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[TAME]-esterase--a new cardiovascular risk factor in smokers.

A mathematical model has been proposed to study the effect of [TAME] esterase on blood clotting time. Using this model, clotting time was found to decrease by 30% with increasing plasma [TAME] esterase activity in a group of smokers. It is hypothesized that [TAME] esterase through its effect on Hageman factor could affect clotting time. However mechanism of clotting by [TAME] esterase remains to be elucidated. It is concluded that [TAME] esterase is involved in the cascade of reactions leading to blood coagulation and increased [TAME] esterase activity could be an additional risk factor for possible cerebro-vascular accidents in smokers.

Adult↗

Evaluation of bedside prothrombin time and activated partial thromboplastin time measurement by coagulation analyzer CoaguCheck Plus in various clinical settings.

In the present study CoaguCheck Plus (CCP), a coagulation test system using whole blood, was evaluated with respect to its comparability with widely distributed conventional routine coagulation assays. A correlation of r = 0.997 (p < 0.0001) was found between INR of CCP-prothrombin time (CCP-PT) and Thrombotest (KC-1 analyzer) in patients on oral anticoagulant therapy. A correlation of r = 0.899 (p < 0.001) between CCP-aPTT and Actin ES aPTT (STA analyzer) was found in heparinized patients. Impaired hepatic hepatic coagulation factor synthesis in liver cirrhosis patients was detected by CCP-PT with a sensitivity of 0.75 and by Normotest (STA analyzer) with a sensitivity of 0.92. Those patients with normal CCP-PT values and liver disease had, only mild reductions (> 30% of normals) in coagulation factors II, V, VII or X. CCP-aPTT was also performed in patients with a deficiency in the so called endogenous coagulation factors VIII, IX, XI and XII. CCP-aPTT showed a sensitivity similar to that of Actin FS aPTT in the detection even of mild deficiencies in factors VIII, IX and XII; factor XI deficiency was however detected only in patients with severe (< 12% of normals) disease; lupus anticoagulants were detected with a high sensitivity.

Blood Coagulation Tests↗

Mediating systems in inflammatory disease.

This article reviews the mediation systems participating or potentially participating in inflammatory disease, especially in immunologic injury of the glomerulus. Mediator systems are separated into 3 mechanisms: the first involves complement and neutrophils; the second involves systems unrelated to neutrophils and complement components from C3 to C9; and the third involves blood monocytes. Major emphasis is given to an analysis of factors that potentially participate in the second mechanism. These include humoral factors such as the coagulation system and Hageman factor systems and cellular factor such as platelets or cells resident in the glomerulus. Studies on a role of vasoactive amines are presented. The importance of separating neutrophil-dependent and -independent mechanisms in these studies is emphasized. A review of current knowledge of the biochemical mechanisms involved in the Hageman factor system is presented because of the potential role of these components in the development of inflammation.

Animals↗

The value of age- and sex-matched controls for coagulation studies.

Several coagulation parameters and plasminogen levels were studied in 80 normal people divided into eight paired and sex-matched age groups: prepubertal children, postpubertal children, young adults, and adults over 50. The data indicate that factor-VII and -IX activities increase with age, with a cluster of lower activity for children and higher activity for adults. Factor-VIII levels appear to decrease with age, although this effect could be due to greater anxiety in the pre- and postpubertal children at the time of venipuncture. The adults showed no significant change in factor-VIII activity with age, but partial data indicate that factor-VIII levels are higher in adults with blood group A than those with blood group O. The age-related changes in factor-VII, -IX, and possibly -VIII activities did not vary between sexes. By contrast, plasminogen increased strikingly with age in males and decreased with age in females. With fibrinogen, a similar effect was found for adults, though not for the entire population. These findings indicate the importance of using appropriate age- and sex-matched controls for coagulation and plasminogen assays, especially in patients with mild inherited or acquired coagulation disorders.

ABO Blood-Group System↗

Fibrinolysis in normal plasma and blood: evidence for significant mechanisms independent of the plasminogen-plasmin system.

Fibrinolytic activity of normal plasma and blood has been measured by 125l-fibrin solid phase assay. Activity of plasma is not affected by removal of plasminogenplasmin by affinity chromatography. Activities of euglobulin and pseudoglobulin fractions are approximately equal. epsilon-aminocaproic acid (EACA) (10 mM), tranexamic acid (10 mM), diisopropylfluorophosphate (DFP, 50 mM), and soybean and lima bean trypsin inhibitors (100 mug/ml) do not inhibit plasma activity at concentrations that inhibit pure plasmin and urokinase-activated plasma. Activity is not affected by glass contact and is not inhibited by inhibitors of contact or enzymatic activation of Hageman factor (hexadimethrine bromide, 100 mug/ml; cytochrome C, 250 mug/ml; spermidine, 2 mM; phenylmethylsulfonylfluoride, 1 mM). It is inhibited partially (30%-40%) by heating (56 degrees C, 30 min) and by zymosan (2.5 mg/ml; 40%-90% inhibition), and is increased by hydrazine (20 mM), salicylaldoxime (20 mM), DFP (50 mM), and tosyl-L-arginine methyl ester (TAMe, 10 mM)-the latter two at concentrations known to inhibit Cls of the classic, and factor D of the alternate complement pathways. Increase fibrinolytic activity with TAMe is associated with reciprocal decrease in classic and alternate complement pathway activity. It is concluded that normal plasma fibrinolytic activity is relatively independent of plasmin as the ultimate fibrinolytic enzyme, that Hageman factor-dependent pathways are of minor importance, and that significant heat-stable and heat-labile nonplasmin fibrinolytic activities are operative. These may include proteinases involved in complement activation, and in common control of classic and alternate complement pathways, as well as other nonplasmin proteinases.

Aminocaproates↗

Prekallikrein activation by Hageman factor: potentiation by proteins in the absence of high molecular weight kininogen.

Proteins which potentiate the conversion of prekallikrein to kallikrein by Hageman factor fragments are present in cryoprecipitate prepared from the plasma of an individual lacking HMW kininogen as well as in purified von Willebrand's factor preparations. However, the potentiator activity could be separated from the von Willebrand's antigen and ristocetin cofactor activity by chromatography on QAE-Sephadex. Moreover, it was present in plasma from an individual lacking von Willebrand's factor. These observations indicate that von Willebrand's factor is not responsible for the potentiator activity in cryoprecipitate.

Blood Coagulation↗

[Diagnosis of active inflammatory process in juvenile rheumatoid arthritis].

Assessment of the laboratory parameters of the activity of an inflammatory process (red cell sedimentation rate, C-reactive protein, sialic acids, seromucoid, protein fractions) and the parameters of the hemostasis system in 128 patients with juvenile rheumatoid arthritis (JRA) showed that the traditional laboratory parameters are not sufficiently sensitive in JRA, and the absence of positive responses is not a reliable criterion for discontinuing antiinflammatory therapy. The following hemostasis system tests are proposed for detecting and assessing the activity of inflammation in JRA patients: Hageman-dependent fibrinolysis (HDF), level of Willebrand's factor in the blood (WF), and leukocyte-platelet aggregation. The tests are highly sensitive to low-active and latent inflammatory processes in JRA and are nonspecific. In addition, HDF and WF permit the detection of proliferative inflammation.

Adolescent↗

Activation of human coagulation system by liver-derived clotting factors of Banna minipig inbred line.

The liver synthesizes most of the coagulation factors that play a major role in arresting hemorrhage. Matching hepatic coagulation factors is an important premise in successful xenotransplantation. As a unique inbred pig, the Banna minipig inbred (BMI) animals have a huge potential value for pig-to-human xenotransplantation, due to its clear genetic background and tiny interindividual differences. Whether the coagulation factors synthesized by porcine liver can trigger human clotting pathways has not been reported. This study focused on the activities of BMI coagulant factors synthesized exclusively by the liver to activate human clotting pathways. In these experiments we prepared coagulant factors II, V, VII, X, and XII synthesized exclusively by liver from BMI and humans. The factors were used in common correction tests, added to the corresponding factor-deficient human plasma to determine prothrombin times or activated partial thromboplastin time, thereby calculating BMI and human coagulant factor activities. BMI clotting factors XII, VII, and X triggered human intrinsic, extrinsic, and common pathways, respectively. BMI clotting factors II, V, VII, X, and XII activities were 3.2-, 3.7-, 4.7-, 2.9-, and 4.5-fold as potent as those from humans.

Adult↗

Thyroxine and fetal blood coagulation: a fetal lamb study.

Glucocorticoids have been shown to accelerate the development of blood coagulation in the fetal lamb (Kisker, Robillard & Bohlken, 1983). The current studies examine the influence of high levels of triiodothyronine (T3) on the development of blood coagulation in the fetal lamb. Eight twin fetal lambs were studied during the last trimester of pregnancy (109-138 days gestation) using chronically placed arterial and venous catheters for infusion of T3 and withdrawal of blood samples. One fetus of each twin was infused intravenously with T3 at a constant rate of 0.6 micrograms T3/0.4 ml/h for 48 h. The other twin was infused with 5% dextrose at 0.4 ml/h for 48 h. Blood samples for measuring PT, PTT, TT, fibrinogen, factors II, V, VII, VIII, IX, X, XI and XII were obtained prior to and at the completion of the infusions. The results were analyzed for differences between the samples from paired control and T3 treated animals. Factor V significantly decreased in the T3 infused animals from 51.2% +/- 12.5% to 44.8% +/- 13.8% (P = 0.038). Factor VII also decreased in the treated animals 57.8% +/- 20% to 43.6% +/- 10.8%, but the changes were not statistically significant (P = 0.06). Factor XII significantly increased in the treated animals from 37% +/- 10.5% to 45% +/- 13.7% (P = 0.004). High levels of T3 in third trimester fetal lambs are accompanied by a moderate decrease in factor V and an increase in factor XII activity.

Animals↗

Unbalanced haemostatic changes following strenuous physical exercise. A study in young sedentary males.

During acute exercise both coagulant and fibrinolytic potential increase. Since strenuous exertion is associated with an enhanced risk for cardiac events, especially in untrained individuals, it is important to determine whether the initial haemostatic balance is maintained during exercise. Twenty-nine sedentary males (20-30 years) were subjected to a standardized cycle ergometer test. Blood samples were obtained at two exercise levels, 70% VO2max (submaximal), 100% VO2max (maximal) and during 25 min recovery. Both during submaximal and maximal performance, tissue type plasminogen activator antigen, urokinase plasminogen activator antigen and tissue type plasminogen activator activity were increased. A concomitant enhancement of clotting activity of factors VII, VIII, IX, XII and fibrinogen resulted in a shortening of clotting times. Following correction for changes in plasma volume, the results for factor VII:c were reversed, and factor XII:c and fibrinogen no longer demonstrated exercise-related changes. Increases in coagulant (activated partial thromboplastin time) and fibrinolytic (tissue type plasminogen activator activity) potential proceeded in parallel during exercise. However, during recovery while there was a sustained increase in coagulant potential, fibrinolytic potential demonstrated a sharp fall. We conclude that during physical activity, while parallel changes in coagulant and fibrinolytic activity occur, this haemostatic balance is not maintained during recovery. This phenomenon could constitute an enhanced risk for coronary artery thrombosis which may contribute to exercise-related cardiovascular events.

Blood Coagulation Factors↗