Von Willebrand disease laboratory findings: Difference between revisions
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When von Willebrand factor antigen is undetectable (or the level is <5 IU per deciliter, according to the latest disease classification), type 3 von Willebrand’s disease is diagnosed<ref name="pmid16889557">{{cite journal |vauthors=Sadler JE, Budde U, Eikenboom JC, Favaloro EJ, Hill FG, Holmberg L, Ingerslev J, Lee CA, Lillicrap D, Mannucci PM, Mazurier C, Meyer D, Nichols WL, Nishino M, Peake IR, Rodeghiero F, Schneppenheim R, Ruggeri ZM, Srivastava A, Montgomery RR, Federici AB |title=Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor |journal=J. Thromb. Haemost. |volume=4 |issue=10 |pages=2103–14 |year=2006 |pmid=16889557 |doi=10.1111/j.1538-7836.2006.02146.x |url=}}</ref><ref name="pmid25673639">{{cite journal |vauthors=Sanders YV, Groeneveld D, Meijer K, Fijnvandraat K, Cnossen MH, van der Bom JG, Coppens M, de Meris J, Laros-van Gorkom BA, Mauser-Bunschoten EP, Leebeek FW, Eikenboom J |title=von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease |journal=Blood |volume=125 |issue=19 |pages=3006–13 |year=2015 |pmid=25673639 |doi=10.1182/blood-2014-09-603241 |url=}}</ref> | When von Willebrand factor antigen is undetectable (or the level is <5 IU per deciliter, according to the latest disease classification), type 3 von Willebrand’s disease is diagnosed<ref name="pmid16889557">{{cite journal |vauthors=Sadler JE, Budde U, Eikenboom JC, Favaloro EJ, Hill FG, Holmberg L, Ingerslev J, Lee CA, Lillicrap D, Mannucci PM, Mazurier C, Meyer D, Nichols WL, Nishino M, Peake IR, Rodeghiero F, Schneppenheim R, Ruggeri ZM, Srivastava A, Montgomery RR, Federici AB |title=Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor |journal=J. Thromb. Haemost. |volume=4 |issue=10 |pages=2103–14 |year=2006 |pmid=16889557 |doi=10.1111/j.1538-7836.2006.02146.x |url=}}</ref><ref name="pmid25673639">{{cite journal |vauthors=Sanders YV, Groeneveld D, Meijer K, Fijnvandraat K, Cnossen MH, van der Bom JG, Coppens M, de Meris J, Laros-van Gorkom BA, Mauser-Bunschoten EP, Leebeek FW, Eikenboom J |title=von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease |journal=Blood |volume=125 |issue=19 |pages=3006–13 |year=2015 |pmid=25673639 |doi=10.1182/blood-2014-09-603241 |url=}}</ref> | ||
If these first-level tests reveal definitive abnormalities, a diagnosis of [[VWD]] can be made; if the results are not conclusive, second-level tests are required. | If these first-level tests reveal definitive abnormalities, a diagnosis of [[VWD]] can be made; if the results are not conclusive, second-level tests are required. | ||
Second level testing involves repeating the initial tests and then measurement of VWF multimer distribution using gel electrophoresis and ristocetin-induced platelet aggregation (RIPA). | Second level testing involves repeating the initial tests and then measurement of VWF multimer distribution using gel electrophoresis and ristocetin-induced platelet aggregation (RIPA). | ||
Other tests performed in any patient with bleeding problems include: [[complete blood count]] (especially [[platelet]] counts), [[APTT]] (activated partial thromboplastin time), [[prothrombin time]], | |||
[[thrombin]] time, [[fibrinogen]] level, testing for [[factor IX]] if [[hemophilia B]] is suspected and other [[coagulation factor]] assays may be performed depending on the results of a coagulation screen. | |||
*Patients with Von Willebrand disease will typically display a normal prothrombin time and a variable prolongation of partial thromboplastin time. | |||
==Laboratory Findings== | ==Laboratory Findings== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Prince Tano Djan, BSc, MBChB [2]
Overview
The diagnosis of von Willebrand’s disease (VWD) begins with a relevant personal or family history of mucocutaneous bleeding. When VWD is suspected, several levels of testing are needed in order to make diagnosis[1][2][3][4]
Initail tests involve measurement of VWF antigen (VWF:Ag) level, Factor VIII activity (FVIII:C) and VWF–ristocetin cofactor activity [VWF:RCo].
When the results of all first-level tests are normal, VWD is ruled out; because of biologic variability, however, the tests should be repeated if values are at the low end of the normal range or if VWD is strongly suspected.[3]
Persons with a bleeding tendency who have VWF levels between 30 and 50 IU per deciliter (the lower limit of the normal range) are classified as having “low VWF” or “possible type 1 disease” but are not classified as having definitive VWD.[3]
When von Willebrand factor antigen is undetectable (or the level is <5 IU per deciliter, according to the latest disease classification), type 3 von Willebrand’s disease is diagnosed[5][3] If these first-level tests reveal definitive abnormalities, a diagnosis of VWD can be made; if the results are not conclusive, second-level tests are required. Second level testing involves repeating the initial tests and then measurement of VWF multimer distribution using gel electrophoresis and ristocetin-induced platelet aggregation (RIPA).
Other tests performed in any patient with bleeding problems include: complete blood count (especially platelet counts), APTT (activated partial thromboplastin time), prothrombin time, thrombin time, fibrinogen level, testing for factor IX if hemophilia B is suspected and other coagulation factor assays may be performed depending on the results of a coagulation screen.
- Patients with Von Willebrand disease will typically display a normal prothrombin time and a variable prolongation of partial thromboplastin time.
Laboratory Findings
The diagnosis of von Willebrand’s disease (VWD) begins with a relevant personal or family history of mucocutaneous bleeding. When VWD is suspected, several levels of testing are needed in order to make diagnosis as shown below:[1][2][3][6]
Initial tests:
- VWF antigen (VWF:Ag) level
- Factor VIII activity (FVIII:C).
- VWF–ristocetin cofactor activity [VWF:RCo] as a measure of platelet-binding activity of VWF
- The VWF:RCo assay may be replaced by newer assays that measure the binding of VWF to a recombinant wild-type GPIb fragment with the use of ristocetin or the spontaneous binding of VWF to a gain-of-function recombinant mutant GPIb fragment.
| Type | vWF antigen level |
|---|---|
| low vWD or possible Type 1 | 30-50 IU[3] |
| 1 | <30 IU |
| 2 | Ratio of von Willebrand factor–ristocetin cofactor activity to von Willebrand factor antigen ≤0.6 |
| 3 | < 5 IU[5][3] |
- When the results of all first-level tests are normal, VWD is ruled out; because of biologic variability, however, the tests should be repeated if values are at the low end of the normal range or if VWD is strongly suspected.[3]
- If these first-level tests reveal definitive abnormalities, a diagnosis of VWD can be made; if the results are not conclusive, second-level tests are required.
- A proportional decrease in von Willebrand factor antigen and von Willebrand factor–ristocetin cofactor activity fits the diagnosis of type 1 von Willebrand’s disease.
Second-level tests
Second level testing involves repeating the initial tests and then measurement of the following:
- VWF multimer distribution using gel electrophoresis
- Ristocetin-induced platelet aggregation (RIPA)
- The above second level tests are required to determine the phenotypic characteristics that define types 2A, 2B, and 2M
- A rare platelet defect due to a gain-of-function mutation in the GPIbα receptor, known as platelet-type VWD, has a phenotype similar to that of type 2B VWD; the two disorders can be distinguished with the use of genetic testing.
- A platelet aggregation assay will show an abnormal response to ristocetin with normal responses to the other agonists used. A platelet function assay (PFA) will give an abnormal collagen/adrenaline closure time and in most cases a normal collagen/ADP time. Type 2N can only be diagnosed by performing a "factor VIII binding" assay. Detection of vWD is complicated by vWF being an acute phase reactant with levels rising in infection, pregnancy and stress.
Other tests
Other tests performed in any patient with bleeding problems are:
- complete blood count (especially platelet counts),
- APTT (activated partial thromboplastin time),
- prothrombin time,
- thrombin time
- fibrinogen level.
- Testing for factor IX may also be performed if hemophilia B is suspected.
Other coagulation factor assays may be performed depending on the results of a coagulation screen.
- Patients with Von Willebrand disease will typically display a normal prothrombin time and a variable prolongation of partial thromboplastin time.
References
- ↑ 1.0 1.1 Bodó I, Eikenboom J, Montgomery R, Patzke J, Schneppenheim R, Di Paola J (2015). "Platelet-dependent von Willebrand factor activity. Nomenclature and methodology: communication from the SSC of the ISTH". J. Thromb. Haemost. 13 (7): 1345–50. doi:10.1111/jth.12964. PMID 25858564.
- ↑ 2.0 2.1 Flood VH, Gill JC, Morateck PA, Christopherson PA, Friedman KD, Haberichter SL, Hoffmann RG, Montgomery RR (2011). "Gain-of-function GPIb ELISA assay for VWF activity in the Zimmerman Program for the Molecular and Clinical Biology of VWD". Blood. 117 (6): e67–74. doi:10.1182/blood-2010-08-299016. PMC 3056647. PMID 21148813.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Sanders YV, Groeneveld D, Meijer K, Fijnvandraat K, Cnossen MH, van der Bom JG, Coppens M, de Meris J, Laros-van Gorkom BA, Mauser-Bunschoten EP, Leebeek FW, Eikenboom J (2015). "von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease". Blood. 125 (19): 3006–13. doi:10.1182/blood-2014-09-603241. PMID 25673639.
- ↑ F. Stufano, A. S. Lawrie, S. La Marca, C. Berbenni, L. Baronciani & F. Peyvandi (2014). "A two-centre comparative evaluation of new automated assays for von Willebrand factor ristocetin cofactor activity and antigen". Haemophilia : the official journal of the World Federation of Hemophilia. 20 (1): 147–153. doi:10.1111/hae.12264. PMID 24028703. Unknown parameter
|month=ignored (help) - ↑ 5.0 5.1 Sadler JE, Budde U, Eikenboom JC, Favaloro EJ, Hill FG, Holmberg L, Ingerslev J, Lee CA, Lillicrap D, Mannucci PM, Mazurier C, Meyer D, Nichols WL, Nishino M, Peake IR, Rodeghiero F, Schneppenheim R, Ruggeri ZM, Srivastava A, Montgomery RR, Federici AB (2006). "Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor". J. Thromb. Haemost. 4 (10): 2103–14. doi:10.1111/j.1538-7836.2006.02146.x. PMID 16889557.
- ↑ F. Stufano, A. S. Lawrie, S. La Marca, C. Berbenni, L. Baronciani & F. Peyvandi (2014). "A two-centre comparative evaluation of new automated assays for von Willebrand factor ristocetin cofactor activity and antigen". Haemophilia : the official journal of the World Federation of Hemophilia. 20 (1): 147–153. doi:10.1111/hae.12264. PMID 24028703. Unknown parameter
|month=ignored (help)