Thromboembolic Disease

Question 1

Virchows triad in thromboembolism

Answer 1

Thrombus formation and propagation depend on the presence of abnormalities of blood flow, blood vessel wall, and blood clotting components

Question 2

How do abnormalities of blood flow occur?

Answer 2

Occur after prolonged immobility or confinement to bed.
Venous obstruction can arise from external compression by enlarged lymph nodes, bulky tumours, or intravascular compression by previous thromboses.

Increased oestrogens at pharmacological levels, as seen with oral contraceptive use and with hormone replacement therapy in postmenopausal women,

Question 3

Risk factors and conditions predisposing to venous thromboembolism

Answer 3

History of venous thromboembolism

Prolonged immobility

Prolonged confinement to bed or lower limb paralysis

Surgery, particularly lower limb orthopaedic operations, and major pelvic or abdominal operations

Trauma—For example, hip fractures and acute spinal injury

Obesity

Major medical illnesses such as acute myocardial infarction, ischaemic stroke, congestive cardiac failure, acute respiratory failure

Oestrogen use in pharmacological doses—For example, oral contraception pills, hormone replacement therapy

Cancer, especially metastatic adenocarcinomas

Age >40 years

Aquired hypercoagulable states—Lupus anticoagulant and antiphospholipid antibodies, hyperhomocysteinaemia, dysfibrinogenaemia, myeloproliferative disorders such as polycythaemia rubra vera

Inherited hypercoaguable states—Activated protein C resistance (factor V Leiden mutation), protein C deficiency, protein S deficiency, antithrombin deficiency, prothrombin gene mutation

Question 4

Indications for the heparin group

Answer 4

Treatment of DVT and PE
Anticoagulation through open heart surgery and renal dialysis
Treatment of ACS to unstable angina and acute non-STEMI
Prophylaxis for DVT and PE after stroke, MI, surgery

Question 5

Heparin unfractionated pharmacokinetics

Answer 5

Immediate onset of action with IV and 1-2hours if subcutaneous injection. High degree of protein binding. Average half life 1 and half hours. Metabllsied in liver and excretion of inactive metabolites in urine.

Question 6

Unfractionated heparin MOA

Answer 6

It produces its major anticoagulant effect by inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism.

Heparin binds to AT through a high-affinity pentasaccharide, which is present on about a third of heparin molecules. For inhibition of thrombin, heparin must bind to both the coagulation enzyme and AT, whereas binding to the enzyme is not required for inhibition of factor Xa

Question 7

Drugs with saturable metabolism

Answer 7

Paracetamol
Phenytoin
Alcohol

Question 8

How do people with thrombophilia present

Answer 8

DVT

PE

Question 9

Thrombophilia

Answer 9

SLE
Antiphospholipid syndrome
Protein C and S
Malignancy

Question 10

How to diagnose DVT

Answer 10

D dimers

Question 11

Role of PTT

Answer 11

In unfractionated heparin

Question 11

Role of PTT

Answer 11

In unfractionated heparin

Question 12

MOA of LMWH

Answer 12

Affects factor 10a

Question 13

Protamine sulphate

Answer 13

Antidote for unfractionated heparin