VON WILLEBRANDíS DISEASE

 

Epidemiology:the most common inherited disorder of hemostasis, affecting approx 1 in 1,000.Presents as bleeding during trauma or surgery, spontaneous mucosal bleeding (epistaxis, GIB, ecchymoses, menorrhagia, hemarthroses)

 

von Willebrandís Factor:a heterogeneous multimeric plasma glycoprotein with 2 major funtions-

1.†† plasma carrier for FVIII (stabilizes)

2.†† facilitates platelet adhesion under high stress (crosslinks to epithelium)

 

Classification:

1.†† Type 1: partial quantitative defect of vWF- 80% of cases, mild symptoms (bleeding after surgery or trauma)

2.†† Type 2: qualitative defect (near nml levels of dysfunctional protein)

A-††††††††††† deficiency of medium and high MW multimers, leads to impaired platelet aggregation

B-††††††††††† deficiency of high MW multimers 2ndary to inappropriate binding to platelets

M-††††††††††† decreased plt function but high MW present

N-††††††††††† defective binding to FVIII

1.†† Type 3: total absence of vWF- severe disease, similar to FVIII def.

2.†† Pseudo-von Willebrandís disease: platelet GpIb receptor defect.Detect by reciprocal mixing studies of nml/pt plasma/plt.

 

Laboratory tests:

1.†† Bleeding time: incision on volar aspect of forearm w/ 40mmHg cuff around arm

2.†† vWF:Ag: ELISA

3.†† Multimer analysis: electrophoresis

4.†† Ristocetin-induced platelet aggregation (RIPA): dif concentration of Risto added to plama/platelets

5.†† Ristocetin cofactor activity: dilutions of plasma added to platelets and Risto

 

 

Laboratory findings:

Type

FVIII

vWF:Ag

vWFD:Rcof

RIPA

Multimeric pattern

1

d

d

d

d/n

all sizes

2A

d

d

dd

d

no l/m

2B

d/n

n/d

dd

u

no l

2M

d/n

d

dd

d/n

all sizes

2N

dd

n/d

n/d

n/d

all sizes

3

dd

none

none

dd

none

 

Treatment:

1.††††† Desmopressin: stimulates release of vWF from endothelium.Peak effect 30-60min, lasts 6hrs.

2.†† Amicar: inhibits fibrinolysis.

Type

Primary rx

Secondary rx

1

Desmopressin

Factor conc/Cryo

2A,M

Desmopressin

Factor conc/Cryo

2B

Factor conc/Cryo

?? Desmopressin

2N

Factor conc

Desompressin

3

Factor conc/Cryo

Plt/Desmopressin

Acquired

Desmopressin

Plt/Factor conc

 

Acquired VWD

1.†† Antibody inhibitors: s/p mult transfusions, autoimmune, lymphoproliferative d/o

2.†† Adsorption of vWF: lymphoma, Waldenstromís Wilmís.

 

Ewenstein. Annu Rev Med. 1997 48:525-42