Hemorrhagic disorders

Question 1

Coagulation pathway

Answer 1

Question 2

What helps to balance coagulation out?

Answer 2

Antithrombin, Protein C, Protein S -> to balance coagulation out and break clots down (this is as body is at the state of constantly making clots) -> if any of these ‚balancing’ molecules will be impaired = thrombotic problem

Question 3

What’s Von Willebrand factor? What’s its role?

Answer 3

VWF -> large adhesive glycoprotein that is required from platelet adhesion to endothelium at site of vessel injury, platelet aggregation (to form platelet plug) and stabilisation of factor VIII in a circulation (factor VIIIa is required for factor X activation)

Question 4

What questions to ask in the Hx in order to identify the possibility of a pt having a bleeding disorder?

Answer 4

• Questions about iron deficiency and blood transfusions -> to what extend they bleed (what treatment was required)
• Ask about tonsillectomy -> if pt had a procedure and did not bleed -> high chance that no bleeding disorder
• Dental extraction -> did they need to stitch it/ go back to dentist (due to heavy bleeding)
• Did they start having bleeding problem after starting anti-coagulant (that may be the cause)
• if bruises come out possibly in the places where we do not expect to hit ourselves/bump onto things

Question 5

What’s the normal number of platelets? ( range)

Answer 5

Normal number of platelets 150 - 450 (this is considered as more than we need)

Question 6

At what point (level) do we treat low number of platelets?

Answer 6

We treat platelets that are about 30 or less

Question 7

Ix in suspected bleeding disorder (and justification)

Answer 7

• Renal function -> uraemia can interfere with platelet function
• Liver function -> coagulation proteins
• Haematinics: folate and B12 -> we need it to make platelets
• Paraprotein -> is there an abnormal protein?
• PT (extrinsic pathway/factor VII)
• APTT (intrinsic pathway; factor XII)

Question 8

What does PT look at?

Answer 8

Prothrombin Time (PT)

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• PT looks at extrinsic pathway (factor VII etc)
• long prothrombin time -> long for the blood to clot

Question 9

What does APTT look at?

Answer 9

APTT looks at intrinsic pathway (factor XII, kallakerin etc)

Question 10

Causes of long PT

Answer 10

Question 11

causes of long APTT

Answer 11

Question 12

What findings may be suggestive of coagulation problems? (2)

Answer 12

•Factor inhibitors = autoantibodies against coagulation factors

•Lupus anticoagulant = autoantibodies directed against phospholipid -> can cause artificially prolonged APTT (due to consumption of phospholipids that are put into the tube - so blood
cannot clot properly -> it is a false positive result)

Question 13

What ‘other’ Ix we perform in a pt with suspected coagulopathy?

Answer 13

• Bleeding time - we lancet somebody arm and see how long it takes to bleed
• Mixing studies- patient’s plasma and somebody else’ plasma mixed together; if there is a deficiency of coagulation factor -> patient sample will get better (as normal stuff are put with it); if anti-body against factors causes the problem - it will not get better as it will destroy somebody else’s factors
• D-dimer - breakdown product of fibrin
• Factor assays - we can see how the factors behave in terms of their activity levels
• Genetics -> to directly look for mutations

• Global coagulations assays -> used in trauma and surgical setting; how long does it take for

the blood to clot

Question 14

What factors deficiencies are there in:

Haemophilia A

Haemophilia B

Answer 14

• Haemophilia A -> factor VIII deficient
• Haemophilia B -> factor XI deficient

Question 15

What is (a simple) genetic mechanism of hemophilia?

Answer 15

X linked

Question 16

What abnormality is seen on Ix of Haemophilia?

Answer 16

As factors VIII and IX belong to intrinsic cascade -> prolonged APTT (as intrinsic cascade is affected)

Question 17

Complications/consequences of haemophilia

Answer 17

• Haemarthrosis - bleeding into joint spaces
• Haemophilic Arthropathy -> result of haemarthrosis
• Intramuscular bleeds
• Intracranial bleeds
• Haematuria
• ‘hidden bleeds’

Question 18

Pathology of Haemophilic Arthropathy

Answer 18

recurrent bleed into joint space -> inflammation is activated -> destruction of the joint -> changes in the joint -> functional problems

Question 19

Treatment of haemophilia

Answer 19

To replace what’s missing - clotting factors:

• So for patient with haemophilia A -> we give factor VIII -> to bring missing factors levels up to normal
• DDAVP -> desmopressin injection -> to release endogenous stores of factor VIII and vWF (as vWF will be released so more factor VIII too as it is bound to vWF) -> for people with mild disorders we can push up the factor levels to normal) *only effective for Haemophilia A treatment
• Tranexamic acid -> stops bbreakdown of clots (anti- thrombolytic)

Question 20

Possible complications of Haemophilia treatment

Answer 20

•Person with severe haemophilia is not used to high levels of missing factors -> so if they are administrated -> antibody against them can be developed*

*more common in haemophilia A

• immune modulation -> someone is given immuno-active protein
• Thrombosis -> perhaps over-treated -> too much coagulation -> clot
• anaphylaxis
• infections (e.g. Hep B, HIV, Hep C, etc - before the screening was introduced)