von Willebrand Profile
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Detection of deficiency or abnormality of von Willebrand factor and related deficiency of factor VIII coagulant activity
Subtyping von Willebrand disease as Type 1 (most common), Type 2 variants (less common), or Type 3 (rare)
Profile Information A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.
|Test ID||Reporting Name||Available Separately||Always Performed|
|F8A||Coag Factor VIII Activity Assay, P||Yes||Yes|
|VWAG||von Willebrand Factor Ag, P||Yes||Yes|
|VWFX||von Willebrand Factor Activity, P||Yes||Yes|
Reflex Tests Lists test(s) that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial test(s)
|Test ID||Reporting Name||Available Separately||Always Performed|
|F8IS||Coag Factor VIII Assay Inhib Scrn,P||No||No|
|RIST||Ristocetin Cofactor, P||No||No|
|VWFM||von Willebrand Factor Multimer, P||Yes, (order #8844)||No|
|CCC2||Special Coagulation Interpretation||No||No|
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Initial testing includes: coag factor VIII activity assay, von Willebrand factor (VWF) antigen, and VWF activity.
If the factor VIII, VWF antigen, and VWF activity are normal, and VWF activity:VWF antigen ratio is > or =0.8, a computer-generated interpretive comment indicating no evidence of von Willebrand’s disease will be provided.
If VWF activity assay is <55%, VWF ristocetin cofactor activity assay will be performed. If VWF antigen is <55%, the VWF activity is <55%, or the VWF activity:VWF antigen ratio is <0.8, VWF multimer analysis will be performed.
If any test results are abnormal, all results will be reviewed by a coagulation consultant and a Special Coagulation Consultant Interpretation will be provided.
See von Willebrand Disease Profile in Special Instructions.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
F8A, F8IS, IBETH: Activated Partial Thromboplastin Time-Based Clotting Assay
VWAG: Automated Latex Immunoassay (LIA)
VWFX: Latex Particle Enhanced Immunoassay
RIST: Ristocetin Induced Aggregation of Washed Normal Platelets
VWFM: Agarose Gel Electrophoresis/Infrared Dye-Labeled Antibody Detection
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
von Willebrand Prof
von Willebrand Profile
von Willebrand Profile
Specimen Type Describes the specimen type needed for testing
Plasma Na Cit
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
See Coagulation Studies in Special Instructions.
Specimen Type: Platelet-poor plasma
Collection Container/Tube: Light-blue top (citrate)
Submission Container/Tube: Plastic vials
Specimen Volume: 3 mL in 3 plastic vials each containing 1 mL
1. Specimen must be drawn prior to factor replacement therapy.
2. Spin down, remove plasma, and spin plasma again.
3. Freeze specimens immediately at < or =-40 degrees C, if possible.
4. Send specimens in the same shipping container.
1. Double-centrifuged specimen is critical for accurate results as platelet contamination may cause spurious results.
2. If priority specimen, mark request form, give reason, and request a call-back.
3. Each coagulation assay requested should have its own vial.
4. If multiple coagulation profiles are ordered, each profile must be on a separate order.
Forms: Coagulation Patient Information Sheet (Supply T675) in Special Instructions
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
2 mL in 2 plastic vials each containing 1 mL
Mild OK; Gross reject
Mild OK; Gross reject
Mild OK: Gross reject
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Plasma Na Cit||Frozen||14 days|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
von Willebrand factor (VWF) is synthesized by the endothelial cell and megakaryocyte and is present in these cells, as well as in platelets, subendothelial tissue, and plasma.
VWF serves as an adhesive protein important in adhering platelets to subendothelial tissue at the site of vascular injury and for adhering platelets to each other (aggregation). Platelet adhesion and aggregation are essential to form a mechanical hemostatic "plug" and as the focus for interaction of clotting factors and phospholipid required for the formation of the fibrin platelet clot. VWF also stabilizes plasma factor VIII by binding it and protecting it from proteolysis and serves as a carrier protein for that clotting factor.
VWF circulates in the blood in 2 distinct compartments. Plasma VWF mainly reflects VWF synthesis and release from vascular endothelial cells. Platelet VWF (about 10% of the blood VWF) reflects VWF synthesis by bone marrow megakaryocytes with storage primarily in the alpha granules of circulating platelets.
Plasma VWF circulates normally in multimeric forms with molecular weights ranging from 500,000 to as much as 20,000,000. The high- molecular-weight (HMW) forms of VWF are the most effective components for interaction with platelets. This primary activity of plasma VWF is measured in the laboratory with the VWF activity assay, whereas VWF antigen testing measures the amount of VWF protein, and factor VIII coagulant activity indirectly reflects VWF interaction with factor VIII. VWF multimer analysis visualizes the distribution of VWF multimers and is useful as a reflexive test for subtyping von Willebrand disease (VWD).
Levels of factor VIII, VWF antigen, and VWF activity may vary greatly within each individual over time and also with blood type (normal type "O" individuals may have VWF lower than normals of other blood groups). VWF levels (and factor VIII) can be elevated in liver disease, pregnancy, estrogen therapy, inflammation, and after exercise (acute-phase reactant). VWF levels in hemophilia are normal.
VWF antigen measurement assesses the mass of plasma VWF protein but does not reflect VWF functions or platelet VWF. The function of VWF (mediating platelet-platelet or platelet-vessel interaction) is most commonly assessed by measurement of plasma VWF activity.
VWD is the most common inherited bleeding disorder, affecting up to 1% of the population. It can also occur as an acquired bleeding disorder. Bleeding symptoms in all types of VWD are primarily mucosal, including epistaxis, menorrhagia, gastrointestinal bleeding, and ease of bruising, but surgical or posttraumatic bleeding can also occur.
Subtypes of inherited VWD are:
Type 1 VWD:
VWF plasma levels (antigen and activity) typically are both concordantly reduced in Type 1 VWD. Because of this reduction, the level of coagulation factor VIII is often secondarily reduced also. Type 1 VWD is the most common VWD variation, representing 70% to 80% of clinical VWD. It is typically inherited in autosomal dominance fashion, although recessively inherited VWD also occurs (eg, Type 3 VWD). Clinical severity ranges from mild or minimal to a moderately severe bleeding diathesis and tends to correlate most closely with VWF activity. Severe Type 1 disease is also called Type 3 VWD, but the distinction between the 2 may sometimes be difficult.
Type 2 VWD:
Type 2 VWD variants represent 20% to 30% of clinical VWD, typically autosomal dominant in inheritance. There are 4 subtypes of Type 2 VWD: 2A, 2B, 2M, and 2N. Abnormal plasma HMW VWF function and multimeric structure with decreased or absent HMW multimers are characteristic of Types 2A and 2B, but are normal in Type 2M or 2N.
VWF activity is decreased in Types 2A, 2B, and 2M and typically is discordantly lower than VWF antigen. Type 2N (Normandy) has substantially decreased factor VIII coagulant activity (typically 5%-30% of mean normal), with normal VWF antigen and activity and normal VWF multimers with clinical manifestation as autosomally inherited mild hemophilia (in contrast to classical X chromosome-linked hemophilia A).
Type 2A is the most common of the 4. Type 2B manifests thrombocytopenia, either persistent or transient, and is distinguished from Type 2A by abnormally heightened aggregation response of patient platelets and plasma to low dose ristocetin stimulation. Type 2M typically demonstrates hypofunctional VWF with decreased VWF activity discordantly lower than VWF antigen not due to loss of HMW multimers. One variant of Type 2M, Vicenza variant VWD, has ultralarge VWF multimers in plasma.
Type 3 VWD:
VWF is absent or markedly decreased in Type 3 VWD (VWF antigen and activity either undetectably low or below 5% to 10% of mean normal, with secondary decrease of factor VIII coagulant activity (5%-30%). VWF multimers may be undetectable or, if present, have a normal distribution. Platelet VWF may also be absent.
VWD can also occur on an acquired basis by a variety of mechanisms not well understood. Disorders associated with acquired VWD include certain myeloproliferative or lymphoproliferative disorders, plasma cell dyscrasias including monoclonal gammopathy of undetermined significance, autoimmune disorders (eg, rheumatoid arthritis, systemic lupus erythematosus), and a variety of other diseases. In some cases, no associated disorder is detected. Laboratory testing currently cannot distinguish between congenital and acquired VWD; clinical correlation is required.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
FACTOR VIII ACTIVITY
von WILLEBRAND FACTOR ACTIVITY
von WILLEBRAND FACTOR ANTIGEN
An interpretive report will be provided when testing is complete.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Testing should be performed prior to and in the absence of recent transfusion or von Willebrand factor (VWF) replacement therapy, (eg Humate P or DDAVP [desmopressin]). If the patient has received any such therapy, this information should be provided. von Willebrand disease (VWD) patients receiving Humate P therapy may have a VWF activity level 10% to 20% lower than the VWF ristocetin cofactor activity level. Low normal levels of VWF antigen or activity do not exclude possible diagnosis of VWD (repeat testing may be indicated). Use of estrogens may result in a mild increase in VWF levels, thus masking a diagnosis of mild VWD.
Borderline low or slightly decreased levels of VWF antigen or activity may be observed in clinically normal individuals of blood group "O."
This test is not useful for differentiating Type 2A versus 2B VWD or platelet-type VWD (pseudo-VWD). This differentiation requires ristocetin-induced platelet aggregation testing which must be performed using freshly obtained patient platelets and plasma.
Clinical correlation is required for differentiating acquired from congenital (hereditary) forms of VWD. Repeat testing may be helpful for confirming or evaluating low or borderline low levels of VWF (antigen and/or activity), especially when there is strong suspicion of VWD.
The milder forms of the disease, especially Type 1 VWD, can be difficult to diagnose or exclude, reflecting the variability of baseline VWF levels. In addition to demonstration of persistently decreased levels of VWF, clinical correlation is required for diagnosis of all VWD subtypes, especially mild Type 1 VWD.
Patient should not be receiving anticoagulant treatment (eg, heparin, Coumadin). If so, please note.
This test is not useful for detection of hemophilia carriers.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Federici AB, Mannucci PM: Advances in the genetics and treatment of von Willebrand disease. Curr Opin Pediatr 2002 Feb;14(1):23-33
2. Budde U, Schneppenheim R: von Willebrand factor and von Willebrand disease. Rev Clin Exp Hematol 2001 Dec;5(4):335-368
3. Kumar S, Pruthi RK, Nichols WL: Acquired von Willebrand disease. Mayo Clin Proc 2002 Feb;77(2):181-187
Method Description Describes how the test is performed and provides a method-specific reference
See Individual Unit Codes
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday; Varies
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
See individual unit codes
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test has been cleared or approved by the U.S. Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
85240-Coagulation factor VIII assay
85246-von Willebrand factor antigen
85397-von Willebrand factor activity
85245-von Willebrand factor ristocetin cofactor activity (if appropriate)
85247-von Willebrand factor multimer (if appropriate)
85335-Bethesda titer (if appropriate)
85335-Coagulation factor VIII inhibitor screen (if appropriate)
85390-26-Special coagulation interpretation (if appropriate)
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|F8A||Coag Factor VIII Activity Assay, P||3209-4|
|VWAG||von Willebrand Factor Ag, P||27816-8|
|VWFX||von Willebrand Factor Activity, P||68324-3|