RésuméL’agitation d’un plasma intact en présence de surfaces activant le facteur Hageman: kaolin (1 mg/cm3), célite (1 mg/cm3), ballotini (20 mg/cm3), bentonite (1 mg/cm3), accélère la fibrinolyse à condition que le taux de facteur Hageman soit normal dans les plasmas étudiés.L’activation du système fibrinolytique d’un plasma intact agité avec kaolin ou célite est très importante avec plasma normal, le plasma d’hémophile A, le plasma d’hémophile B, le plasma d’hypoconvertinémie, le plasma dicoumarolé et le plasma de déficit en PTA.Le système fibrinolytique du plasma de Hageman-trait n’est pas activable dans les mêmes conditions, bien que le taux de plasminogène et d’antiplasmine soit normal et que ce plasma n’inhibe pas l’activation de la fibrinolyse d’un plasma normal. Les mêmes constatations sont faites en utilisant un plasma privé artificiellement du facteur contact (“plasma épuisé”).Ces résultats sont discutés, et les auteurs se demandent si l’absence de fibrinolyse physiologique chez les sujets porteurs de Hageman-trait ne pourrait pallier au trouble de la coagulation et peut-être expliquer l’absence d’hémorragie.

Trigramin (Mr weight 10 kDa), an acidic, cysteine rich peptide purified into homogeneity from Trimeresurus gramineus snake venom contained a single protein chain with EAGE at the NH2 terminal end. It inhibited platelet aggregation induced by various agents without affecting release reaction. It blocked competitively the binding of 125I-fibrincgen to AEP stimulated and chymotrypsin treated platelets (Ki= 2 × 10−8). 125-I trigramin bound to intact and to AEP stimulated platelets in a saturable manner (approx. 16,000 sites per platelet). However, AEP increased 5 fold, the binding affinity of trigramin to platelets (to Kd = 4 × 10−8M) suggesting that AEP is changing the conformation of receptors associated with GPIIb/GPIIIa complex. The binding of trigramin to thran-basthenic platelets was markedly reduced. The binding to normal platelets was significantly inhibited by EDTA and by monoclonal antibodies directed against GPIIb/GPIIIa complex but not by the antibodies directed against GPIIb or GPIIIa molecules. The binding of 125I-trigramin to AEP-stimulated platelets was inhibited by RGES (IC50 = 125 μM) and by YHHLGGAKOAGDV (C-terminal fragment of fibrinogen gamma chain, IC50 = 250 μM) suggesting that these or similar peptide sequences are required for interactions of various ligands with GPIIb/GPIIIa complex

SummaryIt has been found that Hageman factor is adsorbed from normal human plasma by collagen and elastin. The adsorption is dependent upon the concentration of both substances and upon the adsorption time. The adsorption by collagen is almost selective. By the procedure of the repeated adsorption it is possible to obtain plasma containing 3-5% of Hageman factor normal value and normal amount of PTA (factor XI). At pH 9.5-10.0 the Hageman factor can be eluted in part from collagen shaken previously with human or pig plasma, its recovery in the eluates from elastin is poor.Experimental evidence is presented that the Hageman factor is activated following adsorption on collagen. The eluates from collagen have been compared with those prepared in a similar manner from kaolin and celite. All eluates possess clot promoting, TAMe arginine esterase and fibrinolytic activities. They shorten considerably the clotting time of the whole blood in siliconized tubes.It has been suggested that collagen may act as an intrinsic trigger of the blood coagulation in vivo by adsorbing and activating the Hageman factor.

The role of platelet fibrinogen receptors and platelet-protein interaction in platelet consumption during simulated cardiopulmonary bypass was investigated. In five recirculation experiments, with whole blood, the platelet count fell to 13% of initial values and in two experiments, with blood from patients with Bernard-Soulier syndrome, to 3% of normal values. However, in three experiments with blood from the patients with Glanzmann's thrombasthenia, the platelet count decreased to 69% of initial values. The extent of platelet consumption in normal blood was diminished to only 72% by addition of 0.5 microM prostaglandin E1 (PGE1) (5 experiments) and to 80% by precoating surfaces of the circuit with 2.5% human albumin (5 experiments). beta-Thromboglobulin antigen (beta TG) loss from platelets was associated with thrombocytopenia. The extent of beta TG loss was significantly reduced by the addition of PGE1 to blood or precoating surfaces with albumin. Proteins adsorbed on the surface of the circuit exposed to normal blood were removed with 0.5% Triton X-100. Some of these proteins were identified to be glycoprotein IIIa (GPIIIa) (3.4-4.3 micrograms/ml), beta TG (1.0-1.6 micrograms/ml), and fibrinogen (1.9-3.7 micrograms/ml). The amount of GPIIIa recovered in the Triton X-100 eluates correlated with the number of platelets lost during recirculation. These studies indicate that exposure of fibrinogen receptors associated with GPIIb-GPIIIa complex contributes to platelet consumption during cardiopulmonary bypass.

The protective action of protease inhibitors (Trasylol, IP-315) the synthetic antifibrinolytic agent (EACA) and heparin in the prevention of acute pancreatic necrosis was evaluated on the basis of serum amylase, histological examination and survival of dogs. Heparin was found to be the most efficient agentin protecting dogs from pancreatic necrosis, the other protease inhibitors were much less effective.In dogs pretreated with heparin no elevation of fibrinogen level and no inhibition of fibrinolysis were observed. These changes were markedly expressed in control dogs with pancreatic necrosis and those receiving profease inhibitors. The total proteolytic activity of pancreas homogenates was investigated. A significant difference in the heparin-treated dogs in comparison with the controls was observed. Similar differences were obtained on testing acid phosphatase in both groups. Successful prevention of acute pancreatitis by heparin can also be explained as being due to the anti-clotting properties of this drug as well as to its action on the level of the pancreatic cell. It is also possible that heparin has a stabilizing effect on lysosomes, known to be the main source of hydrolases.

SummaryThe fibrinolytic system has been studied in 37 patients with essential hypertension, with arterial hypertension of various etiology (renal hypertension and hypertension with atherosclerosis). It has been found that in all these patients euglobulin fibrinolysis is inhibited and fibrinogen, factor VIII, plasminogen, plasminogen proactivator and antiplasmin increase considerably.On the basis of the above findings and other literature data, the authors present a hypothesis that the fibrinolytic system is involved in the regulation of arterial blood pressure and that the impairment of plasminogen activator production in the renal tissue is one of the contributory factors in the development of arterial hypertension.

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