trombocituli hemostazis Sefaseba

Transcription

1 Tbilisis saxelmwifo samedicino universitetis alergologiisa da klinikuri imunologiis mimartuleba davit Telias klinikuri leqciebis cikli trombocituli hemostazis Sefaseba Tbilisi 2009 w.

2 Tbilisis saxelmwifo samedicino universitetis alergologiisa da klinikuri imunologiis mimartuleba 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. 2

3 Trom bo ci tuli hemostazis Sefaseba Trombocituli hemostazis darrveva ukav- Sirdeba Trombocitebis raodenobriv da Tvisobriv cvlilebebs, romelta Sedegadac vitardeba peteqiebi, purpura, msubuqi, zomieri an Zlieri sisxldena. Trombocitebis raodenobrivi cvlilebebi vlindeba TrombocitopeniiT, TrombocitoziT, TrombocitemiiT (rac gamowveulia granulocituri leikemiit, mieloiduri metaplaziit da a.s.). Uspn!cp!dj!up!qf!oj!bt safuzvlad SeiZleba edos rogorc am ujredebis warmoqmnis Semcireba, 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 Trombocitebis adheziis darrveva, pirveladi da meoreuli agregaciis defeqtebi da sxva SedarebiT isviati izolirebuli defeqtebi (cxrili #1). cxri li #1 Trom bo ci te bis fun qciata mem kvid re o bi Ti dar Rve ve bi (de feq te bi) sxva sin dro meb Tan ad he zi is de feq te bi da kav Si re bu li cik lo oq si ge na zis ber nar -su li es sin dro mi de fi ci ti pir ve la di ag re ga ci is Trom boq sa nis sin Te ta zis de feq te bi de fi ci ti is vi a Ti izo li re bu li glan cma nis Trom bas Te nia de feq te bi Trom bo ci tu li faq to ri esen ci u ri at rom bia 3-is de fi ci ti me o re u li ag re ga ci is fos fa ti di li no zi to lis de feq te bi dar Rve ve bi de po ni re bis dar Rve ve bi afib ri no ge ne mia Trom bo ci teb Si mzi med mim di na re izo li re bu li de feq te bi he mo fi lia 3

4 Trom bo ci te bis ag re ga ci is Se fa se ba Trombocitebis agregaciis Seswavlis miznit atareben e.w Born-tests: TrombocitebiT mdidar plazmas atavseben agregometrsi da TvaliT afaseben Trombocitebis agregacias (optikuri agregometria). agregometri warmoadgens speqtrofotometrs. massi motavsebul TrombocitebiT mdidar plazmas emateba agregaciuli agentebi. Trombocitebis agregaciis Sedegad miireba drostan asocirebuli mzardi sinatlis mrudi, romelzec SesaZlebelia agregaciis pirveladi da meoreuli talrebis garceva [1-3]. swored am mruds afasebs mkvlevari. mtlian sisxlsi Trombocitebis agregaciis gansazrvrisas pirobebi ufro metad uaxlovdeba Trombocitebis fiziologiur garemos, magram aset SemTxvevaSi antagonistebis damatebis Semdeg Trombocitebi avtomatur mtvlelsi unda daitvalos [4]. avtomaturi mtvlelis sasualebit Trombocitebis defeqtis armocena SesaZlebelia agonistebis damatebidan fiqsirebuli periodis Semdeg. samwuxarod, am metodit monofazuri da bifazuri pasuxebis garceva SeuZlebelia. impedansuri agregometri orive xelsawyos sauketeso Tvisebebs itavsebs. optikuris msgavsad, impedansuri agregometritac SesaZlebelia agregaciis mrudis mireba drostan mimartebit. misi upiratesobaa Trombocitebis gamokvlevis SesaZlebloba mtlian sisxlsi. axali aparatebi sasualebas izleva, luminescenciis gzit ganisazrvros adenozintrifosfatis (atf) gamoyofa. agregaciuli reagentit atf-is gamoyofa izomeba lumi-agregometrit, romelic fotometriul- Tan ertad fluorometriuli kameritac aris ar- Wurvili. SuqmnaTi luciferaza (atf-aza, 3,0 mg/ml) atf-is gamoyofis sapasuxod gamoimusavebs sinatles, rac drostan mimartebit mrudit gamoisaxeba. Cveulebriv, Seiswavleba Trombocitebis agregacia adf-is (adenozindifosfati), epinefrinis, Trombinis, ristocetinis, serotoninis, araqidonis mjavas an kolagenis sapasuxod. epinefrini, wesisamebr, gamoiyeneba ori sxvadasxvagvari koncentraciit: 2, moli (marali koncentracia) da 2, moli (dabali koncentracia). adf-c orgvari koncentraciit gamoiyeneba: 2, moli (marali koncentracia) da 2, moli (dabali koncentracia). sxva reagentebis saboloo koncentraciebi asetia: kolagenisa _ 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 kolagens axasiatebs, epinefrinis sapasuxod ki miireba bifazuri mrudi. adf-is sapasuxod ganvitarebuli Trombocitebis agregacia ukuproporciulad ukavsirdeba hematokrits, xolo Trombocitebisa da leikocitebis raodenobis mimart pirdapirproporciul kavsirs avlens. kolagenistvis tipuria dagvianebuli faza [5]. ristocetinis gamoyenebisas arinisneba normaluri agregacia, magram atf-azis gamoyofa sxva reagentebis umravlesobis 35%-s utoldeba. Trombocitebis aqtivaciis dros gamoiyofa Trombocitebis mravali faqtori, romelta gamoyenebac SesaZlebelia pretrombozuli da Trombozuli mdgomareobebis diagnostikistvis. Trombocituli faqtori 4, β-tromboglobulini da A 2 Tromboqsani usualod Trombocitebis aqtivaciisas gamoiyofa, xolo B 2 Tromboqsani gamo- Tavisufldeba ciklooqsigenazis moqmedebis periodsi, araqidonis mjavas zegavlenit Trombocitebis aqtivaciis dasrulebis Semdeg [6]. arnisnuli faqtorebis odenoba izrdeba Trombocitdamokidebuli Trombozuli mdgomareobis, Trombozuli insultis, Rrma venebis Trombozis, filtvis arteriis emboliis, miokardiumis mwvave infarqtisa da arastabiluri stenokardiis dros [7; 8]. aspirini da antitrombocituli moqmedebis sxva preparatebi mat gamoyofas Trgunavs. Trombocitebis aqtiuri moxmarebis paralelurad xdeba mati gazlierebuli warmoqmna, ris Sedegadac icvleba am ujredebis forma, ker- Zod, Cndeba axalgazrda da didi zomis Trombocitebi. am cvlilebebis dadgena advilia avtomaturi aparatis mesveobit, sadac arinisneba Trombocitebis sasualo moculobis zrda [1-3]. bernar-sulies sindromis (Bernard-Soulier syndrome) dros glikoprotein lb-ix-v kompleqsi defeqturia. klinikurad es SesaZloa gamovlindes mzime sisxldenit, TrombocitopeniiT da 4

5 metismetad didi zomis Trombocitebis gacenit. damaxasiatebelia ristocetinisa da Trombinis mimart agregaciis daqveiteba an sruli uqonloba, sxva agonistebis umravlesobis mimart ki sapasuxo reaqciebi ucvlelia [9]. Trombocitebis agregaciis normaluri profilis mireba SesaZlebelia mxolod Trombinis marali koncentraciis pirobebsi [10]. bernar-sulies sindromi SesaZloa SecdomiT von-vilebrandis daavadebad iqnes micneuli. mati diferencirebistvis gadamwyveti mnisvneloba aqvs Sededebis VIII faqtoris aqtivobas (adheziis faqtori VII:C), von-vilebrandis faqtoris antigenisa (vwf:ag) da ristocetinis kofaqtoris aqtivobis (vwf:rco) Seswavlas. von-vilebrandis daavadebisgan gansxvavebit, bernar-sulies sindromis dros Sededebis sistemasi arsebuli defeqtis koreqcia normaluri plazmis damatebis gzit SeuZlebelia. von-vilebrandis faqtori da Trombini ukavsirdeba glikoprotein lb-s, romelic glikoprotein lb-ix-v kompleqsis Trombocituli receptoris aucilebeli komponentia. es receptori Trombocitebis adheziasi monawileobs da defeqturia bernar-sulies sindromis dros [9]. glancmanis TrombasTenias (Glanzmann thrombasthenia) axasiatebs agregaciis sruli uqonloba adf-is, Trombinis, epinefrinis, kolagenisa da araqidonis mjavas mimart, CamoTvlili agonistebis sapasuxod atf-is gamoyofa ki normaluri an daqveitebulia. glancmanis TrombasTeniisTvis tipuria agregaciis sruli uqonloba da atf-is normaluri gamoyofa araqidonis mjavas sapasuxod. aseve, arsanisnavia, rom am dros ar arsebobs glikoprotein IIb/IIIa receptorebi, romlebic Trombocitebis 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) ukmarisoba. normasi am granulebsi sxvadasxva nivtiereba grovdeba: alfa granulebsi _ fibrinogeni, vilebrandis faqtori, betasi _ kalciumi, serotonini, adeninis nukleotidebi da sxva. daavadebistvis damaxasiatebelia advilad ganvitarebadi spontanuri sisxlcaqcevebi, sisxldena kanidan da lorwovani garsebidan, hematuria da epistaqsisi, peteqiebi ki ufro metad Trombocitebis pirveladi agregaciis darrvevisas Cndeba. deponirebis darrvevis SemTxvevaSi arinisneba agregaciis pirveladi talrebi, xolo meoreuli sapasuxo tal- Rebi adf-isa da epinefrinis mimart damaxasiatebeli ar aris. kolagenis mimart pasuxi saertod ar aris gamoxatuli, xolo ristocetinis mimart normaluri pasuxi miireba [1-3]. deponirebis defeqtis diagnostikis sauketeso sasualebaa transmisiuli eleqtronuli mikroskopia. ciklooqsigenazisa da Tromboqsanis sintezis memkvidreobiti deficiti isviatia da aspirinismagvar defeqts hgavs. adf-isa da epinefrinis mimart ar vitardeba meoreuli talra, aseve, ar arinisneba pasuxi kolagenis mimart. ruxi Trombocitebis sindromis SemTxveva- Ta umravlesobasi, romlebic alfa granulebis naklebobit aris gamowveuli, Trombocitebis agregacia da atf-is gamoyofa yvela agonistis mimart daqveitebulia. miuxedavad amisa, P seleqtinis deficitit mimdinare ruxi Trombocitebis sindromis dros adf-isa da ristocetinis sapasuxod vitardeba normaluri agregaciuli pasuxi, xolo kolagenis mimart pasuxi saertod ar arinisneba. Trombocitebis raodenoba 1 mkl-si, Cveulebriv, ia, mati zoma ki 2,5- jer aremateba normalurs [12]. P seleqtinis sawinaarmdego monoklonuri antisxeulebi Trgunavs ristocetinis sapasuxo agregacias [13]. acetilsalicilis mjavastan dakavsirebuli cvlilebebis armocena SesaZlebelia Trombocitebis lumiagregaciis gamoyenebit. TrombocitopaTiebis dros, iseve rogorc acetilsalicilis mjavati mkurnalobisas, irrveva agregaciis procesebi da kolagenis, epinefrinis, adf-isa da araqidonis mjavas sapasuxod atf-is gamoyofa. Trombocitebis Tandayolili defeqtebis armocenis mgrznobeloba 80%-s utoldeba, acetilsalicilis mjavas mirebisa ki _ 100%-s [14]. Trombocitebis agregaciis SeswavliT qirurgiuli operaciis dros sisxldenis ganvitarebis albatobis gansazrvra SeuZlebelia [5]. gulis isemiuri daavadebebi, rogorc Cans, Trombocitebis agregaciul Taviseburebebze ar aris 5

6 damokidebuli [7]. msgavsad amisa, arteriebis periferiuli daavadebebis dros ar Seiswavleba Trombocitebis aqtivaciis markerebi: Trombocituli faqtori 4, plazmisa da Trombocitebis β- Tromboglobulini, Sardis 11-dehidroTromboqsani B 2. ar xdeba agretve Trombocitebis agregaciis Seswavla [8]. zemot CamoTvlili daavadebebis diagnostikistvis specialistebi gvtavazoben Semdeg testebs: 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 Sedegad miireba protrombinis fragmenti 1.2 da Trombini. es ukanaskneli Sededebis kaskadis ert-ert aqtiur komponents warmoadgens. Trombini Slis fibrinogens A fibrinopeptidad da fibrinis monomerad, romelic Semdeg spontanur polimerizacias ganicdis. Trombini inaqtivirdeba antitrombin III-is zemoqmedebit, romelic Trombin-antiTrombin III-is kompleqsis warmoqmnas uzrunvelyofs. aqtiuri fibrinis mirebis dros izrdeba protrombinis fragment 1.2-is, Trombin-antiTrombin III-is kompleqsis, A fibrinopeptidisa da D dimeris raodenoba. rogorc zemot arinisna, Xa faqtoris zemoqmedebit protrombinis Trombinad gardaqmnis dros warmoiqmneba 1.2 fragmenti. es fragmenti Trombinis formirebis mgrznobiare indikatoria. Trombinis formirebis dasrulebis Semdeg mas daukavsirdeba antitrombin III. sisxlsi am kompleqsis (Trombin-antiTrombin III-is) arseboba Trombinis gazlierebul warmoqmnaze miutitebs, A fibrinopeptidi ki imis macvenebelia, rom momatebulia Trombinis odenoba da fibrinogenze misi zemoqmedebis Sedegad miireba TviTon A fibrinopeptidi. plazmini jvaredinad dakavsirebul fibrins fibrinis degradaciis produqtebad Slis. es produqtebia XY, DD (D dimeri), DDEE da DY. plazmini Slis fibrinogensac, ris Sedegadac miireba arajvaredindakavsirebuli fibrinogenis degradaciis produqtebi, mat Soris _ X, Y, D da E [15; 16]. infeqciebis, travmis, sameano gartulebebis, avtvisebiani daavadebebisa da antebiti procesebis dros SesaZloa ganvitardes masiuri hemostazuri darrveva, romlistvisac damaxasiatebelia sisxlzarrvsiga Sededebis procesebis mosla da koagulaciuri faqtorebis iseti Warbi moxmareba, rom gamofituli plazma kargavs hemostazis unars. diseminirebuli sisxlzarrvsiga Sededebis dros plazma, faqtobrivad, Sratad iqceva. sawyisi fazistvis damaxasiatebelia hiperkoagulacia da Trombozebi, gansakutrebit _ stazis SemTxvevaSi. Trombozisa da sisxldenis Tanaarsebobisas didia dainvalidebisa da letalobis albatoba. diseminirebuli sisxlzarrvsiga Sededebis tipuri laboratoriuli nisania koagulaciuri faqtorebis deficiti. vitardeba Trombocitopenia, hipofibrinogenemia an afibrinogenemia. Trombin-antiTrombin III-is, 1.2 fragmentisa da D dimeris marali koncentracia Trombozis mimdinareobis macvenebelia [17; 18], Trombolizisze ki metyvelebs fibrinogenis degradaciis iseti produqtebis armocena, rogoric aris, magalitad, xsnadi fibrinis monomeri da plazmin-α-2-anti p- lazminis kompleqsis momatebuli raodenoba [19; 20]. I, II, V, VIII : C, XIII faqtorebi, antitrombin III da Trombocitebi diseminirebuli sisxlzarrvsiga Sededebis sindromis dros swrafad moixmareba, VII, IX, X da XI faqtorebi ki SesamCnev cvlilebebs ar ganicdis. fibrinis degradaciis produqtebis raodenobis momateba (Cveulebriv, 25 mg/ml) fibrinolizze metyvelebs, rac dss-istvis tipuria. amdenad, fibrinis degradaciis produqtebis ararseboba dss-s gamoricxavs, Tumca unda gavitvaliswinot, rom isviatad es sindromi fib- 6

7 rinis degradaciis produqtebis ucvleli koncentraciis fonzec mimdinareobs. dss-is dros arnisnul produqtebze Catarebuli analizis uaryofiti pasuxi SesaZloa imit iyos ganpirobebuli, rom analizi naklebad mgrznobiarea mcire zomis fragmentebis (D da E) mimart an SedarebiT didi fragmentebi (X da Y) ukve moxmarda Trombogenezs Trombinis damatebis Sedegad. D dimeri jvaredindakavsirebuli fibrinis degradaciis produqtia. is fibrinogenisgan ar warmoiqmneba da fibrinis dagrovebit mimdinare koagulaciis macvenebelia. am faqtorebis koncentraciis 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-anti plazminis kompleqsisa da D dimeris koncentracia ertmanetisgan umnisvnelod gansxvavdeba [21; 22]. amastanave, arsanisnavia, 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 aremateba im avadmyofebis xsnadi fibrinis monomeris koncentracias, romlebsac dss ar arenisnebat. gabeqsatis mezilatit mkurnalobis Sedegad xsnadi fibrinis monomeris koncentraciis daqveiteba daavadebis sasiketo dasasrulis mauwyebelia, 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 macvenebeli gansakutrebit maralia gardacvlilebsi [20]. heparinoterapiis dawyebis Semdeg 1.2 fragmentis koncentracia mkvetrad mcirdeba da dabali rceba oraluri antikoagulantebit mkurnalobis periodsi. oraluri antikoagulantebit mkurnalobis stabilur fazasi INR-sa da 1.2 fragmentis koncentracias Soris arsebobs ukuproporciuli kavsiri [23]. dss-is heparinit mkurnalobis kontroli aptt-is mesveobit xorcieldeba. unda SenarCundes misi iseti koncentracia, romelic sawyis mnisvnelobas 1,5-jer aremateba. Tu mdgomareoba ar gaumjobesda an fibrinis (fibrinogenis) degradaciis produqtebis done marali darca, heparinis doza SeiZleba gaizardos. α-2-anti plazminis koncentraciis 50%-iT daqveiteba dss-is fibrinolizur komponentze miutitebs. aset dros unda daisvas mkurnalobasi fibrinolizuri preparatebis CarTvis sakitxi. heparinis gamoyenebidan 6 saatis Semdeg sagrznoblad 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-antiTrombin III-is koncentracia [25]. dss sindromis diagnostikistvis specialistebi gvtavazoben Semdeg testebs: α-2-an ti p 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 garegani, SeZenili da memkvidreobiti riskfaqtorebis kombinirebuli moqmedebis Sedegia. is invalidizaciisa da letalobis ert-erti wamyvani mizezia dan ert bavsvs yovelwliurad arenisneba venuri Trombozi. asaktan ertad es macvenebeli izrdeba da xandazmul pirebsi 1:100- s Seadgens. SemTxvevaTa 30-40% spontanuria. venuri TrombozebisTvis damaxasiatebeli hiperkoagulaciuri mdgomareoba memkvidreobitic SeiZleba iyos da SeZenilic [26]. xsiria genetikuri da SeZenili mizezebis Tanxvedra. memkvidreobiti Trombofilia anu memkvidreobiti Trombozuli daavadeba sxvadasxva cnobil meqanizms ukavsirdeba [26]. Trombinis inaq- 7

8 tivaciisa da koltis warmoqmnis sawinaarmdegod aris mimartuli xuti umtavresi antikoagulantis moqmedeba: antitrombin III usualod aneitralebs Trombins, proteini C uzrunvelyofs gaaqtiurebuli Va da VIIIa faqtorebis inaqtivacias, proteini S protein C-s kofaqtoria, Trombomodulini ganapirobebs protein C-s aqtivacias Trombinis mesveobit, xolo qsovilovani faqtoris inhibitori aneitralebs koagulaciis sawyis (gamsveb) komponentebs. protein C-s, protein S-is da antitrombin III-is mutaciis Sedegad Sesabamisi alelebi gadadis arafunqciur mdgomareobasi, ris gamoc plazmasi mcirdeba Sededebis 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 mosaxleobasi ufro fartod (2-10%-Si) aris gavrcelebuli [27]. ert-erti matgania leidenis V faqtoris mutacia, (FII) G20210A protrombinis mutacia da VIII, IX da XI prokoagulaciuri faqtorebis koncentraciis momateba, romelta memkvidreobiti buneba gaurkvevelia. leidenis V faqtoris mutaciis Sedegad vitardeba gaaqtiurebuli C proteinis memkvidreobiti rezistentoba, rac Trombofiliis ert-erti mnisvnelovani mizezia. 3 aratranslaciur ubansi (FII) G20210A protrombinis mutacia ganapirobebs protrombinis koncentraciis momatebas, ris Sedegadac izrdeba venuri Trombozis ganvitarebis riski (cxrili #1). prokoagulaciuri (V, II, VIII da von-vilebrandis faqtorebi) da antikoagulaciuri faqtorebis (S proteini, C proteini, antitrombin III, Z proteini da protein Z-is inhibitori) koncentraciebi umtavresad genetikurad aris determinirebuli [27]. memkvidreobiti Trombozuli daavadebis laboratoriuli kvleva utardebat mxolod Sesabamisi anamnezis mqone pacientebs da ara Trombozis nebismieri klinikuri gamovlinebis mqone pirebs. unda gamoiricxos Trombozis gamomwvevi SeZenili faqtorebi: avtvisebiani da mieloproliferaciuli daavadebebi, xangrzlivi imobilizacia, anatomiuri defeqtebi, orsuloba, oraluri kontraceptivebis mireba da qirurgiuli operaciebi. memkvidreobit Trombozul daavadebaze metyvelebs venuri Tromboemboliis SemTxvevebi 45 wlamde asaksi, morecidive Trombozuli daavadeba (Recurrent thrombotic disease) da venuri Tromboembolizmis ojaxuri anamnezi [26]. ganmeorebiti venuri Trombozi ufro xsirad gvxvdeba mamakacebsi, xandazmul pirebsi, aseve _ imobilizaciisa da avtvisebiani daavadebebis dros. asidan xut SemTxvevaSi is sasikvdiloa. ganmeorebiti Trombozi xsiria aseve protein C-s, protein S-is da antitrombin III-is deficitis pirobebsi da SemTxvevaTa 60-80%-Si vitardeba, am faqtorebis deficitis ararsebobisas ki morecidive Trombozuli daavadeba mxolod 6-10%-Si gvxvdeba. ganmeorebiti Trombozi arinisneba agretve leidenis V faqtoris homozigoturi mutaciis fonze. amjamad sakamatoa, izrdeba Tu ara ganmeorebiti Tromboembolizmis sixsire leidenis V faqtorisa da (FII) G20210A protrombinis heterozigoturi mutaciebis dros. hiperhomocisteinemia da mastan dakavsirebuli metilenis tetrahidrofoliumis reduqtazis fermentis Trombolabiluri variantuli forma memkvidreobiti Trombozuli daavadebis potenciuri mizezia. ganmeorebiti Trombozis riski izrdeba aseve homocisteinisa da VIII faqtoris plazmuri koncentraciis momatebis Sem- TxvevaSi. hiperhomocisteinemiit daavadebulebs morecidive Trombozuli daavadeba asidan daaxloebit 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 gansxvavebit, Trombozi SedarebiT axalgazrda asak- Si vitardeba. kerzod, pacientebis 50%-s Trombozis pirveli SemTxveva 40 wlamde asaksi uv- 8

9 lindeba, 85%-s ki _ 50 wlamde asaksi. Tu pirveli rigis aranakleb ori natesavi simptomuria (anamnezsi Trombozi arenisneba), 98%-ia albatoba, avadmyofis Trombozuli movlena memkvidreobiti Trombozuli daavadeba iyos. amastanave, uaryofiti ojaxuri anamnezi memkvidreobit Trombozul daavadebas ar gamoricxavs. protein C-s, protein S-i sa da antitrombin III-is deficitis dasadgenad laboratoriuli analizebis Catareba ar aris mizansewonili oraluri antikoagulaciuri Terapiis fonze. analizebis Catarebamde sul cota ori kvirit adre kumarinebi unda Seicvalos heparinit. aseve ar aris rekomendebuli avadmyofis gamokvleva usualod Trombozuli movlenis Semdgom periodsi, 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, mowodebulia antifosfolipiduri sindromis skriningi. rogorc pirvelad, ise meoreul antifosfolipidur sindroms axasiatebs kardiovaskuluri da cerebrovaskuluri arteriuli da venuri Trombozebi, nevrologiuri darrvevebi, ganmeorebiti spontanuri aborti da Trombocitopenia mgluras antikoagulantebis arsebobisa da/an anionuri fosfolipidebis sawinaarmdego autoantisxeulebis (kardiolipinis, fosfatidilserinis, b 2 glikoproteinis I-is sawinaarmdego autoantisxeulebi) momatebuli koncentraciis fonze [28]. antifosfolipiduri sindromis skriningistvis mizansewonilia aseve dabali simkvrivis lipoproteinebis gansazrvra. bavsvta asaksi fosfolipiduri autoantisxeulebi Trombozuli movlenebis SemTxvevaTa mesamedsa da idiopatiuri ce- 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 Trom bo ze bis mqo ne pa ci en te bi (%) pre va len si (six Si re) Zi ri Ta di mo sax le o ba (%) Trom bo ze bis gan vi Ta re bis ris ki Se far de bi Ti SedarebiTi ris ki ris ki C ci lis de fi ci ti an tit rom bin III-is de fi ci ti S ci lis de fi ci ti hi per ho mo cis te i ne mia prot rom bi nis mo ma te ba le i de nis V faq to ri VIII faq to ris mo ma te ba hi per fib ri no ge ne mia

10 surati #1 bunebrivi antitrombozuli meqanizmebi rebruli isemiis SemTxvevaTa or mesamedsi arinisneba [29]. memkvidreobiti Trombozuli daavadebis yvelaze xsiri mizezebis dasadgenad unda ganisazrvros protein C-sa da protein S-is aqtivoba, agretve _ leidenis V faqtoris genotipi (gaaqtiurebuli protein C-s genetikuri rezistentulobis SemTxvevaSi). plazmasi homocisteinis koncentraciis gansazrvra martivi analizia da hiperhomocisteinemiis dasadgenad gamoiyeneba. Tu homocisteinis koncentracia ma- Ralia, avadmyofs utardeba metilenis tetrahidrofoliumis reduqtazis genotipireba, ris safuzvelzec SesaZlebelia Trombozebis memkvidreobiti mizezis garkveva. antitrombin III-is deficiti memkvidreobit Trombozul daavadebas isviatad iwvevs. is mxolod im SemTxvevaSi ganisazrvreba, Tu sxva analizebis Sedegebi uaryofiti armocnda [30; 31]. sameano gartulebebi da Trombozebi ertmanets mwidrod ukavsirdeba. pacients, romelsac antifosfolipiduri sindromi arenisneba, anamnezi datvirtuli aqvs mravlobiti abortit. iset sameano gartulebebs, rogoric aris mzimed mimdinare eklamfsia, placentis naadrevi acla, na yo - fis zrda Si CamorCena da mkvdradsobadoba, Tan axlavs metilenis tetrahidrofoliumis reduq- 10

11 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 mutaciebi armoacnda im qalebis 52%-s, romlebsac dedisa 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 arenisneba venuri Tromboembolizmi an ramdenime aborti, mas orsulobis adreul etapze unda Cautardes Trombozis skrininguli analizi, vinaidan, arsebuli monacemebis Tanaxmad, profilaqtikuri heparinoterapia aset SemTxvevebSi Sedegiania [33]. leidenis V faqtoris fonze oraluri kontraceptivebi zrdis Trombozis ganvitarebis risks [34], ris gamoc, zogierti avtoris azrit, oraluri kontraceptivebis danisvnamde sasurvelia am mutaciis skriningi. martalia, arteriuli da venuri Trombozebis riskfaqtorebi ertmanetisgan gansxvavdeba, magram mattvis saertoa fibrinis formirebis procesi, romelic orive SemTxvevaSi Sededebis saboloo etaps warmoadgens. Trombozebis genetikuri kontroli ori sxvadasxva meqanizmit xorcieldeba. esenia: koagulaciuri faqtorebis koncentraciis genetikurad pirobadebuli momateba da genetikurad pirobadebuli protrombuli statusi (mdgomareoba). am ukanasknels Sededebis sistemis gaaqtiureba da Trombinis produqciis 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 midrekilebis dasadgenad unda ganisazrvros protrombozuli statusis iseti markerebis plazmuri koncentracia, rogoric aris 1+2 protrombinis fragmentebi, Trombin-antiTrombinis kompleqsi da D dimeri. li te ra tu ra: 1. Fuse I., Disorders of platelet function. Crit Rev Oncol Hematol 1996; 22: Bick R.L., Platelet function defects: A clinical review. Sem Thromb He most 1992;18: Bick R.L., Laboratory evaluation of platelet dysfunction. Cli nics Lab Med 1995;15: Narjes H., Muller TH, Weisenberger H, Guth B, Brickl R. Inhibition of platelet aggregation as a surrogate marker. J Clin Phar ma col 1997;37:59S-64S 5. Kabakibi A., Vamvakas EC, Cannistraro PA, Szczepiorkowski ZM, Laposata M. Collagen-induced whole blood platelet aggregation in patients undergoing surgical procedures associated with minimal to moderate blood loss. Am J Clin Pat hol 1998;109: Fa re ed J., Hop pen ste adt DA, Le ya F, Iqbal O, Wolf H, Bick R. Useful laboratory tests for studying thrombogene sis in acu te car di ac syndro mes. Clin Chem 1998;44: Meade T.W., Cooper J.A., Miller G.J., Platelet counts and aggregation measures in the incidence of ischaemic heart disease (IHD). Thromb Haemost 1997;78: Gresele P., Catalano M., Glammarresi C., Volpato R. et al. Platelet activation markers in patients with peripheral arterial disease: a prospective comparison of different platelet function tests. Thromb Haemost 1997;78: Lopez J.A., Andrews R.K., Afshar-Karghan V., Berndt M.C., Bernard-Soulier Syndrome. Blood 1998;91: McNicol A., Sutherland M., Zou R., Drouin J., Defective thrombin-induced calcium changes and aggregation of Bernard-Soulier platelets are not associated with deficient moderate-affinity receptors. Arterioscler Thromb Vasc Bi ol 1996;16: 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 - pression analysis of two novel mutations in a kindred with type I glanzmann thrombasthenia. Thromb Haemost 1998;80:

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