Von Willebrand disease laboratory findings: Difference between revisions
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{{Von Willebrand disease}} | {{Von Willebrand disease}} | ||
{{CMG}} | {{CMG}} {{shyam}} {{AE}} {{PTD}} {{N.F}} | ||
==Overview== | ==Overview== | ||
The diagnosis of [[von Willebrand 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. Initial 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. Persons with a bleeding tendency who have vWF levels between 30 and 50 IU per deciliter are classified as having “low vWF” or “possible type 1 disease” but are not classified as having definitive vWD. 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 disease is diagnosed. 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== | ==Laboratory Findings== | ||
The diagnosis of [[von Willebrand 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:<ref name="pmid25858564">{{cite journal |vauthors=Bodó I, Eikenboom J, Montgomery R, Patzke J, Schneppenheim R, Di Paola J |title=Platelet-dependent von Willebrand factor activity. Nomenclature and methodology: communication from the SSC of the ISTH |journal=J. Thromb. Haemost. |volume=13 |issue=7 |pages=1345–50 |year=2015 |pmid=25858564 |doi=10.1111/jth.12964 |url=}}</ref><ref name="pmid21148813">{{cite journal |vauthors=Flood VH, Gill JC, Morateck PA, Christopherson PA, Friedman KD, Haberichter SL, Hoffmann RG, Montgomery RR |title=Gain-of-function GPIb ELISA assay for VWF activity in the Zimmerman Program for the Molecular and Clinical Biology of VWD |journal=Blood |volume=117 |issue=6 |pages=e67–74 |year=2011 |pmid=21148813 |pmc=3056647 |doi=10.1182/blood-2010-08-299016 |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><ref>{{Cite journal | |||
| author = [[F. Stufano]], [[A. S. Lawrie]], [[S. La Marca]], [[C. Berbenni]], [[L. Baronciani]] & [[F. Peyvandi]] | |||
| title = A two-centre comparative evaluation of new automated assays for von Willebrand factor ristocetin cofactor activity and antigen | |||
| journal = [[Haemophilia : the official journal of the World Federation of Hemophilia]] | |||
| volume = 20 | |||
| issue = 1 | |||
| pages = 147–153 | |||
| year = 2014 | |||
| month = January | |||
| doi = 10.1111/hae.12264 | |||
| pmid = 24028703 | |||
}}</ref> | |||
===Screening tests=== | |||
Screening testing include the following 3 tests: | |||
* [[vWF]] antigen (vWF:Ag) level | |||
** Normal values are between 50 and 200 IU/dL | |||
** Levels below 50 are considered to be low | |||
* [[Factor VIII]] activity (FVIII:C) | |||
** Type 1&2 has somewhat lower levels of [[Factor VIII|FVIII]] | |||
** Type 3 has markedly reduced levels of [[Factor VIII|FVIII]] | |||
* vWF–ristocetin cofactor activity [VWF:RCo] as a measure of platelet-binding activity of vWF | |||
** The normal range of VWF:RCo is 50 to 200 IU/dL | |||
{| class="wikitable" | |||
!Type | |||
!vWF antigen level | |||
|- | |||
|low vWD or possible Type 1 | |||
|30-50 IU<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> | |||
|- | |||
|1 | |||
|<30 IU | |||
|- | |||
|2 | |||
|Ratio of von Willebrand factor–ristocetin cofactor activity to von [[Willebrand factor]] antigen ≤0.6 | |||
|- | |||
|3 | |||
|< 5 IU<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 | |||
<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 the results of the screening tests are normal, the tests should be repeated, if values are at the low end of the normal range or if VWD is strongly suspected.<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 the screening tests reveal definitive abnormalities, a diagnosis of [[VWD]] can be made. | |||
* | *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]]. | ||
==='''Confirmatory tests'''=== | |||
These tests are required to determine the phenotypic characteristics that define types 2A, 2B, and 2M: | |||
* VWF [[Multimeric protein|multimer]] distribution using [[gel electrophoresis]] | |||
* [[Ristocetin]]-induced platelet aggregation (RIPA) | |||
*A [[Platelet aggregation|platelet aggregation assay]] will show an abnormal response to [[ristocetin]] with normal responses to the other agonists used. | |||
*Type 2B can be distinguished by enhanced ristocetin-induced platelet aggregation in the presence of low-dose ristocetin. | |||
*Type 2N can only be diagnosed by performing a "[[factor VIII]] binding" assay. | |||
==='''Other tests'''=== | |||
Other tests performed in any patient with bleeding problems are: | Other tests performed in any patient with bleeding problems are: | ||
*[[complete blood count]] | *[[complete blood count]] shows normal platelets except in | ||
*[[APTT]] (activated partial thromboplastin time) | *[[APTT]] (activated partial thromboplastin time) may be normal or prolonged | ||
*[[prothrombin time]] | *[[prothrombin time]] is normal | ||
*[[thrombin]] time | *[[thrombin]] time | ||
*[[fibrinogen]] level. | *[[fibrinogen]] level. | ||
Latest revision as of 23:27, 20 December 2018
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2] Associate Editor(s)-in-Chief: Prince Tano Djan, BSc, MBChB [3] Nazia Fuad M.D.
Overview
The diagnosis of von Willebrand 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. Initial 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. Persons with a bleeding tendency who have vWF levels between 30 and 50 IU per deciliter are classified as having “low vWF” or “possible type 1 disease” but are not classified as having definitive vWD. 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 disease is diagnosed. 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 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][4]
Screening tests
Screening testing include the following 3 tests:
- vWF antigen (vWF:Ag) level
- Normal values are between 50 and 200 IU/dL
- Levels below 50 are considered to be low
- Factor VIII activity (FVIII:C)
- vWF–ristocetin cofactor activity [VWF:RCo] as a measure of platelet-binding activity of vWF
- The normal range of VWF:RCo is 50 to 200 IU/dL
| 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 the screening tests are normal, the tests should be repeated, if values are at the low end of the normal range or if VWD is strongly suspected.[3]
- If the screening tests reveal definitive abnormalities, a diagnosis of VWD can be made.
- 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.
Confirmatory tests
These tests are required to determine the phenotypic characteristics that define types 2A, 2B, and 2M:
- VWF multimer distribution using gel electrophoresis
- Ristocetin-induced platelet aggregation (RIPA)
- A platelet aggregation assay will show an abnormal response to ristocetin with normal responses to the other agonists used.
- Type 2B can be distinguished by enhanced ristocetin-induced platelet aggregation in the presence of low-dose ristocetin.
- Type 2N can only be diagnosed by performing a "factor VIII binding" assay.
Other tests
Other tests performed in any patient with bleeding problems are:
- complete blood count shows normal platelets except in
- APTT (activated partial thromboplastin time) may be normal or prolonged
- prothrombin time is normal
- 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
- ↑ 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.
- ↑ 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 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) - ↑ 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.