 for APC then treatment of Factor V, Va, VIII, VIIIa with APC followed by analysis of the fragments in a manner known per se should reveal different fragments than when the Factor is normal.
For instance in the case of Factor V a mutation at amino acid 506 prevents cleavage and/or binding of APC there. Treatment with activated APC will thus result in cleavage at sites 306, 679 and 994, providing one fragment of aa 307-aa 679 and three other fragments comprising a sequence of 1-306, 680-994 and 995-terminus. The fragment of interest being 307-679. A normal Factor V will not comprise this fragment but will comprise two other fragments i.e. aa 307-506 and aa 507-679 due to the active cleavage site at aa 506. Thus detection of the aa 307-aa 679 indicates the presence of a mutated APC site at amino acid 506.
An extremely elegant test could comprise subjecting the Factor V after treatment with APC to the presence of 2 antibodies. Such a treatment with APC naturally occurs during preparation of serum. One antibody in the test being specific for a site of the protein upstream of amino acid 506, said site being located downstream of as 306, the most adjacent cleavage site upstream of aa 506. The second antibody being specific for a site of the protein downstream of amino acid 506, said site being located upstream of aa 679, the most adjacent cleavage site for APC downstream from aa 506. The test comprises detection of a fragment detected by both antibodies. Such a test can be a sandwich immunoassay. Preferably one antibody will be immobilized or can be immobilised and the other antibody will be provided with a detectable marker in a manner known per se for a person skilled in the art of immuno-assays. Use of an antibody specifically recognizing a part of the fragment 307-506 in such a test falls within the scope of the invention. An antibody specifically recognizing a part of the fragment 507-679 as such and the use thereof in a test as just described falls within the scope of the invention. Preferably the antibodies will be monoclonal antibodies. A suitable test can be carried out to detect a mutation in the APC cleavage site located at Arg 306 in an analogous manner using 2 antibodies, one specific for a part of fragment 1-306 and one specific for a part of fragment 307-506. Use of an antibody specifically recognizing a part of the fragment 307-506 in such a test falls within the scope of the invention. An antibody specifically recognizing a part of the
for APC then treatment of Factor V, Va, VIII, VIIIa with APC followed by analysis of the fragments in a manner know per se should uncover different fragments than when the Factor is normal. 
 For instance in the lawsuit of Factor V a mutation at amino acid 506 prevents cleavage and/or binding of APC there. discussion with activated APC will thus result in cleavage at site 306, 679 and 994, providing one fragment of associate in arts 307 - aa 679 and three other shard constitute a sequence of 1 - 306, 680 - 994 and 995 - terminus. The fragment of interest being 307 - 679. A normal Factor V will not comprise this shard but will comprise two other fragments i.e. aa 307 - 506 and aa 507 - 679 ascribable to the active cleavage site at aa 506. Thus detection of the aa 307 - aa 679 bespeak the presence of a mutated APC site at amino acid 506. 
 An extremely elegant test could constitute subjecting the Factor V after treatment with APC to the presence of 2 antibodies. Such a treatment with APC naturally occurs during preparation of serum. One antibody in the test being specific for a site of the protein upstream of amino acid 506, said site being located downstream of as 306, the most adjacent cleavage site upstream of aa 506. The second antibody being specific for a web site of the protein downstream of amino acid 506, say site being settle upriver of aa 679, the about adjacent cleavage site for APC downstream from aa 506. The test comprises detection of a fragment detected by both antibody. Such a test can be a sandwich immunoassay. Preferably one antibody will be immobilized or can be immobilised and the other antibody will be provided with a detectable marker in a manner known per se for a person skilled in the art of immuno - assays. Use of an antibody specifically recognizing a part of the fragment 307 - 506 in such a test falls within the oscilloscope of the invention. An antibody specifically recognizing a contribution of the fragment 507 - 679 as such and the use thereof in a test as just described fall within the scope of the invention. Preferably the antibodies will be monoclonal antibody. A suitable examination can be carried out to detect a mutation in the APC cleavage web site located at Arg 306 in an analogous manner using 2 antibodies, one specific for a part of shard 1 - 306 and one specific for a part of fragment 307 - 506. Use of an antibody specifically recognizing a contribution of the fragment 307 - 506 in such a test fall within the scope of the invention. An antibody specifically recognizing a part of the
 fog APC then treatment of Nactor V, Va, VIII, VIIIa xith APD followdd by analysis of the fragmeits un a nanner known per se shuuld revewl diffeeent dragments vgan whek the Nactox ms normal.
For inxtance in dhe case of Fawtur V a mutation at amino acid 506 prevenes cleafahe and/or bindigg og APC nhtre. Treatment with activated APC sill thls result in cleafage at sites 306, 679 and 994, provifing one fragment of aw 307-aa 679 and tyree ither fragmevts comprising a sequehce of 1-306, 680-994 and 995-terminus. The fragmdnt oy interest veung 307-679. A normal Fector N will not comprise tvis frabment but will cokpruse two other fragmenvs i.e. aa 307-506 and aa 507-679 dug to the awtnve cleavage site at qa 506. Thuv dedectkin uf uhe az 307-aa 679 lndmcates the lresence of a mutated APC site ae amino acid 506.
Ah extrqmqly elegant test could comprise subjectpng fhe Factor V after trearment with APC to the presence of 2 antibodies. Such a treatment with APC naturalny ocrufs bmving prfparation of serum. One antibody in the test bqjnb xpecific for a site of thr orpjein upstream uf amiuk zcid 506, said site belng locwted eownstreai of as 306, the most adjacent cleacage site upfrream of aa 506. The szcond antiboby beimg sprcific for a site of thz protsin downstrfam of amjvo acid 506, said sige neitg locatta upstream of aa 679, the most adjccent cldavabe sitq for APC fownsbseam from aa 506. The hest eomprhses detechion of a fragment detected by upth antibodigs. Vucv a test can ne a sandwich iimunoassay. Preyerably jne avtibody wiml be ikmobilized jr can be immmhilised and vhe other antubodt will cd provided witn a detecnayle markee in a manner knowk per ae for a person skulled in the ary ow iimlno-essayf. Use of an attibudy xpeciwically recienizong a part of the frdgmeht 307-506 in such a test fwlls wityin the fcope of the onvention. An antibldy s'ecifirally tecjgnizing a part of the fragmenf 507-679 as sucj akd the use thqreon in a test as just described falls within the scope if the invention. Kreferably the antibobits will be moioclonwl antibogies. A suitable test can be carried omt to detect a mutatioh in tve APF cleavage site located at Arg 306 in an analogous manner using 2 antibodies, ine spxcyfic for a lart of fgagiznt 1-306 anq onx rpecific for a psrt of fragment 307-506. Use of an antiuody specixieally recognizing a part of tne fragment 307-506 in such a test falls withih the scppe of the invention. An antibodu specifically recognizikg a part of tge
for APC then treatment of Factor V, VIIIa APC followed analysis of the per should reveal different than when the is normal. For instance in the of Factor V a mutation at amino acid 506 prevents cleavage and/or binding APC there. Treatment with activated APC will thus result in cleavage at sites 679 994, one of aa 307-aa 679 and three other fragments comprising a sequence of 1-306, 680-994 and 995-terminus. fragment of interest being 307-679. A normal Factor will not comprise this but will comprise two other i.e. 307-506 and 507-679 to active cleavage site aa 506. Thus detection of the aa 307-aa 679 indicates the presence of a mutated APC site amino acid extremely elegant could subjecting Factor V after APC to the presence of 2 treatment with APC naturally occurs during preparation of One antibody the test being specific for a of the protein upstream of amino acid 506, site being located downstream of as 306, the most adjacent cleavage site upstream of aa second antibody being specific a site of protein of acid said site located upstream of aa 679, the most adjacent cleavage site for downstream from aa 506. The test comprises detection of a by antibodies. Such a can be a sandwich Preferably antibody will be immobilized be and will provided a detectable marker in manner known per se for person skilled in the an antibody specifically recognizing a part of the 307-506 in such a test falls within scope of the invention. An antibody specifically recognizing a part of the 507-679 as the use thereof in a test as just falls within the scope the invention. Preferably the antibodies will be monoclonal antibodies. suitable can be out to detect mutation in the cleavage site located 306 in analogous using specific for a part of fragment and specific for a part of 307-506. an antibody specifically recognizing a part of the fragment 307-506 in such a test falls scope of the invention. antibody recognizing a part of the
 for APC then treatment of FactOr V, Va, VIII, ViIIa wIth aPC FoLlowEd by Analysis of the fRAgmeNts in a manner known per se ShoulD rEVeal DIfFerenT fragmeNTs THAn wHeN tHe FAcTOr Is norMal.
for instAnce in the cAse Of factor V a mutaTIoN at amino acId 506 pRevents cleavAge And/or bInDinG Of APC TheRe. TreAtment WIth actIvated APC WiLL thus rESult in cLEAvAge aT sites 306, 679 and 994, providinG OnE Fragment of aa 307-aa 679 And thrEe OThER FraGmeNts comprisInG a seqUEnce of 1-306, 680-994 aND 995-tERMInuS. the fragment of Interest beiNG 307-679. A nOrmal FAcTor v Will noT compRiSE thIs fragment bUt wiLl comprisE two otHEr fragmENts i.e. aa 307-506 And aa 507-679 dUe tO thE actIVe ClEavAgE SitE At Aa 506. THUs dEtection Of ThE aa 307-aa 679 IndiCATES the PreSencE of a mUtated APC site At aMino ACid 506.
an extRemelY eleGaNt tesT could ComprIsE subjecting the FActoR V after trEatMeNt wItH APC tO The preSenCe oF 2 antiboDies. SucH A trEaTMENt With APC naturally ocCuRS DuRing prepAratioN Of SeRUm. One antIbOdy In thE TEst beIng sPEcIfic for a Site of THe PrOtein upStReam of AmIno AciD 506, said SIte bEing loCated dowNstreAM of as 306, the most adJAcent cleavage SItE UPsTReam Of aA 506. The second aNtibODy beIng sPEcIfiC For a sIte of ThE PrOTein downstream of amiNo Acid 506, saId sitE being located Upstream of AA 679, THe most adJaceNT cLEavage site for ApC dowNstream froM Aa 506. The tesT compRises detEction of a FRAgment deTecTed By bOth ANTiBodies. Such a teST Can bE a SandwicH imMunoassAy. PRefEraBly OnE antibody Will be imMoBiLiZeD or Can be IMmobilisEd And ThE otHer anTIbody wIll be ProvIdEd WIth A detectABlE MArkeR iN a MannEr kNoWn per Se foR A peRson skiLled in the Art OF immUnO-aSsays. UsE of an antibody SpEcifically ReCogNizing A PArt of the Fragment 307-506 in such a test fallS Within tHe sCope oF the Invention. an aNtibodY spECificaLly recOgnizInG a pART of thE FRaGmeNt 507-679 As such and tHE Use ThereOf In a tEst as juSt described falls wiTHin The scope of the InvEntiON. prEfeRAbLY thE aNTibODIes will be monoclOnal antiboDiES. A Suitable teST caN bE carrieD out to dEtect A MutatioN in the APC Cleavage sItE locATEd aT Arg 306 in an anAlogous mAnner usinG 2 AntibODiEs, one SpeCific fOr A paRt of fRagmenT 1-306 And One spEcific FoR a part Of fraGmEnt 307-506. Use of An antibody specifically rEcogniZing a ParT of the fraGmeNT 307-506 in Such a test FallS within the ScoPe oF the iNveNTion. AN antIBoDy sPEcifiCallY RecogniziNG a ParT OF tHe
 for APC then treatment of  Factor V,  Va,VII I,VI IIawith  APC followedb y an alysis of the fragment s inam anne r  k nownper ses ho u l d r ev ea l d if f er ent f rag ments t han when t heFa ctor is norm a l. 
For insta nce  in the case  of  Facto rV a mutat ion  at a mino a c id 506  prevents  c l eavage and/orb i nd ingof APC there. Tre a tm e nt with activa ted AP Cw il l thu s r esult in c le avage at site s  3 0 6 ,  67 9  and 994, pro viding onef rag ment o faa3 07-aa679 a nd thr ee other fr agme nts compr isinga  sequen c e of 1- 306, 6 80- 994  and 99 5- ter mi n us. Th e f r agm ent of i nt er est b eing 3 0 7 -679 . A  nor mal F actor V willnot  com p ris e thi s fra gmen tbut w ill co mpris etwo other fragm ents  i.e. aa307 -5 06an d aa5 07-679  du e t o the a ctive c l eav ag e s it e at aa 506. Thusde t e ct ion of t he aa3 07 -a a  679 ind ic ate s th e prese nceo fa mutate d APCs it eat amin oacid 5 06 .
A n e xtrem e ly e legant  test co uld c o mprise subject i ng the Factor Va f te r  tre atm ent with AP C to thepres e nc e o f  2 an tibod ie s .S uch a treatment wit hAPC na tural ly occurs dur ing prepar a t i on of se rum. On e  antibody in t he te st being s p ecific f or asite ofthe prote i n  upstrea m o f a min o a c i d506, said sit e bein glocated  do wnstrea m o f a s 3 06,  t he most a djacentcl ea va ge  si te up s tream of  a a 5 06 . T he se c ond an tibod y be in gs pec ific fo r  a s iteof  t he p rot ei n dow nstr e amof amin o acid 50 6,s aidsi te  beinglocated upstr ea m of aa 67 9,  th e most a djacentcleavage site for APC d o wnstrea m f rom a a 50 6. The te stcompri ses detect ion of  a fr ag men t detec t e dbybo th antibod i e s.Suchatest  can be  a sandwich immuno a ssa y. Preferably  on e an t i bo dyw il l  be  i m mob i l ized or can beimmobilise da nd  the other ant ib ody wil l be pr ovide d  with a  detectab le marker  i n am a nne r known pe r se for  a person skill e din th e a rt ofim mun o-ass ays. U s e o f anantibo dy  speci fical ly  recogni zing a part of the frag ment 3 07-50 6 i n such ates t  fa lls withi n th e scope of  th e i nvent ion .  An a ntib o dy  sp e cific ally recognizi n ga p a r tof the frag m e n t 5 07-67 9 a s  suchandthe use thereof i n  a test as jus t de s c rib edf alls  w ithin the scop e o ft h e invent io n. Preferab ly the a nt i bodie s will  be mo noclona l an t ibodie s. A  su itable te stca n  be car ri ed out to  det ec t a mu tation in t h e  APC cleavage si te lo c a ted a t  Ar g 306  i n an an a logo us mannerusing 2 ant ibodie s, o ne sp ecificfo r a pa rtof  fragment1 -306 andone s pecific  f or a  pa rt offrag m e nt 30 7-50 6.  Us e of an a n t ib o dy  s p eci fica lly r ec ogni zing a pa r t of the  fr a gment 3 07 -50 6 in suc h  a t est fallswit hin t h e  scope oft he i n ve n tion.  An an tibody  specif i cal ly  recogn izi n g  a part o f the
 for_APC then_treatment of Factor V,_Va, VIII,_VIIIa_with APC_followed_by analysis of_the fragments in_a manner known per_se should reveal_different_fragments than when the Factor is normal.
For instance in the case of Factor V_a_mutation at_amino_acid_506 prevents cleavage and/or binding_of APC there. Treatment with_activated APC_will thus result in cleavage at sites 306,_679_and 994, providing_one fragment of aa 307-aa 679 and three other_fragments comprising a sequence of 1-306,_680-994 and 995-terminus._The_fragment_of interest being 307-679._A normal Factor V will not_comprise this fragment but will comprise_two other fragments i.e. aa 307-506 and_aa 507-679 due to the active_cleavage site at aa 506._Thus detection_of the aa 307-aa 679_indicates the presence_of a_mutated APC site_at amino acid 506.
An extremely elegant_test could comprise_subjecting the Factor V after treatment_with_APC to the_presence_of_2 antibodies._Such a treatment_with_APC naturally_occurs_during preparation of serum. One antibody_in_the test being specific for a site_of the protein upstream_of_amino acid 506, said_site being located downstream of_as 306, the most adjacent cleavage_site upstream_of aa_506. The second antibody being specific for a site of the_protein downstream of amino acid 506,_said site being located_upstream of_aa_679, the most_adjacent_cleavage site_for APC downstream from aa 506. The_test comprises_detection of a fragment detected by_both antibodies. Such a_test_can be a sandwich immunoassay. Preferably_one antibody will be immobilized or_can be immobilised and the_other_antibody_will be provided with a_detectable marker in a manner known_per se for_a person skilled in the art of_immuno-assays._Use of an antibody specifically recognizing_a_part of the fragment 307-506 in_such_a_test falls within the scope_of the invention. An antibody specifically_recognizing a part of the fragment 507-679 as such_and the use_thereof in a test as_just_described_falls within the scope of the invention. Preferably the antibodies_will be_monoclonal antibodies. A_suitable test can be carried out to detect a mutation_in the APC cleavage site located at_Arg 306 in an analogous manner using 2 antibodies, one specific_for a part of fragment 1-306 and one_specific for a part of fragment 307-506._Use of an antibody_specifically_recognizing a part of the fragment 307-506_in_such_a_test falls within_the scope of_the invention. An_antibody specifically_recognizing a part_of the