T7-L3: Introduction to Bleeding Disorders

Question 1

What are the components of a platelet?

Answer 1

• Alpha granules - contain adhesive proteins, coagulations factors, fibrinolytic factors etc.
• Lysosomal granules
• Dense granules - Contain ADP/ATP, calcium, serotonin, histamine etc.
• Receptors for primary agonists such as ADP, TXA, PZY
• Metabolites - such as TXA, PAF
• Membrane glycoproteins

Question 2

How does aspirin act as a anti-thrombotic agent?

Answer 2

Asprin inhibits cyclooxyrgenase - Prostaglandins and many other thrombotic agents such as thromboxane are produced from arachidonic acid through the cyclooxygenase pathway.

Question 3

How does Clopidogrel work?

Answer 3

Blocks ADP receptor - used in stroke prevention. They are irreversible platelet inhibitors of the P2Y12 receptor.

Question 4

What part of the coagulation cascade does the aTTP Test?

Answer 4

Intrinsic Pathway

Question 5

Describe the extrinsic pathway. What can we use to test this?

Answer 5

The Prothrombin Time

The extrinsic pathway occurs when Fc VII binds to tissue factor found on the surface of cells - activated or diseased endothelial cells and in other tissues such as WBC. This activates Fc VII forming Fc VIIa. Fc VIIa can directly activate Fc X. Fc Xa with its cofactor Fc V can activate thrombin. The coagulation pathway is quite quick as it does not have any steps.

Question 6

Give anticoagulants in the blood.

Answer 6

• Anti-thrombin III
• Protein C
• Protein S

Proteins S acts as a principal cofactor to protein C. The two work together to help regulate and control blood clot formation by inactivating specific coagulation factors (factors V and VIII) that are required to generate and form blood clots.

• Fibrinolytic Pathway

Question 7

Give examples of bleeding disorder that show a normal coagulation screen.

Answer 7

• vWD
• Factor XIII deficiency
• Thrombocytopenia
• Disorder of platelet function
• Mild coagulation factor deficiency
• Vascular disorder
• Disorders of fibrinolysis

Question 8

Give examples of platelet abnormalities.

Answer 8

• Abnormal vessel wall such as Elhers Danlos syndrome
• Abnormal interaction between platelets and vessel wall e.g. vWD
• Abnormal platelet function
• Reduced number of platelets

Question 9

What is the difference in presentation between a vascular/platelet and coagulation disorder?

Answer 9

Vascular/platelet defect:

• Petechiae and Superficial bruises
• Haemarthrosis
• Spontaneous bleeding
• Bleeding immediate; prolonged and non-recurrent

Coagulation defect:

• Deep spreading haematoma
• Skin and mucous membranes bleeding
• Retroperitoneal bleeding
• Bleeding prolonged and often recurrent

Question 10

What is Von Willebrand Disease?

Answer 10

It is the most common bleeding disorder. The most common type is type I vWD - reduced production of vWF but the molecule is normal and functioning normally. Type II is the next most common - the patient produces enough vWF but it is structurally abnormally - often the multimeric structure is not formed properly leading to lower molecular weight polymers and poorly functioning molecules. Absent vWF is more rare. This is severe type III. It has spontaneous bleeding.

It is mostly AD in inheritance. There is a variable reduction in Fc VIII levels.

Blood group O show physiologically lower level of vWF.

Treatment is tranexamic acid - antifibrinolytic. Also DDAVP for type I vWD. Also factor concentrates containing vWD.

Question 11

What results of a coagulation screen would we see in Haemophilia A?

Answer 11

Haemophilia A - reduced levels of Fc VIII. Therefore see a prolonged aPPT test, normal thrombin time and prothrombin test.

Question 12

What types of bleeds do we see in Haemophilia?

Answer 12

• Spontaneous/Post traumatic bleeds
• Haemarthrosis (hallmark of severe haemophillia)
• Muscle haemorrhage
• Soft tissue bleeds such as in the soft palette or tongue
• Can also see life-threatening bleeding such as intracranial bleeding

Question 13

What is used in the treatment of Haemophilia?

Answer 13

• Replacement of missing clotting protein - can be on demand or prophylaxis
• DDVAP - DDAVP causes the release of von Willebrand’s antigen from the platelets and the cells that line the blood vessels where it is stored. Used in mild to moderate haemophillia
• Factor concentrates
• Antifibrinolytic agents (such as Tranexamic acid)
• Vaccination against Hepatitis A and B
• Supportive measures

Question 14

What are the complications of Haemophilia treatment?

Answer 14

• Inhibitor development - more common in Haemophilia A

- Infections such as Hepatitis A, HIV and parvovirus