Download - ST Thromb Embo Shock DIC TTP HUS 09
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Normal hemostasis
Thrombosisfactors, morphology
EmbolismShock
DIC
TTP,HUS
Doc. MUDr. L. Boudov, Ph. D.
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Hemostasisnormal vessels
maintain blood fluid, clot-freevessel injury
induce rapid localized hemostatic plug
Thrombosis
inappropriate activation of normal
hemostatic processes
Vascular wall, platelets, coagulation cascade
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EndotheliumNormal: antithrombotic
1. Anticoagulant - heparin-like moleculesthrombomodulin
2. Antiplateletbarrier between plt and ECM;PGI2, NO, ADPase
3. Fibrinolytict-PA
Injured, activated: prothrombotic
1. Procoagulanttissue factor
2. Platelets - vWF
3. Antifibrinolytic - PAI
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ThrombosisVirchow's 3
Alteration of:1. Vessel wall - endothelial injury - dominant
2. Blood flow- stasis, turbulence
3. Bloodhypercoagulability
may combine
intravital
intravascular
clotting
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1. Vessel wallendothelial injurydominant
exposure of subendothelial collagen
+ adherence of plateletsexposure of tissue factor, local depletion
of prostacyclin and plasminogen activator
Atherosclerosisulceration Necrosismyocardial infarction
Trauma
Inflammationvasculitis Hypertension, turbulent flow, bact. endotoxins
Homocystein, cholesterol, radiation, smoking
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2. Alterations in normal blood flow
Normal = laminar
Turbulencearteries, heart;
combined turb. + stasis (endot. injury + stasis)
Stasisveins, heart
Ulcerated atherosclerotic plaquesendot. +turb.
Aneurysmslocal stasisMitral valve stenosisstasisleft atrial dilation
Hyperviscosity syndromespolycythemia; sickle
cell anemia (occlusions stasis; small vessels)
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3. Hypercoagulability
Primary (genetic)
Mutations in factor V = Leiden mutation
2-15% of popul. APC resistanceantithrombin III, protein C, S deficiencies
fibrinolysis def., hyperhomocysteinemia
prothrombin levels - 1%, allelic variations Thrombo(embolism)recurrent, young,
no or insignificant other causes
Secondary (acquired) -high risk or low risk
Any alteration of coagulation pathway
predisposing to thrombosis
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3. Hypercoagulability
Secondary (acquired)
High risk of thrombosis -immobilization, myoc.infarction, tissue damage (trauma, burns,
surgery), cancer, prosthetic cardiac valves, DIC,
heparin-induced thrombocytopenia,antiphospholipid antibody syndrome (with/out
autoimmune dis. - SLE)
Lower risk of thrombosis -atrial fibrillation,
cardiomyopathy, nephrotic syndrome,
hyperestrogenic states, oral contraceptives (3x),
pregnancy (8x), sickle cell anemia, smoking
Thrombotic diathesis - often complicated, multifactorial
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Thrombi
- overview of morphology, localisation
relationship to the vessel wall, lumen
mural OR occlusive; line of attachment
localization
anywhere - heart (chambers, valves), arteries,
veins, capillariessizes, shapes, components (colours)
red, white, mixed (coral), hyaline
mechanismarteries, heart: endothelial injury, turbulence
veins: stasis
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Thrombi
Localization - detailed
Arterialocclusive; mixed
coronary, cerebral, femoral
atherosclerosis, vasculitis, traumaVenousocclusive, long cast; red; 90% legs
autopsy dif. dg. postmortem clot
Heartvalvesvegetationsinfective or sterile (rheum., NBTE, SLE)
Heart chambers, aneurysms of heart or aorta
Mural; infarction; embolisation: brain, kidney, spleen
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Further fate of thrombi
1.Propagation
2. Dissolution - fibrinolysis3. Organization and recanalization; fibrosis
4. Enz. digestionPuriform. degen.
5. !Embolization!6. Calcification
1
2 35
7.Infection
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Clinical significance of thrombosis1. Vascular obstruction (mainly arteries)
2. Source of embolism (mainly veins)
Veins: mainly lower extremities
Spf.: trophic changes - cong., edem., pain; ulcersDeep: 50% asympt.! thromboembolism!
Regardless specific clinical setting: high age
immobilization
!high risk of venous thrombosis!
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Embolisma detached intravascular mass
- solid, liquid, gaseouscarried by the blood to a site distant from its origin
Thrombus99%
Fat
Gas
Fluidamniotic;
Atherosclerotic debris, tumor fragments, foreign bodies
VASCULAR BLOCK
(ISCHAEMIAINFARCTION)
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SOURCE: DEEP LEG VEIN THROMBI
ABOVE THE KNEE
Clinical manifestation
1. Clin. silent (75%), organization, fibrous bridging
web
2. Acute cor pulmonalesudden death (60% circ.)
3. Pulmonary hemorrhage/infarction4. Pulmonary hypertension (multiple emb.)
Pulmonary thromboembolism
Saddle embolus
Paradoxical embolism
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Systemic thromboembolismEmboli travelling in the syst. arterial circulation
SOURCE: intracardiac mural thrombi (80%)
aort. aneurysms, atherosclerotic plaques,
valvular vegetations; paradoxical emboli RECIPIENTS: various
legs (75%), brain (10%), intestines, kidneys,
spleen, upper extr.
CONSEQUENCES: collateral blood supply,
tissue vulnerability to ischaemia, size of theoccluded vessel MAINLY INFARCTION
F b li
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Fat embolism fractures of long bones, soft tissue trauma, burns
90% of people with severe skeletal injuries
only 10% symptomatic
sudden onset: tachypnea, dyspnea, tachycardia,neurol. symptoms, petechiae; (thrombo, ery )
mechanical and biochemical injury
may be lethal
HISTOLOGICAL DIAGNOSIS ?
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Air embolismGas bubbles
Obstetric procedures
Dural venous sinuses Neck, chest wall trauma
Decompression sickness -nitrogen bubbles
focal ischemia:
muscles, jointsbends; brain, heart;
lungs - RDS (chokes)
treatment: compression chamber Chronic decompression sicknesscaisson disease
persistence of gas embolimultiple foci of ischemicnecrosis(heads of femur, tibia, humerus)
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Amniotic fluid embolism
Rare but ! High mortality
Mechanism: amniotic fluid in maternal circulationHow: tear in the placental membranes, rupture ofuterine veins
Mother: lungs: diffuse alveolar damagecapillaries: epithelial squamous cells from fetal skin,lanugo hair, fat from vernix caseosa, mucin from fetalrespiratory tract and GIT
Clinically: sudden; severe dyspnea, cyanosis,hypotension, shock, seizures, coma; pulmonary edema,DIC (thrombogenic substances from amnioticfluid);death
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SHOCKSystemic hypoperfusion
caused by reduction of cardiac output
effective circulating blood volume
hypotension, hypoperfusion, hypoxia
Cellular injury: first reversible
if persistence of shock - irreversible
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1. Cardiogenicpump failure (intrinsic myoc.
causeIM, ventr. arrhytmias, extrinsiccompressiontamponade, outflow obstr.- emb.)
2. Hypovolemic - loss of blood or plasma
(hemorrhage, burns, trauma)3. Septicsystemic microbial infection
(G- endotoxic, G+, fungal)
4. Neurogenicspinal cord injury - VSD
5. Anaphylacticgener. IgE-med. response, VSD,
vascular permeability vascular bed
capacitance
SHOCK
P h i f i h k
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Pathogenesis of septic shockMost G-, endotoxinslipopolysaccharides
Mononuclear cell activation, cytokines (IL-1, TNF)
Isolate microbes, activate immune system,
eradicate microbes but also! further aggravation
cytokines and secondary mediators:
systemic VSD - hypotension,myoc. contractility,
endothel. injury, RDS, coagulation disorder DIC
multiorgan system failure
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Stages of shock
1. Nonprogressiveneurohumoral compensatory
mechanisms, vital organ perfusion
2. Progressivetissue hypoperfusion, anaerobicglycolysis, lactate acidosis, VSD, cardiac
output, anoxic injury of endothelium, DIC risk;
vital organs begin to fail3. Irreversiblelysosomal enzyme leakage
M h l f h k
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Morphology of shock
Hypoxic injury, multiple organ systems
Brain - ischemic encephalopathy
Heart - coagulation necrosis, hemorrhageKidneys - acute tubular necrosis
Lungs - shock lung (normally resistant to hypoxia)
Adrenals - cortical lipid depletionGIT - hemorrhages and necroses
Liver - fatty change, central hemorrhagic necrosis
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secondary complication
of some serious condition
consumption coagulopathy
thrombohemorrhagic diathesis
acute, subacute, chronic
Disseminated intravascular
coagulation (DIC)
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Disseminated intravascular
coagulation (DIC)
activation of coagulation sequence
microthrombi
- consumption of platelets and clotting factors
activation of fibrinolysissecondary
DIC
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DICThrombotic andhemorrhagic diathesis
Microthrombi infarctions
depletion of platelets and clotting factors
+ secondary activation of fibrinolysis
hemorrhages
Consequences
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Mechanisms of DIC trigger
1. Release of tissue factor
or thromboplastic substances
2. Widespread endothelial injury
DIC
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DIC
1.obstetrics50%; abruptio placentae, retaineddead fetus, septic abortion, amniotic fluid
embolism, toxemia
2. neoplasms30%; adenocarcinomas, AML3.infectionsgram-negative sepsis
4.trauma, burns, extensive surgery
5.othersnakebite, heat stroke, giant
hemangioma, aortic aneurysm etc.
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DIC Morphology microthrombi
kidneys hemorrhages
lungs
brain
adrenals
placenta
CLIN.: microangiopathic hemol. anemia,
RDS, neurologic sympt., oliguria, ac. ren.
and circul. failure, SHOCK
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Thrombotic microangiopathies
thrombotic thrombocytopenic purpura (TTP)
hemolytic-uremic syndrome (HUS)
Versus
Disseminated intravascular coagulation
Common: hyaline thrombi
!!Differences:DIC: primary importance:
activation of clotting system
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Thrombotic microangiopathiesrelated clinical syndromes
thrombotic thrombocytopenic purpura (TTP)hemolytic-uremic syndrome (HUS)
ENDOTHELIAL INJURYWIDESPREAD HYALINE MICROTHROMBI
OVERLAP - common features (TTP, HUS):
thrombocytopenia microangiopathic hemolytic anemia
fever
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Thrombotic microangiopathies
TTP
neurological deficits(transient)
renal failure
adult women
ADAMTS 13 defic.
HUS
mostly no neurol. sympt.acute renal failure
DOMINANT!children; E. coli O157:H7,verotoxin
Common: thrombocytopenia, microangiopathic
hemolytic anemia, fever