Haematology Coagulation 1 Flashcards
Cell Based haemostasis: Model involves
Vessel wall
Platelet
Coagulation factors
Coagulation pathway
Enable regulated generation of
Thrombin
Thrombin polymerises
Fibrinogen to fibrin
Cell Based haemostasis: Model involves Stage 1
Collagen and TF exposed
Von Willebrand factor in plasma binds collagen
Cell Based haemostasis: Model involves Stage 2
Primary Haemostasis:
• Platelets adhere to vWF collagen
• Platelets activated
Cell Based haemostasis: Model involves Stage 3
Generation of Thrombin:
• TF initiates rapid thrombin generation on activated platelets
• Thrombin converts fibrinogen to fibrin clot
Serine proteases: (FVII, FX, FIX, FXI)
Co-factors: (FVIII and FV)
Cell Based haemostasis: Model involves Stage 4
Stable fibrin-platelet clot is formed
Regulation of haemostasis (3)
Thrombin is neutralised by antithrombin
Thrombin makes APC to stop new thrombin generation
Thrombin + tPA activated Plasmin which lyses fibrin
Clinical disorders of haemostasis →
- Primary haemostasis disorders:
2. Coagulation pathway disorders
- Primary haemostasis disorders:
a. Platelets
b. VWF
c. Vessel Wall
- Coagulation pathway disorders
a. Coagulation factors
b. Fibrinogen
Features of potential disorders of haemostasis
Abnormal bruising - primary haemostasis
Deep tissue bleeding – coagulation pathway
First line investigation
- Platelet count + blood film
2. Coagulation screen
Platelet count + blood film
Indicates platelet number (not function)
Coagulation screen
Indicates function of different parts of coagulation pathway:
- Prothrombin (PT)
- Activated partial thromboplastin time (aPTT)
Assay principle
Add coagulation ‘activator’ + Ca2+
Incubate at 37oC
Measure time to fibrin clot formation
Prothrombin information
‘Thromboplastin’ (tissue factor) activator added and measure clotting time
→ Detects abnormal FVII (extrinsic factor)
• FX, FV, FII, Fibrinogen
Long if there is a problem
aPPT information
Kaolin or ‘contact activator’ Detects abnormal: • FVIII, FIX, FXI (intrinsic factors) • FX, FV, FII, Fibrinogen Normal aPPT – can rule out certain things in conjunction with PT
Special coagulation tests
Used after clinical assessments and first line diagnosis:
- Coagulation factor activity assays
- Von Willebrand factor activity
- Fibrinogen level
- D-dimer level measures fibrinolysis)
- Platelet function tests
- Bone Marrow morphology
Platelets are made from
Megakaryocytes in marrow and are removed by spleen and liver (4 days life expectancy)
Low because:
• Reduced production
• Increased destruction
Reduced production seen in
- Chemo or radio therapy
- Leukaemia or other malignancy
- Aplastic anaemia
Destruction seen in
- Autoimmune thrombocytopenia
- Hyperslenism – reduced platelets because the spleen is larger and so stimulated to work faster
- Consumptive coagulopathies (eg DIC)
- Sepsis
Autoimmune Thrombocytopenia: Description
Abnormal auto-antibodies bind platelet glycoproteins causing rapid platelet destruction in spleen
Autoimmune Thrombocytopenia: Causes
Idiopathic
2ary to infection, drugs, connective tissue disease, lymphoproliferative disorders (eg. CLL)
Autoimmune Thrombocytopenia: Clinical features
Abnormal primary haemostasis
Cutaneous purpura
Autoimmune Thrombocytopenia: Investigations
Reduced platelets count (FBC) and reduced Platelet count on film
Marrow shows increased megakaryocytes
No confirmatory test
Autoimmune Thrombocytopenia: Treatment
Corticosteroids (immunosuppression)
Iv Immunoglobulin -
Splenectomy
TPO receptor agonists
Von willebrand Disease: Description
Deficiency of VWF, commonest genetic haemostatic disorder
Von willebrand Disease: VWF function
Mediates PT adhesion to collagen AND stabilises coagulation factor VII in the plasma
Von willebrand Disease: MILD VWF
Defective primary haemostasis only causes with mild bleeding symptoms
Von willebrand Disease: SEVER VWD
Additional coagulopathy pathway defect due to low FVIII
Von willebrand Disease: Bleeding symptoms
Epitaxis
Easy bruising
Traumatic skin bleeding
Von willebrand Disease: First line investigations
Platelet count normal
Long aPPT only in moderate or severe VWD (when FVIII level is low)
Von willebrand Disease: Special coagulation tests
Reduced VWF activity
Reduced FVIII activity
Von willebrand Disease: Treatment
- Tranexamic acid – reduced clot breakdown (anti-fibrinolytic)
- DDAVP/Desmopressin – release exogenous FVIII/VWF
- VWF/FVIII concentrate
Reduced platelet function: Definition
Abnormal platelet function can cause bleeding even with normal platelet number
Reduced platelet function: Causes
- Drugs: Aspirin, clopidogrel, NSAIDS
- Renal or Liver failure
- Cardiopulmonary bypass, haemofiltration
- Genetic platelet function disorders
Abnormal Blood Vessel Wall:
- Senile Purpura – age related changes in blood vessels
* Scurvy – malnourishment (elderly) – Vit C
Disorders of Coagulation Pathway:
- Acquired coagulation factor disorders
2. Heritable coagulation factor disorders (Coag 2)
- Acquired coagulation factor disorders
a. Massive transfusion (dilution) – e.g. colloid, RBC’s w/o platelets
b. Liver disease (synthetic)
c. Disseminated intravascular coagulation (consumption)
Liver disease affects
Primary Haemostasis and coagulation pathway
How does liver disease effect this
- Reduces Synthesis of all clothing factors and fibrinogen
- Reduced Platelet number (Hypersplenism) and reduced PLT function
- Biliary obstruction gives vit K malaabsorption (reduced synthesis of Factors II, VII, IX and X)
Presentation
- Sub-conjunctival haemorrhage, jaundice and corneal arcus
* Oesophageal varices from portal hypertension
Lab investigation in liver disease
- Increased PT, increased aPPT and reduced PLT count
- Fibrinogen and all clotting factors
- Reduced anticoagulant proteins e.g. anti-thrombin
Treatment of coagulopathy in liver disease
- Stable abnormal clotting test results usually doesn’t need treatment
- To treat or prevent surgical bleeding replace specific factors
Treatment of bleeding liver disease
- Vit K
- Vit K dependent clotting factor concentrate
- Fresh Frozen Plasma
Disseminated intravascular coagulation (consumption): Description
Widespread activation of coagulation pathway (microvascular thrombosis) from excess thrombin generation – ischaemic tissue
- Activation of inflammation, complement, fibrinolysis - multisystem
- Consumption of platelets/coagulation factors- bleeding (because its widespread using up of clotting factors because of the excess thrombosis)
Disseminated intravascular coagulation (consumption): Causes of DIC
Any sever illness:
- Sepsis
- Major Trauma
- Obstetric emergencies (pre-eclampsia, amniotic fluid embolism, retained POC)
- Advanced malignancy
Disseminated intravascular coagulation (consumption): Diagnosis of DIC
- Very high PT
- Very high aPPT
- Very low PLT count in sick patient
- Very low fibrinogen
- Very High D-dimer
Disseminated intravascular coagulation (consumption): Treatment of DIC
- Usually requires full supportive care and aggressive treatment of underlying causes
- Support coagulation with FFP, cryoprecipitate and PLT transfusion
