TAP CHl Y DUOC LAM SANG 108 Tap 11-565/2016
Nghien cihi m6i lien quan gi&a mot so y§u td dong mau va sinh hoa mau 6* benh nhan hoi chung than hxr nguyen phat ngwoi Ion
studying co-relationship between serum ATIII, protein C, protein S concentration with urine protein concentration and some bio-chemical parameters in the patients with nephrotic syndrome
Nguyin Thi Bich Ng9c*, Dinh Thi Kim Dung*, *Benh vien Bgch Mai Nguygn Xuan Hi^n*, Ha Hoang Ki^m** **^^"^ ^^^« 2««« y i03
Muc tiiu: Nghien edu sU thay ddi ndng do ATIII, protein C, protein S d benh nhan trUdng thanh ed hdi chdng than hu nguyen p h l t va sU tUOng quan gida ndng dp ATIII, protein C, protein S vdi mdc protein nieu va mot sd thdng so sinh hda mau. Doi tugng vd phUOng phdp: Nghien cdu 200 benh nhan ngudi Idn bj hpi chLftig than h u nguyen phat va 40 ngudi khde manh. Kit qud vd kit ludn: 6 hgl ehdng than h u nguyen phat ngUdl Idn, ndng do ATIII trong mau: 97,76 ± 9,68%, g i l m thap hon so vdi ehdng:
114,05 ± 10,17% (p<0,001). Ndng dp protein S: 67,28 ± 10,17%, g i l m t h I p hon so vdi ehdng: 114,15 ± 12,6 (p<0,01). Ndng do protein C: 117,13 ± 20,1%, khdng k h i c biet so vdi ehdng: 118,78 ± 19,37%
(p=0,634). Ndng dp ATIII trong m l u cd tUOng quan thuan mde do chat vdi albumin mau (r = 0,62, p<0,01), tuong quan nghjch mdc d d chat vdi ndng do protein ni&u 24h va ndng dp cholesterol m l u (r = - 0,55, p<0,05 va r = -0,56, p<0,01). Ndng dp protein S trong m l u cd tUdng quan thuan mde dp vda vdi albumin mau (r = 0,33, p<0,05), tdong quan nghjch mdc d d Vda vdi protein nieu va cholesterol m l u (r = -
0,30, p<0,05 va r = -0,39, p<0,05). » TUkhda: Hpi ehdng t h i n hd, rdi loan ddng mau, ATIII, protein S, protein C.
Summary
Objective: Studying change of serum ATIII, protein C, protein S concentration in adult patients with nephrotic syndrome and co-relationship between serum ATIII, protein C, Protein S concentration with urine protein level and some serum bio-chemical parameters. Subject and method: 200 adult patients with nephrotic syndrome from 16 t o 60 years old and 40 health persons were studied. Result and conclusion: In the adult patients with nephrotic syndrome, serum ATIII concentration: 97.76 ± 9.68% was decreased with p<0.001. Serum protein S concentration: 67.28 ± 10.17% was decreased with p<0.001.
Serum protein C: 117.13 ± 20.1% was not changed, p=0.634. There are positive co-relationship between
Ng^ nhdn 03/10/2016, ngdy chap nhgn 20/10/2016
Ngudi phdn hSv Nguyin Le Ngoc Khanh - B4nh vien Rang Hdm Mdt Trung uong
JOURNALOF 108-CLINICAL MEDICINEAND PHARMACY Vol.11-N-5/2016 serum ATIII concentration with serum albumin concentration (r = 0.62, p<0.01) and negative co- relationship with urine protein 24h and serum cholesterol concentration (r = -0.55, p<0.05 and r = -0.56, p<0.01). Serum protein S concentration had positive co-relationship with serum albumin concentration (r = 0.33, p<0.05) and negative co-relationship with urine protein 24h and serum cholesterol concentration (r = -0.30, p<0.05 and r = -0.39, p<0.01).
Keywords: Nephrotic syndrome, ATIII, protein C, protein S, coagulation disorders.
1. Dat van de
Hdi ehdng than hd (HCTH) thudng xay ra trong giai doan tien trien nang cua eae benh cau t h i n . HCTH gay ra nhilu biln chdng, cac bien chdng nly lai lam cho HCTH tien trien nang them.
Cac biln chdng thudng gap II suy t h i n cap, suy than man, tang ddng mau v l nghen tie maeh, nhiem trung, suy dinh dudng... Trong dd biln chdng tang ddng mlu va nghen tac mach la mdt trong ele biln chdng nang, nguy hilm, gap vdi tl l# 10 - 42% 15] tuy theo tdng t i e g i l , cao hdn 8 lan so vdi quan t h i dan cd ndi ehung [6]. Rdi loan ddng mlu 6 benh nhln HCTH theo nhieu nghien edu thi gilm ATIII, gilm protein C, gilm protein S trong mau do mat qua nddc t i l u ddng vai trd quan trpng. Mot s6 nghien edu nUdc ngoai cho thay ndng do eac chat nay gilm cd lien quan vdi ndng do protein nieu. Trong nude ehung tdi chUa thay cd nghien cdu nao ddgc cdng bd ve van d l nay, vl vay ehung tdi t i l n hanh nghien edu de t i i nay vdi hai mue tieu: Khdo sdt nong do ATIII, protein C, protein S trong huyit thanh d binh nhdn HCTH nguyen phdt ngudi Idn. Ddnh gid moi tuang quan glUa ATIII, protein C, protein S huyit thanh vdi nong do protein niiu 24h vd mot so thdng so sinh hda mdu d cdc benh nhdn trin.
2. €>oi tugng va phUcfng phap 2.1. Ddi tugng
Gdm 200 benh nhln (BN) ddgc chin doan xac djnh HCTH nguyen phlt cd tudi 16-60, dllu trj tai Benh viln Bach Mai td 4/2008 - 4/2011 v l 40 ngudi khde manh, cd tudi tddng dddng.
2.2. Phuang phdp '*'~:i
Tien cdu, md ta cat ngang cd doi chdng. -^
Tiiu chudn chgn doi tugng
Nhdm benh: BN dugc chan doan xlc dinh HCTH nguyen phat, tudi 16 - 60, chUa duge dilu trj, ed mu'c loc cau thin > 60ml/ph.
Nhdm chdng la ngUdi ed sdc khde binh thudng den kham sdc khde tai Benh vien.
Ddng y tham gia nghiln edu.
Tiiu chudn logi trU BN dang duge dieu trj HCTH.
BN bj mac cac benh khic anh hudng din ddng- cam mlu nhU eac benh v l mau, chly mau cap hoac man tfnh, suy gan nang, nhiem trung nang...hoac dang sd dung cac thude Inh hudng d i n ddng - cam mlu nhusyntrom...
Khdng ddng y tham gia nghien edu.
Tieu chuan chan doan va xet nghiem.
Chan doln HCTH nguyin phat [1]: PhOi ^ protein mau < 60g/l albumin m l u < 30g/l, protein nilu > 3,5g/24h, lipid mau tang. Trong do bat budc phli cd t i l u chuan protein nieu, protein va albumin mau.
Djnh lugng ATIII, protein C, protein S tai Khoa Huyet hpc va truyin mlu Benh vien Bach Mai, sH dung may CAI 500 cda hang SYSMEX, chat kich hoat la npc ran Russell.
XUIysoliiu: Tfnh gia trj trung binh, ti II % va ve
do thj. Sd dung phan mem SPSS 16.0.
TAP CHf Y Di;pc U M SANG 108 Tap 11-So 5/2016
3. Ket qua
3.1. Dgc diem doi tifang
Bdng 1 . Tuoi va gidi
Tlldng so
Tuoi {x±SD) Nam:n(%) Na:n(%)
Nli6m ciiumg (n = 40) 38,47 ±14,18
16(40) 24 (60)
Nllom Benh (n = 200) 35,31 ±11,09
93 (46,5) 107(53,5
P 0,678 0,418 0,437 Khdng cd su k h i e biet v l t u d i gida n h d m benh va n h d m e h d n g .
BSng 2 . T r i l u chijlng llim sang cua n h o m benh Tiiong so
PhutochiJTcdadida Tran dich da mang T i i u It (< 5G0ml/24h) Tang huyet ap M^t, k^m an
Benli niian 200 136 78 22 155
%
100 68 39 11 92,5 PhCi gap 100% BN, tran djeh da mang gap 6 8 % BN.
Bkng 3. Trieu chiing xet nghiem huyet hpc va sinh hoa d n h o m b^nh (n = 200) Thong s6
N6ng do Hb So liicfng tieu cau Hematocrit IMong d6 ure mau Nong dp creatinin mau Nong do protein nieu g/24h (X±SD)
Tang n (%) 0 178(89) 56 (28,0) 97 (48,5) 67 (54,5)
Binh thUcfng n (%) 88 (44,0) 22(11,0) 144(72) 103(51,5)
91 (45,5)
Giam n (%) 112(56,0)
0 0 0 0 » 24,51 ±9,58
Co 56% BN thieu mau (Hb: nam < 130g/l, n f l < 120g/l), 8 9 % BN t a n g so Itrong t i i u cau (> 280G/I), 2 8 % BN CO dac mau (Het > 0,471/1). Cac so t h a m c h l i u theo gia t n cua Vien H u y i t hoc va Truyen m a u Trung UOng.
3.2. Ket qua xet nghiem mot so yiu to dong mau
Bdng 4. So sanh cac thong so dong mau d hai nhom
Thong so ATlil (%) Protein C (%) Protein S (%)
Nhom chOfng: n = 40 (X + SD) 114,05±10,17 118,78 ±19,37 114,15±12,16
Nhom benh: n = 200 ( ] ( ± S D ) 97,76 ± 9,68 117,13±20,10 67,28 ±10,17
<0,001 0,634
<0,001
JOURNAL OF 108 - CLINICAL IMEDICINE AND PHARIMACY Vol.11-N"5/2016;
ATIII, Protein S d n h 6 m benh t h a p hon n h o m churng (p<0,001). Chi/a thay sir khac biet ciia p r o t e i n C gida n h o m benh va n h o m c h i j n g .
Bang S. T^ le benh nhan co gidm ATIII, protein C, p r o t e i n S 4 n h o m b e n h so v 6 i chlJng
Thong so
ATIII giam (< 70%) Protein C giSm (< 70%) Protein S gISm (< 60%)
Nhom chihig: n = 40 n ( % ) 3(7,5) 1 (2,5) 1 (2,5)
Nhom benh: n ='200 n ( % ) 179(89,5) 44(22,0) 163(81,5)
P
<0,001 p=0,042» ' i
<0,001
Gia trj t h a m chieu c h i i n g toi s i l d u n g t h e o labo xet n g h i e m Vien Huyet hoc va Truyen m a u Trung uong.
Tl le b i n h nhan co ATIII, protein C, protein S gISm d n h o m b e n h d i u cao h o n n h o m c h i i n g co y nghTa.
Bang 6. MSi t u o n g quan giOa ATIII, protein S vdi protein nieu 2 4 h v^ m o t so thong so sinh hoa m a u
Thong s6 Albumin mau
Cholesterol mau
Protein nieu 24h
ATIII R = 0,62(p<0,01)
y = 3,2x-10,25 r = -0,56(p<0,01) y = -0,09x + 21,25 r = -0,55(p<0,05) y =-3,1+79,1
Protein C R = 0,27(p<0,05)
y = 4 , 8 x - 7 , 3 r = 0,18(p>0,05)
r = -0,21 (p<0,05) y = - 4 , 2 + 34,6
Protein S R = 0,33(p<0,05)
Y = 4 , l x - 4 , 7 R = -0,39(p<0,05) y = -0,23x +17,32 r = -0,3(p<0,05) y = -0,03x+14,63
1
ATlll va protein S cd tUdng quan thuan vdi albumin m a u , t d d n g quan n g h j c h vdi cholesterol mau va protein nieu 24h.
Arm (%)
150 y = 3,2x-i0,25 r = 0,62(p<0,01)
Albumin mau (g/l) 0 5 10 15 20 25 30 Bieu do 1 . Tuong quan gida ATlll vdi albumin mau
TAP CHlYDLTOCLAjVl SANG 108 T i p 11-565/2016
Protein S (%)
90 y=4,1x-4,7 r=-0,33 (p< 0,05)
Albumin mau (g/l)
Bieu 66 2 . Tuong quan gliJa protein 5 vdi albumin mau
Khi bj HCTH, luong protein bj mat qua nu6c t i i u rat nhieu va keo dai, t r o n g do bao g o m ca cac y ^ u t d d o n g mau n h u ATIII, protein C, protein S, d o d o lam giam cac thSnh phSn nay t r o n g mau. ATIII \i m o t a2 globulin do gan t o n g hop, la m 6 t d o n g y i u t o c6 tac dung bat hoat t h r o m b i n . ATIII tao phUc vdi heparin, phUc h g p nay lam bat hoat y i u t o Xa. Trong nghien cUu nay c h i i n g toi thay nong do ATIII 4 BN co HCTH giam thap k h i c bi6t so vffl chUng (p<0,001) va co t u o n g quan t h u a n chat vdi giam n o n g do albumin mau, t u a n g quan nghjch mile do chat v4l nong d 6 cholesterol mau va protein nieu 24h. Ket qua nay t u o n g t u k i t qua nghien ciJu cUa cac tac gia nude ngoai. Kauffman RH [3) n g h i i n cUu 48BN H Q H thSy cd t u o n g quan thuan giOra ATIII mau va albumin mau. Boneu B [2] va Vazlrl ND [6] t h i y n d n g d o ATIII mau t u o n g quan nghjch vdi vdi n o n g dp protein nieu 24h. ATlll cd t r o n g luong phan t i l t h a p t u o n g t u albumin mau, do d o he sd thanh t h j i cda ATIII t u o n g t u he so thanh thSI cCia albumin d BN HCTH,
Protein S la mot zymogen phu thupc vitamin K.
Khi nong dp protein S giam thi hoat tfnh khang d o n g cua protein C gISm. Trong nghien cdu nay, nong dp protein S t r o n g mau co t u o n g quan thuan mUc d6 Vila vdi albumin mau, tuong quan nghjch vdi ndng dp cholesterol mau va nong dp protein n i i u 24h. K i t qua nay t u o n g t u k i t quS ciia cac tac gia nude ngoai
n h u Kanfer A [4], Bellormo R. Trong nghien cdu nay chung t o i chua t h i y sir khac biet ciia protein C v i gia trj t r u n g binh so vdi chdng, nhung t i le % b i n h nhan cd giam protein C khac biet so vdi chdng.
Giam ATlll, protein C va protein S trong mau la nguy co gay tang d d n g va nghen tac mach. TUOng quan chat che glOra cac y i u t o nay vdi ndng d d albumin mau, goi j? cac b i n h nhan cd g l i m nang albumin mau can de phong bien chdng nghen t^c mach.
5 . Ket l u a n
N g h i i n cdu 200 benh nhan hdi c h d n g t h a n h u n g u y i n phat ngudi Idn va 40 ngudi cd sdc khoe b i n h t h u d n g , chdng t d i rdt ra m o t sd k i t luan sau: ,
1. 0 benh nhan hpi chiing t h i n h u nguyen phat n g u d i Idn, n o n g dp ATIII t r o n g mau: 97,76 ± 9,68%
t h i p hon chiing (114,05 ± 10,17%, p<0,001), t i le benh nhan giam ATIII t r o n g mau: 89,5% cao hon chiJng (p<0,001). Ndng d d protein S: 67,28 ± 10,17%
thap hon chung (114,15 ± 12,6%, p<0,001), t l le benh nhan gISm protein S: 81,5% cao hon chdng (p<0,001). Ndng d p protein C: 117,13 ± 20,1 % k h d n g khac biet so vdi chdng (118,78 ± 19,37%, p>0,05), nhung ti le benh nhan giam protein C: 22,0% cao hon chdng (p=0,042).
2. Ndng dp ATIII t r o n g mau cd tUdng quan t h u a n mdc dp chat vdi a l b u m i n m a u (r = 0,62, P<0,01), t u o n g quan nghjch mile d p chat vdi n d n g
JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol.n-N''5/20i;^
eld protein n i l u va cholesterol m l u (r = -0,55, p<0,05.
va r = -0,56, p<0,Dl). Ndng d o protein S t r o n g m a u cd t d d n g quan t h u a n mdc d o vda vdi a l b u m i n mau (r = 0,33, p<0,05), tUdng quan nghjch mdc do vda vdi protein nieu va cholesterol m a u (r = -0,30, p<0,05 va r = -0,39, p<0,05). N d n g d o protein C t r o n g m a u cd tUdng q u a n t h u a n yeu v d i a l b u m i n mau r = 0,27 {p<0,05), t d d n g quan nghich y l u vdi protein n i l u r =-0,21 (p<0,OS).
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concentration of three thrombin inhibitors in nephrotic syndrome. Thrdmb Haemost 46:623-625.
Kauffmann RH, Veltkamp JJ, Van Tilburg NH (2008) Acquired antithrombin III deficiency and thrombosM in the nephritic syndrome. A m J Med 65:607-613. 'i'^
Kanfer A (1990) Coagulation factors In nephriti(^
syndrome service de nephrology B. Hospital Tenou;^
Paris, France. Am-J-nephrol 10(1): 63.
Llach F (1994) Hypercoagulability in the nephrotii syndrome, Asian nephrology. Oxford university press: 53.
Vaa'ri ND, Paule P, Toohey L (2007) Acquired defidency and urinary excretion of antithrominn ill in nephritic syndrome. Arch Intem Md 144:1802-1803.
