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| Primary information |
|---|
| ID | 15165 |
| Therapeutic ID | Th1569 |
| Protein Name | Antihemophilic factor human |
| Sequence | >Th1569_Antihemophilic_factor_human
MQIELSTCFFLCLLRFCFSATRRYYLGAVELSWDYMQSDLGELPVDARFPPRVPKSFPFNTSVVYKKTLFVEFTVHLFNIAKPRPPWMGLLGPTIQAEVYDTVVITLKNMASHPVSLHAVGVSYWKASEGAEYDDQTSQREKEDDKVFPGGSHTYVWQVLKENGPMASDPLCLTYSYLSHVDLVKDLNSGLIGALLVCREGSLAKEKTQTLHKFILLFAVFDEGKSWHSETKNSLMQDRDAASARAWPKMHTVNGYVNRSLPGLIGCHRKSVYWHVIGMGTTPEVHSIFLEGHTFLVRNHRQASLEISPITFLTAQTLLMDLGQFLLFCHISSHQHDGMEAYVKVDSCPEEPQLRMKNNEEAEDYDDDLTDSEMDVVRFDDDNSPSFIQIRSVAKKHPKTWVHYIAAEEEDWDYAPLVLAPDDRSYKSQYLNNGPQRIGRKYKKVRFMAYTDETFKTREAIQHESGILGPLLYGEVGDTLLIIFKNQASRPYNIYPHGITDVRPLYSRRLPKGVKHLKDFPILPGEIFKYKWTVTVEDGPTKSDPRCLTRYYSSFVNMERDLASGLIGPLLICYKESVDQRGNQIMSDKRNVILFSVFDENRSWYLTENIQRFLPNPAGVQLEDPEFQASNIMHSINGYVFDSLQLSVCLHEVAYWYILSIGAQTDFLSVFFSGYTFKHKMVYEDTLTLFPFSGETVFMSMENPGLWILGCHNSDFRNRGMTALLKVSSCDKNTGDYYEDSYEDISAYLLSKNNAIEPRSFSQNSRHPSTRQKQFNATTIPENDIEKTDPWFAHRTPMPKIQNVSSSDLLMLLRQSPTPHGLSLSDLQEAKYETFSDDPSPGAIDSNNSLSEMTHFRPQLHHSGDMVFTPESGLQLRLNEKLGTTAATELKKLDFKVSSTSNNLISTIPSDNLAAGTDNTSSLGPPSMPVHYDSQLDTTLFGKKSSPLTESGGPLSLSEENNDSKLLESGLMNSQESSWGKNVSSTESGRLFKGKRAHGPALLTKDNALFKVSISLLKTNKTSNNSATNRKTHIDGPSLLIENSPSVWQNILESDTEFKKVTPLIHDRMLMDKNATALRLNHMSNKTTSSKNMEMVQQKKEGPIPPDAQNPDMSFFKMLFLPESARWIQRTHGKNSLNSGQGPSPKQLVSLGPEKSVEGQNFLSEKNKVVVGKGEFTKDVGLKEMVFPSSRNLFLTNLDNLHENNTHNQEKKIQEEIEKKETLIQENVVLPQIHTVTGTKNFMKNLFLLSTRQNVEGSYEGAYAPVLQDFRSLNDSTNRTKKHTAHFSKKGEEENLEGLGNQTKQIVEKYACTTRISPNTSQQNFVTQRSKRALKQFRLPLEETELEKRIIVDDTDTQWSKNMKHLTPSTLTQIDYNEKEKGAITQSPLSDCLTRSHSIPQANRSPLPIAKVSSFPSIRPIYLTRVLFQDNSSHLPAASYRKKDSGVQESSHFLQGAKKNNLSLAILTLEMTGDQREVGSLGTSATNSVTYKKVENTVLPKPDLPKTSGKVELLPKVHIYQKDLFPTETSNGSPGHLDLVEGSLLQGTEGAIKWNEANRPGKVPFLRVATESSAKTPSKLLDPLAWDNHYGTQIPKEEWKSQEKSPEKTAFKKKDTILSLNACESNHAIAAINEGQNKPEIEVTWAKQGRTERLCSQNPPVLKRHQREITRTTLQSDQEEIDYDDTISVEMKKEDFDIYDEDENQSPRSFQKKTRHYFIAAVERLWDYGMSSSPHVLRNRAQSGSVPQFKKVVFQEFTDGSFTQPLYRGELNEHLGLLGPYIRAEVEDNIMVTFRNQASRPYSFYSSLISYEEDQRQGAEPRKNFVKPNETKTYFWKVQHHMAPTKDEFDCKAWAYFSDVDLEKDVHSGLIGPLLVCHTNTLNPAHGRQVTVQEFALFFTIFDETKSWYFTENMERNCRAPCNIQMEDPTFKENYRFHAINGYIMDTLPGLVMAQDQRIRWYLLSMGSNENIHSIHFSGHVFTVRKKEEYKMALYNLYPGVFETVEMLPSKAGIWRVECLIGEHLHAGMSTLFLVYSNKCQTPLGMASGHIRDFQITASGQYGQWAPKLARLHYSGSINAWSTKEPFSWIKVDLLAPMIIHGIKTQGARQKFSSLYISQFIIMYSLDGKKWQTYRGNSTGTLMVFFGNVDSSGIKHNIFNPPIIARYIRLHPTHYSIRSTLRMELMGCDLNSCSMPLGMESKAISDAQITASSYFTNMFATWSPSKARLHLQGRSNAWRPQVNNPKEWLQVDFQKTMKVTGVTTQGVKSLLTSMYVKEFLISSSQDGHQWTLFFQNGKVKVFQGNQDSFTPVVNSLDPPLLTRYLRIHPQSWVHQIALRMEVLGCEAQDLY
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| Molecular Weight | 480000 |
| Chemical Formula | NA |
| Isoelectric Point | 5.5-6 |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The mean half-life of human antihemophilic factor administered in hemophilic A patients is 14.8 hours.[L1056] |
| Description | Antihemophilic factor human, also known as Coagulation Factor VIII or Anti-Hemophilic Factor (AHF), is a non-recombinant, lyophilized concentrate of coagulation factor VIII, an endogenous protein and essential component of the coagulation cascade. Antihemophilic factor is manufactured with reduced amounts of von Willebrand Factor antigen (VWF:Ag) and purified from extraneous plasma-derived protein by affinity chromatography. The small amount of VWF:Ag is used to purify factor VIII complex and then removed from the final preparation. The final purified concentrate contains albumin as a stabilizer.[L1053]. The complex was developed by CSL Behring or Baxter Healthcare Corporation and approved in the 90s. Endogenous Factor VIII is essential to the clotting process in the body due to its involvement in the clotting cascade where it is responsible for acting as a co-factor to Factor IX. Activation of Factor IX leads to a cascade of signals that results in activation of Factor X, which then results in the conversion of prothrombin to thrombin, and as a result, leads to the conversion of fibrinogen to fibrin, the fibrous protein that creates the scaffold of the clot. Replacement of Factor VIII is essential for the treatment of Hemophilia A, which is caused by mutations in the Factor VIII gene, leading to a functional deficiency or complete loss of protein. Congenital loss or deficiency of Factor VIII results in the physiologic impairment of the coagulation clotting cascade, and as a result, leads to easy bruising and bleeding. Bleeding can range in severity from minor concerns, such as nosebleeds, to more serious events such as hemorrhaging in the joints, brain, or digestive tract [A32280]. Exogenous replacement of Factor VIII is currently the cornerstone of Hemophilia treatment and is used for the prophylaxis and control of bleeding episodes. Treatment has drastically improved since the 1960s when Factor VIII protein was primarily purified from human plasma, rather than being produced through recombinant DNA technology. Unfortunately, purification of protein from human plasma carries an increased risk of transmission of blood-borne diseases such as HIV and Hepatitis, which in part contributed to the Tainted Blood Scandal in the 1980s and 1990s [A31551, A32272]. Other drug products with similar structure and function to Antihemophilic factor human include [DB13999], which is produced by recombinant DNA technology and is identical in sequence to endogenously produced Factor VIII, but does not contain the B-domain, which has no known biological function and [DB11607], which is a fully recombinant factor VIII-Fc fusion protein which has an extended half-life compared with conventional factor VIII due to conjugation to the dimeric Fc domain of human immunoglobulin G1, a long-lived plasma protein [A31551]. Antihemophilic factor human is approved by the Food and Drug Administration for use in hemophilia A (classical hemophilia) for the prevention and control of hemorrhagic episodes [FDA Label]. |
| Indication/Disease | The human antihemophilic factor is indicated for the cases of hemophilia A, also known as classical hemophilia for the prevention and control of hemorrhagic episodes.[L1055] If surgery is needed in patients with hemophilia A there is a need of correction of the clotting abnormality. In this cases, the human antihemophilic factor may be administered followed by intermittent maintenance doses.[L1053] The hemophilia A is characterized by the deficiency of the coagulation factor VIII that results in prolonged blood flow after injury or surgery as well as recurrent bleeding.[T56] |
| Pharmacodynamics | The human antihemophilic factor assists in the convertion of prothrombin to thrombin.[T57] Its administration generates the formation of a complex constituted by the Factor IXa, Factor X and the antihemophilic factor which triggers the normal coagulation cascade for the formation of blood clots.[A31288] The human antihemophilic factor is increased in the plasma thus enabling temporary correction of the hemophilia A bleeding.[L1056] Its effect is reported as the normalization of the partial thromboplastin time.[L1057] |
| Mechanism of Action | The human antihemophilic factor replaces the coagulation factor VIII. It acts as a co-factor for factor IX to activate factor X in the intrinsic pathway of blood coagulation.[L1056, L1057] |
| Toxicity | The highest toxicity is the risk of viral hepatitis transmition as well as intravascular hemolyisis can occur if large or frequent doses are used in blood groups A, B or AB.[T57] |
| Metabolism | The metabolism of the human antihemophilic factor is identical to the normal inactivation and elimination pathway of the natural coagulation factor VIII. After activation, the human antihemophilic factor gets metabolized by activated protein C in R336 and R562 and this action inactivates this cofactor. The proteolysis generates two major fragments which are recognized by an anti-factor VIII A2 domain antibody. This process is followed by a further degradation into smaller fragments.[A31393] |
| Absorption | After intravenous administration of the human antihemophilic factor the values of Cmax, AUC and Tmax were 100 IU/ml, 1450 IU h/ml and 0.43 h respectively. In a second clinical trial, the treatment was administered for six months and the values of Cmax, AUC and Tmax were 99 units/ 100 ml, 1471 units h/ 100ml and 16 h, respectively.[L1057] |
| The pharmacokinetic profile of the human antihemophilic factor needed to be studied by the two-compartment theory as not all of it stays just in blood plasma. The central and peripheral volume of distribution in adults weight an average of 68 kg were 2.81 L and 1.90 L respectively.[A31392] |
| Clearance | The reported clearance for the administration of antihemophilic factor is 0.15 L/h in adults with an average weight of 68 kg. In the same study, there was a separation of the intercompartment clearance which is 0.16 L/h. The clearance rate was reported to be significantly decreased with increasing age and significantly increased in patients that presented a blood type of gourp O.[A31392] |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | NA |
| Brand Name | Wilate - von Willebrand Factor/Coagulation Factor VIII Complex (Human) |
| Company | Octapharma USA Inc |
| Brand Description | Octapharma USA Inc |
| Prescribed For | Intravenous |
| Chemical Name | NA |
| Formulation | WILATE is contraindicated in patients with known hypersensitivity reactions, including anaphylactic or severe systemic reactions, to human plasma-derived products, any ingredient in the formulation [see DESCRIPTION], or components of the container. |
| Physical Appearance | The most common adverse reactions to treatment with WILATE ( ≥ 1%) in patients with VWD were hypersensitivity reactions, urticaria, and dizziness. |
| Route of Administration | WILATE is a human plasma-derived, sterile, purified, double virus inactivated von Willebrand Factor/Coagulation Factor VIII Complex. WILATE is supplied as a lyophilized powder for reconstitution for intravenous injection. The diluent for reconstitution of the lyophilized powder is Water for Injection with 0.1% Polysorbate 80. |
| Recommended Dosage | WILATE is indicated in children and adults with von Willebrand disease for: On-demand treatment and control of bleeding episodes Perioperative management of bleeding |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |