Haemostasis abnormalities Flashcards
Broadly speaking, what are the common causes of abnormal haemostasis?
Lack of a specific factor Defective function of a specific factor Increased clearance of a specific factor Genetic defects (Rarer) Acquired defects - drugs, synthetic defect, inhibition
VASCULAR WALL PROBLEMS
What can cause thrombocytopenia?
Failure of production – bone marrow failure e.g. leukaemia, B12 deficiency, Autoimmune thrombocytopenia (ITP) VERY COMMON
What is a distinctive clinical feature of thrombocytopenia?
Petechiae
What are the causes of impaired platelet function?
Thrombocytopenia - Bone marrow failure (e.g leukaemia, B12 deficiency) Accelerated clearance (e.g. ITP immune thrombocytopenia, DIC) Pooling and destruction in enlarged spleen
Impaired function
Hereditary absence of glycoprotein receptors or storage granules
Glanzmann’s thrombasthenia - absence of GPIIb (autosomal reccessive, RARE)
Bernard Soulier syndrome - GPIb absence
Storage Pool syndrome - granule defects
Drug acquired - aspirin, NSAIDs, clopidogrel
What are some causes of defective vWF?
Hereditary decrease of levels/function (common)
acquired due to antibody (rare)
VWD - type 1 (deficiency VWF), type 2 (VWF with abnormal function), type 3 (absence of VWF)
What are some causes of haemostatic vessel walls?
Hereditary haemorrhagic telangiectasia
Ehlers-Danlos syndrome
Other connective tissue disorders
Acquired - Scurvy, steroid therapy, Ageing purpura, Vasculitis
Describe the presentation of primary haemostasis disorders
General
- Immediate bleeding
- Prolonged bleeding from cuts or trauma
- Epistaxes
- Gum bleeding
- Menorrhagia
- Easy bruising
Specific
- Thrombocytopenia = petechia
- Severe VWD can resemble haemophilia due to reduced factor 8 (vWF stablises FVIII)
What is done to diagnose primary haemostasis disorders?
- Platelet counts/morphology
- Bleeding time (PFA100 in lab)
- Assays of von Willebrand factor
- Clincal observation
What are the causes of secondary haemostasis disorders? (coagulation disorders)
Genetic
Haemophilia A - VIII absence, B - VIX absence (Severe, spontaneous joint and muscle bleeding)
F II deficiency - Incompatible with life
F XI deficiency - Bleed after trauma but not spontaneously
F XII deficiency - No excess bleeding
Acquired
Liver disease - reduced production
Dilution - (inadequately replaced after haemorrhage)
Anticoagulant drugs - Intentional to reduce clotting
Disseminated intravascular coagulation - (Increased consumption)
What happens in disseminated intravascular coagulation?
DIC - inappropriate expression of TF. Asscoiated with Sepsis, major tissue damage, inflammation
Deposition of fibrin in vessels causes organ failure, deficiency in other areas causes bleeding
How do coagulation disorders present?
- Superficial cuts don’t over bleed
- Bruising common
- Nosebleeds rare
- Deep spontaneous bleeding into muscle and joints
- Bleeding after trauma may be prolonged and delayed
- Bleeding frequently restarts
Haemarthrosis - Haemophilia hallmark (Continually bleeding into joints leading to dissability)
What is haemophilia caused by? What is its pattern of inheritance?
Lack of Factor 8 (A) or Factor 9 (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
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 - Promthrombin time APTT (Activated partial thromboplastin time) - Full blood count Factor assays for specific facts Test for inhibitors
What do PT, APTT and TCT measure?
APTT – detects abnormalities in the INTRINSIC and COMMON pathways (coagulation is triggered by activation of factor 12)
PT – detects abnormalities in the EXTRINSIC and COMMON pathways (tissue factor is added to trigger the extrinsic pathway)
TCT – shows abnormality in the fibrinogen to fibrin conversion (not important any more)
