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Tbilisis saxelmwifo samedicino universitetis alergologiisa da klinikuri imunologiis mimarTuleba daviT Telias klinikuri leqciebis cikli trombocituli hemostazis Sefaseba Tbilisi 2009 w.

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Page 1: trombocituli hemostazis Sefaseba - telia.ge hemostazi-d.t.-pas.pdf · orebiTi venuri Trombozi ufro xSirad gvxvde-ba mamakacebSi,xandazmul pirebSi,aseve _ imobi-lizaciisa da avTvisebiani

Tbilisis saxelmwifo samedicino universitetis

alergologiisa da klinikuri imunologiis mimarTuleba

daviT Telias

klinikuri leqciebis cikli

t r o m b o c i t u l i

h e m o s t a z i s

S e f a s e b a

Tbilisi

2009 w.

Page 2: trombocituli hemostazis Sefaseba - telia.ge hemostazi-d.t.-pas.pdf · orebiTi venuri Trombozi ufro xSirad gvxvde-ba mamakacebSi,xandazmul pirebSi,aseve _ imobi-lizaciisa da avTvisebiani

Trom bo ci tuli hemostazis Sefaseba

daviT Telias klinikuri leqciebis cikli2

Tbilisis saxelmwifo samedicino universitetis

alergologiisa da klinikuri imunologiis mimarTuleba

daviT Telias klinikuri leqciebis cikli

Trom bo ci tuli hemostazis Sefaseba

naSromi gankuTvnilia

umaRlesi samedicino saswavleblebis

studentebisTvis, alergologebisTvis,

TerapevtebisTvis, pediatrebisTvis, ojaxisa da

zogadi praqtikis mqone eqimebisTvis.

naSromze yvela saavtoro ufleba ekuTvnis daviT Telias.

avtoris nebarTvis gareSe naSromis sruli an

nawilobrivi kopireba da gavrceleba akrZalulia.

Tbilisi, 2009 w.

Page 3: trombocituli hemostazis Sefaseba - telia.ge hemostazi-d.t.-pas.pdf · orebiTi venuri Trombozi ufro xSirad gvxvde-ba mamakacebSi,xandazmul pirebSi,aseve _ imobi-lizaciisa da avTvisebiani

3daviT Telias klinikuri leqciebis cikli

Trom bo ci tuli hemostazis Sefaseba

Trombocituli hemostazis darRveva ukav-

Sirdeba Trombocitebis raodenobriv da Tvisob-

riv cvlilebebs, romelTa Sedegadac viTardeba

peteqiebi, purpura, msubuqi, zomieri an Zlieri

sisxldena.

Trombocitebis raodenobrivi cvlilebebi

vlindeba TrombocitopeniiT, TrombocitoziT,

TrombocitemiiT (rac gamowveulia granuloci-

turi leikemiiT, mieloiduri metaplaziiT da

a.S.).

Uspn!cp!dj!up!qf!oj!bt safuZvlad SeiZleba

edos rogorc am ujredebis warmoqmnis Semcire-

ba, ise maTi hb[!mj!f!sf!cv!mj!ebT!mb-!Uspn!cp!dj!uf!.

cjt!Uwj!tfc!sj!wj!ef!gfr!uf!cj!lj!nfn!lwje!sf!p!cjU-!Tf!.

[f!ojm!eb!nf!ej!lb!nfo!uvs!qb!Up!mp!hj!vs!nehp!nb!sf!p!.

cfct!vlbw!Tjs!ef!cb/

Trombocitebis paTologiur cvlilebaTa

gamo warmoqmnili peteqiebi da purpura mTel

sxeulze simetriulad vrceldeba. bnjU!hbo!tywbw!.

ef!cb!jtj!oj!tjt!ym[bs!Swf!cjt!eb!{j!b!of!cjU!hb!npx!wf!v!.

mj! tjt!ymDbr!df!wf!cjt!hbo-! spn!mf!cjd-! Dwf!v!mf!cj!tb!.

nfcs-!btj!nfu!sj!v!mbe!bsjt!hbo!mb!hf!cv!mj!vqj!sb!uf!.

tbe!rwf!np!lj!ev!sfc!{f [1].

memkvidreobiTi defeqti SedarebiT iSvia-

Tia. aseT defeqtebs Soris mniSvnelovania Trom-

bocitebis adheziis darRveva, pirveladi da meo-

reuli agregaciis defeqtebi da sxva SedarebiT

iSviaTi izolirebuli defeqtebi (cxrili #1).

Trom bo ci tuli hemostazis Sefaseba

cxri li #1

Trom bo ci te bis fun qciaTa

mem kvid re o bi Ti dar Rve ve bi (de feq te bi)

ad he zi is de feq te bisxva sin dro meb Tan

da kav Si re bu li

ber nar -su li es sin dro micik lo oq si ge na zis

de fi ci ti

pir ve la di ag re ga ci is

de feq te bi

Trom boq sa nis sin Te ta zis

de fi ci ti

glan cma nis Trom bas Te niaiS vi a Ti izo li re bu li

de feq te bi

esen ci u ri aT rom biaTrom bo ci tu li faq to ri

3-is de fi ci ti

me o re u li ag re ga ci is

de feq te bi

fos fa ti di li no zi to lis

dar Rve ve bi

de po ni re bis dar Rve ve bi

Trom bo ci teb Si afib ri no ge ne mia

izo li re bu li de feq te bimZi med mim di na re

he mo fi lia

Page 4: trombocituli hemostazis Sefaseba - telia.ge hemostazi-d.t.-pas.pdf · orebiTi venuri Trombozi ufro xSirad gvxvde-ba mamakacebSi,xandazmul pirebSi,aseve _ imobi-lizaciisa da avTvisebiani

Trom bo ci te bis ag re ga ci is Se fa se ba

Trombocitebis agregaciis Seswavlis miz-

niT atareben e.w Born-tests: TrombocitebiT

mdidar plazmas aTavseben agregometrSi da Tva-

liT afaseben Trombocitebis agregacias (opti-

kuri agregometria). agregometri warmoadgens

speqtrofotometrs. masSi moTavsebul Trombo-

citebiT mdidar plazmas emateba agregaciuli

agentebi. Trombocitebis agregaciis Sedegad mi-

iReba drosTan asocirebuli mzardi sinaTlis

mrudi, romelzec SesaZlebelia agregaciis pirve-

ladi da meoreuli talRebis garCeva [1-3]. swo-

red am mruds afasebs mkvlevari.

mTlian sisxlSi Trombocitebis agregaci-

is gansazRvrisas pirobebi ufro metad uaxlov-

deba Trombocitebis fiziologiur garemos, mag-

ram aseT SemTxvevaSi antagonistebis damatebis

Semdeg Trombocitebi avtomatur mTvlelSi unda

daiTvalos [4]. avtomaturi mTvlelis saSuale-

biT Trombocitebis defeqtis aRmoCena SesaZle-

belia agonistebis damatebidan fiqsirebuli pe-

riodis Semdeg. samwuxarod, am meTodiT monofa-

zuri da bifazuri pasuxebis garCeva SeuZlebe-

lia.

impedansuri agregometri orive xelsawyos

saukeTeso Tvisebebs iTavsebs. optikuris msgav-

sad, impedansuri agregometriTac SesaZlebelia

agregaciis mrudis miReba drosTan mimarTebiT.

misi upiratesobaa Trombocitebis gamokvlevis

SesaZlebloba mTlian sisxlSi. axali aparatebi

saSualebas iZleva, luminescenciis gziT gani-

sazRvros adenozintrifosfatis (atf) gamoyofa.

agregaciuli reagentiT atf-is gamoyofa izome-

ba lumi-agregometriT, romelic fotometriul-

Tan erTad fluorometriuli kameriTac aris aR-

Wurvili. SuqmnaTi luciferaza (atf-aza, 3,0

mg/ml) atf-is gamoyofis sapasuxod gamoimuSa-

vebs sinaTles, rac drosTan mimarTebiT mrudiT

gamoisaxeba.

Cveulebriv, Seiswavleba Trombocitebis ag-

regacia adf-is (adenozindifosfati), epinefrinis,

Trombinis, ristocetinis, serotoninis, araqido-

nis mJavas an kolagenis sapasuxod. epinefrini,

wesisamebr, gamoiyeneba ori sxvadasxvagvari kon-

centraciiT: 2,5×10-5 moli (maRali koncentra-

cia) da 2,5×10-6

moli (dabali koncentracia).

adf-c orgvari koncentraciiT gamoiyeneba:

2,0×10-5

moli (maRali koncentracia) da

2,0×10-6

moli (dabali koncentracia). sxva rea-

gentebis saboloo koncentraciebi aseTia: kola-

genisa _ 0,19 mg/ml, ristocetinisa _ 1,5 mg/ml,

araqidonis mJavasi _ 0,5 mg/ml [1-3].

monofazuri mrudebi (~yvela an arc erTi~)

adf-s, ristocetins, araqidonis mJavasa da kola-

gens axasiaTebs, epinefrinis sapasuxod ki miiRe-

ba bifazuri mrudi. adf-is sapasuxod ganviTare-

buli Trombocitebis agregacia ukuproporciu-

lad ukavSirdeba hematokrits, xolo Tromboci-

tebisa da leikocitebis raodenobis mimarT pir-

dapirproporciul kavSirs avlens.

kolagenisTvis tipuria dagvianebuli faza

[5]. ristocetinis gamoyenebisas aRiniSneba nor-

maluri agregacia, magram atf-azis gamoyofa sxva

reagentebis umravlesobis 35%-s utoldeba.

Trombocitebis aqtivaciis dros gamoiyofa

Trombocitebis mravali faqtori, romelTa gamo-

yenebac SesaZlebelia preTrombozuli da Trom-

bozuli mdgomareobebis diagnostikisTvis. Trom-

bocituli faqtori 4, β-Tromboglobulini da

A2 Tromboqsani uSualod Trombocitebis aqti-

vaciisas gamoiyofa, xolo B2 Tromboqsani gamo-

Tavisufldeba ciklooqsigenazis moqmedebis pe-

riodSi, araqidonis mJavas zegavleniT Trombo-

citebis aqtivaciis dasrulebis Semdeg [6]. aR-

niSnuli faqtorebis odenoba izrdeba Trombo-

citdamokidebuli Trombozuli mdgomareobis,

Trombozuli insultis, Rrma venebis Trombozis,

filtvis arteriis emboliis, miokardiumis mwva-

ve infarqtisa da arastabiluri stenokardiis

dros [7; 8]. aspirini da antiTrombocituli

moqmedebis sxva preparatebi maT gamoyofas

Trgunavs.

Trombocitebis aqtiuri moxmarebis para-

lelurad xdeba maTi gaZlierebuli warmoqmna,

ris Sedegadac icvleba am ujredebis forma, ker-

Zod, Cndeba axalgazrda da didi zomis Trombo-

citebi. am cvlilebebis dadgena advilia avtoma-

turi aparatis meSveobiT, sadac aRiniSneba Trom-

bocitebis saSualo moculobis zrda [1-3].

bernar-sulies sindromis (Ber nar d-So u li er

syndro me) dros glikoprotein lb-IX-V kompleq-

si defeqturia. klinikurad es SesaZloa gamov-

lindes mZime sisxldeniT, TrombocitopeniiT da

4 daviT Telias klinikuri leqciebis cikli

Trom bo ci tuli hemostazis Sefaseba

Page 5: trombocituli hemostazis Sefaseba - telia.ge hemostazi-d.t.-pas.pdf · orebiTi venuri Trombozi ufro xSirad gvxvde-ba mamakacebSi,xandazmul pirebSi,aseve _ imobi-lizaciisa da avTvisebiani

metismetad didi zomis Trombocitebis gaCeniT.

damaxasiaTebelia ristocetinisa da Trombinis

mimarT agregaciis daqveiTeba an sruli uqonlo-

ba, sxva agonistebis umravlesobis mimarT ki sa-

pasuxo reaqciebi ucvlelia [9]. Trombocitebis

agregaciis normaluri profilis miReba SesaZ-

lebelia mxolod Trombinis maRali koncentra-

ciis pirobebSi [10]. bernar-sulies sindromi Se-

saZloa SecdomiT von-vilebrandis daavadebad iq-

nes miCneuli. maTi diferencirebisTvis gadam-

wyveti mniSvneloba aqvs Sededebis VIII faqto-

ris aqtivobas (adheziis faqtori VII:C), von-vi-

lebrandis faqtoris antigenisa (vWF:Ag) da

ristocetinis kofaqtoris aqtivobis (vWF:RCo)

Seswavlas. von-vilebrandis daavadebisgan gan-

sxvavebiT, bernar-sulies sindromis dros Sede-

debis sistemaSi arsebuli defeqtis koreqcia

normaluri plazmis damatebis gziT SeuZlebe-

lia. von-vilebrandis faqtori da Trombini

ukavSirdeba glikoprotein lb-s, romelic glikop-

rotein lb-IX-V kompleqsis Trombocituli re-

ceptoris aucilebeli komponentia. es recepto-

ri Trombocitebis adheziaSi monawileobs da de-

feqturia bernar-sulies sindromis dros [9].

glancmanis TrombasTenias (Glan zmann throm -

bas the ni a) axasiaTebs agregaciis sruli uqonlo-

ba adf-is, Trombinis, epinefrinis, kolagenisa da

araqidonis mJavas mimarT, CamoTvlili agoniste-

bis sapasuxod atf-is gamoyofa ki normaluri an

daqveiTebulia.

glancmanis TrombasTeniisTvis tipuria ag-

regaciis sruli uqonloba da atf-is normalu-

ri gamoyofa araqidonis mJavas sapasuxod. aseve,

aRsaniSnavia, rom am dros ar arsebobs glikop-

rotein IIb/IIIa receptorebi, romlebic Trombo-

citebis aqtivaciisTvis aris saWiro [11].

meoreuli agregaciis darRvevebi ufro

xSiria, vidre pirveladis defeqtebi. maT Soris

yvelaze metad aris gavrcelebuli elementebis

deponirebis darRveva TrombocitebSi. es is

mdgomareobaa, rodesac TrombocitebSi aRiniSneba

alfa da beta granulebis (an orives) ukmariso-

ba. normaSi am granulebSi sxvadasxva nivTiereba

grovdeba: alfa granulebSi _ fibrinogeni, vileb-

randis faqtori, betaSi _ kalciumi, serotonini,

adeninis nukleotidebi da sxva. daavadebisTvis

damaxasiaTebelia advilad ganviTarebadi sponta-

nuri sisxlCaqcevebi, sisxldena kanidan da lor-

wovani garsebidan, hematuria da epistaqsisi, pe-

teqiebi ki ufro metad Trombocitebis pirvela-

di agregaciis darRvevisas Cndeba. deponirebis

darRvevis SemTxvevaSi aRiniSneba agregaciis pir-

veladi talRebi, xolo meoreuli sapasuxo tal-

Rebi adf-isa da epinefrinis mimarT damaxasiaTe-

beli ar aris. kolagenis mimarT pasuxi saerTod

ar aris gamoxatuli, xolo ristocetinis mimarT

normaluri pasuxi miiReba [1-3]. deponirebis de-

feqtis diagnostikis saukeTeso saSualebaa

transmisiuli eleqtronuli mikroskopia.

ciklooqsigenazisa da Tromboqsanis sinTe-

zis memkvidreobiTi deficiti iSviaTia da aspi-

rinismagvar defeqts hgavs. adf-isa da epinefri-

nis mimarT ar viTardeba meoreuli talRa, aseve,

ar aRiniSneba pasuxi kolagenis mimarT.

ruxi Trombocitebis sindromis SemTxveva-

Ta umravlesobaSi, romlebic alfa granulebis

naklebobiT aris gamowveuli, Trombocitebis ag-

regacia da atf-is gamoyofa yvela agonistis mi-

marT daqveiTebulia. miuxedavad amisa, P seleqti-

nis deficitiT mimdinare ruxi Trombocitebis

sindromis dros adf-isa da ristocetinis sapa-

suxod viTardeba normaluri agregaciuli pasu-

xi, xolo kolagenis mimarT pasuxi saerTod ar

aRiniSneba. Trombocitebis raodenoba 1 mkl-Si,

Cveulebriv, 100 000-200 000-ia, maTi zoma ki 2,5-

jer aRemateba normalurs [12]. P seleqtinis sa-

winaaRmdego monoklonuri antisxeulebi Trgu-

navs ristocetinis sapasuxo agregacias [13].

acetilsalicilis mJavasTan dakavSirebuli

cvlilebebis aRmoCena SesaZlebelia Tromboci-

tebis lumiagregaciis gamoyenebiT. Trombocito-

paTiebis dros, iseve rogorc acetilsalicilis

mJavaTi mkurnalobisas, irRveva agregaciis pro-

cesebi da kolagenis, epinefrinis, adf-isa da ara-

qidonis mJavas sapasuxod atf-is gamoyofa.

Trombocitebis Tandayolili defeqtebis aRmoCe-

nis mgrZnobeloba 80%-s utoldeba, acetilsali-

cilis mJavas miRebisa ki _ 100%-s [14].

Trombocitebis agregaciis SeswavliT qi-

rurgiuli operaciis dros sisxldenis ganviTa-

rebis albaTobis gansazRvra SeuZlebelia [5].

gulis iSemiuri daavadebebi, rogorc Cans, Trom-

bocitebis agregaciul Taviseburebebze ar aris

5daviT Telias klinikuri leqciebis cikli

Trom bo ci tuli hemostazis Sefaseba

Page 6: trombocituli hemostazis Sefaseba - telia.ge hemostazi-d.t.-pas.pdf · orebiTi venuri Trombozi ufro xSirad gvxvde-ba mamakacebSi,xandazmul pirebSi,aseve _ imobi-lizaciisa da avTvisebiani

damokidebuli [7]. msgavsad amisa, arteriebis pe-

riferiuli daavadebebis dros ar Seiswavleba

Trombocitebis aqtivaciis markerebi: Tromboci-

tuli faqtori 4, plazmisa da Trombocitebis β-

Tromboglobulini, Sardis 11-dehidroTromboqsa-

ni B2. ar xdeba agreTve Trombocitebis agrega-

ciis Seswavla [8].

zemoT CamoTvlili daavadebebis diagnosti-

kisTvis specialistebi gvTavazoben Semdeg tes-

tebs:

� VIII faq to ris aq ti vo bis Ses wav las;

� re ti ku lo ci te bis ra o de no bis gan sazR vras;

� ris to ce ti nis ko faq to ris fun qci is Ses wav -

las;

� von -vi leb ran dis faq to ris an ti ge nis gan sazR -

vras.

di se mi ni re bu li sisxlZarRvSiga Se de -de bis (dsS) sin dro mis Se fa se ba

Trombogenezis dros gamoTavisuflebuli

zogierTi daSlis produqti SesaniSnavi markeria,

romlis saSualebiTac Trombozuli aqtivobis

gansazRvra SeiZleba. proTrombinis daSlis Se-

degad miiReba proTrombinis fragmenti 1.2 da

Trombini. es ukanaskneli Sededebis kaskadis

erT-erT aqtiur komponents warmoadgens. Trom-

bini Slis fibrinogens A fibrinopeptidad da

fibrinis monomerad, romelic Semdeg spontanur

polimerizacias ganicdis. Trombini inaqtivirde-

ba antiTrombin III-is zemoqmedebiT, romelic

Trombin-antiTrombin III-is kompleqsis warmoq-

mnas uzrunvelyofs.

aqtiuri fibrinis miRebis dros izrdeba

proTrombinis fragment 1.2-is, Trombin-antiTrom-

bin III-is kompleqsis, A fibrinopeptidisa da D

dimeris raodenoba.

rogorc zemoT aRiniSna, Xa faqtoris ze-

moqmedebiT proTrombinis Trombinad gardaqmnis

dros warmoiqmneba 1.2 fragmenti. es fragmenti

Trombinis formirebis mgrZnobiare indikatoria.

Trombinis formirebis dasrulebis Semdeg mas

daukavSirdeba antiTrombin III. sisxlSi am kom-

pleqsis (Trombin-antiTrombin III-is) arseboba

Trombinis gaZlierebul warmoqmnaze miuTiTebs,A

fibrinopeptidi ki imis maCvenebelia, rom momate-

bulia Trombinis odenoba da fibrinogenze misi

zemoqmedebis Sedegad miiReba TviTon A fibrino-

peptidi. plazmini jvaredinad dakavSirebul fib-

rins fibrinis degradaciis produqtebad Slis.

es produqtebia XY, DD (D dimeri), DDEE da

DY. plazmini Slis fibrinogensac, ris Sedega-

dac miiReba arajvaredindakavSirebuli fibrino-

genis degradaciis produqtebi, maT Soris _ X,

Y, D da E [15; 16].

infeqciebis, travmis, sameano garTulebebis,

avTvisebiani daavadebebisa da anTebiTi procese-

bis dros SesaZloa ganviTardes masiuri hemos-

tazuri darRveva, romlisTvisac damaxasiaTebe-

lia sisxlZarRvSiga Sededebis procesebis moS-

la da koagulaciuri faqtorebis iseTi Warbi

moxmareba, rom gamofituli plazma kargavs he-

mostazis unars.

diseminirebuli sisxlZarRvSiga Sededebis

dros plazma, faqtobrivad, Sratad iqceva. sawyi-

si fazisTvis damaxasiaTebelia hiperkoagulacia

da Trombozebi, gansakuTrebiT _ stazis SemTxve-

vaSi. Trombozisa da sisxldenis Tanaarsebobisas

didia dainvalidebisa da letalobis albaToba.

diseminirebuli sisxlZarRvSiga Sededebis

tipuri laboratoriuli niSania koagulaciuri

faqtorebis deficiti. viTardeba Trombocitope-

nia, hipofibrinogenemia an afibrinogenemia.

Trombin-antiTrombin III-is, 1.2 fragmentisa da D

dimeris maRali koncentracia Trombozis mimdi-

nareobis maCvenebelia [17; 18], Trombolizisze ki

metyvelebs fibrinogenis degradaciis iseTi pro-

duqtebis aRmoCena, rogoric aris, magaliTad,

xsnadi fibrinis monomeri da plazmin-α-2-antip-

lazminis kompleqsis momatebuli raodenoba [19;

20]. I, II, V, VIII : C, XIII faqtorebi, antiTrombin III

da Trombocitebi diseminirebuli sisxlZarRvSi-

ga Sededebis sindromis dros swrafad moixmare-

ba, VII, IX, X da XI faqtorebi ki SesamCnev cvli-

lebebs ar ganicdis. fibrinis degradaciis pro-

duqtebis raodenobis momateba (Cveulebriv, 25

mg/ml) fibrinolizze metyvelebs, rac dsS-isTvis

tipuria. amdenad, fibrinis degradaciis produq-

tebis ararseboba dsS-s gamoricxavs, Tumca unda

gaviTvaliswinoT, rom iSviaTad es sindromi fib-

6 daviT Telias klinikuri leqciebis cikli

Trom bo ci tuli hemostazis Sefaseba

Page 7: trombocituli hemostazis Sefaseba - telia.ge hemostazi-d.t.-pas.pdf · orebiTi venuri Trombozi ufro xSirad gvxvde-ba mamakacebSi,xandazmul pirebSi,aseve _ imobi-lizaciisa da avTvisebiani

rinis degradaciis produqtebis ucvleli kon-

centraciis fonzec mimdinareobs. dsS-is dros

aRniSnul produqtebze Catarebuli analizis

uaryofiTi pasuxi SesaZloa imiT iyos ganpiro-

bebuli, rom analizi naklebad mgrZnobiarea mci-

re zomis fragmentebis (D da E) mimarT an Seda-

rebiT didi fragmentebi (X da Y) ukve moxmar-

da Trombogenezs Trombinis damatebis Sedegad.

D dimeri jvaredindakavSirebuli fibrinis

degradaciis produqtia. is fibrinogenisgan ar

warmoiqmneba da fibrinis dagrovebiT mimdinare

koagulaciis maCvenebelia. am faqtorebis koncen-

traciis cvlilebebi ar Seesabameba dsS-is sim-

Zimis xarisxs. dsS-is ganviTarebis Semdeg gadar-

Cenili da gardacvlili avadmyofebis sisxlSi

xsnadi fibrinis monomeris, Trombin-antiTrombin

III-is, plazmin-α-2-antiplazminis kompleqsisa da

D dimeris koncentracia erTmaneTisgan umniSvne-

lod gansxvavdeba [21; 22]. amasTanave, aRsaniSna-

via, rom Camoyalibebuli dsS-is dros plazmaSi

xsnadi fibrinis monomeris koncentracia bevrad

ufro maRalia, vidre pre-dsS-is dros. Tavis

mxriv, pre-dsS-is dros misi mniSvneloba aRema-

teba im avadmyofebis xsnadi fibrinis monomeris

koncentracias, romlebsac dsS ar aReniSnebaT.

gabeqsatis mezilatiT mkurnalobis Sedegad

xsnadi fibrinis monomeris koncentraciis daqve-

iTeba daavadebis sasikeTo dasasrulis mauwyebe-

lia, xolo Tu aRniSnuli mkurnaloba uSedego

aRmoCnda, prognozi naklebad saimedoa.

xsnadi fibrinis monomeris koncentracia

dsS-is mimdinareobaze ar aris damokidebuli

[21]. janmrTel pirebSi misi koncentraciaa

5,9+/_1,4 mkg/ml, dsS-is dros _ 363+/_314

mkg/ml, xolo pre-dsS-is dros _ 181+/_132

mkg/ml [21].

dsS-isTvis damaxasiaTebelia plazmis

Trombomodulinis donis momateba. misi maCvenebe-

li gansakuTrebiT maRalia gardacvlilebSi [20].

heparinoTerapiis dawyebis Semdeg 1.2 frag-

mentis koncentracia mkveTrad mcirdeba da daba-

li rCeba oraluri antikoagulantebiT mkurna-

lobis periodSi. oraluri antikoagulantebiT

mkurnalobis stabilur fazaSi INR-sa da 1.2

fragmentis koncentracias Soris arsebobs ukup-

roporciuli kavSiri [23].

dsS-is hepariniT mkurnalobis kontroli

aPTT-is meSveobiT xorcieldeba. unda SenarCun-

des misi iseTi koncentracia, romelic sawyis

mniSvnelobas 1,5-jer aRemateba. Tu mdgomareoba

ar gaumjobesda an fibrinis (fibrinogenis) deg-

radaciis produqtebis done maRali darCa, hepa-

rinis doza SeiZleba gaizardos. α-2-antiplaz-

minis koncentraciis 50%-iT daqveiTeba dsS-is

fibrinolizur komponentze miuTiTebs. aseT

dros unda daisvas mkurnalobaSi fibrinolizu-

ri preparatebis CarTvis sakiTxi.

heparinis gamoyenebidan 6 saaTis Semdeg sag-

rZnoblad iklebs A fibrinopeptidis done. misi

mniSvneloba dabalia, rodesac aPTT-is sawyis

maCvenebels 1,5-jer aRemateba. heparinoTerapiis

Sewyvetisa da aspirinis daniSvnis SemTxvevaSi

imatebs A fibrinopeptidisa da Trombin-antiT-

rombin III-is koncentracia [25].

dsS sindromis diagnostikisTvis specia-

listebi gvTavazoben Semdeg testebs:

� α-2-an tip laz mi ni;

� fib ri no li zis deg ra da ci is pro duq te bi;

� proT rom bi nis frag men ti 1.2;

� Trom bi nis dro.

Trom bo ze bis Se fa se ba laborato ri u -li ana li ze bis sa fuZ vel ze

venuri Trombozi da Tromboembolia gare-

gani, SeZenili da memkvidreobiTi riskfaqtore-

bis kombinirebuli moqmedebis Sedegia. is invali-

dizaciisa da letalobis erT-erTi wamyvani mi-

zezia. 100 000-dan erT bavSvs yovelwliurad

aReniSneba venuri Trombozi. asakTan erTad es

maCvenebeli izrdeba da xandazmul pirebSi 1:100-

s Seadgens. SemTxvevaTa 30-40% spontanuria. ve-

nuri TrombozebisTvis damaxasiaTebeli hiperko-

agulaciuri mdgomareoba memkvidreobiTic SeiZ-

leba iyos da SeZenilic [26]. xSiria genetikuri

da SeZenili mizezebis Tanxvedra.

memkvidreobiTi Trombofilia anu memkvid-

reobiTi Trombozuli daavadeba sxvadasxva cno-

bil meqanizms ukavSirdeba [26]. Trombinis inaq-

7daviT Telias klinikuri leqciebis cikli

Trom bo ci tuli hemostazis Sefaseba

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tivaciisa da koltis warmoqmnis sawinaaRmdegod

aris mimarTuli xuTi umTavresi antikoagulan-

tis moqmedeba: antiTrombin III uSualod aneit-

ralebs Trombins, proteini C uzrunvelyofs ga-

aqtiurebuli Va da VIIIa faqtorebis inaqtiva-

cias, proteini S protein C-s kofaqtoria, Trom-

bomodulini ganapirobebs protein C-s aqtivaci-

as Trombinis meSveobiT, xolo qsovilovani faq-

toris inhibitori aneitralebs koagulaciis

sawyis (gamSveb) komponentebs. protein C-s, pro-

tein S-is da antiTrombin III-is mutaciis Sede-

gad Sesabamisi alelebi gadadis arafunqciur

mdgomareobaSi, ris gamoc plazmaSi mcirdeba Se-

dedebis inhibitorebis koncentracia. xsnebuli

antikoagulaciuri faqtorebis deficitis dros

Trombozebis riski 10-jer ufro maRalia, Tumca

maTi deficiti iSviaTad (0,02-0,2%) gvxvdeba.

marTalia, genebis funqciuri mutaciebi

Trombozebis SedarebiT susti riskfaqtoria

(maT fonze Trombozebis ganviTarebis albaToba

2-5-jer imatebs), magram es cvlilebebi mosaxle-

obaSi ufro farTod (2-10%-Si) aris gavrcele-

buli [27]. erT-erTi maTgania leidenis V faqto-

ris mutacia, (FII) G20210A proTrombinis muta-

cia da VIII, IX da XI prokoagulaciuri faqto-

rebis koncentraciis momateba, romelTa memkvid-

reobiTi buneba gaurkvevelia. leidenis V faq-

toris mutaciis Sedegad viTardeba gaaqtiurebu-

li C proteinis memkvidreobiTi rezistentoba,

rac Trombofiliis erT-erTi mniSvnelovani mi-

zezia. 3´ aratranslaciur ubanSi (FII) G20210A

proTrombinis mutacia ganapirobebs proTrombi-

nis koncentraciis momatebas, ris Sedegadac iz-

rdeba venuri Trombozis ganviTarebis riski

(cxrili #1). prokoagulaciuri (V, II, VIII da

von-vilebrandis faqtorebi) da antikoagulaci-

uri faqtorebis (S proteini, C proteini, antiT-

rombin III, Z proteini da protein Z-is inhibi-

tori) koncentraciebi umTavresad genetikurad

aris determinirebuli [27].

memkvidreobiTi Trombozuli daavadebis

laboratoriuli kvleva utardebaT mxolod Se-

sabamisi anamnezis mqone pacientebs da ara Trom-

bozis nebismieri klinikuri gamovlinebis mqone

pirebs. unda gamoiricxos Trombozis gamomwvevi

SeZenili faqtorebi: avTvisebiani da mielopro-

liferaciuli daavadebebi, xangrZlivi imobiliza-

cia, anatomiuri defeqtebi, orsuloba, oraluri

kontraceptivebis miReba da qirurgiuli opera-

ciebi.

memkvidreobiT Trombozul daavadebaze

metyvelebs venuri Tromboemboliis SemTxvevebi

45 wlamde asakSi, morecidive Trombozuli daa-

vadeba (Re cur rent throm bo tic di se a se) da venuri

Tromboembolizmis ojaxuri anamnezi [26]. ganme-

orebiTi venuri Trombozi ufro xSirad gvxvde-

ba mamakacebSi, xandazmul pirebSi, aseve _ imobi-

lizaciisa da avTvisebiani daavadebebis dros.

asidan xuT SemTxvevaSi is sasikvdiloa. ganmeo-

rebiTi Trombozi xSiria aseve protein C-s, pro-

tein S-is da antiTrombin III-is deficitis piro-

bebSi da SemTxvevaTa 60-80%-Si viTardeba, am faq-

torebis deficitis ararsebobisas ki morecidi-

ve Trombozuli daavadeba mxolod 6-10%-Si

gvxvdeba. ganmeorebiTi Trombozi aRiniSneba ag-

reTve leidenis V faqtoris homozigoturi mu-

taciis fonze.

amJamad sakamaToa, izrdeba Tu ara ganmeore-

biTi Tromboembolizmis sixSire leidenis V

faqtorisa da (FII) G20210A proTrombinis hete-

rozigoturi mutaciebis dros.

hiperhomocisteinemia da masTan dakavSire-

buli meTilenis tetrahidrofoliumis reduqta-

zis fermentis Trombolabiluri variantuli

forma memkvidreobiTi Trombozuli daavadebis

potenciuri mizezia. ganmeorebiTi Trombozis

riski izrdeba aseve homocisteinisa da VIII faq-

toris plazmuri koncentraciis momatebis Sem-

TxvevaSi. hiperhomocisteinemiiT daavadebulebs

morecidive Trombozuli daavadeba asidan daax-

loebiT 75 SemTxvevaSi aReniSnebaT.

protein C-s, protein S-is da antiTrombin

III-is deficitis dros, leidenis V faqtoris

homozigoturi da heterozigoturi mutaciisa

da hiperhomocisteinemiis SemTxvevebisgan gan-

sxvavebiT, Trombozi SedarebiT axalgazrda asak-

Si viTardeba. kerZod, pacientebis 50%-s Trom-

bozis pirveli SemTxveva 40 wlamde asakSi uv-

8 daviT Telias klinikuri leqciebis cikli

Trom bo ci tuli hemostazis Sefaseba

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cxri li #2

proT rom bo ge nu li faq to re bis Se far de bi Ti ris ki Trom bo ze bis gan vi Ta re ba Si

pir ve la di

proT rom bo ge nu li

faq to re bi

pre va len si (six Si re) Trom bo ze bis gan vi Ta re bis ris ki

Trom bo ze bis

mqo ne

pa ci en te bi (%)

Zi ri Ta di

mo sax le o ba (%)

Se far de bi Ti

ris kiSedarebiTi ris ki

C ci lis de fi ci ti 2.1 0.3 7.1 1.8

an tiT rom bin III-is de fi ci ti 1.1 0.2 5.6 0.9

S ci lis de fi ci ti 2.2 0.2 11.2 2.0

hi per ho mo cis te i ne mia 10 4.8 2.2 5.4

proT rom bi nis mo ma te ba 6.2 2.3 2.8 4.0

le i de nis V faq to ri 20 4 6.0 16.7

VIII faq to ris mo ma te ba 25 11 2.7 15.6

hi per fib ri no ge ne mia 15 8 2.0 7.4

lindeba, 85%-s ki _ 50 wlamde asakSi. Tu pir-

veli rigis aranakleb ori naTesavi simptomuria

(anamnezSi Trombozi aReniSneba), 98%-ia albaTo-

ba, avadmyofis Trombozuli movlena memkvidreo-

biTi Trombozuli daavadeba iyos. amasTanave, uar-

yofiTi ojaxuri anamnezi memkvidreobiT Trombo-

zul daavadebas ar gamoricxavs.

protein C-s, protein S-i sa da antiTrom-

bin III-is deficitis dasadgenad laboratoriu-

li analizebis Catareba ar aris mizanSewonili

oraluri antikoagulaciuri Terapiis fonze.

analizebis Catarebamde sul cota ori kviriT

adre kumarinebi unda Seicvalos hepariniT. ase-

ve ar aris rekomendebuli avadmyofis gamokvle-

va uSualod Trombozuli movlenis Semdgom pe-

riodSi, vinaidan am dros antiTrombin III-isa da

protein S-is moxmarebis gamo maTi koncentracia

Seusabamod dabali iqneba.

hiperkoagulaciis yvelaze xSiri mizezebis

gamoricxvis Semdeg, uwinares yovlisa, mowodebu-

lia antifosfolipiduri sindromis skriningi.

rogorc pirvelad, ise meoreul antifosfolipi-

dur sindroms axasiaTebs kardiovaskuluri da

cerebrovaskuluri arteriuli da venuri Trom-

bozebi, nevrologiuri darRvevebi, ganmeorebiTi

spontanuri aborti da Trombocitopenia mglu-

ras antikoagulantebis arsebobisa da/an anionu-

ri fosfolipidebis sawinaaRmdego autoantisxe-

ulebis (kardiolipinis, fosfatidilserinis, b2glikoproteinis I-is sawinaaRmdego autoantisxe-

ulebi) momatebuli koncentraciis fonze [28].

antifosfolipiduri sindromis skriningisTvis

mizanSewonilia aseve dabali simkvrivis lipop-

roteinebis gansazRvra. bavSvTa asakSi fosfoli-

piduri autoantisxeulebi Trombozuli movle-

nebis SemTxvevaTa mesamedsa da idiopaTiuri ce-

9daviT Telias klinikuri leqciebis cikli

Trom bo ci tuli hemostazis Sefaseba

Page 10: trombocituli hemostazis Sefaseba - telia.ge hemostazi-d.t.-pas.pdf · orebiTi venuri Trombozi ufro xSirad gvxvde-ba mamakacebSi,xandazmul pirebSi,aseve _ imobi-lizaciisa da avTvisebiani

rebruli iSemiis SemTxvevaTa or mesamedSi aRi-

niSneba [29]. memkvidreobiTi Trombozuli daava-

debis yvelaze xSiri mizezebis dasadgenad unda

ganisazRvros protein C-sa da protein S-is aq-

tivoba, agreTve _ leidenis V faqtoris geno-

tipi (gaaqtiurebuli protein C-s genetikuri

rezistentulobis SemTxvevaSi). plazmaSi homo-

cisteinis koncentraciis gansazRvra martivi

analizia da hiperhomocisteinemiis dasadgenad

gamoiyeneba. Tu homocisteinis koncentracia ma-

Ralia, avadmyofs utardeba meTilenis tetrahid-

rofoliumis reduqtazis genotipireba, ris sa-

fuZvelzec SesaZlebelia Trombozebis memkvidre-

obiTi mizezis garkveva. antiTrombin III-is defi-

citi memkvidreobiT Trombozul daavadebas iSvi-

aTad iwvevs. is mxolod im SemTxvevaSi ganisazR-

vreba, Tu sxva analizebis Sedegebi uaryofiTi

aRmoCnda [30; 31].

sameano garTulebebi da Trombozebi erTma-

neTs mWidrod ukavSirdeba. pacients, romelsac

antifosfolipiduri sindromi aReniSneba, anamne-

zi datvirTuli aqvs mravlobiTi abortiT. iseT

sameano garTulebebs, rogoric aris mZimed mim-

dinare eklamfsia, placentis naadrevi acla, na yo -

fis zrda Si CamorCena da mkvdradSobadoba, Tan

axlavs meTilenis tetrahidrofoliumis reduq-

10 daviT Telias klinikuri leqciebis cikli

Trom bo ci tuli hemostazis Sefaseba

suraTi #1

bunebrivi antiTrombozuli meqanizmebi

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11daviT Telias klinikuri leqciebis cikli

Trom bo ci tuli hemostazis Sefaseba

tazis, leidenis V faqtorisa da (FII) G20210A

proTrombinis mutaciebi, agreTve _ protein C-s,

protein S-i sa da antiTrombin III-is deficiti

[7]. leidenis V faqtoris (R506Q), meTilenis

tetrahidrofoliumis reduqtazisa (C677T da

A1298C) da (FII) G20210A proTrombinis muta-

ciebi aRmoaCnda im qalebis 52%-s, romlebsac de-

disa da nayofis sisxlis mimoqcevis moSla aqvT

gamoxatuli [7]. aqedan SeiZleba davaskvnaT, rom

faqtorebi, romlebic Trombozebis ganviTarebis

risks zrdis, ganmeorebiTi abortis paTogenezSic

unda monawileobdes [33]. Tu qals anamnezSi aRe-

niSneba venuri Tromboembolizmi an ramdenime

aborti, mas orsulobis adreul etapze unda Ca-

utardes Trombozis skrininguli analizi, vinai-

dan, arsebuli monacemebis Tanaxmad, profilaqti-

kuri heparinoTerapia aseT SemTxvevebSi Sedegia-

nia [33].

leidenis V faqtoris fonze oraluri

kontraceptivebi zrdis Trombozis ganviTarebis

risks [34], ris gamoc, zogierTi avtoris azriT,

oraluri kontraceptivebis daniSvnamde sasurve-

lia am mutaciis skriningi.

marTalia, arteriuli da venuri Tromboze-

bis riskfaqtorebi erTmaneTisgan gansxvavdeba,

magram maTTvis saerToa fibrinis formirebis

procesi, romelic orive SemTxvevaSi Sededebis

saboloo etaps warmoadgens. Trombozebis gene-

tikuri kontroli ori sxvadasxva meqanizmiT

xorcieldeba. esenia: koagulaciuri faqtorebis

koncentraciis genetikurad pirobadebuli moma-

teba da genetikurad pirobadebuli proTrombu-

li statusi (mdgomareoba). am ukanasknels Sede-

debis sistemis gaaqtiureba da Trombinis pro-

duqciis gansazRvruli done axasiaTebs [27; 35].

proTrombuli statusi maRalia im pirebs Soris,

romlebsac koronaruli arteriebisa da sxva

Trombozuli daavadebebis ganviTarebis maRali

riski aqvT [35], proTrombozuli statusi ki

mdgomareobaa, rodesac gamoxatulia Sededebisa

da fibrinolizuri sistemebis gaaqtiureba. es

statusi didwilad genetikuri faqtorebiT aris

determinirebuli [35]. Trombozebisadmi midreki-

lebis dasadgenad unda ganisazRvros proTrom-

bozuli statusis iseTi markerebis plazmuri

koncentracia, rogoric aris 1+2 proTrombinis

fragmentebi,Trombin-antiTrombinis kompleqsi da

D dimeri.

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