HAEM - COAGULATION AND HAEMOPHILIA Flashcards
Name two (2) acquired factors that can cause platelet inhibition (½x2 = 1)
Antiplatelet drugs – aspirin. Uraemia
Describe the function of von Willebrand’s factor (1)
Facilitates platelet vessel wall interaction
List six (6) basic routine coagulation tests you can perform to evaluate the ability of a patient to clot during major surgery (½x6 = 3)
VWB, PTT, INR, FBG, Bleeding time, Platelet count / morphology and function
Describe the function of low molecular weight heparin and what the advantage is over unfractionated heparin (½x4 = 2)
Works via binding to antithrombin
This complex primarily inhibits FXa and Thrombin
Little or no monitoring required in LMWH
Outline the basic function of recombinant tissue plasminogen activator drugs & state what these drugs are used for (½x4 = 2)
Serine protease enzyme
Activates plasminogen to plasmin
Initiates thrombolysis
Resolution of clot – MI and stroke (sometimes peripheral arterial obstruction)
List six (6) common causes of acquired thrombophilia (½x6 = 3)
Pregnancy, COC, Obesity, Immobility, Malignancy, Surgery – orthopaedic and abdominal especially
The patient has a prolonged Prothrombin Time.
a) What pathway of the coagulation cascade does this laboratory test assess? (½)
b) List 5 coagulation factors and / or cofactors that are assessed by the prothrombin time (2.5)
c) List 2 causes of a prolonged Prothrombin Time (1)
a) Extrinsic pathway
b) Factors VII, X, V, II (Prothrombin) and fibrinogen
c) Liver disease & Warfarin therapy
Give a brief explanation of the mechanism of the coagulation cascade (5)
The coagulation cascade consists of a series of enzyme reactions (1), which require cofactors, Ca++ and phospholipid (1.5). Each step amplifies the previous one (1), and the end result is the formation of large amounts of fibrin to form a stable clot (1.5) or the student may draw the cascade with explanations.
The doctor may decide to put Mr Olivier on aspirin therapy. Outline the mechanism of the anti-thrombotic action of aspirin (3½)
- Aspirin irreversibly inhibits (1/2) the enzyme cyclooxygenase (½) in platelets (½).
- This prevents the formation of Thromboxane A2 from arachidonic acid (1) Thromboxane A2 is a vasoconstrictor and platelet aggregator (1)
Mr Smart’s platelet count has also dropped, which raises concerns about bleeding. In the coagulation cascade, there is an initiation phase, an amplification phase and a propagative phase. In the amplification phase, the formation of thrombin is important. List any FOUR important consequences of the activation of thrombin [½x4 = 2]
- Cleavage of proteins of the coagulation cascade:
o Activation of co-factors V and VIII
o Activation of the enzyme FXI - Platelet Activation
Initiation phase
- Damaged endothelium exposes tissue factor [TF]
- Activation of Factor VII
- Activation of Factor X
- Activation of Factor V
- Formation of complex FactorXaVa
Amplification phase: Via prothrombinase complex [Factor XaVa]
- Enhance platelet aggregration
- Activate prothrombin to thrombin
- Activate fibrinogen to fibrin
- Activate Factor XIII to stabilise clot
Propagation phase: Via ten-ase complex [Factor IXaVIIIa]
- Increase prothrombiase complex
- Increase prothrombin to thrombin
- Increase fibrinogen to fibrin
- Activate Factor XIII to stabilise clot
Mrs Petersen is an 83-year-old pensioner living in a home for the elderly. One morning the day nurse finds Mrs Petersen lying on her bedroom floor. She was conscious but was unable to speak and could not stand or move her arms or legs on command. She was transferred to hospital where the doctor did further tests. A CT scan on the brain showed a substantial Left-sided cerebral infarct. Mrs Petersen’s family was called and the doctor informed them of the poor prognosis. Palliative care was discussed.
Mrs Petersen has two sons with haemophilia. Her father died from a brain haemorrhage at the age of 22 and her father’s healthy sister has a son with haemophilia.
Draw the pedigree (4)
State the risk that Mrs Petersen’s daughter is a haemophilia carrier (½)
50%
State what type of factor deficiency is most likely to cause haemophilia in her family. Explain your answer (2½)
Factor VIII deficiency as X linked inheritance pattern and factor VIII most common in all populations
State whether Mrs Petersen’s stroke is related to her family history of haemophilia and explain your answer (2)
No as she had a cerebral infarct and being a haemophilia carrier should not predispose in any way to arterial ‘blockage”
