Abnormalities of Homeostasis Flashcards
Broadly speaking, what are the two causes of abnormal haemostasis?
Lack of a specific factor
Defective function of a specific factor
What can cause thrombocytopenia?
Failure of production – bone marrow failure e.g. leukaemia, B12 deficiency
Accelerated clearance - DIC (disseminated intravascular coagulation), auto-ITP (autoimmune thrombocytopenia purpura)
State one very common cause of thrombocytopenia.
Autoimmune thrombocytopenia
What is a distinctive clinical feature of thrombocytopenia?
Petechiae
State three hereditary platelet defects and what causes them.
Glanzmann’s Thrombasthenia:
absence of GlpIIb/IIIa (aka integrin αIIbβ3)
prevents platelet aggregation
Bernard Soulier Syndrome:
absence of GlpIb
prevents binding to von Willebrand factor
Storage Pool Disease:
storage granules are not able to release adequately
Broadly speaking, state three mechanisms of thrombocytopenia.
Failure of platelet production by the megakaryocytes
Shortened half-life of platelets
Increased pooling of platelets in an enlarged spleen (hypersplenism)
State a broad acquired cause of impaired platelet function.
Drugs e.g. Asprin, NSAIDs, clopidogrel
What are the two roles of von Willebrand factor in haemostasis?
Binding to collagen and trapping platelets
Stabilising factor 8 (if VWF is low, factor 8 may be low)
Von Willebrand Disease is usually hereditary. What are the threetypes of von Willebrand disease? State their pattern of inheritance.
Type 1 – deficiency of VWF but it functions normally (autosomal dominant)
Type 2 – VWF does not function normally (autosomal dominant)
Type 3 – VWF not made at all (autosomal recessive)
State two inherited vessel wall conditions that cause defects in primary haemostasis.
Hereditary haemorrhagic telangiectasia
Ehlers-Danlos Syndrome
State some acquired causes of vessel wall conditions that cause defects in primary haemostasis.
Scurvy
Steroid therapy
Ageing (senile purpura)
Vasculitis
Describe the pattern of bleeding in defects of primary haemostasis.
The primary platelet plug isn’t strong enough to stop the bleeding Bleeding is immediate Prolonged from cuts Epistaxes Gum bleeding Menorrhagia Easy bruising Prolonged bleeding after trauma and surgery
How are the clotting factors affected in severe von Willebrand disease?
Reduced factor 8 (because VWF stabilizes factor 8)
This causes haemophilia type bleeding patterns
What tests can be done for disorders of primary haemostasis?
Platelet count
Bleeding time
Assays for VWF
Clinical observation
What is haemophilia caused by?
What is its pattern of inheritance?
Lack of Factor 8 (A) or Factor 9 (B)
This leads to impaired thrombin generation
In haemophilia you get failure to generate fibrin to stabilize the platelet plug
It is X-linked recessive
Describe the difference in outcome for deficiencies of factors 2, 8 & 9, 11 and 12.
II - lethal
VIII & IX (haemophilia) – severe but compatible with life
Spontaneous joint and muscle bleeding
XI – bleeding after trauma but not spontaneously
XII – no excess bleeding
State some acquired causes of deficiency of coagulation factors.
Liver disease
Dilution - haemorrhage and only red cells (not plasma) replaced
Anti-coagulant drugs (e.g. warfarin)
State some disorders of coagulation that are due to increased consumption.
Disseminated intravascular coagulation (DIC)
Autoimmune thrombocytopenia
What happens in Disseminated Intravascular Coagulation (DIC)?
Generalised activation of coagulation – Tissue factor expressed inappropriately
Associated with sepsis, major tissue damage, inflammation
Consumes and depletes coagulation factors
Platelets consumed
Activation of fibrinolysis depletes fibrinogen
Deposition of fibrin in vessels causes organ failure
Describe the pattern of bleeding in coagulation disorders.
Superficial cuts DO NOT bleed (because primary haemostasis is fine)
Bruising is common
Spontaneous bleeding is DEEP, into muscles and joints
Bleeding after trauma may be delayed and prolonged
Frequently restarts after stopping
What is the hallmark of haemophilia?
Haemarthrosis
What simple medical procedure must you avoid doing to patients with haemophilia?
Intramuscular injection – it can cause deep bleeding patterns
State some tests that are used for coagulation disorders.
Screening Tests – APTT, PT; Platelet Count
Factor Assays
Tests for inhibitors
Describe the APTT and PT results for a patient with haemophilia.
Prolongs APTT but normal PT
This is because the defect lies in the intrinsic pathway (factor 8 or 9)
