HEPARIN V NG DNG HEPARIN TRONG LM SNG

PGS. TS. Nguyn Anh Tr

Vin Huyt hc Truyn mu Trung ng

Phn mt: NHNG VN CHUNG

C 2 loi :
- Heparin tiu chun
- Heparin c trng lng phn t thp.
I. Heparin tiu chun:
- Cn gi l heparin t nhin, hay heparin cha phn on (unfractionated heparin).
- Ngun gc: T t bo mast ca t chc lin kt.
- Trng lng phn t: 15.000 dalton.
- Heparin c th gn n mc bo ho vi Protein huyt tng, t bo ni mc,
monocyt.
- C ch tc dng: Ch yu tc ng vo con ng ni sinh.
+ To phc: Heparin + AT-III + Thrombin.
Qua :
c ch tc dng ca Thrombin.
Gia tc s phn hu Thrombin.
+ Ngoi ra: Cn bt hot c c Xa, IXa.
- ng dng:
+ Tnh mch lin tc.
+ Tnh mch ngt qung.
+ Tim di da.
- Cc xt nghim c thay i khi s dng Heparin:
+ Thi gian mu ng: Ko di.
+ Thi gian Howell: Ko di.
+ Thi gian Prothrombin (PT): Ko di.
+ Thi gian Cephalin (PTT): Ko di.
+ Thi gian Cephalin Kaolin (APTT): Ko di.
+ S lng tiu cu: Gim dn.

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 + nh lng anti-thrombin III (AT-III): Gim.
+ Ch s (r + k) (trong TEG): Ko di.
- La chn xt nghim theo di khi s dng Heparin tiu chun:
+ Xt nghim c la chn l APTT (nu khng lm c xt nghim ny th c
th thay th bng xt nghim Howell).
+ Hoc nh lng anti-Xa; c bit khi s dng Heparin vi liu thp (< 0,2
UI/ml) hoc khi bnh nhn c khng ng lupus.
II. Heparin trong lng phn t thp (Low molecular weight heparin = LMWH).
- L loi Heparin c trng lng phn t trung bnh bng 6.000 dalton.
- LMWH c hot tnh chng Xa cao hn so vi hot tnh chng Thrombin.
- Khng gn vi protein plasma, i thc bo hoc t bo ni mc.
- LMWH t gy ra gim tiu cu v chy mu hn.
- La chn xt nghim theo di:
+ Nn dng xt nghim nh lng anti-Xa.
+ APTT: Cng c, nhng khng nhy bng.
- Mt s bit dc:
+ Lovenox (Levenox).
+ Fragmin (Tedelparin).
+ Fraxiparine.

Phn hai: CC CH NH IU TR BNG HEPARIN.

1. Nghn mch huyt khi tnh mch (iu tr d phng v iu tr cha bnh).
2. Huyt khi ng mch vnh.
3. ng mu ri rc trong lng mch (DIC).
4. Phu thut bypass tim phi.
5. Huyt khi gy nghn mch no.
6. phng huyt khi trong chy thn nhn to.
7. Cc ch nh khc:
- Phng nga tc tnh mch gan sau ghp tu xng.
- Hen do tp th dc...
Phn ba: MT S PHC C S DNG HEPARIN.
I. Cc phc c s dng Heparin n c:

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1. Heparin tiu chun
1.1. Trong iu tr d phng (preventive therapy).
- Liu 200 UI/kg/24h (phc Kakkar).
- Sau tim di da 5.000 UI/ln, ngy tim 2 3 ln).
- Theo di: Bng xt nghim APTT hoc nh lng nng anti-Xa, ly mu gia 2
ln tim.
+ APTT: Ko di hn so vi chng 10 12 giy.
+ Hoc nng anti-Xa = 0,1 0,5 UI/ml.
1.2. Trong iu tr cha bnh(curative therapy):
1.2.1. Cch th nht:
- Liu: 400 800 UI/kg/24h.
Theo di iu tr bng Heparin (liu 400 800 UI/kg/24h).
Hng dn Thi im ly mu theo di Kt qu cn t c
1. Truyn tnh Bt c lc no - APTT = 2-3 ln so vi chng.
mch lin tc - Anti- Xa = 0,4 0,6 UI/ml.
2. Tim di da - Ly mu vo 1 gi trc khi -APTT = 1,2 2,0 ln so vi chng.
tim mi tip theo. - Anti-Xa = 0,15 0,3 UI/ml.
- Ly mu gia 2 ln tim - APTT = 2 3 ln.
- Anti-Xa = 0,4 0,6 UI/ml
3. Tim tnh mch Ly mu 1 gi trc khi tim - APTT = 1,5 2,0 ln.
cch hi (nay t dng) mi tip theo - Anti-Xa = 0,15 0,30 UI/ml.
1.2.2. Cch th hai:
- Liu v cch dng:
+ Tim tnh mch mi u tin 5000 UI.
+ Sau truyn tnh mch lin tc vi liu 30.000 40.000 UI/ngy.
- Theo di: Ly mu 4 6h sau khi tim.
Xt nghim APTT = 1,5 2,5 ln so vi chng.
- iu chnh liu:
+ Khi APTT < 1,2 ln Tim thm liu 5.000UI.
+ Khi APTT < 1,5 ln Tim thm liu 2.500 UI.
I.2.3 Cch th ba:
- Pha thuc: 20.000 UI/trog 500 ml dch truyn (nng thuc c nh 40 UI/ml).

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 - Cch dng:
+ Tim tnh mch liu u 5.000 UI (bolus).
+ Truyn tnh mch lin tc:
Bnh nhn c nguy c chy mu cao, liu 31ml/h
(31ml x 40UI x 24h = 29.760 UI).
Bnh nhn c nguy c chy mu thp, liu 42 ml/h
(42ml x 40UI x 24h = 40.320 UI).
- Cch theo di v iu chnh liu:
Ly mu sau 4 6h, iu chnh v theo di theo bng sau:
Xt nghim
Thay i t l Thay i liu Cn lm tip
APTT
Thm 5.760 IU/ngy Sau 4 6 gi lm li xt
giy Thm 6ml/gi
(= 40IU x 6ml x 24 gi) nghim APTT
Sau 4 6 gi lm li xt
46 54 giy Thm 3ml/gi Thm 2.880 IU/ngy
nghim APTT
55 85 giy Khng Khng Khng
Ngng truyn Heparin 1 gi,
Gim 2.880 IU/ngy sau th truyn li. Ly
86 110 giy Bt 3ml/gi
(= 40 IU x 3ml x 24gi) mu kim tra APTT sau khi
dng li Heparin 4 6 gi
Ngng truyn Heparin 1 gi,
sau th truyn li. Ly
> 110 giy Bt 6ml/gi Gim 5.760 IU/ngy
mu kim tra APTT sau khi
dng li Heparin 4 6 gi

2. Heparin trng lng phn t thp (Fraxiparin).

2.1. iu tr d phng: Tu vo mc ch.
- Liu 25 35 UI anti-Xa/12h.
- Tim di da ngy 1 ln.
- Ly mu 3 4h sau khi tim xt nghim anti-Xa.
- Kt qu cn t c: Nng anti-Xa = 0,4 UI/ml
2.2 . iu tr cha bnh:
- Liu 100 UI anti-Xa/12h.
- Tim di da 2 ln/ngy.

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 - Ly mu 3 4h sau khi tim.
- Kt qu t c: Nng anti-Xa = 0,5 -1,0 UI/ml.
II. Cc phc s dng Heparin phi hp vi cc thuc khc.
1. Phi hp Heparin vi thuc khng ng ng ung:
- L mt phc rt ph bin trong iu tr bnh l huyt khi.
- Phc tng qut:
+ Bt u l dng Heparin (di da hoc tnh mch).
+ Sau 4 5 ngy th dng Warfarin phi hp vi Heparin.
+ Sau 3 5 ngy th ct Heparin s dng Warfarin n c.
- Xt nghim theo di:
+ Giai on s dng Heparin: APTT v/hoc nh lng anti-Xa.
+ Giai on s dng Warfarin: PT (%, giy), INR. Duy tr INR = 2 -3 l c.
2. Phc s dng Heparin vi nhiu thuc khc:
- in hnh l trong phc iu tr ng mu ri rc trong lng mch (DIC).
- Cc thuc s dng trong phc tng hp , bao gm:
+ Huyt tng ti ng lnh;
+ Ta lnh yu t VIII;
+ Khi tiu cu;
+ Heparin;
+ Transamin;
- Phc iu tr v theo di DIC c th (xem phn sau).

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 Phn bn: NHNG VN CN LU TRONG S DNG HEPARIN
I. Bin chng trong iu tr Heparin:
1. Chy mu:
- C th gp khong 5% cc bnh nhn iu tr Heparin liu.
- Hay gp cc bnh nhn ang phu thut, t qu; c tin s chy mu tiu ho;
bnh thn, tui cao, s lng tiu cu gim (<100 x 10 9/l); hoc cc bnh nhn
ng thi c iu tr bng cc thuc khng tiu cu, hoc tiu ng.
2. Gim tiu cu do Heparin:
- Gp 3 5% bnh nhn sau iu tr Heparin 5 10 ngy.
- Do khng th chng li phc hp Heparin vi yu t 4 tiu cu.
- Biu hin: C th c xut huyt, nhng t; ch yu l xy ra huyt khi, c bit l
huyt khi ng mch. Nguyn nhn do tiu cu c hot ho In-vitro.
- X l: Trc ht nn ngng s dng Heparin khi c hin tng gim tiu cu. S
lng tiu cu s tr li bnh thng trong vng 4 ngy sau khi ngng s dng
Heparin.
* Ch : phng cc bin chng chy mu hoc gim tiu cu do iu tr bng
Heparin nht thit phi s dng cc xt nghim ng mu theo di.
Bng thm d cc bnh nhn b chy mu trong khi ang iu tr Heparin.
Kt qu xt nghim L do v x l
- APTT: Di gp 2- 3 ln so vi chng. - Qu liu Heparin.
- Tiu cu bnh thng. - Gim hoc ngng iu tr Heparin.
- Fibrinogen: Bnh thng.
- APTT: Trong gii hn bnh thng hoc - Gim tiu cu do dng Heparin.
ko di. - Ngng s dng Heparin.
- Tiu cu: Thp.
- Fibrinogen: Bnh thng
- APTT: Rt di. - C th DIC? hoc bnh l gan hay thn?
- Tiu cu: Thp. - Nu ang s dng Heparin th:
- Fibrinogen: Thp + nh lng li nng Heparin (bng k
thut Anti-Xa assay).
+ iu chnh li liu Heparin.

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 3. Long xng:
Khi s dng Heparin liu cao (> 20.000IU/ngy) v ko di (> 5thng)th c th
xy ra bin chng long xng, do bi tng hot ng ca hu ct bo (Osteoclast).
4. Cc tc dng ph khc:
- Gim aldosteron.
- Phn ng qu mn.
- Tng men gan.
- Cng au dng vt.
- Hoi t da khu tr...
II. Ni v hin tng khng Heparin.
- Gi l khng Heparin khi phi s dng vi liu > 35.000 IU/24h mi to ra c hiu
qu khng ng trung bnh.
- Nguyn nhn: L do tng vic gn Heparin vi cc protein huyt tng (nh
vitronectin), yu t 4 tiu cu, monocyt hoc t bo ni mc.
Mc khc cng chng t: Qu trnh huyt khi vn cn xy ra mnh m (mc du ang
c iu tr chng ng); Hoc y c s bt lc tng i ca phc hp Heparin-
ATIII trong vic trung ho Thrombin.
- X l: Nhanh chng loi b nguyn nhn gy ra huyt khi; C th tng liu
Heparin ln di s kim sot cht ch ca xt nghim APTT; Tuy nhin khng
c qu lm dng v rt d gy ra bin chng gim tiu cu, chy mu do dng
qu liu Heparin.
III. Qu liu Heparin.
S dng Heparin qu liu c th gy ra mt s bin chng nghim trng nh tng
nguy c xut huyt, gim tnh ng mu ca cc serin protease.
hu b tc dng ca Heparin nn s dng Protamin . 1mg protamin sulphat c
th trung ho c 100IU Heparin. Protamin ch trung ho c hiu lc chng
Thrombin nhng khng trung ho c hiu lc chng Xa ca Heparin.
Cc liu thng thng c s dng theo ng tnh mch ngi ln l:
+ 3ml (= 3.000 UAH) protamin nu s trung ho c thc hin trong vng 6 gi u
k t khi tim liu Heparin cui cng.
+ 2ml (= 2.000 UAH) protamin nu s trung ho c thc hin sau 6 gi u k t
khi tim liu Heparin cui cng.
C th s dng lp li sau mi 2 hoc 3 gi cho n 12 gi sau nu cha trung ho
ht ton b lng Heparin.