Thrombotic Disorders I

Question 1

Explain Virchows triad.

Answer 1

HypercoagulabilityVenous stasisVessel damage

Question 2

Explain the origin of heparin, thrombomodulin, anti thrombin III, Protein C and Protein S.Explain their MOA and their effects on coagulation cascade.

Answer 2

Heparin and thrombomodulin is expressed on the surface of endothelial cells whereas antithrombin, Protein C and Protein S are made by the liver and are found in plasma.Heparin binds to antithrombin, causes a conformational change such that antithrombin then inhibits several coagulation factors, most of the anticoagulent effect of heparin comes from inhibition of thrombin (FII).Protein C and Protein S together inactivates FV and FVIII so they have an anticoagulent effect.

Question 3

What factors predisoposes a patient for greatest risk of DVT?

Answer 3

Major surgery/trauma and history of thrombosis

Question 4

What are the symptoms of DVT and what test can be done to confirm the dx?

Answer 4

Unilateral leg pain, swelling and non specific symptomsCompression ultrasound can be done to confirm the diagnosis. Additionally venography of proximal leg veins can also be done.

Question 5

What are the symptoms of PE?What diagnosis testing can be done?

Answer 5

Pulmonary Embolism Clinical Features
* Dyspnea
* Wheezing
* Chest pain (pleuritic -infarction)
* Hemoptysis (infarction with bleeding into airway)
* Right sided heart failure; cor pulmonale (hypotension, syncope, coma)
* Hypoxemia
* These features are nonspecific; objective testing required for diagnosis
Diagnostic testing may involve spiral CT that has a high positive predictive value and D dimer test that has a high negative predictive value.Additionally ventilation perfusion scan or pulmonary angiography can also be done.

Question 6

Explain the function of Protein C.

Answer 6

Protein C and Protein S are vitamin K dependent proteins that play a role in anticoagulation pathway.

Question 7

Explain Factor V Leiden mutation.

Answer 7

• Production of mutant factor V (G ->ŽA, DNA point mutationŽ near the cleavage site, Arginine to Glutamine) that is resistant to degradation by activated protein C.
• Most common cause of inherited hypercoagulability in Caucasians.
• Complications include DVT, cerebral vein thromboses, recurrent pregnancy loss.
• Heterozygotes also have increased risk
  Diagnosis:
• Activated Protein C (APC) resistance test is used as a screening test. APC causes prolonged PTT in normal individuals, there is less PTT prolongation in people with Factor V Leiden mutation.
• Mutation analysis PCR can then be done as a confirmatory test.