Haemostasis And Bleeding

Question 1

What is haemostasis?

Answer 1

The process of stopping bleeding and maintaining vascular patency

Question 2

What are the requirements for effective haemostasis?

Answer 2

Permanent state of readiness
Prompt and localised response
Protection against unwanted thrombosis

Question 3

What are stages of normal haemostatic response?

Answer 3

Primary haemostasis - platelet plug formation
Secondary haemostasis - secondary haemostasis

Fibrinolysis
Anticoagulant defences

Question 4

Platelets- lifespan, formation

Answer 4

Small anucleate discs with a 7-10 day lifespan
Formed in marrow via budding of megakaryocytes

Question 5

Describe the process of primary haemostasis

Answer 5

Vasoconstriction at injury site to reduce blood flow

Endothelial wall damage -> VWF release

Platelets adhere to VWF at injury site, and the platelets secrete various chemicals which cause aggregation

Question 6

What causes failure of platelet plug formation?

Answer 6

Vascular-
Hereditary eg Marian’s and Ehlers Danos
Acquired eg HSP, age, vitamin C deficiency

Thrombocytopenia-
DIC
Autoimmune- ITP
Hypersplenism
Reduced production

Acquired reduced function-
Drugs ie aspirin/NSAIDs, renal failure

Von Willerbrand disease

Question 7

What are the consequences of platelet plug formation abnormalities?

Answer 7

Spontaneous purpura and easy bruising
Epistaxis and menorrhagia
Petechiae (pinpoint spots due to capillary bleeding)

Eye symptoms

Question 8

Screening test primary haemostasis activity

Answer 8

Platelet count

Question 9

What are the clotting factors in the clotting cascade?

Answer 9

I- fibrinogen
II- prothrombin
IIa- thrombin
IV- calcium ions
V- proaccelerin (labile factor)
VI- part of factor 5
VII- proconvertin (stable factor)
VIII- antihemophillic factor
IX- Christmas factor (plasma thromboplastin component)
X- Stuart-Prower factors
XI- plasma thromboplastin antecedent
XII- Hagemans factor

Question 10

What is secondary haemostasis ?

Answer 10

The fibrin clot formation- stabilisation of the temporary platelet plug

Made up of extrinsic intrinsic and common pathway, which are all interlinked

Question 11

Explain process of extrinsic pathway

Answer 11

Initiation of the process

Tissue Factor (III) exposed when blood vessel is injured

Binds to factor VII which activates it to VIIa

The VIIa-TF complex activates factor X to Xa, which triggers common pathway

Question 12

Explain the process of intrinsic pathway

Answer 12

Endothelium damage exposes it to subendothelial collagen

Activates factor XII to XIIa -> activates Factor XI to Factor XIa -> activates IX to IXa

IXa along with VIIIa amplifies X -> Xa activation

Question 13

Explain the common pathway

Answer 13

Xa and Va forms prothrombinase complex

Converts II to IIa (prothrombin to thrombin)

Thrombin coverts I to Ia (fibrinogen to fibrin), forming a mesh that stabilises a platelet plug

XIIIa cross links fibrin strands to create a stable clot

Question 14

What causes failure of a fibrin clot formation?

Answer 14

Single clotting factor deficiencies eg haemophilia
Isolated prolonged APTT

Multiple clotting factor deficiencies eg DIC
Vit K deficiency/warfarin
Liver disease
Prolonged PT and APTT

Increased Fibrinolysis- seen as part of complex coagulopathies

Question 15

How do we test for fibrin clot formation deficiencies?

Answer 15

PT and APTT time

Question 16

What is PT?

Answer 16

Prothrombin time
Tests to see if extrinsic pathway is working

Affected in anticoagulant use, liver failure, and DIC

Question 17

What is APTT?

Answer 17

Activated partial thromboplastin time
Tests to see if intrinsic pathway is working Affected

Measures VIII, IX, XI, XII

Haemophilia A and VWD increases time

Question 18

What could it mean if both PT and APTT are altered?

Answer 18

Multiple clotting factor deficiencies

Question 19

What factors are carboxylated by vitamin K?

Answer 19

2 7 9 10

Question 20

Sources of vitamin K

Answer 20

Diet
Intestinal synthesis
Absorbed in upper intestine

Question 21

What are some causes of vitamin K deficiency

Answer 21

Poor dietary intake
Malabsorption
Obstructive jaundice
Warfarin (Vit K antagonists)

Haemorrhaging diseases of the newborn

Question 22

What is Fibrinolysis?

Answer 22

The process of breaking down a blood clot after injury has been repaired

Needed for prevention of thrombosis

Question 23

What is the process?

Answer 23

Plasminogen binds to fibrin within the clot

Tissue plasminogen activator (tPA) and urokinase “ “ (uPA) leads to activation of Plasmin

Plasmin breaks down fibrin into various things

Question 24

How can clot breakdown be assessed and by what product?

Answer 24

one of the degradation products is D-dimers

Measured to clinically assess clot breakdown

Question 25

What binds to free plasmin to prevent excess Fibrinolysis?

Answer 25

Alpha 2 antiplasmin

Question 26

What inhibits tPA and uPA and why?

Answer 26

PAI-1 (plasminogen activator inhibitor)

Controls plasminogen activation

Question 27

What are the consequences of impaired/excessive fibrinolysis?

Answer 27

Impaired- pathological clot persistence -> DVT/PE

Excessive- uncontrolled bleeding (DIC)

Question 28

What are the anticoagulant defences?

Answer 28

Protein C and S- circulating plasma protein from liver

Combine to form thrombomodulin

Thrombomodulin inactivates factor V and VIII to slow down coagulation

Antithrombin III -> affects factors 2 7 9 10 12