Basic Blood Coagulation Physiology, Lab Tests and Disorders

Question 1

How does primary haemostasis work?

Answer 1

• Injury causes vessels to constrict to reduce blood flow, mediated by endothelin - Biochemistry of vessel walls change and negatively charged platelets are attracted to the damaged surfaces - Platelets adhere to exposed collagen via vWF - vWF combines with platelet surface receptor glycoprotein 1B9 and links platelet to collagen - GP6 binds as well leading to further platelet activation - Activation causes platelets to release granule contents (ADP and thromboxane) enhancing the effect - Binding of GP6 to collagen activated GPIIb/IIIa which binds to fibrinogen, acting as a bridge between platelets

Question 2

How is primary haemostasis assessed?

Answer 2

• Bleeding time - FBC (platelet count) - Platelet function

Question 3

How is secondary haemostasis assessed?

Answer 3

• PT (stimulates activation via extrinsic pathway) - aPTT (stimulates activation via intrinsic pathway) - TCT (conversion of fibrinogen to fibrin)

Question 4

What is DIC?

Answer 4

• Process involves systemic activation of coagulation (activation of the extrinsic tissue factor VIIa pathways) leading to intravascular deposition of fibrin and thrombosis as well as depletion of platelets and coagulation factors
• Causes include sepsis, malignancy, massive haemorrhage, severe trauma and pregnancy complications

Question 5

What is Haemophilia?

Answer 5

• Haemophilia A - Factor VIII deficiency
• Haemophilia B - Factor IX deficiency
• X-linked recessive inheritance - men only requrie one copy, women require two
• Spontaneous haemorrhage without any trauma (i.e. bleeding into joints)
• Diagnosed with bleeding scores, coagulation factor assays and genetic testing
• Prolonged aPTT
• Treated with replacement of clotting factors IV
• Can also use desmopressin to stimulate the release of vWF and TXA

Question 6

What is Von Willebrand disease?

Answer 6

• Most common inherited cause of abnormal bleeding
• AD with variable penetrance
• Mucosal type bleeding pattern (gums, nose, HMB)
• Reduced vWF +/- reduced platelet aggregation +/- reduced VIII
• Management:
  
  • Desmopressin can be used to stimulate release of vWF
  • vWF can be infused
  • Factor VIII can be infused along with plasma derived vWF
• In HMB can also use:
  
  • TXA
  • Mefanamic acid
  • Norethisterone
  • COCP
  • Mirena coil
  • Hysterectomy in severe cases

Question 7

What is Lupus anticoagulant?

Answer 7

• Phospholipid dependent antibody - aPTT prolonged

Question 8

What is antiphospholipid syndrome?

Answer 8

• Disrupts annexin V shield - Exposes excess phospholipid

Question 9

What is thrombophilia?

Answer 9

• Inherited
• Deficiencies of natural anticoagulants (antithrombin, Protein C, Protein S)

Question 10

How does secondary haemostasis work?

Answer 10