Antihemophilic Factor: Mechanism, Targets, and Sequence
Learn about Antihemophilic Factor, a protein used for treating hemophilia, von Willebrand disease, and Factor XIII deficiency. Discover its pharmacodynamics, mechanism of action, targets, and protein sequence. Explore how this factor binds with other coagulation factors to facilitate the clotting cascade.
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Presentation Transcript
Antihemophilic Factor Drugbank ID : DB00025 Protein chemical formula : C11794H18314N3220O3553S83 Protein average weight : 264725.5000 Half life : 8.4-19.3 hrs
Description : Human recombinant antihemophilic factor (AHF) or Factor VIII, 2332 residues, glycosylated, produced by CHO cells Indication : For the treatment of hemophiliaA, von Willebrand disease and Factor XIII deficiency. Pharmacodynamics : Antihemophilic Factor binds factor IXa along with calcium and phospholipid, This complex converts factor X to factor Xa to facilitate clotting cascade.
Mechanism of action : Antihemophilic factor (AHF) is a protein found in normal plasma which is necessary for clot formation. The administration of AHF provides an increase in plasma levels of AHF and can temporarily correct the coagulation defect of patients with hemophiliaA (classical hemophilia). Clearance : * 4.1 mL/h.kg [Previously treated pediatric patients]
Targets : Coagulation factor X,Coagulation factor IX,von Willebrand factor,Phytanoyl- CoA dioxygenase, peroxisomal,Asialoglycoprotein receptor 2,78 kDa glucose- regulated protein,Calreticulin,Calnexin,Protein ERGIC-53,Prolow-density lipoprotein receptor-related protein 1,Multiple coagulation factor deficiency protein 2 Affected organisms : Humans and other mammals . Categories : Coagulants and Thrombotic Agents Patents : Country Patent Number Canada 2124690 Canada 1339477 Approved 2007-09-11 1997-09-23 Expires 2013-10-01 2014-09-23
Sequence : ATRRYYLGAVELSWDYMQSDLGELPVDARFPPRVPKSFPFNTSVVYKKTLFVEFTDHLFNIAKPRPPWMGLLGPTIQAEVYDT VVITLKNMASHPVSLHAVGVSYWKASEGAEYDDQTSQREKEDDKVFPGGSHTYVWQVLKENGPMASDPLCLTYSYLSHVDL VKDLNSGLIGALLVCREGSLAKEKTQTLHKFILLFAVFDEGKSWHSETKNSLMQDRDAASARAWPKMHTVNGYVNRSLPGLI GCHRKSVYWHVIGMGTTPEVHSIFLEGHTFLVRNHRQASLEISPITFLTAQTLLMDLGQFLLFCHISSHQHDGMEAYVKVDSC PEEPQLRMKNNEEAEDYDDDLTDSEMDVVRFDDDNSPSFIQIRSVAKKHPKTWVHYIAAEEEDWDYAPLVLAPDDRSYKSQ YLNNGPQRIGRKYKKVRFMAYTDETFKTREAIQHESGILGPLLYGEVGDTLLIIFKNQASRPYNIYPHGITDVRPLYSRRLPKGVK HLKDFPILPGEIFKYKWTVTVEDGPTKSDPRCLTRYYSSFVNMERDLASGLIGPLLICYKESVDQRGNQIMSDKRNVILFSVFDE NRSWYLTENIQRFLPNPAGVQLEDPEFQASNIMHSINGYVFDSLQLSVCLHEVAYWYILSIGAQTDFLSVFFSGYTFKHKMVYE DTLTLFPFSGETVFMSMENPGLWILGCHNSDFRNRGMTALLKVSSCDKNTGDYYEDSYEDISAYLLSKNNAIEPRSFSQNSRH PSTRQKQFNATTIPENDIEKTDPWFAHRTPMPKIQNVSSSDLLMLLRQSPTPHGLSLSDLQEAKYETFSDDPSPGAIDSNNSLS EMTHFRPQLHHSGDMVFTPESGLQLRLNEKLGTTAATELKKLDFKVSSTSNNLISTIPSDNLAAGTDNTSSLGPPSMPVHYDS QLDTTLFGKKSSPLTESGGPLSLSEENNDSKLLESGLMNSQESSWGKNVSSTESGRLFKGKRAHGPALLTKDNALFKVSISLLKT NKTSNNSATNRKTHIDGPSLLIENSPSVWQNILESDTEFKKVTPLIHDRMLMDKNATALRLNHMSNKTTSSKNMEMVQQKK EGPIPPDAQNPDMSFFKMLFLPESARWIQRTHGKNSLNSGQGPSPKQLVSLGPEKSVEGQNFLSEKNKVVVGKGEFTKDVG LKEMVFPSSRNLFLTNLDNLHENNTHNQEKKIQEEIEKKETLIQENVVLPQIHTVTGTKNFMKNLFLLSTRQNVEGSYDGAYAP VLQDFRSLNDSTNRTKKHTAHFSKKGEEENLEGLGNQTKQIVEKYACTTRISPNTSQQNFVTQRSKRALKQFRLPLEETELEKRI IVDDTSTQWSKNMKHLTPSTLTQIDYNEKEKGAITQSPLSDCLTRSHSIPQANRSPLPIAKVSSFPSIRPIYLTRVLFQDNSSHLPA ASYRKKDSGVQESSHFLQGAKKNNLSLAILTLEMTGDQREVGSLGTSATNSVTYKKVENTVLPKPDLPKTSGKVELLPKVHIYQ KDLFPTETSNGSPGHLDLVEGSLLQGTEGAIKWNEANRPGKVPFLRVATESSAKTPSKLLDPLAWDNHYGTQIPKEEWKSQEK SPEKTAFKKKDTILSLNACESNHAIAAINEGQNKPEIEVTWAKQGRTERLCSQNPPVLKRHQREITRTTLQSDQEEIDYDDTISV EMKKEDFDIYDEDENQSPRSFQKKTRHYFIAAVERLWDYGMSSSPHVLRNRAQSGSVPQFKKVVFQEFTDGSFTQPLYRGEL NEHLGLLGPYIRAEVEDNIMVTFRNQASRPYSFYSSLISYEEDQRQGAEPRKNFVKPNETKTYFWKVQHHMAPTKDEFDCKA WAYFSDVDLEKDVHSGLIGPLLVCHTNTLNPAHGRQVTVQEFALFFTIFDETKSWYFTENMERNCRAPCNIQMEDPTFKENY RFHAINGYIMDTLPGLVMAQDQRIRWYLLSMGSNENIHSIHFSGHVFTVRKKEEYKMALYNLYPGVFETVEMLPSKAGIWRV ECLIGEHLHAGMSTLFLVYSNKCQTPLGMASGHIRDFQITASGQYGQWAPKLARLHYSGSINAWSTKEPFSWIKVDLLAPMII HGIKTQGARQKFSSLYISQFIIMYSLDGKKWQTYRGNSTGTLMVFFGNVDSSGIKHNIFNPPIIARYIRLHPTHYSIRSTLRMEL MGCDLNSCSMPLGMESKAISDAQITASSYFTNMFATWSPSKARLHLQGRSNAWRPQVNNPKEWLQVDFQKTMKVTGVTT QGVKSLLTSMYVKEFLISSSQDGHQWTLFFQNGKVKVFQGNQDSFTPVVNSLDPPLLTRYLRIHPQSWVHQIALRMEVLGCE AQDLY
Brands : Advate Description : Advate contains antihemophilic factor, a naturally occurring protein in the blood that helps blood to clot.Advate works by temporarily raising levels of factor VIII in the blood to aid in clotting. Used for/Prescribed for : ADVATE is a medicine used to replace clotting factor (factor VIII or antihemophilic factor) that is missing in people with hemophiliaA (also called "classic" hemophilia). ADVATE is used to prevent and control bleeding in adults and children (0-16 years) with hemophiliaA. Form : powder form Route of administration : intravenous injection Dosage : Dose (IU) = body weight (kg) Desired Factor VIII Rise (IU/dL or % of normal) 0.5 (IU/kg per IU/dL). So example, assuming assuming patient's baseline Factor VIII level is < 1% of normal = A dose of 1750 IU ADVATE administered to a 70 kg patient should be expected to result in a peak post-infusion Factor VIII increase of 1750 IU {[2 IU/dL]/[IU/kg]}/[70 kg] = 50 IU/dL (50% of normal).
Contraindication : ADVATE is contraindicated in patients who have life-threatening hypersensitivity reactions, including anaphylaxis, to mouse or hamster protein or other constituents of the product. Side effects : chest pain; easy bruising, increased bleeding episodes; or bleeding from a wound or where the medicine was injected.
General references : # Titheradge MA, Coore HG: Initial rates of pyruvate transport in mitochondria determined by an "inhibitor-stop" technique. Biochem J. 1975 Sep;150(3):553-6. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/2157
References: http://www.advate.com/assets/pdf/advate_iri_pi.pdf http://www.baxter.com/healthcare_professionals/products/advate.html http://www.drugs.com/advate.html
