EXPLANATION OF THROMBOSIS AND EMBOLISM xx.pdf

Linical ThromboEmbolism

1. THROMBOSISAND
EMBOLISM
DRIJEOMAOKWUDIRE-EJEH
LECTURERANDCONSULTANTANATOMICPATHOLOGISTDEPARTMENT
OFANATOMICPATHOLOGYANDFORENSICMEDICINECOLLEGEOF
HEALTHSCIENCES
NILEUNIVERSITYOFNIGERIA,ABUJA

2. THROMBOSISANDEMBOLISM
HAEMOSTASIS
•Haemostasisisapreciselyorchestratedprocess
involvingplatelets,clottingfactors,and
endotheliumthatoccursatthesiteofvascular
injuryandculminatesintheformationofablood
clot,whichservestopreventorlimittheextent
ofbleeding.

3. •Abnormalitiesofhaemostasisaredividedinto
haemorrhagicdisordersandthrombotic
disorders
Sequenceofeventsleadingto
haemostasis•Arteriolarvasoconstriction
–reflexneurogenicmechanismandlocalsecretionof
vasoconstrictors
•Primaryhaemostasis
–formationofplateletplugduetocontactwith

4. subendothelialvonwilibrandsfactor(vWF)andcollagen•
Secondaryhaemostasis
–depositionoffibrinduetoactivationofcoagulation
cascadebytissuefactor(TF)exposedinthe
subendothelium
•Clotstabilizationandresorption
–viacounter-regulatorymechanisms(e.gtissueplasminogen
activator,t-PA)
•Arteriolarvasoconstriction

5. reflexneurogenic
mechanism
andlocal
secretionof
vaso
constrictors

7. formationofplateletplugduetocontactwithsubendothelialvon
wilibrandsfactor(vWF)andcollaen

9. depositionoffibrinduetoactivationofcoagulationcascadeby
tissuefactor(TF)exposedinthesubendothelium

11. viacounter-regulatorymechanisms(e.gtissueplasminogen
activator,t-PA)
ROLEOFTHROMBININ
HAEMOSTASIS

13. HAEMOSTASIS…Factorsthatlimit
coagulation•Dilution
•Absenceofnegativelychargedphospholipids
beyondsiteofinitiation
•Endothelialcounter-regulatoryeffects•
Fibrinolysis
–largelyaccomplishedbyplasminwhichisderived
fromplasmaplasminogen
•plasminogenisenzymaticallyconvertedby

14. plasminogenactivators(e.gt-PA)synthesizedby
endothelium

16. HAEMOSTASIS…Factorsthatlimit
coagulation…•EndothelialAnti-thromboticproperties
–Plateletinhibitoryeffects
•shieldssubendothelialvWFandcollagen,releasesPGI
2,
NO
2,andAdenosinediphosphatase,bindsandmodulates
thrombin
–Anticoagulanteffects
•Shieldscoagulationfactorsfromtissuefactorin
subendothelialspace
•Expressionoffactorsthatopposecoagulationsuchas;

17. thrombomodulin,endothelialproteinCreceptor,heparin
likemolecules,tissuefactorpathwayinhibitor

19. THROMBOSIS
•Thrombosisistheformationofbloodclots
withinintactbloodvesselsorcardiac
chambers
•Primaryabnormalitiesthatleadtothrombosis
–VirchowTriad
•1.Endothelialinjury
•2.Stasisandturbulentbloodflow

20. •3.Hypercoagulabilityofblood
VirchowTriad
VirchowTriad…EndothelialInjury•

21. EndothelialinjuryexposesvWFandtissuefactor•
Endothelialinjuryleadstoplateletactivation
mostespeciallyinthearterialcirculation–In
arteriesbloodflowimpedesclotformation
thereforethrombiinarterialcirculationareplatelet
rich
•Inflammationandothernoxiousstimulimay
shiftthepatternofgeneexpressiononendothelial
cellstoaprothromboticform,calledendothelial

22. activationordsfunction
VirchowTriad…Endothelial
Injury•Causesofendothelialinjury
–Physicalinjury
–Infectiousagents
–Abnormalbloodflow
–Inflammatorymediators

23. –Metabolicabnormalities(homocystinaemia,
hypercholesterolemia)
–Toxinse.gcigarette
VirchowTriad…Endothelial
Injury•Featuresofprothromboticendothelium
–Procoagulantchanges
•Downregulationofthrombomodullinwhich
naturallymodulatestheactivityofthrombin

24. •DownregulationofproteinC
•Downregulationoftissuefactorproteininhibitor
–Antifibrinolyticchanges
•secretionofplasminogenactivatorinhibitor
•Downregulateexpressionoft-PA
VirchowTriad…Alterationofblood
flow•Turbulence
–endothelialinjuryandactivationseenmainlyinarterial

25. andcardiacthrombosis
•Stasis
–mainlyinvenousthrombosis
•Effectsofstasisandturbulence
–Endothelialactivation
–Distortionoflaminarflow
–Preventwashoutofactivatedclottingfactorsand
inflowofclottinfactorinhibitors
VirchowTriad…Alterationofblood

26. flow•Clinicalsettingswithalteredbloodflow
–Ulceratedatheroscleroticplaques
•exposureofvWF,tissuefactor
•turbulence
–Aorticandarterialaneurysm
•stasis
–Acutemyocardialinfarction
•noncontractilemyocardiumanddilatation

27. stasis
VirchowTriad…Alterationofblood
flow•Clinicalsettingswithalteredbloodflow
–Rheumaticmitralvalvestenosis
•leftatrialdilationandfibrillationstasis
–Hyperviscosity
•polycythemiavera
stasisinsmallvessels

28. –Sicklecellanaemia
•stasisinsmallvessels
VirchowTriad…
Hypercoagulability•Hypercoagulability
(akathrombophilia)•Disordersofblood
thatpredisposetothrombosis
–canbeprimary(genetic)orsecondary

29. (acquired)
–importantinvenousthrombosis
VirchowTriad…
Hypercoagulability•1°(genetic)
•Common
–FactorVmutation(ArgtoGlusubstitutioninAA
residue506)
•resistancetoactivatedproteinC

30. –Prothrombinmutation(G20210Anoncoding
sequence)•increasedprothrombinlevels
–IncreasedlevelsoffactorsVII,IX,XIor
fibrinogen(unknowngenetics)
VirchowTriad…
Hypercoagulability•1°(genetic)
•Rare
–AntithrombinIIIdeficiency

31. –ProteinCdeficiency
–ProteinSdeficiency
•VeryRare
–Fibrinolysisdefects
–Homozygoushomocystinuria(deficiencyof
cstathione-snthetase
VirchowTriad…
Hypercoagulability•2°(acquired)

32. •HighRiskforThrombosis
–Prolongedbedrestorimmobilisation
–Myocardialinfarction
–Tissueinjury(surgery,fracture,burn)
–Cancer
–Prostheticcardiacvalves
–DIC
–Heparin-inducedthrompbocytopenia
–Antiphospholipidantibodysyndrome

33. VirchowTriad…
Hypercoagulability•2°(acquired)
•LowerRiskforThrombosis
–Cardiomyopathy
–Nephroticsyndrome
–Hyperestrogenicstates(pregnancy&postpartum)
–Oralcontraceptiveuse
–Sicklecellanaemia

34. –Smoking
–COVID-19vaccination
THROMBOSIS…arterialvs
venous Arterial Venous
Riskfactors Atheroma
Immobility

35. PathogenesisTurbulentflow
Damagedendothelium
Stasis
Hypercoagulability
Symptoms Suddenonset
Slowonset
Complications
Infarction
Arterialembolism
Pulmonary

36. embolism27
THROMBOSIS…
Morphology•All
thrombigrowtowards
theheart
–arterial=retrograde
–Venous=directionofflow
•LINESOFZAHN
–paleplateletandfibrin
depositsalternatingwith

37. darkerredcellrichlayers
canbeseengrosslyand
microscopically
–Theirpresence
distinguishesthrombifrom
postmortemclots
•Thrombiareattachedto
involvedvascularsurface
LINESOFZAHN:paleplateletandfibrindeposits
alternatingwithdarkerredcellrichlayerscanbeseen
grosslyandmicroscopically!
THROMBOSIS…Morphology…
types•Muralthrombi

38. –thrombiinheartchambersandaorticlumen
•Cardiacmuralthrombi
–seeninarrhythmias,dilatedcardiomyopathy,
myocardialinfaction,endomyocardiacinjury
(myocarditis,cathetertrauma)
•Aorticthrombi
–seeninulceratedatheroscleroticplaques,
aneurysmaldilation

39. THROMBOSIS…Morphology…
types•Arterialthrombi
–consistsoffriablemeshworkofplatelets,
fibrin,redbloodcellsanddegenerating
leucocytes
–Sitesinclude
•coronary,cerebralandfemoralarteriesin
thatorder

40. THROMBOSIS…Morphology…
types•Venousthrombi(redcastsorstasis
thrombi)–containsmoreenmeshedRBCwithrelatively
fewplateletsbecausetheyforminsluggishflow–arealso
attachedandhavelinesofZahn–Sitesofvenous
thrombosis
•90%occurinthelowerextremities!
•Othersincludeupperextremities,peri-prostatic

41. plexus,ovarianveins,periuretericveins,andless
commonlyduralsinuses,portalvein&hepaticvein
THROMBOSIS…Morphology…
types•Thrombiofheartvalves
–Infectiveendocarditisinrheumaticfever
–Non-bacterialthromboticendocarditisin
hypercoagulablestates
•Libman-sacksendocarditisinSLE

42. •mitralregurgitation,aorticstenosis,aortic
regurgitation,ventricularseptaldefect,and
complexcongenitalheartdisease
THROMBOSIS…Morphology…
types•POSTMORTEM CLOT
–Canbemistakenfora
venousthrombus
–Itisanunattached
gelatinousmass,with

43. adarkreddependent
portionofsettled
redbloodcellsanda
yellowchickenfat
upperportion
THROMBOSIS…Fateof
Thrombi•Ifpatientsurviveslong
enoughthethrombusmayundergo

44. –Dissolution
–Propagation
–Organizationandrecanalization
–Embolization
Dissolution
•Thethrombusiscompletelyremovedleadingto
completerecanalisation

45. •Occurscommonlyinthesmallveinsofthelower
limbasthevenousintimacontainsmore
plasminogenactivatorthanarterialintima.
•Bygivingstreptokinasewecanenhancethe
processofthrombolysis
•Butitshouldbegivenearlyafterthombosisas
theeffectisgoingtobelessonpolymerisedfibrin
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THROMBOSIS…ClinicalFeatures•

46. Deepvenousthrombiareasymptomaticinabout50%of
casesandmaybecomeapparentonlyafterembolization
•Theycancausepainfulcongestionandoedemadistal
totheobstructionespeciallyinsuperficialvenous
thrombi
•Superimposedinfectionandulcerationmayoccurin
varicoseulcers
•Arterialthrombicancauseinfarctioninaffectedtissues
liketheheartandbraintheycanalsoembolize

47. THROMBOSIS…Clinical
Features

49. EMBOLISM
•Anembolusisadetachedintravascularsolid,
liquid,orgaseousmassthatiscarriedbytheblood
fromitspointoforigintoadistantsite,whereit
oftencausestissuedysfunctionorinfarction
•COMMONTYPESOFEMBOLISM
–Thromboembolism
–Fatandmarrowembolism
–Atheroscleroticdebris(cholesterolemboli)
–Airembolism

50. –Amnioticfluidembolism
–Foreignbodies
PULMONARYEMBOLISM
•Originatefromdeepvenousthrombosis(DVT)and
aremostcommonformofthromboembolicdisease
–Inmorethan95%ofcasespulmonaryembolisms
originatefromDVTs
•ThrombusfragmentsfromDVTstraveltotheright
sideoftheheartandreachthepulmonary

51. vasculature
–Rarely,avenousemboluspassesthroughaninteratrialor
interventriculardefectandgainsaccesstothesystemic
arterialcirculation(paradoxicalembolism)
PULMONARYEMBOLISM
•Dependingonthesizeoftheembolus,itcan:
–occludethemainpulmonaryartery
–straddlethepulmonaryarterybifurcation
(saddleembolus)

52. –passoutintothesmaller,branchingarteries.•
Frequentlyshowersofembolifromasingle
largethrombusoccursequentiallyor
simultaneously
PULMONARYEMBOLISM…
Consequences•Maybeclinicallysilent(60%-80%)-
smallemboli•Mayleadtosuddendeath,rightheartfailure
(cor
pulmonale),orcardiovascularcollapsewhenemboliobstruct

53. 60%ofpulmonarycirculation
•Pulmonaryhaemorrhageincasesofmediumsizedarteries
–Infarctiononlyoccursifbronchialarterialflowis
compromised(e.gleftsidedcardiacfailure)
•Smallendarteriolarobstructionalsoleadstohaemorrhageor
infarction
•Multipleemboliovertimemaycausepulmonaryhypertension
andrightheartfailure
SYSTEMICTHROMBOEMBOLISM•80%
arisefromintracardiacmuralthrombi,2/3rdsofwhich

54. areassociatedwithleftventricularwall
infarctsandtherestwithleftatrialdilatationand
fibrillation
•Othersources
–Aorticaneurysms
–Atheroscleroticplaques
–Valvularvegetations
–Venousthrombi(paradoxicalemboli)
SITESOFARTERIAL

55. EMBOLIZATION•Lowerextremities75%
•Brain10%
•Othersites:intestines,kidneys,spleen,upper
extremities
•Theconsequencesofsystemicembolidependon–
thevulnerabilityoftheaffectedtissuestoischemia–the
caliberoftheoccludedvessel,and
–whetheracollateralbloodsupplyexists

56. –generally,theoutcomeistissueinfarction
FATANDMARROW
EMBOLISM•SeeninFracturesoflong
bones,SofttissuetraumaandBurns
•Maybeofnoclinicalconsequence
•Fatembolismsyndrome
–referstofeaturesseeninsymptomaticpatientsandis
characterizedby:

57. •pulmonaryinsufficiency
•neurologicsymptoms
•anaemia,andthrombocytopaenia
•Itisfatalin5-15%ofcases!

59. BONEMARROWEMBOLUSINPULMONARYCIRCULATION
AIREMBOLISM
•Canbeiatrogenic
–coronarysurgeryorneurosurgeryinsitting
position
•obstructionofcoronaryandcerebral
circulationoccurrespectively
•Inthepulmonarycirculation100ccor

60. moreofairisnecessarytoproduce
clinicaleffects–canoccurinobstetricor
laparoscopicsurgery,or–fromachestwallinury
AIREMBOLISM…Decompressionsickness(Caisson
disease)•Seeninrapiddecreasesofpressuresuchas
indeepseadivesandrapidascentinunpressurized
aircraft
•tissueinfarctioncanoccur!
•Clinicalfeatures

61. –thebends(musculoskeletal)
•fatigueandpaininmusclesandjoints
•moreseveresymptomsincludenumbness,tingling,armor
legweakness,unsteadiness,vertigo(spinning),difficulty
breathing,andchestpain
AIREMBOLISM...Decompressionsickness(Caisson
disease)•Clinicalfeatures…
–thechokes(thelungs)

62. •ararebutgravemanifestation!!
–symptomsincludeshortnessofbreath,chest
pain,cough,duetopulmonaryoedema
–Massivebubbleembolizationofthe
pulmonaryvasculartreecanresultinrapid
circulatorycollapseanddeath
AMNIOTICFLUID
EMBOLISM•Acommoncauseofmaternal

63. mortality
–Mortalityisupto80%,&majorityofsurvivorssufferneurologic
deficit
–Occursduringlabororpost-partum
–Manifestationsarisemainlyfrombiochemicalactivationof
coagulationfactorsandinnateimmunesystembysubstancesin
amnioticfluid
•Clinicalfeatures
–Suddenonsetofdyspnoea,cyanosisandshock
–Headache,seizuresandcomamayfollow
–Ifpatientssurvive,pulmonaryoedemafrequentlyaccompaniedby

64. DICmayfollow

66. AMNIOTICFLUIDEMBOLISM
SEPTICEMBOLISM
•Embolismthatisinfectedwithbacteria•May
befataljustasanyembolus
•CommonlycausedbyFusobacterium
necrophorum(gram–ve,Anaerobicbacillus)
•Usuallyoriginatesfromextrapulmonary
locations–InfectedIVaccess(thrombophlebitis)
–Tricuspidvalveendocarditis

67. –InfectedDVT
–Infectedcatheters
–Periodontaldisease
THANKYOU!
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