HEMATOLOGY II n
REVIEWER NOTES n
KYLE BERNIE S. RAMOS 2022
n n n n
Reference: Rodak's Hematology Clinical Principles and Applications 6th Edition & Hematology_112 L
n n n n n n n n n n n
ecture - J.A. Ganding, RMT
n n n n
, Introduction: Hemostasis n
HEM_112:nHEMATOLOGYn2nLECTUR
En(PRELIMINARY)
SirnJomarnAdamsnGanding,nRMT
OUTLINE ABNORMALnSTATE
I. DefinitionnofntermsnrelatedntonHemostasis ● Thrombosis
A. PrimarynHemostasis ○ Excessivenclottingninsidenthenbloodnvesseln→norgan
1. Platelets
ndeprivationnofnoxygennandnnutrientsn→ntissue/celln
2. VascularnSystem
3. Mechanism death.
B. SecondarynHemostasis ● Hemorrhagicndisease
1. Coagulationnfactors ○ Noncoagulationn→ndeficientnprocoagulants.
2. CoagulationnInhibitor
3. Mechanism KEYnCOMPONENTSnOFnHEMOSTASIS
C. Fibrinolysis
● Cellularncomponents:
NOTE:nThencontentsnofnthisnreviewernisnmostlynfromntheninstructor’ ○ CellsnofnthenVascularnIntiman(EndothelialnCells)
snlecture.nPleasenreadnRodak'snHematologyn6thnEditionnfornanm ○ ExtravascularnTissuenFactornBearingnCells
orendetailednstudy.nThanknyou! ○ Platelets
● Plasmancomponents:
HEMOSTASIS ○ Coagulationnproteinsn-nfavorsncoagulation
○ Fibrinolyticnproteinsn-
ntriggersnfibrinolysisntonendnclotting.
○ Inhibitors:
(1) Fornfibrinolysisn-
ninhibitsnunderntimenclotting;nincomplet
entissuenrepair.
(2) Forncoagulationn-
neliminatesnbystandernclotnformationninsid
enthenbloodnvessel.
PRIMARYnHEMOSTASIS
● ActivatednbynSMALLninjuriesninnbloodnvessels.
● Rapid,nshort-livednreponse.
● “Firstnaid”;nfirstntonbenactivated.
● Hemostasisnisnancomplexnphysiologicnprocessnthatnkeeps
ncirculatingnbloodninnanfluidnstaten(Rodak’sn6thnEd).
COMPONENTS
● involvesntheninteractionnofnvasoconstriction,nplateletn ● VascularnSystem
adhesionnandnaggregation,nandncoagulationnenzyme ○ Arteries
nactivationntonstopnbleedingn(Rodak’sn6thnEd). ○ Veins
● Anprocessninnwhichnbloodnisnretainednwithinnthenvascular ○ Capillariesn-nsmallest.
nsystemnduringninjury.
● Responsiblenfornbothncoagulationnandnmaintainingnbloodnin “ThenmainncomponentnresponsiblenfornPrimarynHemostasisnisny
nliquidnstate. ournVascularnIntima/nEndothelium/nEndothelialnCellsn-
● “Bloodnshouldncoagulatenatnthenperfectntime,nperfectnplace ninnernmostnlayernofnthenBloodnVessel.”n-nJAnGanding
,nandnfornthenrightnpurpose.”n-nJAnGanding.
● Platelets
BLOODnENVIRONMENT
● InsidenthenBloodnVessel MECHANISM
○ Normal 1. VascularnSystem
○ Noncoagulationn→nremainnfluidnfornbloodnflow/nblood ○ Contractsntonsealnthenwoundn(vasoconstriction)n→n
ncirculation.
Initialnhemostaticnresponsenofnthenbodyn→nprevents
nexcessivenbloodnloss.
● OutsidenthenBloodnVessel
○ Duringninjury/ntissuendamage 2. Platelets
○ Needsncoagulationn→nhemostaticnreaction ○ Thrombocytesnfillnthenopennspacentonformnanplateletn
plugn(primarynhemostaticnplug),nmadenupnofnplatelets
nalone.
1 RAMOS
, INTRODUCTION:nHEMOSTASIS
FIBRINOLYSIS
● AlsonknownnasnThrombolysis.
AdditionalnInfo: ● Finalnstagenofncoagulation.
● VascularnIntimancontainsnanninternalnelasticnlaminan(elastin ● Onlynhappensnwhennthenwoundnisnalreadynsealed,nread
nandncollagen)nwherenwhennplateletsnarenexposednto,nthenl
ynfornvascularnrepair.
atternisnactivatednenablingnadhesionntonthensitenofninjury. ● Digestionnofnfibrinnclotnkeepsnthenvascularnsystemnfreeno
● Essencenofnfibroblastsn- fndepositednfibrin/nfibrinnclotn →nImportance?nFibrin/nfibri
nfornvascularnrepairnandncellngenerationnfornclosingn
nnclotncannclognthenbloodnvesselsn(magigingnbarado).
theninjury.
MECHANISM
SECONDARYnHEMOSTASIS ● Releasenofntissuenplasminogennactivator.
○ Plasminogennisnanzymogenn(inactive)nthatnneeds
nthrombinn(activator)ntonbenconvertedntonplasmin.
● Conversionnofnplasminogenntonplasmin.
● Conversionnofnfibrinntonfibrin-degradationnproduct.
○ Plasminninducesnfibrinnclotntonlyseninnordernt
onre-establishnbloodnflow.
REVIEWnQUESTIONS
● Whatnarenthenkeyncomponentsnofnhemostasis?
● Whatnarenthencellularncomponents?
● Whatnarenthenplasmancomponents?
● Whatnisnthendifferencenbetweennprimarynandnsecondary
nhemostasis?
● Betweennthentwontypesnofnhemostasis,nwhatnisnrapid?nAn
dnwhatnisndelayed?nWhatnisnthenresponsenfornsmallninjurie
s?nLargeninjuries?
● Activatednwhennprimarynhemostasisnisnnotnenough. ● Whatnarenthencomponentsnofnprimarynhemostasis?
● ActivatednbynLARGEninjuriesntonbloodnvessels. ● Whatnarenthencomponentsnofnsecondarynhemostasis?
● Delayed,nlong-termnresponse. ● Thisnisnalsontermednasnthenprimarynhemostaticnplug.
● Thisnisnalsontermednasnthensecondarynhemostaticnplug.
COMPONENTS ● Whatnisnthenimportancenofnfibroblastsninnthenvascula
rnintima?
● Coagulationnfactors
● Whatnisnthenfactornthatnpreventsnfibrinnclotnfromnbreaking?
○ Promotesncoagulation;nprocoagulants.
● Itnisnthenlastnstagenofncoagulation.
● Coagulationninhibitors
○ Preventsnanynunwantednclotnformation.
MECHANISM
1. Interactionnofncoagulationnfactorsntonproducenanfibrin
nclotn(secondarynplateletnplug).
○ InducednbynCoagulationnFactornI
○ Thrombinn→nultimate/needednproteinntonconvert
nfibrinogenntonfibrin.
2. FibrinnStabilization
○ FactornXIIIn→npreventsnfibrinnclotnfromnbreaking.
2 RAMOS
, MEGAKARYOCYTOPOIESIS PART I n n
HEM_112:nHEMATOLOGYn2nLECTUR
En(PRELIMINARY)
SirnJomarnAdamsnGanding,nRMT
OUTLINE ● MegakaryocytopoiesisnPathway
I. Megakaryocytopoiesis ○ HematopoieticnStemnCelln(Pluripotent)n→nCommon
A. Definitionnofnterms nMyeloidnProgenitorn(Multipotent)n→
B. Sitenofnorigin Megakaryocyte-ErythrocytenProgenitorn–nCFU-
II. Stagesn n of Development GEMMnxnThrombopoietinn→nMegakaryoblastn(Precur
A. ProgenitornCells sor)
B. Megakaryoblast
● “Nakadependensanhormonen(TPO/EPO)nkungnanong
C. Promegakaryocyte
nprecursorncellnangnmapo-produce”n-nJAnGanding
D. Megakaryocyte
III. Thrombocytopoiesis
IV. Platelets NOTE:nPluripotentnvsnMultipotent
V. HormonesnandnCytokinesnofnMegakaryopoiesis ○ Pluripotentn-
ngeneratesncellsnofnallnlineagesn(ex.nHSCn-
NOTE:nThencontentsnofnthisnreviewernisnmostlynfromntheninstructor’ ncommitsntonanspecificnlineageneithernCMPnornCLP)
snlecture.nPleasenreadnRodak'snHematologyn6thnEditionnfornanm ○ Multipotentn-
orendetailednstudy.nThanknyou!
ndividesnintondifferentncellsn(ex.nCMPndifferentiat
esnintonWBCs,nRBCs,n&nPlatelets)
MEGAKARYOCYTOPOIESIS
● IsnitndifferentnfromnMegakaryopoiesis?nNO,nbothntermsnare
STAGESnOFnDEVELOPMENT
nthensame.
● Innthisnportion,nthendifferentnstagesnofnMegakaryopoiesisna
● ThenproductionnandndevelopmentnofnanMegakaryocyte.
rentranscribed,nfromnthenprogenitorsntonthenprecursorsnandn
○ Takennote:nMegakaryocytesnarendifferentnfrom
thenundifferentiatedntonthendifferentiated.
nThrombocytes.
MEGAKARYOCYTEnPROGENITORS
BONEnMARROW
● Sitenofnoriginnfor:
NOTE:nThenCFU-GEMMnwillngivenrisentonthenMegakaryocyte-
○ Megakaryocytopoiesisn- Erythrocyten ProgenitornwhichnwillnreactnwithnTPO,nMeg-CSF,nandnIL-
nproductionnofnMegakaryocytes. 3ntondevelopninton BFU-
○ Thrombocytopoiesisn-nproductionnofnplatelets. Meg.nThenordernofnsucceedingncellsnarenfromnleastntonmostnmature.
● WherenmaturenMegakaryocytesnarenlocalizedninnthenalb ● BurstnFormingnUnitn-nMegakaryocyten(BFU-Meg)
uminalnsurfacen ornnon- ○ Dividesnintonhundredsnofndaughterncells.
bloodnsurfacenofnthensinusoidnliningnendothelialncellsn→ni ○ Undergoesnmitoticndivision.
nnpreparationnfornplateletnshedding. ● ColonynFormingnUnitn-nMegakaryocyten(CFU-Meg)
○ Dividesnintondozensnofndaughterncells.
○ Undergoesnmitoticndivision.
● LightnDensitynCFUn-nMegakaryocyten(LD-CFU-Meg)
○ Unablentondividenbynmitosis
○ Undergoesnendomitosisn-
nanformnofnmitosisnthatnlacksntelophasenandncytokinesi
sn(separationnintondaughterncells).
○ Megakaryocytesndiscontinuentongrow.
○ WillnemployntheirnmultiplenDNAncopiesntonsynthesize
nabundant/largerncytoplasm,nwhichnultimatelyndiffer
entiatesnintonplatelets.
1 RAMOS
REVIEWER NOTES n
KYLE BERNIE S. RAMOS 2022
n n n n
Reference: Rodak's Hematology Clinical Principles and Applications 6th Edition & Hematology_112 L
n n n n n n n n n n n
ecture - J.A. Ganding, RMT
n n n n
, Introduction: Hemostasis n
HEM_112:nHEMATOLOGYn2nLECTUR
En(PRELIMINARY)
SirnJomarnAdamsnGanding,nRMT
OUTLINE ABNORMALnSTATE
I. DefinitionnofntermsnrelatedntonHemostasis ● Thrombosis
A. PrimarynHemostasis ○ Excessivenclottingninsidenthenbloodnvesseln→norgan
1. Platelets
ndeprivationnofnoxygennandnnutrientsn→ntissue/celln
2. VascularnSystem
3. Mechanism death.
B. SecondarynHemostasis ● Hemorrhagicndisease
1. Coagulationnfactors ○ Noncoagulationn→ndeficientnprocoagulants.
2. CoagulationnInhibitor
3. Mechanism KEYnCOMPONENTSnOFnHEMOSTASIS
C. Fibrinolysis
● Cellularncomponents:
NOTE:nThencontentsnofnthisnreviewernisnmostlynfromntheninstructor’ ○ CellsnofnthenVascularnIntiman(EndothelialnCells)
snlecture.nPleasenreadnRodak'snHematologyn6thnEditionnfornanm ○ ExtravascularnTissuenFactornBearingnCells
orendetailednstudy.nThanknyou! ○ Platelets
● Plasmancomponents:
HEMOSTASIS ○ Coagulationnproteinsn-nfavorsncoagulation
○ Fibrinolyticnproteinsn-
ntriggersnfibrinolysisntonendnclotting.
○ Inhibitors:
(1) Fornfibrinolysisn-
ninhibitsnunderntimenclotting;nincomplet
entissuenrepair.
(2) Forncoagulationn-
neliminatesnbystandernclotnformationninsid
enthenbloodnvessel.
PRIMARYnHEMOSTASIS
● ActivatednbynSMALLninjuriesninnbloodnvessels.
● Rapid,nshort-livednreponse.
● “Firstnaid”;nfirstntonbenactivated.
● Hemostasisnisnancomplexnphysiologicnprocessnthatnkeeps
ncirculatingnbloodninnanfluidnstaten(Rodak’sn6thnEd).
COMPONENTS
● involvesntheninteractionnofnvasoconstriction,nplateletn ● VascularnSystem
adhesionnandnaggregation,nandncoagulationnenzyme ○ Arteries
nactivationntonstopnbleedingn(Rodak’sn6thnEd). ○ Veins
● Anprocessninnwhichnbloodnisnretainednwithinnthenvascular ○ Capillariesn-nsmallest.
nsystemnduringninjury.
● Responsiblenfornbothncoagulationnandnmaintainingnbloodnin “ThenmainncomponentnresponsiblenfornPrimarynHemostasisnisny
nliquidnstate. ournVascularnIntima/nEndothelium/nEndothelialnCellsn-
● “Bloodnshouldncoagulatenatnthenperfectntime,nperfectnplace ninnernmostnlayernofnthenBloodnVessel.”n-nJAnGanding
,nandnfornthenrightnpurpose.”n-nJAnGanding.
● Platelets
BLOODnENVIRONMENT
● InsidenthenBloodnVessel MECHANISM
○ Normal 1. VascularnSystem
○ Noncoagulationn→nremainnfluidnfornbloodnflow/nblood ○ Contractsntonsealnthenwoundn(vasoconstriction)n→n
ncirculation.
Initialnhemostaticnresponsenofnthenbodyn→nprevents
nexcessivenbloodnloss.
● OutsidenthenBloodnVessel
○ Duringninjury/ntissuendamage 2. Platelets
○ Needsncoagulationn→nhemostaticnreaction ○ Thrombocytesnfillnthenopennspacentonformnanplateletn
plugn(primarynhemostaticnplug),nmadenupnofnplatelets
nalone.
1 RAMOS
, INTRODUCTION:nHEMOSTASIS
FIBRINOLYSIS
● AlsonknownnasnThrombolysis.
AdditionalnInfo: ● Finalnstagenofncoagulation.
● VascularnIntimancontainsnanninternalnelasticnlaminan(elastin ● Onlynhappensnwhennthenwoundnisnalreadynsealed,nread
nandncollagen)nwherenwhennplateletsnarenexposednto,nthenl
ynfornvascularnrepair.
atternisnactivatednenablingnadhesionntonthensitenofninjury. ● Digestionnofnfibrinnclotnkeepsnthenvascularnsystemnfreeno
● Essencenofnfibroblastsn- fndepositednfibrin/nfibrinnclotn →nImportance?nFibrin/nfibri
nfornvascularnrepairnandncellngenerationnfornclosingn
nnclotncannclognthenbloodnvesselsn(magigingnbarado).
theninjury.
MECHANISM
SECONDARYnHEMOSTASIS ● Releasenofntissuenplasminogennactivator.
○ Plasminogennisnanzymogenn(inactive)nthatnneeds
nthrombinn(activator)ntonbenconvertedntonplasmin.
● Conversionnofnplasminogenntonplasmin.
● Conversionnofnfibrinntonfibrin-degradationnproduct.
○ Plasminninducesnfibrinnclotntonlyseninnordernt
onre-establishnbloodnflow.
REVIEWnQUESTIONS
● Whatnarenthenkeyncomponentsnofnhemostasis?
● Whatnarenthencellularncomponents?
● Whatnarenthenplasmancomponents?
● Whatnisnthendifferencenbetweennprimarynandnsecondary
nhemostasis?
● Betweennthentwontypesnofnhemostasis,nwhatnisnrapid?nAn
dnwhatnisndelayed?nWhatnisnthenresponsenfornsmallninjurie
s?nLargeninjuries?
● Activatednwhennprimarynhemostasisnisnnotnenough. ● Whatnarenthencomponentsnofnprimarynhemostasis?
● ActivatednbynLARGEninjuriesntonbloodnvessels. ● Whatnarenthencomponentsnofnsecondarynhemostasis?
● Delayed,nlong-termnresponse. ● Thisnisnalsontermednasnthenprimarynhemostaticnplug.
● Thisnisnalsontermednasnthensecondarynhemostaticnplug.
COMPONENTS ● Whatnisnthenimportancenofnfibroblastsninnthenvascula
rnintima?
● Coagulationnfactors
● Whatnisnthenfactornthatnpreventsnfibrinnclotnfromnbreaking?
○ Promotesncoagulation;nprocoagulants.
● Itnisnthenlastnstagenofncoagulation.
● Coagulationninhibitors
○ Preventsnanynunwantednclotnformation.
MECHANISM
1. Interactionnofncoagulationnfactorsntonproducenanfibrin
nclotn(secondarynplateletnplug).
○ InducednbynCoagulationnFactornI
○ Thrombinn→nultimate/needednproteinntonconvert
nfibrinogenntonfibrin.
2. FibrinnStabilization
○ FactornXIIIn→npreventsnfibrinnclotnfromnbreaking.
2 RAMOS
, MEGAKARYOCYTOPOIESIS PART I n n
HEM_112:nHEMATOLOGYn2nLECTUR
En(PRELIMINARY)
SirnJomarnAdamsnGanding,nRMT
OUTLINE ● MegakaryocytopoiesisnPathway
I. Megakaryocytopoiesis ○ HematopoieticnStemnCelln(Pluripotent)n→nCommon
A. Definitionnofnterms nMyeloidnProgenitorn(Multipotent)n→
B. Sitenofnorigin Megakaryocyte-ErythrocytenProgenitorn–nCFU-
II. Stagesn n of Development GEMMnxnThrombopoietinn→nMegakaryoblastn(Precur
A. ProgenitornCells sor)
B. Megakaryoblast
● “Nakadependensanhormonen(TPO/EPO)nkungnanong
C. Promegakaryocyte
nprecursorncellnangnmapo-produce”n-nJAnGanding
D. Megakaryocyte
III. Thrombocytopoiesis
IV. Platelets NOTE:nPluripotentnvsnMultipotent
V. HormonesnandnCytokinesnofnMegakaryopoiesis ○ Pluripotentn-
ngeneratesncellsnofnallnlineagesn(ex.nHSCn-
NOTE:nThencontentsnofnthisnreviewernisnmostlynfromntheninstructor’ ncommitsntonanspecificnlineageneithernCMPnornCLP)
snlecture.nPleasenreadnRodak'snHematologyn6thnEditionnfornanm ○ Multipotentn-
orendetailednstudy.nThanknyou!
ndividesnintondifferentncellsn(ex.nCMPndifferentiat
esnintonWBCs,nRBCs,n&nPlatelets)
MEGAKARYOCYTOPOIESIS
● IsnitndifferentnfromnMegakaryopoiesis?nNO,nbothntermsnare
STAGESnOFnDEVELOPMENT
nthensame.
● Innthisnportion,nthendifferentnstagesnofnMegakaryopoiesisna
● ThenproductionnandndevelopmentnofnanMegakaryocyte.
rentranscribed,nfromnthenprogenitorsntonthenprecursorsnandn
○ Takennote:nMegakaryocytesnarendifferentnfrom
thenundifferentiatedntonthendifferentiated.
nThrombocytes.
MEGAKARYOCYTEnPROGENITORS
BONEnMARROW
● Sitenofnoriginnfor:
NOTE:nThenCFU-GEMMnwillngivenrisentonthenMegakaryocyte-
○ Megakaryocytopoiesisn- Erythrocyten ProgenitornwhichnwillnreactnwithnTPO,nMeg-CSF,nandnIL-
nproductionnofnMegakaryocytes. 3ntondevelopninton BFU-
○ Thrombocytopoiesisn-nproductionnofnplatelets. Meg.nThenordernofnsucceedingncellsnarenfromnleastntonmostnmature.
● WherenmaturenMegakaryocytesnarenlocalizedninnthenalb ● BurstnFormingnUnitn-nMegakaryocyten(BFU-Meg)
uminalnsurfacen ornnon- ○ Dividesnintonhundredsnofndaughterncells.
bloodnsurfacenofnthensinusoidnliningnendothelialncellsn→ni ○ Undergoesnmitoticndivision.
nnpreparationnfornplateletnshedding. ● ColonynFormingnUnitn-nMegakaryocyten(CFU-Meg)
○ Dividesnintondozensnofndaughterncells.
○ Undergoesnmitoticndivision.
● LightnDensitynCFUn-nMegakaryocyten(LD-CFU-Meg)
○ Unablentondividenbynmitosis
○ Undergoesnendomitosisn-
nanformnofnmitosisnthatnlacksntelophasenandncytokinesi
sn(separationnintondaughterncells).
○ Megakaryocytesndiscontinuentongrow.
○ WillnemployntheirnmultiplenDNAncopiesntonsynthesize
nabundant/largerncytoplasm,nwhichnultimatelyndiffer
entiatesnintonplatelets.
1 RAMOS
