Thrombosis and Embolus Flashcards
What distinguishes a thrombus from a postmortem clot?
- Lines of Zahn
- Attachment to vessel wall
What do layers of Zahn look like on histology?
Lines of RBCs and fibrin
What is Virchow’s triad?
- Endothelial injury
- Stasis
- Hypercoguable state
WHat does the endothelium produce to reduce risk of thrombosis?
- 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
What does endothelial damage cause?
- Atherosclerosis
- Vaculitis
- High levels of homocysteine (B12 and folate also increase these levels slightly)
What does can an increased homocysteine level cause?
- Thrombosis
- Homocystinuria
CBS deficiency (Cystathionine beta synthase)
- Thrombosis
- Mental retardation
- Lens discolouration
- Long slender fingers
What does CBS (Cystathionine beta synthase) do?
Converts homocysteine to cystathionine
What are the characteristic signs of a inherited hypercoagulable disorders?
- Recurrent DVTs
- DVTs at young age
- Thrombosis in hepatic or cerebral veins
What type of adverse drug reaction are individuals with a protein C or S deficiency at risk of?
Warfarin skin necrosis
What does vitamin K epoxide reductase activate?
Vitamin K
What does vitamin K activate?
- Factors II, VII, IX, X
- Protein C and S
How does warfarin cause warfarin skin necrosis?
- 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
What medication is given with warfarin?
Heparin - to reduce the risk of thrombus formation - warfarin skin necrosis
What is factor V Leiden?
Mutated factor V that lacks cleavage site for deactivation by proteins C and S
What is prothrombin 20210A?
- Point mutation in prothrombin
- Results in increased gene expression
- Promotes thrombus formation
What is ATIII deficiency?
- Decreases protective effect of heparin-like molecules produced by endothelium, increasing the risk of thrombus
What happens when patients with AT3 deficiency are given heparin?
- PTT does not rise with standard dosing - high doses are needed to activate limited supply
- Warfarin is given after to maintain hypercoagulable state
What does estrogen increase the production of/
Coagulation factors
Name the hypercoagulable disorders?
- Protein C or S deficiency
- AT3 deficiency
- Factor V Leiden (most common)
- Prothrombin 20210A
What are the different types of embolus?
- Thromboembolus (~95%)
- Atherosclerotic embolus (due to plaque that dislodges)
What is a characteristic finding in atherosclerotic emboli?
Presence of cholesterol clefts (crystals) in the embolus
When would a patient get a fat embolus?
- After bone fractures (long bones) and soft tissue trauma
- Develops while fracture is still present or shortly after repair
What is a characteristic finding in a patient with a fat embolus?
Dyspnea and petechiae on the skin overlying the chest
- Circular white spaces in lumen on histology
Where else will there be pain in patients with a gas emboli?
Joint and muscle pain (the bends) as well as resp symptoms
What is the chronic form of decompression sickness?
Caisson disease
- Mutifocal ischemic necrosis of bone
- Chronic nitrogen emboli
When else other than from decompression can a patient get a gas embolus?
- Laproscopic surgery
What are the characteristic symptoms of an amniotic fluid embolus?
- During labour or delivery
- SOB, Neurological symptoms
- DIC (due to tissue thromboplastin in amniotic fluid)
- Squamous cell and keratin debris in amniotic fluid
Why are PEs often clinically silent?
- Lung has dual blood supply
- Embolus is usually small and self-resolves
How many PEs cause infarction and what may this be due to?
- ~10%
- Obstruction of large or medium sized artery with pre-existing cardiopulmonary compromise
What are the clinical features of PE?
- 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
What will a PE show on imaging?
- Hemorrhagic
- Wedge shaped infarct
How may a PE cause sudden death?
- Large saddle embolus or significant occlusion of a large pulmonary artery
- Death due to electromechanical dissociation
How can emboli cause pulmonary hypertension?
Chronic emboli may reorganise over time
What is the source of most systemic emboli?
Arise in the left heart
- Travel down systmeic circulation to occlude flow to organs, most commonly lower extremities
