Abnormalities of Haemostasis Flashcards
What constitutes abnormal bleeding?
- Epistaxis not stopped by 10 mins compression or requiring medical attention/transfusion
- Bruising without apparent trauma (esp. multiple/large)
- Prolonged bleeding from trivial wounds, or in oral cavity or recurring spontaneously in 7 days after wound. Spontaneous GI bleeding leading to anaemia.
- Menorrhagia requiring treatment or leading to anaemia, not due to structural lesions of the uterus.
- Heavy, prolonged or recurrent post-operative bleeding
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?
- Bone marrow failure e.g. leukaemia, B12 deficiency
- Shortened half life of platelets
- Increased pooling of platelets in an enlarged spleen
State one very common cause of thrombocytopenia. State some clinical features
Autoimmune thrombocytopenia
purpura
multiple bruises
ecchymoses
What is a distinctive clinical feature of thrombocytopenia?
Petechiae = small spots of bleeding under the skin
Name and describe three 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 in platelets aren’t able to be release adequately
Give three examples of drugs which cause impaired platelet function (acquired platelet defects)
aspirin, NSAIDs, clopidogrel
In addition to binding to collagen and trapping platelets, state another role of VWF
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 the pattern of inheritance for each
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 (rare)
2. Ehlers-Danlos Syndrome (connective tissue disorder)
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 disorders of primary haemostasis.
The primary platelet plug isn’t strong enough;
- Bleeding is immediate
- Prolonged bleeding from cuts
- Epistaxes
- Gum bleeding
- Menorrhagia
- Easy bruising
- Prolonged bleeding after trauma and surgery
What is an important effect of severe von Willebrand disease? What does this result in symptomatically?
Reduced factor 8
This causes haemophilia type bleeding patterns
What tests are done for disorders of primary haemostasis?
Platelet count and morphology
Bleeding time
Assays for VWF
Clinical observation
What is haemophilia caused by?
Lack of Factor 8 (A) or Factor 9 (B) => impaired thrombin generation + failure to generate fibrin
State 3 acquired causes of deficiency of coagulation factors (more common in hospital practice). Say why in each case
- Liver disease - since most coagulation factors are synthesised in the liver
- Dilution - low concentration of clotting factors
- Anti-coagulant drugs (e.g. warfarin)
State some disorders of coagulation that are due to increased consumption.
Disseminated intravascular coagulation (DIC)
Immune - autoantibodies
What is disseminated intravascular coagulation (DIC)? What is it associated with, and what are some consequences?
Excessive activation of the whole coagulation process (including primary and secondary haemostasis, and fibrinolysis)
=> increased consumption and depletion of coagulation factors + platelets
=> activation of fibrinolysis depletes fibrinogen
=> deposition of fibrin in vessels causes organ failure
- It is associated with sepsis, inflammation and major tissue damage
Describe the pattern of bleeding in coagulation disorders (i.e. disorders of secondary haemostasis)
- superficial cuts do not bleed
- bruising is common, but nosebleeds are rare
- spontaneous bleeding is deep, into muscles
and joints - bleeding after trauma may be delayed and is prolonged
- bleeding frequently restarts after stopping
What is the hallmark of haemophilia?
Haemarthrosis (bleeding into joint spaces)
What simple medical procedure must you avoid doing to patients with haemophilia? Why?
Intramuscular injection – it can cause deep bleeding patterns
State some tests that are used for coagulation disorders.
Screening Tests:
- Prothrombin time (PT)
- Activated partial thromboplastin time (APTT)
- Platelet count
Factor Assays
Tests for inhibitors
PT and APTT tests are used to assess which pathways within the coagulation cascade?
APTT - intrinsic
PT - extrinsic
Describe the APTT and PT results for a patient with haemophilia.
Prolonged APTT but normal PT
This is because the defect lies in the intrinsic pathway (factor 8 or 9)
