4 Haemostasis and Coagulation

Question 1

Identify the major components of the coagulation cascade

Answer 1

2 coagulation pathways

Intrinsic
- exposed collagen from injured blood vessel wall (test tube)

Extrinsic
- damaged tissue releases thromboplastin

Question 2

Describe the intrinsic coagulation pathway

Answer 2

Coagulation factors XII (12) is catalysed once exposed collagen Is released from the injured blood vessel wall

• Factor 12 activated, XIIa, which activates factor XI (11)
• Factor XIa (activated 11) activates Factor IX (9)
• Factor IXa (9) then activates Factor X (10)

Factor 10 converts prothrombin to thrombin (which stabilises factor 13)

• Thrombin also converts fibrinogen to fibrin
• And factor 13 converts fibrin to a stable fibrin clot

Question 3

Describe the extrinsic coagulation pathway

Answer 3

Tissue damage releases Tissue Factors (TF):

• Tissue factors bind to factor 7
• Activated Factor X (with TF) activates factor 10

which then activates prothrombin to thrombin
- which converts fibrinogen to fibrin

Hence, factor 13 converting fibrin to a stable fibrin clot

Question 4

Describe platelets

Answer 4

They are non-nuclear cellular fragments derived by:

• Large cells in bone marrow (Megakaryocytes)
• They form mechanical plugs during blood vessel injury

Question 5

Define adhesion reactions

(and aggregation reactions)

Answer 5

Adhesion:
- to subendothelial surface on damage/disease - due to binding to Von Willebrand’s factor

• adhesion causes release reaction: ADP and thromboxane which promote platelet aggregation

Question 6

Describe how adhesion and aggregation reaction aid in platelet function

Answer 6

Adhesion and aggregation lead to platelets mass to plug area of endothelial damage
- promotes coagulation reaction: -vely charged phospholipids on activated platelets which have adhered to the site of damage to localise fibrin formation

Coagulation is involved in Haemostasis

Question 7

Describe Haemostasis

Answer 7

The process of stopping blood loss through damaged blood vessels

Question 8

Describe the differences between haemostasis and thrombosis

Answer 8

Haemostasis is the process of stopping blood loss through damaged blood vessels

whereas

Thrombosis is unwanted blood clots

Question 9

Describe some laboratory tests that can be used to investigate coagulation and haemostasis

Answer 9

Bleeding time

• Incisions to the forearm with venous cuff
• Increases in platelet dysfunction or thrombocytopenia

Prothrombin time (INR)

• International normalised ratio
• It is the time for coagulation following the addition of thromboplastin
• It can be prolonged by abnormalities of factors VIII, X, V, II, or I, liver disease, or warfarin

Activated partial prothrombin time (APTT)

• Examines ‘intrinsic pathway’
• Altered by changes in factors XII, XI, IX, VIII, X, V, II, or I

Question 10

List some common disorders of clotting and bleeding

Answer 10

Thrombosis - unwanted blood clots

Venous - clots (thrombi) form in veins (DVT) due to stasis of blood, may travel to the lungs (and result in pulmonary embolism)

Atrial Fibrillation - risk of TIA (transient ischaemic attack) or stroke

Question 11

Describe thrombotic genesis

Answer 11

Thrombotic genesis can be described by Virchow’s triad:

• Alterations in blood flow (stasis) - poor movement, bed-bound (DVT)
• Vascular endothelial injury - atherosclerosis
• Alteration in the constitution of blood - e.g. polycythaemia (increase in viscosity of blood)

Question 12

Describe atrial fibrillation may give rise to a clot

Answer 12

When the atrium doesn’t work as it should:

• Arrhythmia causes uncoordinated contraction of the atrium
• Result = blood flow in altered - leading to clot in the atrium

Question 13

Describe how arterial thrombosis may arise

Answer 13

They form at atherosclerotic sites, and lead to arterial blockage:

• In heart: heart attack, myocardial infarction (MI)
• In cerebral vessels: stroke

Aterial thrombosis is a platelet evetns (MIs and ischaemic strokes)

Venous thrombosis is a coagulation factor event (DVTs)

Question 14

Describe Haemophilia A

Answer 14

It is a genetic condition
- carried on X-chromosome, so males (XY) are most affects, and females (XX) are carriers)

It is characterised by:

• Lack of factors VIII in the clotting cascade
• Haemorrhage and prolonged bleeding

Question 15

Give treatments for haemophilia A

Answer 15

Treat with:
- factor VIII from blood d
donors
- analogue of vasopressin (ADH) which increases patients factor VIII release (severe condition)

Question 16

Describe Haemophilia

Answer 16

It is a deficiency of factor IX
Results in:
- Bleeding in joints - movement - friction is common
- Abdominal cavity in the skin (platelet defects)

Treated with prophylactic factor IX (severe condition)

Question 17

Describe Von Willebrand’s Disease

Answer 17

It is a hereditary lack/defect in vWF

Leads to:

• increased bruising
• node bleeds
• mucosal bleeding

Treatment:
- analogue of vasopressin (ADH), factor VIII or vWF

Question 18

Describe liver disease (that has complication related to coagulation)

Answer 18

Reduced synthesis of clotting factors leads to increased bleeding
- Intrinsic coagulation component is affected = prolonged prothrombin time

Question 19

Describe thrombocytopenia

Answer 19

Reduced platelet number.
- Can result in spontaneous skin bleeding (purpura)

Causes:

• idiopathic
• viral
• drug-induced
• toxins

Question 20

Describe drug-induced thrombocytopenia

Answer 20

By immune mechanisms
- e.g. analgesics, anti-inflammatory, Abx, sedatives, anticonvulsants, diuretics, antidiabetic, cytotoxic anticancer drugs

Treatment:

• steroids (that suppress the immune response)
• if unresponsive - splenectomy

Question 21

Describe Disseminated Intravascular Coagulation (DIC)

Answer 21

Disseminated intravascular coagulation

Large amounts of fibrin generated by procoagulant material (amniotic fluid)

• Vast consumption of clotting factors and platelets
• Widespread haemorrhage - but may also by thrombosis

treatment:
- Give platelets and fresh forzon plasma