Abnormalities of Haemostasis Flashcards
Broadly speaking, what are the 2 causes of abnormal haemostasis?
Lack of a specific factor (failure of production or increased clearance)
Defective function of a specific factor (genetic or acquired)
What can cause a failure of production leading to thrombocytopenia?
Bone marrow failure
e.g. leukaemia, B12 deficiency
What can cause increased clearance leading to thrombocytopenia?
Autoimmune thrombocytopenia (ITP) (common) DIC
What is a distinctive clinical feature of thrombocytopenia?
Petechiae
State 3 hereditary platelet defects.
Glanzmann’s Thrombasthenia: absence of GpIIb/IIIa (prevents platelet aggregation)
Bernard Soulier Syndrome: absence of GpIb (prevents binding to vWF)
Storage Pool Disease: storage granules not able to release adequately
State 3 mechanisms/ causes of thrombocytopenia.
Failure of platelet production by the megakaryocytes
Shortened half-life of platelets
Increased pooling of platelets in an enlarged spleen (hypersplenism) + destruction
State a broad acquired cause of impaired platelet function.
Drugs e.g. Aspirin, NSAIDs, clopidogrel
What are the 2 roles of von Willebrand factor in haemostasis?
Binding to collagen + trapping platelets
Stabilising factor 8 (if vWF is low, factor 8 may be low)
Von Willebrand Disease is usually hereditary. What are the 3 types 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 2 inherited vessel wall conditions that cause defects in primary haemostasis.
Hereditary haemorrhagic telangiectasia
Ehlers-Danlos Syndrome
State 4 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.
Primary platelet plug isn’t strong enough to stop the bleeding Immediate Prolonged from cuts Epistaxes Gum bleeding Menorrhagia Easy bruising Prolonged bleeding after trauma + surgery
How are the clotting factors affected in severe von Willebrand disease?
Reduced factor 8 (because vWF stabilizes factor 8)
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)
Leads to impaired thrombin generation
Failure to generate fibrin to stabilise the platelet plug
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, spontaneous joint + muscle bleeding
11: bleeding after trauma but not spontaneously
12: no excess bleeding
State 3 acquired causes of deficiency of coagulation factors.
Liver disease
Dilution (need to replace plasma as well as RBC + platelets)
Anti-coagulant drugs (e.g. warfarin)
State 2 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
It’s associated with sepsis, major tissue damage + inflammation
It consumes + depletes coagulation factors
Platelets are 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 (primary haemostasis is fine)
Bruising is common, nosebleeds rare
Spontaneous bleeding is DEEP, into muscles + joints
Bleeding after trauma may be delayed + 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: can cause deep bleeding patterns
State 3 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
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) Platelet disorders Excessive fibrinolysis Vessel wall disorders Metabolic disorders (e.g. uraemia) (Thrombotic disorders)
State a hereditary disorder of fibrinolysis.
Antiplasmin deficiency
State 2 acquired disorders of fibrinolysis.
Drugs such as tissue plasminogen activator (tPA)
Disseminated intravascular coagulation (DIC)– because everything has been used up
What is the treatment that is considered for a patient whose abnormal haemostasis is caused by immune destruction of platelets?
Immunosuppression (e.g. prednisolone)
Splenectomy for ITP
What clotting factors are found in cryoprecipitate?
Fibrinogen
Factor VIII
Factor XIII
vWF
Factor concentrates are available for all factors except which one?
Factor V
Describe the use of Desmopressin (DDAVP) in von Willebrand disease.
Desmopressin makes the endothelial cells release their stored vWF
Good for people with mild von Willebrand disease (causes release of endogenous stores of vWF)
State 2 other drugs that are used as haemostatic treatments.
Tranexemic acid (inhibits fibrinolysis) Fibrin glue
List 5 examples contributing to significant bleeding history
Epistaxis not stopped by 10 mins compression
Cutaneous haemorrage/ bruising with no apparent trauma
>15 mins bleeding from trivial wounds/ recurrence spontaneously in 7 days after
Menorrhagia requiring treatment/ leading to anaemia
Heavy, prolonged, recurrent bleeding after surgery
What impaired function causes a disorder of primary haemostasis?
Hereditary absence of glycoproteins/ storage granules
What is the role of the coagulation cascade?
To generate a burst of thrombin which will convert fibrinogen to fibrin
What does deficiency of any coagulation factor result in?
Failure of thrombin generation + hence fibrin formation
What is required to stop the platelet plug from falling apart in large vessels?
Fibrin formation (stabilises plug)
Describe the inheritance pattern of common bleeding disorders
Haemophilia: Sex linked recessive
Von Willebrand disease: Autosomal dominant T1+2, Autosomal recessive T3
The rest are autosomal recessive
How is failure of production/ function treated?
Replace missing factors/ platelets
How is increased consumption treated?
Treat cause
Replace as necessary in meanwhile
What does plasma contain? (when given as replacement therapy)
All coagulation factors
