Use of a thrombopoietin receptor agonist in von Willebrand disease type 2B (p.V1316M) with severe thrombocytopenia and intracranial hemorrhage

Platelets ◽  
2016 ◽  
Vol 28 (5) ◽  
pp. 518-520 ◽  
Author(s):  
O. Espitia ◽  
C. Ternisien ◽  
C. Agard ◽  
P. Boisseau ◽  
C. V. Denis ◽  
...  
Keyword(s):  
Intracranial Hemorrhage ◽  
Receptor Agonist ◽  
Disease Type ◽  
Von Willebrand Disease ◽  
Severe Thrombocytopenia ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist ◽  
Von Willebrand

Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 5832-5837 ◽  
Author(s):  
Alessandro Pecci ◽  
Paolo Gresele ◽  
Catherine Klersy ◽  
Anna Savoia ◽  
Patrizia Noris ◽  
...  
Keyword(s):  
Platelet Count ◽  
Receptor Agonist ◽  
Severe Thrombocytopenia ◽  
Bleeding Tendency ◽  
Platelet Counts ◽  
Related Disease ◽  
Increase Platelet Count ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist ◽  
Inherited Thrombocytopenia

Abstract Platelet transfusion is currently the primary medical treatment for reducing thrombocytopenia in patients with inherited thrombocytopenias. To evaluate whether stimulating megakaryopoiesis could increase platelet count in these conditions, we treated patients with a severe thrombocytopenia induced by MYH9 mutations (MYH9-related disease) with a nonpeptide thrombopoietin receptor agonist, eltrombopag. Twelve adult patients with MYH9-RD and platelet counts of less than 50 × 109/L received 50 mg of eltrombopag orally per day for 3 weeks. Patients who achieved a platelet count higher than 150 × 109/L stopped therapy, those with 100 to 150 platelets × 109/L continued treatment at the same eltrombopag dose for 3 additional weeks, while those with less than 100 platelets × 109/L increased the eltrombopag dose to 75 mg for 3 weeks. Major responses (platelet count of at least 100 × 109/L or 3 times the baseline value) were obtained in 8 patients, minor responses (platelet counts at least twice the baseline value) in 3. One patient did not respond. Bleeding tendency disappeared in 8 of 10 patients with bleeding symptoms at baseline. Mild adverse events were reported in 2 patients. The availability of thrombopoietin mimetics opened new prospects in the treatment of inherited thrombocytopenias. This study is registered at www.clinicaltrials.gov as NCT01133860 (European Union Drug Regulating Authorities Clinical Trials number 2008-001903-42).

Response to DDAVP in children with von Willebrand disease type 2

2009 ◽  
Vol 29 (02) ◽  
pp. 143-148 ◽  
Author(s):  
U. Budde ◽  
K. Beutel ◽  
W.-A. Hassenpflug ◽  
H. Hauch ◽  
T. Obser ◽  
...  
Keyword(s):  
Disease Type ◽  
Von Willebrand Disease ◽  
Molecular Defect ◽  
Variable Response ◽  
Functional Parameters ◽  
Functional Defect ◽  
Biologic Response ◽  
High Level ◽  
Von Willebrand

SummaryWe have prospectively evaluated the biologic response to desmopressin (DDAVP) in 28 children with type 2 von Willebrand disease (VWD) in correlation with the phenotype and the molecular defect of VWF. The diagnosis of VWD type 2 was mainly based on VWF functional parameters and/or an aberrant VWF multimer pattern. Seventeen different mutations were identified (6 of them novel). No response with respect to the functional parameters VWF:RCo and/or VWF:CB was seen in patients with severe abnormality of the VWF multimer pattern. One patient with VWD type 2A phenotype IIC Miami did not respond with respect to VWF:CB, but showed a good response of VWF:Ag and FVIII:C as expected. Interestingly he showed a persistently high level of VWF:Ag and FVIII:C up to 4 hours after DDAVP infusion. Patients with minor alterations of multimer structure and particular mutations responded well to DDAVP, whereas patients with normal multimer structure but a defect in platelet dependent functional parameters did not respond with VWF:RCo. Conclusion: Children with VWD type 2 show a variable response to desmopressin depending on the mutation that correlates with the functional defect and the presence or absence as well as the half-life of large VWF multimers. Our data emphasize the usefulness of DDAVP testing even in patients with VWD type 2, possibly with the exception of VWD type 2B.

Von Willebrand disease type 2N: an update

2021 ◽  
Author(s):  
Omid Seidizadeh ◽  
Flora Peyvandi ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Disease Type ◽  
Von Willebrand Disease ◽  
Von Willebrand

Recessive von Willebrand Disease Type 2 Normandy: Variable Expression of Mild Hemophilia and VWD Type 1

2009 ◽  
Vol 121 (2-3) ◽  
pp. 119-127 ◽  
Author(s):  
Jan Jacques Michiels ◽  
Alain Gadisseur ◽  
Inge Vangenegten ◽  
Wilfried Schroyens ◽  
Zwi Berneman
Keyword(s):  
Disease Type ◽  
Von Willebrand Disease ◽  
Variable Expression ◽  
Von Willebrand

Mutation-specific hemostatic variability in mice expressing common type 2B von Willebrand disease substitutions

Blood ◽  
2010 ◽  
Vol 115 (23) ◽  
pp. 4862-4869 ◽  
Author(s):  
Mia Golder ◽  
Cynthia M. Pruss ◽  
Carol Hegadorn ◽  
Jeffrey Mewburn ◽  
Kimberly Laverty ◽  
...  
Keyword(s):  
Ferric Chloride ◽  
Von Willebrand Disease ◽  
Expression Vectors ◽  
Severe Thrombocytopenia ◽  
Normal Platelet ◽  
Injury Model ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Type 2B von Willebrand disease (2B VWD) results from von Willebrand factor (VWF) A1 mutations that enhance VWF-GPIbα binding. These “gain of function” mutations lead to an increased affinity of the mutant VWF for platelets and the binding of mutant high-molecular-weight VWF multimers to platelets in vivo, resulting in an increase in clearance of both platelets and VWF. Three common 2B VWD mutations (R1306W, V1316M, and R1341Q) were independently introduced into the mouse Vwf cDNA sequence and the expression vectors delivered to 8- to 10-week-old C57Bl6 VWF−/− mice, using hydrodynamic injection. The resultant phenotype was examined, and a ferric chloride–induced injury model was used to examine the thrombogenic effect of the 2B VWD variants in mice. Reconstitution of only the plasma component of VWF resulted in the generation of the 2B VWD phenotype in mice. Variable thrombocytopenia was observed in mice expressing 2B VWF, mimicking the severity seen in 2B VWD patients: mice expressing the V1316M mutation showed the most severe thrombocytopenia. Ferric chloride–induced injury to cremaster arterioles showed a marked reduction in thrombus development and platelet adhesion in the presence of circulating 2B VWF. These defects were only partially rescued by normal platelet transfusions, thus emphasizing the key role of the abnormal plasma VWF environment in 2B VWD.

scholarly journals A common 253-kb deletion involving VWF and TMEM16B in German and Italian patients with severe von Willebrand disease type 3

2007 ◽  
Vol 5 (4) ◽  
pp. 722-728 ◽  
Author(s):  
R. SCHNEPPENHEIM ◽  
G. CASTAMAN ◽  
A. B. FEDERICI ◽  
W. KREUZ ◽  
R. MARSCHALEK ◽  
...  
Keyword(s):  
Disease Type ◽  
Von Willebrand Disease ◽  
Type 3 ◽  
Von Willebrand

Quality of Life Improvements Following Eltrombopag Treatment in Children with Chronic Immune Thrombocytopenia: Case Report

2021 ◽  
Vol 104 (4) ◽  
pp. 672-675
Keyword(s):  
Quality Of Life ◽  
Platelet Count ◽  
Receptor Agonist ◽  
Immune Thrombocytopenia ◽  
Case Series ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist ◽  
Low Platelet Count ◽  
Chronic Immune Thrombocytopenia

The present case series described six chronic immune thrombocytopenia patients (cITP), with a median age of 7.7 (7.0 to 13.0) years and low platelet count at 15,500 (7,000 to 20,000)/uL. They were suffering from bleeding symptoms and side effects of treatment. After enrollment, they were treated with thrombopoietin receptor agonist (eltrombopag). Five patients responded positively, showing a median platelet count of 115,000 (39,000 to 433,000)/uL. The median dose of eltrombopag used was 1.3 (0.8 to 2.2) mg/kg/day. The quality of life (QoL) improved for all patients, with their median overall score using a Pediatric QoL questionnaire showing 25.0% improvement. Median scores also showed improvements in each sphere of life functioning as physical (30.8%), emotional (26.4%), social (16.4%), and school (21.4%). The present report demonstrated that a select group of cITP patients, with low platelet count and bleeding symptoms, benefitted from treatment with eltrombopag, as shown by increased platelet counts and improved QoL. Keywords: Chronic ITP, Thrombopoietin receptor agonist, Children

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