GRANULOCYTE ELASTASE RELEASE DURING BLOOD COAGULATION

1987 ◽  
Author(s):  
T Miura ◽  
M Inagaki ◽  
M Taki ◽  
N Saito ◽  
T Meguro ◽  
...  

Granulocyte elastase (ELP) has a high-potency fibrinolytic activity. Hence, there is a possibility that ELP acts as a thrombolytic enzyme like plasmin in thrombolysis. We investigated the release of ELP from granulocytes, especially during blood coagulation.The biological activity of ELP was measured using a synthetic substrate, Suc-Ala-Tyr-Leu-Val-pNA. The immunological activity assayed as an alpha-l-antitrypsin-ELP complex was measured using an anti-ELP antibody (Merck), because more than 90% of ELP in blood forms alpha-l-antitrypsin-ELP complexes.The ELP activity in granulocytes extracted by 2 mol/1 KSCN was 10 mU/106 cells. This fibrinolytic activity corresponds to 1-2 U of plasmin in the fibrin plate method.The ELP release from separated granulocytes was observed by adding Ca2+, and the release was increased by Ca ionophore A 23187. The release was dose-dependent as far as 10 mM Ca2+ (final concentration) and the maximum release was obtained within 15 minutes. However, the ELP release was not produced by thrombin.The level of alpha-l-antitrypsin-ELP complex in serum was twice higher and that in heparinized plasma was 1.5 times higher than that in sodium citrated plasma. ELP was not released from granulocytes incubated in both prekallikrein deficient plasma and Factor XII deficient plasma containing 10 mM Ca2+. But addition of normal plasma (about 10%) resulted in ELP releaseThese results suggest that the ELP release from granulocytes is dependent on Ca2+ and the release is relevant to the blood coagulation system, especially to contact factors.

1977 ◽  
Author(s):  
F. H. M. Tsakok ◽  
S. S. Ratnam

Intravascular coagulation has been previously suspected in hydatidiform molar pregnancy (McKay 1965) and isolated cases have been described (Egley 1974). Recently a comprehensive coagulation profile in 18 intact hydatidiform molar pregnancies has been reported (Tsakok 1976). These studies showed evidence of abnormal proteolysis with activation of the coagulation system and the fibrinolytic system in varying degrees. In the present work the fibrinolytic activity of fresh molar tissue from 16 patients was studied by the fibrin plate method (Nilsson 1962) and by histochemistry (Pandolfi 1972). The fibrinolytic activity was compared with fresh normal placental tissue.Marked fibrinolytic activity was found in the hydatidiform molar tissue as compared to none in the normal placenta. Increased fibrinolytic activity of hydatidiform mole may be the cause of early, prolonged and heavy uterine bleeding in such abnormal pregnancies. This may be due to local activation of the fibrinolytic system.


1977 ◽  
Author(s):  
I.S. Chohan ◽  
I. Singh ◽  
J. Vermylen ◽  
M. Verstraete

Plasma fibrinolytic activity, as measured by the fibrin-plate method, is enhanced after an intravenous injection of 40 mg furosemide. The effect is evident within 30 minutes of the injection and attains a peak after 6 hours. If a second injection of furosemide is given at this stage, the increased fibrinolytic activity persists, and a slightly higher peak than the first is obtained again 6 hours after this injection. After the furosemide injection, there is an initial decrease of urokinase excretion which returns to normal after 3 to 6 hours.The decrease of urokinase excretion is attributed to a dilution effect during increased diuresis and the rise in fibrinolytic activity by furosemide is attributed to its vasodilatory activity and cyclic-AMP phosphodiesterase inhibitory capacity. It also appears related to the Hageman factor dependent pathway of fibrinolysis. In the treatment of high altitude pulmonary oedema, furosemide restores factor XII and fibrinolytic activity, which are both depressed in this disease (I. Singh and I.S. Chohan, Int. J. Biometeor. 18, 33, 1974).


1969 ◽  
Vol 21 (02) ◽  
pp. 294-303 ◽  
Author(s):  
H Mihara ◽  
T Fujii ◽  
S Okamoto

SummaryBlood was injected into the brains of dogs to produce artificial haematomas, and paraffin injected to produce intracerebral paraffin masses. Cerebrospinal fluid (CSF) and peripheral blood samples were withdrawn at regular intervals and their fibrinolytic activities estimated by the fibrin plate method. Trans-form aminomethylcyclohexane-carboxylic acid (t-AMCHA) was administered to some individuals. Genera] relationships were found between changes in CSF fibrinolytic activity, area of tissue damage and survival time. t-AMCHA was clearly beneficial to those animals given a programme of administration. Tissue activator was extracted from the brain tissue after death or sacrifice for haematoma examination. The possible role of tissue activator in relation to haematoma development, and clinical implications of the results, are discussed.


2020 ◽  
Vol 27 (11) ◽  
pp. 1159-1170
Author(s):  
Mohamed Azarkan ◽  
Mariana Marta González ◽  
Rafaèle Calvo Esposito ◽  
María Eugenia Errasti

Background: Antiplatelet, anticoagulant and fibrinolytic activities of stem bromelain (EC 3.4.22.4) are well described, but more studies are still required to clearly define its usefulness as an antithrombotic agent. Besides, although some effects of bromelain are linked to its proteolytic activity, few studies were performed taking into account this relationship. Objective: We aimed at comparing the effects of stem bromelain total extract (ET) and of its major proteolytic compounds on fibrinogen, fibrin, and blood coagulation considering the proteolytic activity. Methods: Proteolytic fractions chromatographically separated from ET (acidic bromelains, basic bromelains, and ananains) and their irreversibly inhibited counterparts were assayed. Effects on fibrinogen were electrophoretically and spectrophotometrically evaluated. Fibrinolytic activity was measured by the fibrin plate assay. The effect on blood coagulation was evaluated by the prothrombin time (PT) and activated partial thromboplastin time (APTT) tests. Effects were compared with those of thrombin and plasmin. Results: Acidic bromelains and ananains showed thrombin-type activity and low fibrinolytic activity, with acidic bromelains being the least effective as anticoagulants and fibrinolytics; while basic bromelains, without thrombin-like activity, were the best anticoagulant and fibrinolytic proteases present in ET. Procoagulant action was detected for ET and its proteolytic compounds by the APTT test at low concentrations. The measured effects were dependent on proteolytic activity. Conclusion: Two sub-populations of cysteine proteases exhibiting different effects on fibrin (ogen) and blood coagulation are present in ET. Using well characterized stem bromelain regarding its proteolytic system is a prerequisite for a better understanding of the mechanisms underlying the bromelain action.


1987 ◽  
Author(s):  
G Castaman ◽  
F Rodeghiero ◽  
M Ruggeri

Sporadic cases of thromboembolic events have been reported in patients with congenital factor XII deficiency and a relationship with a reduced intrinsic fibrinolysis has been suggested.We report here the results of clinical and laboratory investigations in 10 new families comprising 15 homozygotes (age 16-72) and 14 heterozygotes (age 18-65).In homozygotes, kaolin-activated-PTT was indefinitely prolonged and F XII activity and antigen were undetectable, whereas functional assays . of high molecular weight kininogen ahd kallikrein yielded normal values. Intrinsic fibrinolytic activity - assayed on fibrin plate by measuring lysis zones determined i. by euglobulin fraction, obtained in presence of dextran sulphate and flufenamate (Blood activator inventory test, Kluft 1979) - was reduced in all homozygous pts. to about 50% of normal (range 15-70%; normal range 80-120%); normal values were observed in all heterozygotes. Basal extrinsic fibrinolytic activity (measured after addition of Cl-inhibitor) was absent or minimal as in normal controls. None of our patients showed evidence of thrombotic diathesis.In conclusion, our study demonstrates that a reduced intrinsic fibrinolysis, as assayed by blood activator inventory test, is a common finding in F XII deficiency. The absence of thrombotic diathesis in our cases suggests that, this defect is probably devoid of any clinical significance.


2017 ◽  
Vol 98 (5) ◽  
pp. 758-763
Author(s):  
R A Oruzhov ◽  
R A Zhafarova

Aim. To experimentally study the changes occurring in blood coagulation system in exposure to low-dose benzene. Methods. The experiment was performed on 36 rabbits by chronic exposure of the animals to benzene during 4 months on a daily basis 4 hours a day with 1 non-exposure day a week and a one-month recovery period after the end of exposure. The average poisoning concentration of benzene in the chambers was between 1240±82 mg/m3. The animals were divided into three groups: group 1 was exposed to gradually increasing concentration of benzene, group 2 - to fluctuating (intermittent) concentrations of benzene, group 3 included unexposed to benzene animals and was used as the control group. Overall blood clotting activity, blood clotting time, blood clot retraction, plasma recalcification time, plasma tolerance to heparin, prothrombin index, fibrinogen concentration, blood fibrinolytic activity were determined. Results. In a month after exposure blood clot retraction rates in groups 1 and 2 increased by 79.8 and 23.1% respectively. Plasma tolerance to heparin most significantly changed in animals from group 2 (by 15.4%). Prothrombin time increased by 11.4% in group 1 while in group 3 this parameter decreased by 0.4%. Prothrombin index in group 1 decreased by 4.3%, and in group 2 the changes were not statistically significant. Concentration of fibrinogen in the blood in group 1 had no significant changes and decreased by 4.2% while in group 2 it decreased by 10.4%. Fibrinolytic activity in group 1 and 2 decreased by 47.5 and 5.8% respectively. Conclusion. The studied benzene concentrations impair blood coagulation and anti-coagulation systems including two stages of hemostasis: 1st stage - from factor XII activation, 2nd stage - from prothrombin (factor II) activation.


1998 ◽  
Vol 45 (2) ◽  
pp. 493-499 ◽  
Author(s):  
M Kyogashima ◽  
J Onaya ◽  
A Hara ◽  
T Taketomi

Sulfatide (galactosylceramide I3 -sulfate) has been reported to activate blood coagulation factor XII (Hageman factor), which suggests that it exhibits coagulant activity (Fujikama et al., 1980 Biochemistry 19, 1322-1330) However, sulfatide administered into animals as a bolus shot without subsequent thrombus formation, prolonged conventional clotting times and bleeding time (Hara et al., 1996 Glycoconjugate J. 13, 187-194). These findings suggest that it may exhibit anticoagulant rather than coagulant activity. Following this suggestion we found in vitro that binding of sulfatide to fibrinogen resulted in disturbance of fibrin formation. To examine a possible pharmacological effect of sulfatide on blood coagulation in vivo we continuously infused sulfatide into rats through plastic cannulae and found formation of giant thrombi around the tips of the cannulae. These data suggest that sulfatide may exhibit contradictory functions in the blood coagulation system.


1966 ◽  
Vol 15 (01/02) ◽  
pp. 231-237 ◽  
Author(s):  
P de Nicola ◽  
A Gibelli ◽  
G Turazza

SummarySix different nicotinic acid derivatives were given intravenously into rabbits for 28 days. The dosage was calculated on the basis of equivalents of nicotinic acid. Fibrinolytic activity in plasma was studied by means of the fibrin plate method (heated plates; euglobulinic precipitate, with and without the addition of activator). Plasmin and plasminogen activities were evaluated. The most significant results concern the differences in duration, intensity and type (plasmin and/or plasminogen increase) of effect of the different nicotinic acid derivatives.


Sign in / Sign up

Export Citation Format

Share Document