Activated Hageman Factor Research Articles

The Formation and “Decay” of Xlla

SummaryVarious materials and conditions have been investigated for their effect on Hageman factor activation. Fatty acid soaps, purified phospholipids, ellagic acid, platelets, and freezing and thawing were among those studied.Under certain circumstances XIIa activity disappeared spontaneously; the factors affecting the kinetics of this “decay” have been evaluated. Successful regeneration of this “decayed” XII a has been achieved. On the basis of these observations, it is postulated that during its “decay”, XIIa reverts to XII by spontaneous molecular refolding.

Release of kallikrein from guinea pig lung during anaphylaxis.

An antigen-antibody reaction occurring in the perfused sensitized guinea pig lung, has been demonstrated to release kallikrein, a proteolytic enzyme related to the formation of kinins. This lung kallikrein is similar to plasma kallikrein in all properties studied, including susceptibility to the same inhibitors, electrophoretic mobility, and heterogeneity in molecular size. The release of kallikrein during anaphylaxis in the guinea pig lung occurs in the presence of ethylenediaminetetraacetate. Perfusion of ellagic acid into nonsensitized lungs will also release kallikrein, presumably through activation of Hageman factor. On the basis of these findings the hypothesis is suggested that the kallikrein in perfused lung activated by the antigen-antibody reaction is, in fact, plasma kallikrein. It is further suggested that activation of such kallikrein by the antigen-antibody reaction proceeds through Hageman factor.

Effects of Ellagic Acid upon the Human Fibrinolytic System

SummarySuitable test systems are described for demonstrating a fibrinolysis enhancing effect of ellagic acid (in vitro), which resembles that of other surface-active agents (e. g., kaolin) in its dependence upon Hageman factor activation, but differs in certain relatively minor particulars. These differences may be explained, at least in part, by demonstrated inhibitory actions of ellagic acid, also shown in suitable test systems. Balances between activations and inhibitions may very well depend on particular types of surface. In the complex interplay between plasma factor and surfaces resides, in all probability, the balances between clotting (or thrombosis) and fibrinolysis (or thrombolysis), upon which depend the integrity and functions of the blood-flow systems, and the understanding of bleeding and thrombosis problems.

Experimental Thrombosis in Rabbits: Evidence that Alkaline Phosphatase Enhances the Thrombogenic Effect of the Injected Ellagic Acid

SummaryIntravenous injection of ellagic acid plus alkaline phosphatase in rabbits, induces a thrombotic tendency, which correlates with a hypercoagulability of the blood revealed by thrombelastography. Either ellagic acid (which suboptimally activates Hageman factor) or alkaline phosphatase, separately, gave negative results concerning the incidence of thrombosis. This clearly indicates that alkaline phosphatase in vivo, as was previously shown in vitro, acts only in the presence of an active SF. The electrophoretic study of the distribution of alkaline phosphatase, in platelet-poor plasma samples secured from rabbits, with and without injection of an alkaline phosphatase preparation, suggests the probability that it is the alkaline phosphatase activity which is located in the “beta” fraction that contributes the responsible co-factor for the thrombogenesis.

Biophysical Mechanisms in Vascular Homeostasis and Intravascular Thrombosis

ABSTRACT Since the time of Virchow it has been postulated that a change in the chemistry of the endothelium lining blood vessels is one of the primary events in the initiation of thrombosis. It is well-known that negatively charged surfaces, such as glass, are clot-promoting in vitro as a direct result of their ability to activate Hageman factor (Factor XII). The problem has been, whether Hageman factor must be activated in vivo for thrombosis to occur and, if so, what kind of a biochemical and biophysical process takes place at the endothelial surface to initiate the coagulation.There have been two methods of approach to this problem. The first is that of the coagulationist who examines the result of treating coagulation proteins with various surfaces in vitro. The second is that of the investigator who measures the biophysical counterparts of normal blood flow and thrombus formation. This monograph is the written

Hageman factor: alterations in physical properties during activation.

Highly purified preparations of Hageman factor, a potent clotpromoting agent in normal mammalian plasma, had a sedimentation coefficient of approximately 5S before activation. After activation, the Hageman factor behaved as a much less soluble or larger molecule during ultracentrifugation and gel filtration. No significant change in sedimentation behavior was noted when the Hageman factor in plasma deficient in plasma thromboplastin antecedent was activated. The altered sedimentation behavior of purified activated Hageman factor probably reflects its decreased solubility in aqueous media.

Plasminoplastin generation test of normal, HF-, PTA-, X-, PTC-, and AHF- platelet-poor plasmas: evidence that only HF- plasma has an abnormal fibrinolytic activity.

SINCE Hageman factor (HF) was found to participate in fibrinolytic activity1,2 several investigations have been carried out to explore its role in fibrinolysis. Iatridis and Ferguson3, in a detailed analysis of this phenomenon, suggested that Hageman factor has a lysokinase activity which converts plasminogen-proplasminoplastin (proactivator) into plasminoplastin (activator). Aznar et al.4 investigated the fibrinolytic activity of Hageman factor by means of thrombelastography and concluded that the active form itself has a similar character to that of the plasmatic proactivator. Haanen et al.5 showed that the fibrinolytic activity of a purified Hageman factor is only measurable in the presence of plasminogen, and therefore Hageman factor is an activator of plasminogen. But Iatridis and Ferguson3 had shown that chicken plasma, which is deficient in proplasminoplastin (proactivator) and in Hageman factor, did not develop any plasminoplastin (activator) activity, despite the addition of streptokinase or kaolin-SF (surface factor or activation product). Thus, from this experiment and from others using normal or Hageman deficient plasmas, they concluded that activated Hageman factor is only efficient for the generation of endogenous plasminoplastin when its precursor (the proplasminoplastin) is available.

Activation of Hageman factor by sodium urate crystals.

Activation of Hageman factor by sodium urate crystals.

PATHOGENESIS OF INFLAMMATION. II. IN VIVO OBSERVATIONS OF THE INFLAMMATORY EFFECTS OF ACTIVATED HAGEMAN FACTOR AND BRADYKININ.

Activated Hageman factor, when injected into the rabbit ear chamber, produces a delayed and prolonged inflammatory response characterized by prominent sticking and emigration of leucocytes. In contrast, preformed bradykinin evokes an immediate and more transient response in which leucocytic emigration occurs less frequently. It is concluded that either Hageman factor produces its inflammatory effects by mechanisms other than kinin release, or bradykinin released endogenously has effects quite different from those resulting from a single injection of the exogenous material.

The Plasmatic Atmosphere of Blood Platelets. Evidence that only Fibrinogen, AcG, and Activated Hageman Factor are Present on the Surface of Platelets.

SummaryWashed platelet suspensions contain active SF (surface factor or activation product), when prepared from normal (N) subjects or from patients deficient in factors Vili, IX or X, but not from a Hageman-deficient. Factor V-deficient plasmas were normalized by platelets from N, XII- and other subjects. Allowing for (a) the platelet prothromboplastic phospholipids, and (b) the above SF and AcG (V) effects, there was no evidence of any significant factors Vili, IX or X in the platelet plasmatic atmosphere. Since XII-platelets showed no true correction of plasmas deficient in Vili, IX or X, the minor “improvement” of test results in these (and N) plasmas on adding N, Vili-, IX- or X-platelets can be explained as a nonspecific surface factor effect. XII-platelets when incubated with normal plasma were normalized by adsorbing Hageman factor (XII) on their surface.

ACTIVATION OF HAGEMAN FACTOR BY SOLUTIONS OF ELLAGIC ACID.

Abstract Aged solutions of tannic acid and of certain o-dihydroxyl compounds similar in structure to its gallic acid moiety accelerated clotting. One of many compounds tested, ellagic acid (4,4′,5,5′,6,6′-hexahydroxydiphenic acid 2,6:2′,6′-dilactone), at concentrations as low as 10 −8 M, accelerated clotting and appeared to activate Hageman factor in a manner analogous to that of glass surfaces. The chemical nature of the action of ellagic acid was not elucidated but seemed to be related to the presence of o-dihydroxyl groups in its molecule.

EFFECT OF HEXADIMETHRINE BROMIDE ON PLASMA KININ FORMATION, HYDROLYSIS OF P-TOSYL-L-ARGININE METHYL ESTER AND FIBRINOLYSIS.

The antiheparin agent hexadimethrine bromide, in concentrations of 20 to 200 mug/ml., inhibited the activation by active Hageman factor of the plasma enzyme which releases kinin from substrate. Once activated, this kinin-forming enzyme was not consistently inhibited by hexadimethrine in a concentration of 1 mg/ml. Surfaces which induce kinin formation by activating Hageman factor in plasma (glass, kaolin, celite, barium carbonate and carboxymethylcellulose) were inactivated by bathing in aqueous solutions of hexadimethrine. The effects of hexadimethrine on Hageman factor and on glass were not abolished by amounts of heparin which neutralize most other actions of hexadimethrine. Hexadimethrine prevented the activation by kaolin, but not by streptokinase, of p-tosyl-L-arginine methyl ester-splitting and fibrinolytic factors in plasma; once these enzymes were activated by kaolin, they could not be inhibited by hexadimethrine. Hexadimethrine, given locally or intravenously into guinea-pigs, reduced the increase in capillary permeability produced by intracutaneous injections of kaolin suspensions.

Surface Factor Mechanisms in Relation to Blood Platelets: Evidence that Activated Hageman Factor is Present on the Surface of Platelets*

SummaryBlood platelet suspensions from normal (N) or hemophilia A (VIII-) subjects contain active SF (surface factor or activation product) in their plasmatic atmosphere. Since factor XII is an essential precursor, SF is not formed on platelets from a Hageman-deficient. Experimental evidence establishing these facts was obtained by means of clotting tests (PCa and PTT) and the thrombelastograph (TEG). The SF activity of normal platelets, like a plasma SF preparation, corrects the deficiencies in XII- plasmas, best tested in silicone or the stainless steel cuvette of the TEG. An anti-SF preparation inhibited the platelet SF activity. Allowing for the SF effect, there was no evidence for any significant factor VIII (AHF) in the platelet plasmatic atmospheres.How surface factor (SF) activation from precursors (XII, XI) in the plasma and plasmatic atmosphere of altering platelets may combine in a mutually reinforcing reaction to trigger intrinsic blood clotting is discussed. When stress, vascular injury, stasis, and other factors enter the picture, the stage may be set for the occurrence of thrombosis in vivo.

HAGEMAN FACTOR DEFICIENCY IN A CHILD

A case of Hageman factor deficiency in a 13-year-old white female is presented and the laboratory procedures necessary for identification of this abnormality are outlined. No bleeding was observed at the time of tonsillectomy and adenoidectomy, confirming the benign nature of the disorder. Decreased Hageman factor activity was found in the plasma of other family members, being in accord with the autosomal recessive nature of the characteristic responsible for this factor.

Activation of Hageman Factor (Factor XII) by Long-Chain Saturated Fatty Acids

Summary1. Long-chain saturated fatty acids accelerate the clotting of blood by activating Hageman factor (HF, factor XII). Their effect is proportional to their chain length.2. The hypothesis is discussed that long-chain saturated fatty acids in the circulating blood of man may exert a similar effect, and may thus be one of the factors in the etiology of clinical thrombosis.

One-stage Assay for Hageman Factor (Factor XII). Further Studies on the Role of Hageman Factor in Blood Coagulation

SummaryA one stage assay for Hageman Factor (HF) activity is described. Maximal standardization was achieved by lyophilizing substrate plasma, cephalin suspension and standard reference plasma in small aliquots. A dilution curve was constructed, using a highly purified HF preparation. The assay is not completely specific and is invalidated by the presence of activated Factor IX and XI. So all materials to be tested were first adsorbed on Al(OH)3-gel to exclude Factor IX and possibly most of Factor XI.Purified activated HF still possesses a high affinity for glass surfaces, thus activation may not alter the molecule at the side of affinity for the glass surface. Moreover purified activated HF is still more active in the presence of glass thus in the adsorbed state. These observations support the idea that the so called activation of Hageman Factor is a reversible phenomenon, whereby the molecule unfolds and uncovers active groups as soon as it is adsorbed on a negatively charged surface.

Activation of Hagemen Factor by saturated fatty acids.

SUMMARYThe effect of suspensions of saturated fatty acids or oleic acid on the coagulation of plasma and on the release of plasma kinin was determined by quantitative methods. The activity of the saturated series (C8‐C22) increases enormously with the length of the carbon chain. Oleic acid is practically inactive. Evidence is presented that the reaction is mediated by adsorption and activation of Hageman factor by the fatty acid micelles. The differences between the activity of the fatty acids are related to the physical conditions at the surface of the particles.

The purification of activated Hageman factor (activated factor XII).

The purification of activated Hageman factor (activated factor XII).

Arginine Esterase Activity of the Contact (Hageman) Factor

SummaryIt was found that alcaline eluates obtained from kaolin shaken with normal intact plasma accelerated the clotting time of Hageman or exhausted plasma and exhibited significant arginine esterase activity. Alcaline kaolin eluate obtained in the same manner from Hageman plasma was lacking in any significant clotting and arginine esterase activity.Arginine esterase activity of the alcaline kaolin eluate was inhibited by soybean trypsin inhibitor (SBI) and pancreatic trypsin inhibitor (PI) and was completely destroyed after 1 hour incubation at 65° C. Optimal conditions for this activity were found at pH 7,5—8,0.Arginine esterase activity of the alcaline kaolin eluates was not connected with the thrombin or plasmin contaminations. Purified preparations of a plasma thromboplastin were devoided of any significant arginine esterase activity.It is concluded that arginine esterase activity contained in alcaline kaolin eluate is connected with the active Hageman factor or related to its activation by silica surfaces.

A Two-Stage Assay Method for Hageman Factor Activity

SummaryA two-stage assay method for assaying Hageman factor (HF) activity has been described. The method is based on the ability of a diluted test plasma or surface factor preparation to correct the clotting defect of a HF-deficient substrate plasma in a modified thromboplastin screening test. This method, being designed for investigating relative increase or decrease of HF activity, could also be used in a system with optimal amount of kaolin for assaying maximal HF activity.