Hauv ntau cov kab mob hemolytic, pathologies uas ua rau muaj qhov txawv txav ntawm cov ntshav los tsim cov ntshav txhaws tsim ib pab pawg tshwj xeeb. Qhov muaj peev xwm ua kom coagulate tuaj yeem tau txais los yog caj ces hauv qhov xwm txheej. Raws li kev txheeb cais, feem ntau ua rau muaj kab mob thrombophilia yog kev hloov pauv hauv cov noob F2 thiab F5, ib qho uas hu ua "Leiden factor".
nce congenital coagulopathy ib txwm cuam tshuam nrog kev txawv txav ntawm tus nqi lossis cov qauv ntawm cov protein koom nrog hauv cov ntshav txhaws. Nyob rau hauv rooj plaub ntawm kev hloov pauv ntawm Leiden, nws yog vim muaj kev hloov pauv hauv cov amino acid muaj pes tsawg leeg ntawm prothrombin, uas yog encoded los ntawm qhov ua kom ntshav khov F5.
Leiden mutation - yog dab tsi?
Hauv cov tshuaj, qee cov kab mob muaj npe raws li qhov ua rau lawv tshwm sim. Hauv qhov no, qhov xwm txheej ntawm lub npe ntawm pathology qhia tau hais tias kev hloov pauv Leiden yog kev ua txhaum cai cuam tshuam nrog kev hloov pauv txawv txav.ib feem ntawm tib neeg genotype. Phenotypically, nws manifests nws tus kheej nyob rau hauv lub synthesis ntawm ib tug txawv txav daim ntawv ntawm ib tug ntawm cov coagulation yam, uas ua rau ib tug hloov nyob rau hauv homeostasis rau nce ntshav txhaws.
Yog li, Leiden kev hloov pauv yog ib yam kab mob uas tau tshwm sim, qhia nyob rau hauv ib qho kev tshwm sim rau kev tsim cov hlab ntsha txawv txav uas txhaws cov hlab ntsha, thiab yog vim muaj kev hloov pauv hauv cov noob encoding FV yam. Cov tsos mob tshwm sim ntawm qhov tsis xws luag yog tus yam ntxwv tsuas yog rau qee tus neeg nqa khoom ntawm cov kab mob, tab sis qhov kev pheej hmoo ntawm thrombosis yog nce ntxiv.
Qhov zaus ntawm qhov tshwm sim ntawm F5 (Leiden) noob hloov pauv yog tib yam rau txiv neej thiab poj niam. Qhov kev tsis sib haum xeeb no yog ua rau thrombosis hauv 20-60% ntawm cov neeg mob. Ntawm tag nrho cov neeg nyob sab Europe, 5% ntawm cov neeg muaj kev hloov pauv Leiden.
yam ntxwv ntawm kev hloov pauv
Kev hloov pauv Leiden tshwm sim nws tus kheej hauv polymorphism ntawm F5 noob, uas tau qhia hauv kev hloov ntawm ib qho ntawm nucleotides nrog lwm tus. Hauv qhov no, adenine yog hloov los ntawm guanine ntawm txoj hauj lwm G1691A ntawm tus qauv ua ntu zus. Raws li qhov tshwm sim, thaum kawg ntawm kev sau thiab txhais lus, ib qho protein yog synthesized, cov qauv tseem ceeb ntawm qhov txawv ntawm qhov tseem ceeb (yog) version los ntawm ib qho amino acid (arginine yog hloov los ntawm glutamine). Nws yuav zoo li qhov txawv me ntsis, tab sis nws yog qhov tseeb uas ua rau muaj qhov tsis zoo ntawm cov ntshav coagulation.
Txhawm rau nkag siab txog kev sib raug zoo ntawm cov amino acid hloov pauv hauv F5 protein thiab hypercoagulability, nws yuav tsum nkag siab tias yuav ua li cas cov ntshav txhaws. Lub ntsiab lus tseem ceeb hauv cov txheej txheem no yog hloov pauv ntawm fibrinogen rau hauv fibrin, uas yog ua ntej los ntawm tag nrho cov saw ntawm cov tshuaj tiv thaiv.
Hloov ua li cas?
Kev tsim cov thrombus yog ua raws li polymerization ntawm fibrinogen, ua rau kev tsim cov ceg peb sab ntawm cov protein filaments uas cov qe ntshav tau daig. Yog li ntawd, ib qho txhaws tau tsim uas txhaws lub nkoj. Txawm li cas los xij, fibrinogen molecules pib txuas nrog ib leeg tsuas yog tom qab kev ua haujlwm proteolytic, uas yog ua los ntawm thrombin protein. Nws yog cov protein no uas ua raws li lub zog tig hauv cov ntshav coagulation circuit. Txawm li cas los xij, thrombin feem ntau muaj nyob rau hauv cov ntshav hauv daim ntawv ntawm nws cov precursor, prothrombin, uas yuav tsum muaj tag nrho cov saw hlau txuas ntxiv los ua kom qhib.
Cov proteins uas koom nrog hauv qhov cascade no yog hu ua cotting factor. Lawv muaj lub npe Roman raws li qhov kev txiav txim ntawm lawv qhov kev tshawb pom. Feem ntau yog cov proteins. Cov activators rau txhua qhov txuas txuas ntxiv hauv cov saw ntawm cov tshuaj tiv thaiv yog yav dhau los.
Kev tso tawm ntawm coagulation cascade pib nrog kev nkag ntawm cov ntaub so ntswg rau hauv lub nkoj. Ntau cov proteins yog tom qab ntawd qhib rau hauv cov saw hlau, uas thaum kawg ua rau kev hloov pauv ntawm prothrombin mus rau thrombin. Txhua theem ntawm cov cascade tuaj yeem raug ncua vim qhov kev txiav txim ntawm tus neeg sib raug zoo inhibitor.
Factor V
Factor V yog globular plasma protein tsim nyob rau hauv daim siab thiab koom nrog cov txheej txheem ntawm coagulation. Cov protein no txawvhu ua proaccelerin.
Ua ntej thrombin ua kom, FV protein muaj ib qho kev sib tw. Tom qab proteolytic cleavage nrog kev tshem tawm ntawm D-domain, lub molecule tau txais kev sib haum xeeb ntawm ob lub subunits txuas los ntawm cov nyiaj tsis muaj zog uas tsis yog-covalent. Daim ntawv no ntawm proaccelerin yog hu ua FVa.
Activated FV protein ua raws li coenzyme rau coenzyme Xa, uas converts prothrombin rau thrombin. Proaccelerin ua hauj lwm raws li ib tug catalyst rau cov tshuaj tiv thaiv no, tsub kom nws 350,000 zaug. Yog li, yam tsis muaj V, theem kawg ntawm coagulation cascade yuav siv sij hawm ntev heev.
Mechanism ntawm pathological kev txiav txim ntawm kev hloov pauv
Cov protein FV ib txwm tsis ua haujlwm los ntawm cov protein C, uas tuaj yeem ua si thaum nws tsim nyog los nres coagulation. Factor C khi rau ib qho chaw FVa tshwj xeeb thiab hloov mus rau FV daim ntawv, txwv tsis pub cov catalysis ntawm thrombin tsim. Nyob rau hauv lub xub ntiag ntawm Leiden kev hloov pauv, ib qho protein yog synthesized uas tsis cuam tshuam rau qhov kev txiav txim ntawm cov protein C (APC), txij li cov amino acid hloov pauv tau tshwm sim meej ntawm qhov chaw ntawm kev cuam tshuam nrog cov inhibitor. Raws li qhov tshwm sim, qhov cuam tshuam Va tsis tuaj yeem ua tsis tau, txo qhov ua tau zoo ntawm cov kev cai tsis zoo uas xav tau los nres kev tsim cov ntshav txhaws thiab tom qab liquefy nws.
Yog li, peb tuaj yeem xaus tias Leiden kev hloov pauv yog ib qho kab mob uas tshwm sim nws tus kheej los ntawm kev tiv thaiv kev ua haujlwm anticoagulant thiab yog li ua rau muaj kev pheej hmoo ntawm thrombosis. Qhov tshwm sim no hu ua protein-C-resistance.
Cov khoom ntawm mutant protein
Ntxiv rau qhov tsis kam rau cov protein C, polymorphism ntawm F5 noob muab cov protein ua ke los ntawm nws lub hauv paus ob lub zog ntxiv:
- muaj peev xwm txhim kho prothrombin ua kom;
- nce hauv cofactor kev ua ub no hauv kev cuam tshuam rau qhov tsis ua haujlwm ntawm FVIIIa protein, uas koom nrog hauv inhibition ntawm coagulation.
Yog li, qhov hloov pauv V ib txhij ua haujlwm hauv ob qho kev qhia. Ntawm ib sab, nws pib cov txheej txheem ntawm cov ntshav coagulation, thiab ntawm qhov tod tes, nws tiv thaiv kev tswj hwm cov protein los ntawm kev txwv nws. Tab sis nws yog qhov tseeb ntawm cov txheej txheem ntawm kev tawm tsam (kev tawm tsam) uas tiv thaiv lub cev los ntawm pathological tshwm sim ntawm ntau yam kev xav ntawm lub cev (piv txwv li, cov kab mob inflammatory).
Yog li, peb tuaj yeem hais tias Leiden kev hloov pauv yog ib qho tshwm sim ntawm kev hloov pauv uas cuam tshuam rau kev tswj hwm ntawm cov ntshav txhaws, ua rau muaj kev pheej hmoo ntawm cov ntshav txhaws uas ua rau muaj kev phom sij rau kev ua haujlwm ntawm lub cev. Nrog xws li ib tug pathology, ib qho ntawm cov coagulation yam yog ib txwm nquag.
Txawm li cas los xij, txhua qhov thib ob thiab nthuav dav ntawm cov ntshav txhaws hauv cov neeg zoo li no tseem tsis tau tshwm sim, vim tias muaj ntau cov proteins koom nrog hauv cov ntshav txhaws, sib cuam tshuam nrog ib leeg thiab nrog kev tswj hwm. Yog li ntawd, kev cuam tshuam ntawm kev ua hauj lwm ntawm ib yam dab tsi tsis ua rau ib tug radical tsis ua hauj lwm ntawm tag nrho cov mechanism ntawm coagulation inhibition. Txawm li cas los xij, V yam tsis yog qhov tseem ceeb ntawm kev tswj lub zog ntawm cov hlab ntshav.
Raws li qhov tshwm sim, los sib cav tias Leiden kev hloov pauv yog ib yam kab mob caj ces uas ua rau thrombophilia,tsis raug, txij li cov protein tsis ua ncaj qha, tab sis tsis ncaj, los ntawm kev ua txhaum ntawm kev tswj tsis zoo. Ntxiv nrog rau kev xa tawm qhov cuam tshuam V hauv lub cev, muaj lwm txoj hauv kev los nres cov txheej txheem coagulation. Yog li ntawd, qhov kev hloov pauv ntawm Leiden tsuas yog ua rau lub cev tsis ua haujlwm ntawm coagulation, thiab tsis ua kom nws puas tsuaj tag nrho.
Tsis tas li ntawd, pathology tshwm sim nws tus kheej tsuas yog thaum tsim cov ntshav txhaws tau pib los ntawm ib qho laj thawj. Txog thaum pib ntawm coagulation cascade, lub xub ntiag ntawm cov protein mutant tsis ua rau muaj kev hloov hauv lub cev.
Pathogenesis thiab cov tsos mob
Feem ntau, kev hloov pauv Leiden tsis muaj cov tsos mob tshwm sim. Tus neeg nqa khoom tuaj yeem nyob hauv kev thaj yeeb nyab xeeb, tsis txawm xav tias nws muaj nyob. Tab sis qee zaum muaj kev hloov pauv ua rau lub sijhawm tsim cov ntshav txhaws. Hauv qhov no, cov tsos mob yuav nyob ntawm qhov chaw ntawm cov ntshav txhaws.
Qhov kev pheej hmoo ntawm kev tsim cov thrombosis nyob ntawm tus lej ntawm cov noob F5 hloov pauv. Lub xub ntiag ntawm ib daim ntawv yuav ua rau muaj qhov tshwm sim ntawm qhov txawv txav los ntawm 8 zaug piv nrog tus tswv ntawm cov genotype ib txwm nyob ntawm qhov chaw no. Hauv qhov no, kev hloov pauv Leiden suav tias yog heterozygous. Yog tias muaj homozygote hauv genotype (ob daim ntawv theej ntawm cov noob hloov), qhov kev pheej hmoo ntawm thrombophilia nce mus txog 80 npaug.
Feem ntau cov tsos mob tshwm sim ntawm Leiden kev hloov pauv yog provoked los ntawm lwm yam ntawm thrombosis, suav nrog:
- txo qis hauv kev ncig;
- mob hnyav ntawm cov hlab plawv;
- kev ua neej nyob;
- noj cov tshuaj hormone hloov kho(HRT);
- kev ua haujlwm;
- pregnancy.
Kev tsis txaus ntshav txhaws tshwm sim hauv 10% ntawm cov neeg nqa khoom hloov pauv. Feem ntau cov kab mob tshwm sim nws tus kheej hauv DVT (kev sib sib zog nqus vein thrombosis).
YDeep vein thrombosis
Cov hlab ntsha sib sib zog nqus feem ntau nyob hauv thaj chaw qis, tab sis kuj tuaj yeem txhim kho hauv lub hlwb, qhov muag, ob lub raum thiab daim siab. Qhov tshwm sim ntawm cov ntshav txhaws hauv ob txhais ceg tuaj yeem nrog:
- sawv;
- pain;
- kub nce;
- redness.
Qee zaum DVT tsis muaj tsos mob.
Thrombosis ntawm cov leeg sab nraud nrog Leiden kev hloov pauv yog qhov tsawg dua li cov leeg sib sib zog nqus. Nws feem ntau yog nrog liab, kub taub hau, thiab rhiab ntawm qhov chaw ntawm cov hlab ntsha.
Clot formation in the ntsws
Kev tsim cov ntshav txhaws hauv lub ntsws (txawm li cas los xij pulmonary embolism) yog ib qho kev phom sij txaus ntshai ntawm Leiden kev hloov pauv, nrog rau cov tsos mob xws li:
- sudden ua tsis taus pa;
- mob plab thaum nqus tau;
- hnoos qeev thaum hnoos;
- tachycardia.
Cov kab mob no yog ib qho teeb meem ntawm DVT thiab tshwm sim thaum cov ntshav txhaws tawm ntawm phab ntsa venous thiab taug kev los ntawm sab xis ntawm lub plawv mus rau lub ntsws, thaiv cov ntshav ntws.
Kev phom sij ntawm kev hloov pauv thaum cev xeeb tub
Thaum cev xeeb tub, Leiden kev hloov pauvnrog los ntawm qhov pheej hmoo me me ntawm kev nchuav menyuam lossis yug ntxov ntxov. Qhov zaus ntawm cov xwm txheej zoo li no hauv cov poj niam uas muaj F5 gene polymorphism yog 2-3 zaug siab dua. Kev xeeb tub kuj ua rau muaj kev pheej hmoo ntawm thrombosis hauv cov neeg nqa khoom ntawm kev hloov pauv.
Qee qhov kev tshawb fawb qhia tias qhov muaj qhov tshwm sim Leiden ua rau muaj kev pheej hmoo ntawm kev tsim cov teeb meem hauv qab no:
- preeclampsia (siab ntshav siab);
- fetal loj hlob qeeb;
- kev sib cais ntxov ntawm cov placenta ntawm phab ntsa uterine.
Txawm tias muaj kev pheej hmoo no, feem ntau cov poj niam uas muaj qhov hloov pauv no muaj qhov cev xeeb tub. Leiden qhov tseem ceeb txawm tias muaj qhov txiaj ntsig zoo hauv kev txo qis qhov tshwm sim ntawm qhov loj tom qab yug me nyuam. Txawm li cas los xij, txhua tus poj niam uas muaj kev hloov pauv Leiden tau pom zoo kom muaj kev saib xyuas kev kho mob nruj thaum cev xeeb tub.
Kev kho mob
Kev kho ntawm Leiden kev hloov pauv tsuas yog ua tiav thaum muaj thrombophilia thiab muaj cov tsos mob. Nws tsis tuaj yeem tshem tawm qhov ua rau tus kab mob, vim tias cov tshuaj tsis muaj txoj hauv kev uas tso cai rau koj hloov cov genome.
Pathological tshwm sim ntawm Leiden kev hloov pauv yog tshem tawm los ntawm kev noj tshuaj tiv thaiv kab mob. Nyob rau hauv cov ntaub ntawv ntawm thrombosis rov tshwm sim, cov tshuaj no tau sau ib ntus.
