Thrombosis and Embolus

Question 1

What distinguishes a thrombus from a postmortem clot?

Answer 1

• Lines of Zahn

- Attachment to vessel wall

Question 2

What do layers of Zahn look like on histology?

Answer 2

Lines of RBCs and fibrin

Question 3

What is Virchow’s triad?

Answer 3

• Endothelial injury
• Stasis
• Hypercoguable state

Question 4

WHat does the endothelium produce to reduce risk of thrombosis?

Answer 4

• PGI2 (prostaglandin I2) - blocks platelet aggregation
• NO - vasodialtion
• Heparin-like molecules - activate AT3 (inactivates thrombin)
• tPA
• Thromobomodulin - redirects function of thrombin to activate protein C

Question 5

What does endothelial damage cause?

Answer 5

• Atherosclerosis
• Vaculitis
• High levels of homocysteine (B12 and folate also increase these levels slightly)

Question 6

What does can an increased homocysteine level cause?

Answer 6

• Thrombosis
• Homocystinuria

CBS deficiency (Cystathionine beta synthase)

• Thrombosis
• Mental retardation
• Lens discolouration
• Long slender fingers

Question 7

What does CBS (Cystathionine beta synthase) do?

Answer 7

Converts homocysteine to cystathionine

Question 8

What are the characteristic signs of a inherited hypercoagulable disorders?

Answer 8

• Recurrent DVTs
• DVTs at young age
• Thrombosis in hepatic or cerebral veins

Question 9

What type of adverse drug reaction are individuals with a protein C or S deficiency at risk of?

Answer 9

Warfarin skin necrosis

Question 10

What does vitamin K epoxide reductase activate?

Answer 10

Vitamin K

Question 11

What does vitamin K activate?

Answer 11

• Factors II, VII, IX, X

- Protein C and S

Question 12

How does warfarin cause warfarin skin necrosis?

Answer 12

• Proteins C and S are degraded first, before the clotting factors
• This causes an increased risk of thrombus as factors 2,7,9,10 are increased relatively

Question 13

What medication is given with warfarin?

Answer 13

Heparin - to reduce the risk of thrombus formation - warfarin skin necrosis

Question 14

What is factor V Leiden?

Answer 14

Mutated factor V that lacks cleavage site for deactivation by proteins C and S

Question 15

What is prothrombin 20210A?

Answer 15

• Point mutation in prothrombin
• Results in increased gene expression
• Promotes thrombus formation

Question 16

What is ATIII deficiency?

Answer 16

• Decreases protective effect of heparin-like molecules produced by endothelium, increasing the risk of thrombus

Question 17

What happens when patients with AT3 deficiency are given heparin?

Answer 17

• PTT does not rise with standard dosing - high doses are needed to activate limited supply
• Warfarin is given after to maintain hypercoagulable state

Question 18

What does estrogen increase the production of/

Answer 18

Coagulation factors

Question 19

Name the hypercoagulable disorders?

Answer 19

• Protein C or S deficiency
• AT3 deficiency
• Factor V Leiden (most common)
• Prothrombin 20210A

Question 20

What are the different types of embolus?

Answer 20

• Thromboembolus (~95%)

- Atherosclerotic embolus (due to plaque that dislodges)

Question 21

What is a characteristic finding in atherosclerotic emboli?

Answer 21

Presence of cholesterol clefts (crystals) in the embolus

Question 22

When would a patient get a fat embolus?

Answer 22

• After bone fractures (long bones) and soft tissue trauma

- Develops while fracture is still present or shortly after repair

Question 23

What is a characteristic finding in a patient with a fat embolus?

Answer 23

Dyspnea and petechiae on the skin overlying the chest

- Circular white spaces in lumen on histology

Question 24

Where else will there be pain in patients with a gas emboli?

Answer 24

Joint and muscle pain (the bends) as well as resp symptoms

Question 25

What is the chronic form of decompression sickness?

Answer 25

Caisson disease

• Mutifocal ischemic necrosis of bone
• Chronic nitrogen emboli

Question 26

When else other than from decompression can a patient get a gas embolus?

Answer 26

• Laproscopic surgery

Question 27

What are the characteristic symptoms of an amniotic fluid embolus?

Answer 27

• During labour or delivery
• SOB, Neurological symptoms
• DIC (due to tissue thromboplastin in amniotic fluid)
• Squamous cell and keratin debris in amniotic fluid

Question 28

Why are PEs often clinically silent?

Answer 28

• Lung has dual blood supply

- Embolus is usually small and self-resolves

Question 29

How many PEs cause infarction and what may this be due to?

Answer 29

• ~10%

- Obstruction of large or medium sized artery with pre-existing cardiopulmonary compromise

Question 30

What are the clinical features of PE?

Answer 30

• SOB
• Hemoptysis, pleuritic chest pain, pleural effusion
• V/Q mismatch
• Spiral CT shows a vascular filling defect in the lung
• Elevated d dimer
• Doppler US in leg

Question 31

What will a PE show on imaging?

Answer 31

• Hemorrhagic

- Wedge shaped infarct

Question 32

How may a PE cause sudden death?

Answer 32

• Large saddle embolus or significant occlusion of a large pulmonary artery
• Death due to electromechanical dissociation

Question 33

How can emboli cause pulmonary hypertension?

Answer 33

Chronic emboli may reorganise over time

Question 34

What is the source of most systemic emboli?

Answer 34

Arise in the left heart

- Travel down systmeic circulation to occlude flow to organs, most commonly lower extremities