Abnormalities of Homeostasis Flashcards
Broadly speaking, what are the two causes of abnormal haemostasis?
Lack of a specific factor (quantitative problem)
Defective function of a specific factor (qualitative problem)
State some quantitative causes of thrombocytopenia? (qualitative in another card)
QUANTITATIVE:
Not produced enough or removed too quickly:
Failure of production – bone marrow failure e.g. leukaemia, B12 deficiency
Accelerated clearance leading to shortened half life- e.g DIC, autoimmune thrombocytopenic purpura (ITP)
Pooling of platelets in enlarged spleen followed by destruction
State one very common cause of thrombocytopenia.
ITP (immune and idiopathic are the same thing)
What is a distinctive clinical feature of thrombocytopenia?
What is does bleeding resemble in VWD patients?
Petechiae
Severe VWD – haemophilia-like bleeding (because vWF is needed to stabilise factor 8. Low vWF=low factor 8=haemophilia)
State three hereditary platelet defects leading to impaired platelet FUNCTION (qualitative) .
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. (qualitative,slide 21)
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 three types of von Willebrand disease?State their pattern of inheritance
Types 1 and 3 are quantitative issues. Type 2 is qualitative.
Type 1 – partial 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 (HHT)
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.
Primary haemo goes before secondary (sort of) and it is normally involved in haemostasis in small blood vessels. Without this, its bad….
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 (not used anymore, brutal)
Assays for VWF (its level and activity)
Clinical observation
What is haemophilia caused by?
What is its pattern of inheritance?
Lack of Factor 8 (haemo A) or Factor 9 (haemo 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
Outline the different clotting factors that could be deficient as a result of a hereditary disease and their different patient outcomes
2(prothrombin) – lethal
8/9 (haemophilia) – severe but compatible with life, spontaneous bleeding in joints and muscles
11 – bleeding after trauma but not spontaneously
12 – no excess bleeding at all (F12 is part of intrinsic pathway which doesnt really matter)
State some acquired causes of deficiency of coagulation factors and hence inadequate secondary haemostasis
Liver disease
Dilution (slide 45 for more deets)
Anti-coagulant drugs (e.g. warfarin)
State some causes of coagulation/secondary haemostasis due to increased consumption of clotting factors
Disseminated intravascular coagulation (DIC)
Autoimmune thrombocytopenia
What happens in Disseminated Intravascular Coagulation (DIC)? What is it associated with?
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?
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.
PT - measures how long it takes to clot after activating extrinsic pathway
APTT - same as above but for intrinsic pathway
full blood count (look at platelets)
factor assays to look at clotting factors
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) Platelet disorders Excessive fibrinolysis Vessel wall disorders Metabolic disorders (e.g. uraemia) NOTE: urea interferes with platelet function
State a hereditary cause of fibrinolytic disorder.
State an acquired cause of a fibrinolytic disorder.
Hereditary: Antiplasmin deficiency
Acquired: drugs e.g tPA, disease eg DIC which uses up ingredients needed for haemostasis including fibrinolytic factors
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 drug treatment that is considered for a patient whose abnormal haemostasis is caused by immune destruction of platelets?
Immunosuppression (e.g. prednisolone)
What clotting factors are found in cryoprecipitate?
Fibrinogen
Factor VIII
Factor XIII
Von Willebrand Factor
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
vWF stabilises factor 8=good for haemophilia
State two other drugs that are used as haemostatic treatments.
Tranexamic acid (inhibits fibrinolysis): an antifibrinolytic drug. tPA binds to plasminogen to activate it to plasmin which then breaks down clot. Tranexamic acid mimics the binding site for tPA so that it does not activate plasminogen. = less plasmin= less fibrinolysis
Fibrin glue
What is a hallmark of haemophilia
haemarthosis slide 49
Compare the bleeding in disorders affecting primary and secondary haemostasis
slide 52
give some examples of factor replacement therapies
- Plasma
- Contains all coagulation factors - Cryoprecipitate
- Rich in Fibrinogen, FVIII, VWF, Factor XIII - Factor concentrates
- Concentrates available for all factors except factor V.
4.Recombinant forms of FVIII and FIX are available.
What advanced treatment can be used on patients with haemophilia? hint: haemophilia is a genetic disorder
gene therapy
