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Cardiorespiratory 2 PBL > PBL 2 > Flashcards

PBL 2 Flashcards

1
Q

What is prothrombin time

A

it is used to measure the effectiveness of the extrinsic and common pathways involved in the secondary haemostasis

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2
Q

what factors does prothrombin time check to see are present

A

I, II, V, VII, and X

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3
Q

what is activated partial thrombroplastin time

A

this is a blood test that measures the effectiveness of the intrinsic and common pathways, it measures the time taken for the coagulation cascade,

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4
Q

what factors does APTT measure

A

I, II, V, VIII, X, XI, XII

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5
Q

what is thrombin time

A

– 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

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6
Q

what is factor VIII

A

is known as the anti-haemophilic factor, defects result in haemophilia A which is a recessive X linked disorder

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7
Q

What is factor IX

A

it is one of the serine proteases of the coagulation system, deficiency of this protein causes haemophilia B

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8
Q

what is von williebrand factor antigen

A

this measures the quantity of a protein called VWF

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9
Q

Describe how the platelet plug forms

A
  • 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
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10
Q

what is briefly happens in definitive clot formation

A
  • 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
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11
Q

describe how the extrinsic pathway works

A
  • 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
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12
Q

describe how the intrinsic pathway works

A
  • 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
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13
Q

describe how the common pathway works

A
  • 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
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14
Q

how is PT measured

A
  • A tissue thromboplastin is incubated with citrated plasma and then recalcfieid and time taken for clot formation is measured, also used to measure INR
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15
Q

describe what TT measures

A
  • Sensitive to deficiency of fibrinogen or inhibition of thrombin
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16
Q

describe how bleeding time is measured

A
  • 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
17
Q

what do the tests indicate

A

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

18
Q

what is Sharons diagnosis

A

Von Willebrand disease - Can start at any age

19
Q

what is the genetics of VWF

A
  • Autosomal dominant – mother has it

- People with blood group O more effected

20
Q

What are the types of VWF

A

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

21
Q

what are the symptoms of VWF

A
  • 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
22
Q

What is the treatment of VWF

A

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
23
Q

what is primary haemostasis

A

Primary haemostasis = formation of the platelet plug

Platelet aggregation

24
Q

what is secondary haemostasis

A

Secondary haemostasis = formation of fibrin to stabilise plug and create clot
Clotting cascade

25
Q

what is VWF

A

Large multimeric plasma glycoprotein

26
Q

where is VWF produced and stored

A

Produced and stored in endothelial cells

27
Q

what is the function of VWF

A

Promote platelet aggregation for primary haemostasis

  • Binds to exposed collagen in vascular ECM and undergoes conformational change
  • Binds platelets in plasma via GpIb
  • Platelets become activated and continue to bind each other and VWF via GpIIb/IIIa

Carrier molecule for FVIII in plasma which otherwise has a very short half life
- Important for the propagation of secondary haemostasis (clotting cascade)

28
Q

what is the inhertience of VWD

A

Autosomal dominant (apart from type 2N)

29
Q

How do you diagnose VWD

A

Bloods: FBC, platelet, clotting screen
Plasma levels of VWF
- Quantitative: VWF antigen assay
- Qualitative deficiency: many methods e.g. glycoprotein binding assay

Coagulation screen

  • APTT (activated partial prothrombin time) – intrinsic pathway
  • PT – extrinsic pathway
  • TT – common pathway

Special test

  • FVIII clotting assay – reduced (not being stabilised by VWF)
  • FIX clotting assay – normal
  • VWF:AG – reduced
30
Q

what is an FVIII and an FIX clotting assay carried otu

A

to rule out haemophilia

31
Q

why is the FVIII clotting assay reduced in her results

A
  • not being stablised by VWF
32
Q

what is the mechanism of action of tranxamic acid

A

Tranexamic acid binds to plasminogen preventing its conversion to plasmin. Plasmin is the physiologic molecule that breaks down fibrin (final product of coagulation cascade, stabilises clot). By preventing plasmin’s degradation of fibrin, tranexamic stabilises clots and reduces bleeding.

33
Q

what is the manegment of VWD

A

Educate patients about bleeding risk and NSAIDs

Tranexamic acid
- Anti-fibrinolytic agent*

Desmopressin (DDAVP)

  • Synthetic ADH analogue
  • Stimulates release of FVIII and VWF from endothelial stores
  • Intranasally or parentally

Contraceptive options
- Oral contraceptive or IUD to reduce menorrhagia

Platelet transfusion

Prophylaxis

  • Surgery or major bleeding episodes
  • VWF-containing FVIII concentrate

Genetic counselling

34
Q

what are VWFs main functions

A

Binds platelets to form primary haemostatic plug and carrier molecule for FVIII

35
Q

what is type 2 VWD

A

Normal VWF levels with abnormal function

Cardiorespiratory 2 PBL (10 decks)

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