- Email: [email protected]
Platelet plasminogen activator inhibitor type 1 (PAI-1) in insulin-dependent diabetes mellitus
Fw (1992) 6, Supp:3,89-91 @ Langman Croup UK IAd 1992
Platelet Plasminogen Activator Inhibitor Type 1 (PAL1) in Insulin-Dependent Diabetes Mellitus
B.J. Potter van Loon*, H.J.G. Bile**, C. Brumsen***, P. Meijer****, P.H.L.M. Geelhoed-Duijvesteijn***, Khlft****
C.
SUMMARY. The major part of blood plasminogen activator inhibitor type 1 (PAL1) is present in platelets. Reduction of platelet PAL1 could promote lysis of (micro-)thrombi and thereby prevent the development of atherosclerotic vascular occlusion. We performed two pilot studies on platelet PAL1 in poorly-regulated insulindependent diabetes mellitus (IDDM) patients. In study A, platelet PAL1 remained stable despite the administration of the platelet-modifying agents aspirin and yohimbine. In study B, improvement of glycaemic control did not alter platelet PAL1. KEYWORDS. Platelets. Plasminogen activator inhibitor type 1 (PAL1). Insulin-dependent diabetes mellitus
effects of aspirin and of yohimbine on platelet PAIantigen. Yohimbine is an a2-adrenoceptor antagonist which decreases platelet catecholamine-uptake.61n study B we examined the effect of improvement of glycaemic control on platelet PAI- antigen.
INTRODUCTION In insulin-dependent diabetes mellitus (IDDM) atherosclerotic cardiovascular disease is often already present at an early age. Increased platelet aggregability and a reduced fibrinolytic activity may contribute to the development of atherosclerotic disease in IDDM.’ In vivo platelet aggregability in IDDM is related to the degree of glycaemic control and can be reduced by aspirin.2 The mechanism resulting in increased aggregability is poorly understood. Increased platelet catecholamine-uptake has been suggested as a cause.3 Plasminogen activator inhibitor type 1 (PAI-1) accumulates in thrombi and inhibits spontaneous thrombolysis.4The accumulation of PAI- in thrombi is probably the result of the release of PAI- by platelets within the thrombus, as platelets contain SO-95% of total blood PAI- antigen.’ Drugs, or conditions, that decrease platelet PAIcontent could, therefore, possibly increase spontaneous fibrinolysis. The improvement of spontaneous librinolysis is probably of benefit in retarding premature atherosclerotic vascular occlusion in poorly-controlled IDDM. We therefore performed two pilot studies in poorlycontrolled IDDM patients. In study A we examined the
METHODS Study A 7 IDDM patients (4 male, 3 female, 32 + 9 yrs (mean & SD), duration of IDDM 13 + 11 yrs, body mass index 22.7 ? 1.2 kg/m’) with poor glycaemic control (HbA#.6 t 1.5%, normal values 4-6%) were studied before treatment (basal values). Thereafter, they were treated for 2 weeks with either placebo (plac), 40 mg aspirin (asp) daily or 5 mg yohimbine (yoh) daily in a latin-square design trial. Platelet pellet was made by centrifugation (20 min, 2500 x g, 4C) of platelet-rich plasma (PRP) from CTAD-anticoagulated blood (13 min, 100 x g, 2O’C). Platelets were counted in PRP. Serum was made by adding 10 U of thrombin to 10 ml of fresh blood. PAI- antigen was measured in platelet pellet after freezing and thawing three times,‘and in serum (Monozyme, Charlottenlund, Denmark).
*Dept. Internal Medicine, St. Lucas Ziekenhuis, J. Tooropstraat 164, 1061 AE Amsterdam, The Netherlands; *‘Dept. Internal Medicine, Ziekenhuis “De Weezenlanden”, Zwolle, The Netherlands; ***Dept. Internal Medicine, Westeinde Ziekenhuis, The Hague, The Netherlands; ?? ***Gaubius Laboratory IWO-TNO, Leiden, The Netherlands
Study B In 7 IDDM patients (2 male, 5 female, 30 + 10 yrs (mean t SD), duration of IDDM 14 + 7 yrs, weight 69
89
%ugnpal 38 patup2 uoyuaalavy leql uo!lsa%?nsaql sihpug raglEaaqlol ppe puE8sa~els asEas!p30.xaqtunu e u! a[qeP d[-'!ys! [=a[ I-Ivd la[av[daql leql '[E lauosduus30 sfhupugrayEa ayl WJ~UOD sl[nsal asayL *s[aAa[ I-Iv,-J ]a[alE[d 30 suo!]Elal[E u! i[nsal01 ulaas IOU op bl!agaEa~ la[alE[d 8uupnpalI&?pam!e ale qa!q~ NaaI pa[[onuo34[loodu! suoyuaA.talu! ‘JaAoalow 6*sAEssE uai$ue pasn aql 304srjpads u!saauara33rp 01palE[al aq hu sy~,<.[ela 3oqI!nq6qpuno3 s]unomE aylyl~au![u!a.towaJEpue laMo[c oJz~oPe3 a a.xE sa!pnjs mo u!slunowe aln[osqE ayl jnq ,‘lyaaI u! san[Eh[EWJOU pun03 OHM *[Ela nosduus30 asoy]~1% auq u! alE s%pug .uto*luElraqs IOUaJe s[aAa[ I-Ivd la[alE[d MaaI pa[[o.woad[.tood u! )Eyia~uap~apapyorda~Eqa~sa!pn]slo[!do~lasay]UI
.as 5 ueaw aJe sanleA .(yoL) au!qugqoA JO ‘(dse) up!dse ‘(Jeld) oqaxld Jaql!a q,F ddeJaql iluynp Queqa IOU Saop pile S(OJlUOJ dq,leX, UlOJJ lUaJaJJ!p I(l)WB!J!U%!S IOU SeM ,OJ,UOJ +laeJ&i Jood l[ly naa[ u! lla%!iue I-Ivd lalaleld ‘v Lpnls 1 ‘%!A
002
xunms WOJJ paJaAooJa1 wq~ slalle.red swlad $alaleld waj parahoJaJ ua%!we I-Ivd 8 pue v sa!pw qloq u1 2 ‘%!d
OOL
OS
0 0
B
2: : 0
OOE
x 0 S
oat
GI) OL’OPue (VI IL’0 aJe slua!agJaos uo!lelauo3
(dtld IWfiU) wiled wlwqd 091
OS
OOL
L
'('S-N) ++13adsar ‘["/gu 62 T 96 puE ‘& + (l6‘8s T 26 '9~ T 26 alaM au!qw!qo6pw u!.qdsE ‘oqaas[d‘uoyeu -!wlaiap[EsEq@Jnp ua?$luEI-Ivd uxnJas~03san[EA '(1'% aas)(‘S’N) wwqd ,ol/sd 68 + 6vz pue POT. + ZSZ ‘65 T 8SZ aJaM slunowe aAgDadsaraqL 'awq -w!qorC 10 ‘upidse‘oqaaE[d.xayl!a yl$ Aderayl%u!mp ua8yuE I-Ivd la[alE[d ui a%Ey:, ou SBM araqJ *(sla[ -alE[d@8d sp T ~61)s[owoa Ayqeay ~IOJJiuaqgp dlluq!u8!s IOU ‘sla[ale[d,o@d,59T 8s~ SBM [o~luoa a!waEad[8.Joodql!M KaaI
2 3
u! uaiFl!iukz I-Ivd ia[alE[d
v 4ws
P g
'as T uealuse passaldxaaJE sqnsar[[v 091
ii 2 2.
002
*as $10’0 > d ‘SS = u ‘g dpnls) x0 pup (TOO’0 > d ‘IP = u ‘v Apes) gs’o aJaM d&J y sluno3 ]a[aqd pm sla[[ad la[ale[d u! ua8yue I-Ivd uaahwq slua!arJJaoa uoye[arlo3 ‘8 6pnis u! (lp = u) [/8 01 + 73 7 cti SBM luno:, ~ap~qd d&j pale~!l= pW V %pw y (SS = u) [/%&I . 86 T ggs SEA luno:,la[ajE[d dad ‘(2 ‘s!l!tIaas) (UIO-0 > d) (6s = u ‘8 dPn)s) OL’O pm (1~ = u ‘v 6pnJs) 1~0 ale san[m umras pue ]a[[ad la[ala[d uaaMlaq sluag3ao3 uoye[alJoa aqL *san[m ua8 -!W I-IVd tumas Jo (6S = u ‘8 dpnls) 9&I T 99 pue (w = u ‘v Apw) %pz + 98 p[afi w[[ad v[w[d ‘(8 = u) umas [tu/%n 1Z T ~01 pua sla[ale[d Or/%d 98 ? m SlFMua%iue I-IVd ‘(O?&‘O7 S’LJ’vqHq lasuo je [o~~uoa a!uxaea@ ambapa yl~ ygyaaI paqsww-a% u! ‘uosytzdmoa JOJ *L[aA!gadsaJ ‘[owe:, (puZ) alenb -ape i?u!.mp pue (IS-I) .xood %u!mp [ux/% f=Z T ~6 pue gZ + 66 aiam mm u! ua8yua I-Ivd 30 san[eA ‘(Sp’O = d) w[ale[d Gr/8d 08 + 88~.'SA753T 90~ :ua8yue I-Ivd Ja[ale[d Jal[e iou p!p [OJIUO~$uam@ 30 JUatUaAO~dwI 8
4ws
T ueatusEpassa~dxaalesl[nsar [[v's!sA[eue uo!ssar%al .tEauypue isal-s,luapnls papn[au!sisal[esysfwis v dpnis u! paq!Jasapspoqiaw aql 01 i%up~oaaEpa.tnsEawSEM ua8yue I-Ivd pue apew aJaMsla[[ad la[alqd(s&i1~.T E ‘a[Ewa3s ‘a[et.u S) siaafqns [omos Lqqeaq 01 UI *v dpnisu! paq!Jasapse pau!waiap REM ua&luE T-IVd pUE apEUJ SBM UInJafj 'dad-(JV,J3II!.IaqUIt'lU aqi u!Eiqo 01 (roiaE3pau!waiap d[[vluaur!ladxa) ~'1dq paydy[ntupw poo[q paiE[n%?ogluE-vL(g us paiunoaaJaM sla[alE[d '(~~02‘8x 0s~ ‘uy.u01) poo[q pw[n~~ogiue-av~
UXJq d&J 30 (3.p ‘2 x eon
‘yu 0~) uo!ie%jyua:,hq apeux SBM la[[ad la[aie[d ‘(‘S’N ‘12 ZT + SS) asop uynsu! d[!ep [elolJE[!W!SE al!dsap lale[ sqluom aAg (S@O > d ‘(oj,‘_‘O T 6’~ J’vqH) [OJ~UO:,?wat?a 618 30 lUauIa,iOJdw! u! pa][nsal s!y~, *sluawa.uw?aux asoy poo[q [osu03-3[as 01 %up~oaae paisnipa sehi asop uynsu! pm pagsuaiu! SEM san[Ehasoar@ poo[q 30 %U!.lOl!UOUl (%9'0 7 L'6"vqH) [OJlUOaa!UIaE+ rood ql%
snlylayy salaqe!a iuapuadaa-uynsuI
(n
~1: T ps
asop ugnsu! @p
u! (r-Iv& 1 cd& JowquI Jomyv
91
L T
ua%u!wswd laiawd
06
Pibrinolysis 91
Differences in PAI- amounts recovered from platelet pellets may reflect differences in platelet count in PRP, as we and othersl’have found a significant correlation between platelet count in PRP and PAI- antigen recovered from the pellets. This may explain the differences found between PAI- antigen levels in PRP and in serum in our and other” studies. Obviously, the differences in centrifugation technique between our studies A and B and in platelet counting (in PRP vs. in blood) contributed to the differences in the PRP-pellet to serum ratio of PAI- antigen (0.66 vs. 0.86). These considerations may render it more practical to collect and measure serum for platelet PAI- determination, rather than to isolate platelets and measure PAI- in the platelet pellets.
REFERENCES Colwell J A, Lopes-Virella M F 1988 A review of the development of large-vessel disease in diabetes mellitus. Am J Med 85 (Supp 5A): 113-118 Davi G, Catalan0 I, Avema M et al 1990 Thromboxane synthesis and platelet function in type II diabetes mellitus. N Engl J Med 322: 1769-1774 Wilson A P, Smith C C T, Prichard B N C et al 1987 Platelet
catecholamines and platelet function in normal human subjects. Clin Sci 73: 99-103 4. Potter van Loon B J, Rijken D C, Brommer E J P 1992 The amount of plasminogen, tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in human thrombi and the relation to ex viva @ability. Thromb Haemostas 67: lOl10s 5. Kruithof E K 0, Nicolosa G, Bachmann F 1987 Plasminogen activator inhibitor 1: development of a radioimmunoassay and observations on its plasma concentrations during venous occlusion and after platelet aggregation. Blood 70: X45-1653 6. Goodman and Gilman’s 1985 The Pharmacological Basis of Therapeutics, 7th ed. Goodman-Gilman A, Goodman L S, Rail T W, Murad F (eds), MacMillan, New York 7. Griep E N, Van der Zee M C, Den Ottolander G J H 1990 Determination of plasminogen activator inhibitor in human plasma and blood platelets and its clinical relevance. Fibrinolysis 4, supp 2: 141-144 8. Simpson A J, Booth N A, Moore N R et al 1990 The platelet and plasma pools of plasminogen activator inhibitor (PAI-1) vary independently in disease. Br J Haematol 75: 543-548 9. Kluft C, Jie A F H 1990 Comparison of specificities of antigen assays for plasminogen activator inhibitor 1 (PAI-1). Fibrinolysis 4, supp2: 136-137 10. Booth N A, Simpson A J, Croll A et al 1988 Plasminogen activator inhibitor (PAI-1) in plasma and platelets. Br J Haematol 70: 327-333 11. Booth N A, Croll A, Bennett B 1990 The activity of plasminogen activator inhibitor 1 (PAI-1) of human platelet. Fibrinolysis 4, supp 2: 138-140
Platelet Plasminogen Activator Inhibitor Type 1 (PAL1) in Insulin-Dependent Diabetes Mellitus
B.J. Potter van Loon*, H.J.G. Bile**, C. Brumsen***, P. Meijer****, P.H.L.M. Geelhoed-Duijvesteijn***, Khlft****
C.
SUMMARY. The major part of blood plasminogen activator inhibitor type 1 (PAL1) is present in platelets. Reduction of platelet PAL1 could promote lysis of (micro-)thrombi and thereby prevent the development of atherosclerotic vascular occlusion. We performed two pilot studies on platelet PAL1 in poorly-regulated insulindependent diabetes mellitus (IDDM) patients. In study A, platelet PAL1 remained stable despite the administration of the platelet-modifying agents aspirin and yohimbine. In study B, improvement of glycaemic control did not alter platelet PAL1. KEYWORDS. Platelets. Plasminogen activator inhibitor type 1 (PAL1). Insulin-dependent diabetes mellitus
effects of aspirin and of yohimbine on platelet PAIantigen. Yohimbine is an a2-adrenoceptor antagonist which decreases platelet catecholamine-uptake.61n study B we examined the effect of improvement of glycaemic control on platelet PAI- antigen.
INTRODUCTION In insulin-dependent diabetes mellitus (IDDM) atherosclerotic cardiovascular disease is often already present at an early age. Increased platelet aggregability and a reduced fibrinolytic activity may contribute to the development of atherosclerotic disease in IDDM.’ In vivo platelet aggregability in IDDM is related to the degree of glycaemic control and can be reduced by aspirin.2 The mechanism resulting in increased aggregability is poorly understood. Increased platelet catecholamine-uptake has been suggested as a cause.3 Plasminogen activator inhibitor type 1 (PAI-1) accumulates in thrombi and inhibits spontaneous thrombolysis.4The accumulation of PAI- in thrombi is probably the result of the release of PAI- by platelets within the thrombus, as platelets contain SO-95% of total blood PAI- antigen.’ Drugs, or conditions, that decrease platelet PAIcontent could, therefore, possibly increase spontaneous fibrinolysis. The improvement of spontaneous librinolysis is probably of benefit in retarding premature atherosclerotic vascular occlusion in poorly-controlled IDDM. We therefore performed two pilot studies in poorlycontrolled IDDM patients. In study A we examined the
METHODS Study A 7 IDDM patients (4 male, 3 female, 32 + 9 yrs (mean & SD), duration of IDDM 13 + 11 yrs, body mass index 22.7 ? 1.2 kg/m’) with poor glycaemic control (HbA#.6 t 1.5%, normal values 4-6%) were studied before treatment (basal values). Thereafter, they were treated for 2 weeks with either placebo (plac), 40 mg aspirin (asp) daily or 5 mg yohimbine (yoh) daily in a latin-square design trial. Platelet pellet was made by centrifugation (20 min, 2500 x g, 4C) of platelet-rich plasma (PRP) from CTAD-anticoagulated blood (13 min, 100 x g, 2O’C). Platelets were counted in PRP. Serum was made by adding 10 U of thrombin to 10 ml of fresh blood. PAI- antigen was measured in platelet pellet after freezing and thawing three times,‘and in serum (Monozyme, Charlottenlund, Denmark).
*Dept. Internal Medicine, St. Lucas Ziekenhuis, J. Tooropstraat 164, 1061 AE Amsterdam, The Netherlands; *‘Dept. Internal Medicine, Ziekenhuis “De Weezenlanden”, Zwolle, The Netherlands; ***Dept. Internal Medicine, Westeinde Ziekenhuis, The Hague, The Netherlands; ?? ***Gaubius Laboratory IWO-TNO, Leiden, The Netherlands
Study B In 7 IDDM patients (2 male, 5 female, 30 + 10 yrs (mean t SD), duration of IDDM 14 + 7 yrs, weight 69
89
%ugnpal 38 patup2 uoyuaalavy leql uo!lsa%?nsaql sihpug raglEaaqlol ppe puE8sa~els asEas!p30.xaqtunu e u! a[qeP d[-'!ys! [=a[ I-Ivd la[av[daql leql '[E lauosduus30 sfhupugrayEa ayl WJ~UOD sl[nsal asayL *s[aAa[ I-Iv,-J ]a[alE[d 30 suo!]Elal[E u! i[nsal01 ulaas IOU op bl!agaEa~ la[alE[d 8uupnpalI&?pam!e ale qa!q~ NaaI pa[[onuo34[loodu! suoyuaA.talu! ‘JaAoalow 6*sAEssE uai$ue pasn aql 304srjpads u!saauara33rp 01palE[al aq hu sy~,<.[ela 3oqI!nq6qpuno3 s]unomE aylyl~au![u!a.towaJEpue laMo[c oJz~oPe3 a a.xE sa!pnjs mo u!slunowe aln[osqE ayl jnq ,‘lyaaI u! san[Eh[EWJOU pun03 OHM *[Ela nosduus30 asoy]~1% auq u! alE s%pug .uto*luElraqs IOUaJe s[aAa[ I-Ivd la[alE[d MaaI pa[[o.woad[.tood u! )Eyia~uap~apapyorda~Eqa~sa!pn]slo[!do~lasay]UI
.as 5 ueaw aJe sanleA .(yoL) au!qugqoA JO ‘(dse) up!dse ‘(Jeld) oqaxld Jaql!a q,F ddeJaql iluynp Queqa IOU Saop pile S(OJlUOJ dq,leX, UlOJJ lUaJaJJ!p I(l)WB!J!U%!S IOU SeM ,OJ,UOJ +laeJ&i Jood l[ly naa[ u! lla%!iue I-Ivd lalaleld ‘v Lpnls 1 ‘%!A
002
xunms WOJJ paJaAooJa1 wq~ slalle.red swlad $alaleld waj parahoJaJ ua%!we I-Ivd 8 pue v sa!pw qloq u1 2 ‘%!d
OOL
OS
0 0
B
2: : 0
OOE
x 0 S
oat
GI) OL’OPue (VI IL’0 aJe slua!agJaos uo!lelauo3
(dtld IWfiU) wiled wlwqd 091
OS
OOL
L
'('S-N) ++13adsar ‘["/gu 62 T 96 puE ‘& + (l6‘8s T 26 '9~ T 26 alaM au!qw!qo6pw u!.qdsE ‘oqaas[d‘uoyeu -!wlaiap[EsEq@Jnp ua?$luEI-Ivd uxnJas~03san[EA '(1'% aas)(‘S’N) wwqd ,ol/sd 68 + 6vz pue POT. + ZSZ ‘65 T 8SZ aJaM slunowe aAgDadsaraqL 'awq -w!qorC 10 ‘upidse‘oqaaE[d.xayl!a yl$ Aderayl%u!mp ua8yuE I-Ivd la[alE[d ui a%Ey:, ou SBM araqJ *(sla[ -alE[d@8d sp T ~61)s[owoa Ayqeay ~IOJJiuaqgp dlluq!u8!s IOU ‘sla[ale[d,o@d,59T 8s~ SBM [o~luoa a!waEad[8.Joodql!M KaaI
2 3
u! uaiFl!iukz I-Ivd ia[alE[d
v 4ws
P g
'as T uealuse passaldxaaJE sqnsar[[v 091
ii 2 2.
002
*as $10’0 > d ‘SS = u ‘g dpnls) x0 pup (TOO’0 > d ‘IP = u ‘v Apes) gs’o aJaM d&J y sluno3 ]a[aqd pm sla[[ad la[ale[d u! ua8yue I-Ivd uaahwq slua!arJJaoa uoye[arlo3 ‘8 6pnis u! (lp = u) [/8 01 + 73 7 cti SBM luno:, ~ap~qd d&j pale~!l= pW V %pw y (SS = u) [/%&I . 86 T ggs SEA luno:,la[ajE[d dad ‘(2 ‘s!l!tIaas) (UIO-0 > d) (6s = u ‘8 dPn)s) OL’O pm (1~ = u ‘v 6pnJs) 1~0 ale san[m umras pue ]a[[ad la[ala[d uaaMlaq sluag3ao3 uoye[alJoa aqL *san[m ua8 -!W I-IVd tumas Jo (6S = u ‘8 dpnls) 9&I T 99 pue (w = u ‘v Apw) %pz + 98 p[afi w[[ad v[w[d ‘(8 = u) umas [tu/%n 1Z T ~01 pua sla[ale[d Or/%d 98 ? m SlFMua%iue I-IVd ‘(O?&‘O7 S’LJ’vqHq lasuo je [o~~uoa a!uxaea@ ambapa yl~ ygyaaI paqsww-a% u! ‘uosytzdmoa JOJ *L[aA!gadsaJ ‘[owe:, (puZ) alenb -ape i?u!.mp pue (IS-I) .xood %u!mp [ux/% f=Z T ~6 pue gZ + 66 aiam mm u! ua8yua I-Ivd 30 san[eA ‘(Sp’O = d) w[ale[d Gr/8d 08 + 88~.'SA753T 90~ :ua8yue I-Ivd Ja[ale[d Jal[e iou p!p [OJIUO~$uam@ 30 JUatUaAO~dwI 8
4ws
T ueatusEpassa~dxaalesl[nsar [[v's!sA[eue uo!ssar%al .tEauypue isal-s,luapnls papn[au!sisal[esysfwis v dpnis u! paq!Jasapspoqiaw aql 01 i%up~oaaEpa.tnsEawSEM ua8yue I-Ivd pue apew aJaMsla[[ad la[alqd(s&i1~.T E ‘a[Ewa3s ‘a[et.u S) siaafqns [omos Lqqeaq 01 UI *v dpnisu! paq!Jasapse pau!waiap REM ua&luE T-IVd pUE apEUJ SBM UInJafj 'dad-(JV,J3II!.IaqUIt'lU aqi u!Eiqo 01 (roiaE3pau!waiap d[[vluaur!ladxa) ~'1dq paydy[ntupw poo[q paiE[n%?ogluE-vL(g us paiunoaaJaM sla[alE[d '(~~02‘8x 0s~ ‘uy.u01) poo[q pw[n~~ogiue-av~
UXJq d&J 30 (3.p ‘2 x eon
‘yu 0~) uo!ie%jyua:,hq apeux SBM la[[ad la[aie[d ‘(‘S’N ‘12 ZT + SS) asop uynsu! d[!ep [elolJE[!W!SE al!dsap lale[ sqluom aAg (S@O > d ‘(oj,‘_‘O T 6’~ J’vqH) [OJ~UO:,?wat?a 618 30 lUauIa,iOJdw! u! pa][nsal s!y~, *sluawa.uw?aux asoy poo[q [osu03-3[as 01 %up~oaae paisnipa sehi asop uynsu! pm pagsuaiu! SEM san[Ehasoar@ poo[q 30 %U!.lOl!UOUl (%9'0 7 L'6"vqH) [OJlUOaa!UIaE+ rood ql%
snlylayy salaqe!a iuapuadaa-uynsuI
(n
~1: T ps
asop ugnsu! @p
u! (r-Iv& 1 cd& JowquI Jomyv
91
L T
ua%u!wswd laiawd
06
Pibrinolysis 91
Differences in PAI- amounts recovered from platelet pellets may reflect differences in platelet count in PRP, as we and othersl’have found a significant correlation between platelet count in PRP and PAI- antigen recovered from the pellets. This may explain the differences found between PAI- antigen levels in PRP and in serum in our and other” studies. Obviously, the differences in centrifugation technique between our studies A and B and in platelet counting (in PRP vs. in blood) contributed to the differences in the PRP-pellet to serum ratio of PAI- antigen (0.66 vs. 0.86). These considerations may render it more practical to collect and measure serum for platelet PAI- determination, rather than to isolate platelets and measure PAI- in the platelet pellets.
REFERENCES Colwell J A, Lopes-Virella M F 1988 A review of the development of large-vessel disease in diabetes mellitus. Am J Med 85 (Supp 5A): 113-118 Davi G, Catalan0 I, Avema M et al 1990 Thromboxane synthesis and platelet function in type II diabetes mellitus. N Engl J Med 322: 1769-1774 Wilson A P, Smith C C T, Prichard B N C et al 1987 Platelet
catecholamines and platelet function in normal human subjects. Clin Sci 73: 99-103 4. Potter van Loon B J, Rijken D C, Brommer E J P 1992 The amount of plasminogen, tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in human thrombi and the relation to ex viva @ability. Thromb Haemostas 67: lOl10s 5. Kruithof E K 0, Nicolosa G, Bachmann F 1987 Plasminogen activator inhibitor 1: development of a radioimmunoassay and observations on its plasma concentrations during venous occlusion and after platelet aggregation. Blood 70: X45-1653 6. Goodman and Gilman’s 1985 The Pharmacological Basis of Therapeutics, 7th ed. Goodman-Gilman A, Goodman L S, Rail T W, Murad F (eds), MacMillan, New York 7. Griep E N, Van der Zee M C, Den Ottolander G J H 1990 Determination of plasminogen activator inhibitor in human plasma and blood platelets and its clinical relevance. Fibrinolysis 4, supp 2: 141-144 8. Simpson A J, Booth N A, Moore N R et al 1990 The platelet and plasma pools of plasminogen activator inhibitor (PAI-1) vary independently in disease. Br J Haematol 75: 543-548 9. Kluft C, Jie A F H 1990 Comparison of specificities of antigen assays for plasminogen activator inhibitor 1 (PAI-1). Fibrinolysis 4, supp2: 136-137 10. Booth N A, Simpson A J, Croll A et al 1988 Plasminogen activator inhibitor (PAI-1) in plasma and platelets. Br J Haematol 70: 327-333 11. Booth N A, Croll A, Bennett B 1990 The activity of plasminogen activator inhibitor 1 (PAI-1) of human platelet. Fibrinolysis 4, supp 2: 138-140