Von Willebrand Syndrome Flashcards
VWS subtypes that are not autosomal dominant
Type 2N
Type 3
(autosomal recessive)
von willebrand factor primary functions
1) Facilitate platelet binding to subendothelial collagen
2) facilitate platelet-platelet interactions
3) Protect clotting factor VIII
What chromosome is VWF located on?
12
What is VWS type 1?
mild quantitative, partial deficiency
VWS type 1 lab profile
***concurrent reduction of activity (ristoecetin) and antigen (21%-25% still considered concordant)
Low Factor 8 (VWF is a carrier protein)
Low antigen level
Ristocetin low or normal
RIPA low or normal
VWS Type 1c 1) physiology 2) how to determine
1) Quantitative decrease in VWF with preserved ratios between VWF antigen, activity, and factor III
*increased clearance (think of letter c) of Von willebrand factor antigen
2) Response to DDAVP - rapid increase and then rapid decrease/clearance
VWS type 3 labs
- Factor VIII very low
- VWF antigen very low to nonexistent
- ristocetin very low
- RIPA very low
VWS type 2A - 1) Factor VIII 2) VWF antigen 3) RIPA 4) multimere assay
- Factor VIII low
- VWF antigen low
- ristocetin very low
- RIPA very low
- large and intermediate sized multimeres are absent
VWS type 2B labs 1) Factor VIII 2) VWF antigen 3) ristocetin 4) RIPA 5) multimeres
- gain of function, tight bond between platelets and VWF
- Factor VIII low
- VWF antigen low
- ristocetin very low
***RIPA high (heightened sensitivity to ristocetin) leading to thrombocytopenia
*large multimeres absent
Drug contraindicated in type 2B
DDAVP (will exacerbate thrombocytopenia)
VWS type 2N physiology
Low affinity for factor VIII
VWS type 2N labs 1) Factor VIII 2) VWF antigen 3) ristocetin 4) RIPA
- Factor VIII very low (NO 8, lack of binding to Factor VIII so there’s no Factor VIII in circulation)
- VWF antigen normal
- ristocetin normal
- RIPA normal (measures platelet aggregation with VWF, not Factor VIII)
**looks like hemophilia A due to low factor VIII, which is common board question, but will be a female (VWS is not x linked)
-
VWS type 2M - 1) FVIII 2) RIPA 3) multimeres
- FVIII normal or decreasd
- RIPA decreased
- *normal multimeres
DDAVP SE’s
- hypotension
- flushing
- hyponatremia and seizures
*tachyphylaxis
causes of acquired VWS
- lymphoproliferative
- plasma cell disorders
- autoimmune
*hypothyroidism - medications
- aortic stenosis
- LVADs
- ECMO
*wilm’s tumor
Unique aspect of VWS secondary to MGUS
Typically responds to IVIG
acquired VWS subtype from hypothyroidism
Type 1
acquired VWS subtype from valvular disorders
Type 2
acquired VWS subtype from MPN
type 2 VWD
VWS type 1 pathophys
Partial quantitative deficiency of VWF
Type 2 VWS pathophys
- decreased VWF-dependent platelet adhesion without selective deficiency of multimeres
Functional assay now recommended by ASH over ristocetin cofactor assay
VWF:GPIbM or VWF:GP1bR
Confirmed diagnosis on basis of VWF antigen
<30% = VWF antigen (even in absence of bleeding)
OR
<50% + bleeding
Management of menstrual bleeding in Type 1 patient
Type 1 - hormonal therapy (OCP or levonorgestrel IUD) OR TXA starting on first day of menses and continuing for 3-5 days with each cycle
Goal VWF activity for neuraxial anesthesia in VWD
VWF activity level of ≥0.50 IU/dL is considered adequate for neuraxial anesthesia
IF below, give VWF concentrate (Goal is 0.50-1.50 IU/mL
Management of postpartum bleeding in VWD
TXA
Next step after diagnosing VWD Type 2
Send multimere analysis
IF normal, then 2M
IF abnormal it’s 2A or B and you need genetic testing
Ratio of VWF activity: VWF:Ag confirming type 2 VWD
<0.7
Next step in Type 2 VWS after determining multimeres are abnormal
Genetic testing to differentiate Type 2 A vs. B
Why is DDAVP contraindicated for Type 2B?
Can worsen thrombocytopenia
Management of chronic frequent bleeding in VWS patients
weekly prophylaxis with VWF concentrate
Perioperative FVIII + VWF goal for VWD for major surgeries
Target both Factor VIII and VWF activity levels of >0.50 IU/mL for at least 3 days following major surgery (ASH guidelines)
*
Characteristic of all Type 2
VWF activity is decreased out of proportion to VWF antigen
Higher VWF propeptide to antigen level suggests
- Type 1c (protein is being made but being cleared)
