Haemophilia Flashcards
Define haemophilia.
Haemophilia is a bleeding disorder, usually inherited with an X-linked recessive inheritance pattern, which results from the deficiency of a coagulation factor.
What is the most common type of haemophilia?
Haemophilia A - factor 8 deficiency
How common is haemophilia? Who is most affected?
Haemophilia A affects 1 in 5,000-10,000 males
Haemophilia B affects 1 in 25,000-30,000 males
Haemophilia C more common in Ashkenazi Jews
What is the aetiology of haemophilia?
Haemophilia A and B - X linked recessive inheritance. 30% of cases are new mutations and many mutations in FVIII and FIX genes have been described.
Acquired haemophilia has AI aetiology, resulting from development of auto-antibodies to coagulation factors, most commonly FVIII. Cause is unknwon.
Rare cases of girls/women with severe haemophilia are described because of extreme lyonization, homozygosity, mosaicism, or Turner syndrome.
Which part of the coagulation cascade is affected in haemophilia?
Intrinsic pathway
Factor VIII is a cofactor for factor IXa, which, in the presence of Ca2+ and phospholipids, forms a complex that converts factor X to the activated form Xa
Factor IXa activates factor X to Xa
What are the symptoms of haemophilia?
Symptoms begin in early childhood
- Haemarthroses - most common
- Painful bleeding into muscles
- Haematuria
- Excessive bruising
- Prolonged bleeding after surgery/trauma
Female carriers - usually asymptomatic but may have low-enough levels to have excess bleeding after trauma.
A+B are indistinguishable clinically.
What are the signs of haemophilia?
- Multiple bruises
- Muscle haematomas, haemarthrosis, joint deformity
- Painful, distended abdomen - intra-abdominal
- Nerve palsies (nerve compression by haematoma)
- Signs of iron-deficiency anaemia - pallor, fatigue
What investigations would you do for haemophilia?
Clotting screen - play Table Tennis outside, Play Tennis inside (extrinsic = aPTT, intrinsic = PT)
- raised APTT (intrinsic and common).
- normal PT (extrinsic )
- normal bleeding time, thrombin time and prothrombin time.
FBC - normal; low Hb if there has been significant bleeding
Coagulation factor assays (III, IX). Severity is based on level of factor present (see later card).
Mixing study - incubating patient plasma with normal plasma for 2 hours at 37°C and repeating aPTT –> correction of aPTT = suggests coagulation factor deficiency. In patients with acquired haemophilia, prolonged aPTT cannot be corrected.
Closure time/bleeding time and platelet aggregation studies - normal; used to evaluate platelet function.
Other investigations:
- Arthroscopy
- Play x-ray - may show acute joint bleeding (haemarthrosis), or bone changes more consistent with chronic arthropathy
- Abdominal USS/ abdo/pelvic CT
What are the types of anaemia?
Most common:
- Haemophilia A results from the deficiency of clotting factor VIII.
- Haemophilia B results from the deficiency of clotting factor IX. (Christmas disease, after first patient)
Other:
- Haemophilia C (rare) - mild form affecting both sexes, due to factor XI deficiency. It predominantly occurs in Ashkenazi Jews.
- Acquired haemophilia It is much rarer and has autoimmune-related aetiology with no genetic inheritance pattern.
What is the difference in clinical presentation of coagulation defects and platelet disorders generally?
Type of presentation:
- Mucosal/skin petechiae/purpura - due to lack of coagulation factors
- Local bleeding/haematoma/joint bleeding – platelet disorder
Timing of presentation:
- Immediate – lack of formation of platelet plug, so platelets are the cause
- Delayed – coagulation
How is severity of haemophilia categorised?
Related to factor level…
- <1% of normal - Severe - spontaneous bleeding
- 1-5% of normal - Moderate - bleeding with mild injury
- 5-25% of normal- Mild - bleeding with surgery or trauma
What is the immediate treatment of bleeding in haemophilia?
Elevate and apply ice and pressure (RICE) - physiotherapy soon after the joint bleeding has ceased. Needle aspiration not necessary unless clearly infective.
Analgesia (not aspirin or NSAIDs)
Factor concentrate infusion - given until a specific calculated % of factor is reached usually >50%
Antifibrinolytic e.g. TXA or aminocaproic acid - work by inhibiting plasmin, enzyme involved in fibrinolysis. Contraindicated in haematuria as will cause clots.
Refer to haematology if concerned
+/- Desmopressin - those with mild haemophilia A may benefit.
What is a major side effect to factor IX concentrate?
Anaphylaxis - so treatment for first 10-20 days should be given in hospital setting
What is a major side effect to factor IX concentrate?
Anaphylaxis - so treatment for first 10-20 days should be given in hospital setting
What bleeding prophylaxis may be used in haemophilia?
In those with severe haemophilia (<1% of normal factor levels):
- Factor infusion - x2-3/week
- Emicizumab - mAb which mimics function of F8; weekly, biweekly or 4-week intervals.
- Desmopressin - can be given prior to minor surgery for those with mild haemophilia A (>5% of normal factor)
- Factor infusioin pre-procedure
- Antifibrinolytic - best for mucosal procedure like dental. Given every 6hrs for 7-10days beginning the night before the procedure.
