Type 2B von Willebrand Disease in Pregnancy: A Systematic Literature Review

2021 ◽  
Vol 47 (02) ◽  
pp. 201-216
Author(s):  
Mona M. Makhamreh ◽  
Melissa L. Russo ◽  
Taylor Karl ◽  
Natalie Delgado ◽  
Katherine Lackritz ◽  
...  
Keyword(s):  
Von Willebrand Disease ◽  
Cochrane Central Register ◽  
Severe Thrombocytopenia ◽  
Maternal Characteristics ◽  
Central Register ◽  
Concentrate Treatment ◽  
Red Blood Cell Transfusions ◽  
Factor Concentrate ◽  
Von Willebrand ◽  
In Pregnancy

AbstractOur objective was to review the maternal characteristics and obstetric complications in women with type 2B von Willebrand disease (VWD). A systematic literature search was conducted using PubMed, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. We included all publications that addressed type 2B VWD in pregnancy. Our primary and secondary outcomes were incidence of postpartum hemorrhage (PPH) and incidence of thrombocytopenia in pregnancy. Two reviewers independently identified eligible studies and abstracted data including maternal characteristics, hematologic characteristics, treatment, and delivery outcomes. Twenty studies met inclusion criteria. There were 27 women (32 pregnancies) with type 2B VWD. Primary PPH was reported in 9/20 women (45%) and secondary PPH was reported in 6/13 women (46%). Thrombocytopenia in pregnancy was present in 27/28 women (96%); 23/27 women (85%) had platelet count <100 × 109/L, mean 33.7 ± 22.7 × 109/L. Factor concentrate treatment was administered before delivery (n = 16) and postpartum (n = 18), some women received both. Seventeen deliveries required blood products postpartum with 13/17 (76%) platelet transfusions and 6/17 (35%) red blood cell transfusions. No maternal mortality was reported. Women with type 2B VWD have significant morbidity in pregnancy related to high incidence of severe thrombocytopenia and primary and secondary PPH.

Type 3 von Willebrand Disease in Pregnancy: A Systematic Literature Review

2019 ◽  
Author(s):  
Mona M. Makhamreh ◽  
Stephanie L. Kass ◽  
Melissa L. Russo ◽  
Homa Ahmadzia ◽  
Huda B. Al-Kouatly
Keyword(s):  
Pregnant Women ◽  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
Maternal Characteristics ◽  
Pregnancy And Delivery ◽  
Concentrate Treatment ◽  
Rare Phenotype ◽  
Type 3 ◽  
Von Willebrand ◽  
In Pregnancy

Abstract Objective von Willebrand disease (VWD) is a hereditary bleeding disorder. Type 3 VWD is the most severe and rare phenotype that presents many challenges for management of pregnant women. The aim of this study was to review the maternal characteristics and complications in pregnant women with Type 3 VWD. Study Design A systematic literature search was performed to include all publications that address Type 3 VWD in pregnancy. Results Thirteen studies met the inclusion criteria. There were 28 pregnancies with Type 3 VWD in 17 women. All were diagnosed with Type 3 VWD prior to pregnancy. Concentrate treatment was administered before delivery for 19 pregnancies and postpartum for 26 pregnancies. Eight pregnancies required blood products postpartum. Primary postpartum hemorrhage (PPH) was reported in 48% (10/21) and secondary PPH was reported in 56% (5/9). Secondary PPH occurred between 7 and 22 days. No study reported hysterectomies, intensive care unit admissions, or maternal mortality. All 28 pregnancies resulted in 28 live births at term. Conclusion Our review highlights the maternal outcomes in patients with Type 3 VWD and the different approaches in management during pregnancy and delivery. Despite prior knowledge of this bleeding disorder, PPH was still a significant complication.

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.

Unexpected presentation of type 2N von Willebrand disease in pregnancy

Haemophilia ◽  
2000 ◽  
Vol 6 (6) ◽  
pp. 696-697 ◽  
Author(s):  
M. W. Dennis ◽  
V. Clough ◽  
C. H. Toh
Keyword(s):  
Von Willebrand Disease ◽  
Von Willebrand ◽  
In Pregnancy

scholarly journals Successful management of multiple pregnancies in a family with varying severity of Von Willebrand disease

2018 ◽  
Vol 11 (4) ◽  
pp. 192-194
Author(s):  
Patrick Harrington ◽  
Pippa Kyle ◽  
Jacky Cutler ◽  
Bella Madan
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
The Other ◽  
Severe Phenotype ◽  
Mild Phenotype ◽  
History Of ◽  
Specialist Treatment ◽  
Factor Concentrate ◽  
Von Willebrand ◽  
Willebrand Factor

We present the obstetric history of a family of three sisters with Von Willebrand disease, managed in our centre over the course of nine successful pregnancies. The abnormalities result from inheritance of an exon 50 skipping mutation in the Von Willebrand factor gene, resulting from consanguinity. Two of the sisters were identified as having a severe phenotype with a Von Willebrand factor level of less than 5 IU/dl, with the other having a mild phenotype. Of the sisters with a severe phenotype, one had a number of prenatal complications and required early onset prophylaxis with Von Willebrand factor concentrate, whilst the other had a less complicated clinical course, only requiring Von Willebrand factor concentrate to cover labour. The sister with mild Von Willebrand disease had a rise in Von Willebrand factor levels during pregnancy and required no specialist treatment. The report highlights the markedly different clinical courses that can occur in patients with Von Willebrand disease and the different approaches to management.

Spontaneous pyohaemothorax in a teenager with von Willebrand disease: a case report and review of literature

2021 ◽  
Vol 14 (8) ◽  
pp. e241613
Author(s):  
Vaishnavi Divya Nagarajan ◽  
Asha Shenoi ◽  
Lucy Burgess ◽  
Vlad C Radulescu
Keyword(s):  
Case Report ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Surgical Drainage ◽  
Review Of Literature ◽  
History Of ◽  
Factor Concentrate ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

An 18-year-old man with a history of type 3 von Willebrand disease (VWD) presented with a spontaneous pyohaemothorax. Type 3 VWD may present with both mucocutaneous and deep-seated bleeds, such as visceral haemorrhages, intracranial bleeds and haemarthrosis. There have been very few cases described in children of spontaneous pyohaemothorax. Management of this patient was challenging due to risks of bleeding following surgical drainage, requiring constant replacement with von Willebrand factor concentrate, while monitoring factor VIII levels to balance the risks of thrombosis.

von Willebrand disease in pregnancy

2016 ◽  
Vol 20 (5) ◽  
pp. 501-505 ◽  
Author(s):  
Cheryl K. Roth ◽  
Lindsey J. Syed
Keyword(s):  
Von Willebrand Disease ◽  
Von Willebrand ◽  
In Pregnancy

First Case of Platelet-Type Von Willebrand Disease (PT-VWD) Associated with Type 2B Von Willebrand Disease (2B VWD)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5313-5313
Author(s):  
Marie Dreyfus ◽  
Celine Desconclois ◽  
Corinne Guitton ◽  
Marie-Jeanne Baas ◽  
Helene Mandard ◽  
...  
Keyword(s):  
Platelet Count ◽  
Von Willebrand Disease ◽  
Biological Study ◽  
High Dose ◽  
Severe Thrombocytopenia ◽  
First Case ◽  
Platelet Receptor ◽  
Biological Phenotype ◽  
Neonatal Thrombocytopenia ◽  
Von Willebrand

Abstract Abstract 5313 Introduction VWD 2B and PT-VWD are rare diseases, due to mutations inducing a gain of function respectively of von Willebrand factor (VWF) and of its platelet receptor, Glycoprotein (GP)1bα Case history We report here the case of a young girl, born with an extensive purpura and a severe thrombocytopenia: platelet count: 16G/L. There was no associated biological nor clinical abnormality. A high dose of 1g/kg of immunoglobulin G infused on day 1 was unsuccessful, and a HPA-1a (−) platelet concentrate infusion led to a partial and transient increase of the platelet count up to 60G/L. Thrombocytopenia then resolved spontaneously. Biological study showed no sign of materno-fetal allo- or auto-immunity, parents were not consanguineous. The diagnosis of type 2B VWD was performed when she was 5 months old: VWF:RCo < 13 IU/dl, VWF:Ag 60 IU/dl, positive ristocetin induced platelet aggregation (RIPA) at a low ristocetin concentration (0.5 mg/ml). RIPA mixing studies were unconclusive. The same biological abnormalities were found in the father, whereas the mother had normal hemostasis tests. The biological phenotype also included a study of the multimeric VWF structure, showing a marked decrease in percentage of VWF high and intermediate molecular multimers. Genetic analysis performed on VWF gene showed the heterozygous p.Pro1266Leu missense mutation in the VWF A1 domain. This mutation ( o ) is only slightly deleterious, and induces usually a mild disease, without thrombocytopenia, even in stress situations, with normal VWF multimeric distribution; therefore, it could not explain the biological phenotype severity in this family. GPIBA was then analysed, and a candidate point mutation p.Met239Ile was evidenced. This mutation had not been described yet, but p.Met255Val had already been found in diagnosed cases of PT-VWD. Conclusion This case underlines the utmost importance to characterize precisely neonatal thrombocytopenia mechanism. Furthermore, it points out the difficulties to performing PT-VWD diagnosis, which incidence is most probably underestimated. In our case, it was the systematic and extensive biological workout performed in this case of isolated neonatal thrombocytopenia, without any obvious cause, which led to the diagnosis of a PT-VWD, inducing a severe biological phenotype, associated with type 2B VWD characterized by a mild expression. It is, to our knowledge, the first case described to date of such a morbid association. Disclosures: No relevant conflicts of interest to declare.

Von Willebrand Disease in Pregnancy

2011 ◽  
Vol 25 (2) ◽  
pp. 335-358 ◽  
Author(s):  
Brea C. Lipe ◽  
Maura A. Dumas ◽  
Deborah L. Ornstein
Keyword(s):  
Von Willebrand Disease ◽  
Von Willebrand ◽  
In Pregnancy
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