Intro to Haemostasis

Question 1

give the definition of Haemostasis?

Answer 1

the arrest of bleeding and the maintenance of vascular patency

Question 2

name the 4 requirements of haemostasis?

Answer 2

permanent state of readiness
Prompt response
Localised response
Protection against unwanted thrombosis

Question 3

Name the steps and components of a normal Haemostatic system? (4)

Answer 3

Primary Haemostasis:
Formation of platelet plug

Secondary haemostasis:
formation of fibrin clot

Fibrinolysis

Anticoagulant defences

Question 4

how are platelets formed?

Answer 4

in the BM by budding off from megakaryocytes

Question 5

describe the structure of platelets?

• describe the function of platelets?
• Name one protein released by endothelial damage?

Answer 5

-small nucleated discs with a mean life span of 7-10 days

-platelets have receptors that detect protein produced as a result of endothelial damage and this causes platelet adhesion at the site of injury
There is then secretion of various chemicals from the platelets leading to platelet aggregation

-Von Willebrand Factor

Question 6

what is primary haemostasis?

describe how this process occurs?

Answer 6

-the formation of a platelet plug

-3 different stages
stage 1- vasoconstriction
smooth muscle in endothelium constricts

stage 2- platelet adhesion
blood vessel injury causes VWF to be released by the endothelial cells.
The VWF binds to sub endothelial collagen and also to platelets
the platelet is activated and changes shape, degranulation occurs releasing VWF and fibrin al well as serotonin, ADP and Ca.
serotonin- constricts sm
ADP- activates platelets and promotes aggregation
Ca- needed for secondary haemostasis

Stage 3-Platelet aggregation
this is mediated by 2B/3A receptor on surface of platelets and cause the formation of a PLATELET PLUG

Question 7

give reasons for failure of the platelet plug? (4)

Answer 7

Vascular

reduced no. platelets e.g. thrombocytopenia
platelets unable to function

Von Willebrand factor absent or inactive

Question 8

what are the consequences of a failure of primary haemostasis? (4)

Answer 8

spontaneous bruising and purpura
mucosal bleeding (epistaxis, GI, Conjunctival, Menorrhagia)
inter cranial haemorrhage
Retinal haemorrhage

Question 9

screening test for primary haemostasis? (1)

Answer 9

Platelet count

no simple tests for other components

Question 10

What is secondary haemostasis?

-describe the process?

Answer 10

Fibrin clot formation

platelets are made up of phospholipids which are negatively charged
Degranulation of the platelet causes the release of Calcium onto the + charged platelet surface
clotting factors are - charged and so are attracted to the platelets.

Tissue factor is released from the damaged endothelial cell and activates clotting factor VII
This in turn activates factors V and X to produce Thrombin from prothrombin which produces Fibrin generated from fibrinogen

Thrombin produces XII and IX which activates more V/X to initiate a rapid feedback loop and causes a prompt response at site of injury

Question 11

why might secondary haemostasis fail?

Answer 11

single clotting factor deficiency
(usually hereditary e.g. haemophilia)

multiple clotting factor deficiencies
(usually acquired, e.g. DIC/liver failure)

Increased fibrinolysis
(usually part of a coagulopathy)

Question 12

Give the 3 types of haemophilia?

-give an example of a clinal sign?

Answer 12

-Haemophilia A- missing factor VIII

Haemophilia B- missing factor IX

Haemophilia C- missing factor XI

-Haemarthrosis into major weight bearing joints

Question 13

• What is fibrinolysis?
• What enzyme meditates the process?
• What are the products?

Answer 13

the process whereby fibrin is degraded by plasmin.

• Plasmin, activated from plasminogen by Tissue plasminogen activator
• FDPs, the cross linked form of which is D-dimers

Question 14

What are the consequences of secondary haemostasis failure?

Answer 14

no characteristic clinical syndrome

may be combined primary/secondary haemostatic failure

pattern of bleeding will depend on abnormalities and clotting factors involved

Question 15

Name the screening tests for fibrin clot formation?

• if both of these are prolonged what does it indicate?
• which factors do warfarin and Heparin effect?

Answer 15

prothrombin time (PT)
tests clotting factor VII

activated partial thromboplastin time (APTT)
tests clotting factors VIII & IXa

-global problems with haemostasis and multiple clotting factors or and intrinsic problem with clotting factors V/X

-Warfarin: affects VII
Heparin: affects VII/IX

Question 16

Important questions to ask in bleeding disorder hx?

Answer 16

any bleeding bruising?
duration- life long?
prev surgery/ dental extractions?
Drug Hx
Family Hx
\+ exam

Question 17

Name the naturally occurring anticoagulants?

-what is the risk in deficiency of these?

Answer 17

• Serine protease inhibitors
  i. e. Thrombin binds to thrombomodulin to switch off thrombin and factors V & VIII and achieve haemostasis

Protein C and protein S
these inhibit factors V/X/VIII/IX

-venous thrombosis

Question 18

What is thrombophilia?

Answer 18

• deficiency of naturally occurring anticoagulants, may be hereditary
• increased risk of PE/DVT