Disorders of Haemostasis COPY Flashcards
Give examples of minor bleeding symptoms
Easy bruising Gum bleeding Frequent nosebleeds Bleeding after tooth extraction Post-operative
Give examples of minor bleeding symptoms in women
Menorrhagia
Post-partum bleeding
Family history
What are the elements of a significant bleeding history
Epistaxis not stopped by 10 minutes compression pr requiring medical attention/transfusion
Cutaneous haemorrhage or bruising with no trauma
Prolonged (>15min) bleeding from trivial wounds
Menorrhagia requiring treatment that leads to anaemia
Heavy, prolonged or recurrent bleeding after surgery or dental extraction
Why might abnormal haemostasis occur
Lack of a specific factor
Failure of production (congenital and acquired) or increased consumption/clearance
Defective function of a specific factor
Genetic defect or acquire defect (drugs, synthetic defect, inhibition)
Give examples of disorders of primary haemostasis due to platelets
Low numbers - thrombocytopenia
Bone marrow failure e.g. leukaemia, B12 deficiency
Accelerated clearance e.g. immune (ITP), DIC
Impaired function
Hereditary absence of glycoproteins or storage granules
Acquired due to drugs
Describe auto-immune thrombocytopenic purpura
- Antiplatelet antibodies bind to a sensitised platelet
- Sensitised platelet binds to a macrophage via antibodies
Very common cause of thrombocytopenia
What are the mechanisms and causes of thrombocytopenia
- Failure of platelet production by megakaryocytes
- Shortened half life of platelets
- Increased pooling of platelets in an enlarged spleen
(hypersplenism) + shortened half life
Give examples of hereditary platelet defects
Glanzmann’s thrombasthenia
Bernard Soulier syndrome
Storage Pool disease
No GPIIb/IIIa or GpIb or dense granules
Which drugs may cause one to acquire impaired function of platelets
Aspirin
NSAIDs
Clopidogrel
What are the functions of VWF in haemostasis
Binding to collagen and capturing platelets
Stabilising factor VIII (may be low if VWF is low)
Describe the cause of VWF disease
Hereditary - deficiency of VWF (Type 1 or 3) or VWF with abnormal function (type 2)
Acquired due to antibody (rare)
Give examples of primary haemostasis disorders involving the vessel wall
Inherited (rare) - Hereditary haemorrhagic telangiectasia Ehlers-Danlos syndrome and other connective tissue disorders
Acquired - Scurvy, steroid therapy, ageing (senile purpura), vasculitis
Describe the typical bleeding of primary haemostasis
Immediate Prolonged bleeding from cuts Epistaxes Gum bleeding Menorrhagia Easy bruising Prolonged bleeding after trauma or surgery
What might be the typical bleeding specific to thrombocytopenia and severe VWD
thrombocytopenia - petechiae
Severe VWD - haemophilia-like bleeding
What are the tests done for disorders of primary haemostasis
Platelet count, platelet morphology
Bleeding time (PFA100 in lab)
Assays of von Willebrand Factor
Clinical observation
Which clotting factors are not serine proteases
V - co-factor
VIII - co-factor
XIII - transglutamidase
Which factors require post-transitional vit K dependent modification
II
VII
IX
X
Describe the concentration-time graph for thrombin generation
After a TF trigger there is a surge in thrombin which then quickly decreases
Haemophilia - very small and slow peak (when thrombin is lowest)
Describe haemophilia
Failure to generate fibrin to stabilise platelet plug
Deficiency in factor VIII/IX
Sex-linked recessive
Describe the different bleeding in coagulation factor deficiencies (FVIII, IX, II, XI, XII)
VIII/IX - severe but compatible with life, spontaneous joint and muscle bleeding
Prothrombin - lethal
XI - bleed after trauma, not spontaneous
XII - no excess bleeding
What are some acquired disorders of coagulation
Liver disease
Dilution
Anticoagulant drugs – warfarin
How does liver failure lead to a coagulation disorder
Most coagulation factors are synthesised in the lvier
Describe coagulation disorders due to dilution
Red cell transfusions no longer contain plasma
Major transfusions require plasma as well as rbc and platelets
What are the causes of increased consumption
Acquired
Disseminated intravascular coagulation (DIC)
Immune - autoantibodies
Describe disseminated intravascular coagulation
Generalised activation of coagulation – Tissue factor
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 typical bleeding in coagulation disorders (Secondary)
superficial cuts do not bleed (platelets)
bruising is common, nosebleeds are rare
spontaneous bleeding is deep, into muscles
and joints
bleeding after trauma may be delayed and is prolonged
frequently restarts after stopping
How is bleeding due to platelet and coagulation defects clinically distinguished
Platelet - superficial bleeding into skin, mucosal membranes. Immediate after injury
Coagulation- bleeding into deep tissue, muscle and joints, delayed but severe and prolonged bleeding
What are the tests for coagulation disorders
Screening tests (clotting screen)
Prothrombin time (PT)
Activated partial thromboplastin time (APTT)
Full blood count (platelets)
Factor assays (for Factor VIII etc)
Tests for inhibitors
Which bleeding disorders are not detected by routine clotting tests
Mild factor deficiencies von Willebrand disease Factor XIII deficiency (cross linking) Platelet disorders Excessive fibrinolysis Vessel wall disorders Metabolic disorders (e.g. uraemia) (Thrombotic disorders)
What are some causes of fibrinolysis disorders
hereditary - antiplasmin deficiency
Acquired - drugs (tPA), disseminated intravascular coagulation
Describe the genetics of von willebrand disease
Autosomal dominant
Type 2 = AD
type 3 = AR
Describe the genetics of most bleeding disorders
Autosomal recessive
What is the treatment for abnormal haemostasis from failure of production/function
Replace missing factor/platelets
- Prophylactic
- Therapeutic
Stop drugs
What is the treatment for abnormal haemostasis from immune destruction
What is the treatment for abnormal haemostasis from failure of production/function
What is the treatment for abnormal haemostasis from increased consumption
Treat cause
Replace as necessary
What can be used in factor replacement therapy
Plasma
Cryoprecipitate
Factor concentrates
Recombinant forms of FVIII and FIX
Describe plasma and cryoprecipitate for replacement therapy
Plasma = contains all coagulation factors
Cryoprecipitate = rich in fibrinogen, FVIII, VWF, FXIII
Describe factor concentrates
Concentrates available for all factors except factor V.
Prothrombin complex concentrates (PCCs) Factors II, VII, IX, X
What are the the principle treatments of Haemostatic
Disorders Causing Bleeding
Factor replacement therapy
Gene therapy (haemophilia)
Platelet replacement therapy
What are some additional haemostat treatments
DDAVP
Tranexamic acid
Fibrin glue/spray
Describe DDAVP
Desmopressin
Vasopressin derivative
2-5 fold rise in VWF-VIII (VIII>vWF)
Releases endogenous stores -
Hence only useful in mild disorders
Describe transexamic acid
Inhibits fibrinolysis
Widely distributed – crosses placenta
Low concentration in breast milk
