Coagulation - Normal and Abnormal

Question 1

Describe the term haemostasis

Answer 1

Haemostasis is the mechanism that leads to cessation of bleeding from a blood vessel.

Question 2

Describe the ideal coagulation system

Answer 2

Allows blood to flow through vessels

Cope with leaks, big and small, whilst allowing the rest to flow.

Repair mechanisms to dissolve clots

Question 3

Main constituents of coagulation

Answer 3

Vessel wall lined by endothelium

Platelets derived from megakaryocytes in marrow.

Coagulation factors in pre-activated state

Inhibitors of coagulation

Fibrinolytic system and inhibitors

Question 4

Function of endothelial cells

Answer 4

Line blood vessels and form a barrier

Question 5

What do endothelial cels produce ?

Answer 5

Produce thrombomodulin and heparin sulphate to inhibit thrombin production.

Enzymes to degrade platelet granule-derived moleucles

Prostacyclin and nitric oxide to reduce platelet adhesion.

Question 6

Describe the production of platelets

Answer 6

Fragments of megakaryocytic
Budded off into lumen of marrow sinusoids

Production stimulated by thrombopoetin (TPO) which is liver derived.

Question 7

Describe the function of platelets

Answer 7

Form a plug when attracted by lowered prostacyclin and by collagen exposure.

Thromboxane A2 and serotonin from platelets cause vasoconstriction.

Question 8

State the lifespan of platelets

Answer 8

Circulate for 5-10 days with around 30% stored in spleen

Question 9

Location of platelets

Answer 9

Adhere to vessel wall via Von Willibrand’s factor and Glycoprotein Ib.

Adhere to each other via Glycoprotein IIb-IIa and fibrinogen

Question 10

State the 2 pathways of the coagulation cascade

Answer 10

Intrinsic Pathway - endothelial collagen

Extrinsic Pathway - Trans-membrane protein in connective tissue around vessels named tissue factor

Question 11

Outline the main elements of the coagulation cascade

Answer 11

Fibrin is the final product of the clotting cascade.

Fibrinogen is the precursor for fibrin, and is activated by thrombin (IIa).

Thrombin is activated in 2 ways :

• Intrinsic
• Extrinsic

Question 12

What does the common pathway to produce thrombin involve ?

Answer 12

Involves Factor 5 (Va) and Factor 10 (Xa), which generate thrombin

Question 13

What slows down the coagulation cascade ?

Answer 13

TFPI
Antithrombin
Active Protein C

Question 14

Describe protein C

Answer 14

Activated by thrombomodulin thrombin complex

Question 15

Describe antithrombin

Answer 15

Inhibits Xa and IIa

Question 16

Function of heparin

Answer 16

Heparin stimulates antithrombin and heparin cofactor II

Heparin cofactor II inhibits IIa

Question 17

Co-factor (factor S)

Answer 17

Va and VIIIa are degraded

Question 18

How is plasminogen activated ?

Answer 18

Activated to plasmin by tissue plasminogen activator - from endothelial cells

Question 19

What is a measurement of fibrinolysis ?

Answer 19

Fibrin broken down into fibrin degradation products - including D dimers

Question 20

Therapeutic use of the fibrinolytic system

Answer 20

Use with streptokinase or tPA for clot busting

e.g. Acute myocardial infarction to thrombotic stroke.

Question 21

Measurement of coagulation

Answer 21

Full blood count
Bleeding time
Prothrombin time

Question 22

Reference range for FBC

Answer 22

150-400 x 10^9/L

Easy bruising and purport <30-50

Risk of major bleeding <10

Question 23

Describe bleeding time

Answer 23

In vivo test of overall clotting - mainly platelet function

Lots of poorly controlled variables so not often done.

Question 24

Prothrombin Time

(measures extrinsic pathway)

Answer 24

Done on citrated plasma which removes Ca2+

At 37C thromboplastin and Ca2+ are added

Measure the time until clot forms

Prolonged by levels of II, X, VII

Question 25

Function of citrated plasma

Answer 25

Removed Ca2+ Ionised calcium makes things clot

Question 26

Describe the activated partial thromboplastin test

Answer 26

Ca2+, kaolin and phospholipids are added to citrated plasma. Measure of the intrinsic and common pathway Prolonged in haemophilia and by heparin

Question 27

PT time APPT

Answer 27

Extrinsic pathway Intrinsic / Common pathway

Question 28

How can prolonged PT or APTT be tested ?

Answer 28

50:50 mix with normal plasma to see if prolongation corrects.

Question 29

How can fibrinogen be measured ?

Answer 29

BY measuring clot density OR Thrombin time - thrombin and calico added to citrated plasma

Question 30

Inherited blood disorder

Answer 30

Haemophilia - X linked defect in VIII or IX gene

Question 31

Haemophilia stats

Answer 31

Approx 1:5000 of males Female carriers not affected can be mild - chance finding or issue from surgery

Question 32

Severe haemophilia

Answer 32

<1% VIII level Frequent bleed into joints and soft tissues

Question 33

Treatment of haemophilia

Answer 33

Prophylaxis or Treatment Clotting factors Gene Therapy - factor 9 deficiency

Question 34

Be aware of examples of congenital and acquired coagulation disorders

Answer 34

Von Willebrand disease Haemophilia Acquired coagulation disease : - liver - disseminated intra-vascular coagulation (DIC)

Question 35

Von Willebrand

Answer 35

Usually autosomal dominant Defect in platelet adhesion and binding of VIII Up to 1% of pop

Question 36

Acquired coagulation disease - liver

Answer 36

Liver disease - alcohol, autoimmune, viral hepatitis PT and fibrinogen abnormal Bleeding due to abnormal clotting, low platelets Portal hypertension causing oesophageal varices ad uper GI bleeding

Question 37

Where are coagulation factors produced ?

Answer 37

Liver

Question 38

Acquired coagulation disease - DIC

Answer 38

Activation of clotting cascade Causes depletion of clotting factors and damage due to clot. Treat the cause and replace clotting factors

Question 39

Describe factors which increase risk of clotting

Answer 39

Trauma Malignancy e.g. prostate cancer Sepsis Amniotic fluid embolism

Question 40

Thrombocytopenia

Answer 40

Low platelets Could be due to : - under production - increased use - abnormal distribution

Question 41

Causes of low platelet count

Answer 41

Abnormal marrow function Drug adverse effete Cytotoxic chemotherapy Immune thrombocytopenia Splenomegally Large haemangioma

Question 42

Increased risk of clotting

Answer 42

Abnormal : - vessel wall - flow - blood component

Question 43

Thrombophilia

Answer 43

Increased risk of clotting - inherited defect in coagulation inhibitors

Question 44

Abnormal vessel wall

Answer 44

Atheroma Plaque Varicose veins Aneurysm

Question 45

Abnormal flow

Answer 45

Atrial fibrillation Immobile - plane flight, surgery Varicose veins

Question 46

Abnormal blood components

Answer 46

Increased haemoglobin/ RBC count Increased platelet / WBC count Increased viscosity of plasma Reduced coagulation factor inhibitors