1: Haemostasis Flashcards
What is haemostasis?
Arrest of bleeding while maintaining vascular patency
What is primary haemostasis?
Formation of a fibrin plug at a site of bleeding
Which protein is involved in secondary haemostasis?
Fibrin
forms a CLOT around the platelet plug
Which two processes keep haemostasis in check after the formation of the fibrin clot?
Fibrinolysis
Anticoagulation
Which blood cells form platelets?
Megakaryocytes
Are platelets cells?
No
Buds of cytoplasm from megakaryocytes
How long do platelets last for?
Why is this clinically relevant?
7 - 10 days
Anti-platelets e.g aspirin are stopped 7-10 days before surgery to avoid bleeding
What is the accumulation of platelets at a site of injury called?
Aggregation
Platelets ___ to form a plug in ___ haemostasis.
aggregate
primary haemostasis
Why do elderly patients bruise easily?
Express less collagen at sites of injury
Leading to less efficient haemostasis
What is Vitamin C required to produce?
What is Vitamin C deficiency called?
Collagen
Scurvy
What is a reduced number of platelets called?
Thrombocytopaenia
What proteins encourage platelet adhesion at the site of an injury?
Collagen
Von Willebrand factor
What is an autoimmune disease which causes a rash and thrombocytopaenia?
Immune thrombocytopaenic purpura
What symptoms may a patient have if they cannot form a platelet plug?
Bruising
Purpuric rash
Exaggerated bleeding
What diseases, causing platelet dysfunction, can cause abnormal bleeding?
Vitamin C deficiency (reduced collagen expression)
Autoimmune thrombocytopaenic purpura
Von Willebrand disease
Why do purpuric rashes often appear on the lower limbs?
Oncotic pressure due to gravity
Fluid (inc. blood) squeezed out of capillaries
Elderly / thrombocytopaenic patients cannot stop this “bleeding”
What is measured to diagnosed primary haemostasis?
Platelet count
What molecules are platelets made of?
Phosphoplipids
Which are negatively charged
Which ion is secreted by platelets?
Calcium
Ca2+, binds to -ve phospholipids
Which proteins bind to Ca2+ ions, found on the platelet plug, to cause secondary haemostasis?
Clotting factors
Which clotting factors initiate coagulation?
Tissue factor and Factor VIIa
Which two clotting factors convert prothrombin to thrombin?
Factor V and Factor Xa
___ ___ and factor ___ initiate clotting.
Tissue factor and Factor VIIa
The factor V/Xa complex converts ___ to ___.
prothrombin to thrombin
Thrombin converts ___ to ___, forming a clot.
fibrinogen to fibrin
What converts fibrinogen to fibrin to form a clot?
Thrombin
which is produced from prothrombin by factors V/Xa
Apart from converting fibrinogen to fibrin to form a clot, what else does thrombin activate during coagulation?
Factors VIII/IXa
Which reactivates Factor V/Xa
Which converts more prothrombin to thrombin…
Which protein, generated midway through the clotting cascade, activates other clotting factors?
Thrombin
What is the end product of the clotting cascade?
Fibrin
forming a clot
What is the first clotting factor which binds to the platelet plug?
Tissue factor <=> VIIa
What diseases are caused by a deficiency of
a) Factor VIII
b) Factor IX?
a) Haemophilia A
b) Haemophilia B
Which clotting factors are deficient in
a) Haemophilia A
b) Haemophilia B?
a) Factor VIII (haemophilia A)
b) Factor IX (haemophilia B)
Why might a patient with an increased reticulocyte count (e.g haemorrhage, haemolysis) also have thrombocytosis?
Red blood cells and megakaryocytes are derived from the same progenitor cells
So when you get an increase in red cell production, you get an increase in platelets
What is disseminated intravascular coagulation?
How is it related to clotting factors?
What triggers it?
Widespread clotting
Depletes clotting factors and platelets, thereby causing widespread bleeding
Trauma, sepsis, complicated pregnancy, malignancy, autoimmune disease…
i.e in anyone with widespread bleeding and thrombocytopaenia consider DIC
Which protein breaks down fibrin?
Plasmin
What is a notable fibrin breakdown product?
D dimer
Which protein converts plasminogen to plasmin?
Tissue plasminogen activator (tPA)
Where can blood escape in haemophilia?
Epistaxis, menorrhagia, malaena etc…
Into muscles
Into joints (haemarthrosis)
What is the mode of inheritance of haemophilia A and B?
X linked recessive
Which blood tests measure time taken for action of
a) tissue factor / factor VIIa?
b) factor VIII / IXa?
a) Prothrombin time (PT or INR)
b) Activated partial thromboplastin time (APTT)
Which clotting times are useful for
a) warfarin monitoring
b) heparin monitoring?
a) Warfarin monitoring - prothrombin time (factor VII)
b) Heparin monitoring - APTT (factor VIII/IXa)
What should you look at specifically on examination of someone with a suspected bleeding disorder?
Lower limbs - purpura
Mouth - the same
Eyes - retinal haemorrhage
Bleeding into muscles and joints
Which naturally occurring anticoagulant acts on thrombin?
Anti-thrombin III
Which anticoagulants act on clotting factors?
Protein C
(aided by protein S)
Which protein does thrombin use to switch functions and inhibit (instead of promote) coagulation?
Thrombomodulin
switches on Protein C and S
Which inherited disorder causes a tendency for venous thrombosis?
Thrombophilia
What is the most common type of inherited thrombophilia?
Factor V Leiden
