Y HQC VigT NAM T H A N G 5 - SO OAC BIET /2011
HEMOPHILIA MllrC DO NHE:
MOT TINH TRANG BENH LY THACH THIJnc CHAN DOAN
Nguydn Thi Nur*
OMTAT
Benh Hemophilia dupc chia l^m 3 mdc do, ly theo nong do boat tinh yeu td Vlll /IX: bpnh ian dupc xep vao mCrc do nang khi nong 66 iu td dong mau thap hon 1%; mdc dp vCra khi Dng do tCr 1 den 5% va mdc dp nhe khi nong 3 6 mdc 5 den 30%. Ben canh nhOrng thuan Ipi Jn so v6i nhOfng benh nhan Hemophilia mPc dp 5ng va vira trong dieu tn cam mau, nhCTng benh han Hemophila myc dp nhe co kh^ nhieu van 3 thach thiic trong chan doan. Trong nhom benh han Hemophilia thi ty le bo sot cha'n doan, chan oan nham chu yeu roi vao nhPm benh nhan emophilia mdc dp nhe. Chfnh vi vay, tim hieu guyen nhan gay nen sai sot trong chan doan va irPng khac phuc la mpt trong nhOfng mdi quan im tren The gidi cung nhu d Viet nam.
UMMARY:
Hemophilia patients is divided in 3 levels epending on the level of factor VIII/IX: It can be 3vere if clotting factor is less than 1%, moderate in the range of 1 % 5% and mild when in the inge of 5% - 30%. Though the patients with mild Bmophilia have many advantages in treatment comparison with the ones with moderate and 3vere hemophilia, they still face many lallenges in diagnosis. Among three groups of lild, moderate and severe hemophilia, the rate f missed diagnosis and misdiagnosis mainly ills into the group of patients with mild emophilia. Therefore, understanding the cause f errors in diagnosis and finding the solution to lose problems is one of the concerns in the orld as well as in Vietnam.
OAT V A N OE
Hemophilia dupc dac trung bdi chay
\^ien Huyet lipc - Truyen mdu TW
mau kho edm do thie'u hut yd'u td dPng mau (VIIIAX/XI). vAn con mpt sd tranh luan nhung noi chung, boat tfnh ciia yd'u td dong mau trong bdnh Hemophilia thudng dudi 30%. Vd miic dp ciia bdnh, Hemophilia dupc chia lam: Hemophilia miic dp nang khi boat tfnh yeu td bi thie'u hut dudi 1 %,; Miic dp vira khi boat tinh d miic 1 den 5 % va miic dp nhe khi boat tfnli yd'u td d trong khoang 5 dd'n 30%.
Trong cac bdnh nhan Hemophilia thi nhirng trudng hpp miic dp nhe dupc quan tam d khia canh chdn doan nhat bdi ty Id bi bo sot chan doan cao nhdt, ngay ca d nhung bdnh vidn ldn. Qua thyc te chan doan va didu trj Hemophilia trong mpt thdi gian dai, chiing toi xin trao ddi vd mpt sd vdn dd vd chdn doan tinh trang bdnh ly nay.
II. MOT S6 THONG TIN CHUNG VE HEMOPHILIA MCTC OO NHE
Hemophilia miic dp nhe chid'm ty Id kha cao trong sd cac bdnh nhan bi Hemophilia ndi chung. Ty Id nhdm bdnh nhan nay bi anh hudng nhidu yd'u td, dac bidt la ky thuat dp dung trong chdn doan Hemophilia, chfnh vi vay, phu thupc ca thdi didm tid'n hanh khao sat ciia ngay mpt co sd nghidn ciiu. Theo kd't qua ciia mpt nghidn ciiu da trung tam ciia Geraghry S. cho thdy Hemophilia miic dp nhe chid'm 32% trong bdnh Hemophilia [4].
Trong khi dd nghidn ciiu ciia Aznar JA. trdn 2.905 bdnh nhdn Hemophilia, ty Id nay la 51,5% [ 2 ]. Kd't qua nghidn ciiu cua Poon MC. va cdng sy cho thd'y co 16% bdnh nhdn Hemophilia miic dp nhe trong tdng sd 5.043 bdnh nhdn Hemophilia [6].
KY Y^'U C A C ^ C 6 N G TRINH NGHlfeN CLfU KHOA HQC C H U Y S N NGANH H U Y £ ' T HQC - TRUYJN MAU
Tai Vien HHTMTW, chiing tdi gap 41,3
% Hemophilia miic dp nhe [1].
III. MpT S6 VAN of LUU Y TRONG CHAN
OOAN HEMOPHILIA
Mirc Op NHE
\ V bieu hien lam .sdng:
Thdng thudng, khac vdi nhiing bdnh nhdn bi Hemophilia miic dp nang va vira, nhidu trudng hpp bdnh nhan Hemophilia miic dp nhe dupc phdt hidn va chdn doan tinh cd qua sang Ipc bdt thudng ddng edm mau hoac cd chay mau bdt thudng sau chdn thuong, can thidp, phdu thuat. Vi vay, nhihig bdnh nhan nay thudng dupc chdn doan mupn hon, tudi trung binh bao gid cung cao hon; Cd kha nhidu bdnh nhan Hemophilia miic dp nhe dupc phat bidn khi da d tudi trudng thanh [6].
Ve thay ddi xet nghiem:
Nd'u nhu d bdnh nhdn Hemophilia miic dp nang va viia, kd't qua xet nghidm APTT keo dai la mdt trong nhiing bdt thudng thudng gap va la mdt tidu ehudn ciia chan doan thi day lai la mdt trong nhihig didm cdn luu y va ban ludn d bdnh nhdn Hemophilia
miic dp nhe.
Thdng thudng, APTT keo dai khi hoat tinh ydu td VIII:C/IX:C ciia bdnh nhdn giam;
Tuy nhidn, cdn luu y rdng, dp nhay ciia xet nghidm nay dd'i vdi miic dp giam cua cac y^u td Vlll:C/IX:C bi anh hudng bdi kha nhi^u nhidu td, dac bidt la loai hod chd't sinh phdm, ky thudt dp dung. Ngudng ndng dp boat tinh ydu td VII1:C/1X:C gay APTT keo dai ciia cdc loai hda chdt khac nhau thudng kh6ng gidng nhau. Didu nay giai thich vi sao m6ts^
bdnh nhdn Hemophilia miic dd nhe, APTT khPng kdo dai va ddy la mdt trong nhiing nguydn nhdn chinh gdy bd sdt, chdn doan nhdm thd bdnh nay. Hod chd't, sinh phim sii dung cho xet nghidm APTT cdn dupc lua chpn dya vao tidu chi cd dp nhay tdt vdi sii thidu hut ndng dp yeu td VIII:C/IX:C.
Nhu vay, dd tranh bd sdt Hemophilia miic dp nhe, cdn ti^n hanh dinh lupng ydu td VIII: CAX:C ngay ca khi ket qua APTFyong gidi ban binh thudng n^u tridu chiing trSn ldm sang hoac tidn sir ban thdn, tidn sir gia dinh nghi ngd Hemophilia.
Do nhay cua cdc loai hod chdt sinh phdm trong xet nghiem APTT
Ty le bat thudng cua APTT
Loai hoa chdt Ndng dp yeutd Vlll 4 2 % Nong dP ydu td IX 38 %
Bo 54 65
B v d A 77 88
KPS 41 83
IL 70 96
M 91 100
OA 35 100
OP 16 83
(theo Steve Kitchen) [7].
Dinh lupng y^u td VIII:C/IX:C: Ndng dp 1%: Hemophilia miic dp nang, tir 1 ddn 5 %:
boat tinh cac yd'u td nay la tidu ehudn chdn miic dp vira va ttr 5 % dd'n 30%: miic dp nh?.
doan Hemophilia cung nhu tieu ehudn xd'p Tuy nhidn cdn luu y cd sy khdng ddng nh^' loai miic dp bdnh nay: boat tinh yd'u td dudi
Y HQC VIET NAM T H A N G 5 • SO D A C BigT /2011
'i ndng dp yd'u td khi sir dung cac phuong )hap dinh lupng khac nhau.
Hidn nay, cd 3 phuong phdp dinh lupng
^d'u td VIII:C/IX:C dang dupc dp dung trdn [hd gidi: Phuong phap 1 thi (one - stage: OS nethod), phuong phap 2 thi (two - stage: TS nethod) va phuong phap co chat tao mau phromogenic substrate: CS method). Phuong )hap 1 thi dang dupc dp dung rpng rai nhdt d
^idt nam vd day lai la phuong phap dd bo sdt Hlemopbilia miic dp nhe nhdt.
Nghidn ciiu ciia Steve Kitchen cho thdy cd khoang 5-10% bdnh nhan bi Hemophilia miic dp nhe bi bd sdt chdn dodn nd'u chi tid'n hanh xet nghidm APTT va djnh lupng yd'u td V1II:C/IX:C theo phuong phap 1 thi [ 7 ].
Chinh vi vay, cdn tid'n hdnh dinh lupng va so sanh vdi it nhdt I phuong phap khac dd tranh bd sot nd'u kd't qua dinh lupng khPng phii hpp vdi bidu hidn chay mau trdn lam sang cung nhu tid'n sir ban than va gia dinh bdnh nhan.
Hoat tinh yeu tdVIILC d 7 benh nhdn bi Hemophilia A mdc do nhe dinh luong bdng cdc ohuang phdp khde nhau [7]
Benh nhan 1 2 3 4 5 6 7
Hoat tfnh VIII:C phuong phap One - stage
101 (%) 88 63 55 58 72 84
Hoat tfnh VIII:C phuong phdp Two - stage
34 (%) 15 30 24 21 21 19
Hoat tfnh VllhC phuong phap Chromogenic
13(%) 28 40 40 33 36 45
Trong mpt sd trudng hpp, tham chi cdn :ien hanh xet nghidm danh gia kha nang tao hrombin (TTuombin Generation), nghidn ciiu /d dpt bid'n gen dd chdn doan chinh xac Eiemophilia miic dp nhe.
Gidi thieu mot trudng hap bi Hemophilia mdc do nhe, kho chdn dodn:
Bdnh nhdn nam, 26 tudi, cd chay mau did edm sau nhd rang. Tidn sii gia dinh cd Jdu bi Hemophia A. Kd't qua xet nghidm Dong Cdm mau binh thudng (bao gdm ca
\PTT, PFA). Kd't qua dinh lupng yd'u td
^III:C theo cac phuong phap khac nhau cho cdt qua nhu sau:
Yd'u to VIILC phuong phap OS: 71%
Yd'u to VIIIiC phuang phap CS: 33%
Yeu td VIILC phuong phdp TS: 24%
- Khang nguydn va boat tinh yeu td vonWillebrand ddu trong gidi ban binh thudng
Bdnh nhdn dupc chdn doan: Hemophilia A miic dp nhe. Ddy la vi du kha dien hinh vd sy khac bidt kd't qua giiia cac phuong phap khi dinh lupng yd'u td VIILC.
Rodgers trong mdt nghidn ciiu d 97 bdnh nhdn bi Hemophilia A miic d6 nhe cho tha'y CO 8 bdnh nhan ndng dp yd'u td VIILC trong gidi ban binh thudng khi tid'n hanh dinh lupng bang phuong phap 1 thi.
Bdn canh dd, cd khd nhidu yd'u td anh hudng dd'n ndng do boat tinh yd'u td Vni:C/IX:C: Ndng dp cac yd'u td nay thudng tang phan iing khi co thd cd chay mau, chd'n thuong, nhidm trung, sau phdu thudt... va
K'V' Ye'u CAC C 6 N G T R I N H NGHIEN C(S\J KHOA HQC CHUYDN N G A N H H U Y ^ ' T HQC - TRUYJN MAU
thdm chi ca tudi tdc ciia bdnh nhdn. Sy tang khi xd'p loai bdnh nhdn Hemophilia theo mfe hoat tinh VIll:C/lX:C trong nhOng trudng dp nang nhe, cdn luu ^ thdi didm tidn hanh hpp ndy sc lam lu md, tham chi xoa nhoa tinh dinh lupng ydu td ddng mdu dd x6p loai cho tiang giam nhe hoat tinh ciia cac yd'u td nay d bdnh nhdn.
bdnh nhdn bi Hemophilia miic dd nhe. Hon Mat khac, trong thyc td' quan ly vd di^u nda kd't qua ciia nhidu nhdm nghidn ciiu tri bdnh nhdn Hemophilia, ndu mpt benli cung cho thdy, d nhdm bdnh nhdn nhdn bi Hemophilia thupc nhdm miic dp nhe Hemophilia nay, hoan toan khdng co mdi xud't hidn nhirng bidu bidn ldm sang nhu;
tuong quan thudn giCTa ndng dp hoat tfnh yd'u chay mau ty phdt, chay mau nang, didu tri td V111:C/1X:C vdi bidu hidn chay mau tren theo phdc dd cho nhdm bdnh nhan nay kh6ng lam sang. dap iing, cdn xem xet sy chuydn thd cung nhu
Nhu vay, cd kha nhidu nguydn nhan cd danh gid chdt lie chd d nhirng bdnh nhdn nay, thd gay ndn tinh trang chdn doan nhdm, bd
sdt chdn doan. Vi vay Hemophilia miic dp y. OIEU TRj BENH NHAN Bj HEMOPHIUA nhe, thdm chi cdn dupc gpi Id nhdm bdnh I^(JQ O 6 NHE
"cd nhidu bp m^t thd hidn va ldm thach thiic j^du hd't bdnh nhdn Hemophilia A mdc trong chan doan" [ 6] ^^ ^^^^ ^^^ ^j^p ^ g ^f^^ j^j,- ^^^ ^j-y t^ ^^^
, demopressin: ndng dd y^u td VIILC tang 2 IV. VAN OE THAY OOI M Q C O O BENH 0 ddn 4 ldn. Ndng dd ydu td VIILC dat dinho BENH N H A N HEMOPHILIA MCTC 0 0 NHE: vao khoang 5- 8 gid sau khi dua demopressin Trong thyc te, chung ta cd the gap mpt vao co the ngudi bdnh. Ngoai mpt sd tac bdnh nhan dupc chdn doan Hemophilia miic dung khdng mong mudn nhu dau ddu, tang dp nhe nhung qua thdi gian lai trd ndn nang nhip tim..., demopressin da cho thdy kha hon. Mdt trong nhihig nguydn nhan gdy ndn hidu qua trong lam tang ndng dp ydu to tmh trang nay la xud't hidn chd't lie che yd'u td VIILC d nhOng bdnh nhdn bi hemophilia A ddng mau bi thid'u hut do didu trj thay thd'gdy miic dp nhe; Didu tn demopressm da IJim ndn. Chd't lie chd' yd'u td dPng mau xud't hidn d gidm sd ldn cung nhu lidu lupng chd phib nhihig bdnh nhdn nay cd tac dung trung hoa didu tri thay thd', nhd vdy, lam giam nguycd y^u td qua phan ihig khang nguydn -khang xud't hidn lie chd', nguy co ldy truydn cac tiie thd, lam giam ndng dp cac yd'u td ddng mdu nhdn nhidm trung qua truydn mdu va giam trong mau bdnh nhdn. chi phi didu tri cho nhihig bdnh nhan nay.
Ttr 1990 vd trudc, vdn dd chat lic chd d Demopressin kd't hpp vdi thudc lie chd tieu bdnh nhdn Hemophilia miic dp nhe rd't it spi huyd't la chpn lya hidu qua nhd't cho benh dupc dd cdp bdi hdu nhu khdng gdp. Tuy nhdn Hemophilia A miic dp nhe co xuKt nhidn, gdn ddy, mdt sd tac gia qua kd't qua huyd't nidm mac.
nghidn cihi ciia minh da chi ra rdng nhihig Nhihig bdnh nhdn bi Hemophilia mifc d6 bdnh nhdn nay cQng cd thd xud't hidn chd't lie nhe khdng dap iing didu tri vdi demopressin che yd^u td ddng mau bi thid'u hut. Tuy nhidn hoac cdn ndng ndng dp yd'u td VIIIiC ldn cao ty Id xud't hidn chd't lic che d nhdm bdnh dam bao ydu edu cdm mau cho m6t cu6c nhdn Hemophila nay thudng thdp [1], [5]. phdu thudt ldn, nhihig chdn thuong nang ^
Chmh vi vdy dd dam bao dp chmh xac didu tri thay thd' de cdm mau vdn la lua chon
Y HOC VI^T NAM T H A N G 5 - SO OAC BI§T /2011
ma thdy thudc. Lupng yd'u td cdn truydn, dioang each giua cac ldn truyen, thdi gian ruydn...tuong ty nhu dd'i vdi bdnh nhdn bi Hemophilia miic dp nang va vira.
Ddi vdi bdnh nhdn Hemophilia B miic dd [ihe, didu tri chii yd'u la chd' phdm cd yd'u td IX, nd'u bdnh nhdn cd chay mdu nidm mac, cdn kd't hpp thudc lie chd' tidu spi huyd't.
Demopressin khdng cd tac dung dd'i vdi bdnh nhan bi Hemophilia B miic dp nhe.
VI. KET LUAN
Vail dd cdn quan tdm nhd't dd'i vdi bdnh Hemophilia, dac bidt la Hemophilia miic dp nhe la phat hidn, chdn doan chinh xdc, kip thdi, khdng bi bd sdt, nhdt la trong qua trinh tid'n hanh sang Ipc phat hidn bdt thudng ddng cdm mau ehudn bi cho mpt cupc md, can thidp. Cd khoang 5 dd'n 10% bdnh nhdn Hemophilia miic dp nhe se bi bd sdt nd'u chdn doan chi dya vao kd't qua cua APTT va dinh lupng yd'u td VHI: C theo phuong phap 1 thi mpt phuong phap dang sur dung rdng rai d Viet Nam.
Cin ket hpp tham kham ky Idm sang, tim hieu ddy du tidn s& ban thdn va gia dinh bdnh nhdn vd bdt thudng ddng cdm mau kd't hop vdi lya chpn boa chd't thudc thii, dp dung cac ky thudt cd dp nhay va dp dac hidu cao trong chdn doan mdi cd the khong bd sdt Hemophiha miic dp nhe - mpt bdnh ly chay mau kho cdm, mdt bid'n chiing de doa tinh
mang bdnh nhdn, nhd't la trong cac cupc can thidp, phdu thuat.
TAI LIEU THAM KHAO
1. Nguydn Thi Huong Que (2008), Nghien ciiu tdc dung khong mong mudn a benh nhdn Hemophilia dugc truyen che phdm mdu tai Vien HHTMTW. Lufin van Thac sy Y hpc, Dai hoc Y Ha npi.
2. Azna JA.(2009), The national registry cf Hemophilia A and B in Spain: results from a census o/par/e/j/i", Hemophlia 2009; 15; 1327-1330.
3. D'Oiron R.(2008), MildlModerate hemophilia A: New insights into molecular mechanisms and inhibitor development.
Hemophilia; 14:138-146.
4. Geraghty S (2006), Practice patterns in Hemophilia A therapy - global progresstoward optimal care. Haemophilia,
12,75-81
5. Jacquemin M. (2003), Molecular mechanisms of mild and moderate Hemophilia A, J. Thromb Haemost; 1; 456-463.
6. Peerling CK (2010), Mild Hemophilia: a disease with many faces and many unexpected pitfall. Haemophilia, 16, supl 5, 100 -106.
7. Steve Kitchen (2010), New developments in laboratoiy diagnosis and monitoring,li&emophi^a, 16 (Suppl. 5), 61 - 66.
8. Stonerbrack JS. (2009), A study of variation in the reported Haemophilia A prevalence around the World, Haemophilia, 15, 75 - 81