Type 2B von Willebrand Disease: Early Manifestation as Neonatal Thrombocytopenia

David Kranzhöfer; Anna Pavlova; Hendryk Schneider; Peter Franck; Hannah Glonnegger; Martin Büchsel; Ayami Yoshimi-Nöllke; Johannes Oldenburg; Barbara Zieger

doi:10.1055/a-1665-6185

Hämostaseologie, Inhaltsverzeichnis

Hamostaseologie 2021; 41(06): 469-474
DOI: 10.1055/a-1665-6185

Case Report

Type 2B von Willebrand Disease: Early Manifestation as Neonatal Thrombocytopenia

David Kranzhöfer

¹Department for General Pediatrics, Adolescent Medicine and Neonatology, University Medical Center Freiburg, Freiburg, Germany

,

Anna Pavlova

²Institute of Experimental Haematology and Transfusion Medicine (IHT), University Hospital Bonn, Bonn, Germany

,

Hendryk Schneider

¹Department for General Pediatrics, Adolescent Medicine and Neonatology, University Medical Center Freiburg, Freiburg, Germany

,

Peter Franck

¹Department for General Pediatrics, Adolescent Medicine and Neonatology, University Medical Center Freiburg, Freiburg, Germany

,

Hannah Glonnegger

³Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, University of Freiburg, Freiburg, Germany

,

Martin Büchsel

⁴Clinical Chemistry, University Medical Center Freiburg, Freiburg, Germany

,

Ayami Yoshimi-Nöllke

³Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, University of Freiburg, Freiburg, Germany

,

Johannes Oldenburg

²Institute of Experimental Haematology and Transfusion Medicine (IHT), University Hospital Bonn, Bonn, Germany

,

Barbara Zieger

³Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, University of Freiburg, Freiburg, Germany

› Institutsangaben

Abstract

Here, we report about a preterm female newborn with a prolonged course of severe thrombocytopenia and hematomas. The family history was positive for von Willebrand disease type 2B (VWD 2B). Diagnosis of VWD 2B was identified analyzing von Willebrand factor (VWF) parameters (VWF:antigen, VWF:activity, VWF multimer analyses) and performing light transmission aggregometry (with half concentration of ristocetin). In addition, the diagnosis was confirmed by molecular genetic analysis: identification of a disease-causing missense mutation (Val1316Met) in the VWF gene associated with a severe course of VWD 2B, which had been previously reported. Treatment with a VWF-containing plasma concentrate was initiated. Because the combination of prematurity and very low platelet count is often associated with intracranial bleeding, at the beginning platelet concentrates were transfused. Fortunately, the patient did not develop serious bleeding episodes. Interestingly, the patient had a mutation in the VWF gene, which had been described to be associated with aggravation of thrombocytopenia especially in stressful situations. Therefore, we replaced venous blood withdrawals by capillary blood samplings when possible and, consequently, we observed an increase of the platelet count after this change in management. At the age of 2 months, the patient was discharged after stabilization of the platelet count without any bleeding signs and without a need of long-term medication.

Keywords

von Willebrand disease - thrombocytopenia - neonate

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Referenzen

References
1 Leebeek FWG, Eikenboom JCJ. Von Willebrand's disease. N Engl J Med 2016; 375 (21) 2067-2080
2 Mikhail S, Aldin ES, Streiff M, Zeidan A. An update on type 2B von Willebrand disease. Expert Rev Hematol 2014; 7 (02) 217-231
3 Goodeve A. Diagnosing von Willebrand disease: genetic analysis. Hematology (Am Soc Hematol Educ Program) 2016; 2016 (01) 678-682
4 Connell NT, Flood VH, Brignardello-Petersen R. et al. ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease. Blood Adv 2021; 5 (01) 301-325
5 James PD, Connell NT, Ameer B. et al. ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease. Blood Adv 2021; 5 (01) 280-300
6 de Jong A, Eikenboom J. Von Willebrand disease mutation spectrum and associated mutation mechanisms. Thromb Res 2017; 159: 65-75
7 Federici AB, Mannucci PM, Castaman G. et al. Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: a cohort study of 67 patients. Blood 2009; 113 (03) 526-534
8 Mathew P, Greist A, Maahs JA, Lichtenberg EC, Shapiro AD. Type 2B vWD: the varied clinical manifestations in two kindreds. Haemophilia 2003; 9 (01) 137-144
9 Proud L, Ritchey AK. Management of type 2b von Willebrand disease in the neonatal period. Pediatr Blood Cancer 2017; 64 (01) 103-105
10 Burlingame J, McGaraghan A, Kilpatrick S, Hambleton J, Main E, Laros RK. Maternal and fetal outcomes in pregnancies affected by von Willebrand disease type 2. Am J Obstet Gynecol 2001; 184 (02) 229-230
11 McLaughlin D, Kerr R. Management of type 2B von Willebrand disease during pregnancy. Acta Haematol 2017; 137 (02) 89-92
12 Fan J, Ling J, Zhou H, He J, Hu S. Case report: an infant with severe thrombocytopenia diagnosed with type 2B von Willebrand disease due to a de novo p.Val1316Met mutation. Turk J Haematol 2020; 37 (04) 296-298
13 Kalbhenn J, Schlagenhauf A, Rosenfelder S, Schmutz A, Zieger B. Acquired von Willebrand syndrome and impaired platelet function during venovenous extracorporeal membrane oxygenation: rapid onset and fast recovery. J Heart Lung Transplant 2018; 37 (08) 985-991
14 Heilmann C, Geisen U, Beyersdorf F. et al. Acquired von Willebrand syndrome in patients with extracorporeal life support (ECLS). Intensive Care Med 2012; 38 (01) 62-68
15 Cremer M, Sallmon H, Kling PJ, Bührer C, Dame C. Thrombocytopenia and platelet transfusion in the neonate. Semin Fetal Neonatal Med 2016; 21 (01) 10-18
16 Casari C, Berrou E, Lebret M. et al. von Willebrand factor mutation promotes thrombocytopathy by inhibiting integrin αIIbβ3. J Clin Invest 2013; 123 (12) 5071-5081
17 Casari C, Paul DS, Susen S. et al. Protein kinase C signaling dysfunction in von Willebrand disease (p.V1316M) type 2B platelets. Blood Adv 2018; 2 (12) 1417-1428
18 Kruse-Jarres R, Johnsen JM. How I treat type 2B von Willebrand disease. Blood 2018; 131 (12) 1292-1300