Inherited Bleeding Disorders

Question 1

Describe haemophilia

Answer 1

-Commonest severe inherited bleeding disorder
-Haemophilia A – FVIII deficiency
=1/5000 males
-Haemophilia B – FIX deficiency (Christmas disease)
=1/30,000 males
-X-linked recessive inheritance- sons 50% chance affected, daughters 50% carriers, 1/3 new mutation (no family history)

Question 2

Blood coagulation

Answer 2

-Intrinsic pathway cascade- Factor 8/9
=Measured by activated partial thromboplastin time
=In haemophilia, isolated prolonged APTT in coagulation screen
=Normal prothrombin time and fibrinogen

Question 3

Detection/diagnosis of haemophilia

Answer 3

-Family history
=Carrier mother, antenatal counselling
-Clinical suspicion
=Prolonged bleeding/ rebleeding
=Unusual surgical bleeding - circumcision
=Bleeding with IM injections/ vaccinations

-Coagulation screen
=Prolonged APTT, normal PT and fibrinogen
=APTT corrects with 1:1 mix

Question 4

Features of haemophilia

Answer 4

haemarthrosis, joint damage and deformity
-Compartment syndrome
haematomas
prolonged bleeding after surgery or trauma
Most cases present in neonates or early childhood. It can present with intracranial haemorrhage, haematomas and cord bleeding in neonates

Other areas of bleeding include:

Oral mucosa
Nosebleeds (epistaxis)
Gastrointestinal tract
Urinary tract, causing haematuria
Intracranial haemorrhage
Surgical wounds

Question 5

Classification of haemophilia with level of F8/9 and associated complications

Answer 5

-Reduced Factor VIII or IX
=Normal range 50-150% iu/ml
=Mild 6-49% (bleeding with surgery or dental work/ major trauma)
=Moderate 1-5% (bleeding with minor trauma, subcutaneous or intramuscular
=Severe < 1% (recurrent spontaneous joint bleeds, chronic joint damage, spontaneous intracranial bleeds-rare)

Question 6

Complications of haemophilia

Answer 6

-Spontaneous bleeding - severe patients
=Joint bleeds – target joints
-Increased bleeding with trauma
=subcutaneous, intramuscular
=Head injury
-Surgical/iatrogenic bleeding
=Vaccinations
=Circumcision
=Dental extractions

Question 7

Historical treatment of haemophilia

Answer 7

-None
-Whole blood transfusion
=Low levels of factor 8/9, large quantities needed
-Plasma infusion
-Plasma derived specific factors
=HIV, Hepatitis C

Question 8

Current management of haemophilia

Answer 8

-The affected clotting factors (VIII or IX) can be given by intravenous infusion, either regularly or in response to bleeding. A complication of this treatment is the formation of antibodies (called inhibitors) against the treatment, resulting in it becoming ineffective.

-Anti-fibrinolytics
-DDAVP in mild disease
-Recombinant specific factor
=On-demand for bleeding episodes
=Prophylaxis
==severe -> moderate phenotype conversion
==Surgery
=Home treatment
-Physiotherapy (joints and muscles)

Up to 10-15% of patients with haemophilia A develop antibodies to factor VIII treatment.

Question 9

Inhibitor formation complications

Answer 9

-Anti-FVIII antibodies
-Increased bleeding unresponsive to FVIII therapy
-Needs bypassing agents and immune tolerance induction

Question 10

Describe Von Willebrand Disease

Answer 10

-Commonest inherited bleeding disorder
-VWB factor:
=Defective platelet adhesion & aggregation
=Protects FVIII from degradation
-Autosomal dominant inheritance
-Variable phenotype severity (amount/ function)
-Mucosal bleeding
=Easy bruising, dental bleeding, epistaxis, menorrhagia (behaves like a platelet disorder)
=Surgical and post-traumatic bleeding

type 1: partial reduction in vWF (80% of patients)
type 2*: abnormal form and function of vWF
type 3**: total lack of vWF (autosomal recessive)

-I: prolonged bleeding time, prolonged APTT, factor 8 levels may be moderately reduced, defective platelet aggregation with ristocetin

-M: tranexamic acid for mild bleeding, desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cell, factor VIII concentrate

Question 11

What is involved in a pre-op bleeding assessment?

Answer 11

-Family history and personal history
=Surgical or dental challenges – may be absent
=Menorrhagia, peripartum, epistaxis
-Consider acquired bleeding disorders
-Coagulation screen indicated if
=High risk surgery with no challenges
=History suggests inherited or acquired disorder
May be normal – discuss with haematology if concerns

Question 12

Examples of acquired bleeding disorders

Answer 12

-DIC (disseminated intravascular coagulation)
-Drugs
-Liver disease
-Iatrogenic BM failure