Haemostasis Physiology Flashcards
what is haemostasis?
arrest of bleeding and maintenance of vascular patency
what is primary haemostasis?
formation of the platelet plug (in severe bleeding can be washed away)
what is secondary haemostasis?
formation of the fibrin clot
what is fibrinolysis
maintaining vascular patency and switching haemostasis off
what are platelets?
small anucleate discs with a lifespan of 7-10 days
what does endothelial wall damage cause?
exposes collagen and releases VWF
what does VWF do?
platelets have receptors to VWF leading to platelet adhesion at the site of the injury
also carries factor VIII
what do the bound platelets secrete?
ADP
thromboxane A2
what does the secretion of ADP and thromboxane A2 from the platelets cause?
further aggregation
what do platelets bind to at the site of injury?
subendothelial collagen via:
- VWF
- glycoprotein 1b
what allows platelets to attach to one and other?
GPIIbIIIa
fibrinogen
causes of failure of formation of the platelet plug
vascular
thrombocytopenia
VWF deficiency
what are vascular causes of failure of formation of the platelet plug?
lack of collagen leads to weakened endothelial walls e.g. ageing and scurvy
three causes of thrombocytopenia
- reduced production
- increased destruction
- functional defects
what causes reduced production thrombocytopenia?
bone marrow failure
what causes increased destruction thrombocytopenia?
coagulopathy (DIC)
AI (ITP)
hypersplenism
how does alcohol cause hypersplenism and thrombocytopenia?
alcohol causes portal hypertension and cirrhosis backs up to the spleen causing hypersplenism that traps platelets reducing count
alcohol can also have a toxic effect on the spleen
functional defects causes of thrombocytopenia
drugs (aspirin, NSAIDs)
renal failure
inheritance of VWF deficiency
AD
presentation of failure of primary haemostasis
easy bruising/ purpura/ petechiae
mucosal bleeding (epistaxis, conjunctival haemorrhage)
menorrhagia
diagnosis of failure of primary haemostasis
FBC for platelet count
causes of failure of formation of the fibrin clot
single clotting factor deficiency
multiple clotting factor deficiencies
increased fibrinolysis
what is a single clotting factor deficiency?
haemophilia
causes of multiple clotting factor deficiencies
DIC
liver failure
vitamin K deficiency/ warfarin therapy
presentation of failure of secondary haemostasis
bleeding into muscles and joints (ankles and knees)
diagnosis of failure of secondary haemostasis
PT (TF/VIIa)
APTT (VIII/IXa)
where are all coagulation factors synthesised?
hepatocytes
which coagulation factors are carboxylated by vitamin K?
II
VII
IX
X
what does the addition of vitamin K to coagulation factors II, VII, IX and X cause?
gives them a negative charge to bind to Ca2+ on phospholipids
what does vitamin K require for absorption?
bile salts
causes of vitamin K deficiency?
poor dietary intake malabsorption obstructive jaundice head of pancreas cancer lack of bile salts vitamin K antagonists e.g. warfarin HDFN
what are some naturally occurring anticoagulants?
serine protease inhibitors (anti-thrombin)
protein C
protein S
what is thrombophilia?
deficiency of naturally occurring anticoagulants leading to an increased tendency to develop venous thrombosis
action of anti-thrombin
binds to thrombin to switch haemostasis off
action of protein S and C
bound by thrombomodulin which switches off clotting factors V/Xa and VIII/IXa
two pathways in the coagulation cascade
- extrinsic
2. intrinsic
what is the extrinsic pathway of the coagulation cascade?
TF and VIIa initiates haemostasis
act on Va/Xa
which act on prothrombin (factor II) of the common pathway
this is cleaved to form thrombin (IIa)
acts on fibrinogen (factor I) > fibrin (Ia)
what is the intrinsic pathway of the coagulation cascade?
activated by IIa (thrombin) are VIIIa/IXa
these are also activated by XI and XII
which pathway does PT measure?
extrinsic / factor VII
how is the PT carried out
thromboplastin is added to the blood sample and timed how long it takes to clot
normal PT
10-12 seconds
what pathway does APTT measure?
intrinsic/ factor VIII IX
how is the APTT test carried out?
a contact activator with calcium and phospholipid is added to blood and timed how long it takes to clot
normal APTT
30-40 seconds
what does a prolonged APTT indicate?
single clotting factor deficiency
causes of a single clotting factor deficiency
haemophilia A or B (X-linked) XI or XII deficiency heparin VWF deficiency APLS
how VWF deficiency prolong APTT?
VWF carries VIII so if deficient can prolong APTT
what does a prolonged PT and APTT indicate?
multiple clotting factor deficiency
causes of multiple clotting factor deficiency
heparin warfarin vitamin K deficiency liver disease DIC
what is tested to distinguish DIC from liver disease?
D-dimers
