Version 1.1 Bleeding Disorders (Diatheses) 19/03/2013
Congenital bleeding disorders
Von Willebrand's disease - most common 1:1000. Mainly AD. M=F. Usually mild without spont
bleeding. ↓Prod or abnormality of vWF (req for normal plt fn and stabilisation of factor VIII).
Haemophilia A (factor VIII deficiency) & B (factor IX deficiency or Christmas disease) -
X-linked recessive. Incid: A > B (1:10,000 vs 1:60,000). Severe (<2% factor – spont muscle & jt
bleeding → to crippling joint disease), mod (2-5%) & mild (bleeding only post trauma or Sx).
Other genetic disorders – rarer, AR e.g. prothrombin (factor II) deficiency is 1:2,000,000.
Glanzmann's thrombasthenia and Bernard-Soulier's disease - Rare AR diseases affecting
platelet membrane glycoproteins and causing abnormal platelet binding and aggregation
Acquired disorders
• Liver disease and cirrhosis → ↓synthesis of clotting proteins and thrombocytopenia.
• Vit K def from dietary def, GI malabsorption or absence of gut bacteria in newborns.
• Shock, sepsis or malignancy → ↑bleeding tendency, often by DIC
• Renal disease causes platelet dysfunction and reduced aggregation.
• AutoAb to coag factors (e.g. in lymphoma and SLE) or to plts (as in ITP).
• Amyloidosis where factor X deficiency occurs as well as infiltration of blood vessels.
• Old age, prolonged steroid use and vitamin C deficiency all ↓integrity of blood vessel wall.
Presentation
Haemophilias – onset in early childhood, dental bleeds, haematomas & haemarthrosis.
vWD – often asymptomatic, post-surg, mucocutaneous bleeding common. Spont. bleeding rare.
Investigations
Bloods: FBC and film, APPT (↑with factor VIII and IX def), INR (↑ with factors I, II, V, VII
and X def), fibrinogen, FDPs, bleeding time (↑ with vWD)
Gene & specific factors assays: VIII & IX for haemophilias; VIII & vWF & ristocetin in vWD
Acquired Disease Platelet Count INR APTT Thrombin time
Liver disease Low Prolonged Prolonged Normal (rarely prolonged)
DIC Low Prolonged Prolonged Grossly prolonged
Massive transfusion Low Prolonged Prolonged Normal
Oral anticoagulants Normal Grossly prolonged Prolonged Normal
Heparin Normal (rarely low) Mildly prolonged Prolonged Prolonged
Circulating anticoagulant Normal Normal or prolonged Prolonged Normal
Management
Haemophilia
• Care via a regional haemophilia centre.
• Early factor VIII (1U/kg →↑level by 2%) or IX (1U/kg →↑level by 1%) transfusions if
bleeding, aim for 30-40% in mild, >50% in mod & 100% in sev bleeding.
• Symptomatic relief - analgesia, rest, physiotherapy etc - for muscle/jt bleeds.
• Prophylaxis: Tranexamic acid may prevent bleeding after minor ops in those with mild
haemophilia A/B or desmopressin (DDAVP) for mild or moderate haemophilia A only.
• Gene therapy – not yet.
Von Willebrand's disease
• Mild cases are treated with desmopressin, tranexamic acid and OCP for menorrhagia.
• Severe cases may need vWF concentrate.
• Avoid NSAIDs and aspirin
Acute ITP - rarely needs treating but steroids may be useful.
If inherited disorder: genetic counselling and prenatal diagnosis.
Congenital bleeding disorders
Von Willebrand's disease - most common 1:1000. Mainly AD. M=F. Usually mild without spont
bleeding. ↓Prod or abnormality of vWF (req for normal plt fn and stabilisation of factor VIII).
Haemophilia A (factor VIII deficiency) & B (factor IX deficiency or Christmas disease) -
X-linked recessive. Incid: A > B (1:10,000 vs 1:60,000). Severe (<2% factor – spont muscle & jt
bleeding → to crippling joint disease), mod (2-5%) & mild (bleeding only post trauma or Sx).
Other genetic disorders – rarer, AR e.g. prothrombin (factor II) deficiency is 1:2,000,000.
Glanzmann's thrombasthenia and Bernard-Soulier's disease - Rare AR diseases affecting
platelet membrane glycoproteins and causing abnormal platelet binding and aggregation
Acquired disorders
• Liver disease and cirrhosis → ↓synthesis of clotting proteins and thrombocytopenia.
• Vit K def from dietary def, GI malabsorption or absence of gut bacteria in newborns.
• Shock, sepsis or malignancy → ↑bleeding tendency, often by DIC
• Renal disease causes platelet dysfunction and reduced aggregation.
• AutoAb to coag factors (e.g. in lymphoma and SLE) or to plts (as in ITP).
• Amyloidosis where factor X deficiency occurs as well as infiltration of blood vessels.
• Old age, prolonged steroid use and vitamin C deficiency all ↓integrity of blood vessel wall.
Presentation
Haemophilias – onset in early childhood, dental bleeds, haematomas & haemarthrosis.
vWD – often asymptomatic, post-surg, mucocutaneous bleeding common. Spont. bleeding rare.
Investigations
Bloods: FBC and film, APPT (↑with factor VIII and IX def), INR (↑ with factors I, II, V, VII
and X def), fibrinogen, FDPs, bleeding time (↑ with vWD)
Gene & specific factors assays: VIII & IX for haemophilias; VIII & vWF & ristocetin in vWD
Acquired Disease Platelet Count INR APTT Thrombin time
Liver disease Low Prolonged Prolonged Normal (rarely prolonged)
DIC Low Prolonged Prolonged Grossly prolonged
Massive transfusion Low Prolonged Prolonged Normal
Oral anticoagulants Normal Grossly prolonged Prolonged Normal
Heparin Normal (rarely low) Mildly prolonged Prolonged Prolonged
Circulating anticoagulant Normal Normal or prolonged Prolonged Normal
Management
Haemophilia
• Care via a regional haemophilia centre.
• Early factor VIII (1U/kg →↑level by 2%) or IX (1U/kg →↑level by 1%) transfusions if
bleeding, aim for 30-40% in mild, >50% in mod & 100% in sev bleeding.
• Symptomatic relief - analgesia, rest, physiotherapy etc - for muscle/jt bleeds.
• Prophylaxis: Tranexamic acid may prevent bleeding after minor ops in those with mild
haemophilia A/B or desmopressin (DDAVP) for mild or moderate haemophilia A only.
• Gene therapy – not yet.
Von Willebrand's disease
• Mild cases are treated with desmopressin, tranexamic acid and OCP for menorrhagia.
• Severe cases may need vWF concentrate.
• Avoid NSAIDs and aspirin
Acute ITP - rarely needs treating but steroids may be useful.
If inherited disorder: genetic counselling and prenatal diagnosis.
