Haemophilia (CH) Flashcards
Define haemophilia.
Bleeding disorder, usually inherited with an X-linked recessive inheritance pattern, which results in the deficiency of a coagulation factor leading to impaired secondary haemostasis
Who does haemophilia primarily affect and why?
Males
- X-linked: females may be carriers and show mild Sx, but males only have one X chromosome
- therefore it is almost impossible for females to have haemophilia
What is haemophilia A?
- factor VIII deficiency
- most common
- X-linked recessive
- due to flip tip inversion in FVIII gene in X chromosome
What is haemophilia B?
- factor IX deficiency
- X-linked recessive
- due to point mutations and deletions
- behaves clinically like haemophilia A
What is haemophilia C?
Deficiency in factor XI - rare
What is acquired haemophilia?
Separate non-inherited condition, much rarer than congenital haemophilia and has an autoimmune-related aetiology with no genetic inheritance pattern
Suddenly appearing autoantibodies that interfere with factor VIII
How can females have haemophilia?
Female carriers have clotting factors in haemophilia range due to lyonization - random inactivation of normal X chromosome
What are the clinical features of haemophilia? (6)
- recurrent or severe bleeding
- bleeding into muscles –> haematoma (high pressure –> nerve palsies and compartment syndrome)
- haemarthrosis without trauma - bleeding into joints –> swollen painful joints spontaneously
- excessive bruising/haematoma
- recurrent nasal/oral mucosa bleeding
- intracranial haemorrhage (rare)
What might you see on examination in haemophilia? (7)
- multiple bruises
- muscle haematomas
- haemarthroses
- joint deformity
- nerve palsies (due to compression by haematomas)
- signs of IDA
- extensive cutaneous purpura (acquired haemophilia)
How do neonates with haemophilia present?
Prolonged bleeding following heel prick or circumcision
How do female carriers with haemophilia present?
Usually asymptomatic, but may experience excessive bleeding after trauma, or menorrhagia and bleeding following surgical procedures/childbirth
Generally, what is the bleeding like in haemophilia?
Deep - into muscles and joints
What is the hallmark feature of haemophilia?
Musculoskeletal bleeding - spontaneous bleeding into muscles and joints
How does acquired haemophilia present?
Extensive cutaneous purpura (bleeding into the joints is NOT a prominent feature)
What are the risk factors for haemophilia? (2+2)
- male
- family history - maternal side
- age>60 (acquired haemophilia)
- autoimmune disorders, IBD, DM, hepatitis, pregnancy etc (acquired haemophilia)
What are the first-line investigations for haemophilia? (4)
- clotting screen
- coagulation factor assays
- mixing study
- FBC
What clotting factors are involved in the intrinsic pathway (APTT)?
VIII, IX, XI, XII
What clotting factors are involved in the extrinsic pathway (PT)?
III (tissue factor), VII
What clotting factors are involved in the common pathway?
I, II, V, X, XIII
What does a clotting screen show in haemophilia?
- prolonged APTT - VIII and IX in intrinsic pathway
- normal PT (if prolonged check factor V and VII)
- bleeding time typically prolonged
What is requested in suspected haemophilia if APTT is prolonged?
Mixing study - correction of APTT with mixing study suggests coagulation factor deficiency
(Incubate patient plasma with normal plasma for 2h at 37C –> repeat APTT is normal)
What do coagulation factor assays show in haemophilia?
- haemophilia A - low VIII
- haemophilia B - low IX
- (haemophilia C - low XI)
How is the diagnosis of haemophilia confirmed?
Prolonged APTT + plasma factor VIII and IX (and XI) assay = low
What might FBC show in haemophilia?
Anaemia
What are some differential diagnoses for haemophilia? (8)
- von Willebrand disease - male and female, more mucosal bleeding Sx
- platelet dysfunction - mucocutaneous bleeding
- deficiency of other coagulation factors - MSK bleeding uncommon, PT&APTT prolonged, thrombosis
- Ehlers-Danlos syndrome - mucosal bleeding, skin hyperextensibility, joint laxity
- scurvy - mucosal bleeding
- Fabry’s disease - mucosal bleeding, skin lesions, pain in extremities, renal/heart disease, ocular signs
- DIC - decreased platelets, underlying cause
- antiphospholipid syndrome - raised APTT and normal PT + thrombocytopenia
How is haemophilia managed? (3)
- factor concentrates - substitution of clotting factors
- desmopressin (mild haemophilia A) - triggers release of VWF from endothelial cells –> increase in factor VIII plasma concentration
- antifibrinolytic therapy (tranexamic acid/aminocaproic acid) - inhibits break down of clots to reduce bleeding risk
How do we manage an acute bleed in haemophilia? (4)
- factor concentrates
- resuscitation and ABC - IV fluids
- anticonvulsants for intracranial haemorrhage
- antifibrinolytic agent (tranexamic acid) - if life threatening
When do we give bypassing agents for haemophilia?
- recombinant factor VIIa or VIII inhibitor bypassing fraction
- 2nd line if factor concentrates do not cause haemostasis
- 1st line if high-titre factor inhibitor - DO NOT give factor concentrates
How do we manage muscle/joint pains in haemophilia?
- RICE
- analgesia - paracetamol, opioids, COX-2 inhibitors
- physiotherapy
When is emicizumab used for haemophilia?
Humanised monoclonal antibody - approved for prophylaxis in haemophilia A patients with and without inhibitors
How do we manage recurrent bleeds into a single specific joint in haemophilia?
Radioactive synovectomy (synoviorthesis)
What are some complications of haemophilia? (6)
- compartment syndrome (treat with aggressive factor replacement NOT fasciotomy)
- joint/muscle damage
- bleeding/life-threatening haemorrhage
- allergic reaction
- development of treatment-related inhibitors to factors VIII and IX
- bloodborne infections
Describe the prognosis of haemophilia.
Advances in treatment allow a near-normal lifestyle and lifespan for most patients with haemophilia A and B
What can cause a grossly elevated APTT? (3)
- heparin therapy
- haemophilia - low factor VIII/IX
- antiphospholipid syndrome - prothrombotic; normal PT, high APTT, thrombocytopenia
