Abnormalities of haemeostasis Flashcards Preview

Yr 3 - December lectures 2018 > Abnormalities of haemeostasis > Flashcards

Flashcards in Abnormalities of haemeostasis Deck (15)
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1

What are the components of a haemostatic response?

platelets
von willebrand factor
clotting factors
- proteases (FVII, FX, FXI, FIX (vit K dependent), prothrombin)
- cofactors (FV, FVIII)
- fibrinogen and FXIII
White cells

2

What is normal homeostasis dependent upon?

vessel wall integrity
adequate numbers of platelets
properly functioning platelets
adequate levels of clotting factors
proper function of fibrinolytic pathway

3

What are the sequence of events following blood vessel injury?

1) localized vasoconstriction at the site of the injury
- platelet adhesion to sub endothelium of damaged blood vessel => platelet aggregation/activations => thrombus formation
- activation of coagulation cascade => fibrin formation => thrombus formation
2) thrombus formation => fibrinolytic degradation of clot/vessel repair

4

What are the basic laboratory tests used to investigate haemeostatic system?

platelet count
prothrombin time
activated partial thromboplastin time
fibrinogen level

5

What is type 3 von willebrand disease?

arteriolar bleeding
- von willebrand protein is forced to open up into a long chain state under shear forces of arterioles

6

What does von willebrand protein bind to?

binds to GP1b on platelets and once activated exposes GPIIB/IIIA to bind more platelets

7

What are the 2 types of quantitative deficiency of vWF ad what do they mean?

type 1: partial deficiency of VWF
type 3: virtually complete deficiency of VWF

8

What are the different types of qualitative defects of vWF ad what do they mean?

TYPE 2 VARIANTS
- type 2a = decreased interaction of VWF with platelets associated with the loss of HMW VWF multimers
- type 2b = increased affinity of VWF for platelet GP Ib
- type 2M = decreased interaction of VWF with platelets NOT associated with loos of HMW VWF multimers
- type 2N = decreased affinity of VWF for factor VIII

9

How do you check if platelets are aggregating properly?

centrifuge blood to extract platelets then add some agonists to stimulate them

10

CASE 1: What has she got?
- 14 YR old girl, very heavy menstrual bleeding (passing large clots, changing pads hourly, flooding at night), epistaxis as child, easy bruising, prolonged bleeding time, fhx of bleeders)
VWF levels:
- VWF antigen = 28u/dl (50-150)
- VWF activity = 30u/dl (50-150)
- VIII 52 u/dl (50-150)
- normal platelet function testing by light aggregometry

quantitative defect - type 1 von Hillebrand disease

11

CASE2: What have they got?
- 27 yr old, unwell several days, gross hematuria
- urology team: Hb 72g/l, WCC 8.9, plus 5
- creatinine 130umol/l
- mildly jaundice and seems confused
- blood film reported = red cell fragments
- grand mal seizures and transfers to ITU but dies several hours later of cardiac failure

almost opposite of von willebrand disease
Thrombotic thrombocytopenia purpura (TTP)
- ADAM-13 prevents spontaneous clotting of platelets= have enzymes against ADAM-13 therefore nothing to prevent aggregation of vwb

extensive micro thrombi
before plasma exchange mortality 90%
some patients have neurological symptoms
essential to treat as quick as possible - transfusing platelets can worse things
give ADAM-13

12

CASE 3: 12 month old boy brought to A&E swollen knee
- crying during exam
- mother mentions he sometimes has large bruises after tumbles
- APTT = 78 seconds (28-36)
- PT = 12 seconds (10-13)

Hemophilia A = FVIII deficiency

Whereas FVIX deficiency = hemophilia b

13

What is a treatment for hemophilia a?

emicizumab
- antibody construct = binds FIX and X = giving a surrogate FVIII
given by subcut injection

14

What is a d-dimer a marker of?

specific monoclonal antibody that's a marker for thrombosis

15

What is transexamic acid?

antifibrinolytic = stops plasminogen being converted to plasmin = clot stabilizer