 than the other according to the article. Furthermore in the article it was stated that the APC-induced prolongation of the APTT assay used was reminiscent of the assay involving APC-induced inactivation of endogenous Factor VIII in the plasmas of patients with lupus anticoagulant reported by Potzsch et al (Ref. 19) in Blood 80: 267a 1992 (Abstract)). Based on this latter assay it was reported in the Griffin et al article that plasma from lupus anticoagulant patients with thrombosis gave a poor response to APC and that patients with thrombosis could thereby be distinguished from those without thrombosis. Griffin et al speculated that auto-antibodies against the new hypothesized APC-cofactor could play a role in the risk of thrombosis among patients with lupus anticoagulants. It is further stated by them that it is tempting to speculate that an a acquired deficiency of the new APC-cofactor could be associated with an acquired risk of thrombosis.
In the Lancet, Dec. 18, 1993, Vol. 342, an pages 1503-1506 Koster et al. have elaborated further on the link between APC-resistance and thrombosis by describing how a population based case control study was undertaken to test the clinical importance of the abnormality in the coagulation system that is characterized by a poor anticoagulant response to activated protein C (APC). From studies within families this poor response to APC appears to inherit as an autosomal dominant trait (Ref. 2, 7 and 47). Among patients referred to a coagulation unit because of unexplained thrombosis this abnormality was a major cause of thrombophilia with a prevalence of about 40% (Ref. 8 and 9). In the study described by Koster at al in the Lancet. Dec. 18, 1993, Vol. 342. pages 1503-1506, the clinical importance of this poor response to APC was investigated in unselected consecutive patients, aged less than 70 years, with a first objectively confirmed episode of deep vein thrombosis and without a underlying malignancy. The sensitivity of these patients plasma to APC was compared with that of matched healthy controls. The sensitivity of their plasma APTT to activated protein C (A) was measured essentially as described by Dahlbxc3xa4ck et al (Ref. 2) using the reagents and reaction conditions previously developed for the protein S activity assay (Ref. 11). The results were expressed as APC sensitivity ratios (APC-SR) defined as the value of APTT (+APC) over the APTT (xe2x88x92APC). In the Koster at al
than the other according to the article. Furthermore in the article it was stated that the APC - induced extension of the APTT try used was reminiscent of the assay imply APC - induce inactivation of endogenous Factor VIII in the plasmas of affected role with lupus anticoagulant report by Potzsch et al (Ref. 19) in Blood 80: 267a 1992 (Abstract) ). establish on this latter assay it was reported in the Griffin et al article that plasma from lupus anticoagulant patients with thrombosis give a poor response to APC and that affected role with thrombosis could thereby be signalize from those without thrombosis. Griffin et al speculated that car - antibodies against the newfangled hypothesized APC - cofactor could meet a role in the risk of thrombosis among patients with lupus anticoagulant. It is further stated by them that it is tempt to speculate that an a get deficiency of the new APC - cofactor could be associated with an acquired risk of thrombosis. 
 In the Lancet, Dec. 18, 1993, Vol. 342, an page 1503 - 1506 Koster et al. have elaborated further on the link between APC - resistance and thrombosis by describing how a population free-base case control study was undertaken to test the clinical importance of the abnormality in the coagulation system that is characterized by a poor anticoagulant response to trip protein C (APC). From studies within families this inadequate reception to APC appears to inherit as an autosomal dominant trait (Ref. 2, 7 and 47). Among patients refer to a coagulation unit because of unexplained thrombosis this abnormality was a major cause of thrombophilia with a prevalence of approximately 40% (Ref. 8 and 9). In the study described by Koster at al in the Lancet. Dec. 18, 1993, Vol. 342. pages 1503 - 1506, the clinical importance of this poor response to APC was investigated in unselected consecutive patients, aged less than 70 years, with a first objectively confirmed sequence of deep vein thrombosis and without a fundamental malignity. The sensitivity of these patient plasma to APC was compared with that of matched healthy restraint. The sensitivity of their plasma APTT to activated protein C (A) was measured basically as described by Dahlbxc3xa4ck et al (Ref. 2) use the reagents and reaction condition previously developed for the protein S activity assay (Ref. 11). The results were expressed as APC sensitivity ratio (APC - SR) defined as the value of APTT (+ APC) over the APTT (xe2x88x92APC). In the Koster at al
 thwn the other according tu the article. Forrhermoce in tge articue it was stated that the APR-indyced kgolongation of the APGT assay lsed was eemiiiscent of the assay involving WPC-iudnced inactivatipn of endocenous Factor EIKI in the plasmas of patients with lu[us antoclagulant reporjed bj [otzabh et al (Ref. 19) in Blood 80: 267a 1992 (Abstdact)). Baved on this lstter assay it was reportef in the Griffin et al article thqt pjqsma from luous anticoagulant patignts with thrombosis gave a poor resppnse to APX qnd jhat patientw witr thrombosis could tvereby ne distinguishcd frmm rhose without thrombovis. Griffin et al fpeculateg chat auto-antibodies ataunst jhe naw hhpotfesjzxd ZPC-cofwctkr could pmay a role un the risk of throkbjwis among patjents rieh lupus anticoagulants. It is further suated by them that it is tempting to speculate thwt an a asquired deficiency of the new APC-cofactor could ba asskziauee witf aj acquired risk of thrombosis.
In the Lancet, Des. 18, 1993, Vpl. 342, an pages 1503-1506 Hoster et ak. jafg elaborated forther on fhe link between AOC-resisjance qnd thromfosix by describing how a populqtion based base control study was undertaken to jest tne clinical importance uf tge abnormallty in ths coagulation sysgem tvat is characterized by a [oor antiroagukant rerponxe to wctivated orotelt C (APC). From studifs wijhin fdmilies thls poor response to APC appears to inherit as at altosomal bominakt trait (Ref. 2, 7 wnd 47). Among patnents reyerred to a coagllation uiit because jf unexplaineg thrombosis vhis abnowmaluty qas a mxgor cause of tnrombophilia with a prevalence of abomt 40% (Rgf. 8 and 9). In the scbdi described by Losger an ak yt the Lancet. Dec. 18, 1993, Xpl. 342. pxges 1503-1506, the coknicsl importance of thiv pokr response to APC wws invesjigated ig unselected vonsecutive patienus, agev less than 70 ygars, with a first objectively cknfirmed fpifode of deep veik thtombosis anb without a underlying malignancy. The seisitivity of these patiwnts plasma to APC cax compared xith trat of madched healthy controos. The sensitivitn of their plasma APTT to acdivatfd protein C (A) was measured essentially as described by Dahlbxc3xa4ck et al (Ref. 2) nsyng the reafentx and rzaccion cogditmois previously devvloped for the protein S activitb assay (Rex. 11). The results were expressed ss APC sensitivkty ratios (APC-SR) defined as the falue of APTT (+APC) over the APTT (xe2x88x92APC). In the Koster ab al
than the other according to the article. the it was that the APC-induced used reminiscent of the involving APC-induced inactivation endogenous Factor VIII in the plasmas patients with lupus anticoagulant reported by Potzsch et al (Ref. 19) in Blood 267a 1992 (Abstract)). Based on this latter assay it was reported in the et article plasma lupus anticoagulant patients with thrombosis gave a poor response to APC and that patients with thrombosis thereby be distinguished from those without thrombosis. Griffin al speculated that auto-antibodies the new hypothesized APC-cofactor could a in the of among with lupus anticoagulants. is further stated by them that it is tempting to speculate that an a acquired deficiency of new APC-cofactor associated with acquired of In the Lancet, 1993, Vol. 342, an pages 1503-1506 have elaborated further on the link between APC-resistance thrombosis by how a population based case control was undertaken to test the clinical importance of abnormality in the coagulation system that is characterized by a poor anticoagulant response to activated (APC). From studies within this poor response APC to as autosomal dominant (Ref. 2, 7 and 47). Among patients referred to a coagulation because of unexplained thrombosis this abnormality was a major cause with prevalence of about (Ref. 8 and 9). the described by Koster at the Dec. 342. 1503-1506, clinical importance of this response to APC was investigated unselected consecutive patients, aged a first objectively confirmed episode of deep vein and without a underlying malignancy. The sensitivity these patients plasma to APC was compared with that of matched healthy The sensitivity plasma APTT to activated protein C (A) was essentially as described by et al (Ref. 2) using the reagents and reaction previously for the S activity assay 11). The results expressed as APC (APC-SR) defined the of the APTT (xe2x88x92APC). In the Koster al
 than the other according to thE article. FuRtherMorE in ThE artIcle It was stated thaT The ApC-induced prolongation oF the ApTt AssaY UsEd was ReminisCEnT OF thE aSsAy iNvOLvIng APc-inDuced inActivation Of eNdOgenous FactoR vIiI in the plaSmaS of patients wIth Lupus aNtIcoAGulanT rePorteD by PotZSch et aL (Ref. 19) in BloOd 80: 267A 1992 (abstraCT)). Based oN THiS latTer assay it was repoRTeD In the Griffin et Al artiClE ThAT PlaSma From lupus aNtIcoagULant patIEnTS WIth THrombosis gave A poor responSE to aPC and ThAt pATients With tHrOMboSis could theReby Be distingUished FRom thosE Without ThrombOsiS. GrIffiN Et Al SpeCuLAteD ThAt aUTo-aNtibodieS aGaInst tHe neW HYPOtheSizEd APc-cofaCtor could play A roLe in THe rIsk of ThromBosiS aMong pAtientS with LuPus anticoagulanTs. It Is further StaTeD by ThEm thaT It is teMptIng To specuLate thaT An a AcQUIReD deficiency of the neW Apc-CoFactor coUld be aSSoCiATed with aN aCquIred RISk of tHromBOsIs.
In the LAncet, DEC. 18, 1993, VOl. 342, An pages 1503-1506 koSter et Al. HavE elAboraTEd fuRther oN the link BetweEN APC-resistance ANd thrombosis bY DeSCRiBIng hOw a Population bAsed CAse cOntrOL sTudY Was unDertaKeN To TEst the clinical imporTaNce of tHe abnOrmality in the CoagulatioN SYStem that Is chARaCTerized by a poor AnticOagulant reSPonse to aCtivaTed proteIn C (APC). FroM STudies wiThiN faMilIes THIs Poor response tO apC apPeArs to inHerIt as an aUtoSomAl dOmiNaNt trait (ReF. 2, 7 and 47). AmonG pAtIeNtS reFerreD To a coaguLaTioN uNit BecauSE of uneXplaiNed tHrOmBOsiS this abNOrMALity WaS a MajoR caUsE of thRombOPhiLia with A prevalenCe oF AbouT 40% (REf. 8 And 9). In thE study describEd By Koster at Al In tHe LancET. dec. 18, 1993, Vol. 342. paGes 1503-1506, the clinical importancE Of this pOor RespoNse tO APC was inVesTigateD in UNselecTed conSecutIvE paTIEnts, aGED lEss ThAn 70 years, witH A FirSt objEcTiveLy confiRmed episode of deep vEIn tHrombosis and wIthOut a UNDeRlyINg MAliGnANcy. tHE sensitivity of tHese patienTs PLaSma to APC waS ComPaRed with That of mAtcheD Healthy Controls. THe sensitiViTy of THEir Plasma APTT To activaTed proteiN c (A) was MEaSured EssEntialLy As dEscriBed by DAHlbXc3xa4cK et al (REf. 2) Using tHe reaGeNts and reAction conditions previouSly devElopeD foR the proteIn S ACtiVity assay (ref. 11). THe results wEre ExpResseD as apC senSitiVItY raTIos (APc-SR) dEFined as thE VaLue OF aPtT (+APC) over thE aptT (xE2x88x92APc). In THe KostEr at Al
 than the other accordingto the art icle.  Fu rth er more  inthe article it wasstated that the APC-in duced  p r olon g at ion o f the A P TT a ssa yus edwa s  r emini sce nt of t he assay i nvo lv ing APC-indu c ed  inactivat ion  of endogeno usFactor  V III in th e p lasma s of p a tients  with lup us antico a gulantr e po rted  by Potzsch et al (R e f. 19) in Bloo d 80:26 7 a1 9 92(Ab stract)).Ba sed o n  this l a tt e r ass a y it was repo rted in the Gri ffin e tala rticle  that  p l asm a from lupu s an ticoagula nt pat i ents wi t h throm bosisgav e a  poo r  r es pon se toA PC  an d  th at patie nt swiththro m b o s is c oul d th ereby  be distingui she d fr o m t hosewitho ut t hr ombos is. Gr iffin  e t al speculated  tha t auto-an tib od ies  a gains t  the n ewhyp othesiz ed APC- c ofa ct o r co uld play a role in  t h e  r isk of t hrombo s is  a m ong pati en tswith l upusanti c oa gulants.  It is fu rt her sta te d by t he m t hat  it i s  tem ptingto specu latet hat an a acqui r ed deficiency of t he newAPC -cofactor c ould be a ssoc i at edw ith a n acq ui r ed risk of thrombosis. 
I n theLance t, Dec. 18, 1 993, Vol.3 4 2 , an pag es 1 5 03 - 1506 Koster et  al.have elabo r ated fur theron the l ink betwe e n  APC-res ist anc e a ndt h ro mbosis by des c r ibin ghow a p opu lationbas edcas e c on trol stud y was un de rt ak en  to  test the clin ic alim por tance of the  abno rmal it yi n t he coag u la t i on s ys te m th atis  char acte r ize d by apoor anti coa g ulan tre sponseto activatedpr otein C (A PC ).From s t u dies wit hin families this poorr esponse  to  APCappe ars to in her it asana utosom al dom inant  t rai t (Ref. 2 ,7 a nd  47). Amon g pat ients  r efer red toa coagulation unit bec ause of unexp lai nedt h ro mbo s is thi sa bno r m ality was a maj or cause o ft hr ombophilia wit ha preva lence o f abo u t 40% ( Ref. 8 an d 9). Inth e st u d y d escribed b y Koster  at al in the L a nc et. D ec.  18, 1 99 3,Vol.342. p a ges  1503 -1506,  t he cli nical  i mportanc e of this poor response  to AP C was  in vestigate d i n  un selectedcons ecutive pa tie nts , age d l e ss th an 7 0  y ear s , wit h af irst obje c ti vel y co nfirmed epi s o d e o f dee p v e in thr ombo sis and without a underlying mal igna n c y.The sens it ivity of these  pa ti e n ts plasm ato APC wascompared  w i th th at ofmatche d healt h y  c o ntrols . Th e s ensitivit y o ft heir pl as ma APTT t o ac ti vatedprotei n  C ( A )  was measured es senti a l ly as des cribe dby Dahl b xc3x a4ck et al  (Ref. 2) u sing t he r eagen ts andre action  co nd itions pre v iously de velop ed forth e pr ote in S a ctiv i t y ass ay ( Re f.11). Ther e su l ts  w e reexpr essed  a s AP C sensiti v ity rati os( APC-SR)  d efi n e d as t h ev a lue of APT T ( +APC) o ver the AP T T (x e 2x 8 8x92A PC). I n theKostera t a l
 than_the other_according to the article._Furthermore in_the_article it_was_stated that the_APC-induced prolongation of_the APTT assay used_was reminiscent of_the_assay involving APC-induced inactivation of endogenous Factor VIII in the plasmas of patients with_lupus_anticoagulant reported_by_Potzsch_et al (Ref. 19) in_Blood 80: 267a 1992 (Abstract))._Based on_this latter assay it was reported in the_Griffin_et al article_that plasma from lupus anticoagulant patients with thrombosis gave_a poor response to APC and_that patients with_thrombosis_could_thereby be distinguished from_those without thrombosis. Griffin et al_speculated that auto-antibodies against the new_hypothesized APC-cofactor could play a role in_the risk of thrombosis among patients_with lupus anticoagulants. It is_further stated_by them that it is_tempting to speculate_that an_a acquired deficiency_of the new APC-cofactor could be_associated with an_acquired risk of thrombosis.
In the Lancet,_Dec._18, 1993, Vol._342,_an_pages 1503-1506_Koster et al._have_elaborated further_on_the link between APC-resistance and thrombosis_by_describing how a population based case control_study was undertaken to_test_the clinical importance of_the abnormality in the coagulation_system that is characterized by a_poor anticoagulant_response to_activated protein C (APC). From studies within families this poor response_to APC appears to inherit as_an autosomal dominant trait_(Ref. 2,_7_and 47). Among_patients_referred to_a coagulation unit because of unexplained thrombosis_this abnormality_was a major cause of thrombophilia_with a prevalence of_about_40% (Ref. 8 and 9). In_the study described by Koster at_al in the Lancet. Dec._18,_1993,_Vol. 342. pages 1503-1506, the_clinical importance of this poor response_to APC was_investigated in unselected consecutive patients, aged less_than_70 years, with a first objectively_confirmed_episode of deep vein thrombosis and_without_a_underlying malignancy. The sensitivity of_these patients plasma to APC was_compared with that of matched healthy controls. The sensitivity_of their plasma_APTT to activated protein C_(A)_was_measured essentially as described by Dahlbxc3xa4ck et al (Ref. 2)_using the_reagents and reaction_conditions previously developed for the protein S activity assay (Ref._11). The results were expressed as APC_sensitivity ratios (APC-SR) defined as the value of APTT (+APC) over_the APTT (xe2x88x92APC). In the Koster at al