Haematology Coagulation 1

Question 1

Cell Based haemostasis: Model involves

Answer 1

Vessel wall
Platelet
Coagulation factors
Coagulation pathway

Question 2

Enable regulated generation of

Answer 2

Thrombin

Question 3

Thrombin polymerises

Answer 3

Fibrinogen to fibrin

Question 4

Cell Based haemostasis: Model involves Stage 1

Answer 4

Collagen and TF exposed

Von Willebrand factor in plasma binds collagen

Question 5

Cell Based haemostasis: Model involves Stage 2

Answer 5

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

Question 6

Cell Based haemostasis: Model involves Stage 3

Answer 6

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)

Question 7

Cell Based haemostasis: Model involves Stage 4

Answer 7

Stable fibrin-platelet clot is formed

Question 8

Regulation of haemostasis (3)

Answer 8

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

Question 9

Clinical disorders of haemostasis →

Answer 9

1. Primary haemostasis disorders:

2. Coagulation pathway disorders

Question 10

1. Primary haemostasis disorders:

Answer 10

a. Platelets
b. VWF
c. Vessel Wall

Question 11

2. Coagulation pathway disorders

Answer 11

a. Coagulation factors

b. Fibrinogen

Question 12

Features of potential disorders of haemostasis

Answer 12

Abnormal bruising - primary haemostasis

Deep tissue bleeding – coagulation pathway

Question 13

First line investigation

Answer 13

1. Platelet count + blood film

2. Coagulation screen

Question 14

Platelet count + blood film

Answer 14

Indicates platelet number (not function)

Question 15

Coagulation screen

Answer 15

Indicates function of different parts of coagulation pathway:

1. Prothrombin (PT)
2. Activated partial thromboplastin time (aPTT)

Question 16

Assay principle

Answer 16

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

Question 17

Prothrombin information

Answer 17

‘Thromboplastin’ (tissue factor) activator added and measure clotting time
→ Detects abnormal FVII (extrinsic factor)
• FX, FV, FII, Fibrinogen
Long if there is a problem

Question 18

aPPT information

Answer 18

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

Question 19

Special coagulation tests

Answer 19

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

Question 20

Platelets are made from

Answer 20

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

Question 21

Reduced production seen in

Answer 21

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

Question 22

Destruction seen in

Answer 22

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

Question 23

Autoimmune Thrombocytopenia: Description

Answer 23

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

Question 24

Autoimmune Thrombocytopenia: Causes

Answer 24

Idiopathic

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

Question 25

Autoimmune Thrombocytopenia: Clinical features

Answer 25

Abnormal primary haemostasis | Cutaneous purpura

Question 26

Autoimmune Thrombocytopenia: Investigations

Answer 26

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

Question 27

Autoimmune Thrombocytopenia: Treatment

Answer 27

Corticosteroids (immunosuppression) Iv Immunoglobulin - Splenectomy TPO receptor agonists

Question 28

Von willebrand Disease: Description

Answer 28

Deficiency of VWF, commonest genetic haemostatic disorder

Question 29

Von willebrand Disease: VWF function

Answer 29

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

Question 30

Von willebrand Disease: MILD VWF

Answer 30

Defective primary haemostasis only causes with mild bleeding symptoms

Question 31

Von willebrand Disease: SEVER VWD

Answer 31

Additional coagulopathy pathway defect due to low FVIII

Question 32

Von willebrand Disease: Bleeding symptoms

Answer 32

Epitaxis Easy bruising Traumatic skin bleeding

Question 33

Von willebrand Disease: First line investigations

Answer 33

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

Question 34

Von willebrand Disease: Special coagulation tests

Answer 34

Reduced VWF activity | Reduced FVIII activity

Question 35

Von willebrand Disease: Treatment

Answer 35

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

Question 36

Reduced platelet function: Definition

Answer 36

Abnormal platelet function can cause bleeding even with normal platelet number

Question 37

Reduced platelet function: Causes

Answer 37

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

Question 38

Abnormal Blood Vessel Wall:

Answer 38

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

Question 39

Disorders of Coagulation Pathway:

Answer 39

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

Question 40

1. Acquired coagulation factor disorders

Answer 40

a. Massive transfusion (dilution) – e.g. colloid, RBC’s w/o platelets b. Liver disease (synthetic) c. Disseminated intravascular coagulation (consumption)

Question 41

Liver disease affects

Answer 41

Primary Haemostasis and coagulation pathway

Question 42

How does liver disease effect this

Answer 42

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)

Question 43

Presentation

Answer 43

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

Question 44

Lab investigation in liver disease

Answer 44

* Increased PT, increased aPPT and reduced PLT count * Fibrinogen and all clotting factors * Reduced anticoagulant proteins e.g. anti-thrombin

Question 45

Treatment of coagulopathy in liver disease

Answer 45

* Stable abnormal clotting test results usually doesn’t need treatment * To treat or prevent surgical bleeding replace specific factors

Question 46

Treatment of bleeding liver disease

Answer 46

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

Question 47

Disseminated intravascular coagulation (consumption): Description

Answer 47

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)

Question 48

Disseminated intravascular coagulation (consumption): Causes of DIC

Answer 48

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

Question 49

Disseminated intravascular coagulation (consumption): Diagnosis of DIC

Answer 49

* Very high PT * Very high aPPT * Very low PLT count in sick patient * Very low fibrinogen * Very High D-dimer

Question 50

Disseminated intravascular coagulation (consumption): Treatment of DIC

Answer 50

* Usually requires full supportive care and aggressive treatment of underlying causes * Support coagulation with FFP, cryoprecipitate and PLT transfusion