Haemostasis

Question 1

What are the essntials for haemostasis?

Answer 1

Essentials for haemostasis
• Keep blood moving – heart, venous valves, calf
pump 
• Blood vessels are important 
• Platelets 
• Coagulation factors 
• Anticoagulant factors

Question 2

What are platelets produced from and what is the normal platelet count?

Answer 2

• Megakaryocytes produce platelets in the bone marrow
• Platelets ‘bud’ from cytoplasm
• Normal platelet count is 150-400 x 109/L (dont tend to get much bleeding until platelet count is below 20-30)
• Normal life span 7-10 days

Question 3

What is platelet adhesion?

Answer 3

• Damage to vessel wall
• Exposure of underlying tissues
• Platelets adhere to collagen via vWF/receptor

Question 4

What is platelet activation?

Answer 4

• Secrete ADP, thromboxane and other substances
to become activated and activate other platelets
• Involved in activation of the clotting cascade
• Provide some coagulation factors by secretion from internal stores

Question 5

What is platelet aggregation?

Answer 5

Cross liking o platelets to form a platelet plug

Question 6

What are the medicating factors of haemostasis?

Answer 6

• Plt receptors – glycoprotein complexes e.g. GP1b-V-IX, GPIIb-IIIa
P• Von willebrands factor
• Fibrinogen
• Collagen
• ADP
• Thromboxane/arachidonic acid (aspirin inhibits thromboxane)
• Thrombin

Question 7

What is the clotting cascade?

Answer 7

• Amplification system activation of precursor proteins to generate thrombin (IIa)
• Thrombin converts soluble fibrinogen into insoluble fibrin which strengthens the clot
• Enmeshes initial platelet plug to make stable clot
• ……controlled
– Natural anticoagulants to inhibit activation
– Clot destroying proteins which are activated by the clotting
cascade (carefully balanced!) - dont want coagulation to occur abnormally

Question 8

How is coagulation measured?

Answer 8

Extrinsic and intrinsic join to form a common pathway
tissue factor activates factor 7
intrinsic pathway - different factors activate each tother

Can measure aptt (intrinsic pathway) - measures the amount of time that takes for clot to be made - rewatch
Can measure appt (extrinsic pathway)

low in factor 7 - pt prolonged
low in factor 9 - aptt prolonged
if deficient in smth in common fpathway both prolonged

Question 9

What is PT?

Answer 9

Prothrombin time - measures extrinsic an common pathway, INR is derived/calculated from this and is used in measuring warfarin

Question 10

Deficiency of which factors leads to an increase in PT (prothrombin time)?

Answer 10

VII (extrinsic)

V, X,prothrombin, fibrinogen (common)

Question 11

What is APTT?

Answer 11

Activated partial thromboplastin time - measures intrinsic and common pathway

Question 12

Deficiency of which factors leads to an increase in APTT?

Answer 12

VII, IX, XI, XII (intrinsic)

V, X, prothrombin, fibrinogen (common)

Question 13

What is Von willer and factor?

Answer 13

• Involved in platelet adhesion to the vessel

wall, platelet aggregation, and also carries (stabilises) FVIII

Question 14

What occurs in the vessel wall in haemostasis?

Answer 14

• Vasoconstriction
• Production of Von Willebrands factor (vWF)
– Essential for plt adhesion
– Carrier and ‘protector’ of Factor 8
(clotting protein)
• Exposure of collagen and Tissue factor
which initiates activation of clotting factors (proteins)

Question 15

What are natural anticoagulants?

Answer 15

• Stop further coagulation - control mechanisms of haemostasis
– Protein C
– Protein S
– Anti-Thrombin

Question 16

What is fibrinolysis

Answer 16

When clot no longer needed
plasminogen converted to plasmin
clot dissolved
plasminogen activator activates the process
we can make recombinant plasminogen activators
dugs break down the clots
patienst that have had an acute stroke - recombinant plasminogen activator - thrombolysis durg - breaks down cult

Question 17

What are fibrinogen count and D diners used to measure?

Answer 17

Fibrinogen count measures the amount of fibrinogen

D dimers measures fibrin degradation products

Question 18

What is the clinical relevance of haemostasis?

Answer 18

• Bleeding disorders • Arterial thrombotic disorders • Venous thrombotic disorders • Abnormal blood test results • Drug therapy for pro- or anti-thrombotic
purposes

Question 19

What are bleeding disorders?

Answer 19

• Due to abnormality in the vessel wall, platelets or coagulation factors
• Inherited and acquired

Question 20

What are coagulation factor disorders?

Answer 20

 Congenital
Haemophilia A (congenital reduction in Factor 8)
Haemophilia B (congenital reaction in Factor 9) etc
 Acquired
Liver disease Vit K deficiency Anticoagulants (factors II, VII, IX and X dependednt on Vit K) including Warfarin (inhibits Vit K)

Question 21

Describe coagulation factor disorders?

Answer 21

Clinical severity correlates with extent of deficiency
• Muscle haematomas with very little trauma
• Recurrent haemarthroses
• Joint pain and deformity
• Prolonged bleeding post dental extraction
• Life threatening post op and post traumatic bleeding
• Intracerebral haemorrhage

Question 22

What is haemophilia A?

Answer 22

• Haemophilia A
– X-linked recessive
– Congenital lack of factor VIII
– Mild/moderate/severe depending on amount of factor VIII
present
– Diagnosed pre-natally or soon after birth if family history, or usually in infancy if new spontaneous mutation
– Bleeding into muscles and joints, and post-operatively
– Treated with recombinant factor VIII or DDAVP
– What abnormalities would you expect to see in the blood
results of a patient with haemophilia A?

Question 23

What is haemophilia b?

Answer 23

Haemophilia B
– Similar presentation to haemophilia A
– Congenital reduction in factor IX

Question 24

What is Von Willebrands disease?

Answer 24

• Relatively common
• Usually autosomal dominant, affects males and females
• VWF carries factor VIII and mediates platelet adhesion to the endothelium
• Abnormal platelet adhesion to vessel wall
• Reduced FVIII amount/activity
• Factor VIII levels can be low in addition to low VWF levels

• Several genetic defects cause this condition
• Main type due to a reduction in vWF
production ie not enough
• (others where activity reduced)

Question 25

What is platelet associated bleeding in vWD?

Answer 25

• Skin and mucous membrane bleeding
• epistaxis • gum bleeding • bruising
• Prolonged bleeding after trauma
• Heavy periods • Post surgery • Post dental extraction

Spontaneous joint or muscle bleeds are rare

Question 26

What are vessel wall abnormalities?

Answer 26

• Easy bruising • Spontaneous bleeding from small vessels • Skin mainly • Can be mucous membranes

Question 27

What are problems that can occur with vessels?

Answer 27

Congenital
• Hereditary Haemorrhagic Telangiectasia (HHT)
– Autosomal dominant
– Dilated microvascular swellings increase with time
– GI haemorrhage can lead to iron deficiency anaemia
-blood vessels can become leaky in payments with meningitis
• Connective Tissue disorders-Ehlers Danlos

Acquired
• Senile purpura
• Steroids
• Infection eg measles, meningococcal infection
• Scurvy-Vit C def causing defective collagen production

Question 28

What is disseminated intravascular coagulopathy?

Answer 28

• Type of microangiopathic haemolytic anaemia
• Pathological activation of coagulation
• Numerous microthrombi are formed in the circulation
• This leads to consumption of clotting factors and platelets, and a haemolytic anaemia
• Clotting tests are affected - usually raised PT/INR, raised APTT, low fibrinogen and raised D dimers/fibrin
degradation products
• Must always be a trigger
– Malignancy – Massive tissue injury eg burns – Infections – usually gram negative sepsis – Massive haemorrhage and transfusion – ABO transfusion reaction – Obstetric causes – placental abruption, pre-
eclampsia, amniotic fluid embolism
• You will learn more about DIC and acquired
coagulation disorders over the next few years

Question 29

What are thrombophilias?

Answer 29

• These are acquired or congenital defects of
haemostasis which can increase a patient’s risk of
thrombosis
• Congenital causes include deficiency in natural
anticoagulants (protein C, protein S and antithrombin) and an abnormal factor V (factor V Leiden)
• Acquired causes include antiphospholipid syndrome
• These are relatively rare conditions and many patients with them do not develop clots unless they have additional risk factors