Haemostasis & transfusion

Question 1

What are the laboratory tests that are used to assess the clotting system?

What do they assess?

Answer 1

Prothrombin time (PT):

• Tests the extrinsic pathway, by addition of a tissue factor substitute to the patient’s plasma
• It is prolonged in liver disease or if the patient is on warfarin

International normalised ratio (INR)

• Ratio of patient’s PT to a normal control whilst using an international reference preparation
• 0.9-1.1 is the normal range
• Used for warfarin dosing

Activated partial thromboplastin time (APTT)

• Addition of a surface activator to the plasma
• Tests the intrinsic (contact) pathway
• Its is the monitoring required for unfractional heparin

Thrombin time:

• Addition of thrombin to the patient’s plasma
• Prolonged with fibrinogen deficiency or abnormal function, or inhibitors such as heparin
• Tests final common pathway

Question 3

Describe the coagulation cascade

Answer 3

Question 4

Describe the role of liver in the coagulation cascade

Answer 4

• Clotting factors are primarily synthesised in the liver, and many act as serine proteases to activate other factors

Factors produced by the liver:

• I (fibrinogen), II (prothrombin), IV, V, VI, and VII

Question 6

What is the role of vitamin K?

Answer 6

• It is a cofactor necessary for the production of the blood clotting factors:
  
  • Factor II, VII, IX and X
• Deficiency thus leads to clotting factor deficiencies, leading to an increased PT and haemorrhage
• Protein C is dependent on vitamin K, activated protein C inactivates factors V and VIII, stopping further thrombin generation

It is absorbed in upper ileum and stored in the liver

Question 7

Describe the ABO blood group system

Answer 7

ABO system:

• Red cells can be A, B, AB or O: named according to their surface antigens
• They will carry IgM antibodies against any antigen that they do not carry
  
  • O group blood will carry anti-A and anti-B antibodies
  • AB group blood will not carry any anti-A or anti-B antibodies (has A and B antigens)

Question 8

What is the significance of the ABO blood groups in blood transfusion?

Answer 8

• Incompatibilities involving many of the other antigens can cause haemolytic transfusion reactions
• Blood groups are determined by antigens of the surface of red cells, with the ABO/Rhesus group the two major blood groups

Question 9

Describe the Rhesus antigen system

(not an objective)

Answer 9

• Blood cells can either show the rhesus D antigen (rhesus positive) or not (rhesus negative)
• If a rhesus negative individual is exposed to rhesus positive blood products, then they can develop IgG antibodies directed against the rhesus D antigen
• If exposed to rhesus positive blood products again, there will be haemolysis
• This is the pathology behing haemolytic disease of the newborn, as well as transfusion reactions

Question 10

Describe the principles of cross-matching blood

(describe the tests used)

Answer 10

• Blood grouping: ABO and RhD groups of patients are determined
• Antibody screening: Patient serum/plasma screened for atypical antibodies that would cause significant haemolysis of transfused cells
• These two processes are automated, and donor blood of the same ABO/Rh group, and without specific antigens if atypical antibodies are found, is then crossmatched
  
  • Indirect agglutination test: donor RBCs added to patients serum, then Coomb’s reagent is added, agglutination indicates that the patients serum has antibodies for the donor RBCs. This test is always performed pre-transfusion
  • Direct agglutination: patients ‘washed’ RBCs are added to Coomb’s reagent, and if they agglutinate that indicates that there is an autoimmune haemolytic process occuring, with the RBCs coated with immunoglobulins. This is rarely required pre-transfusion
    
    • This is known as ‘Coomb’s’ test

All blood products need to be cross-matched except platelets