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Flashcards in Haematology Coagulation 1 Deck (50):
1

Cell Based haemostasis: Model involves

Vessel wall
Platelet
Coagulation factors
Coagulation pathway

2

Enable regulated generation of

Thrombin

3

Thrombin polymerises

Fibrinogen to fibrin

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Cell Based haemostasis: Model involves Stage 1

Collagen and TF exposed
Von Willebrand factor in plasma binds collagen

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Cell Based haemostasis: Model involves Stage 2

Primary Haemostasis:
• Platelets adhere to vWF collagen
• Platelets activated

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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)

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Cell Based haemostasis: Model involves Stage 4

Stable fibrin-platelet clot is formed

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Regulation of haemostasis (3)

Thrombin is neutralised by antithrombin
Thrombin makes APC to stop new thrombin generation
Thrombin + tPA activated Plasmin which lyses fibrin

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Clinical disorders of haemostasis →

1. Primary haemostasis disorders:
2. Coagulation pathway disorders

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1. Primary haemostasis disorders:

a. Platelets
b. VWF
c. Vessel Wall

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2. Coagulation pathway disorders

a. Coagulation factors
b. Fibrinogen

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Features of potential disorders of haemostasis

Abnormal bruising - primary haemostasis
Deep tissue bleeding – coagulation pathway

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First line investigation

1. Platelet count + blood film
2. Coagulation screen

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Platelet count + blood film

Indicates platelet number (not function)

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Coagulation screen

Indicates function of different parts of coagulation pathway:
1. Prothrombin (PT)
2. Activated partial thromboplastin time (aPTT)

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Assay principle

Add coagulation ‘activator’ + Ca2+
Incubate at 37oC
Measure time to fibrin clot formation

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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

18

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

19

Special coagulation tests

Used after clinical assessments and first line diagnosis:
1. Coagulation factor activity assays
2. Von Willebrand factor activity
3. Fibrinogen level
4. D-dimer level measures fibrinolysis)
5. Platelet function tests
6. Bone Marrow morphology

20

Platelets are made from


Megakaryocytes in marrow and are removed by spleen and liver (4 days life expectancy)
Low because:
• Reduced production
• Increased destruction

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Reduced production seen in

1. Chemo or radio therapy
2. Leukaemia or other malignancy
3. Aplastic anaemia

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Destruction seen in

1. Autoimmune thrombocytopenia
2. Hyperslenism – reduced platelets because the spleen is larger and so stimulated to work faster
3. Consumptive coagulopathies (eg DIC)
4. Sepsis

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Autoimmune Thrombocytopenia: Description

Abnormal auto-antibodies bind platelet glycoproteins causing rapid platelet destruction in spleen

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Autoimmune Thrombocytopenia: Causes

Idiopathic
2ary to infection, drugs, connective tissue disease, lymphoproliferative disorders (eg. CLL)

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Autoimmune Thrombocytopenia: Clinical features

Abnormal primary haemostasis
Cutaneous purpura

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Autoimmune Thrombocytopenia: Investigations

Reduced platelets count (FBC) and reduced Platelet count on film
Marrow shows increased megakaryocytes
No confirmatory test

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Autoimmune Thrombocytopenia: Treatment

Corticosteroids (immunosuppression)
Iv Immunoglobulin -
Splenectomy
TPO receptor agonists

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Von willebrand Disease: Description

Deficiency of VWF, commonest genetic haemostatic disorder

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Von willebrand Disease: VWF function

Mediates PT adhesion to collagen AND stabilises coagulation factor VII in the plasma

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Von willebrand Disease: MILD VWF

Defective primary haemostasis only causes with mild bleeding symptoms

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Von willebrand Disease: SEVER VWD

Additional coagulopathy pathway defect due to low FVIII

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Von willebrand Disease: Bleeding symptoms

Epitaxis
Easy bruising
Traumatic skin bleeding

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Von willebrand Disease: First line investigations

Platelet count normal
Long aPPT only in moderate or severe VWD (when FVIII level is low)

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Von willebrand Disease: Special coagulation tests

Reduced VWF activity
Reduced FVIII activity

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Von willebrand Disease: Treatment

• Tranexamic acid – reduced clot breakdown (anti-fibrinolytic)
• DDAVP/Desmopressin – release exogenous FVIII/VWF
• VWF/FVIII concentrate

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Reduced platelet function: Definition

Abnormal platelet function can cause bleeding even with normal platelet number

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Reduced platelet function: Causes

• Drugs: Aspirin, clopidogrel, NSAIDS
• Renal or Liver failure
• Cardiopulmonary bypass, haemofiltration
• Genetic platelet function disorders

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Abnormal Blood Vessel Wall:

• Senile Purpura – age related changes in blood vessels
• Scurvy – malnourishment (elderly) – Vit C

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Disorders of Coagulation Pathway:

1. Acquired coagulation factor disorders
2. Heritable coagulation factor disorders (Coag 2)

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1. 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)

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Liver disease affects

Primary Haemostasis and coagulation pathway

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How does liver disease effect this

1. Reduces Synthesis of all clothing factors and fibrinogen
2. Reduced Platelet number (Hypersplenism) and reduced PLT function
3. Biliary obstruction gives vit K malaabsorption (reduced synthesis of Factors II, VII, IX and X)

43

Presentation

• Sub-conjunctival haemorrhage, jaundice and corneal arcus
• Oesophageal varices from portal hypertension

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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

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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

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Treatment of bleeding liver disease

• Vit K
• Vit K dependent clotting factor concentrate
• Fresh Frozen Plasma

47

Disseminated intravascular coagulation (consumption): Description



Widespread activation of coagulation pathway (microvascular thrombosis) from excess thrombin generation – ischaemic tissue
1. Activation of inflammation, complement, fibrinolysis - multisystem
2. Consumption of platelets/coagulation factors- bleeding (because its widespread using up of clotting factors because of the excess thrombosis)

48

Disseminated intravascular coagulation (consumption): Causes of DIC

Any sever illness:
1. Sepsis
2. Major Trauma
3. Obstetric emergencies (pre-eclampsia, amniotic fluid embolism, retained POC)
4. Advanced malignancy

49

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

50

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

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