Platelet function, blood coagulation and fibrinolysis in Behcet's syndrome

In 10 patients with Behcet's syndrome, various parameters of platelet function, blood coagulation and fibrinolysis were studied. With varying frequency the following abnormalities were found: increased retention of platelets in glass bead column, reduced platelet aggregation to low concentrations of adenosine diphosphate, elevated plasma levels of fibrinogen concentration and factor VIII activity, increased plasma antiheparin activity and impairment of fibrinolytic activity. The above abnormalities were found long after the last thrombotic episode and were more frequent in patients with a history of thrombophlebitis. It is suggested that certain hemostatic abnormalities accompany or form part of Behcet's syndrome and that they are related to the thrombotic complications characteristic of this syndrome.     

Fasting (acute energy deprivation) in man: effect on blood coagulation and fibrinolysis

Blood coagulation and fibrinolysis parameters were studied during 10 days of total fasting in healthy, normal weight males. A reduction of plasma levels of factor VIII activity with a concomitant decrease in factor VIII antigen was found, without other laboratory evidence for a disseminated intravascular coagulation. The effect of 10 days' starvation on blood coagulation appears to be small but the effect of more prolonged starvation might implicate impaired hemostasis.     

Postprandial effects of an oleic acid-rich oil compared with butter on clotting factor VII and fibrinolysis in healthy men

BACKGROUND: Factor VII coagulant activity (FVII:c) is associated with an increased risk of fatal ischemic heart disease, is correlated with plasma triacylglycerol concentration, and increases after a meal rich in long-chain fatty acids. OBJECTIVE: We planned to compare effects of meals rich in oleate and butter fat with those of a low-fat meal on FVII:c and fibrinolytic activity. DESIGN: A crossover design was used to compare the postprandial effects on coagulant and fibrinolytic activities in 12 men of 3 high-fat (95 g) meals--high oleate, butter, and oleate + medium-chain triacylglycerols (oleate+MCT)--with an isoenergetic low-fat meal (18 g MCT). The oleate+MCT blend was used to mimic the ratio of long-chain to shorter-chain fatty acids in butter. RESULTS: Neither the amount nor type of fat consumed influenced plasminogen activator inhibitor 1 or t-plasminogen activator activities or D-dimer concentration. FVII:c increased by 12.5% (95% CI: 4.6%, 20.5%) after the high-fat meals at 3 h and by 6.7% (95% CI: 1.6%, 11.7%) at 7 h and changed 7 h after the low-fat meal by -14.3% (95% CI: -3.3%, -25.4%). The responses to the high-fat meals did not differ. Measurements of activated FVII (FVIIa), FVII zymogen, and activated FXII (FXIIa) concentrations made after the low-fat and high-oleate meals showed a significant increase in FVIIa only after the high-oleate meal. CONCLUSIONS: The results of this study confirm that FVII:c falls after a low-fat meal and suggests that postprandial activation of FVII occurs rapidly after a fat-rich meal without involving an increase in FXIIa.     

The effect of recombinant human erythropoietin on hemostasis, fibrinolysis, and blood rheology in autologous blood donors

We report three cases of Castleman's disease mimicking the features of collagen disease. Case 1: A 39-year-old woman presented with intermittent arthralgia and fever. Laboratory findings were positive results for antinuclear antibody (80x speckled type), the LE test, anti-SSA antibody, anti-RNP antibody, and Coombs test. The patient was suspected to have systemic lupus erythematosus (SLE) or Sj?gren syndrome, but a lymph node biopsy revealed the plasma cell type of Castleman's disease. Steroid treatment led to resolution of her symptoms. Case 2: A 60-year-old man with mixed type Castleman's disease had proteinuria with renal dysfunction, autoimmune thrombocytopenia, antinuclear antibody, anti-RNP antibody, anti-DNA antibody and anti-cardiolipin antibody. The patient was suspected to have SLE but cervical lymph node biopsy revealed the mixed type of Castleman's disease. Symptoms were not controlled with steroid therapy. He developed renal failure that required for hemodialysis and died of gastrointestinal bleeding due to severe thrombocytopenia. Case 3: A 46-year-old woman had Raynaud's phenomenon, sclerodactylia, and nail fold bleeding. Laboratory tests were revealed positive for antinuclear antibody, anti-ENA antibody, and LE cell preparation. Radiographic study showed multiple masses in the retroperitoneal spaces, which necessitated laparotomy. Firstly, the patient was suspected to have systemic sclerosis or mixed connective tissue disease (MCTD). A biopsy revealed the hyaline-vascular type of Castleman's disease. The serum level of IL-6 by ELISA was high in all of three cases. In case 1, symptoms improved and the IL-6 level normalized after steroid treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Abnormalities in oxygenation, coagulation, and fibrinolysis in colonic blood of horses with experimentally induced strangulation obstruction

OBJECTIVE: To measure arterial and venous blood gas, coagulation, and fibrinolysis variables in blood from isolated segments of control and ischemic large colons for the purpose of identifying variables for rapid, indirect assessment of colonic mucosal injury. DESIGN: Variables were determined at specific intervals during the 4-hour study (3 hours of ischemia and 1 hour of reperfusion). ANIMALS: Seven clinically normal horses between 2 and 15 years old. PROCEDURES: Horses underwent laparotomy and occlusion of the lumen and vasculature of the mid-portion of the pelvic flexure of the large colon. During ischemia of 1 randomly-chosen colonic segment, variables were measured to determine colonic mucosal damage and were compared with histologic scores of colonic biopsy specimens. RESULTS: Significant (P < 0.05) differences from control values were observed over time for venous pH, PCO2, PO2, oxygen saturation, oxygen content, arteriovenous oxygen difference, and lactate and glucose concentrations. Mean histologic scores of biopsy specimens obtained from ischemic colons were significantly (P < 0.05) greater (indicating greater damage) than those from control colons, and increased significantly (P < 0.05) with duration of ischemia. CONCLUSIONS: Venous lactate, oxygen saturation, and PO2 values were the most significant predictors of the severity of histologic damage within the ischemic colons (R2 = 0.661). CLINICAL RELEVANCE: Venous blood gas and lactate values in the large colon are good predictors of the amount of intestinal damage incurred during 3 hours of ischemia, and may be clinically useful for the rapid determination of colonic viability.     

Nutrition and endothelial cell integrity: implications in atherosclerosis

Loss of functional integrity of the vascular endothelium may be one of the initiating events in the etiology of atherosclerosis. Endothelial cells interact with blood components and the abluminal tissues, thus playing an active role in many aspects of vascular functions, such as permeability and vessel tone regulation. Endothelial cells constantly are exposed to nutrients which can modulate enzymes, receptors, transport molecules and various vasoactive mediators, resulting in significant functional changes of the endothelium and the underlying tissues. Nutrition may play an important role in the atherosclerotic disease process. There is evidence that certain vitamins and minerals prevent some metabolic and physiological perturbations of the vascular endothelium. This review focuses on selected lipids which cause endothelial cell injury or dysfunction and on nutrients which may exhibit antiatherogenic properties by being able to function as antioxidants or membrane stabilizers.     

Changes in the activation markers of blood coagulation and fibrinolysis in the neonatal period

BACKGROUND: Activation markers of the clotting and fibrinolytic systems are elevated immediately after birth and decline to near adult levels during the first 24 hours of life. The aims of this study were to investigate, whether the activation of both clotting and fibrinolysis is dependent on the mode of delivery, and to measure activation markers in newborns with infection beyond the first days of life. PATIENTS: We have studied activation markers thrombin-antithrombin III complex, prothrombin fragment 1 + 2, D-dimer and plasmin-antiplasmin complex by use of commercially available ELISA techniques in 20 newborns after elective Cesarean sections because of previous sections, in 20 newborns after Cesarean sections and a trial of labor with uterine contractions over a period of > 20 hours and in 20 newborns (34.-41. gestational week) aged 10-25 days with infection. 20 healthy adults served as controls. RESULTS: A significant elevation of all activation markers was observed both in the newborns after Cesarean sections and in the 10-25 days old children with infection. There were no differences among newborns after elective sections compared to newborns after section and a trial of labor with uterine contractions over a period of > 20 hours. CONCLUSIONS: The clotting and fibrinolytic systems reveal increased activation immediately after delivery, but uterine contractions over a period of > 20 hours seem not to make a difference. During infection, the activation markers of the hemostatic system in newborns aged 10-25 days behaves similarly to the mature adult system.     

Minimal daily variations of plasma and urinary endothelin-1 in healthy subjects

The daily profiles of both the plasma level and the urinary excretion rate of endothelin-1 were examined in 13 healthy volunteers (9 males and 4 females, aged 22 +/- 1 [SEM]). Plasma endothelin-1 (PET) was measured after a one-hour recumbency every 6 hours at 8 a.m., 2 p.m., 8 p.m. and 2 a.m. and the urinary excretion rate of endothelin-1 (UET) was determined in the urine collected every 6 hours. PET was found to be quite stable throughout the day, being 1.57 +/- 0.25 pg/ml at 8 a.m., 1.88 +/- 0.21 at 2 p.m., 2.2 +/- 0.24 at 8 p.m. and 1.90 +/- 0.20 at 2 a.m. After a one-hour ambulation, PET showed no statistical difference. UET also remained unchanged for each 6-hour collecting period, measuring 4.61 +/- 0.69, 3.98 +/- 0.46, 4.63 +/- 0.73 and 3.42 +/- 0.49 ng/hr, respectively. The absence of any daily variations in either PET or UET thus suggests that apparently no specific considerations need be applied regarding the time of taking samples to measure the plasma and urinary endothelin-1.     

Increase by tri-iodothyronine of endothelin-1, fibronectin and von Willebrand factor in cultured endothelial cells

Hyperthyroidism is associated with elevated plasma levels of endothelium-derived proteins such as von Willebrand factor (vWF), fibronectin (FN) and endothelin-1 (ET-1). This study was designed to characterize the mechanisms involved in this phenomenon at the cellular level. vWF, FN and ET-1 secretion and mRNA expression were measured in human umbilical vein endothelial cells (HUVECs) exposed to tri-iodothyronine (T3) for 13 +/- 1 days, using ELISA, Western blot, RIA and Northern blot analysis respectively. Exposure of HUVECs to T3 significantly increased vWF secretion (50 ng T3/ml: 117 +/- 5%, P < 0.01; 100 ng T3/ml: 127 +/- 26%, P < 0.01) as well as vWF mRNA expression (50 ng/ml: 116 +/- 13%, P < 0.001; 100 ng/ml: 136 +/- 30%, P < 0.002) (results are means +/- S.D. analysed by the Wilcoxon signed rank test). FN secretion was significantly affected by 50 (145 +/- 42% of control, P < 0.05) and 100 (116.8 +/- 16% of control, P < 0.05) ng T3/ml, and FN mRNA expression by 50 ng T3/ml (123 +/- 20%, P < 0.05). Long-term incubation with T3 increased both ET-1 secretion (25 ng/ml: 124 +/- 25%, P < 0.001; 50 ng/ml: 165 +/- 53%, P < 0.05; 100 ng/ml: 116 +/- 17%, P < 0.05) and prepro-ET-1 mRNA expression (25 ng/ml: 112 +/- 16%, P < 0.05; 50 ng/ml: 134 +/- 43%, P < 0.02; 100 ng/ml: 120 +/- 20%, P < 0.02). Protein kinase C (PKC) isoforms epsilon and beta II were not significantly affected by T3, whereas PKC alpha was increased in whole cell lysates and in membrane fractions of cells incubated with 100 but not 50 ng T3/ml. Prepro-ET-1 mRNA stability, cell numbers and proliferation, measured by [3H]thymidine assays, remained unaffected in HUVECs after exposure to T3. These data indicate thyroid hormone-induced upregulation of mRNA expression and protein synthesis of vWF, FN and ET-1, by PKC alpha-, beta II- and epsilon-independent pathways, explaining, at least in part, increased plasma concentrations of endothelial proteins and peptides in the hyperthyroid state.     

Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis

The thrombin thrombomodulin dependent activation of the plasma protein TAFI (Thrombin Activatable Fibrinolysis Inhibitor) and Subsequent Inhibition of Fibrinolysis by the TAFIa is described. Work to date indicates that TAFIa is a carboxypeptidase B enzyme that suppress fibrinolysis most likely by down regulating the cofactor functions of partially degraded fibrin. The existence of TAFI provides the explanation for the apparent profibrinolytic effect of activated protein C. and implies the existence of an explicit molecular connection between the blood coagulation of fibrinolytic cascades that is expressed through the thrombin thrombomodulin dependent activation of TAFI. Thus, thrombin generation can, in principle, result in the suppression of fibrinolysis.     

Effects of extensive oral surgery and hemorrhage on coagulation and fibrinolysis

The changes in coagulation and fibrinolytic activity in 22 patients with oral cancer undergoing extensive surgical procedures were studied. The patients were divided into two groups: group I patients suffered blood loss of less than 2,000 mL and group II patients had blood loss of more than 2,000 mL. The platelet count decreased significantly during surgery, at the end of surgery and on the 1st postoperative day in both groups. Fibrinogen was decreased during and at the end of surgery in both groups, but increased significantly on the 3rd postoperative day and reached about two times the preoperative levels on the 7th postoperative day. Fibrin degradation products increased significantly after surgery and reached the maximum value on the 1st postoperative day in both groups. Plasmin inhibitor complex and plasminogen increased significantly on the 3rd and 7th postoperative days. There was no clear evidence regarding the influence of blood loss on coagulation and fibrinolytic factors except for platelets. It was concluded that coagulation and fibrinolysis are enhanced between the 3rd and 7th postoperative days.     

Activation of coagulation and fibrinolysis in open and laparoscopic cholecystectomy

BACKGROUND: Activation of coagulation and fibrinolysis occurs as a stress response to surgery and may predispose the patient to thromboembolic complications. Other components of the surgical stress response (cytokine release, neurohumoral response, etc.) have been shown to differ between laparoscopic and open cholecystectomy, and the aim of this study was to investigate the effects of laparoscopic and open surgery on the coagulation and fibrinolytic pathways. METHODS: Fourteen patients undergoing laparoscopic cholecystectomy and 12 patients undergoing open cholecystectomy had blood taken in the perioperative period for fibrinopeptide A (FPA) prothrombin fragment F1.2, antithrombin 3, tissue plasminogen activator (tPA) and its fast-acting inhibitor plasminogen activator inhibitor-1 (PAI-1 antigen and activity), and the euglobulin clot lysis time (ECLT). RESULTS: The only significant differences between the two groups occurred 6 h after surgery when the ECLT was longer (p < 0.005; Mann Whitney), and PAI-1 antigen and activity were higher (p < 0.01 and p < 0.001, respectively; Mann Whitney) after open cholecystectomy than laparoscopic cholecystectomy. CONCLUSIONS: Other changes in fibrinolysis and coagulation were similar for open and laparoscopic cholecystectomy. With respect to hemostasis, laparoscopic cholecystectomy does not increase the risk of thromboembolic complications compared to the conventional procedure.     

Losartan but not verapamil inhibits angiotensin II-induced tissue endothelin-1 increase: role of blood pressure and endothelial function

Endothelin partially mediates angiotensin (Ang) II-induced vascular changes in vivo. This study investigated the effects of the angiotensin type 1 receptor antagonist losartan and the calcium channel blocker verapamil on vascular reactivity and tissue endothelin-1 levels in aortas of Wistar-Kyoto rats treated for 2 weeks with Ang II (200 ng x kg(-1) x min(-1)). Ang II increased systolic blood pressure (39+/-4 mm Hg, P<0.05). Concomitant treatment with losartan abolished the Ang II-induced pressure increase (P<0.05), whereas verapamil reduced it only partially (P<0.05). In the aortas of rats with Ang II-induced hypertension, tissue endothelin-1 content was increased threefold and contractions to endothelin-1 were impaired (P<0.05). Interestingly, these alterations were normalized by losartan (P<0.05) but not by verapamil. Hence, there was a strong, negative correlation between contractions to endothelin-1 and tissue endothelin-1 content (r=-0.733, P<0.0001). In contrast, both antihypertensive drugs normalized impaired endothelium-dependent relaxations to acetylcholine and reduced the sensitivity of vascular smooth muscle to sodium nitroprusside compared with Ang II-treated rats (P<0.05). Ang II-induced hypertension enhanced endothelium-dependent contractions to acetylcholine, and these were normalized by either drug. In conclusion, these findings suggest that long-term treatment with Ang II modulates endothelin-1 protein expression in the rat aorta. Although both antihypertensive agents lowered blood pressure and normalized endothelial function, only losartan prevented the increase in tissue endothelin-1 content, suggesting that angiotensin type 1 receptor antagonists but not calcium antagonists modulate tissue endothelin-1 in vivo.