9. Haemostasis and Coagulation

Question 1

what is haemostasis

Answer 1

one of the most important survival mechanisms and is the ability to minimise blood loss following injury
the haemostatic system represents a delicate balance between the normal function of blood and preventing blood loss following injury

Question 2

5 main components of haemostasis

Answer 2

have complex interactions
blood vessels - vasoconstriction. first to respond to injury
platelets
coagulation factors
coagulation inhibitors
fibrinolysis: lysis of the stable fibrin clot

Question 3

blood vessels , platelets and coagulation in haemostasis

Answer 3

see diagram slide 4
damaged blood vessel, collagen exposure, platelet adhesion and activation, to vasoconstriction, platelet aggregation, blood coagulation and a stable haemostatic plug
serotonin is a vasoconstrictor
thrombin platelet activator

Question 4

endothelium and endothelial cells

Answer 4

maintaining vascular integrity
potent antihaemostatic influence(release certain factors that will allow us to prevent clots being formed pathologically
-prostacyclin and nitric oxide
-vasodilatory properties
-inhibit adhesion of platelets
source of
-von Willebrand factor is present in cells, carry tPA which is important in fibrinolysis
-tissue plasminogen activator tPA
a fully intact endothelial lining inhibits platelets from sticking to surface so they go round circulation

Question 5

blood vessels - vasoconstriction

Answer 5

immediate 
smooth muscle cells 
effect is for a few minutes 
other mechanisms take over very quickly 
note is not a step by step process

Question 6

platelets

Answer 6

produced in bone marrow
fragmentation of megakaryocyte cytoplasm
1 megakaryocyte = 4000 platelets
size 2-4um diameter
circulating platelets have lifespan of 9-10 days
normal platelet count150-400x10^9
destroyed in spleen and in liver(Kupffer cells) by macrophages
myeloid cell line

Question 7

platelet production

Answer 7

platelets are produced in bone marrow by endomitotic synchronous nuclear replication
cytoplasmic volume increases as the number of nuclear lobes increase in multiples of two
cytoplasm becomes granular and platelets are released
1 megakaryocyte can produce 4000 platelets
from stem cell to platelet takes ten days

Question 8

platelt production is controlled by

Answer 8

negative feedback: number of circulating platelets
stimulated by thrombopoietic TPO - produced in liver and increases numbers
IL3 and GM-CSF are growth factors that stimulate anything down granulocyte, monocyte, myeloid route. will also stimulate precursor cells

Question 9

ratio of rbc:platelet:wbc

Answer 9

700 to 40 to 1

Question 10

platelet structure

Answer 10

plasma membrane mitochondria
Glycocalyx:
-glycoproteins eg GPIa, GPIb, GPIIb
-allows platelet yo adhere to surfaces such as collagen of damaged vessels
glycogen:
-energy reserve/store in cell
Dense tubular system:
-site of prostaglandin and thromboxane A2 synthesis
Platelet contractile proteins
-submembraneous filaments which make platelet aggregation irreversible

Question 11

aggregation

Answer 11

platelets sticking/ clumping together at the surface of the damaged blood vessel. irreversible so platelets cant come apart and cant topen up the platelet plug

Question 12

platelet structure continued

Answer 12

2 types of granules
electron dense (delta) granules and alpha granules
-used for platelet aggregation
-delta granules contain Ca2+ (important for coagulation), ADP, ATP and serotonin which can enhance vasoconstriction by feeding back into blood vessel
-alpha granules including platelet derived growth factor (which enhances platelet production, acts on bone marrow), vWF (released from platelet granules when activated), factors v and viii needed for speed of coagulation
All coagulation factors are released from the liver, some are already in circulation and present already at the needed site
Canalicular system allows the platelet to be released and when the platelets are activated this will lead to the release of granules - secretion stage of haemostasis

Question 13

platelet function - platelet plug formation

Answer 13

adhesion
secretion (granule release reaction)
aggregation - pseudopodia allow movement within the region of dmaged blood vessel, can roll over and form contact with other platelets
platelet plug formation

Question 14

start of platelet plug diagram slide 14

Answer 14

exposed collagen on damaged blood wall vessel
vWF factor released from endothelial cell
platelet going past can adhere to vWF fsctor, in this case GPII but could adher to other GPs on platelet membrane

Question 15

haemostatic platelet plug

Answer 15

secrete ADP (released upon activation and adhesion)and thromboxane A2 which both lead to increased aggregation
platelets swell due to ADP (facilitates adhesion)
positive feedback releases more ADP and TXA2
vWF
platelet plug formed

Question 16

blood coagulation - coagulation factors

Answer 16

coagulation factors suc as co factors, serine proteases, coagulation related proteins
some are well known by their description name eg tissue factor III (FIII), prothrombin (FII)
but others by their factor number FVIII and FIX

Question 17

initation of coagulation cascade: tissue factor

Answer 17

tissue factor (TF) on the surface of endothelial cells and leukocytes 
not normally in direct contact with circulating blood
tissue factor comes into contact with factor VII and activates it to factor VIIa

Question 18

events of coagulation (see slides) : initiation

Answer 18

1. initiation
   (I) formation of extrinsic tenase complex
   product is FXa
   (ii) generation of trace thrombin
   common pathway, FXa acts upon prothrombin FII to produce thrombin FIIa
   (iii) down regulation of initiation by TFPI
   trace of thrombin because of inhibitor tissue factor pathway inhibitor

Question 19

events of coagulation after initiation

Answer 19

(2) amplification
thrombin allows us to activate more platelets so they can become involved in platelet plug production
allows us to activate our cofactors eg V and VIII, which are two cofactors factor V is a cofactor for factor IX
(3) propogation
(i) formation of intrinsic tenase complex
forming fibrin clot on surface of platelets
combine and prduce more Xa
(ii) formation of prothrombinase complex
(iii) burst of thrombin generation
-fibrin polymer formation
-thrombin activates FXIII-FXIIIa
STABLE FIBRIN CLOT
fibrinogen to fibrin
clot traps rbc

Question 20

key points

Answer 20

primarily surface of activated platelets
each complex coprises an enzyme, a cofactor and a substrate
-extrinsic tenase: FVIIa, TF, FX respectively
-intrinsic tenase FIXa, FVIIIa, FX respectively
-prothrombinase FXa, FVa, FII respectively
-vitamin K dependence
-calcium ions