Pharmacology 16 - Haemostasis and Thrombosis

Question 1

Describe presentation of DVT

Answer 1

• Immobility (eg. surgery, long haul flight)
• Leg is swollen and collateral superficial veins are present.
• Palpation reveals localised tenderness, and pitting oedema.

Question 2

List the investigations, diagnosis and treatment of DVT

Answer 2

• Wells score (test for DVT, survey to see if someone is likely to have DVT)
• Positive D dimer test suggests DVT (fibrin degradation products)
• Ultrasound for confirmation
• Treat with anticoagulant (low molecular weight heparin interim, then oral anticoagulant eg. rivaroxaban/warfarin)

Question 3

Describe the initial stages of thrombosis

Answer 3

• Tissue factor bearing cells activate factors X and V forming prothrombinase complex
• Prothrombinase complex activates factor II (prothrombin to thrombin)
• Antithrombin inactivates fIIa and fXa

Question 4

How do anticoagulants act on initiation of thrombus formation?

Answer 4

• Inhibit factor IIa (dabigatrin - direct oral anticoagulant)
• Inhibit factor Xa (rvaroxaban - oral anticoagulant)
• Increase activity of AT-III (heparin, low molecular weight heparins - not oral)
• Reduce levels of other factors (warfarin is a vitamin K antagonist, vitamin K is required for generation of factors II, VII, IX, X taken orally, slow onset)

Question 5

Describe presentation of pulmonary embolism

Answer 5

• Chest pain
• Dyspnoea and tachypnoea
• BP decrease
• O2 sat decrease

Question 6

List investigations, diagnosis and treatment of pulmonary embolism

Answer 6

• Computed tomographic pulmonary angiography confirms diagnosis of pulmonary embolism (daltepain/heparin given as it is fast acting)
• Ultrasound scan for DVT (origin of embolus)
• Rivaroxaban/warfarin orally for maintenance

Question 7

List the risk factors for DVT

Answer 7

• Rate of blood flow (slow rate means no replenishment of anticoagulant factors, so the balance is in favour of coagulation)
• Consistency of blood (imbalance between pro-coagulation and anti-coagulation factors)
• Blood vessel wall integrity (damaged endothelium exposes blood to procoagulation factors)

Question 8

Compare causes and treatment of NSTEMI and STEMI

Answer 8

• Non-st elevated is a white thrombus, partially occluded coronary artery. Requires antiplatelets.
• STEMI is ST elevated on ECG, white thrombus but fully occluded coronary artery, usually due to atherosclerosis following hypertension and vessel wall damage. Requires antiplatelets and thrombbolytics.

Question 9

Describe the amplification stage of thrombosis

Answer 9

• FIIa (thrombin) binds to protease activated receptor (PAR) on platelet surface, causing Ca2+ to rise intracellularly by release from the internal stores. Causes the platelet to contract and become stellic. Also results in exocytosis of ADP from dense granules
• ADP activates P2Y12 receptors causing platelet activation and aggregation
• PAR activation liberates arachidonic acid, and cyclo-oxygenase generates thromboxane from arachidonic acid
• GPIIb/IIIa receptors are expressed following thromboxane activation, resulting in platelet aggregation

In summary:
- Factor IIa activates platelets, causing them to change shape and attach to other platelets

Question 10

List the drugs targeting platelet aggregation and where they act

Answer 10

• Clopidogrel is an ADP receptor antagonist (blocking P2Y12 receptor - oral)
• Aspirin inhibits production of thromboxane A2 (TXA2 - irreversible cox-1 inhibitor - oral)
• Abciximab (IV,SC) prevents platelet aggregation, by targetting GPIIb/IIIa receptor

Question 11

Describe the propagation stage of clot formation

Answer 11

• Occurs in emboli blocking arteries eg. cerebral artery in stroke
• Large scale thrombin production from activated platelets
• Factor IIa binds to fibrinogen and converts it to fibrin strands

Question 12

Describe the mechanism of thrombolytics

Answer 12

• Convert plasminogen to plasmin
• Plasmin - protease degrades fibrin resulting in dissolution of the clot, however it can cause too much bleeding so is only used in emergency situations.
• Alteplase (IV) is recombinant tissue type plasminogen activator (rt-PA)
• Remove preformed clots unlike anticoagulants and anti-platelets.

Question 13

What are anticoagulants?

Answer 13

Drugs that inhibit coagulation factors

Question 14

How does heparin work?

Answer 14

• IV infusion/ injection

- Activates AT-III to inhibit factor IIa and factor Xa

Question 15

How do low-molecular weight heparins work?

Answer 15

• Subcutaneous injection
• eg. dalteparin
• Activates AT-III to decrease factor Xa
• Given initially as an interim treatment as it acts quickly

Question 16

How is MI investigated?

Answer 16

• Vital signs
• Low oxygen sats
• ECG (NSTEMI vs STEMI)
• Elevated troponin (means damage to the cardiac tissue)

Question 17

Compare white and red thrombus

Answer 17

• Red thrombus red blood cell rich, in veins, treated with anticoagulants. Platelet coagulation.
• White thrombus tend to happen in the blood vessel wall. They have a high concentration of foam cells (macrophages that take up cholesterol). Treatment is antiplatelets and thombolytics.

Question 18

List investigations of stroke

Answer 18

• Serum glucose and elecrolytes (normal ranges)

- CT scan to eliminate possibility of haemorrhagic stroke

Question 19

How is ischaemic stroke treated?

Answer 19

• Thrombolytic therapy

- Eg. Alteplase (first line - tPA)