Abnormalities of haemostasis Flashcards
What are the broad causes of abnormal haemostasis?
- Lack of a specific factor
a) Failure of production: congenital or acquired
b) Increased consumption/clearance - Defective function of a specific factor
a) Genetic defect
b) Acquired defect (more common) e.g. drugs, synthetic defect, inhibition
What are the disorders of primary haemostasis?
- Platelets
a) Thrombocytopenia
b) Impaired function - hereditary (Glanzann’s thombasthenia, Bernard Soulier Syndrome, Storage Pool Disease) or acquired due to drugs - vWF
a) Von Willebrand Disease - Vessel wall
a) Hereditary vascular disorders
b) Scurvy, steroids, age
What 3 things can disorders of primary haemostasis affect?
Platelets
vWF
Vessel wall
What can cause thrombocytopenia?
- BM failure, e.g. leukaemia, B12 deficiency
- Accelerated clearance, e.g. AI thrombocytopenia, DIC
- Pooling and destruction in enlarged spleen
What disorders of primary haemostasis affect the vessel wall?
Inherited (rare):
- Hereditary haemorrhagic telangiectasia
- Ehlers-Danlos syndrome, other CT disorders
Acquired
- Scurvy
- Steroid therapy - atrophy of supporting tissues of BVs –> fragile vessels
- Ageing
- Vasculitis
Describe the bleeding in disorders of primary haemostasis
Primary platelet plug not strong enough to stop bleeding
Immediate Prolonged bleeding from cuts/after trauma or surgery Epistaxis Gum bleeding Menorrhagia Easy bruising
Thrombocytopenia –> petechiae
Severe VWD - FVIII also low - some haemophilia type bleeding
How can you test for disorders of primary haemostasis?
- Platelet count, platelet morphology
- Bleeding time - PFA100 (no longer used)
- VWF assays
- Clinical observation
What is the role of the coagulation cascade?
Generate burst of thrombin to convert fibrinogen to fibrin in order to stabilise platelet plug
What is haemophilia?
Failure to generate fibrin to stabilise platelet plug
What is the effect of a deficiency of any CF?
Failure of thrombin generation and hence fibrin formation
hence plug stabilisation
What are the hereditary deficiencies of CF production?
- FVIII and FIX (haemophilia A/B)
- Severe but compatible with life
- Spontaneous joint and muscle bleeding - Prothrombin (FII) - LETHAL
- FXI - bleed after trauma but not spontaneously
- FXII - no excess bleeding
What are the acquired deficiencies of CF production?
More common in hospital settings
- Liver disease
- Dilution - dilutional coagulopathy in patients with major haemorrhage - lose red cells and plasma
- Anti-coagulant drugs, e.g. warfarin, heparin
How can CF consumption be increased?
Acquired:
- DIC
- AI antibodies
What is DIC?
- Generalised activation of coagulation - TF
- Associated with sepsis, major tissue damage, inflammation
- Consumes and depletes CFs and platelets
- Activation of fibrinolysis depletes fibrinogen
- Deposition of fibrin in vessels causes organ failure
Describe the bleeding in coagulation disorders
- Superficial cuts do not bleed (platelets work fine)
- Bruising is common
- Nosebleeds are rare
- Spontaneous bleeding is deep
- Haemarthrosis
- Bleeding after trauma may be delayed and prolonged
- Frequently restarts after stopping
How can bleeding due to platelet and coagulation defects be clinically distinguished?
Platelet/vascular:
- Superficial bleeding into skin, mucosal membranes
- Bleeding immediate after injury
Coagulation:
- Haemarthrosis
- Delayed, but severe bleeding after injury
- Bleeding often prolonged
How can you test for coagulation disorders?
- Screening tests
a) PT - identify disorders in extrinsic pathway
b) APTT - intrinsic pathway
c) FBC - platelet count - Factor assays
- Tests for inhibitors
What bleeding disorders are not detected by routine clotting tests?
- Mild factor deficiencies
- VWD
- FVIII deficiency
- Platelet disorders
- Excessive fibrinolysis
- Vessel wall disorders
- Metabolic disorders (e.g. uraemia - urea interferes with platelet function)
- Thrombotic disorders
What are the disorders of fibrinolysis?
Cause abnormal bleeding but are rare
Hereditary:
1. Anti-plasmin deficiency
Acquired:
- Drugs, e.g. tPA
- DIC
How is abnormal haemostasis treated?
Failure of production:
- Replace missing factor/platelets - prophylactic or therapeutic
- Stop drugs
Immune destruction:
- Immunosuppression, e.g. prednisolone
- Splenectomy for AI thrombocytopenia
Increased consumption:
- Treat cause
- Replace as necessary
What can be used in factor replacement therapy?
- Plasma - all CFs
- Cryoprecipitate - fibrinogen, FVIII, vWF, FXIII
- Factor concentrates - available for all except FV; prothrombin complex concentrates
- Recombinant forms of FVIII and FIX
When might DDAVP (desmopressin) be used?
Only useful in mild VWD
Vasopressin derivative
Releases endogenous stores of VWF
What is tranexamic acid used for?
Inhibiting fibrinolysis
Widely distributed - crosses placenta
Low conc in breast milk
