Case: VWD Type 2?

Case: VWD Type 2?
May 29, 2017 2:56am

From Dr. Jasmina in India: Hello George. I need some thoughts on a case with bleeding. An 8 month old female child was referred for workup for a bleeding disorder. The mother noticed ecchymotic patches over the arms, legs and back over the previous two weeks and a single episode of epistaxis. The platelet count was 565 X 10E9/L. An elder male sib is fine and the parents are asymptomatic.

The PT is 12 s ( n=13–16 s), aPTT is 26 s (n= 26–32 s), Fib is 2.67 (n=2–4).The urea clot solubility test was normal, blood group was B pos.
The VWF antigen assay on 2 occasions a month apart was 184.3 & 133% (n=66–176%, using the kit cuttoffs, since pediatric norms are not available for our population). Done by LIA on the ACL TOP  500 using the Hemosil VWF antigen kit.
The VWF :RCo assay on 2 occasions a month apart gave results of 47.8 & 44.2%. (n=61–240%, using the kit cuttoffs, since pediatric norms are not available for our population). Done by LIA on the ACL TOP 500 using the Hemosil RiCoF kit. Factor VIII level is 131.6% (n=60–160%). Collagen binding, multimer and mutation analysis are not available, and the parents are to still be screened.

1) Is it all right to label this child as VWD Type 2, since neither VWF antigen nor RiCof is <30?
2) When the VWF antigen is not less than 30, but  the VWF :RCo is less than the reference range, is it even possible to just say that this child is bleeding with low VWF ? I find it hard  to reconcile the normal antigen levels, since I understand that low VWF should go as a differential for type 1 VWD.
3) Could acquired VWD be a possibility? Do these kind of cases need to be retested after a couple of years to exclude an acquired VWD ?
4)  What kind of reference ranges are labs using for the diagnosis of VWD in children, especially if the test are not done on a Stago machine?


Hello, Dr. Jasmina, and thank you for your question and your interesting case. Given the child's symptoms; slightly elevated or high normal VWF :Ag levels and consistently low VWF :RCo levels, It seems appropriate to reach a presumptive diagnosis of VWD type 2. Acquired VWD is relatively rare and usually secondary to various conditions, however given the nature of VWD , it is appropriate to retest the patient at regular intervals. While you may not have access to confirmatory multimeric analysis, IL offers an immunoassay measuring VWF activity that is separate from the VWF :RCo that may help you confirm the child's condition. Finally, you can find reference to Dr. Maureen Andrews' 1990 pediatric reference ranges on the University of Alabama at Birmingham special coag lab web sith at www.uabcoag.net. In the case of an 8-month-old child, the range is similar to the adult range.

4 Comments

From Dr. Jasmina in India: Hello George. I need some thoughts on a case with bleeding. An 8 month old female child was referred for workup for a bleeding disorder. The mother noticed ecchymotic patches over the arms, legs and back over the previous two weeks and a single episode of epistaxis. The platelet count was 565 X 10E9/L. An elder male sib is fine and the parents are asymptomatic.

The PT is 12 s ( n=13–16 s), aPTT is 26 s (n= 26–32 s), Fib is 2.67 (n=2–4).The urea clot solubility test was normal, blood group was B pos.
The VWF antigen assay on 2 occasions a month apart was 184.3 & 133% (n=66–176%, using the kit cuttoffs, since pediatric norms are not available for our population). Done by LIA on the ACL TOP  500 using the Hemosil VWF antigen kit.
The VWF :RCo assay on 2 occasions a month apart gave results of 47.8 & 44.2%. (n=61–240%, using the kit cuttoffs, since pediatric norms are not available for our population). Done by LIA on the ACL TOP 500 using the Hemosil RiCoF kit. Factor VIII level is 131.6% (n=60–160%). Collagen binding, multimer and mutation analysis are not available, and the parents are to still be screened.

1) Is it all right to label this child as VWD Type 2, since neither VWF antigen nor RiCof is <30?
2) When the VWF antigen is not less than 30, but  the VWF :RCo is less than the reference range, is it even possible to just say that this child is bleeding with low VWF ? I find it hard  to reconcile the normal antigen levels, since I understand that low VWF should go as a differential for type 1 VWD.
3) Could acquired VWD be a possibility? Do these kind of cases need to be retested after a couple of years to exclude an acquired VWD ?
4)  What kind of reference ranges are labs using for the diagnosis of VWD in children, especially if the test are not done on a Stago machine?


Hello, Dr. Jasmina, and thank you for your question and your interesting case. Given the child's symptoms; slightly elevated or high normal VWF :Ag levels and consistently low VWF :RCo levels, It seems appropriate to reach a presumptive diagnosis of VWD type 2. Acquired VWD is relatively rare and usually secondary to various conditions, however given the nature of VWD , it is appropriate to retest the patient at regular intervals. While you may not have access to confirmatory multimeric analysis, IL offers an immunoassay measuring VWF activity that is separate from the VWF :RCo that may help you confirm the child's condition. Finally, you can find reference to Dr. Maureen Andrews' 1990 pediatric reference ranges on the University of Alabama at Birmingham special coag lab web sith at www.uabcoag.net. In the case of an 8-month-old child, the range is similar to the adult range.

By Dr. Vadim Kostousov
May 31, 2017 12:13pm
Hello, Dr. Jasmina,

This child has secondary thrombocytosis (primary thrombocytosis is extremely rare in children) probably due to iron deficiency anemia (if hemoglobin is below 10.5–10.7 g/dL) or non-anemic iron deficiency. Reactive thrombocytosis is also accompanied by acquired VWD, however it is usually mild (VWF:RCo > 30%).

"Patients with reactive thrombocytosis exhibit a similar reduction in large VWF multimers in plasma, but their clinical course is usually not complicated by bleeding, probably as a consequence of increased circulating VWF levels due to the behavior of VWF as a reactive protein, which compensates for the relatively decreased levels of large VWF multimers in plasma." Budde U, van Genderen PJ. Acquired von Willebrand disease in patients with high platelet counts. Semin Thromb Hemost. 1997;23:425–31.

Bleeding might be due to acquired platelet aggregation defects that sometimes associated with ID(A) and reversed after treatment:

"Subtle bleeding manifestations can occur in patients with IDA with delay in platelet aggregation and prolongation in PFA-100 closure times which can be reversed by iron therapy." Mokhtar GM, et. al. Alterations of platelet functions in children and adolescents with iron-deficiency anemia and response to therapy. Platelets. 2015;26:448–52
By Dr Jasmina Ahluwalia
Jun 1, 2017 9:07am
Thanks George and Dr Vadim. Dr Vadim's point is certainly interesting. I would have gone with the stream of thought that a platelet disorder would cause bleeding and thus iron deficiency if supplementation is not done/inadequate. Iron deficiency is very common in our part of the world and would be worth exploring in this case .Would LTA help in such a patient?
By Dr. Vadim Kostousov
Jun 1, 2017 12:11pm
Dear Dr. Jasmina,

There is no specific LTA pattern associated with IDA platelet dysfunction, and PLT aggregation changes might be subtle. I think that treatment of IDA should be applied first and CBC/PLT count and bleeding symptoms should be rechecked once IDA is completely cured. If bleeding persist after the PLT count became normal, repeated VWF panel and LTA testing might be appropriate for this child.
By Dr Paul Riley
Jun 8, 2017 10:02pm
Could it be a FXIII deficiency? I know it's very rare but it sounds like the symptoms could be consistent.

Leave A Comment

You must be logged in to Comment - Sign In