Von Willebrand Syndrome Flashcards Preview

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Flashcards in Von Willebrand Syndrome Deck (40)
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1
Q

Treatment options for perioperative VWS management

A

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

2
Q

How desmopressin treats VWS

A

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

3
Q

lysteda generic name

A

tranexamic acid

4
Q

Approach to giving desmopressin prior to surgery

A

Base on VWF level + minor or major procedure

5
Q

most common subtype + inheritance + pathophys

A

Type 1 (autosomal dominant) – partial deficiency

6
Q

Most important SE’s of desmopressin administration

A

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

7
Q

General preop approach for vWF patients

A

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

8
Q

How is desmopressin administered?

A

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

9
Q

causes of acquired vWF

A

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

10
Q

Management options for acquired vWS

A

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

11
Q

Type 1 VWS physiology

A

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

12
Q

Type 2 VWS pathophys (in general)

A

dysfunctional VWF (qualitative defect

13
Q

Type 3 VWS pathophys

A

absent or severely reduced VWF

14
Q

Why you never give DDAVP in type 2B

A
  • 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.
15
Q

Physiology of acquired VWS

A

1) autoantibody to vWF OR

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

16
Q

Caveat about VWS diagnosis

A

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

17
Q

Most common type of VWD

A

Type 1

18
Q

VWD type 1 presentation in terms of disease severity

A
  • milder bleeding symptoms, but occasionally more severe symptoms can occur
19
Q

VWD type 2 presentation in terms of disease severity

A
  • mild to moderate symptoms
20
Q

Type 2A pathophys

A
  • ability of vW factors to coalesce and form large VWF multimers is impaired so you only see small multimer units in the circulation
21
Q

Type 2B pathophys

A
  • 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
22
Q

Testing for VWS

A

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

23
Q

Type 2B and ristocetin cofactor assay

A

hyperresponsiveness to a low ristocetin concentration (excessive binding)

24
Q

Function of ristocetin cofactor

A

stimulates platelet binding and aggregation

25
Q

Subtype in which you never give DDAVP

A

type IIB

26
Q

Blood group associated with lower vWF levels

A

0 (25-30% lower)

27
Q

why do you never give desmopressin with VWF type IIB?

A
  • 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)
28
Q

Which subtype is Heyde’s syndrome? Causes?

A
  • Type IIA VWS

- Aortic stenosis + intestinal angiodysplasia

29
Q

what are the functions of Von Willebrand factor?

A

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)

30
Q

Pathophys of Heyde’s syndrome

A
  • VWF multimeres are degraded by shear stress across diseased aortic valve, loss of large multimeres leads to AVMs in the intestine
31
Q

Lower end of reference range for VWF:ag level

A

50

32
Q

what is stimate? available here?

A
  • nasal desmopressin

- no, drug no longer available anywhere

33
Q

VWS workup

A

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

34
Q

Lab workup in Type 1

A

(Both down)

  • VWF antigen down (20-50% of normal)
  • RiCoF down
35
Q

Lab workup in Type 3

A
  • VWF antigen is 0
36
Q

Lab workup in Type 2

A

-

37
Q

Type 2A is

A
  • Heydes, no HMWM
38
Q

Most common subtype

A

Type 1 (40-80% of all cases)

39
Q

Type (2N) Normandy pathophys + lab results

A

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.

40
Q

Examples of VWF concentrates

A

Humate P

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