Anti-hémophilique factor has

The factor VIII anti-hémophilique or factor has is a Protéine contained in the plasma (left liquid the Sang) with the state of traces, playing a part of cofactor in the cascade of the Coagulation.

Structure

The analysis of the molecule factor VIII shows that it consists of three distinct fields has, B, C. the field has of 330 AA is made of three specimens A1, A2, A3. The field B of 983 AA is single. The field C made of two C1 segments, C2 of 150 AA each one. The sequence of the various fields starting from the Amino-final end is A1-A2-B-A3-C1-C2. There exist homologies of structure enters, the fields has factor VIII and that of the Facteur V (30 to 40%) and the Céruloplasmine.

Synthesis

The production of factor VIII starts with the synthesis of a Polypeptide of 2.351 amino-acids. On the level of the endoplasmic Reticulum, the protein loses its Peptide signal of 19 AA and undergoes a series of Glycosylation. The final molecule has a molecular weight from 265 to 330 kDa, and contains 2.332 AA. The proteins of transport (binding protein) will be detached from the molecule. This one, always Monomérique, forwards in the Appareil of golgi where the modifications are carried out post-traductionnelle. The Monomère of 330 kDa will undergo a cut in a Dimère, formed of a heavy chain of 210 kDa and of a light chain of 80. Association between these two chains is done via a divalent Ion are true nature remains unknown

Gene of factor VIII

It is located on the distal end of the long arm of the X chromosome. It has a length of 186.000 pairs of bases (bp), which accounts for 0,1% of X chromosome. the DNA coding for ARNm of protein consists of 26 Exons containing 69 to 3.106 LP. The 25 Introns are distributed between 207 to 32.400 LP. ARNm has a length of 9.029 LP (8 860 nucleotides). The sequence not coding in 5" with a length of 170 nucleotides, that of the 3" part; not coding comprises 1.692 nucleotides.

Function

Factor viii plays a central role in coagulation. It is about the cofactor of factor IX. Factor VIII, activated by the Thrombin, becomes the Catalyseur of the reaction of activation of factor X by activated factor IX, in the presence of ion calcium and of Phospholipides. The reaction of activation of factor X is accelerated approximately 200.000 times in the presence of factor VIII. Activated factor X acquires a catalytic activity which enables him to transform the Prothrombine into thrombin. This one degrades the Fibrinogène in Fibrine. The clot thus formed will be stabilized by factor XIII, which allows the stop of the bleeding.

Pathology associated with deficiency in factor VIII or has

Symptoms of the hemophilia

external Hemorrhage: the external hemorrhage is visible since blood runs out by a wound located on the surface of the body. The person can bleed of the nose at the time of a cold or after an exposure prolonged to the sun. It can also bleed of the mouth (too intense brushing of the teeth, bite of the mucous membrane of the cheeks at the time of the chewing…).
Hématome: The hématomes can occur at any place of the body. It is consecutive with a traumatism being accompanied by appearance of pains and a perceptible swelling to palpation, at the place of the Traumatisme. Its principal characteristic occurred of a coloring first of all blue violet which is transformed gradually into greenish yellow coloring which disappears at the end of approximately 15 days.
Hémarthrose: Blood runs out inside an articulation (knee, ankle, elbow, finger) and finishes, in the absence of substitute treatment, by the " bloquer". This hemorrhage can be caused by a Traumatisme (blow, falls) or make following a prolonged effort (long walk, practical of a sport, port of an important load). It can also be spontaneous.

Severity

The hemophilia has can be divided into three classes:

the severe forms are generally diagnosed as of the birth in front of a Hématome which has occurred spontaneously or after a tiny traumatism.

the moderate forms they less frequent and are generally caused by an even light traumatism.

In the light forms, the Hémorragies occur only following one serious wound or with an operational act. even a minor surgical operation (dental extraction) can be at the origin of hemorrhagic accidents.

Factor VIII as a medication

Treatments

The basic salary which makes it possible to stop or to prevent the bleedings at the people reached of Hémophilie has is the treatment by factor of replacement. It is about a perfusion (injection in blood circulation) of concentrate of factor VIII managed to prevent or control the hemorrhage. These concentrates come from two sources:

of the human Plasma (a component of blood) or

of a cellular line obtained by genetic engineering (artificial) by the means of the technology of recombination of DNA.

In both cases, the protein of factor VIII is almost identical to that which is lacking in the blood of the hemophiliacs. After a perfusion of concentrate, all the proteins necessary for coagulation are in place. The blood of the hemophiliac becomes " normal " , at least during a few hours. That makes it possible the Caillot to be formed where the blood-vessel is damaged

Complications of the treatments

The complications major of the treatments are:

inhibiters: it happens that the organization reacts against the factor injected by manufacturing Anticorps. One speaks then about occurred about a Inhibiteur. A biological examination makes it possible to proportion its rate.
transmission of infectious agents: three viruses indeed had dramatic consequences in the hemophiliacs: the virus of the human immunodéficience (HIV), the virus of the Hepatitis B and the virus of the Hepatitis C. The contaminations by these three viruses are not observed any more because of the effectiveness of the processes of viral inactivation used currently during the manufacture of the concentrates of factor VIII of coagulation.

Lastly, the risk of contamination by new infectious agents as the Request remains hypothetical in the actual position of knowledge.

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