VWF disease Flashcards
PLT abnormalities dz (Primary Hemostasis)
Muco-cutaneous
- Petechiae
- Epistaxis/gingival bleeding
- Ecchymosis
- Menorrhagia
- GI/GU bleeding
Protein deficiency
Coagulation Related Bleeding
- Hemarthrosis (joint bleeds)
- Deep tissue bleeds
- Prolonged bleeding
vWF structure
- Large multimeric protein (from Weibel bodies/endothelial cells and alpha granule/megakaryocytes)
- Consist of binding sites for sub-endothelium, PLT, and F8
- Globular complex in circular –> bind –> linearizes –> aggregation and activation
- Key in primary hemostasis
vWF with PLT
- Binding PLT to sub-endothelium via GP1b
- Binding PLT to collagen via GP1b
- Binding PLT to PLT via GP2b/3a
vWF with F8
Chaperon for F8: prevent proteolysis and prolong half-life in circulation
vWF disease
1: Reduction in vWF
3: Severe loss of vWF
2A: Loss of the most active site (HW, IW)
2B: Gain of function mutation –> increase PLT binding site –> increase clearance in circulation
2M: Reduction of PLT binding site
2N: Reduction of F8 binding site
Factors affect vWF
Blood type O
Age
Low thyroid –> low circulated vWF
Menstruation: increased late luteal phase
Pregnancy: Incre 2nd, 3rd trimester, decline postpartum
Acute phase reactant (inflammation)
VWF Dx criteria
- VWF:AG:
ELISA or turbidimetric, falsely elevated with Rheumatoid - VWF activity: Ristocetin cofactor assay (VWF: RCo), Collagen binding activity (VWF:CB), others
- F8 activity
VWD 1
Autosomal dominant
Partial quantitative defect (all multimers)
Reduced vwf:ag, VWF activity
F8 normal-low
VWD 3
Autosomal recessive
Severe deficiency of vWF –> mucosal and deep tissue bleeding
Strongly reduced vwf:ag, vwf activity
F8: strong reduced
* Pt with gene deletion can develop anti-VWF Abs
VWD 2A
Autosomal dominant Loss an active multimers (large & int): AT13 cleavage site VWF:Ag normal, VWF activity: low F8: normal - low RIPA: low
VWD 2B
Autosomal dominant Gain of function: enhance GP1b binding site --> increase PLT binding --> clear out of circulation VWF:Ag normal, VWF activity: low F8: normal - low RIPA: POS
- Pseudo-VWD: defect on PLT’s binding site with VWF
VWD 2M
Autosomal dominant Loss of function: Impaired GP1b binding site --> decrease PLT binding site VWF:Ag normal - low, VWF activity: low F8: normal - low RIPA: low
VWD 2N
Autosomal Recessive Impaired of F8 binding site VWF:Ag normal, VWF activity: normal F8: low RIPA: normal * Hard to distinguish with Hemophilia A
VWD Classification
VWF multimers
RIPA (Ristocetin-induced PLT aggregation
F8 binding
Gene analysis
