Abnormalities of Haemostasis Flashcards
What is abnormal bleeding?
- Epistaxes not stopped by 10 minutes of compression
- Cutaneous haemorrhage/bruise without apparent trauma
- Prolonged (>15m) bleeding from trivial wounds
- Menorrhagia requiring treatment or leading to anaemia
- Heavy, prolonged or recurrent bleeding after surgery
What causes abnormal bleeding?
- Lack of a specific factor – failure of production (genetic or acquired), increased consumption/clearance.
- Defective function of a factor – genetic or acquired defect (e.g. drugs)
Where are the defects in primary haemostasis?
platelets, vWF or collagen
How do defects in platelets cause abnormal primary haemostasis>
Low numbers – thrombocytopenia:
- Bone marrow failure – e.g. leukaemia, B12 deficiency
- Accelerated clearance – e.g. ITP, DIC
- Pooling and destruction in splenomegaly
Impaired function:
Hereditary absence of glycoproteins/storage-granules (Gp2b3a, Gp1b, dense granules)
Acquired from drugs – e.g. aspirin, NSAIDs, Clopidogrel
- ITP – Immune Thrombocytopenia.
- Anti-platelet antibodies attack platelets that get engulfed by splenic macrophages
- Very common cause of thrombocytopenia
What are some causes of thrombocytopenia?
- Failure of platelet production by megakaryocytes
- Shortened half-life of platelets
- Increased pooling and decreased half-life of platelets in spleen
What happens in von Williebrand disease?
Hereditary decrease of quantity and function/quality – common form of vWD (more common)
- vWF has two functions – bind collagen (to catch platelets) and stabilise F8.
- vWD is usually hereditary:
> Type 1 (partial), 3 – deficiency of vWF.
> Type 2 – abnormal function of vWF.
Acquired due to an antibody – rare form of vWD
What are some inherited and acquired defects in collagen/ vessel wall?
Inherited (rare)
- Hereditary haemorrhagic telangiectasia
- Ehlers-Danlos syndrome and other connective tissue disorders.
Acquired
- scurvy
- steroid therapy
- ageing (age related purpura)
- vasculitis
What are typical patterns of bleeding?
- Immediate
- Prolonged from cuts and after trauma/surgery
- Epistaxes
- Gum bleeding
- Menorrhagia
- Easy bruising
How can you test for disorders of primary haemostasis?
- Platelet count
- Bleeding time (PFA100 lab test)
- Assays of vWF
- Clinical observation
Where is the defect in disorders of secondary haemostasis?
crosslinked fibrin
What are the consequences of deficiencies of factors 8/9, 2, 11, 12?
- F8/9 – Haemophilia A/B, Haemarthrosis is hallmark, compatible with life
- F2 (thrombin) – lethal
- F11 – bleed after trauma but not spontaneously
- F12 – no excess bleeding at all
What are acquired causes of clotting factor deficiencies?
- Liver disease
- Dilution – e.g. transfusions.
> RBC transfusions don’t contain plasma unless they’re major - Anticoagulant drugs – e.g. Warfarin
What are causes of increased consumption of clotting factors?
Acquired:
- DIC (Disseminated Intravascular Coagulation)
• Generalised activation of coagulation via TF
• Associated with sepsis, major tissue damage and inflammation
• Consumes and depletes coagulation factors, platelets and fibrinogen
• Deposition of fibrin in vessels causes organ failure
Immune – auto-antibodies
What are the typical bleeding patterns of someone with disorders of secondary haemostatsis?
Superficial cuts DO NOT bleed (platelets are fine)
Bruising is common, nosebleeds are rare
Spontaneous bleeding is deep, into muscles and joints
Bleeding after trauma may be delayed but is prolonged
Bleeding frequently restarts after stopping
What tests are used to identify disorders of secondary haemostasis?
What will the results be for haemophilia?
Screening tests (‘clotting screen’): - PT – Prothrombin Time > Extrinsic & Common pathway defects - APTT – Activated Partial Thromboplastin Time > Intrinsic & Common pathway defects - FBC – Full Blood Count (for platelets)
Factor assays – e.g. for F8 etc
Tests for inhibitors
- a contact (e.g. glass) must be made to initiate coagulation.
- So haemophilia will have a normal PT and TT (thrombin time) but an abnormal APTT as the intrinsic pathway is affected
