Haem: Coagulation

Question 1

What are the pro coagulant elements?

Answer 1

Platelets
Endothelium
vWF

Question 2

What are the anti coagulant elements?

Answer 2

Anti-thrombins
Protein C/ S
Tissue factor pathway inhibitor (TFPI)

Question 3

What are the 3 responses to vessel wall injury?

Answer 3

Vasoconstriction- in order to minimise blood loss (as reduces blood flow to this area)
Platelet aggregation and activation- forms the primary haemostatic plug
Activation of the coagulation cascade

Question 4

What forms a stable platelet plug?

Answer 4

vWF

Question 5

How are platelets produced?

Answer 5

In the bone marrow from megakaryocytes

Question 6

What is the life span of platelets?

Answer 6

10 days

Question 7

What regulates platelet production?

Answer 7

Thrombopoietic factors

Question 8

What are the 2 ways platelets adhere to the endothelium?

Answer 8

via glycoprotein 1a

via glycoprotein 1b to vWF

Question 9

How do platelets adhere to each other?

Answer 9

Glycoprotein 2b/3a

Question 10

What happens when platelets attach to the endothelium?

Answer 10

They release ADP and thromboxane A2 to aggregate more platelets

Question 11

What inhibits ADP?

Answer 11

Clopidogrel

Question 12

How does aspirin work and how is it different from NSAIDs

Answer 12

Ireeversibly inhibits COX, while NSAIDs inhibit COX reversibly

Question 13

What is the limiting factor for fibrinogen formation?

Answer 13

Factor 10a

Question 14

What is the most important element of the coagulation cascade?

Answer 14

Thrombin / Factor 2a as this converts fibrinogen to fibrin

Question 15

Explain the coagualtion cascade;

Answer 15

Tissue factor activates factor 7a

Factor 7a activates factors 9a and 10a

10a binds to 5a

10a and 5a will produces 2a/thrombin

Thrombin will activate platelets, 8a and 11a

11a will activate 9a

8a will activate more 5a

Question 16

What causes large activation of thrombin?

Answer 16

Platelets, 5a, 8a and 9a will activate more 10a

10a will not cause massive thrombin release

This thrombin will convert fibrinogen to fibrin thereby forming a stable fibrin clot

*All these would happen only after the formation of a primary platelet plug

Question 17

What happens in Factor 5 Leiden

Answer 17

5a cannot bind to 10a

Higher risk of VTE

Question 18

Why do you need bile to absorb vit k?

Answer 18

As it is fat soluble. So obstruction of the biliary tree can cause vit k deficiency

Question 19

Will you still produce clotting factors in vit k deficiency?

Answer 19

Yes, but they will be inactive

Question 20

How is a fibrin clot broken down?

Answer 20

By tissue plasminogen activator and urokinase

Question 21

What can inhibit fibrin breakdown?

Answer 21

TAFI

Question 22

Which anti thrombin is the most active?

Answer 22

Anti thrombin 3

Question 23

What does LMWH do?

Answer 23

Augments antithrombin 3

Question 24

How do proteinc c and s work?

Answer 24

Work with thrombomodulin to inhibit factors 5a and 8a

Question 25

What happens to protien c in factor 5 leiden?

Answer 25

Protein c resistance Prothrombotic state

Question 26

What are the 2 factors causing protein c resistance?

Answer 26

Factor 5 mutations | High levels of factor 8

Question 27

What are the features of bleeding disorders due to platelet disorders?

Answer 27

Bleeding from skin and mucous membranes Petechiae present Small superficial bruises Rare haemarthrosis Bleeding after cuts and scratches Immediate mild bleeding after trauma

Question 28

What are the features of bleeding disorders due to clotting factor disorders?

Answer 28

Bleeding into soft tissues, joints and muscles Petechiae absent Large deep bruises Haemarthrosis is common No bleeding after cuts and scratches Delayed severe bleeding after trauma

Question 29

When do you need to treat platelet disorders?

Answer 29

When platelet count drops below 30 x 10(9) / L

Question 30

What is It is pseudothrombocytopaenia?

Answer 30

Where the platelets clump together, creating an erroneously low platelet count

Question 31

What is Grey Platelet Syndrome

Answer 31

Large platelets

Question 32

What can cause thrombocytopaenia

Answer 32

``` Drug induced - Quinines, rifampicin, vancomycin SLE Rheum arthiritis CLL Lymphomas Sarcoidosis ``` DIC MAHA

Question 33

What are the features of thrombocytopaenia?

Answer 33

Non blanching petechiae Haematomas Subconjunctival haemorrhages Look for B12 def and acute leukaemia

Question 34

What can cause clotting factor disorders?

Answer 34

DIC Vit K def Warfarin Liver disease Haemophilia A and B vWD

Question 35

What is haemophilia?

Answer 35

Deficiency of factors 8 or 9 | X linked

Question 36

What are the features of haemophilia?

Answer 36

Haemarthroses (fixed joints) Soft tissue haematomas (muscle atrophy) Prolonged bleeding

Question 37

What will the APTT and PT be in haemophilia?

Answer 37

Prolonged APTT - due to problematic intrinsic pathway | Normal PT

Question 38

What is the main feature of vWD?

Answer 38

Mucocutaneous bleeding

Question 39

What are the 3 types of vWD?

Answer 39

Partial quantitative def Qualitative def Total quantitative def

Question 40

What elements of the clotting cascade require vit K?

Answer 40

Factors 2,7,9 and 10 Proteins C and S

Question 41

How to treat Vit K def?

Answer 41

IM Vit K if GI obstruction FFP

Question 42

What happens in DIC?

Answer 42

Emx Activation of both coagulation and fibrinolysis due to sepsis, trauma...

Question 43

What are the features of DIC?

Answer 43

``` Prolonged APTT, PT, TT Decreased fibrinogen Increased FDP Decreased platelets Schistocytes on blood film Elevated D dimer ```

Question 44

How to treat DIC?

Answer 44

Heparin Platelet transfusion FFP

Question 45

How to treat haemostatic defects in liver disease?

Answer 45

PO Vit K, FFP Cryoprecipitate

Question 46

How do you monitor warfarin overdose?

Answer 46

INR The higher it is, the higher the risk of bleeding

Question 47

What is an indicator of the intrinsic pathway?

Answer 47

PTT

Question 48

What is an indicator of the extrinsic pathway?

Answer 48

PT