haemostasis Flashcards
define haemostasis
cessation of bleeding at vascular injury site via the formation of a thrombus
what are the 2 primary components of a thrombus?
platelet plug
fibrin clot
what is primary haemostasis?
aggregation of platelets
what is secondary haemostasis?
fibrin clot formation
what are platelets?
not cells
small bags of cytoplasm shed from megakaryocytes
how many platelets can a megakaryocyte produce?
over 1000 platelets
what is the normal platelet to red cell ratio?
1-2 per 20 red cells
how long do platelets survive for?
8.5-10 days
4 day half life
where are platelets destroyed?
spleen
what chemical regulates megakaryocytes and platelet production?
Thrombopoietin
where is thrombopoietin made?
kidneys and liver
what are the normal levels of platelets?
150-400x10^9 per litre
what is thrombocytopenia?
platelet count less than 150x10^9 per litre
what is thrombocytosis?
platelet count of more than 400 x 10^9 per litre
how does normally intact endothelial lining prevent platelet adhesion?
continuous release of nitric oxide and prostacyclin
when there’s damaged endothelium, what binds to the exposed collagen?
von Willebrand Factor
what type of molecule is von Willebrand factor?
glycoprotein
how can platelets bind directly to exposed collagen?
directly via Gp1a/Gp6
why do platelets need to bind to VWF? why don’t they bind to the collagen directly?
- platelets adherance to the collagen is weak on its own
- VWF acts as a bridge
once platelets have adhered to the VWF, what receptor do they express?
GP2b/3a receptor
what do adherent platelets bind?
fibrinogen –> forms a meshwork
what chemicals do adherent platelets release?
adenosine diphosphate (ADP), thromboxane A2 (TXA2) and serotonin (5-HT) from granules
also release cytokines
what do ADP and TXA2 fo?
attract more platelets to site which aggregates to form platelet plug
what effect does 5-HT have?
acts on local smooth muscle to increase local vasoconstriction
what is the bleeding time?
time taken to form an effective plug and to stop initial haemorrhage
what is the bleeding time test?
make a puncture wound in a superficial area of the skin and monitor the time needed for the bleeding to stop
what is the normal bleeding time in adults?
1-9 mins
what is the normal bleeding time in children?
1-13 mins
what is endothelin?
a powerful vasoconstrictor stored in endothelium, released by damage
what stabilises and strengthens the platelet plug?
thrombin formed by the coagulation cascade
when does the extrinsic pathway trigger coagulation?
when its exposed to factor 7 and tissue damage
which cells express tissue factor?
fibroblasts
smooth muscle cells
explain the extrinsic pathway?
- Factor 7 is exposed to Tissue Factor (7 –> 7a)
- 7a and calcium convert 10 to 10a
- Xa converts prothrombin to thrombin
what is the tenase complex?
the enzymes and calcium which convert factor X to Xa
what is the start of the common pathway?
conversion of prothrombin to thrombin by Xa
what is the function of thrombin?
converts soluble fibrinogen to insoluble fibrin
what factor does thrombin activate?
factor 13
what does factor 13a do?
stabilises polymerised fibrin
explain the positive feedback loop that thrombin is in?
- thrombin converts factors V, VIII and XI (11) into active forms
- XIa (11a) converts factor IX to IXa (9a)
- 9a and 8a increase the conversion of 10 –> 10a
- 5a increases effectiveness of 10a
explain the intrinsic pathway
- factors 12 and 7 are activated by exposure to collagen
- 12a converts 11 to 11a
- 11a converts 9 to 9a
- 9a converts 10 to 10a
when does the intrinsic pathway activate clotting?
when the blood is stagnant e.g. in the atria or in deep vein thrombosis
what does prothrombin time assess?
assesses extrinsic and common pathway
what does the activated partial prothrombin time?
assesses intrinsic and common pathways
explain the process of finding the bleeding time?
Scalpel/lancet makes a shallow 1mm deep incision on the underside of the forearm. Time from incision being made till all the bleeding has stopped = bleeding time
what is the INR derived from?
prothrombin time
what is the normal range for INR?
0.8 - 1.2
what is INR used for?
to assess the coagulability of blood in patients taking warfarin or heparin bc they’re at risk of abnormal clot formation e.g. DVT or pulmonary emboli. In these patients an INR of 2.0-3.0 is aimed for
what does a higher INR mean?
the longer it takes you to clot
what can cause a higher INR?
drugs like heparin or warfarin
what is the function of factor 13a?
Factor XIIIa (from thrombin) increases crosslinking in the fibrin fibrils to form a mechanically stable clot
what is haemophilia A?
deficiency of factor 8
what does a deficiency in factor 8 result in?
reduces the effectiveness of the positive feedback loop forming thrombin
what is haemophilia B?
factor IX deficiency
what is antithrombin?
a small plasma protein that regulates coagulation system activity
binds and inactivates several enzymes in the coagulation cascade
what is a-antithrombin?
dominant form of antithrombin found in blood plasma
what is plasmin?
main enzyme responsible for the removal of clots (fibrinolysis) when the damaged tissue is healed
how does plasmin circulate in the blood?
in the form of an inactive precursor plasminogen
how does plasminogen work?
binds to platelet plugs as they form
gets incorportated into the final clot
how is plasminogen held in its inactive form?
by alpha-2-antiplasmin
circulates in high concentration in the plasma
what does tissue plasminogen activator do?
catalyses plasminogen –> plasmin
stops a clot extending too far along a blood vessel into healthy tissue
where is TPA released from?
from normal endothelial cells
when is TPA released?
when the injury has healed
plasminogen gets converted to plasmin so that the clot can be destroyed
what is D-Dimer?
a product of fibrin breakdown – protein fragment that circulates in the blood
why is d-dimer measured and what does the measurement of it show?
an important test performed in patients with suspected thrombotic disorders (e.g. DVT)
low plasma levels of d-dimer are an indication that thrombosis is not present
what is vitamin K?
Group of vitamins that the body needs for full effectiveness of factors VII, IX and X
why is vitamin K important?
modifies the factors VII, IX and X and allows them to bind to calcium ions
without it, blood coagulation is impaired and uncontrolled bleeding occurs
what are the 2 forms of vitamin K?
K1 and K2
where is vitamin K1 found in highest amounts?
K1 and K2
what can convert K1 to K2?
animals and bacteria in the gut flora
what are risk factors for vitamin K deficiency?
liver disease, poor diet (no green vegetables), poor absorption, antibiotics
how is vitamin K deficiency seen in blood tests?
increased INR
may result in unstable clots
what is vitamin K a risk factor for?
osteoporosis
what is vitamin K a treatment for?
- one of the treatments for bleeding events caused by overdose of the anticoagulant drug warfarin
- Vitamin K is also used to treat poisoning by rat poisons (coumarin poisoning).
what does heaprin do?
binds to and increases the activity of anti-thrombin
what does activated AT inhibit?
thrombin
factor Xa
how is heparin given and why?
Must be given parenterally (i.v. or subcutaneous) as not absorbed through gut
why is heparin given regularly?
has a short half life
how does warfarin work?
Warfarin interferes with the hepatic synthesis of vitamin K–dependent coagulation factors especially Factors VII, IX and X
name a direct thrombin inhibitor
dabigatran
name factor Xa inhibitors
rivaroxaban, apixaban and edoxaban
how do platelets bind to VWF?
Gp1b receptors
