T3 L6: Bleeding disorders

• What are the causes of bleeding?

  Vascular disorders

  Platelet disorders:

  • thrombocytopenia (thrombocyte deficiency)
  • defective function

  Defective coagulation:

  • inherited
  • acquired

  Iatrogenic (caused by medical treatment / examination)

  • Anti-coagulant therapy
  • Anti-platelet therapy
• What pattern of bleeding results from vascular and platelet causes?

  bleeding into mucous membranes and skin
• What pattern of bleeding results from coagulation disorders?

  bleeding into joints and soft tissue (eg muscles)
• What are examples of inherited vascular bleeding conditions?

  • Hereditary haemorrhagic telangiectasia (Oslar-Weber-Rendu syndrome)
  • Ehlers-Danlos syndrome
• What are examples of acquired vascular bleeding conditions?

  Scurvy (vitamin C deficiency)

  Steroids (eg prednisolone)

  Senile (elderly, loss of skin integrity)
• What is Hereditary haemorrhagic telangiectasia?

  genetic bleeding disorder

  small telangiectasia in mucous membranes

  nosebleeds

  
• What is Ehlers-Danlos syndrome?

  genetic bleeding disorder

  loose joints, stretchy skin, hypermobility

  
• What are platelets?

  derived from megakaryocytes (bone marrow)

  stimulated by thrombopoietin

  adhere at site of injury

  activate and secrete:

  • vWF
  • fibrinogen
  • F5
  • F8

  aggregate to form platelet/fibrin plug

  
• What is Thrombocytopenia?

  Low platelet count <150

  symptomatic when <20

  symptoms:

  • epistaxis (nosebleed)
  • GI bleeds
  • menorrhagia (heavy menstrual bleeding)
  • bruising

  Inherited causes (rare): Bernard-Soulier syndrome

  Acquired causes (common): ITP, drug-related, DIC
• What is Immune Thrombocytopenia (ITP)?

  autoimmune disorder

  anti-platelet antibodies

  idiopathic

  complication of CLL

  Treatment: if bleeding or platelets <20:

  • steroids
  • IV immunoglobulins
  • immunosuppression, eg rituximab
  • splenectomy

  
• What are disorders of platelet function?

  normal platelet count

  Inherited: rare, eg Glanzmann's thrombasthenia

  Acquired: drugs (much more common)

  • Aspirin
  • Clopidogrel
  • NSAIDs
• What is haemophilia?

  X-linked (males only)

  Haemophilia A - deficiency of F8

  Haemophilia B - deficiency of F9

  Clinical features:

  • spontaneous bleeding into joints and muscle
  • Unexpected post-operative bleeding
  • Chronic debilitating joint disease
  • Family history
• What is a haematoma?

  internal bleeding forming clots

  
• What is haemarthrosis?

  Joint bleeding

  
• What is the relationship between haemophilia and arthropathy?

  haemophilic arthropathy

  Permanent and irreversible joint damage is the most common complication of hemophilia that leads to disability

  causing chronic joint deformity

  
• What are two complications of haemophilia?

  chronic joint deformity

  intra-cranial bleed

  
• What are the genetic relationships in haemophilia?

  Carrier mothers have haemophilic sons

  Haemophilic fathers have obligate carrier daughters

  
• What is the treatment for haemophilia?

  recombinant F8 and F9

  prophylactic treatment
• What is von Willebrand disease?

  vWF deficiency

  autosomal dominant (family history of bleeding)

  Clinical features:

  • mucocutaneous bleeds
  • nosebleeds
  • menorrhagia
• What is von Willebrand Factor (vWF)?

  protein that carries F8

  binds platelets to endothelial collagen
• How is von Willebrand disease diagnosed?

  Tests:

  • APTT: prolonged
  • PT: normal
  • Low vWF antigen level
  • Low vWF activity
  • Low F8
• How is von Willebrand disease treated?

  desmopressin (DDAVP) - stimulates release of vWF from Weibel-Palade storage bodies

  plasma infusion containing vWF

  anti-fibrinolytics
• What are some acquired disorders of coagulation?

  Liver disease

  Vitamin K deficiency

  Disseminated intravascular coagulation (DIC)
• What is Disseminated intravascular coagulation (DIC)?

  release of pro-coagulant material into circulation

  results in consumption of clotting factors

  causes bleeding and thrombosis
• What two types of patients can have Vitamin K deficiency?

  infants who do not receive vitamin K at birth

  malabsorption due to jaundice
• What is Meningococcal DIC?

  Complication

  (disseminated intravascular coagulation)

  Prolonged PT, APTT, TT

  Raised D-dimers or FDPs

  
• What are some causes of Disseminated intravascular clotting (DIC)?

  cancer, sepsis, obstetric disasters

  
• What are types of anti-coagulant drugs?

  Heparin - MI, PE, DVT

  Warfarin - PE, DVT, AF, prosthetic valves

  DOACs (Direct Oral Anti-coagulants):

  • Direct thrombin inhibitors (dabigatran, argatroban)
  • Factor 10a inhibitors (rivaroxaban, apixaban)