Bleeding disorders Flashcards
What is haemophilia?
Bleeding diatheses resulting from an inherited deficiency of a clotting factor. Note that the clotting factors have no abnormalities, they are just depleted.
What are the types of haemophilia? (x3)
- A (most common): deficiency of factor VIII
- B: deficiency of factor IX (also known as Christmas disease)
- C: deficiency of factor XI
What is the aetiology of haemophilia? (x3 points)
- Haemophilia A and B exhibit X-linked recessive inheritance. Therefore, men are exclusively affected, although many female carriers have clotting factor levels in the haemophilia range due to lyonization (random inactivation of the normal X chromosome)
- 30% of patients with congenital haemophilia have no family history as the mutation is spontaneous
- Acquired haemophilia is much rarer and has an autoimmune aetiology with autoantibodies to coagulation factors.
What is the epidemiology of haemophilia: Gender? Ethnicity?
Almost exclusively MEN. Haemophilia C is more common in Ashkenazi Jews.
What are the signs and symptoms of haemophilia? (x6) Onset?
- Symptoms begin from early childhood
- Bruising
- Hemarthroses with swollen painful joints occurring spontaneously or with minimal trauma
- Painful bleeding into muscles
- Haematuria
- Nerve palsies from nerve compression by haematoma
- Signs of iron-deficiency anaemia if bleeding severe/prolonged
What are the signs and symptoms of female carriers of haemophilia?
Usually asymptomatic though may have excess bleeding after trauma.
What are the investigations for haemophilia? (x2 +2)
- CLOTTING SCREEN: raised APTT but NOT PTT (because FVIII and FIX are involved in only the INTRINSIC PATHWAY and common pathway; PT assesses extrinsic pathway and common pathway)
- COAGULATION FACTOR ASSAYS: low FVIII/IX/XI
- vWF ASSAY: to exclude von Willebrand’s disease
- X-RAY: to assess arthroscopy which can manifest as a complication
What is von Willebrand’s disease?
Inherited bleeding disorder.
What is the pathophysiology of Von Willebrand Disease?
- VWF has two functions in haemostasis – the critical link between platelets (glycoprotein-Ib) and exposed vascular subendothelium collagen, and binds to coagulation factor VIII and prevents its degradation.
- Deficiency of VWF means that initial recruitment steps of platelets are dysfunctional, so bleeding is not initiated.
- It also means that FVIII levels fall, which causes haemophilia-like symptoms.
What is the aetiology of von Willebrand Disease? (x2)
- HEREDITARY mutation results in decrease in quantity or function (common) – autosomal dominant and occasional recessive
- ACQUIRED due to antibody (rare).
What are risk factors for VWD? (x4)
Lymphoproliferative disorders, aortic stenosis, myeloproliferative disorders, hypothyroidism
How is VWD staged? (x3)
- TYPE 1: deficiency of VWF where you don’t make SOME.
- TYPE 2: VWF with abnormal function.
- TYPE 3: complete deficiency of VWF – autosomal recessive.
What is the epidemiology of VWD: Common? Gender?
Most common inherited bleeding disorder. There is no gender split, though women are more likely to be diagnosed due to menorrhagia.
What are the signs and symptoms of VWD? (x5)
- Prolonged bleeding
- Easy and excessive bruising
- Menorrhagia
- Epistaxis
- GI bleeding
What are the investigations for VWD? (x4)
- COAGULATION STUDIES: PT is usually normal; APTT raised when FVIII fall enough (remember vWF usually stabilises FVIII)
- vWF antigen is reduced
- vWF function assay (ristocetin cofactor assay) is reduced (denotes reduced platelet aggregation by vWF in the presence of ristocetin). Apart from in Type 2 because Type 2 is defined as qualitative rather than quantitative changes in vWF
- FVIII: may be decreased
