Von Willebrand Syndrome

Question 1

Treatment options for perioperative VWS management

Answer 1

1) Desmopressin (DDAVP)
2) cryoprecipitates
3) factor concentrates that contain vWF

Question 2

How desmopressin treats VWS

Answer 2

leads to transient release of endogenous VWF + factor VIII from storage sites in endothelial cells

Question 3

lysteda generic name

Answer 3

tranexamic acid

Question 4

Approach to giving desmopressin prior to surgery

Answer 4

Base on VWF level + minor or major procedure

Question 5

most common subtype + inheritance + pathophys

Answer 5

Type 1 (autosomal dominant) – partial deficiency

Question 6

Most important SE’s of desmopressin administration

Answer 6

1) Tachyphylaxis (so can only give 1-2 doses)
2) hyponatremia

Question 7

General preop approach for vWF patients

Answer 7

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

Question 8

How is desmopressin administered?

Answer 8

1) pre challenge
2) weight-based: 0.3 micrograms/kg administered over 20-30 minutes
- can be given intranasally too

Question 9

Clinical conditions associated with acquired vWF

Answer 9

1) MPNs
2) plasma cell dyscrasias
3) Cancer: wilms, lung, gastric
4) autoimmune
5) hypothyroidism, DM
6) Drugs: cipro, valproate
7) Heydes syndrome

Question 10

Management options for acquired vWS

Answer 10

Treat bleeding:
- desmopressin
- factor concentrates
Immunosuppressive:
- high dose IVIG
- plasmapheresis
- steroids
- immunosuppressives

Question 11

Type 1 VWS physiology

Answer 11

quantitative reduction in von Willebrand factor (VWF) protein (both concentration and activity are decreased)

Question 12

Type 2 VWS pathophys (in general)

Answer 12

dysfunctional VWF (qualitative defect

Question 13

Type 3 VWS pathophys

Answer 13

absent or severely reduced VWF

Question 14

Why you never give DDAVP in type 2B

Answer 14

• 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.

Question 15

Physiology of acquired VWS

Answer 15

1) autoantibody to vWF OR

2) destruction of VWF in conditions of high sheer stress (prosthetic heart valves, AS)

Question 16

Caveat about VWS diagnosis

Answer 16

Levels of VWF fluctuate in response to estrogens, stress, exercise, inflammation, and bleeding; repeated assays may be required to make the diagnosis

Question 17

Most common type of VWD

Answer 17

Type 1

Question 18

VWD type 1 presentation in terms of disease severity

Answer 18

• milder bleeding symptoms, but occasionally more severe symptoms can occur

Question 19

VWD type 2 presentation in terms of disease severity

Answer 19

• mild to moderate symptoms

Question 20

Type 2A pathophys

Answer 20

• ability of vW factors to coalesce and form large VWF multimers is impaired so you only see small multimer units in the circulation

Question 21

Type 2B pathophys

Answer 21

• 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

Question 22

Testing for VWS

Answer 22

1) Plasma VWF antigen
2) Plasma VWF activity (typically done with ristocetiin cofactor)
3) Plasma factor VIII activity

Question 23

Type 2B and ristocetin cofactor assay

Answer 23

hyperresponsiveness to a low ristocetin concentration (excessive binding)

Question 24

Function of ristocetin cofactor

Answer 24

stimulates platelet binding and aggregation

Question 25

Subtype in which you never give DDAVP

Answer 25

type IIB

Question 26

Blood group associated with lower vWF levels

Answer 26

0 (25-30% lower)

Question 27

why do you never give desmopressin with VWF type IIB?

Answer 27

• 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)

Question 28

Which subtype is Heyde’s syndrome? Causes?

Answer 28

• Type IIA VWS

- Aortic stenosis + intestinal angiodysplasia

Question 29

what are the functions of Von Willebrand factor?

Answer 29

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)

Question 30

Pathophys of Heyde’s syndrome

Answer 30

• VWF multimeres are degraded by shear stress across diseased aortic valve, loss of large multimeres leads to AVMs in the intestine

Question 31

Lower end of reference range for VWF:ag level

Answer 31

50

Question 32

what is stimate? available here?

Answer 32

• nasal desmopressin

- no, drug no longer available anywhere

Question 33

VWS workup

Answer 33

1) VWF antigen
2) Ristocetin Cofactor activity
3) PTT
4) Factor VIII

Question 34

Lab workup in Type 1

Answer 34

(Both down)

• VWF antigen down (20-50% of normal)
• RiCoF down

Question 35

Lab workup in Type 3

Answer 35

• VWF antigen is 0

Question 36

Lab workup in Type 2

Answer 36

-

Question 37

Type 2A is

Answer 37

• Heydes, no HMWM

Question 38

Most common subtype

Answer 38

Type 1 (40-80% of all cases)

Question 39

Type (2N) Normandy pathophys + lab results

Answer 39

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.

Question 40

Examples of VWF concentrates

Answer 40

Humate P