PBL 2 Flashcards
What is prothrombin time
it is used to measure the effectiveness of the extrinsic and common pathways involved in the secondary haemostasis
what factors does prothrombin time check to see are present
I, II, V, VII, and X
what is activated partial thrombroplastin time
this is a blood test that measures the effectiveness of the intrinsic and common pathways, it measures the time taken for the coagulation cascade,
what factors does APTT measure
I, II, V, VIII, X, XI, XII
what is thrombin time
– it is a blood test that measures the time it takes for a clot to form in the plasma of a blood sample containing anticoagulant after excress thrombin has been added, compares the rate of clot formation to that of a sample of normal pooled plasma
what is factor VIII
is known as the anti-haemophilic factor, defects result in haemophilia A which is a recessive X linked disorder
What is factor IX
it is one of the serine proteases of the coagulation system, deficiency of this protein causes haemophilia B
what is von williebrand factor antigen
this measures the quantity of a protein called VWF
Describe how the platelet plug forms
- damaged endothelium
- this means that collagen underneath the endothelium is exposed to the blood
- Von willebrand factor (VWF) binds to the exposed collagen
- platelets then bind to the VWF via the platelet GP1b receptors (platelets can also bind directly to the collagen via Gp1a and Gp6 receptors but this is very weak)
- the VWF has formed a bridge between the collagen and platelets, this is called platelet adherence
- the adherent platelets express the GP2b/3a receptor
- GP2b/3a receptors bind to fibrinogen which binds more platelets to form a meshwork this is called platelet aggregation
- the binding of platelets cause the platelets to become activated
- they change shape and become spiky and entailed together
- they release ADP and thromboxane A2 (TXA2) and serotonin (5-HT) from granules, this is called the platelet release reaction
- ADP & TXA2 attract more platelets to the site which aggregate to form a platelet plug.
- 5-HT acts on local smooth muscle to increases local vasoconstriction.
- The spiky platelets in turn release cytokines which attract even more platelets and so a positive feedback system operates until a plug large enough to stop the bleeding is formed
what is briefly happens in definitive clot formation
- There is activation of coagulation factor proteases which results in protease thrombin
- Thrombin is essential for the production of fibrin monomers
- These are cross linked and form a meshwork around the platelet plug
describe how the extrinsic pathway works
- Factor VII is exposed to tissue factor (III) when the blood vessel is injured
- the tissue factor (III) converts factor VII to VIIa
- VIIa then reacts with calcium and factor X in the blood to form factor Xa
describe how the intrinsic pathway works
- Factor XII is converted into XIIa
- XI is converted to XIa by XIIa
- IX is converted into Isa by XIa and calcium
- then IXa and calcium is used to convert X to Xa
describe how the common pathway works
- Xa and calcium from the extrinsic pathway cause prothrombin to be converted to thrombin
- thrombin turns fibrinogen to fibrin
- thrombin also creates a bit of XIII
- XIII turns into XIIIa
- XIIIa stabilises the fibrin into a stable clot
how is PT measured
- A tissue thromboplastin is incubated with citrated plasma and then recalcfieid and time taken for clot formation is measured, also used to measure INR
describe what TT measures
- Sensitive to deficiency of fibrinogen or inhibition of thrombin
describe how bleeding time is measured
- A lancet or scalpel blade is used to make a shallow incision 1 millimeter deep on the underside of the forearm.
- The time from when the incision is made until all bleeding has stopped is measured and is called the bleeding time
- Normal values fall between 3 – 10 minutes.
- the formation of the platelet plug determines the bleeding time
what do the tests indicate
Hb Low Bleeding so reduction in blood
APTT 65s (normal 26-40s) APTT high this could mean anything from a bleeding disorder to liver disease, The intrinsic pathway and common pathway is effected
Factor VIII clotting assay: mildly reduced Could mean that she has haemophilia A
X -linked recessive condition, doubt it tho as unlikely to be transferred from mother as she is female
Von Willebrand Factor Antigen (VWF:AG): Reduced Von Willebrand disease
Autosomal dominant
Can be inherited
More likely to be this
what is Sharons diagnosis
Von Willebrand disease - Can start at any age
what is the genetics of VWF
- Autosomal dominant – mother has it
- People with blood group O more effected
What are the types of VWF
Type 1: decreased amount of VWF; 60-80% cases
Type 2: normal amount of VWF with abnormal function; 20-30% cases
Type 3: complete absence of VWF; 1-5% cases
what are the symptoms of VWF
- Bleeding tendency:
- epistaxis- acute hemorrhage from the nostril, nasal cavity, or nasopharynx
- menorrhagia,
- bleeding from minor wounds,
- easy and excessive bleeding,
- post-operative bleeding
- Family history
What is the treatment of VWF
Treatment
- Apply pressure to the wound for a few minutes
- Desmopressin – nasal spray or injection
- Tranexamic acid – tablets, mouthwash, injection
- Von Willebrand factor concentrate – available as an injection
For heavy periods
- Oral contraceptive pill
- IUS
- Tranexamic acid tablets
- Desmopressin nasal spray
- VWF concentrate
what is primary haemostasis
Primary haemostasis = formation of the platelet plug
Platelet aggregation
what is secondary haemostasis
Secondary haemostasis = formation of fibrin to stabilise plug and create clot
Clotting cascade
