Bleeding disorders

Disorders of haemostasis can be due to;

• • Vascular disorders
  • Platelet disorders
  • Coagulation disorders

• The pattern of bleeding is important in distinguishing the type of disorder
• Vascular and platelet disorders lead to bleeding from cuts, mucous membranes
• Coagulation disorders cause delayed bleeding into joints and muscles

Vascular defects

• Congenital
  • Osler-Weber-Rendu syndrome (Hereditary haemorrhagic telangectasia)
    • Telangectasia on the skin and mucous membranes due to dilation of capillaries and small arterioles
    • May cause epistaxis or chronic GI bleeds leading to iron deficient anaemia
    • It is associated with pulmonary, hepatic and cerebral arteriovenous malformations
    • Inheritance is autosomal dominant
  • CT disease e.g. Ehlers-Danlos syndrome
• Acquired
  • Senile purpura
  • Infection e.g. meningococcal, measles, dengue
  • Steroids
  • Scurvy
  • Henoch-Schonlein purpura

Thrombocytopenia

• Reduced marrow production
  • Aplastic anaemia
  • Megaloblastic anaemia
  • Marrow infiltration
  • Marrow suppression e.g. cytotoxic drugs, radiotherapy
• Excess destruction
  • Immune thrombocytopenic purpura
  • Causes by autoantibodies which lead to platelet destruction
  • It can be acute and self limiting (in children) or chronic (women) resulting in fluctuating courses of bleeding, purpura, epistaxis and menorrhagia
  • Treat with immunosuppression or splenectomy
  • DIC
  • Thrombotic thrombocytopenic purpura
  • Haemolytic uraemia syndrome
  • Sequestration e.g. hypersplenism
• Causes of reduced platelet function
  • Myeloproliferative disease
  • NSAIDs
  • Urea

Coagulation disorders

• Congenital
  • Haemophilia
  • Von Willebrand’s disease
• Acquired
  • Anticoagulants
  • Liver disease
  • DIC
  • Vitamin K deficiency (malabsorption)

Haemophilia A

• Factor VIII deficiency
• Inherited in an X-linked recessive manner
• Bleed into joints and muscles
• Management
  • Avoid NSAIDs and IM injections
  • Desmopressin raises Factor VIII levels

Haemophilia B

• Christmas disease
• Factor IX deficiency
• X-linked inheritance
• Behaves clinically like haemophilia A

Liver disease

• Results in;
  • Reduced synthesis of clotting factors
  • Reduced absorption of Vitamin K
  • Abnormalities of platelet function

Fibrinolysis

• The fibrinolytic system causes fibrin dissolution and acts via the generation of plamin
• Starts with release of tissue plasminogen activator (t-PA) from endothelial cells, a process stimulated by fibrin formation
• t-PA converts inactive plasminogen to plasmin which then cleaves fibrin
• t-PA and plasminogen both bind fibrin those localising fibrinolysis to the clot area

Coagulation tests

• Prothrombin time
  • Thromboplastin is added to test the extrinsic system
  • Tests for abnormalities in factors I, II, V, VII and X
  • Prolonged by warfarin, vit K deficiency, liver disease, DIC

• Activated partial thromboplastin time (APTT)
  • Kaolin is added to test the intrinsic system
  • Tests for abnormalities in factors I, II, V, VIII, IX, XII
  • Normal range is 35-45 sec
  • Prolonged by heparin treatment, haemophilia, DIC

Anticoagulants

• Can be used for therapeutic or prophylactic indications

Low molecular weight heparin

• Inactivates factor Xa
• Doesn’t require monitoring
• Accumulates in renal failure

Unfractionated heparin

• Inactivates antithrombin, factor Xa and IXa
• Requires monitoring via APTT
• Both can cause bleeding
• UFH can cause heparin induced thrombocytopenia (HIT) and osteoporosis
• CI – bleeding disorders, low platelets, previous HIT, peptic ulcer, cerebral haemorrhage, severe hypertension, neurosurgery

Warfarin

• Inhibits the reductase enzyme responsible for regenerating the active form of Vitamin K
• CI – peptic ulcer, bleeding disorder, severe hypertension, pregnancy
• Use in caution in the elderly and those with previous GI bleeds
• Generally given at 6pm

Beginning therapeutic anticoagulation

• Start warfarin and heparin together
• Continue heparin until target INR is reached and until day 5 as initially warfarin is prothrombotic

Target INRs

• PE and DVT (2-3 if recurrent aim for 3.5)
• AF – 2-3
• Prosthetic heart valves 3-4