Flashcards in Abnormalities of Homeostasis Deck (32)
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
State one very common cause of thrombocytopenia.
What is a distinctive clinical feature of thrombocytopenia?
State three hereditary platelet defects.
Glanzmann’s Thrombasthenia – absence of GlpIIb/IIIa (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 causes 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. 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
State some acquired causes of vessel wall conditions that cause defects in primary haemostasis.
Ageing (senile purpura)
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
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?
Assays for VWF
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.
2 – lethal
8 & 9 (haemophilia) – severe but compatible with life
11 – bleeding after trauma but not spontaneously
12 – no excess bleeding
State some acquired causes of deficiency of coagulation factors.
Anti-coagulant drugs (e.g. warfarin)
State some disorders of coagulation that are due to increased consumption.
Disseminated intravascular coagulation (DIC)
What happens in Disseminated Intravascular Coagulation (DIC)?
Generalised activation of coagulation
It is associated with sepsis, inflammation and tissue necrosis
It consumes and depletes coagulation factors
Platelets are consumed
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?
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
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)
State some bleeding disorders that are not detected by routine clotting tests.
Mild factor deficiencies
Von Willebrand Disease
Factor 8 Deficiency (cross-linking)
Vessel wall disorders
Metabolic disorders (e.g. uraemia)
NOTE: urea interferes with platelet function
State a hereditary disorder of fibrinolysis.
State two acquired disorders of fibrinolysis.
Drugs such as tissue plasminogen activator
Disseminated intravascular coagulation (DIC) – because everything has been used up
What is the treatment that is considered for a patient whoseabnormal haemostasis is caused by immune destruction of platelets?
Immunosuppression (e.g. prednisolone)
What clotting factors are found in cryoprecipitate?
Von Willebrand Factor