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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.
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.
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
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
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
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
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
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
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
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
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.
�
li te ra tu ra:
1. Fu se I., Di sor ders of pla te let fun cti on. Crit Rev Oncol
He ma tol 1996; 22:1-25
2. Bick R.L., Pla te let fun cti on de fects: A cli ni cal re vi ew.
Sem Thromb He most 1992;18:167-85
3. Bick R.L., La bo ra tory eva lu a ti on of pla te let dysfun cti on.
Cli nics Lab Med 1995;15:1-38
4. Nar jes H., Mul ler TH, We i sen ber ger H, Guth B, Brickl
R. Inhi bi ti on of pla te let ag gre ga ti on as a sur ro ga te mar -
ker. J Clin Phar ma col 1997;37:59S-64S
5. Ka ba ki bi A., Vam va kas EC, Can nis tra ro PA, Szcze pi or -
kow ski ZM, La po sa ta M. Col la gen -in du ced who le blo od
pla te let ag gre ga ti on in pa ti ents un der go ing sur gi cal pro -
ce du res as so ci a ted with mi ni mal to mo de ra te blo od loss.
Am J Clin Pat hol 1998;109:392-8
6. Fa re ed J., Hop pen ste adt DA, Le ya F, Iqbal O, Wolf H,
Bick R. Use ful la bo ra tory tests for stud ying throm bo ge -
ne sis in acu te car di ac syndro mes. Clin Chem
1998;44:1845-53
7. Me a de T.W., Co o per J.A., Mil ler G.J., Pla te let co unts
and ag gre ga ti on me a su res in the in ci den ce of is cha e mic
he art di se a se (IHD). Thromb Ha e most 1997;78:926-9
8. Gre se le P., Ca ta la no M., Glam mar re si C., Vol pa to R. et
al. Pla te let ac ti va ti on mar kers in pa ti ents with pe rip he ral
ar te ri al di se a se: a pros pec ti ve com pa ri son of dif fe rent
pla te let fun cti on tests. Thromb Ha e most 1997;78:1434-7
9. Lo pez J.A., Andrews R.K., Afshar -Kar ghan V., Berndt
M.C., Ber nar d-So u li er Syndro me. Blo od 1998;91:4397-
418
10. McNi col A., Sut her land M., Zou R., Dro u in J., De fec ti -
ve throm bin -in du ced cal ci um chan ges and ag gre ga ti on
of Ber nar d-So u li er pla te lets are not as so ci a ted with de fi -
ci ent mo de ra te -af fi nity re cep tors. Arte ri os cler Thromb
Vasc Bi ol 1996;16:628-32
11. Scott J.P. 3rd, Scott J.P. 2nd, Chao Y.L., New man J.P.,
Ward C.M., A fra mes hift mu ta ti on at Gly975 in the tran -
smem bra ne do ma in of GP IIb pre vents GPIIb-IIIa ex -
pres si on —a nal ysis of two no vel mu ta ti ons in a kin dred
with type I glan zmann throm bas the ni a. Thromb Ha e most
1998;80:546-50
12. Ma zu rov A.V., Vi nog ra dov D.V., Khas pe ko va S.G.,
Krus hinsky A.V., Ger de va L.V., Va si li ev S.A., De fi ci -
ency of P-se lec tin in a pa ti ent with grey pla te let syndro -
me. Eur J Ha e ma tol 1996;57:38-41
13. Bo u ker che H., Ruc ha ud -Spa ra ga no M.H., Ro u en C.,
Broc hi er J., Kap lan C., McGre gor J.L., A mo noc lo nal an -
ti body di rec ted aga inst a gra nu le mem bra ne glycop ro te -
in (GMP-140/PDGEM, P-se lec tin, CD62P) in hi bits ris -
to ce tin -in du ced pla te let ag gre ga ti on. Br J Ha e ma tol
1996;92:442-51
14. Nu gent D.J., PFA-100 system: a new met hod for as ses -
sment of pla te let dysfun cti on. Se min Thromb He most
1998;24:195-202
15. Lij nen H.R., Col len D., Mec ha nisms of physi o lo gi cal
fib ri nol ysis. Ba ill Clin Ha e ma tol 1995;8:277-290
16. Fa re ed J., Hop pen ste adt D.A., Le ya F., Iqbal O., Wolf H.,
Bick R., Use ful la bo ra tory tests for stud ying throm bo ge -
ne sis in acu te car di ac syndro mes. Clin Chem
1998;44:1845-53
17. Pen ner J.A., Dis se mi na ted in tra vas cu lar co a gu la ti on in
pa ti ents with mul tip le or gan fa i lu re of non -sep tic ori gin.
Se min Thromb He most 1998;24:45-52
18. Ta ka has hi H., Wa da K., Ni wa no H., Shi ba ta A., Com pa -
ri son of prot hrom bin frag ment 1 + 2 with throm bin -an tit -
hrom bin III com plex in plas ma of pa ti ents with dis se mi -
na ted in tra vas cu lar co a gu la ti on. Blo od Co a gu la ti on Fib -
ri nol ysis 1992;3:813-8
19. Pfit zner S.A., Dem pfle C-E., Mat su da M., He e ne D.L.,
Fib rin de tec ted in plas ma of pa ti ents with dis se mi na ted
in tra vas cu lar co a gu la ti on by fib rin -spe ci fic an ti bo di es
con sists pri ma rily of high mo le cu lar we ight fac tor XIIIa-
cros slin ked and plas min -mo di fi ed com ple xes par ti ally
con ta i ning fib ri no pep ti de A. Thromb Ha e most
1997;78:1069-78
20. Wa da H., Mo ri Y., Si mu ra M., Hi yo ya ma K. et al. Po or
out co me in dis se mi na ted in tra vas cu lar co a gu la ti on or
throm bo tic throm boc yto pe nic pur pu ra pa ti ents with se -
ve re vas cu lar en dot he li al cell in ju ri es. Am J He ma tol
1998;58:189-94
21. Wa da H., Wa ki ta Y., Na ka se T., Shi mu ra M. et al. Incre -
a sed plas ma- so lub le fib rin mo no mer le vels in pa ti ents
with dis se mi na ted in tra vas cu lar co a gu la ti on. Am J He -
ma tol 1996;51:255-60
22. Oka ji ma K., Uchi ba M., Mu ra ka mi K., Oka be H., Ta kat -
su ki K., De ter mi na ti on of plas ma so lub le fib rin using a
new ELISA met hod in pa ti ent with dis se mi na ted in tra -
vas cu lar co a gu la ti on
23. Bruhn H.D., Co nard J., Man nuc ci M., Mon te a gu do J. et
al. Mul ti cen tric eva lu a ti on of a new as say for prot hrom -
bin frag ment F1 + 2 de ter mi na ti on
24. Tri po di A., Cat ta neo M., Mol te ni, Cesn B.M., Man nuc ci
P.M., Chan ges of prot hrom bin frag ment 1+2 (F 1+2) as
a fun cti on of in cre a sing in ten sity of oral an ti co a gu la ti on
: Con si de ra ti ons on the su i ta bi lity of F 1+2 to mo ni tor
oral an ti co a gu lant tre at ment. Thromb Ha e most
1998;79:571-3
25. Mom bel li G., Mar chet ti O., Ha e ber li A., Stra ub P.W.,
Effect of in tra ve no us he pa rin in fu si on on throm bin -an tit -
hrom bin com plex and fib ri no pep ti de A in un stab le an gi -
na. Am He art J 1998;136:1106-13
26. Se lig sohn U., Lu betsky A., Ge ne tic sus cep ti bi lity to ve -
no us throm bo sis. N Engl J Med 2001;344:1222-3
27. Ro sen da al F.R., Bo vill E.G., He ri ta bi lity of clot ting fac -
tors and the re vi val of the prot hrom bo tic sta te. Lan cet
2002;359:638-9
28. Alar con -Se go via D., Cab ral A.R., The an ti- phos pho li pid
an ti body syndro me: cli ni cal and se ro lo gi cal as pects. Ba -
il li e re’s Clin Rhe u ma tol 2000;14:139-50
29. Ra vel li A., Mar ti ni A., Antip hos pho li pid an ti body
syndro me in pe di at ric pa ti ents. Rhe um Dis Clin N Am
1997;23:657-76
30. Laf fan M., Tud den ham E., Asses sing throm bo tic risk. Br
J Med 1998;317:520-1
31. Adcock D.M., Fink L., Mar lar R.A., A la bo ra tory ap pro -
ach to the eva lu a ti on of he re di tary hyper co a gu la bi lity.
Am J Clin Pat hol 1997;108:434-49
32. Kup fer minc M.J., Eldor M., Ste in man N. et al. Incre a sed
fre qu ency of ge ne tic throm bop hi lia in wo men with com -
pli ca ti ons of preg nancy. N Engl J Med 1999;340:9-13
33. McColl M.D., Wal ker I.D., Gre er I.A., The ro le of in he -
ri ted throm bop hi lia in ve no us throm bo em bo lism as so ci -
a ted with preg nancy. Br J Obstet Gyna e col
1999;106:756-66
34. Van den bro uc ke J.P., Blo e men kamp K.W.M., Mid del dorp
S., et al. Oral con tra cep ti ves and the risk of ve no us
throm bo sis. N Engl J Med 2001;344:1527-35
35. Ari ens R.A.S., de Lan ge M., Sni e der H. et al. Acti va ti on
mar kers of co a gu la ti on and fib ri nol ysis in twins: he ri ta -
bi lity of the pret hrom bo tic sta te. Lan cet 2002;359:667-
71
12 daviT Telias klinikuri leqciebis cikli
Trom bo ci tuli hemostazis Sefaseba