Von Willebrand Syndrome Flashcards
Treatment options for perioperative VWS management
1) Desmopressin (DDAVP)
2) cryoprecipitates
3) factor concentrates that contain vWF
How desmopressin treats VWS
leads to transient release of endogenous VWF + factor VIII from storage sites in endothelial cells
lysteda generic name
tranexamic acid
Approach to giving desmopressin prior to surgery
Base on VWF level + minor or major procedure
most common subtype + inheritance + pathophys
Type 1 (autosomal dominant) – partial deficiency
Most important SE’s of desmopressin administration
1) Tachyphylaxis (so can only give 1-2 doses)
2) hyponatremia
General preop approach for vWF patients
1) Determine subtype
2) Base treatment on whether minor or major procedure:
- desmopressin for minor procedures and mild deficiency (just causes transient elevation)
- vWF concentrate for major procedures or more severe deficiency
How is desmopressin administered?
1) pre challenge
2) weight-based: 0.3 micrograms/kg administered over 20-30 minutes
- can be given intranasally too
Clinical conditions associated with acquired vWF
1) MPNs
2) plasma cell dyscrasias
3) Cancer: wilms, lung, gastric
4) autoimmune
5) hypothyroidism, DM
6) Drugs: cipro, valproate
7) Heydes syndrome
Management options for acquired vWS
Treat bleeding:
- desmopressin
- factor concentrates
Immunosuppressive:
- high dose IVIG
- plasmapheresis
- steroids
- immunosuppressives
Type 1 VWS physiology
quantitative reduction in von Willebrand factor (VWF) protein (both concentration and activity are decreased)
Type 2 VWS pathophys (in general)
dysfunctional VWF (qualitative defect
Type 3 VWS pathophys
absent or severely reduced VWF
Why you never give DDAVP in type 2B
- This is a “gain of function” defect. The ability of the qualitatively defective VWF to bind to glycoprotein Ib (GPIb) receptor on the platelet membrane is abnormally enhanced, leading to its spontaneous binding to platelets and subsequent rapid clearance of the bound platelets and of the large VWF multimers. This DDAVP can stimulate platelet aggregation and cause thrombocytopenia.
Physiology of acquired VWS
1) autoantibody to vWF OR
2) destruction of VWF in conditions of high sheer stress (prosthetic heart valves, AS)
Caveat about VWS diagnosis
Levels of VWF fluctuate in response to estrogens, stress, exercise, inflammation, and bleeding; repeated assays may be required to make the diagnosis
Most common type of VWD
Type 1
VWD type 1 presentation in terms of disease severity
- milder bleeding symptoms, but occasionally more severe symptoms can occur
VWD type 2 presentation in terms of disease severity
- mild to moderate symptoms
Type 2A pathophys
- ability of vW factors to coalesce and form large VWF multimers is impaired so you only see small multimer units in the circulation
Type 2B pathophys
- gain of function defect
- ability of VWF to bind to glycoprotein Ib receptor on the platelet membrane is abnormally enhanced, leading to spontaneous binding to platelets and rapid clearance of large multimers
Testing for VWS
1) Plasma VWF antigen
2) Plasma VWF activity (typically done with ristocetiin cofactor)
3) Plasma factor VIII activity
Type 2B and ristocetin cofactor assay
hyperresponsiveness to a low ristocetin concentration (excessive binding)
Function of ristocetin cofactor
stimulates platelet binding and aggregation
Subtype in which you never give DDAVP
type IIB
Blood group associated with lower vWF levels
0 (25-30% lower)
why do you never give desmopressin with VWF type IIB?
- exacerbates thrombocytopenia (ini type IIB, Von Willebrand protein binds avidly to the receptor on the platelet surface so DDAVP leads to excess platelet aggregation and worsening of thrombocytopenia)
Which subtype is Heyde’s syndrome? Causes?
- Type IIA VWS
- Aortic stenosis + intestinal angiodysplasia
what are the functions of Von Willebrand factor?
1) Mediates platelet adhesion to the sites of vascular damage
2) Enables platelet-to-platelet interactions
3) Also a carrier of factor VIII in plasma and protects it from proteolytic degradation (prolonging half life and localizing it to the site of vascular injury)
Pathophys of Heyde’s syndrome
- VWF multimeres are degraded by shear stress across diseased aortic valve, loss of large multimeres leads to AVMs in the intestine
Lower end of reference range for VWF:ag level
50
what is stimate? available here?
- nasal desmopressin
- no, drug no longer available anywhere
VWS workup
1) VWF antigen
2) Ristocetin Cofactor activity
3) PTT
4) Factor VIII
Lab workup in Type 1
(Both down)
- VWF antigen down (20-50% of normal)
- RiCoF down
Lab workup in Type 3
- VWF antigen is 0
Lab workup in Type 2
-
Type 2A is
- Heydes, no HMWM
Most common subtype
Type 1 (40-80% of all cases)
Type (2N) Normandy pathophys + lab results
Deficiency of the binding of VWF to coagulation factor VIII. The VWF antigen test is normal, indicating normal quantity of VWF. The ristocetin cofactor assay is normal. Assay for coagulation factor VIII will show marked quantitative decrease, equivalent to levels seen in hemophilia A. This has led to some VWD type 2N patients being misdiagnosed as having hemophilia A.
Examples of VWF concentrates
Humate P
