperatively. A plasma fibrinogen level of 200 mg/dL-1 was the cutoff value used to predict blood transfusion. The mean (SD) plasma fibrinogen level was 325 (83) mg/dL-1. Only thirteen patients had levels < 200 mg/dL-1, and only one of them received a blood transfusion, with an absolute risk of 7.69% (1/13; 95%CI: 1.37-33.31%). Preoperative plasma fibrinogen levels were not associated with the need for blood transfusion (p = 0.745). The sensitivity and the positive predictive value of plasma fibrinogen < 200 mg/dL-1 as a predictor of blood transfusion were 4.17% (95%CI: 0.11-21.12%) and 7.69% (95%CI: 1.12-37.99%), respectively. Test accuracy was 82.05% (95%CI: 75.93-87.17%), but positive and negative likelihood ratios were poor. Therefore, preoperative plasma fibrinogen level in hip-arthroplasty patients was not associated with the need for blood-product transfusion.

STUDY OF PLASMA FIBRINOGEN LEVELS IN ACUTE STROKE

Background: Stroke is a disease of paramount public health significance. The role of plasma fibrinogen in determining incidence and severity of stroke has been postulated time and again. Present study was undertaken to determine the correlation between mean plasma fibrinogen level and infarct volume on CT scan in patients with acute stroke. Methods: Source of data: Plasma fibrinogen of 50 consecutive patients presenting with acute stroke admitted in Netaji Shubhas Chandra Bose Medical College &amp; Hospital, Jabalpur from March 2019 to August 2020 and compared with 50 controls not suffering from stroke with matched age, sex and risk factors (controls) such as heart disease, hypertension, Diabetes and obesity, smoking and use of alcohol. Method of collection of data. The study will be carried out on 50 consecutive patients admitted to N S C B Medical College &amp; Hospital, Jabalpur with acute stroke within 24 hours of the onset of symptoms. Detailed history will be taken to find out the risk factors such as hypertension, diabetes, smoking and alcohol consumption. Hypertension will be diagnosed by JNC VII criteria. Diabetes will be diagnosed by American Diabetes Association criteria. Smoking will be recorded in terms of number of cigarette pack years smoked. Thorough general and systemic examination will be carried out. In addition to routine investigations as per standard protocol in the evaluation of stroke patient, fasting plasma fibrinogen level is estimated and compared to age sex and risk factors matched controls. Result: In this study Fibrinogen levels among patients of stroke were estimated. Data on demography (age, sex, habit of smoking, tobacco and alcohol) and clinical parameters (BMI, heart disease, Hypertension and Diabetes) was also collected. All 50 patients of stroke cases was compared with 50 control subjects, matched for age, sex, obesity, clinical parameters like heart disease, hypertension and diabetes and also for habits of smoking, tobacco use and alcohol.

The effect of cigarette smoking in plasma fibrinogen level and platelet count in male Smokers in Nnewi, Anambra State, Nigeria

Cigarette Smoking has been shown to induce hypercoagulability and a hyper thrombotic state, possibly by increased platelet aggregation and adhesiveness as a result of its nicotine content. During tissue and vascular injury, Fibrinogen (factor I) is converted enzymatically by thrombin to fibrin and subsequently to a fibrin-based blood clot. This study was aimed to determine the effect of cigarette smoking in plasma fibrinogen and platelet levels in male smoker in Nnewi, Anambra state. Apparently healthy 80 male cigarette smokers and 80 male non cigarette smokers, aged between 18 and 40 years, resident in Nnewi were recruited for this study. Four milliliters of blood were collected from each participants (test and control samples), 2ml in trisodium citrate anticoagulated tubes and 2ml in EDTA for the estimation of plasma fibrinogen levels and platelets count respectively. Fibrinogen was estimated using the method described by Clauss. Platelets were estimated using Mythic 22 Automated Hematological Analyzers. The results showed a significant difference between the mean plasma Fibrinogen level in cigarette smokers and non-cigarette smokers (365.90±66.79 vs 203.02±47.40; p= 0.001). There was no significant difference observed in the mean platelets count of cigarette smokers when compared to the mean values of non-cigarette smokers (242.80±94.70 VS 202.84±76.31; p = 0.564). The study concluded that cigarettes smoking elicits an increase in the plasma fibrinogen level.

Pattern of Conventional Coagulation and Thromboelastographic Parameters in Patients with COVID-19 Diseases and Association of COVID-Associated Coagulopathy with Mortality in Intensive Care Unit.

Background:Knowledge of underlying pathophysiology of coagulopathy is evolving and the pattern of coagulation parameters in coronavirus disease 2019 (COVID-19)–associated diseases is still not very clear.Aims:In the present study, we aimed to find out the pattern and distribution of conventional coagulation parameters and thromboelastographic (TEG) parameters in COVID-19–associated coagulopathy (CAC) in survivors and nonsurvivors at 28 days.Setting and Design:The present prospective observational study was conducted at a tertiary care COVID-19 intensive care unit (ICU) facility from March 21, 2020, to July 15, 2021.Materials and Methods:Admission clinical and laboratory data (conventional coagulation, inflammatory and TEG parameters, and disease severity parameters) of 64 COVID-19 patients admitted to the ICU were collected. Patients were divided into two groups, i.e., survivors and nonsurvivors.Statistical Analysis:Data were compared between two groups, i.e., survivors versus no survivors on 28 days using Student's t-test/Mann–Whitney U-test or Chi-square test/Fisher's exact test.Results:Admission mean plasma fibrinogen levels (474.82 ± 167.41 mg.dL−1) and D-dimer were elevated (1.78 [0.66, 3.62] mg.mL−1) in the COVID-19 ICU patients. Overall, COVID-19 patients had mean lower normal platelet count (150 ± 50 × 103 cells.mm−3), with marginally elevated prothrombin time (16.25 ± 3.76 s) and activated partial thromboplastin time (38.22 ± 16.72 s). A 65.6% (42/64) TEG profile analysis showed a normal coagulation profile, and the rest 21.9% (14/64) and 12.5% (8/64) had hypercoagulable and hypocoagulable states, respectively. Plasma D-dimer level was markedly elevated in nonsurvivors compared to survivors (P < 0.05), while no other conventional coagulation parameters and TEG profile demonstrated statistically significant between the two groups.Conclusion:Markedly elevated plasma D-dimer level was observed in nonsurvivors of COVID-19 ICU patients. A large portion of COVID-19 ICU patients had a normal TEG profile. Conventional coagulation parameters and TEG profile were similar between survivors and nonsurvivors.

Assessment of plasma fibrinogen as a marker of diabetic nephropathy

Diabetes is one of the most common chronic hyperglycemic syndrome. Diabetic Nephropathy is one of the major complications of DM characterized by persistent albuminuria, increased arterial blood pressure, a relentless decline in glomerular filtration rate (GFR) &amp; a high risk of cardiovascular morbidity &amp; mortality. The biological marker of DN is fibrinogen. Fibrinogen, is increased in diabetic patients. An increase in plasma fibrinogen levels is also considered an independent risk factor for diabetic nephropathy. Fibrinogen is the major coagulation protein in blood.To find out whether the levels of Plasma Fibrinogen levels can be used as markers for the early diagnosis of DN.A case control study. The study includes total of 150 patients, of which 50 were diabetic without any complications, 50 were diabetic nephropathy patients and remaining 50 were age matched healthy controls. The mean plasma fibrinogen level in control group was 190.34 ± 72.83 mg/dl. The mean plasma fibrinogen levels in DM &amp; DN groups were 522.76 ± 115.79 mg/dl &amp; 657.64 ± 124.61 mg/dl respectively. In our study, fibrinogen levels were increased significantly in DM group compared to controls which was further increased in DN group. Hence above studies interpret that fibrinogen increases in diabetes with complications.Fibrinogen correlated positively with FBS, HbA, TC, triglyceride, LDL, Blood Urea, serum creatinine, TC/HDL, LDL/HDL &amp; urine A/C ratio in both DM &amp; DN group, whereas there was negative correlation of fibrinogen with HDL &amp; eGFR. Thus fibrinogen could be used as early biomarkers for the diagnosis of DN.

Correlation of plasma fibrinogen and mean platelet volume in patients of sepsis to the severity of sepsis and its outcome

Background: The prognostic value of mean platelet volume (MPV) and plasma fibrinogen level in terms of survival in patients with sepsis and septic shock is still incompletely documented. The aim of the present study was to find a correlation between MPV and plasma fibrinogen with the severity of sepsis and mortality.Methods: Three hundred eleven patients having quick sequential organ failure assessment score 2/3, systolic blood pressure ≤100 mmHg, respiratory rate ≥22/minute and altered mentation &lt;15 (Glasgow coma scale) were included for this prospective observational study. Acute physiology and chronic health evaluation (APACHE) II score, MPV on days one and four, fibrinogen on days one and seven were tested. The number of days of intensive care unit (ICU), and hospital stay, in-hospital mortality was recorded. Categorical and continuous variables were tested using the chi-square test/Fisher’s exact test and analysis of variance/Kruskal-Wallis H test respectively.Results: The mean plasma fibrinogen at day one and day seven was significantly higher in patients who had septic shock and in expired patients. The mean MPV at day four was significantly higher in patients who expired compared to those who survived. The mean MPV on day four was significantly higher compared to the mean MPV at day one in patients who expired.Conclusions: Fibrinogen level at admission is the predictor of mortality in patients with sepsis or septic shock. An increase in MPV was strongly correlated with mortality and can be used as a prognostic indicator.

Observational Safety Study of Clottafact® Fibrinogen Concentrate: Real-World Data in Mexico.

Background and ObjectiveThe use of fibrinogen concentrate to treat or prevent major bleeding with regard to potential adverse reactions has not been free of controversy. Our objective was to perform a post-authorization safety study to describe the use of Clottafact® (LFB Biomedicaments) fibrinogen concentrate in real-life medical practice in Mexico.MethodsThis was a prospective, observational study that collected and evaluated information between January 2017 and June 2019 related to suspected serious adverse reactions (SUSARs) during and after Clottafact® infusion.ResultsInformation from 40 subjects was analyzed; 43% were women (n = 17), mean age was 39.05 ± 26.8 years (range 0–91 years). The medical specialties included in this analysis were cardiac surgery − 52.5% of the cases, gynecology/obstetrics − 17.5%, general surgery and orthopedics − 12.5% each, and hematology and neurosurgery − 2.5%, respectively. Mean plasma fibrinogen levels before and after Clottafact® infusion were 2.58 g/L and 4.02 g/L; p = 0.001, respectively. The mean Clottafact® dose was 2.20 ± 0.77 g. One patient presented SUSARs (dry mouth and dysgeusia) with drug administration, which ceased after treatment discontinuation.ConclusionsIn this real-life post-marketing study, the safety profile of Clottafact® was very similar to previous reports. Thus, Clottafact® shows a favorable safety profile in clinical practice.

Oxidative Stress Marker and Fibrinogen Level as Indicators of Severity of Diabetic Foot Ulcer

AbstractDiabetic foot ulcer (DFU) is the leading cause of lower extremity amputation and is very common in clinical practice. Oxidative stress is important in the pathogenesis of chronic wound and the lipid per oxidation product malondialdehyde (MDA) is toxic molecule which is also associated with pathogenesis of chronic complications of diabetes mellitus. Fibrinogen is a recognized marker in peripheral arterial disease (PAD) and increasing level predict an increased risk of amputation. The aim of this study was to investigate whether the plasma MDA and fibrinogen are associated with severity of DFU. In this study, the plasma MDA and fibrinogen levels were determined in 23 normal subjects, 25 diabetes without ulcer patients, 24 mild DFU patients and 25 severe DFU patients. The results showed that mean plasma MDA levels of normal subjects, diabetes without foot ulcer patients, mild DFU patients and severe DFU patients were 0.98± 0.12 μmol/L, 1.3±0.21 μmol/L, 1.61±0.22 μmol/L and 2.3±0.35 μmol/L respectively. Mean plasma fibrinogen levels of normal subjects, diabetes without foot ulcer patients, mild DFU patients and severe DFU patients were 307± 61.5 mg/dl, 429±63.8 mg/dl, 513.6±77.8 mg/dl and 643.5±71.3 mg/dl respectively. We found out that mean plasma MDA level of severe DFU patients was significantly higher than that of other groups (p&lt;0.001). Similarly, mean plasma fibrinogen level of severe DFU patients was significantly higher than that of normal subjects, diabetic without ulcer patients and mild DFU patients (p&lt;0.001). Therefore, we concluded that the higher level of plasma MDA and fibrinogen are significantly associated with severity of DFU.

Relationships between the smoking status and plasma fibrinogen, white blood cell count and serum C-reactive protein in Japanese workers

ObjectiveConfirmation of the association between smoking status and biological inflammatory or anticoagulant markers is required in the field of occupational therapy to promote anti-smoking education. The associations between the smoking status and biological markers were clarified. MethodsThe study was performed in 5102 working men aged 30–60 years old. The author measured the plasma fibrinogen, white blood cell count (WBC) and serum high-sensitivity C-reactive protein (CRP) as biomarkers of the smoking status. ResultsAfter adjustment for age, the mean plasma fibrinogen level in never-smokers was significantly lower than that in current smokers. The mean WBC count was also significantly lower in the never-smokers than that in current smokers and ex-smokers who had quit within the previous 1 year. Furthermore, the mean log-transformed serum CRP value in never-smokers was significantly lower than that in current smokers smoking ≥20 cigarettes daily. Spearman's rank correlation coefficients between the plasma fibrinogen and the serum CRP and WBC were 0.561 and 0.243, respectively. The mean plasma fibrinogen, serum CRP and WBC count in the ex-smokers showed a trend toward decreasing as the duration of abstinence became longer. ConclusionAmong the three biomarkers, the plasma fibrinogen was the most strongly associated with the smoking status, its value being to be the highest in current smokers smoking ≥20 cigarettes daily. The same trend was also observed for the WBC count.

Hyperfibrinogenemia in appendicitis: a new predictor of perforation in children.

Acute appendicitis is the most common emergency abdominal inflammation requiring operation in children. As an acute-phase protein, plasma fibrinogen always increases with inflammation or tissue necrosis. This had brought about the assumption that hyperfibrinogenemia in patients with appendicitis may have a predictive ability for the preoperative diagnosis of appendiceal. Aim of this retrospective study was to assess the diagnostic value of hyperfibrinogenemia as a preoperative laboratory marker for appendiceal perforation in children with acute appendicitis. We screened 466 children (168 girls, 298 boys, mean age, 7.6 years) with histologically confirmed acute appendicitis who received laparoscopic or open appendectomy between January 2012 and April 2014 in a pediatric surgery department of an academic teaching hospital. A retrospective review of the medical records including appendiceal perforation rate and laboratory results was conducted. Mean plasma fibrinogen level of all patients was 4.89 g/L (SD 1.74 g/L, range 1.94-15 g/L, median 4.61 mg/dL). Children with appendiceal perforation had a mean fibrinogen level of 6.18 g/L (SD 1.83 g/L, range 3.02-15 g/L, median 5.79 g/L), which was significantly higher than those with non-perforated children (P = 0.0001). The specificity of hyperfibrinogenemia for appendiceal perforation was 0.82 in comparison with 0.25 for white blood count (WBC) and 0.34 for C-reactive protein (CRP). Sensitivity was 0.74 compared with 0.76 for WBC and 0.94 for CRP. Children with hyperfibrinogenemia and clinical symptoms of appendicitis may be regarded as a higher risk of appendiceal perforation than whose fibrinogen level is normal.

Freund's adjuvant-induced inflammation: clinical findings and its effect on hepcidin mRNA expression in horses

Hypoferremia observed during systemic inflammatory disorders is regulated by hepcidin. Hepcidin up-regulation is particularly important during acute inflammation, as it restricts the availability of iron, which is necessary for pathogenic microorganism growth before adaptive immunity occurs. The aim of this study was to evaluate the clinical findings and hepatic hepcidin mRNA expression in horses using a Freund's complete adjuvant (FCA) model of inflammation. The expression of hepcidin mRNA in the liver was determined in healthy horses following two intramuscular injections of FCA at 0 h and 12 h. Plasma iron and fibrinogen concentrations were measured at multiple time points between 0 h and 240 h post-FCA injection (PI). Hepcidin mRNA expression was determined by RT-qPCR using liver biopsy samples performed at 0 h (control), 6 h and 18 h PI. The mean plasma fibrinogen level was significantly different from the control values only between 120 and 216 h PI. The mean plasma iron level was significantly lower than the control between 16 and 72 h PI, reaching the lowest levels at 30 h PI (33 % of the initial value), and returned to the reference value from 96 h PI to the end of the experiment. Hepcidin mRNA expression increased at 6 h PI and remained high at 18 h PI. The iron plasma concentration was an earlier indicator of inflammatory processes in horses when compared with fibrinogen and might be useful for the early detection of inflammation in the horse. FCA administration caused the rapid onset of hypoferremia, and this effect was likely the result of up-regulated hepatic hepcidin gene expression. This study emphasizes the importance of hepcidin and iron metabolism during inflammation in horses.

Platelet count, mean platelet volume and plasma fibrinogen level in the acute phase of different types of stroke

Platelet count, mean platelet volume and plasma fibrinogen level in the acute phase of different types of stroke

Influence of matrix metalloproteinase-12 on fibrinogen level

In vitro studies have shown that matrix metalloproteinase-12 (MMP12) can degrade fibrinogen, a clotting factor whose level predicts risk of advanced atherosclerosis and myocardial infarction. In this study, we found that mean plasma fibrinogen level was approximately 10-fold higher in MMP12 knockout mice than wildtype mice ( p = 0.0006). Differential allelic expression analysis of human MMP12 gene polymorphism rs17368582 in human vascular tissues showed an allele-specific effect on MMP12 expression, with one allele (T) having 1.6 fold higher expression level than the other allele (C) ( p = 0.0006). In a population cohort, we found that individuals homozygous for the MMP12 low expression allele had higher plasma fibrinogen levels (2.95 mg/mL compared with 2.61 mg/mL in other individuals, p = 0.029) and increased risk of advanced atherosclerosis [odds ratio 6.3 (95% CI 1.9–20.8), p = 0.003] and myocardial infarction [hazard ratio 5.6 (95% CI 1.7–18.3), p = 0.005]. In summary, our study in mouse and humans provides in vivo evidence of an effect of MMP12 on fibrinogen level.

Correlation between Angiogenic and Coagulation-Fibrinolysis Factors and Stage of Disease in Non Hodgkin's Lymphoma Patients.

BACKGROUND: Angiogenesis and activation of coagulation system in cancer patients are common and are thought to be unfavorable clinical parameters. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (bFGF) are well-known angiogenic cytokines. The elevations of plasma fibrinogen and D-dimer level indicate coagulation and fibrinolysis activation. There may be links between angiogenic cytokines and coagulation - fibrinolysis factors in cancer. Possible specific interactions include releasing angiogenic factors, such as VEGF by activated platelets and binding of VEGF and bFGF to fibrin and fibrinogen resulting in an increase in endothelial cell proliferation.AIM: The purpose of our study was: (a) to analyze relations of VEGF, bFGF serum levels and fibrinogen, D-dimer plasma levels with stage of disease according to Ann Arbor Staging System (AASS); (b) to evaluate correlation between serum levels of angiogenic cytokines and plasma levels of coagulation-fibrinolysis factors in non Hodgkin's lymphoma patients.MATERIAL AND METHODS: 52 non Hodgkin's lymphoma patients (31 men, 21 women; median age 52,1 ± 14,7 years) in II, III or IV stage of disease according to AASS were assessed. In stage II were 15, in stage III- 10 and in stage IV- 27 persons. Serum VEGF, bFGF and plasma D-dimer levels were measured by enzyme-linked immunosorbent assay (ELISA). Plasma levels of fibrinogen were determined using Behring Coagulation System (BCS) equipment.RESULTS: Plasma level of D-dimer was elevated in majority of patients, mean plasma D-dimer levels [ng/ml] were in stage II: 1654,3 ± 1301,5, in stage III: 1816,6 ± 1370,7, in stage IV: 2747,1 ± 1410,8. There was significantly higher D-dimer level in IV stage of disease in comparison to stage II and III. p<0,01. The mean serum VEGF levels [pg/mL] in following stages of disease were: in II: 387,4 ± 219,8, in III: 399,2 ± 235,0, in IV: 406,9 ± 308,8; mean serum bFGF levels [pg/mL] were: in II: 4,3 ± 2,9, in III: 4,6 ± 2,5, in IV: 4,4 ± 3,4; mean plasma fibrinogen levels [mg%] were: in II: 514,3 ± 198,7, in III: 518,0 ± 209,2, in IV: 495,4 ± 155,3). Differences in levels of VEGF, bFGF and fibrinogen between II, III and IV stage of disease were not statistically significant We observed positive linear correlation between VEGF and fibrinogen (r = 0,45; p<0,01) and between bFGF and fibrinogen (r = 0,52; p<0,05) and negative linear correlation between VEGF and D-dimer (r = −0,69; p<0,001) and between bFGF and D-dimer (r = −0,72; p<0,001).CONCLUSIONS: Our study indicates that D-dimer level correlates with Ann Arbor Staging System in non Hodgkin's lymphoma patients. Significant correlations between levels of VEGF/bFGF and fibrinogen/D-dimer suggest specific interactions between angiogenic and coagulation-fibrinolysis system.

Monitoring of rheologic variables during postoperative high-dose brachytherapy for uterine cancer.

Oxygenation of tumor tissue has recently been assed an important prerequisite for the effectiveness of radiotherapy in cervical cancer. Hyperviscosity is a common phenomenon in malignancy and a cause of reduced oxygen transport capacity that would favour tissue hypoxia. Hemorheological variables were serially tested preoperatively, during four cycles of fractionated adjuvant IR(192) HDR after loading radiation (HDR-AL) of the vaginal vault (weekly intervals), and 6 months postoperatively in patients with cervical (n=12) and endometrial cancer (n=26). Women who were scheduled for benign tumor surgery served as controls (n=29). Preoperatively, in cervical and endometrial cancer patients, mean plasma viscosity (PV: 1.31+/-0.1 mPa s; p<0.05; 1.35+/-0.13 mPa s; p<0.001) and fibrinogen levels (383+/-46 mg/dL; p<0.05; 379+/-117 mg/dL; p<0.05) were higher as compared to the controls (1.25+/-0.07 mPa s; 314+/-89 mg/dL). Red blood cell aggregation at low shear and stasis (RBC agg.: 15.7+/-5.6; p<0.05; 29.6+/-9.1; p<0.05) was higher in endometrial cancer patients as compared to the controls (13.7+/-3.4; 25.3+/-5.6). Postoperatively PV decreased in endometrial cancer patients and transiently increased in cervical cancer patients. After the third session of irradiation in both cancer groups, PV regained and at the 6-month checkup, levels were higher as compared to the values before surgery. Postoperatively fibrinogen levels increased and remained higher throughout HDR-AL and 6 months postoperatively. After surgery and during irradiation, anemia persisted in both cancer groups while hematocrit recovered after 6 months in endometrial cancer patients. Thrombosis was diagnosed in three patients postoperatively (7.9 %) but in none during HDR-AL. While a temporary reduction of hyperviscosity is found postoperatively and during HDR-AL in uterine cancer patients, 6 months after surgery RBC aggregation, PV, and hematocrit returned to the pretreatment range.

A cross-sectional, diurnal, and follow-up study of platelet activation and endothelial dysfunction in malignant phase hypertension

To investigate the hypothesis that abnormalities of thrombogenesis and endothelial damage/dysfunction are greater in malignant hypertension (MHT) compared with uncomplicated nonmalignant essential hypertension (EHT) > 160/90 mm Hg), we measured markers of endothelial function (von Willebrand factor) platelet activation (soluble P-selectin) and fibrinogen in 18 consecutive patients with MHT, 50 patients with untreated EHT, and 34 healthy control subjects. We also investigated whether there was any diurnal variation in the measured indices, as well as the effects of good blood pressure (BP) control after 6-month follow-up. Mean plasma fibrinogen and von Willebrand factor levels were both highest in the MHT group, intermediate in the nonmalignant hypertension group and lowest in the normotensive control subjects ( P < .001). Similarly, mean soluble P-selectin levels were higher in both hypertensive groups compared to normotensive control subjects ( P = .033). There was no significant diurnal variation in plasma fibrinogen, soluble P-selectin, and von Willebrand factor levels over the 24-h study period among the MHT patients. At 6-month follow-up and a reduction in mean BP, there was no significant change in mean plasma fibrinogen levels ( P = .25), but both soluble P-selectin ( P < .001) and von Willebrand factor ( P = .0025) were significantly reduced. In conclusion, malignant hypertension is associated with abnormal endothelial damage (elevated von Willebrand factor), platelet activation (soluble P-selectin), and fibrinogen levels, which may be related to the pathogenesis of this condition, as well as the development of complications. These abnormalities do not undergo any significant diurnal variation and may be beneficially altered by BP reduction.

Abnormal haemorheology, endothelial function and thrombogenesis in relation to hypertension in acute (ictus < 12 h) stroke patients: the West Birmingham Stroke Project.

While the blood vessels are exposed to high pressures in hypertension, the main complications of hypertension (stroke and myocardial infarction) are paradoxically thrombotic rather than haemorrhagic. To investigate abnormalities of haemorheology (plasma viscosity, fibrinogen), endothelial dysfunction (von Willebrand factor), platelet activation (soluble P-selectin) and thrombogenesis (plasminogen activator inhibitor and fibrin D-dimer) in stroke and the effects of concurrent hypertension, we studied 86 consecutive patients (58 male, 28 female) aged < 75 years (mean age +/- SD, 64.2 +/- 9.2 years) with acute stroke (ictus < 12 h). Baseline blood tests on admission were compared with 46 'hospital controls' (patients with uncomplicated essential hypertension; mean age +/- SD, 65.9 +/- 3.8 years) and 24 healthy normotensive controls (mean age +/- SD, 65 +/- 14.0 years). Further comparisons were made between stroke patients with hypertension (systolic blood pressure > 160 mmHg and/or diastolic > 90 mmHg) on admission and those without hypertension. Mean plasma viscosity (one-way analysis of variance, P = 0.026) and fibrinogen levels (P = 0.016) were significantly higher in stroke patients and hospital controls, when compared with healthy controls. The von Willebrand factor, plasminogen activator inhibitor soluble P-selectin and fibrin D-dimer levels were highest in the acute stroke patients, intermediate in hospital controls and lowest in healthy controls (all P < or = 0.001). There were no significant differences in measured indices of haemorheology, endothelial dysfunction and thrombogenesis between the three stroke pathological subtypes (ischaemic/thrombotic, haemorrhagic or transient ischaemic attack). There were also no significant differences in the measured parameters for stroke patients with or without systolic blood pressure > 160 mmHg or diastolic blood pressures > 90 mmHg using clinical (manual) readings or mean daytime or night-time ambulatory blood pressure monitoring recordings. There were no statistically significant differences between the measured parameters on admission and at 3 months follow-up in 26 patients (all P = not significant). Plasma viscosity was significantly correlated with mean daytime systolic blood pressure (r = 0.314, P = 0.021) and mean night-time systolic blood pressure (r = 0.309, P = 0.025). This study of hypertension and haemostasis in acute stroke has demonstrated clear abnormalities of haemorheology, endothelial dysfunction, platelet activation and thrombogenesis, which do not appear to be affected by the height of the blood pressure or the presence of hypertension. This is despite the known hypercoagulable state found in hypertension and the relationship of haemostatic abnormalities to vascular complications.

The effects of fish supplementation of platelet function, count and metabolism in healthy Japanese

To investigate changes in platelet function, count and metabolism following fish intake among Japanese, we conducted an experimental intervention study of seven healthy Japanese volunteers (4 males and 3 females) aged 28-58 years. We supplemented their diets with an approximate daily intake of 200-400 g fish which is equivalent to about 10 g n3-polyunsaturated fatty acids (about 3.5 g eicosapentaenoic acid plus 5.0 g docosahexaenoic acid) during the 17 days. The study continued until the 23rd day after returning to an ad libitum diet. The proportion of serum n3-polyunsaturated fatty acids increased two-fold on 5th day and three-fold on 15th day of fish supplementation, but decreased to one and a half-fold on the 2nd day and returned to the level before fish supplementation on the 12th day after returning to an ad libitum diet. The proportion of serum n6-polyunsaturated fatty acids decreased by 17% to the level before fish supplementation on the 5th day, 33% on the 15th day of fish supplementation. However, the decrease was only 10% on the 2nd day and the proportion returned to the same level as before fish supplementation on the 12th day after returning to an ad libitum diet. As a result, the serum n3/n6 polyunsaturated fatty acid ratio increased four-fold on the 15th day of fish supplementation, and returned to the baseline level on the 12th day after returning to an ad libitum diet. Platelet counts decreased and the mean platelet volume increased during fish supplementation. Both parameters returned to the level before fish supplementation on the 12th day after returning to an ad libitum diet. The counts and proportion of large type platelets increased significantly during fish supplementation. Although platelet aggregation by ADP (adenosine 5'-diphosphate) did not change significantly, platelet aggregation by collagen tended to decrease during fish supplementation. Platelet factor 4, one of the indices of platelet activity, decreased significantly during fish supplementation. The mean serum triglyceride level declined during fish supplementation, but returned to the level just before fish supplementation on the 2nd day after returning to an ad libitum diet. The mean plasma fibrinogen level tended to decline during fish supplementation and remained lower until the 12th day after returning to an ad libitum diet. Habitual fish intake may attenuate the development of atherosclerosis and prevent ischemic heart disease through suppression of platelet activity, and by reducing platelet counts and serum triglyceride levels.

Association of Fibrinogen with Glycemic Control and Albumin Excretion Rate in Patients with Non-Insulin-Dependent Diabetes Mellitus

The high prevalence of classic cardiac risk factors in patients with non-insulin-dependent diabetes mellitus does not explain the increased cardiovascular-related morbidity and mortality in these patients. Fibrinogen may have a role in this excess risk. To evaluate the following in patients with non-insulin-dependent diabetes mellitus: 1) the distribution of plasma fibrinogen levels and the prevalence of hyperfibrinogenemia and 2) the association of fibrinogen level with hemoglobin A1c value and albumin excretion rate. Cross-sectional study of a population-based cohort. Rural area in northern Italy. 1574 patients with non-insulin-dependent diabetes mellitus who represented 81% of the initial cohort of 1967 patients. Albumin excretion rate was measured in urine samples obtained during an overnight collection. Venous blood samples were collected while patients fasted. Fibrinogen levels were available for 1525 of the 1574 patients who were examined (669 men and 856 women). The mean age (+/- SD) was 67.3 +/- 10.3 years for men and 70.7 +/- 10.7 years for women. The mean plasma fibrinogen level (+/- SD) was 3.6 +/- 0.9 g/L; levels slightly differed between men and women. In 50.3% of patients, plasma fibrinogen level exceeded 3.5 g/L. In men, fibrinogen level increased with age (P < 0.001). In both men and women, fibrinogen level adjusted for age and sex was significantly and linearly related to hemoglobin A1c value (P < 0.001) and albumin excretion rate (P < 0.001). In a multiple regression analysis, hemoglobin A1c value (b = 0.06; P < 0.001) and albumin excretion rate (b = 0.09; P = 0.005) were associated with fibrinogen level independent of other cardiovascular risk factors (sex, age, hypertensive status, total cholesterol level, smoking habit, and body mass index). Patients with non-insulin-dependent diabetes mellitus had a high prevalence of hyperfibrinogenemia. Fibrinogen level was independently associated with hemoglobin A1c value and albumin excretion rate, which suggests that fibrinogen may be involved in the increased cardiovascular risk of patients with diabetes mellitus.