Blood Hageman factor

Griffin JH Role of surface in surface-dependent SO activation of Hageman factor (blood coagulation factor XII). Proc Natl Acad Sci USA 1978 75 1998-2002. 

Figure 17.1 Summary of the four cascades that result from trauma or bleeding and the reactions they catalyse. These are all activated by the blood clotting factor, Xlla (also known as the Hageman factor). Details of each cascade are presented in Figures 17.2, 17.4 and 17.6. Factor XII is activated by collagen and negatively charged surfaces to form the active form, Xlla.

Anderson et al. [59, 75,76] have been pursuing their extensive researches on the biomedical behavior of PEUUs having various formulations modified with hydrophobic acrylate (or methacrylate) polymer or copolymer additives. The most distinguished additive was Methacrol 2138F, which is a copolymer between diisopropylaminoethyl methacrylate and decyl methacrylate [co(DIPAM/DM)] (in a 3-to-l ratio). The protein adsorption assay showed that PEUU (Biomer-type) films loaded or coated with Methacrol or poIy(DIPAM) adsorbed significantly lower amounts of human blood proteins (Fb, IgG, factor VIII, Hageman factor and Alb) than the base PEUU or PEUUs modified by other additives. It was revealed from their experiments that poly(DIPAM) as well as Methacrol exhibited a prominent suppressing effect on the protein adsorption process. 

One method of producing a biocompatible surface is to prevent adsorption of proteins. If proteins adsorb or otherwise become attached to a polymer surface, the attachment can interfere with the normal cell functions. The interaction of a polymer surface and blood is equally problematic. A component in blood known as the Hageman factor detects hydrophobic surfaces. The signaling involves attachment of the factor to the surface and by the process of attachment, the factor becomes activated. This is the first step in the inflammation response that can lead to rejection. Thus, the development of a hydrophilic surface with minimal protein adsorption may become a strategy for the development of compatible medical devices. 

FRACTIONATION,BLOOD - PLASMA FRACTIONATION] (Vol 11) Factor XII [9001-30-3], (See also Hageman factor.)... 

Early observations showed that blood clotted faster in clean glass tubes than in siliconized glass. When Mr. Hageman s blood failed to clot in vitro, it was speculated that a Hageman Factor was responsible for the in vitro activation of blood coagulation (see Ref. 2) for a delightful account). 

The cereal dual function a-amylase/trypsin inhibitor proteins are cysteine-rich, disulphide-rich, double-headed, 13-16 kDa, dual function inhibitor proteins that inhibit both of the digestion enzymes a-amylase and trypsin [290-325] (Table 11). Thus the Zea (com) member of this family, com Hageman factor inhibitor (CHFI), is a double-headed 14 kDa protein that inhibits a-amylase and the serine proteases trypsin and blood clotting Factor Xlla [323-324] (Table 11). The structures of the bifunctional a-amylase/trypsin inhibitor proteins from Eleusine (ragi) (RBI) [292-295] and Zea (com) (CHFI) [325] have been determined. These proteins are structurally similar to the lipid transfer proteins, being composed of a bundle of 4 a-helices together with a short [3-sheet element connected by loops, the a-amylase- and protease-inhibitory domains being separately located [325]. 

Figure 6. Triggering of kinin formation, blood coagulation, and fibrinolysis through specific proteolytic activation of the Hageman Factor (Factor XII). In the cascades, the factor on the left side of the reaction (zymogen) is converted to an active enzyme by proteolysis. PL = phospholipids.

What actually happens in the activation of Hageman factor Is it a chemical reaction We know that Hageman factor can be activated and clotting still prevented as a result of the addition of oxylate or citrate to the blood to tie up the calcium ion. This blood containing activated Hageman factor can then be allowed to stand for a period of time and the Hageman factor will be deactivated. Whatever the reaction that is involved, therefore, it is a reversible reaction and probably does not require any apparent chemical resynthesis. 

Since Hageman factor is thought to be helical in form, as is true with other blood proteins, it is possible that the adsorption forces between it and the surface result in an unfolding of the helix with exposure of certain active sites which in turn initiate the clotting of blood. This seems like a reasonable theory, but of course at this stage can be considered nothing more than that. 

What happens to the other proteins that are adsorbed on foreign materials We know that many proteins are quite firmly bound to the surface and that it is difficult to wash some of these off. We also know that many of these proteins have definite biological function other than merely osmotic activity. We also know that the strength of these adsorption forces varies with different proteins, but apparently a dynamic state exists with proteins being adsorbed, desorbed, and new proteins adsorbed. It would seem quite coincidental if Hageman factor were the only one of these proteins that altered its biological function as a result of this adsorption and desorption. It seems quite obvious that materials which are compatible with blood must not appreciably alter any of the vital blood proteins. 

Figure 5.3. Intrinsic and extrinsic blood clotting cascades. Factor I, fibrinogen Factor II, prothrombin (vitamin K-dependent) Factor III, thromboplastin Factor V, proac-celerin Factor VII, proconvertin (vitamin K-dependent) Factor VIII, antihemophilic factor Factor IX, Christmas factor (vitamin K-dependent) Factor X, Stnart factor (vitamin K-dependent) Factor XI, plasma thromboplastin Factor XII, Hageman factor Factor XIII, fibrin-stabilizing factor and Factor XIV, protein C (vitamin K-dependent). What was at one time called Factor IV is calcinm no factor has been assigned nnmber VI.

In addition to activating blood clotting (9), activated Hageman factor activates prekallikrein of the kinin system, which leads to bradykinin that causes vascular vasodilation. Activation of Hageman factor and blood clotting also leads to the... 

Figure 10.37. Blood-Clotting Cascade. A fibrin clot is formed by the interplay of the intrinsic, extrinsic, and final common pathways. The intrinsic pathway begins with the activation of factor XII (Hageman factor) by contact with abnormal surfaces produced by injury. The extrinsic pathway is triggered by trauma, which activates factor VII and releases a lipoprotein, called tissue factor, from blood vessels. Inactive forms of clotting factors are shown in red their activated counterparts (indicated by the subscript "a") are in yellow. Stimulatory proteins that are not themselves enzymes are shovm in blue. A striking feature of this process is that the activated form of one clotting factor catalyzes the activation of the next factor.

Two pathways initiate a fibrin clot. Extrinsic path is mediated by tissue factor, also called thromboplastin. This membrane protein is exposed when pericytes are damaged. It binds to factor Vila in blood. Factor Vila is a protease and the phospholipid-VIIa-TF complex activates (converts) factor X by cleaving it to Xa. Intrinsic path is initiated by factor XII (Hageman factor), whose conformation is changed to a protease (XHa) by contact with a negatively charged surface such as RNA from damaged or necrotic cells. 

Fibrinolysis has recently been reviewed. In order for fibrinolysis to occur, the proenzyme plasminogen must be activated to plasmin by an activator. Several activators can be formed one from Hageman factor components after its activation, or by a tissue activator released from normal blood vessels. Urokinase is an activator considered to be limited in its function to the kidney. Streptokinase, a singlechain protein from 6-hemolytic streptococci, is an activator that has been studied for many years and has found clinical use especially in Europe. 

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