Haemostasis

Question 1

Essentials for haemostasis

Answer 1

To Keep blood moving - done using heart, venous valves, calf pump

Blood vessels are important - as they contain:
Platelets
Coagulation factors - clotting
Anticoagulant factors - preventing/ breaking clots

Question 2

Platelets

Answer 2

Megakaryocytes produce platelets in the bone marrow
Platelets ‘bud’ from cytoplasm
Normal platelet count is 150-400 x 109/L
Normal life span 7-10 days

Platelet adhesion - occurs when there is Damage to vessel wall
Causes exposure of underlying tissues
Platelets adhere to collagen via vWF (Von Willebrands factor)/receptor

Platelet activation - They 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

Platelet aggregation - Cross linking of platelets to form a platelet plug

Question 3

Mediating factors for ability to form a clot

Answer 3

Things that need to be present to form a stable blood clot

Fibrinogen 
Collagen 
ADP
Thrombin 
Thromboxane
Von willebrands factor 
Pit receptors 

If one or more of these are not present then pathology could occur

Question 4

Clotting cascade - what it means

Answer 4

Amplification system leads to activation of precursor proteins to generate thrombin (IIa)

Thrombin converts soluble fibrinogen into insoluble fibrin

Fibrin then enmeshes in the initial platelet plug to make stable clot

This process needs to be well controlled, otherwise constant clotting could occur with pathology following

So we need natural anticoagulants to inhibit activation

And clot destroying proteins which are activated by the clotting cascade

Coagulation and it’s associated factors are synthesised mainly in the liver

Question 5

Measuring coagulation

Answer 5

1) prothrombin time (extrinsic)
2) activated partial thrombophlebitis time (intrinsic)
3) factors 7,8,9,11,12
4) factors 5,10 and prothrombin and fibrinogen

Question 6

Von Willebrand factor:

Answer 6

Involved in platelet adhesion to the vessel wall, platelet aggregation, and also carries Factor VIII

Vessel wall: is key as it’s important in vasoconstriction

Production of Von Willebrands factor - which is essential in platelet adhesion and the carrier and protector of Factor 8 (a clotting protein)

Exposure of collagen and tissue factor which initiates activation of clotting factors (proteins)

Question 7

Natural anticoagulants

Answer 7

Protein C
Protein S
Antithrombin

Question 8

Fibrinolysis

Answer 8

Plaminogen is activated by plasminogen activator

Plasminogen is then converted to plasmin which aids the catalysis of the fibrin clot

The clot is broken down into D-Dimers, which enter circulation and are uptaken and broken down by macrophages and neutrophils

Question 9

Clinical relevance of haemostasis

Answer 9

Patients will present with -
Bleeding disorders

Arterial thrombotic disorders

Venous thrombotic disorders

Abnormal blood test results

Patients will need Drug therapy for pro- or anti-thrombotic purposes

Question 10

Bleeding disorders

Answer 10

Due to abnormality in the vessel wall, platelets or coagulation factors

Can be both Inherited and acquired

When patients is cut with these types of disease - it takes longer to heal/ form a clot (sometimes they cant) so patient loses more blood

Question 11

Coagulation Factor disorders

Answer 11

Congenital - Haemophilia A (lack of Factor 8), Haemophilia B (lack of Factor 9)

Acquired - Liver disease (ALD), Vit K deficiency from diet, Anticoagulants given to a patient e.g.Warfarin (inhibits Vit K)

Clinical severity correlates with extent of deficiency - Muscle haematomas, Recurrent haemarthroses, Joint pain and deformity, Prolonged bleeding post dental extraction, Life threatening post op and post traumatic bleeding
Intracerebral haemorrhage (complications are worse depending on how severe the deficiency is)

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 (A drug - which increase the normal release of factor 8 from blood vessels)
Likely to be abnormal on the APTT test

Haemophilia B -
– Similar presentation to haemophilia A
–but instead its a congenital reduction in factor IX rather than VIII

Question 12

Von Willebrand’s disease

Answer 12

Relatively common - Usually autosomal dominant, affects males and females

VWF carries factor VIII and mediates platelet adhesion to the endothelium

This disorder could develop due to reduced FVIII amount/activity or due to Abnormal platelet adhesion to vessel wall

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) - therefore less factor 8 + platelet adhesion at the site of damage

vWD Clinically seen as: Platelet Associated Bleeding - Skin and mucous membrane bleeding, epistaxis (haemorrage of the nostril)
gum bleeding, easy bruising (all above are minor acute damage)

With chronic bleeding could be seen as 
Heavy periods
Post surgery
Post dental extraction
Spontaneous joint or muscle bleeds are rare

Question 13

Vessel wall abnormalities

Answer 13

Easy bruising
Spontaneous bleeding from small vessels
usually only affects the Skin mainly but can occur in mucous membranes

Problems with Vessels -
Congenital
Hereditary Haemorrhagic Telangiectasia (HHT)
An Autosomal dominant disease
Dilated microvascular swellings increase with time
Leading to tears in the vascular walls, leading to bleed
GI haemorrhage can lead to iron deficiency anaemia

Connective Tissue disorders-Ehlers Danlos

Acquired
Senile purpura
Steroids
Infection eg measles, meningococcal infection
Scurvy-Vit C def causing defective collagen production - scars dont form and old ones re-open

Question 14

Disseminated intravascular Coagulopathy

Answer 14

Type of microangiopathic (in the small blood vessels) haemolytic anaemia - due to clotting factors building up and damaging RBCs when they go past

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 15

Thrombophilias

Answer 15

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