st thromb embo shock dic ttp hus 09

7/31/2019 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

st thromb embo shock dic ttp hus 09

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