PATHOPHYSIOLOGY
Blood vessels have an endothelial system (single cell layer)
● Healthy system required to prevent inappropriate clotting of blood
1. Barrier: hides sub endothelial components that activate clotting cascade from being
exposed to blood
2. Antiplatelet and antithrombotic secretions inhibit platelets and the clotting cascade
3. Fibrinolytic secretions: secretes substances that break down clots
Primary Hemostasis (occurs at the same time as secondary)
● Cell wall is disrupted
● Several sub endothelial particles in the damaged blood vessel are exposed to the circulating blood
○ Von Willebrand factor and collagen
● Interact with platelets at glycoprotein 1A (Collagen) and 1B receptors (vWF) (to form a plug)
● Platelets become activated and secrete substances (ADP, TXA2, 5-HT)
● This recruits other platelets to site of damage
● Platelets link together with glycoprotein 2B and 3A to form larger plug
Secondary Hemostasis (occurs at the same time as primary)
● This is known as the coagulation cascade
● Tissue factor is released
● This activates the extrinsic pathway which eventually activates thrombin (intrinsic is also
happening at the same time → both required to convert thrombin *cannot act as
independent*)
● Thrombin causes further activation and recruitment of other platelets to the site of injury,
accelerates the production of more thrombin (amplifying cascade) and converts fibrinogen to
fibrin which surrounds and stabilizes clot
There is a balance between activation (vWF, TX, TF, factors VII, X, XII, XIII) and inhibition (Protein C,
protein S, antiTX, Tfi) of this pathway. Imbalance on either side is harmful.
*Both intrinsic and extrinsic pathway must happen simultaneously
Thrombosis
● Process that occurs with inappropriate or over-activation of hemostasis in an uninjured or slightly
injured blood vessel
○ Arterial thrombi (dense with platelets) ruptured atherosclerotic plaques in arteries
○ Venous thrombi: (fibrin & RBC) mainly stasis of blood flow in a damaged vein (after
surgery or trauma) causing DVT, PE
,Venous Thromboembolism (VTE)
● Results from a thrombus formation in the venous system (DVT and PE)
● Most PE start as DVTs
○ Deep veins of the leg (proximal veins have a higher risk of developing into a PE)
■ Popliteal, femoral, deep femoral, great saphenous, common femoral, external
iliac, internal iliac, common iliac
Epidemiology
● VTE is common (2nd most common CVD in Canada)
● ⅓ of patients with DVT will develop symptomatic PE or post-thrombotic syndrome or have a
recurrent DVT or PE in the following 10 years
● 50% of patients with VTE have no identifiable risk factors
Pathogenesis
● Virchow’s Triad (thrombosis can occur at any of these, but higher if 1 or more)
○ Vessel wall injury: injury triggers primary and secondary hemostasis
○ Stasis: (slow and turbulent blood flow) promotes higher conc of procoagulant substances
which then have an increased chance of interaction with a slightly damaged vessel
○ Hypercoagulability ***KNOW THESE***
■ Protein C deficiency, Protein S deficiency, prothrombin gene mutation,
antiphospholipid antibodies (Lupus), antithrombin deficiency, factor V Leiden,
pregnancy, estrogen therapy, malignancy
Risk Factors
● Strong (OR more than 10) → involves all 3 of the triad
○ Fracture (hip or leg), hip/knee replacement, major general surgery, major trauma, spinal
cord injury
○ Widespread tissue and vessel damage and often immobility after the acute event, and a
hypercoagulable state because the body's trying to avoid massive blood loss
● Moderate (OR 2-9)
○ Arthroscopic knee surgery, central venous lines, chemotherapy, heart/respiratory failure,
hormone replacement, malignancy, oral contraceptive therapy, paralytic stroke,
pregnancy (PP), previous VTE, thrombophilia
● Weak (OR less than 2)
○ Bed rest 3 days, immobility due to sitting, increasing age, laparoscopic surgery, obesity,
pregnancy, varicose veins
Presentation
● DVT
○ Symptoms: unilateral swelling, erythema, localized pain/tenderness along deep venous
system (warmth around painful area)
○ Signs: dilated superficial veins, palpable cord
○ Labs: elevations of D-dimer, erythrocyte sedimentation rate and white blood cell count
● PE
○ Symptoms: cough, hemoptysis (coughing up blood), chest pain/tightness, shortness of
breath, dizziness, lightheadedness, palpitations
, ○ Signs: tachypnea, tachycardia, diaphoresis, hypoxemia, fever, distended neck veins, ECG
changes (pressure change in right ventricle)
● Labs: similar to DVT
Diagnosis
● Signs and symptoms of VTE are non-specific
● Diagnosis requires objective testing
○ Wells criteria is most common scoring chart (if score 0 = do D-dimer, if score above 0 =
need more specific tests)
○ D dimer test is very sensitive (but not very specific)
■ A D-dimer test is a blood test that measures D-dimer, which is a protein fragment
that your body makes when a blood clot dissolves in your body. D-dimer is
normally undetectable or only detectable at a very low level unless your body is
forming and breaking down significant blood clots.
● DVT diagnosis
○ Compression ultrasonography (most common DVT test)
■ An ultrasound transducer is placed over two landmarks, the femoral artery near
the groin and the popliteal artery behind the knee. When lightly placed on the
skin, both the artery and the vein can be seen on the ultrasound
■ When pressure is placed on the transducer, the muscular artery remains visible,
while the non-muscular healthy vein gets compressed and disappears from view
■ If the vein can't be compressed with the pressure applied, it must be due to
thrombus present in the vein. And this represents the diagnostic criteria for DVT
● PE diagnosis
○ Spiral computed tomography (CT) (most common PE test)
○ Ventilation/perfusion (V/Q) scan (may be used in pregnant patients due to less radiation)
Deep Venous Thromboembolism
● Distal (below knee) → unless symptomatic, treatment w/ anticoag is not always required
○ Don't often become symptomatic until above knee (25% of ppl without treatment
will extend to proximal), If they stay below knee, rarely cause PE
● Proximal (above knee)
○ Without treatment, 50% with symptomatic proximal DVT will develop PE within 3m
● Post-Thrombotic Syndrome (PTS) → most frequent complication of DVT (20-50% of pts)
○ Anticoagulation therapy does not actually lyse thrombus (prevents new ones)
○ Residual thrombus or vessel damage can prevent return to normal vein function
○ Symptoms: pain, heaviness, swelling, cramps, itching/ting of limb (persistent/intermit)
○ Treatment: no good one, best to prevent (GCS may help a bit)
Pulmonary Embolism
● 10% of symptomatic PE are fatal within 1st hour of symptoms
● 25% diagnosed with symptomatic PE die within 1 year of diagnosis (risk highest in first month)
● 1-3% who survive develop Chronic Thromboembolic Pulmonary Hypertension –lead to HF/death
VTE
Blood vessels have an endothelial system (single cell layer)
● Healthy system required to prevent inappropriate clotting of blood
1. Barrier: hides sub endothelial components that activate clotting cascade from being
exposed to blood
2. Antiplatelet and antithrombotic secretions inhibit platelets and the clotting cascade
3. Fibrinolytic secretions: secretes substances that break down clots
Primary Hemostasis (occurs at the same time as secondary)
● Cell wall is disrupted
● Several sub endothelial particles in the damaged blood vessel are exposed to the circulating blood
○ Von Willebrand factor and collagen
● Interact with platelets at glycoprotein 1A (Collagen) and 1B receptors (vWF) (to form a plug)
● Platelets become activated and secrete substances (ADP, TXA2, 5-HT)
● This recruits other platelets to site of damage
● Platelets link together with glycoprotein 2B and 3A to form larger plug
Secondary Hemostasis (occurs at the same time as primary)
● This is known as the coagulation cascade
● Tissue factor is released
● This activates the extrinsic pathway which eventually activates thrombin (intrinsic is also
happening at the same time → both required to convert thrombin *cannot act as
independent*)
● Thrombin causes further activation and recruitment of other platelets to the site of injury,
accelerates the production of more thrombin (amplifying cascade) and converts fibrinogen to
fibrin which surrounds and stabilizes clot
There is a balance between activation (vWF, TX, TF, factors VII, X, XII, XIII) and inhibition (Protein C,
protein S, antiTX, Tfi) of this pathway. Imbalance on either side is harmful.
*Both intrinsic and extrinsic pathway must happen simultaneously
Thrombosis
● Process that occurs with inappropriate or over-activation of hemostasis in an uninjured or slightly
injured blood vessel
○ Arterial thrombi (dense with platelets) ruptured atherosclerotic plaques in arteries
○ Venous thrombi: (fibrin & RBC) mainly stasis of blood flow in a damaged vein (after
surgery or trauma) causing DVT, PE
,Venous Thromboembolism (VTE)
● Results from a thrombus formation in the venous system (DVT and PE)
● Most PE start as DVTs
○ Deep veins of the leg (proximal veins have a higher risk of developing into a PE)
■ Popliteal, femoral, deep femoral, great saphenous, common femoral, external
iliac, internal iliac, common iliac
Epidemiology
● VTE is common (2nd most common CVD in Canada)
● ⅓ of patients with DVT will develop symptomatic PE or post-thrombotic syndrome or have a
recurrent DVT or PE in the following 10 years
● 50% of patients with VTE have no identifiable risk factors
Pathogenesis
● Virchow’s Triad (thrombosis can occur at any of these, but higher if 1 or more)
○ Vessel wall injury: injury triggers primary and secondary hemostasis
○ Stasis: (slow and turbulent blood flow) promotes higher conc of procoagulant substances
which then have an increased chance of interaction with a slightly damaged vessel
○ Hypercoagulability ***KNOW THESE***
■ Protein C deficiency, Protein S deficiency, prothrombin gene mutation,
antiphospholipid antibodies (Lupus), antithrombin deficiency, factor V Leiden,
pregnancy, estrogen therapy, malignancy
Risk Factors
● Strong (OR more than 10) → involves all 3 of the triad
○ Fracture (hip or leg), hip/knee replacement, major general surgery, major trauma, spinal
cord injury
○ Widespread tissue and vessel damage and often immobility after the acute event, and a
hypercoagulable state because the body's trying to avoid massive blood loss
● Moderate (OR 2-9)
○ Arthroscopic knee surgery, central venous lines, chemotherapy, heart/respiratory failure,
hormone replacement, malignancy, oral contraceptive therapy, paralytic stroke,
pregnancy (PP), previous VTE, thrombophilia
● Weak (OR less than 2)
○ Bed rest 3 days, immobility due to sitting, increasing age, laparoscopic surgery, obesity,
pregnancy, varicose veins
Presentation
● DVT
○ Symptoms: unilateral swelling, erythema, localized pain/tenderness along deep venous
system (warmth around painful area)
○ Signs: dilated superficial veins, palpable cord
○ Labs: elevations of D-dimer, erythrocyte sedimentation rate and white blood cell count
● PE
○ Symptoms: cough, hemoptysis (coughing up blood), chest pain/tightness, shortness of
breath, dizziness, lightheadedness, palpitations
, ○ Signs: tachypnea, tachycardia, diaphoresis, hypoxemia, fever, distended neck veins, ECG
changes (pressure change in right ventricle)
● Labs: similar to DVT
Diagnosis
● Signs and symptoms of VTE are non-specific
● Diagnosis requires objective testing
○ Wells criteria is most common scoring chart (if score 0 = do D-dimer, if score above 0 =
need more specific tests)
○ D dimer test is very sensitive (but not very specific)
■ A D-dimer test is a blood test that measures D-dimer, which is a protein fragment
that your body makes when a blood clot dissolves in your body. D-dimer is
normally undetectable or only detectable at a very low level unless your body is
forming and breaking down significant blood clots.
● DVT diagnosis
○ Compression ultrasonography (most common DVT test)
■ An ultrasound transducer is placed over two landmarks, the femoral artery near
the groin and the popliteal artery behind the knee. When lightly placed on the
skin, both the artery and the vein can be seen on the ultrasound
■ When pressure is placed on the transducer, the muscular artery remains visible,
while the non-muscular healthy vein gets compressed and disappears from view
■ If the vein can't be compressed with the pressure applied, it must be due to
thrombus present in the vein. And this represents the diagnostic criteria for DVT
● PE diagnosis
○ Spiral computed tomography (CT) (most common PE test)
○ Ventilation/perfusion (V/Q) scan (may be used in pregnant patients due to less radiation)
Deep Venous Thromboembolism
● Distal (below knee) → unless symptomatic, treatment w/ anticoag is not always required
○ Don't often become symptomatic until above knee (25% of ppl without treatment
will extend to proximal), If they stay below knee, rarely cause PE
● Proximal (above knee)
○ Without treatment, 50% with symptomatic proximal DVT will develop PE within 3m
● Post-Thrombotic Syndrome (PTS) → most frequent complication of DVT (20-50% of pts)
○ Anticoagulation therapy does not actually lyse thrombus (prevents new ones)
○ Residual thrombus or vessel damage can prevent return to normal vein function
○ Symptoms: pain, heaviness, swelling, cramps, itching/ting of limb (persistent/intermit)
○ Treatment: no good one, best to prevent (GCS may help a bit)
Pulmonary Embolism
● 10% of symptomatic PE are fatal within 1st hour of symptoms
● 25% diagnosed with symptomatic PE die within 1 year of diagnosis (risk highest in first month)
● 1-3% who survive develop Chronic Thromboembolic Pulmonary Hypertension –lead to HF/death
VTE
