Thromboembolism Flashcards
(26 cards)
What is a Thrombosis?
- pathological formation of an intravascular blood clot (thrombus) by activating the clotting system
- can occur in artery or vein
- most common location is the deep veins (DVT) of the leg below the knee
What are Lines of Zahn and what do they indicate?
These are microscopic laminations seen in thrombi.
* Composed of:
* Pale layers: platelets and fibrin.
* Dark layers: red blood cells (RBCs).
* Significance: Indicates the thrombus formed in flowing blood, i.e., before death.
What are Antemortem Thrombi?
(Before Death)
* Attached to the vessel wall.
* Dry and friable (easily crumbles).
* Retains shape of the vessel.
* Shows Lines of Zahn (alternate layers of fibrin and platelet)
* Formed due to abnormal blood flow (e.g., stasis, turbulence) and endothelial injury.
What are Postmortem clots?
(After Death)
* Not attached to the vessel wall.
* Appear like “chicken fat” or “currant jelly”:
* Chicken fat: yellow upper part (settled plasma).
* Currant jelly: dark red lower part (settled RBCs).
* No Lines of Zahn.
* Gelatinous, easily break apart.
* Passive process—blood settles after circulation stops.
Clinical Importance:
* Distinguishing thrombus from clot is crucial in autopsy or forensic pathology.
* The presence of Lines of Zahn confirms a thrombus formed before death, helping determine if vascular blockage contributed to death.
* Postmortem clots, in contrast, are incidental and not the cause of death.
What are the 3 things in Virchow’s Triad?
Virchow’s Triad describes the three primary factors that contribute to thrombosis (formation of a blood clot inside a blood vessel). These factors explain why thrombi form and help identify individuals at increased risk for clotting.
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✅ Virchow’s Triad – 3 Major Factors
- Endothelial Injury
- Most important factor in arterial thrombosis.
- Damage to the endothelium (inner lining of blood vessels) exposes subendothelial collagen and tissue factor, triggering platelet adhesion and coagulation.
- Causes include:
- Atherosclerosis
- Hypertension
- Trauma
- Inflammation (e.g., vasculitis)
- Intravascular catheters
- Smoking
- Surgery
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- Abnormal Blood Flow
- Either stasis (slow flow) or turbulence can promote thrombosis.
- Stasis is especially important in venous thrombosis; turbulence can damage endothelium.
- Causes include:
- Atrial fibrillation (irregular heartbeats)
- Immobility (bed rest, long flights)
- Varicose veins
- Aneurysms
- Heart failure
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- Hypercoagulability
- Also called thrombophilia – increased tendency of the blood to clot.
- Can be inherited or acquired.
- Inherited causes:
- Factor V Leiden mutation
- Prothrombin gene mutation
- Protein C, S, or antithrombin III deficiency
- Acquired causes:
- Pregnancy
- Cancer
- Oral contraceptives or hormone replacement therapy
- Antiphospholipid antibody syndrome
- Obesity
- Smoking
- Prolonged immobilization
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🧠 Mnemonic to Remember:
“SHE” helps form clots:
* S: Stasis of blood flow * H: Hypercoagulability * E: Endothelial injury
What is Mural Thrombus?
🔍 Mural Thrombus in the Heart or Aorta
✅ Definition:
* A mural thrombus is a thrombus that adheres to the endocardial (inner) wall of the heart or the intimal wall of the aorta, but does not occlude the entire lumen (space inside the vessel or chamber).
* It is called “mural” because it sticks to the “murus” (Latin for wall).
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❤️ In the Heart:
* Common after myocardial infarction (heart attack)—especially when the ventricular wall becomes akinetic (not moving) or hypokinetic (weakly contracting).
* Blood stagnates in this region, promoting thrombus formation.
* Usually found in the left ventricle.
* Can embolize → cause stroke or systemic infarction.
🩺 Causes:
* Myocardial infarction (MI)
* Dilated cardiomyopathy
* Aneurysms of the ventricular wall
* Arrhythmias like atrial fibrillation (mural thrombus in atrium)
🩸 In the Aorta:
* Most often associated with:
* Atherosclerotic plaques
* Aortic aneurysms
* Trauma or dissection
* These areas disturb normal flow and promote clot adherence to the wall.
🔬 Histology and Morphology:
* May show Lines of Zahn if formed in flowing blood.
* Attached to underlying wall (helps distinguish from postmortem clots).
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⚠️ Clinical Significance:
* Risk of embolization (brain → stroke; limbs → ischemia).
* May require anticoagulation or even surgical removal.
* Important to monitor with echocardiography or CT angiography.
How do endothelial cells prevent Thrombus formations? (anti-thrombotic)
ndothelial cells play a critical antithrombotic role by creating a non-thrombogenic surface and actively inhibiting coagulation and platelet aggregation. Let’s break down these mechanisms in detail for better understanding and retention:
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🛡️ How Endothelial Cells Prevent Thrombosis
✅ 1. Physical Barrier
* Block exposure to subendothelial collagen and tissue factor (TF):
* Intact endothelium hides thrombogenic substances from circulating blood.
* If the endothelium is damaged, collagen and TF become exposed → triggers platelet adhesion and clot formation.
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✅ 2. Vasodilation and Anti-Platelet Action
* Produce prostacyclin (PGI₂) and nitric oxide (NO):
* PGI₂ inhibits platelet aggregation.
* NO causes vasodilation and also inhibits platelet activation.
* Together, they prevent platelets from sticking to the vessel wall and to each other.
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✅ 3. Anticoagulation via Antithrombin Activation
* Secrete heparin-like molecules:
* These molecules enhance the activity of antithrombin III (ATIII).
* ATIII inactivates:
* Thrombin (Factor IIa)
* Factors IXa and Xa
* This slows down the coagulation cascade.
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✅ 4. Fibrinolysis
* Secrete tissue plasminogen activator (tPA):
* tPA converts plasminogen → plasmin.
* Plasmin:
1. Cleaves fibrin → breaks down formed clots.
2. Degrades fibrinogen in circulation.
3. Inactivates coagulation factors.
4. Inhibits platelet aggregation indirectly.
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✅ 5. Regulation of Thrombin Activity
* Secrete thrombomodulin:
* Thrombomodulin binds thrombin and alters its function.
* Instead of promoting clotting, thrombin now:
* Activates Protein C.
* Activated Protein C (with cofactor Protein S) inactivates:
* Factor Va
* Factor VIIIa
* This suppresses further coagulation.
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📌 Clinical Insight
* Loss of these protective functions (due to injury, inflammation, or toxins) shifts the balance toward prothrombotic activity.
* Conditions like atherosclerosis, hypertension, and sepsis can damage endothelium and promote thrombosis.
What does Plasminogen and Plasmin do?
BREAKS DOWN clots
🧼 Plasminogen → Plasmin
* Activated by tPA (tissue plasminogen activator) or urokinase.
* Plasmin’s actions:
* Breaks down fibrin in clots → fibrinolysis.
* Degrades circulating fibrinogen.
* Inhibits clotting by degrading some coagulation factors.
* Clears the clot after the vessel is healed.
What activates Plasminogen to Plasmin?
tPA (tissue plasminogen activator) or urokinase.
What does Prothrombin and Thrombin do?
CREATES clots
Activated by the coagulation cascade. * Thrombin’s actions: * Converts fibrinogen → fibrin → forms the clot scaffold. * Activates platelets. * Amplifies clotting by activating Factors V, VIII, and XI. * Starts clot stabilization.
What is Thrombomodulin?
✅ What is it?
* A transmembrane protein found on endothelial cells.
* It acts as a receptor for thrombin and modifies its function.
⚙️ Function/Activity:
* When thrombin binds to thrombomodulin, it loses its procoagulant function (no more fibrinogen → fibrin).
* Instead, it activates Protein C.
* Activated Protein C (APC) + Protein S → inactivate Factors Va and VIIIa.
* This inhibits further thrombin generation, thereby slowing down the clotting cascade.
📌 Key Point:
Thrombomodulin is a regulator of thrombin, converting it from a clot promoter into an anticoagulant activator.
Thrombomodulin: “Turns thrombin into a peacekeeper” by activating Protein C.
What is tPA (tissue plasminogen activator)?
✅ What is it?
* A serine protease secreted by endothelial cells into the bloodstream.
⚙️ Function/Activity:
* tPA converts plasminogen → plasmin.
* Plasmin breaks down:
* Fibrin clots
* Fibrinogen
* Some coagulation factors
* This is the main pathway for fibrinolysis (clot breakdown).
📌 Key Point:
tPA initiates fibrin breakdown, helping to dissolve clots once they’ve served their purpose.
* tPA: “Sends in the cleanup crew” to remove fibrin clots using plasmin.
What are Primary Hypercoagulable States?
These are genetic disorders that cause an increased tendency to form clots. The person is usually born with a mutation affecting natural anticoagulant or fibrinolytic pathways.
What is Factor V Leiden mutation?
Mutated Factor V is resistant to inactivation by Protein C → increased clotting.
So… protein C can inactivate Factor V to decrease clotting, but this is mutated and ineffective so Factor V persists and clotting still happens.
What is Prothrombin gene mutation (G20210A)?
Increased prothrombin levels → more thrombin → more clotting.
What is Protein C deficiency?
Reduced inactivation of Va and VIIIa → unregulated clotting.
So… protein C would normally inactivate factors V and VIII (5 and 8)
Protein S deficiency?
Cofactor for Protein C is low → reduced anticoagulation.
So…normally Protein C helps with increased coagulation.
What is Antithrombin III deficiency?
Inability to inactivate thrombin and Factor Xa → more clot formation.
What are Secondary Hypercoagulable States?
non-genetic conditions that increase the risk of thrombosis due to external factors or diseases.
Common Causes:
1. Prolonged immobilization or surgery
2. Stasis of blood → clot formation (Virchow’s triad).
3. Pregnancy
4. Increased clotting factors, decreased fibrinolysis.
5. Oral contraceptives or estrogen therapy
6. Increase production of clotting factors.
7. Cancer (Trousseau syndrome)
Tumors produce procoagulant substances.
8. Antiphospholipid antibody syndrome
Autoantibodies promote thrombosis.
9. Nephrotic syndrome
Loss of antithrombin III in urine.
10. Heparin-induced thrombocytopenia (HIT)
Antibodies activate platelets → thrombosis despite low platelet count.
🧠 Mnemonic to Remember Causes:
“CLOT” for secondary hypercoagulability
* C: Cancer
* L: Lifestyle (immobility, OCPs, pregnancy)
* O: Operations (surgery, trauma)
* T: Thrombophilia (APS, HIT)
What is Warfarin Induced Skin Necrosis?
⚠️ The Problem: A Temporary Pro-Clotting State
When you start warfarin, here’s what happens inside your body:
1. Warfarin blocks Vitamin K → this slows down clotting factor production.
2. But Protein C (a natural blood thinner) disappears very quickly — within hours.
3. Meanwhile, clotting factors like II (thrombin) take days to decrease.
✅ Net result (early on): You lose your “brakes” (Protein C) before you lose your “gas pedal” (clotting factors)
➡️ This creates a brief window where the blood clots more easily than before.
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🩸 What Happens in the Skin
This sudden pro-thrombotic shift causes:
* Tiny clots (microthrombi) to form in small blood vessels, especially in skin and fat-rich areas (breasts, thighs, buttocks).
* These clots block blood supply, leading to:
1. Ischemia (lack of oxygen)
2. Infarction (tissue death)
3. Necrosis (rotting skin tissue)
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🧬 Who’s at Risk?
People who are already low on Protein C or Protein S (naturally or due to illness) are much more at risk:
* Congenital Protein C deficiency
* Protein S deficiency
* High-dose warfarin without a heparin bridge
🚨 Why It’s Dangerous
If not recognized early:
* Skin necrosis spreads
* Deep tissue damage may require surgical removal or even skin grafting
* Risk of infection and sepsis
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🩹 How to Prevent This
1. Start warfarin slowly (low dose)
2. Bridge with heparin for the first few days, especially in high-risk patients
3. Monitor closely if history of clotting disorders
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📌 Bottom Line
Warfarin skin necrosis happens because:
You suddenly lose the anticoagulant Protein C before clotting factors drop, → causing mini blood clots in the skin → blocking vessels → causing skin death.
What is Warfarin?
Warfarin is a blood thinner (anticoagulant) used to prevent blood clots. It’s often prescribed for:
* People with atrial fibrillation (irregular heartbeats)
* Those with deep vein thrombosis (DVT) or pulmonary embolism (PE)
* People with mechanical heart valves
But warfarin doesn’t “dissolve” clots. Instead, it prevents new clots from forming and stops existing ones from getting bigger.
How does Warfarin work?
🎯 Target: Vitamin K
Warfarin inhibits an enzyme called Vitamin K epoxide reductase.
This enzyme is needed to activate Vitamin K, and Vitamin K is essential for making several important clotting factors in the liver.
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📉 Warfarin reduces production of:
* Clotting Factors: II (thrombin), VII, IX, X
* Natural anticoagulants: Protein C and Protein S
These are all Vitamin K–dependent
What is Prothrombin?
🔹 What is it?
* A clotting factor made in the liver
* It is inactive until it is converted into Thrombin (Factor IIa)
🔹 What does Thrombin do?
Once activated, thrombin is a key enzyme in clot formation. It:
* Converts fibrinogen → fibrin, which forms the mesh of the clot
* Activates platelets
* Activates other clotting factors (like V, VIII, XI)
* Amplifies clotting in a positive feedback loop
✅ So: Prothrombin → Thrombin → Clot formation
What is Antithrombin?
🛑 Antithrombin III (ATIII)
🔹 What is it?
* A natural anticoagulant protein made by the liver
* It inhibits thrombin and other activated clotting factors (mainly Factor Xa)
🔹 What does it do?
* Binds to thrombin and shuts it down
* Also blocks Factor Xa, which is upstream of thrombin in the clotting cascade
* Prevents too much clotting — it’s part of the body’s safety mechanism
✅ So: Antithrombin III = “brake” on clotting
