Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. This content does not have an English version. This content does not have an Arabic version. Diagnosis Mild forms of von Willebrand disease can be difficult to diagnose because bleeding is common, and, for most people, doesn't indicate a disease.
Request an Appointment at Mayo Clinic. Share on: Facebook Twitter. Show references Von Willebrand disease. Centers for Disease Control and Prevention. Accessed Aug. Von Willebrand disease. Mayo Clinic; Rick ME. Clinical presentation and diagnosis of von Willebrand disease. National Organization for Rare Disorders.
Von Willebrand disease: Treatment of minor bleeding and routine care. This test also measures the time it takes for blood to clot. If the level of any one of these factors is too low, it will take longer than normal for the blood to clot. The results of this test will be normal among most people with VWD. This test is ordered either along with other blood clotting tests or when a patient has an abnormal PT external icon or APTT test external icon result, or both.
The results of this test will be normal among people with VWD. Fibrinogen is another name for clotting factor I 1. Specific tests are required to diagnose which bleeding disorder is there. Often these tests need to be repeated several times before an accurate diagnosis can be made. Skip directly to site content Skip directly to page options Skip directly to A-Z link. Section Navigation. Facebook Twitter LinkedIn Syndicate. Ongoing efforts by investigators are attempting to address this issue.
It is important to mention that multimer analysis is dependent on several preanalytical variables and therefore proper collection and processing methods should be followed. It is important to mention that these tests can be used to determine response to therapeutic interventions such as desmopressin. Once the diagnosis of VWD is made, clinicians have a battery of tests available, mostly in specialized reference laboratories, which will provide additional information for the diagnosis of different subtypes of VWD.
These tests may confirm a rare subtype that will determine therapeutic alternatives. Several assays have been developed to measure plasma VWF binding to collagen and because they are sensitive to the presence of high-molecular-weight multimers, these assays have been proposed as replacements of the VWF:RCo. Most collagen-binding assays use collagens type 1 and 3, but recently the use of collagen type 6 has allowed for the identification of potential VWF-binding defects not identified by other types of collagen.
Because the propeptide of VWF is synthesized and released on a basis with the VWF monomer, quantification of this protein is useful in characterizing clinical situations in which VWF shows accelerated clearance because pathological clearance mechanisms only affect VWF:Ag and not VWFpp.
Genetic testing for VWD is not indicated except for specific cases in which the results of the test would make a difference in the patient's therapeutic management or counseling. There are several complicating factors that make genetic testing difficult for VWD.
VWF is a very large gene that spans kb and contains 52 exons. The presence of a highly homologous partial pseudogene in chromosome 22 makes the sequencing and its interpretation particularly difficult.
Recently, the presence of common variants that affect the VWF:RCo assay have been described, however, they do not appear to increase the risk of bleeding. For example, it might be important to identify large deletions in patients with VWD type 3 that would place them at higher risk of developing neutralizing antibodies and anaphylactic reactions upon treatment or to provide genetic counseling for patients.
Also, genetic testing may also be justified in cases in which the molecular diagnosis will help to guide treatment, such as type 2N and 2B VWD. In these particular cases, mutations are usually clustered in specific areas of VWF , making sequencing and interpretation of the data less cumbersome.
Additionally, several mechanisms have been shown to cause low VWF levels mostly related to decreased cellular secretion of VWF, including mutations that affect gene expression, 43 protein trafficking, 44 or mild increases in VWF clearance. Once the diagnosis of VWD type 1 is made based on clinical history and laboratory testing, no further specialized testing is usually required.
Making a diagnosis of VWD type 1C has significant therapeutic implications because these patients may not be good candidates for desmopressin, due to the decreased half-life of their native VWF. Perhaps no group engenders more controversy in the diagnosis of VWD than the patients who have VWF levels in the 40 to 50 IU range and present with mild mucocutaneous bleeding. It is becoming increasingly evident that borderline normal plasma VWF levels represent 1 among several risk factors for bleeding and cannot be assigned as the only cause for mucocutaneous bleeding in these patients.
Regardless of the label giving to the clinical condition, patients who demonstrate significant bleeding associated with low VWF levels are often treated as VWD type 1 patients as they still may benefit from therapy such as desmopressin to raise the level of plasma VWF. Mechanisms for VWD type 2. VWD type 2A is the most common form of type 2 disease, and is characterized by preferential loss of intermediate- and high-molecular-weight VWF multimers, usually through abnormal synthesis or packaging of VWF prior to endothelial cell release 45 or to increased susceptibility to ADAMTS13 after exocytosis.
The increased binding of VWF especially the high-molecular-weight multimers to platelets under physiologic shear form aggregates that are rapidly cleared from the circulation, resulting in a decreased total amount of VWF, loss of high-molecular-weight multimers, and often thrombocytopenia. It is important to mention that thrombocytopenia is not always present in VWD type 2B.
In patients diagnosed with VWD type 2B that do not respond well to VWF concentrate infusion, it is critical to differentiate VWD type 2B from platelet-type pseudo-VWD because they are clinically indistinguishable, but the therapeutic approach is different. In this case, the distribution of multimers is normal, but they are intrinsically dysfunctional because they cannot bind platelets properly. Type 2N should be suspected in individuals diagnosed with mild hemophilia who belong to families that have affected males and females or who do not respond adequately to FVIII infusions.
A simple algorithm that can be used as a guide to the diagnosis of the several subtypes of VWD is presented in Figure 3. Diagnostic algorithm.
Algorithm of the diagnostic approach to mucocutaneous bleeding with a high clinical suspicion for VWD. Specific groupings are based on the underlying pathophysiology of different VWD types.
RIPA, ristocetin induced platelet aggregation. Although widely used and important in the diagnosis of VWD, the currently available clinical evaluations and laboratory tests are not infallible; often indeterminate or unreliable results can lead to confusion in the diagnosis of VWD.
It is still recommended that all laboratories establish their own normal ranges and follow strict quality control procedures.
Another critical issue is that although VWF:Ag levels generally have low coefficients of variation, they can vary widely in the same individual due to several environmental factors including stress, exercise, and inflammatory states. Therefore, if VWD is highly suspected, laboratory tests may be repeated at a different time to either refute or confirm the diagnosis.
In addition, many preinstrumental variables can play a role in the determination of VWF. Improperly isolated plasma can be contaminated by platelets, leading to protease-induced alterations and causing increased VWF levels but paradoxically decreased activity. Additionally, the refrigeration of whole blood prior to plasma separation may alter VWF multimeric structure. It is becoming more evident that the discrepancies in test values among clinical laboratories as well as the use of more specialized tests can have a significant impact on the diagnosis of VWD.
Large population-based studies have demonstrated that a significant number of patients who had been initially diagnosed with VWD type 1 had multimer distributions compatible with VWD type 2 upon further investigation with high-resolution gels. Perhaps the 2 most significant limitations of current testing for VWD are 1 the inability to simulate the function of VWF under conditions of physiologic flow and 2 the limitations to adequately correlate current clinically available and research-based testing with clinical bleeding.
Presently, all of the standard and more advanced laboratory tests are performed under static conditions.
However, novel examination of the ability of VWF to bind platelets and collagen under flow conditions may reveal abnormal phenotypes in function that are not able to be assessed with current tests. Novel flow-based research assays have been recently developed. These assays may be able to identify not only those individuals at high risk for bleeding, but also, hopefully, safely predict those individuals for whom the risk of clinical bleeding is low. Sign In or Create an Account. Sign In.
Skip Nav Destination Content Menu. Close Introduction. Screening evaluation for VWD. Laboratory testing for VWD. Specialized laboratory testing. Genetic testing.
Quantitative defects of VWF. Article Navigation. Inherited Bleeding Disorders March 26, Christopher Ng , Christopher Ng. This Site. Google Scholar.
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