VON WILLEBRAND’S 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 Willebrand’s 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 Willebrand’s 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, Waldenstrom’s Wilm’s.

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