-este o boala clonala a celulei stem->hiperproductie de trombocite care nu sunt normale
-este alterata agregarea si adezivitatea plachetara
-manifestari:
- &nbs 646i85g p; &nbs 646i85g p; hemoragice->la Tr > 15 milioane;īn orice teritoriu
- &nbs 646i85g p; &nbs 646i85g p; tromboembolice->la numar mai mic de Tr;ex.tromboza arterei splenice->asplenism
-caz clinic->crize de eritromelalgie + epistaxis
-examen obiectiv:
- &nbs 646i85g p; &nbs 646i85g p; paloare
- &nbs 646i85g p; &nbs 646i85g p; purpura petesiala
- &nbs 646i85g p; &nbs 646i85g p; echimoze
- &nbs 646i85g p; &nbs 646i85g p; gingivoragii
- &nbs 646i85g p; &nbs 646i85g p; splenomegalie moderata
-paraclinic:
- &nbs 646i85g p; &nbs 646i85g p; Ht = 35%;Le = 10.000
- &nbs 646i85g p; &nbs 646i85g p; Tr = 2.25 milioane;reticulocite = 7%
- &nbs 646i85g p; &nbs 646i85g p; FAL = 50 μ;cariotip = 46 XY 21 q
- &nbs 646i85g p; &nbs 646i85g p; MC = 3%;PMC = 4%;MMC = 3%
- &nbs 646i85g p; &nbs 646i85g p; St = 3%;Sg = 70%
- &nbs 646i85g p; &nbs 646i85g p; Ly= 10%;Ba = 5%;Mo = 5%
- &nbs 646i85g p; &nbs 646i85g p; MO->hiperplazie megacariocitara
- &nbs 646i85g p; &nbs 646i85g p; vit.B12 ↑
- &nbs 646i85g p; &nbs 646i85g p; colonii megacariocitare endogene si eritroide
- &nbs 646i85g p; &nbs 646i85g p; fibroza nu este foarte accentuata;megacariocitul nu este foarte displazic
- &nbs 646i85g p; &nbs 646i85g p; hiperplazie granulocitara
-criterii de diagnostic:
- &nbs 646i85g p; &nbs 646i85g p; Tr > 1 milion
- &nbs 646i85g p; &nbs 646i85g p; hiperplazie megacariocitara
- &nbs 646i85g p; &nbs 646i85g p; absenta Ph1 sau BCR-ABL
- &nbs 646i85g p; &nbs 646i85g p; absenta ↑ masei eritrocitare
- &nbs 646i85g p; &nbs 646i85g p; absenta sdr.mielodisplazic->5q-,anemia refractara cu sideroblasti inelari (ARSI)
- &nbs 646i85g p; &nbs 646i85g p; absenta unei afectiuni cu ↑ Tr secundara->infectii acute/cronice;boli inflamatorii;colagenoze;boli limfoproliferative;limfom Hodgkin;carcinoame;recul dupa trombocitopenie;tratament cu alcaloizi;deficit de Fe
- &nbs 646i85g p; &nbs 646i85g p; absenta mielofibrozei semnificative
- &nbs 646i85g p; &nbs 646i85g p; splenomegalie moderata
- &nbs 646i85g p; &nbs 646i85g p; colonii endogene megacariocitare
- &nbs 646i85g p; &nbs 646i85g p; dovezi de hematopoieza clonala
- &nbs 646i85g p; &nbs 646i85g p; agregare plachetara anormala (epinefrina,ADP)
-tratament:
1. &nbs 646i85g p; risc scazut->400.000-1 milion Tr;nu exista īn APP boli cardiovasculare,tromboze,boli organice,eritromelalgie
-clinic->crize de ischemie tranzitorie cutanata,cerebrala;tromboflebite superficiale
-aspirina 50-100 mg/zi
2. &nbs 646i85g p; risc intermediar->1-1.5 milioane Tr;nu exista īn APP hemoragie,trombembolie
-clinic->crize vasoocluzive,microcirculatorii;angina pectorala
-anagrelid + IFN->tineri
-citostatice (hidroxiuree >vārstnici
-aspirina 100 mg/zi->crize vasoocluzive,microcirculatorii
3. &nbs 646i85g p; risc crescut-> peste 1.5 milioane Tr
-exista APP de tromboze,ATS,HTA,hemoragii,splemomegalie,mielofibroza,leucocitoza
-peste 65 ani->hidroxiuree 1-3 g/zi
-tineri->anagrelid + IFN 2-3 mg/m²/zi;Tr foarte ↑->alkeram
= boala clonala a celulelor stem hematopoetice
-patogenie:
- &nbs 646i85g p; &nbs 646i85g p; proliferare granulocitara si megacariocitara
- &nbs 646i85g p; &nbs 646i85g p; fibroza medulara->reactiva,citokine elaborate de megacariocitul displazic (tumori fibrohemato-poetice)->TGF-β;PDGF-β;IL-1
- &nbs 646i85g p; &nbs 646i85g p; factori de ↑ aditionali->EGF,Calmodulin,inhibitori de colagenaza eliberati de trombociti
- &nbs 646i85g p; &nbs 646i85g p; mielodisplazie
- &nbs 646i85g p; &nbs 646i85g p; hematopoieza extramedulara
-diagnostic diferential:
- &nbs 646i85g p; &nbs 646i85g p; LGC la debutul MMM->īn frotiul periferic Ebl,Mgc,He īn picatura;ex.citogenetic->cr.Ph
- &nbs 646i85g p; &nbs 646i85g p; PV īn evolutie->metaplazie mieloida mielofibrotica (dupa ani de zile de PV)
- &nbs 646i85g p; &nbs 646i85g p; LA megacarioblastica (LAM ,mielofibroza acuta)->celule imature,hematii īn SP
- &nbs 646i85g p; &nbs 646i85g p; leucemia cu celule paroase (mielofibroza limfoida)->celule ce infiltreaza maduva
-BOM->celule limfoide mari,citoplasma clara,nucleu mic excentric
-SP->limfocite cu prelungiri citoplasmatice
- &nbs 646i85g p; &nbs 646i85g p; intoxicatii
- &nbs 646i85g p; &nbs 646i85g p; carcinoame cu metastaze
- &nbs 646i85g p; &nbs 646i85g p; boli autoimune
- &nbs 646i85g p; &nbs 646i85g p; limfoame maligne
- &nbs 646i85g p; &nbs 646i85g p; TBC miliara hepatosplenica
- &nbs 646i85g p; &nbs 646i85g p; citostatice
-caz clinic->astenie,dureri osoase,balonari
-examen obiectiv->paloare,purpura,ficat la 8 cm,splina la 20 cm,adenopatie axilara stānga
-paraclinic:
- &nbs 646i85g p; &nbs 646i85g p; Ht =35%;Le = 3.000-40.000 (variabil)
- &nbs 646i85g p; &nbs 646i85g p; Tr = 25.000 (initial ↑);reticulocite = 7.5%
- &nbs 646i85g p; &nbs 646i85g p; hematii īn lacrima->dacriocite
- &nbs 646i85g p; &nbs 646i85g p; anemie datorita fibrozei medulare,proliferarii ineficiente (displaziei),sechestrarii īn splina +/- anemie hemolitica autoimuna
- &nbs 646i85g p; &nbs 646i85g p; FAL = 30-200
- &nbs 646i85g p; &nbs 646i85g p; cariotip->11q-;20q-;-7;+8;nu exista cr.Ph
- &nbs 646i85g p; &nbs 646i85g p; devierea la stānga a formulei leucocitare:
- &nbs 646i85g p; &nbs 646i85g p; PMC = 3%;MC = 2%;MMC = 1%
- &nbs 646i85g p; &nbs 646i85g p; Ba = 2%;Eo = 2%;Ly = 6%
- &nbs 646i85g p; &nbs 646i85g p; Ebl = 25%;Mgc = 15%
- &nbs 646i85g p; &nbs 646i85g p; numar ↑ de celule stem circulante mai ales dupa stress-uri aplazice (postcitostatice,īn grefele de celule stem)
- &nbs 646i85g p; &nbs 646i85g p; punctie medulara alba,nu exista sānge deloc->fibroza medulara
- &nbs 646i85g p; &nbs 646i85g p; BOM->megacariociti displazici
-prognostic->infaust
-tratament:
1. &nbs 646i85g p; boala cu trasaturi proliferative (splenomegalie,leucocitoza,trombocitoza)->hidroxiuree +/- iradiere de splina
2. &nbs 646i85g p; anemie->androgeni īn doza mare minim 6 luni
-prednison 1 mg/kgc īn anemia hemolitica autoimuna
3. &nbs 646i85g p; splenomegalie +/- pancitopenie +/- HT partiala īn cazuri bine selectate->splenectomie
-contraindicatii->trombocitoza + fibroza medulara intense->iradiere splenica
-īncercari->IFN (rezultate contradictorii);anticitokine (pentoxifilin)
= proliferari de celule nediferentiate blastice ce infiltreaza MO->insuficienta de tesuturi si organe
-cel mai frecvent etiologia este necunoscuta
-factori etiologici:
- &nbs 646i85g p; &nbs 646i85g p; fizici->radiatii ionizante (mutagene) + radiatii electromagnetice
- &nbs 646i85g p; &nbs 646i85g p; chimici->benzen,cloramfenicol,agenti alchilanti,insecticide
- &nbs 646i85g p; &nbs 646i85g p; virusuri->HTLV-Asia endemic->ATLL
- &nbs 646i85g p; &nbs 646i85g p; genetici
- &nbs 646i85g p; &nbs 646i85g p; incidenta familiala ↑
- &nbs 646i85g p; &nbs 646i85g p; boli congenitale
- &nbs 646i85g p; &nbs 646i85g p; imunodeficiente congenitale->fragilitatea cr.Bloom;sdr.teleangiectazie-ataxie
- &nbs 646i85g p; &nbs 646i85g p; anemia Fanconi
- &nbs 646i85g p; &nbs 646i85g p; anomalii cromozomiale congenitale->trisomia 21 (sdr.Down)
- &nbs 646i85g p; &nbs 646i85g p; boli hematologice predispozante
- &nbs 646i85g p; &nbs 646i85g p; boli mieloproliferative cronice (mai putin LGC,MMM)
- &nbs 646i85g p; &nbs 646i85g p; hemoglobinuria paroxistica nocturna
- &nbs 646i85g p; &nbs 646i85g p; hemopatii maligne tratate cu agenti alchilanti si/sau iradiere
- &nbs 646i85g p; &nbs 646i85g p; sdr.mielodisplazic
-simptome & semne:
- &nbs 646i85g p; &nbs 646i85g p; directe
- &nbs 646i85g p; &nbs 646i85g p; leucocitoza
- &nbs 646i85g p; &nbs 646i85g p; leucostaza
- &nbs 646i85g p; &nbs 646i85g p; organomegalie
- &nbs 646i85g p; &nbs 646i85g p; leucemia SNC
- &nbs 646i85g p; &nbs 646i85g p; leucemie la nivelul tubului digestiv,miocard,pericard
- &nbs 646i85g p; &nbs 646i85g p; indirecte
- &nbs 646i85g p; &nbs 646i85g p; insuficienta medulara
- &nbs 646i85g p; &nbs 646i85g p; eliberare de substante procoagulante si profibrinolitice
- &nbs 646i85g p; &nbs 646i85g p; hiperuricemie
- &nbs 646i85g p; &nbs 646i85g p; hiperfosfatemie,hipersulfatemie,hipocalcemie,hipomagnezemie
- &nbs 646i85g p; &nbs 646i85g p; artrita cu apatita sau pirofosfat
- &nbs 646i85g p; &nbs 646i85g p; lizozimurie ↑->IRA
-copii->LAL
-adulti->LA nonlimfoblastica (LANL,LAM)->M0...M7
-LA mixte (bifenotipice->limfoblasti + mieloblasti >aceeasi celula are determinanti pt.limfoblasti si mieloblasti
-LAL B sau T->L1 (LAL microlimfoblastica->early B sau early T)
-L2 (LAL macrolimfoblastica->pre B sau T intermediar)
-L3 (LAL cu celule Burkitt-like->B matur sau T matur)
-examen obiectiv:
- &nbs 646i85g p; &nbs 646i85g p; paloare
- &nbs 646i85g p; &nbs 646i85g p; sdr.hemoragipar
- &nbs 646i85g p; &nbs 646i85g p; hepato/splenomegalie
- &nbs 646i85g p; &nbs 646i85g p; hemoragii gingivale + hipertrofie gingivala
- &nbs 646i85g p; &nbs 646i85g p; adenopatii
- &nbs 646i85g p; &nbs 646i85g p; tablou de CID
-examen hematologic:
- &nbs 646i85g p; &nbs 646i85g p; Le variabile (↑,↓ sau normale)
- &nbs 646i85g p; &nbs 646i85g p; Tr ↑,↓;hematii ↓
- &nbs 646i85g p; &nbs 646i85g p; MO->infiltrat
- &nbs 646i85g p; &nbs 646i85g p; SP->blasti
- &nbs 646i85g p; &nbs 646i85g p; blastoza medulara
- &nbs 646i85g p; &nbs 646i85g p; ↑ LDH
- &nbs 646i85g p; &nbs 646i85g p; hiperuricemie,hipocalcemie,hiperfosfatemie
- &nbs 646i85g p; &nbs 646i85g p; ↑ lizozim;↓ colesterol
-anomalii citogenetice:
- &nbs 646i85g p; &nbs 646i85g p; t (9,22) ->LAL cu prognostic nefavorabil
- &nbs 646i85g p; &nbs 646i85g p; t (8,14)->Burkitt tip L3
- &nbs 646i85g p; &nbs 646i85g p; t (15,17)->LAM tip M3
- &nbs 646i85g p; &nbs 646i85g p; t (8,21)->LAM tip M2
- &nbs 646i85g p; &nbs 646i85g p; t (4,11)->LAL tip L1 sau bifenotipice
-clasificare:
1. &nbs 646i85g p; LAL
- &nbs 646i85g p; &nbs 646i85g p; tip L1 (microlimfoblastica)->esp.la copii;prognostic bun
- &nbs 646i85g p; &nbs 646i85g p; tip L2 (macrolimfoblastica)->esp.la adulti;prognostic mai putin bun
- &nbs 646i85g p; &nbs 646i85g p; tip L3 (cu celule Burkitt- like)->prognostic rezervat
2. &nbs 646i85g p; LAM
- &nbs 646i85g p; &nbs 646i85g p; M0->citologic neidentificabila ci doar imunologic
- &nbs 646i85g p; &nbs 646i85g p; M1->mieloblastica fara diferentiere
- &nbs 646i85g p; &nbs 646i85g p; M2->mieloblastica cu diferentiere
- &nbs 646i85g p; &nbs 646i85g p; M3->promielocitara
- &nbs 646i85g p; &nbs 646i85g p; M4->mielomonoblastica
- &nbs 646i85g p; &nbs 646i85g p; M5->monoblastica
- &nbs 646i85g p; &nbs 646i85g p; M6->eritroleucemia acuta
- &nbs 646i85g p; &nbs 646i85g p; M7->megacarioblastica
-diagnosticul tipului de LA:
citologie
morfologie
granulatii
corpii Auer
neclar diagnostic clar->M2...M6
-diagnostic diferential:
- &nbs 646i85g p; &nbs 646i85g p; anemia aplastica
- &nbs 646i85g p; &nbs 646i85g p; displazii->SMD (frecvent la vārstnici)
- &nbs 646i85g p; &nbs 646i85g p; mononucleoza infectioasa (diagnostic microscopic)
- &nbs 646i85g p; &nbs 646i85g p; LGC īn puseu blastic
- &nbs 646i85g p; &nbs 646i85g p;
neuroblastom,rabdomiosarcom,sarcom
- &nbs 646i85g p; &nbs 646i85g p; carcinom bronhopulmonar cu celule mici
-factori de prognostic:
- &nbs 646i85g p; &nbs 646i85g p; vārsta < 1 an sau > 10 ani
- &nbs 646i85g p; &nbs 646i85g p; leucocitoza > 40.000/mmc
- &nbs 646i85g p; &nbs 646i85g p; organomegalii
- &nbs 646i85g p; &nbs 646i85g p; leucemia SNC
- &nbs 646i85g p; &nbs 646i85g p; anomalii citogenetice->t (9,22) (evolutie severa;la remisie->transplant medular);t (4,11); t (8,14);+8;7-;5q-
- &nbs 646i85g p; &nbs 646i85g p; L3 si M7
- &nbs 646i85g p; &nbs 646i85g p; LA secundare
- &nbs 646i85g p; &nbs 646i85g p; adenopatii
-LA sunt curabile conventional sau prin transplant de celule stem
-prognostic->80% din adulti au remisiune completa;1/4 se vindeca
-recidiva->foarte precoce->tratament ineficient
->tardiva->se reia tratamentul initial
-definitia remisiunii complete:
- &nbs 646i85g p; &nbs 646i85g p; nu exista organomegalii
- &nbs 646i85g p; &nbs 646i85g p; īn SP->granulocite > 1500 + Tr > 100.000/mmc
- &nbs 646i85g p; &nbs 646i85g p; īn MO < 5% blasti
- &nbs 646i85g p; &nbs 646i85g p; LCR normal
- &nbs 646i85g p; &nbs 646i85g p; cariotip normal
-tratament:
1. &nbs 646i85g p; masuri cu caracter general
- &nbs 646i85g p; &nbs 646i85g p; izolare
- &nbs 646i85g p; &nbs 646i85g p; profilaxia infectiilor fungice
- &nbs 646i85g p; &nbs 646i85g p; tratament substitutiv
- &nbs 646i85g p; &nbs 646i85g p; tratamentul CID
- &nbs 646i85g p; &nbs 646i85g p; profilaxia si tratamentul hiperuricemiei
- &nbs 646i85g p; &nbs 646i85g p; profilaxia meningitei blastice
2. &nbs 646i85g p; tratamentul LAL
- &nbs 646i85g p; &nbs 646i85g p; inducerea remisiunii->prednison
- &nbs 646i85g p; &nbs 646i85g p; profilaxia leucemiei SNC->metotrexat,Ara-C intrarahidian,radioterapie pe ax cerebrospinal
- &nbs 646i85g p; &nbs 646i85g p; consolidare
- &nbs 646i85g p; &nbs 646i85g p; A->Drb,Vcr,L-Asp,prednison->doze ↑
- &nbs 646i85g p; &nbs 646i85g p; B->etoposid,Ara-C
- &nbs 646i85g p; &nbs 646i85g p; 4 cure AB + Mtx
- &nbs 646i85g p; &nbs 646i85g p; īntretinere->6-MP + Mtx timp de 30 luni
- &nbs 646i85g p; &nbs 646i85g p; reinducere
- &nbs 646i85g p; &nbs 646i85g p; LAL la copii->transplant alogenic sau autolog
- &nbs 646i85g p; &nbs 646i85g p; LAL la a 3-a remisiune->transplant medular
3. &nbs 646i85g p; tratamentul LAM
- &nbs 646i85g p; &nbs 646i85g p; inducerea remisiunii->DAT (Drb,Ara-C,6-TG)
- &nbs 646i85g p; &nbs 646i85g p; consolidare->4 cure Ara-C
- &nbs 646i85g p; &nbs 646i85g p; daca nu exista remisiuni->tratamet paliativ
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