Flashcards in Abnormalities of haemeostasis Deck (15)
What are the components of a haemostatic response?
von willebrand factor
- proteases (FVII, FX, FXI, FIX (vit K dependent), prothrombin)
- cofactors (FV, FVIII)
- fibrinogen and FXIII
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
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
What are the basic laboratory tests used to investigate haemeostatic system?
activated partial thromboplastin time
What is type 3 von willebrand disease?
- von willebrand protein is forced to open up into a long chain state under shear forces of arterioles
What does von willebrand protein bind to?
binds to GP1b on platelets and once activated exposes GPIIB/IIIA to bind more platelets
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
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
How do you check if platelets are aggregating properly?
centrifuge blood to extract platelets then add some agonists to stimulate them
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 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
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
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
What is a treatment for hemophilia a?
- antibody construct = binds FIX and X = giving a surrogate FVIII
given by subcut injection
What is a d-dimer a marker of?
specific monoclonal antibody that's a marker for thrombosis