VTE Pathophysiology Flashcards by Pierre Wadeie

What are the 3 functions of endothelium layer that lines blood vessels

Barrier: hides subendothelial components that activate clotting cascade
Antiplatelet/antithrombotic secretions: to inhibit platelets/clotting cascade
Fibronolytic sectrions: to break down any clots that do end up forming

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What occurs in primary hemostasis during a cut?

Collagen and vWF factor are exposed to blood
Interacts with GP Ia and GP Ib to stop blood
Platelet secretes ADP, TXA2, 5-HT
This activates GP IIb/IIIa in other platelets to form plugs

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What occurs in secondary hemostasis during a cut? What is the role of thrombin? (2)

Tissue factor is responsible for triggering the extrinsic pathway
- initiates coagulation cascade

Prothrombin -> Thrombin which further activates + recruits platelets to site of injury (2 outcomes):
1. Accelerates production of more thrombin
2. Converts fibrinogen to fibrin to make clot more stable

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Does primary and secondary hemostasis happen at the same time?

Yes

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What are the roles of activators and inhibitors of the clotting process? Give examples of each

Activators: make platelet plug bigger/stronger
- vWF
- Tissue factor
- Factor 7a, 10a, 12a
- Thrombin
- Factor 13a

Inhibitors: Limit size of platelet plugs
- Heparan
- Thrombomodulin
- Antithrombin
- Protein C, S

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Define thrombosis

Process that occurs with inappropriate, or over-activation of hemostasis in an uninjured or slightly injured blood vessel
- results in a thrombus (blood clot)

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Define arterial thrombi. Give examples

Ruptured atherosclerotic plaques in arteries
- MI
- stroke
- peripheral artery disease

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Define venous thrombi. Give examples

stasis of blood flow in a DAMAGED VEIN (after surgery or trauma)
- DVT
- PE

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Define embolism

An object migrates from one part of the body to cause a blockage of a blood vessel in another part of the body

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Which injury in the leg gives the higher risk of thrombus embolization? Give examples

Proximal deep veins
- All iliac veins
- All femoral veins
- Saphenous vein
- Popliteal vein

Always require treatment

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Which injury in the leg gives the lower risk of thrombus embolization? Why?

Distal deep veins
and superficial veins

Further away from lungs

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T/F VTE is the most common CV disorder in canada

False
2nd most common

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What are the % of people with DVT getting symptomatic PE, PTS, or recurrent DVT or PE in the next 10 years

All 1/3

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What is the % of patients with VTE who have no identifiable risk factors

50%

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What is the in the virchow’s triad?

Vessel wall injury
Stasis of blood flow
Hypercoagulability

Most patients have at least 1. The more, the greater the risk

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Define vessel wall injury in the triad

this exposes subendothelial factors (C and vWF to circulating blood), beginning primary and secondary hemostasis
- Increased risk of over-coagulation

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Define stasis of blood flow in the triad. Which type of blood flow is at an increase risk of coagulation

Thrombotic blood flow (inc risk, sedentary time)
- slow rate
- turbulent

Antithrombotic blood flow
- fast rate
- laminar flow

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What can cause hypercoagulability (inc coagulability)

Protein C or S difficiency (inhibitors of coagulation cascade)
Prothrombin gene mutation
Antiphospholipid antibodies
Antithrombin deficiency
Factor V Leiden
Pregnancy
Estrogen therapy
Malignancy (cancer)

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What are the highest risk factors for VTE

Fracture (hip or leg)
Hip or knee replacement
Major general surgery
Major trauma
Spinal cord injury

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What are the moderate risk factors for VTE

Arthroscopic knee surgery
central venous lines
Chemotherapy
Heart or resp failure
Hormone replacement
Malignancy (cancer)
COCs
Paralytic stroke
pregnancy POSTPARTUM
Previous VTE
thrombophilia

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What are the low risk factors for VTE

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Bed rest 3 days
Immobile due to sitting (car, plane)
Increasing age
laparoscopic surgery
obesity
pregnancy (during)
varicose veins

DVT presentation
Symptoms
Signs
Labs

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Symptoms
- UNIlateral swelling/warmth (one leg)
- erythema (redness)
- localized pain/tenderness

Signs
- dilated superficial veins
- palpable cord

Labs
- elevation of D-dimer (breakdown product of fibrin clots)
- high erythrocyte sedimentation rate
- high WBC

PE presentation
Symptoms
Signs
Labs

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Symptoms
- cough
- hemoptysis (coughing blood)
- chest pain/tightness
- SOB
- dizziness/lightheadedness
- palpitations

Signs
- tachypnea (high breathing rate)
- tachycardia
- diaphoresis (high sweating)
- hypoxemia (low O2 in blood)
- fever
- distended neck veins
- ECG changes

Labs (similar to DVT)
- elevation of D-dimer (breakdown product of fibrin clots)
- high erythrocyte sedimentation rate
- high WBC

What is the scoring system for VTE diagnosis called?

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Well’s cirteria

Explain the D-dimer test What is good for? Describe its sensitivity & specificity

Sensitivity: VERY sensitive - everyone with VTE will have an elevated d-dimer Specificity: not specific, people with VTE can still have an elevated d-dimer SNOUT: negative = good for ruling out VTE If positive --> check with another test

Describe the compression ultrasonography test ? How to tell if there is a thrombus?

1. Ultrasound transducer is applied to leg in femoral artery and popliteal artery (behind knee) and pressure is applied to leg If thrombus present the vein will NOT collapse - Healthy veins collapse easily - arteries have ticker walls and do not collapse with light pressure

What is the most common diagnosis for PE

Spiral computed tomography (CT scan)

Explain the ventilation/perfusion V/Q scan

lower dose of radioactive dye is injected (perfusion) and inhaled (ventilation), machine compares the images of both - mismatch in perfusion/ventilation may indicate PE - useful for pregnant women (lower dose of radioactive dye)

What percent of distal DVT extend above the knee?

25% 1/4

When do we treat Distal DVT

if they are symptomatic

Where do most symptomatic DVTs start? when do they often become symptoamtic

most symptomatic DVTs start below the knee they often become symptomatic when they extend past the knee

WITHOUT treatment, what is the % of patients with symptomatic proximal DVT that will develop PE in 3 months

50%

What % of patients get post-thrombotic syndrome complication of DVT

20-50%

What is the etiology of PTS

Due to an residual thrombus or vessel damage from the first clot - Since anticoagulation therapy doesn’t lyse the original thrombus, only prevents extension/embolization

What are symptoms of PTS?

- pain - heaviness - swelling - cramps - itching/tingling of limb (can be persistent or intermittent)

What is the treatment of PTS?

No good treatments, best to PREVENT DVT - elastic compression stockings may help a bit with symptoms

What is the annual risk of recurrent VTE in the first year after stopping treatment if: transient, reversible risk factor (surgery) unprovoked, continuing risk factors (ex. cancer)

transient, reversible risk factor (surgery) - 1-3% unprovoked, continuing risk factors (ex. cancer) - 10%

What type of VTE will recur that first year? What do the values mean?

Likely the same event PE after initial PE (60% of episodes) DVT after initial DVT (80% of episodes) - Mortality from recurrent VTE is 2-3x higher after PE than DVT

What is the prothrombin time PT ?

the length of time it takes from the addition of calcium until the plasma clots

What does the prothrombin time first developed to measure?

First for liver function - now measures the extrinsic and common coagulation cascades

What is the method of making the prothrombin time test?

decalcified plasma mixed with tissue factor (thromboplastin) - calcium is added to initiate coagulation

What was the problem with prothrombin time measurement?

Different labs using different thromboplastin which varied results

What was the solution to prothrombin time

INR = PT patient / PT reference plasma (WHO) - having a standard PT value

What are the limitations and sources of error in INR testing

Limitations/sources of error: 1. Pretest: sampling/blood collection problems 2. Incorrect handling/storage of blood sample 3. Lab errors 4. Lupus anticoagulants (cause falsely elevated INR) 5. Taking INR during first few days of warfarin - During this time, INR largely reflective of factor VII 7 (clotting factor with shortest half life) - Thromboplastin concentration varies with factor VII levels - INR will be falsely elevated during first few days of warfarin therapy 6. INR results >4.5 - The higher the reading the less certain it is

What does the activated partial thromboplastin time?

Time it takes from the addition of calcium until the plasma clots

What is the method of aPTT

Add to decalcified plasma - phospholipid - contact activator (kaolin) - calcium, to initiate coagulation

What does the aPTT measure? What does it monitor

INTRINSIC and common coagulation casade - monitors unfractionated heparin UFH therapy

What does the Anti-factor Xa assay measure?

Indirectly measures the concentration of anticoagulants that inhibit factor Xa

What are the uses of anti-factor Xa assay?

* LMWH therapy in special cases (pregnancy, renal impairment) * UFH therapy (when patient has factor XII deficiency or antiphospholipid antibodies) * DOACs with anti-Xa activity

Effects of dabigatran, + rivaraxoban edoxaban and apixaban with PT/INR

dabigatran - varbiable effect, (INR <2 at peak blood levels) rivaraxoban/edoxaban - inc PT/INR Apixiban - minimal effect

Effects of dabigatran, + rivaraxoban edoxaban and apixaban with aPTT

dabigatran - non-linear increase rivaraxoban/edoxaban - inc aPTT Apixiban - minimal effect

Effects of dabigatran, + rivaraxoban edoxaban and apixaban with antifactor Xa

dabigatran - no effect rivaraxoban edoxaban and apixaban - Require specific calibrators (for each drug) USE THIS TEST to measure levels of oral factor Xa-inhibitors

VTE Pathophysiology Flashcards

(52 cards)