Abnormalities of haemostasis Flashcards
What are the two main types of abnormal haemostasis?
Lack of a specific factor
Defective function of a specific factor
What can cause you to lack a specific factor?
Failure of production- congenital or acquired
Increased consumption/clearance
What can cause a defective function of a specific factor?
Genetic defect Acquired defect (more common) e.g. drugs, synthetic defect and inhibition
What is thrombocytopenia?
Low number of platelets
What causes thrombocytopenia?
Failure of platelet production by megakaryocytes- Bone marrow failure e.g. leukaemia and B12 deficiency
Shortened half life of platelets- Accelerated clearance e.g. autoimmune thrombocytopenia, disseminated intravascular coagulation
Increased pooling of platelets in enlarged spleen
What else could disorders of primary haemostasis be caused by except from thrombocytopenia?
Impaired function of platelets- absence of storage granules or glycoproteins
What can cause impaired function of platelets?
Acquired due to drugs e.g. aspirin, NSAIDs, clopidogrel
What hereditary platelet defects are there?
Glanzann’s thrombasthenia
Bernard Soulier syndrome
Storage pool disease
What causes Glanzann’s thrombasthenia?
Absent glycoprotein 2b/3a
What does the absence of glycoprotein 2b/3a cause?
Lack of platelet aggregation
What causes Bernard Soulier syndrome?
Lack of glycoprotein 1b
What does the lack of glycoprotein 1b cause?
Platelets can’t bind to von Willebrand factor
What is storage pool disease?
Problem with storage granules so they can’t be released adequately
What is Von Willebrand disease?
Hereditary decrease in quantity and/or function
It can be acquired due to an antibody
What are the two functions of vWF in haemostasis?
Binding to collagen and capturing platelets
Stabilising factor 8
What are the three types of VWD?
Type 1- Deficiency of VWF but functions normally
Type 2- VWF is made but doesn’t function normally
Type 3- VWF isn’t made at all
What are some examples of inherited (rare) disorders of primary haemostasis that affect the vessel wall?
Hereditary haemorrhage telangiectasia
Ehlers-Dalos syndrome
Other connective tissue disorders
What are some examples of acquired disorders of primary haemostasis that affect the vessel wall?
Scurvy Steroid therapy Atrophy of supporting tissues of blood vessels Ageing (senile purpura) Vasculitis
What is typical primary haemophilia bleeding like?
Immediate Prolonged bleeding from cuts Epistaxes Gum bleeding Menorrhagia Easy bruising Prolonged bleeding after trauma Thrombocytopenia gives rise to petechiae
Why can you have haemophilia type bleeding in severe VWD?
VWF levels are very low so factor 8 will also be very low
What is haemophilia?
Failure to generate fibrin to stabilise platelet plug- Lack of factor 8 or 9 resulting in impaired thrombin generation
What is the genomics of haemophilia like?
It is an X linked condition
How severe is deficiency of prothrombin (factor 2) compared to haemophilia?
Deficiency of prothrombin is lethal but haemophilia is severe but compatible with life
How severe are deficiency of factor 11 and factor 12
Factor 11- Bleed after trauma but not spontaneously
Factor 12- No excess bleeding
How can deficiency of coagulation factors be acquired?
Liver disease
Dilution
Anti-coagulant drugs e.g. warfarin
What are two examples of increased consumption leading to disorders of coagulation?
Disseminated intravascular coagulation
Autoimmune antibodies
What is disseminated intravascular coagulation?
Generalised activation of coagulation- tissue factor is exposed and causes activation of cascade
What is DIC associated with?
Sepsis, major tissue damage and inflammation
What does DIC do?
It consumes and depletes coagulation factors
Platelets are consumed
Activation of fibrinolysis depletes fibrinogen
Deposition of fibrin in vessels causes organ failure
What is typical bleeding in coagulation disorders?
Superficial cuts don’t bleed
Bruising is common
Nosebleeds are rare
Spontaneous bleeding is deep into muscles and joints
Bleeding after trauma is delayed and prolonged
In what condition should intramuscular injections be avoided and why?
Haemophilia because it can cause deep bleeding patterns
What tests are there for coagulation disorders?
Screening tests
Prothrombin time- extrinsic path disorders
Activated partial thromboplastin time- intrinsic path disorders
Platelet count
Factor assays
Tests for inhibitors
What bleeding disorders are not detected by routine clotting tests?
Mild factor deficiencies Von Willebrand disease Factor 8 deficiency Platelet disorders Excessive fibrinolysis Vessel wall disorders Metabolic disorders
What hereditary and acquired disorders of fibrinolysis are there?
Rare
Hereditary- Antiplasmin deficiency
Acquired- Drugs such as tap and disseminated intravascular coagulation
How is abnormal homeostasis where production failure is responsible treated?
Replace missing factor/platelets
Prophylactic
Therapeutic
Stop drugs
How is abnormal haemostasis where immune destruction is responsible treated?
Immunosuppression
Splenectomy for autoimmune thrombocytopenia
How is abnormal haemostasis where increased consumption is responsible treated?
Treat cause
Replace as necessary
If you’re give someone factor replacement therapy, what are the different sorts and what do they contain?
Plasma- contains all coagulation factors
Cryoprecipitate- Fibrinogen, factor 8, vWF and factor 13
Factor concentrates- available for all factors except 5
How is desmopressin (DDAVP) used to treat haemostasis?
Vasopressin analogue which makes the endothelial cells release their own VWF that is stored- good for mild VWD
