Thrombosis, Embolism, Infarction

Thrombosis

An inappropriate activation of normal haemostatic processes, such as formation of a thrombus in uninjured vasculature or thrombotic occlusion of a vessel after relatively minor injury.

Thrombus

Solid mass formed within the vascular system (blood vessel or cardiac chamber) in life from the constituents of flowing blood.

Thrombi have laminations called what

Lines of Zahn

How do lines of Zahn form

Lines of Zahn are produced by alternating pale layers of platelets admixed with fibrin and darker layers containing more red cells.

3 primary influences predisposing to thrombus formation according to Virchow’s triad

1. Endothelial injury

2. Alteration of blood flow (stasis, turbulence)

3. Blood hypercoagulability.

What can cause endothelial injury

hypertension

scarred heart valves

atheroma

cigarette smoke

(shear stress)

Give 2 examples of alteration in blood flow & what problems they cause

Stasis → development of venous thrombi

Turbulence → endothelial injury, forms countercurrents & local pockets of stasis

2 causes of stasis

Inactivity

Mitral valve stenosis → left atrial dilatation

Cause of turbulence

Aneurysms

Superficial venous thrombi rarely embolise but may lead to what

varicose ulcers

Risk factors for Venous thrombi

immobilisation (e.g. longhaul travel)

post-surgery

OCP

smoking

advanced age

obesity

cancer

pregnancy

inherited

thrombophilia

Most common sites of Arterial thrombi

coronary, cerebral, & femoral arteries

Arterial thrombi are usually superimposed on what

Usually superimposed on an atherosclerotic plaque, but also superimposed on other vascular injury (e.g. vasculitis, trauma).

True/False Arterial thrombi rarely embolise

True

Cardiac thrombi (mural thrombi) most commonly occur after what

• atrial fibrillation

• after an MI

Is there a risk of embolism with cardiac thrombi

Yes - They may embolise to brain, peripheral arteries, spleen

What are Vegetations

Thrombi which form on cardiac valves. These thrombi may contain bacteria (=bacterial endocarditis) or be sterile (e.g. in acute rheumatic fever).

3 possible fates of a thrombus

Name 7 types of emboli

1. Thromboembolus: Virtually 99% of all emboli represent some part of a detached thrombus.

• Pulmonary thromboembolus

• Systemic thromboembolus

2. Fat/bone marrow embolus

3. Air/nitrogen embolus

4. Cholesterol embolus

5. Amniotic fluid embolus

6. Tumour embolus

7. Foreign matter, e.g. talc in IV drug abusers

>95% of pulmonary thromboembolism cases originate where

Above-knee DVTs

What % of pulmonary thromboembolisms are silent

60-80% are clinically silent because they are small

What is a Saddle embolus & what does it lead to

Large pulmonary embolism (PE) which impacts across the bifurcation of the pulmonary arteries → sudden death due to acute right heart failure

Multiple small emboli: can embolise off a single large mass. What can this lead to?

pulmonary haemorrhage or pulmonary infarction

Multiple emboli over time lead to

pulmonary hypertension and chronic right heart failure

Treatment of DVT/PE (3)

• LMW heparin & oral anticoagulant

• Thrombolytic therapy in PE with haemodynamic instability

• IVC filter (right) indicated if contraindication to/failure of anticoagulation

Where would you find Systemic thromboembolus

Within the arterial circulation

Systemic thromboembolus can lead to what

Infarction

80% of systemic thromboembolus arise from what kind of thrombus

80% arise from intracardiac mural thrombi

Other than intracardiac mural thrombi, what do systemic thromboemboli arise from

Aortic aneurysm

Atherosclerotic plaque fragments (Cholesterol emboli)

Valvular vegetations (endocarditis)

Rarely – paradoxical embolus

Up to 10% - unknown

The majority of intracardiac mural thrombi occur as a result of what 3 things

LV infarction

Atrial dilation

Atrial fibrillation

What is a paradoxical embolism & how does it happen

Normally, venous clots travel to the lungs → pulmonary embolism.

A paradoxical embolism occurs when a venous clot enters the arterial circulation, potentially causing stroke, MI, or limb ischemia.

This can only happen if there is a patent foramen ovale

How does a Fat/bone marrow embolus occur

Fat globules enter the bloodstream through tissue (usually bone marrow or adipose tissue) that has been disrupted by trauma

Occurs after fractures of long bones, e.g. femur.

How long after fracture of long bone & with what signs do fat/bone marrow embolus patients present

Presents 1-3 days after injury.

Classic triad – hypoxemia, neurologic abnormalities, petechial rash

Treatment of Fat/bone marrow embolus

Management is supportive (stabilise patient)

Mortality rate of a fat/bone marrow embolus

5-15%

Two conditions necessary for an air embolus to occur

1. direct communication between a source of air and the vasculature

2. pressure gradient favouring the passage of air into the circulation rather than bleeding

Give 3 examples of what could cause an air embolus

surgical procedures

intravenous catheterisation

trauma

barotrauma (divers come up too quick → alveolar rupture & tearing of pulmonary veins)

How many ml of air do you need to have a clinical presentation of an air embolus

>100 ml

What can cause an air embolism

Decompression sickness (“the bends”) in divers, also patients requiring positive pressure ventilation.

Rapid ascent can result in expansion of gas in the lungs, alveolar rupture and tearing of pulmonary veins. Alternatively, air bubbles may form in the venous system during ascent

Amniotic fluid embolisms have a high/low prevalence & a high/low mortality rate

Very rare, but has mortality of 20-90%

In an amniotic fluid embolism, how does the amniotic fluid enter the maternal circulation

Amniotic fluid enters the maternal circulation through the endocervical veins, the placental insertion site, or a site of uterine trauma

Signs of amniotic fluid embolism

Precipitates cardiogenic shock

Respiratory failure

Inflammatory response

Ischaemia

Restriction in blood supply (from either reduced arterial flow or reduced venous drainage) which causes oxygen deprivation and results in tissue damage.

Can cell injury due to ischaemia be reversible

Only if blood flow is restored

Reperfusion injury

Cells proceed to die after blood flow resumes after ischemic injury

How do reperfusion injuries happen

1. Re-oxygenation increases generation of oxygen free radicals causing new damage

2. Production of cytokines recruits circulating neutrophils to reperfused tissue resulting in inflammation.

Infarction

An area of ischaemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue.

Almost always due to arterial occlusion

If infarction is generally caused by arterial occlusion, what does venous thrombosis usually cause

Venous thrombosis more often induces venous obstruction and congestion rather than infarction

What is the exception to this: Venous thrombosis more often induces venous obstruction and congestion rather than infarction

organs with a single venous outflow channel, e.g. testis or ovary

Name & differentiate between the 2 types of infarcts

Red infarcts

• Seen with venous occlusions (testis/ovary)

• Seen in loose tissues (lug) which allow blood to collect in infarcted zone

• Seen in tissues with dual circulations (lung/liver) allowing flow of blood from the unobstructed vessel into the necrotic zone

White infarcts

• Seen in arterial occlusions or solid organs (heart/spleen/kidney)

• Solidity of the tissue limits the amount of haemorrhage that can seep into the area

All infarcts tend to be what shape

All infarcts tend to be wedge-shaped, with the occluded vessel at the apex and the periphery of the organ forming the base

The dominant histologic characteristic of infarction is …

ischaemic coagulative necrosis

What are septic infarcts & how do they occur

The infarct gets converted into an abscess

These occur when embolisation occurs by fragmentation of a bacterial vegetation from a heart valve or when microbes seed an area of necrotic tissue.