Hemorrhagic disorders Flashcards
Coagulation pathway
What helps to balance coagulation out?
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
What’s Von Willebrand factor? What’s its role?
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)
What questions to ask in the Hx in order to identify the possibility of a pt having a bleeding disorder?
- 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
What’s the normal number of platelets? ( range)
Normal number of platelets 150 - 450 (this is considered as more than we need)
At what point (level) do we treat low number of platelets?
We treat platelets that are about 30 or less
Ix in suspected bleeding disorder (and justification)
- 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)
What does PT look at?
Prothrombin Time (PT)
- PT looks at extrinsic pathway (factor VII etc)
- long prothrombin time -> long for the blood to clot
What does APTT look at?
APTT looks at intrinsic pathway (factor XII, kallakerin etc)
Causes of long PT
causes of long APTT
What findings may be suggestive of coagulation problems? (2)
•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)
What ‘other’ Ix we perform in a pt with suspected coagulopathy?
- 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
What factors deficiencies are there in:
Haemophilia A
Haemophilia B
- Haemophilia A -> factor VIII deficient
- Haemophilia B -> factor XI deficient
What is (a simple) genetic mechanism of hemophilia?
X linked
What abnormality is seen on Ix of Haemophilia?
As factors VIII and IX belong to intrinsic cascade -> prolonged APTT (as intrinsic cascade is affected)
Complications/consequences of haemophilia
- Haemarthrosis - bleeding into joint spaces
- Haemophilic Arthropathy -> result of haemarthrosis
- Intramuscular bleeds
- Intracranial bleeds
- Haematuria
- ‘hidden bleeds’
Pathology of Haemophilic Arthropathy
recurrent bleed into joint space -> inflammation is activated -> destruction of the joint -> changes in the joint -> functional problems
Treatment of haemophilia
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)
Possible complications of Haemophilia treatment
•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)
Genetics behind Von Willebrand Disease
- Type 1 and 2 vWD are autosomal dominant
*sometimes type 2 may be recessive
- Type 3 autosomal recessive
Pathophysiology of Von Willebrand Disease
- Deficiency in quality or quantity of vWF
- Deficiency of vWF will show primarily in organs with extensive small vessels (e.g. skin, GI, uterus)
What type of Von Willebrand Disease is most common + features
Type 1 is most common
- mild bleeding symptoms (e.g. nosebleeds)
- occasional more severe symptoms
*blood type may affect the presentation of vWD and severity of its symptoms
What severity of symptoms type 2 vWD has?
Type 2: second most common type
- mild to moderate symptoms
