Von Willebrand disease (VWD) is one of the most common genetic bleeding disorders and, yet, it tends to be underdiagnosed. By the end of this video from our Hematology and Coagulation Essentials course, you'll be able to understand and interpret the various tests available for the subtypes of VWD.
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Demystify hematology and coagulation with our fascinating Hematology and Coagulation Essentials course. Hematological and coagulation disorders can be difficult to diagnose. By the end of this course, you'll be able to confidently assess the most important diagnostic aspects of hematology and coagulation, and shine during your next night on call! Never again will you wonder what a prolonged PTT really means, how to differentiate between a factor deficiency and an inhibitor, or what test to order next.
[00:00:00] Here, we are going to discuss the various tests for von Willebrand disease. So, patients with von Willebrand disease may demonstrate thrombocytopenia in cases of type 2B or pseudo-von Willebrand disease. In both of these types, there is increased binding of von Willebrand factor with the platelets. This results in increase consumption of the platelets and resultant thrombocytopenia.
[00:00:30] Bleeding time, although not a test, ordered often will be prolonged. This is because in von Willebrand disease there is defective platelet adhesion. In von Willebrand disease, there is reduced levels of factor 8. This will result in prolonged PTT. Mixing study should show correction. There is a test called von Willebrand disease panel and this panel consists of three tests. The first is
[00:01:00] measuring factor 8 levels. The second is measuring von Willebrand factor antigen levels, and the third is measuring von Willebrand factor functional activity and this is also known as ristocetin cofactor activity. Type 1 von Willebrand disease is a mild abnormality. In this type, there is mild deficiency of all the three levels tested. In type 3, there is severe deficiency of all three factors.
[00:01:30] In type 2, results vary according to the subtype. In type 2N, factor 8 levels are low. This is because in type 2N, von Willebrand factor and factor 8 cannot bind properly. Factor 8 is, thus, destroyed. In type 2M, von Willebrand factor antigen levels will be normal, functional activity and factor 8 levels are low. This is because
[00:02:00] in type 2M the multimers are present but do not work properly. In type 2A and B, the results of von Willebrand disease panel varies. Now, I would like to discuss ristocetin-induced platelet aggregation. Ristocetin was originally an antibiotic, which is no longer used, however, it enhances the interaction of von Willebrand factor with GP 1B.
[00:02:30] Ristocetin induces von Willebrand factor and platelet GP 1B to interact and results in platelet clumping. This is normally seen in healthy people, with the high dose of ristocetin but not with the low dose of ristocetin. In von Willebrand disease, there is reduced aggregation of platelets with the high dose of ristocetin. The low dose is not affected. However, in the subtype type 2B, even with the low dose of
[00:03:00] ristocetin, platelet aggregation is observed. This is because in type 2B, the von Willebrand factor has increased affinity for platelet GP 1B and even a small dose of ristocetin is enough to cause aggregation. This is a graph of a patient with ristocetin-induced platelet aggregation and it shows that with ristocetin, the amount of platelet aggregation is negligible. However, platelet aggregation with ADP, collagen, and
[00:03:30] epinephrine are normal. This is the characteristic pattern of ristocetin-induced platelet aggregation for von Willebrand disease. Another test we can order is what's called multimer analysis. Multimer analysis is done by electrophoresis and all the von Willebrand factor multimers line up according to their size. This allows us to analyze if there is global deficiency of the multimers or deficiency of any particular subtype of multimers.
[00:04:00] Here, N stands for normal. If we compare type 1 von Willebrand disease to a normal person, we can see that there is mild deficiency of all the subtypes of multimers. In type 3, there is severe deficiency of all the subtypes of multimers. In type 2A, there is selective loss of the large and intermediate multimers. In type 2B,
[00:04:30] there is selective loss of the large multimers. Individuals with type 2M and type 2N would have a normal multimer analysis. Just wanted to remind you that in type 2M, the multimers are present but they do not function well. In type 2N, everything related to von Willebrand disease is fine, however, the von Willebrand factor and factor 8 cannot bind. How would we go about diagnosing type
[00:05:00] 2N? There is a factor 8 von Willebrand factor binding assay for this condition. In type 2N, the binding of von Willebrand factor and factor 8 is abnormal. This results in easy degradation of factor 8. Low levels of factor 8 in such patients make us think of hemophilia. The factor 8 von Willebrand factor binding assay is an ELISA-based test and is usually sent out to a reference laboratory.