sindroame hemoragipare
TRANSCRIPT
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HEMOSTAZA NORMALAHEMOSTAZA NORMALA
I. Etapa vascularaI. Etapa vasculara
- vasoconstrictie - reflex axonic, serotonina
- vasoconstrictie - reflex axonic, serotonina
II. Etapa trombocitaraII. Etapa trombocitara
III. Etapa coagulareIII. Etapa coagulare
IV. Etapa fibrinolizaIV. Etapa fibrinoliza
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HEMOSTAZA NORMALAHEMOSTAZA NORMALA
I. EndoteliulI. Endoteliul
- functia - functia
1. bariera de permeabilitate1. bariera de permeabilitate
-2. secretie: - F. Willebrand - trombomodulin -
ataseaza trombina, proteina C, S - fibronectina – inhibitorul activatorului tisular al plasminogenului - PGI2 , Endotelina
-2. secretie: - F. Willebrand - trombomodulin -
ataseaza trombina, proteina C, S - fibronectina – inhibitorul activatorului tisular al plasminogenului - PGI2 , Endotelina
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- adeziunea prin receptori Gp I la: - colagenul subendotelial
- fibronectin + f. Willebrand
prin Gp IIb IIIa la: - fibrinogen
- adeziunea prin receptori Gp I la: - colagenul subendotelial
- fibronectin + f. Willebrand
prin Gp IIb IIIa la: - fibrinogen
II. Etapa trombocitaraII. Etapa trombocitara
- agregarea - ADP subendotelial - Tx A2
- agregarea - ADP subendotelial - Tx A2
- secretia - Ca+2 , Factor 3, 4, serotonina
- secretia - Ca+2 , Factor 3, 4, serotonina
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COAGULAREA - extrinsecaCOAGULAREA - extrinseca
- tromboplastina tisulara - tromboplastina tisulara
- III- III
- X Xa - X Xa
Proteina C- VII - VII
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COAGULAREA - intrinsecaCOAGULAREA - intrinseca
- trombocite activatecolagenul subendotelial factorul XII
- trombocite activatecolagenul subendotelial factorul XII
- XII XII a - XII XII a
- XI XI a - XI XI a
- IX IX a - IX IX a
- X Xa - X Xa
Ca, F3plachetar,VIII
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- fibrinogen fibrina +
fibrinopeptid A,B
- fibrinogen fibrina +
fibrinopeptid A,B
COAGULAREA - calea comunaCOAGULAREA - calea comuna
- X Xa - X Xa
- II IIa - II IIa
Ca, F3plachetar,V
Proteina C
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CLASIFICARECLASIFICARE
I Etapa vasculara : Purpura vasculara
- congeniala - dobandita
I Etapa vasculara : Purpura vasculara
- congeniala - dobandita
II Etapa trombocitara : Purpura trombocitara
- trombocitopenie - trombopatii
II Etapa trombocitara : Purpura trombocitara
- trombocitopenie - trombopatii
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III Etapa coagulare - Purpura deficienta factorilor de coagulare - congenitala
- dobandita
III Etapa coagulare - Purpura deficienta factorilor de coagulare - congenitala
- dobandita
V Etapa reologica - Purpura ortostaticaV Etapa reologica - Purpura ortostatica
IV. Etapa fibrinolizei - Purpura fibrinoliticaIV. Etapa fibrinolizei - Purpura fibrinolitica
VI. Etapa activare sistem monocit-macrofag - purpura CIDVI. Etapa activare sistem monocit-macrofag - purpura CID
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I. Purpure vasculareI. Purpure vasculare
- congenitale- congenitale
Ehler Danlos
osteogeneza imperfecta
Rendu - Osler
Ehler Danlos
osteogeneza imperfecta
Rendu - Osler
- dobandite- dobanditescorbutscorbut
senilasenila
Sindrom Henoch SchonleinSindrom Henoch Schonlein
infectioasa - meningococcica, viraleinfectioasa - meningococcica, virale
disglobulinemii - Waldenstrom, mielom, disglobulinemie mixta
disglobulinemii - Waldenstrom, mielom, disglobulinemie mixta
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Boala Rendu OslerBoala Rendu Osler
- congenitala- congenitala
autosomal dominanta
defect perete venos
autosomal dominanta
defect perete venos
fistule arteriovenoase fistule arteriovenoase
(mucoasa digestiva, plaman, ficat, splina, cerebral)
(mucoasa digestiva, plaman, ficat, splina, cerebral)
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Telangiectatizia ereditara
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Manifestari cliniceManifestari clinice
1. telangiectazii cutanate, mucoase
2. epistaxis, hemoptizii, melena,
3. anemie feripriva cronica
4. anevrisme arteriovenoase hepatice cu sindrom hiperkinetic cardiovascular
5. AHC – sugestive boala Rendu
1. telangiectazii cutanate, mucoase
2. epistaxis, hemoptizii, melena,
3. anemie feripriva cronica
4. anevrisme arteriovenoase hepatice cu sindrom hiperkinetic cardiovascular
5. AHC – sugestive boala Rendu
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Diagnostic diferentialDiagnostic diferential
1. Telangiectaziile sclerodermie (CREST)
2. Pete telangiectatice
3. B Fabry (Angiokeratoma corporis difusum)
1. Telangiectaziile sclerodermie (CREST)
2. Pete telangiectatice
3. B Fabry (Angiokeratoma corporis difusum)
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CERST
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Boala Fabry
- boala a metabolismului glicolipidic(ceramide intramacrofagic)
- leziuni nodulare inchise la culoare (aproape negre) periombilical, scrotal,
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Pete telangiectatice
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Tratament boala Rendu OslerTratament boala Rendu Osler
1. Suportiv: tamponament nazal, unguente ( dermatol), cauterizari contraindicate
2. Trat anemiei : fier, ac folic, vit B12 la 3 luni
3. Trat chirurgical al fistulelor mari – greu de abordat
1. Suportiv: tamponament nazal, unguente ( dermatol), cauterizari contraindicate
2. Trat anemiei : fier, ac folic, vit B12 la 3 luni
3. Trat chirurgical al fistulelor mari – greu de abordat
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2. Purpure vasculare anomalii dobandite
ale tesutului conjunctiv
2. Purpure vasculare anomalii dobandite
ale tesutului conjunctiv
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Purpura de staza
Purpura de senila
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Scorbutul
- patogenie: - deficit vit C – deficit de colagen (hidroxiprolina)
- reduce adeziunea, agregarea plachetelor, - clinic : - purura in jurul foliculului pilos, durere - hipercheratoza- rar: HDS, hemoragii musculare
- tratament: Vit C iv
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3. Purpure vasculare dobandite
- boli infectioase - boli de tesut conjunctiv
- hiper/disglobulinemii - Henoch Schonlein
- cauze rare
3. Purpure vasculare dobandite
- boli infectioase - boli de tesut conjunctiv
- hiper/disglobulinemii - Henoch Schonlein
- cauze rare
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Purpure vasculare dobandite –
1.Boli infectioase
Purpure vasculare dobandite –
1.Boli infectioase
- etiopatogenie- etiopatogenie
- complexe imune circulante - post infectii bacteriene, virale, rickettsi- medicamente – penicilina, sulfamide, allopurinol
- complexe imune circulante - post infectii bacteriene, virale, rickettsi- medicamente – penicilina, sulfamide, allopurinol
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Purpura infectioasa
- infectii (virusuri, meningococ, rickettsi)
- patogenie: complexe imune circulante
- clinic : - purura – bule hemoragice
– “purpura fulminans “ - tratament – antiinfectios
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Purpura fulminans post zona zoster
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Endocardita bacteriana
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Sindromul hemolitic uremic
- microtromboze exclusiv in vase renale
- etiologie: infectiasa
- patogenie:
- copii, adolescenti- dupa infectii (E Coli, Shigella)
- leziune de celule endoteliale, microtromboze a. aferenta, glomerul
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Sindromul hemolitic uremic
- microtromboze exclusiv in vase renale
- etiologie: infectiasa
- clinic: - purpura
- insuf renala acuta - HTA
- AH microangiopatica
- evolutie : - deces prin IRA
- 10- 50% cazuri IRC
- tratament - dializa in IRA
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Vasculita poliartrita reumatoida
Purpure vasculare dobandite –
Boli de tesut conjunctiv
Purpure vasculare dobandite –
Boli de tesut conjunctiv
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Purpura disglobulinemica
- gamapati monoclonale (Waldenstrom, mielom multiplu)
- crioglobulinemia – globuline anormale si complexe imune
- patogenie: - vascozitate sangvina cerscuta
- reduce adeziunea, agregarea plachetelor, - clinic : - purura - nefrita
- artarlgii - tratament – controlul de baza, plasmafereza
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Purpura hiperglobulinemica
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Hemoragii subunghiale - crioglobulinemie
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Purpura Henoch SchonleinPurpura Henoch Schonlein
- etiopatogenie- etiopatogenie
infectie streptococica (faringiana – 50%cazuri, respiratorie)
-alergii alimentare, medicamnetoase – (chinidina, sulfamide)
infectie streptococica (faringiana – 50%cazuri, respiratorie)
-alergii alimentare, medicamnetoase – (chinidina, sulfamide)
membrana bazala capilara – - complexe imune IgA2
membrana bazala capilara – - complexe imune IgA2
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Purpura Henoch SchonleinPurpura Henoch Schonlein
Manifestari cliniceManifestari clinice
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Manifestari cliniceManifestari clinice
1. purpura
2. poliartralgii
3. colica abdominala, melena, rar perforatie intestinala
4. Hematurie, proteinurie – GNA ac mesangiala focala
1. purpura
2. poliartralgii
3. colica abdominala, melena, rar perforatie intestinala
4. Hematurie, proteinurie – GNA ac mesangiala focala PrognosticPrognostic
favorabil in generalfavorabil in general
evolutie cu “recidive purpurice”evolutie cu “recidive purpurice”
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TratamentTratament
1. Penicilina – infectie streptococcica
2. Corticoterapie – 1mg/kg prednison
1. Penicilina – infectie streptococcica
2. Corticoterapie – 1mg/kg prednison
PrognosticPrognostic
- favorabil in general- favorabil in general
- evolutie cu “recidive purpurice”- evolutie cu “recidive purpurice”
- IRA - perforatie intestinala- IRA - perforatie intestinala
ComplicatiiComplicatii
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Purpure vasculare rarePurpure vasculare rare
- anticoagulante (heparina nefractionata)
- anticoagulante (heparina nefractionata)
- autoflagelare - autoflagelare
- staza - staza
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Necroza cumarinica
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Purpura trombocitopenicaPurpura trombocitopenica
I. Productie scazuta de trombociteI. Productie scazuta de trombocite
- trombocitopenia < 100 000/mm
- trombocitopenia < 100 000/mm
3
- Nr redus de megacariocite in maduva- Nr redus de megacariocite in maduva
1. infiltrat medular : leucemii, limfoame, mielom, metastaze, granuloame
1. infiltrat medular : leucemii, limfoame, mielom, metastaze, granuloame
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3. anomalii congenitale: pancitopenia Fanconi, trombocitopenia autosomal recisiva, boala May Hegglin,
3. anomalii congenitale: pancitopenia Fanconi, trombocitopenia autosomal recisiva, boala May Hegglin,
2. sindr mielodisplazice: idiopaticasecundara: radiatii, medicamente,
virusuri
2. sindr mielodisplazice: idiopaticasecundara: radiatii, medicamente,
virusuri
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- scurtarea duratei de viata a trombocitelor
- scurtarea duratei de viata a trombocitelor
1. Distructie crescuta :
a) mecanisme imuneb) distructie
- splina - “consum” – CID
1. Distructie crescuta :
a) mecanisme imuneb) distructie
- splina - “consum” – CID
- trombocitopenia < 100000/mm
- trombocitopenia < 100000/mm
3
- nr crescut de megacariocite in maduva - nr crescut de megacariocite in maduva
II. Distructie crescuta trombocite:
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1. Distructie prin mecanisme imune :
- PTI autoimuna acuta, cronica (PTI) - purpura posttransfuzionala
- neonatala alloimuna- post medicamentoasa
- autoimuna secundara
1. Distructie prin mecanisme imune :
- PTI autoimuna acuta, cronica (PTI) - purpura posttransfuzionala
- neonatala alloimuna- post medicamentoasa
- autoimuna secundara
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Purpure trombocitopenica autoimuna idiopaticaPurpure trombocitopenica autoimuna idiopatica
- etiopatogenie- etiopatogenie
- autoanticorpi in plasma si pe membrana trombocitelor
- autoanticorpi in plasma si pe membrana trombocitelor
- distrugere prematura a trombocitelor macrofagele
splinice
- distrugere prematura a trombocitelor macrofagele
splinice
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Purpure trombocitopenica autoimuna idiopatica acutaPurpure trombocitopenica autoimuna idiopatica acuta
- etiopatogenie- etiopatogenie
- autoanticorpi antitrombocitari IgG
- autoanticorpi antitrombocitari IgG
- antigene : virus gripal, rubeolic, hepatitic, HIV, Ebstein Barr,
- antigene : virus gripal, rubeolic, hepatitic, HIV, Ebstein Barr,
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- clinic- clinic- petesii fara splenomegalie - petesii fara splenomegalie
- paraclinic- paraclinic
- trombocitopenie- trombocitopenie
- maduva: megcariocite numeroase oprite in maturatie
- maduva: megcariocite numeroase oprite in maturatie
- TS prelungit- TS prelungit
- IgG antiitrombocitari- IgG antiitrombocitari
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Maduva:
Numar crescut de megacarioocite
Nu megcariocite trombocitogene
Maduva:
Numar crescut de megacarioocite
Nu megcariocite trombocitogene
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- evolutie- evolutie
- boala autolimitata cu vindecare,
- uneori cu purpura “in valuri”
- 20% cronicizare
- boala autolimitata cu vindecare,
- uneori cu purpura “in valuri”
- 20% cronicizare
- tratament- tratament
- cortioterapie in cazuri grave- cortioterapie in cazuri grave
- plasmafereza in risc de hemoragie cerebrala
- plasmafereza in risc de hemoragie cerebrala
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Purpure trombocitopenica autoimuna idiopatica cronica
Purpure trombocitopenica autoimuna idiopatica cronica
- etiopatogenie- etiopatogenie
- anticorpi antitrombocitari anti receptori IIb-IIIa, anti glicoproteina Ib
- anticorpi antitrombocitari anti receptori IIb-IIIa, anti glicoproteina Ib
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- clinic- clinic
- astenie, petesii - “nepalpabile”, fara bule hemoragice, echimoze, - metroragii, sangerari digestive,
- fara splenomegalie
- astenie, petesii - “nepalpabile”, fara bule hemoragice, echimoze, - metroragii, sangerari digestive,
- fara splenomegalie
- paraclinic- paraclinic- trombocitopenie- trombocitopenie
- maduva: megcariocite tinere - maduva: megcariocite tinere
Purpure trombocitopenica autoimuna idiopatica cronica
Purpure trombocitopenica autoimuna idiopatica cronica
- femei / barbati = 3/1 - femei / barbati = 3/1
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- paraclinic- paraclinic
- trombocitopenie- trombocitopenie
- maduva: megcariocite tinere numeroase oprite in
maturatie,
- maduva: megcariocite tinere numeroase oprite in
maturatie,
- TS prelungit- TS prelungit
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- evolutie- evolutie- cronica, remisiuni spontane f rare- cronica, remisiuni spontane f rare
- tratament- tratament- cortioterapie 1mg/kg/zi- cortioterapie 1mg/kg/zi
- 50% remisiune partiala, raspunsuns la 6 saptamani
- 50% remisiune partiala, raspunsuns la 6 saptamani
- splenectomie – forme corticorezistente- splenectomie – forme corticorezistente
- imuran – 3 luni +/- vinblastin- imuran – 3 luni +/- vinblastin
- gama globulina iv – 3luni blocarea sistemului monocit-macrofag
- gama globulina iv – 3luni blocarea sistemului monocit-macrofag
- rituximab – anticorp antiCD20, distruge limfocite B ce sintetizeaza anticorpi antitrombociatari
- rituximab – anticorp antiCD20, distruge limfocite B ce sintetizeaza anticorpi antitrombociatari
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- postnatala- postnatala
- clinic- clinic
- sindrom hemoragipar imediat dupa nastere- sindrom hemoragipar imediat dupa nastere
- manifestari grave la urmatorii copii
- manifestari grave la urmatorii copii
Purpure trombocitopenica alloimuna
Purpure trombocitopenica alloimuna
- anticorpi antitrombocitari ce trec palacenta
- anti sistemului PI
- anticorpi antitrombocitari ce trec palacenta
- anti sistemului PI
A1
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- clinic- clinic
Purpure trombocitopenica posttransfuzionala
Purpure trombocitopenica posttransfuzionala
- la 7 zile de la transfuzie, masa
trombocitara - la 7 zile de la transfuzie, masa
trombocitara
- anticorpi antitrombocitari
- anti sistemului PI
- anticorpi antitrombocitari
- anti sistemului PIA1
- tratament- tratament- corticoterapie, plasmafereza,
exanguinotransfuzie- corticoterapie, plasmafereza,
exanguinotransfuzie
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- actiune maduva osoasa- actiune maduva osoasa
Purpure trombocitopenica postmedicamentoasa
Purpure trombocitopenica postmedicamentoasa
- arabinosid, daunorubicina,
- tiazidice, estrogeni - arabinosid, daunorubicina,
- tiazidice, estrogeni
- distructie imuna- distructie imuna
- antibiotice, sulfamide, - chinidina, chinina
- metildopa - Saruri de aur,
- heparina
- antibiotice, sulfamide, - chinidina, chinina
- metildopa - Saruri de aur,
- heparina
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- mecanism imun:- mecanism imun:
Purpure trombocitopenica postmedicamentoasa
Purpure trombocitopenica postmedicamentoasa
1. complexe imune anti “ medicament + proteina plasmatica”
- absorbtie nespecifica a complexelor pe trombocit “inocent bystander”
1. complexe imune anti “ medicament + proteina plasmatica”
- absorbtie nespecifica a complexelor pe trombocit “inocent bystander”
2. medicament fixat pe trombocit, anticorpi anti complex
“ medicament + trombocit”
2. medicament fixat pe trombocit, anticorpi anti complex
“ medicament + trombocit”
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- clinic- clinic- petesii, frecvent sindrom
hemoragic sever aparut dupa medicamente
- petesii, frecvent sindrom hemoragic sever aparut dupa medicamente
- paraclinic- paraclinic
- intreruperea medictiei, corticoterapie, plasmafereza,
- intreruperea medictiei, corticoterapie, plasmafereza,
- tratament- tratament
- megacariocite normale, intens trombogene ( citoplasma granulata, azurofila, fara vacuole)
- megacariocite normale, intens trombogene ( citoplasma granulata, azurofila, fara vacuole)
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- paraclinic- paraclinic- trombocitopenie- trombocitopenie
- maduva: megacariocite normale, anomalii morfolgice - maduva: megacariocite normale, anomalii morfolgice
Purpure trombocitopenica autoimuna secundara
Purpure trombocitopenica autoimuna secundara
- LES
- LLC, limfoame
- HIV
- LES
- LLC, limfoame
- HIV
- tratament- tratament
- zidovudin- zidovudin
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TrombopatiiTrombopatii
1. Sindromul Bernard Soulier – defect de receptor GpIb/IX ptr vFW
- boala autosomal recesiva
1. Sindromul Bernard Soulier – defect de receptor GpIb/IX ptr vFW
- boala autosomal recesiva
2. Trombastenia Glanzman – defect de receptor GpIIb/IIIa
- boala autosomal recesiva
2. Trombastenia Glanzman – defect de receptor GpIIb/IIIa
- boala autosomal recesiva
3. defecte de sinteza TxA2 – aspirina, AINS
4. defecte ale granulor de stocaj
3. defecte de sinteza TxA2 – aspirina, AINS
4. defecte ale granulor de stocaj
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Sindrom hemoragic prin anomalii de coagulare Sindrom hemoragic prin anomalii de coagulare
1. Hemofilia A deficienta factor VIII1. Hemofilia A deficienta factor VIII
- anomalia genei F VIII – bratul lung cromozom X - anomalia genei F VIII – bratul lung cromozom X
- mutatii punctiforme, deletii importante- mutatii punctiforme, deletii importante
- boala afecteaza aproape exclusiv barbatii, deoarece la femei heterozigote cromozomul X asogura sinteza necesara de f VIII, fapt ce nu este realizat de cromozomul XY la barbati
- boala afecteaza aproape exclusiv barbatii, deoarece la femei heterozigote cromozomul X asogura sinteza necesara de f VIII, fapt ce nu este realizat de cromozomul XY la barbati
- incidenta 1/ 10 000- incidenta 1/ 10 000
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Factorul VIII – proteina 80 000 daltoni, pe suprafata f. von Willebrand
F VIII – sintetizat in ficat
- concentratie plasmatica = 10 g/l - durata de viata 8-12 ore
Hemostaza normala necesita activitate – 25% f VIII
Factorul VIII – proteina 80 000 daltoni, pe suprafata f. von Willebrand
F VIII – sintetizat in ficat
- concentratie plasmatica = 10 g/l - durata de viata 8-12 ore
Hemostaza normala necesita activitate – 25% f VIII
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Hemofilia A - deficienta factor VIIIHemofilia A - deficienta factor VIII
Xy x
x
Xy
Xyx
xXy
X
Xy
Xy x
x
x
xX Xy
x
x
x
xXX
X Xy
Generatia I
Generatia II
Generatia III
Generatia IV
X
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- Clinic- Clinic
- copii - baieti, tineri - hematoame, hemartroza,
- hemoragii: muschi,
orofaringe, cerebrale
- copii - baieti, tineri - hematoame, hemartroza,
- hemoragii: muschi,
orofaringe, cerebrale
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Hemofilia A Hemofilia A
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Hemartroze – hemofilia A Hemartroze – hemofilia A
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- Diagnostic paraclinic- Diagnostic paraclinic
- T sangerare = normal - T sangerare = normal
- T coagulare = prelungit - T coagulare = prelungit
- T tromboplastina partial activata = prelungit
- T tromboplastina partial activata = prelungit
- AND fetal- AND fetal
- Concentratie F VIII = scazuta
- Concentratie F VIII = scazuta
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- Forme- Forme
- severe …….. 1% activitate f VIII- severe …….. 1% activitate f VIII
- medii …….. 1-5% activitate f VIII- medii …….. 1-5% activitate f VIII
- usoare …….. 5% activitate f VIII- usoare …….. 5% activitate f VIII
- f usoare .… 5 - 25% activitate f VIII- f usoare .… 5 - 25% activitate f VIII
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TratamentTratament
- crioprecipitat (efecte secundare: infectie vir hepatitic, HIV, IgG anti F
VIII)
- crioprecipitat (efecte secundare: infectie vir hepatitic, HIV, IgG anti F
VIII)
- concentrat de factor VIII - concentrat de factor VIII
Forme usoare Forme usoare
- desmopresin - desmopresin
- EACA – inainte de extractii dentare inhibitor de fibrinoliza ( inhiba activatorul tisular plasminogen)
- EACA – inainte de extractii dentare inhibitor de fibrinoliza ( inhiba activatorul tisular plasminogen)
Forme medii Forme medii
Forme severeForme severe
- cocentrat VIIa / f tisular - cocentrat VIIa / f tisular
- cocentrat VIIa recombinat - cocentrat VIIa recombinat
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Preventia hemorgiilor chirurgicalePreventia hemorgiilor chirurgicale
- concentrat de factor VIII - concentrat de factor VIII
Postoperator
- 14 (chirurgie generala)
- 21 zile (chirurgia genunchiului)
Postoperator
- 14 (chirurgie generala)
- 21 zile (chirurgia genunchiului)
preoperatorpreoperator
- cocentratia factor VIII – 50%
- cocentratia factor VIII – 50%
- concentrat de factor VIII - concentrat de factor VIII
- cocentratia factor VIII – 50%
- cocentratia factor VIII – 50%
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1. Hemofilia B – boala Christmas deficienta factor IX
1. Hemofilia B – boala Christmas deficienta factor IX
- Anomalia genei IX – bratul lung cromozom X
- mutatii punctiforme, 1/3 spontane
- microdeletii
- 800 pattern- uri de anomalii moleculareex: factor IX Leiden – 11 mutatii punciforme
- Anomalia genei IX – bratul lung cromozom X
- mutatii punctiforme, 1/3 spontane
- microdeletii
- 800 pattern- uri de anomalii moleculareex: factor IX Leiden – 11 mutatii punciforme
- Factor IX - sinteza hepatica dependenta de vit. K
- Factor IX - sinteza hepatica dependenta de vit. K
- 20% din hemofilii, incidenta 1/100 000- 20% din hemofilii, incidenta 1/100 000
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1. Hemofilia B – boala Christmas deficienta factor IX
1. Hemofilia B – boala Christmas deficienta factor IX
- Paraclinic – concentratia fact IX < 1%- Paraclinic – concentratia fact IX < 1%
- Tratament – plasma proaspata, - complex protrombinic liofilizat (
risc de tromboze)
- Tratament – plasma proaspata, - complex protrombinic liofilizat (
risc de tromboze)
- Clinic – sindrom hemoragipar expresie fenotipica variabila
- ameliorare la pubertate, sub androgeni
- Clinic – sindrom hemoragipar expresie fenotipica variabila
- ameliorare la pubertate, sub androgeni
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- Boala Von Willebrand
- 1 la 100 – 500 persoane este cea mai comuna anomalie mostenita de sangrare
- FvW - glicoproteina multimerica heterogena secretata de endoteliu si
plachete
1. favorizeaza adeziunea plachetelor la receptori subendoteliali
2. transportor plasmatic al F VIII- nivel palsmatica 10mg/L
– reduceri modeste FvW sau modificare moleculara determina S hemoragipar
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1. Boala fon Willebrand1. Boala fon Willebrand
- precursor F Willebrand sintetizat de endoteliu si megacariocite- precursor F Willebrand sintetizat de endoteliu si megacariocite
- functii F Willebrand
- adeziunea trombocit la endoteliu- transportor f VIII
- functii F Willebrand
- adeziunea trombocit la endoteliu- transportor f VIII
- concentratia plasmatica: 10 mg/dl- concentratia plasmatica: 10 mg/dl
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- Clinic: - Clinic:
- TS - prelungit- Agregare plachetara la ristocetina= absenta - APTT– normal, T Quik-normal
- TS - prelungit- Agregare plachetara la ristocetina= absenta - APTT– normal, T Quik-normal
- Concentratia plasmatica F Willebrand - scade - Concentratia plasmatica F Willebrand - scade
- femei si barbati- hemoragii cutanate si mucoase- femei si barbati- hemoragii cutanate si mucoase
- Tratament: crioprecipitat, desmopresin - Tratament: crioprecipitat, desmopresin
- forme:- forme:- usoare, medii, severe - usoare, medii, severe
- DG. paralinic:- DG. paralinic:
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Boala von Willebrand:
- boala autosomal dominanta, forma heterozigota vWf este produs de gena normala
- BvW tip I - nivel descrescut cu 50% al FvW
- sangerare la traumatisme, chirurgie, epistaxis, hemoragii mici mucoase, subcutanate
- Diagnostic:
- TS >,
- nivel plasmatic vWF <,
- aglutinare la ristocetina< (activitate biologica)
- spectru normal al multimerilor la electroforeza in agaroza
- activitatea F VIII scazuta
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- Boala von Willebrand:
- BvW tip II - nivel noraml FvW disfunctional pentru multimerii cu greutate moleculara mare si medie, fenomen detectat la electroforeza in agaroza
- BvW tip II a - deficienta a FvW cu greutate moleculara mare sau medie, mutatie in
domeniul A2 – deficienta de secretie sau proteoliza a multimerilor vWF, - FvW si F VIII – concentratii normale
- BvW tip II b – descrestere FvW cu greutate moleculara mare, legare inadecvata de
plachete si eliminare a Pl+FvW anormal, cu trombocitopenie secundara
- mutatie in domeniul I ce se laga de glicoproteina Ib IX
- - FvW si F VIII – concentratii
normale
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1. Deficienta dobandita a factorilor de coagulare
1. Deficienta dobandita a factorilor de coagulare
- vitamina K -
- plante- sintetizata de flora intestinala
- vitamina K -
- plante- sintetizata de flora intestinala
vit K vit K
epoxidazaepoxidaza
reductazareductaza
vit K epoxid vit K epoxid
Anticoagulanti cumarinici
Anticoagulanti cumarinici
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- Deficienta vitamina K influenteaza -
- f II- f VII- f IX- f X
- proteina C si S
- Deficienta vitamina K influenteaza -
- f II- f VII- f IX- f X
- proteina C si S
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- Cauze deficienta vitamina K -
- aport insuficient- antibioterapie per os- sindr biliar obstructive
- boli hepatocelulare grave
- antagonisti de vit K
- Cauze deficienta vitamina K -
- aport insuficient- antibioterapie per os- sindr biliar obstructive
- boli hepatocelulare grave
- antagonisti de vit K
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- Clinic -- sindrom hemoragipar functie de deficienta de vit K- forme usoare - severe
- Clinic -- sindrom hemoragipar functie de deficienta de vit K- forme usoare - severe
- Tratament - - plasma proaspata, sange proaspat - vit K parenteral – 10mg - restabileste depozitele hepatice in 8 -10 ore
- Tratament - - plasma proaspata, sange proaspat - vit K parenteral – 10mg - restabileste depozitele hepatice in 8 -10 ore
- paraclinic -
- TC – prelungit, T Quik - prelungit
- paraclinic -
- TC – prelungit, T Quik - prelungit
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- Cauze de sangerare in boli hepatice
- scade sinteza : fibrinogen, protrombina, fact V, VII, IX, X, - scade sinteza: proteina C,S,
antitrombina III - CID - vit K - scade absorbtia si metabol
- fibrinoliza sistemica primara
- trombocitopenie
- Cauze de sangerare in boli hepatice
- scade sinteza : fibrinogen, protrombina, fact V, VII, IX, X, - scade sinteza: proteina C,S,
antitrombina III - CID - vit K - scade absorbtia si metabol
- fibrinoliza sistemica primara
- trombocitopenie
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Coagulare intravasculara diseminata
Purpura trombotica trombocitopenica
- infectii sistemice: stafilo, meningococ, B Gram neg
- sindr obstetricale: avort, eclampsie, dezlipire placenta - neoplazii: LAM, adenocarcinoame - hemoliza intravasculara- distructii tisulare: traumatisme, arsuri, etc- leziuni endoteliu: SHU, GNA, hemangiom cavernos- ciroza
Coagulare intravasculara diseminata
Purpura trombotica trombocitopenica
- infectii sistemice: stafilo, meningococ, B Gram neg
- sindr obstetricale: avort, eclampsie, dezlipire placenta - neoplazii: LAM, adenocarcinoame - hemoliza intravasculara- distructii tisulare: traumatisme, arsuri, etc- leziuni endoteliu: SHU, GNA, hemangiom cavernos- ciroza
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Factori etiologici
XII a
PDF exces in microcirculatie
XII a
Tromboze
Fibrinoliza in excesActivare coagulare in
microcirculatie
Sangerare difuza
Disfunctie endoteliu – eliberare factor vW, XII a
PDF exces in microcirculatie
PDFcoagulare fibrinoliza
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Tromboze Sangerare difuza
- neurologic : semen focar, convulsii, coma
- piele : ischemie focala, gangrena
- plaman : SDRA
- gastrointestinal : sangerare acuta
- laborator : trombocite <, F VII, V<, Fibrinogen<, PDF> 4g/dl, AH microangiopatica
- petesii,- sangerare - pe mucoase -(gastrointestinala, hemoptizieepisataxis) - sangerare neurologica
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Coagulare intravasculara diseminata
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CID – acut
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Coagulare intravasculara diseminata
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CID – dg. paraclinic
1. trombocitopenie
2. AH microangiopatica
schizocite
3. TC >, aPTT >, TQ >
5. PDF+++
4. Fibrinogen <
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Sindrom hemolitic uremic Sindrom hemolitic uremic
- clinic- clinic
- copii, tineri - copii, tineri
- tratament- tratament
- IRA, sindr hemoragipar, rar sindrom neurologic
- IRA, sindr hemoragipar, rar sindrom neurologic
- prognostic- prognostic
- 50-80% mortalitate- 50-80% mortalitate
- plasmafereza, exanguinotransfuzia
- plasmafereza, exanguinotransfuzia
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- Tratamen CID- tratamentul bolii de baza - reechilibrare hidroelectrolitica - heparina –1000 UI/ora, 5000 UI la 4ore - EACA = 4-6g/24 ore
( blocheaza PDF)
- Tratamen CID- tratamentul bolii de baza - reechilibrare hidroelectrolitica - heparina –1000 UI/ora, 5000 UI la 4ore - EACA = 4-6g/24 ore
( blocheaza PDF)
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- Fibrinoliza - Fibrinoliza
activator tisular plasminogen activator tisular plasminogen
plasminogen tromb
plasminogen tromb
plasminaplasmina
fibrinafibrina
PDFPDF
anti plasmina anti plasmina2
PAI PAI
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- Fibrinoliza primara - Fibrinoliza primara
- deficitul 2 anti plasmina - deficitul 2 anti plasmina
- scade mult fibrinogenul - scade mult fibrinogenul
- sindrom hemoragipar - sindrom hemoragipar
- aPTT, T Quik – aproape normale - aPTT, T Quik – aproape normale
- trombocite normale - trombocite normale
- paraclinic - paraclinic
- tratament - tratament
- plasma proaspata, EACA - plasma proaspata, EACA
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ELEMENTE CLINICE DIAGNOSTIC DIFERENTIAL
ELEMENTE CLINICE DIAGNOSTIC DIFERENTIAL
- varsta, sex - varsta, sex
- Sindromul hemoragipar - Sindromul hemoragipar
- conditii de declansare - conditii de declansare - purpura - purpura
- localizare - localizare
- leziuni palpabile, buloase, micronecrotice
- leziuni palpabile, buloase, micronecrotice
- acuta, cronica - acuta, cronica
- hemoragii: mucoase, articulare, SNC - hemoragii: mucoase, articulare, SNC
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ELEMENTE PARACLINICE DIAGNOSTIC DIFERENTIAL
ELEMENTE PARACLINICE DIAGNOSTIC DIFERENTIAL
- Timp sangerare - Timp sangerare
- Trombocite - Trombocite - Timp coagulare - Timp coagulare
- concentratie f VIII, IX, von willebrand
- concentratie f VIII, IX, von willebrand
- aPTT - aPTT
- t Quik - t Quik
- PDF - PDF
- liza cheagului - liza cheagului
- fibrinogen - fibrinogen