12345

11604 Indiana Avenue 12345

12345
P A M L Spokane, WA 99206
TE S T 12345
12345
12345
509.926.24 0 0
12345
PAT H O L O G Y A S S O C I AT E S
M E D I C A L LA B O R AT O R I E S 80 0.541.7891
Fax 509.92 4.0 0 02 U P DATE 12345

von Willebrand Clarified

William A. Dittman, Jr., M.D., Director of Hematology

VON W ILLEBRAND DISEASE ( vWd) is the most common he-
reditary bleeding disorder with a prevalence estimated to be
between 3 per 100,000 and 1 per 100. Patients with vWd have
either a quantitative or qualitative disorder of von Willebrand
factor (vWF) . These defects result in abnormalities in the
established normal functions of vWF: supporting adhesion of
normal platelets to damaged blood vessels and allowing nor-
mal secretion and stability of coagulation Factor VIII . Clini-
cally, patients with vWd have mucocutaneous bleeding. They
present with eccymoses, epistaxis, menorrhagia, or bleeding
following trauma or at the time of surgery. Severe vWd pa-
tients may present with hemarthroses as is seen in patients
with hemophilia. The patient’s and family histories are the
best indicators of a significant bleeding disorder, although the
expression and penetrance of vWd may vary widely within a
single family.
vWd is a heterogeneous disease both in presentation and
pathology. Laboratory test results may vary significantly for
the same patient tested at different times; therefore, it is fre-
quently necessary to perform repeat testing as well as family
studies to correctly diagnose vWd. Screening tests that may
be abnormal in vWd include prolongation of the bleeding time
(especially in severe or qualitative disorder) and the activated
partial thromboplastin time (aPTT), which reflect decreased
Factor VIII coagulant activity. In mild vWd both these tests
may be normal. Specific testing for vWd includes: Factor VIII
Coagulant Activity, which reflects the levels of circulating
vWF and its ability to support Factor VIII ; vWF Antigen,
which is the level of vWF as determined by immunologic
assay; and vWF Activity, or Ristocetin CoFactor Activity,
which is a measure of the ability of vWF to bind to and
aggregate platelets.
Additional testing can include the evaluation of von Wille-
brand factor multimers, which may be altered in some quali-
tative vWd disorders, and Ristocetin-induced platelet aggre-
gation (distinct from the Ristocetin CoFactor activity), which
can be abnormal in vWd Type 2B.
The most recent classification for vWd divides it into quan-
titative (Types 1 and 3), and qualitative (Type 2) variants. Type
1 is a partial quantitative defect in vWF and is usually inher-
ited as an autosomal dominant defect. Patients will have a
concordant decrease in vWF antigen and vWF Ristocetin
CoFactor activity. Bleeding time and aPTT are variable and
may be normal. Patients with Type 3 will have an absence of
any vWF and will have a severe bleeding disorder, usually
with a prolonged bleeding time and aPTT. The Type 2 vWd
reflects qualitative defects in the vWF protein. Generally there
will be lower levels of vWF activity (Ristocetin CoF) than
vWF antigen. Type 2A is associated with a decrease in high
molecular weight vWF multimers. Type 2B is associated with
a vWF with an abnormally increased affinity for platelets
and can be recognized by an abnormal platelet aggregation
induced by low concentrations of Ristocetin. This test is dis-
tinct from the vWF Activity (Ristocetin CoF) assay. Recog-
nition of Type 2B vWd is important, as these patients may
develop severe thrombocytopenia if treated with DDAVP
(desnospressin). Type 2M vWd has disconcordant antigen and
activity, is not associated with loss of high molecular weight
multimers, and has no increased affinity for platelets. Type
2N vWd is associated with a decreased affinity of vWF for
coagulation Factor V III .

Laboratory Features of von Willebrand’s Disease

Type (old Low Dose
terminology in von Willebrand vFW Activity Factor 8 Ristocetin induced
parentheses) factor antigen (Ristocetin CoF) Coagulation Activity Bleeding Time Platelet Count Multimers Platelet Aggregation

3 (III) <5 <1 ↓↓ ↑↑ Ν none N

1 (I) ↓ ↓ ↓/Ν ↑/Ν N N N
2M (I var) ↓ D ↓↓ ↓/Ν ↑/Ν N N N
2A (IIa, IIc,d,e) ↓ D ↓↓ ↓/Ν ↑ N Abn N
2B (IIb) ↓/Ν ↓/Ν ↓/Ν ↑ ↓/Ν Abn aggregation
2N (FVIII bind) ↓/Ν ↓/Ν D ↓↓ N N N N

N Normal, Abn Abnormal, ↑ Elevated, ↑↑ Markedly Elevated, ↓ Reduced, ↓↓ Markedly Reduced, D Discrepancy in the reduction of activity as compared to vWF antigen

FEBRUARY 1996
Old Terminology New Terminology Description Workpar
Factor 8 Factor 8 Coagulant Activity Amount of Factor 8 activity detected in a FAC8 or FAC8AS
clot-based assay.
Factor 8 Antigen von Willebrand Factor Antigen Amount of von Willebrand factor antigen FAC8AG
detected by immunologic assay.

von Willebrands vWF Activity (Ristocetin CoF) Procoagulant activity of von Willebrand VON
factor as determined by its ability to
aggregate platelets in the presence of
ristocetin.

Terminology for von Willebrand disease testing will be

updated February 26, 1996, to be more descriptive and con-
sistent with the recommendations of the International Soci-
ety on Thrombosis and Haemostasis. The table above lists old
terminology, corresponding new terminology, descriptions,
and workpars for affected procedures.