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.

scholarly journals Type 3 VWD and an inhibitor to VWF: Challenges in diagnosis

2016 ◽  
Vol 3 (2) ◽  
pp. 1-3 ◽  
Author(s):  
S. Jenkins ◽  
Manuel Carcao ◽  
Vanessa Bouskill
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Bleeding Disorders ◽  
Limited Experience ◽  
Recurrent Epistaxis ◽  
History Of ◽  
Factor Concentrate ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Developing an inhibitor to von Willebrand factor (VWF) is extremely uncommon. Consequently, patients with von Willebrand disease (VWD) tend not to be routinely evaluated for inhibitors, leading to the possibility of delay in inhibitor diagnosis. We present such an occurrence to raise awareness, with a view to avoiding such delays. A 1-year-old male with no family history of bleeding disorders or parental consanguinity presented with a tongue bleed lasting three days. Investigations confirmed a diagnosis of Type 3 VWD. Over the next few months, the patient received seven exposures to Humate-P (a plasma derived FVIII containing von Willebrand factor concentrate), but developed an anaphylactic reaction necessitating adrenalin and Benadryl (diphenhydramine). The reaction quickly abated and did not recur with further exposure to Humate-P. In 2013, due to recurrent epistaxis and tonsillar bleeding, the patient was commenced on prophylaxis receiving Humate-P 50 RCo U/kg twice weekly. Despite this regimen, he continued to experience recurrent epistaxis, leading to escalation of prophylaxis to 3/week. In November 2014, he showed persistent tonsillar bleeding, despite having received two doses of Humate-P (each 40 RCo U/kg) in the previous 12 hours. Testing revealed reduced VWF:Ag, VWF:RCo and FVIII:C recoveries. Further testing revealed an anti-VWF antibody (2.6 BU) of unspecified Ig type. Since diagnosis of the inhibitor, he has received 100 RCo U/kg daily for prophylaxis and immune tolerance. He is now bleed-free; however, monthly inhibitor testing shows that his inhibitor persists. Given the limited experience and literature on inhibitors in VWD, the prognosis for such cases is unknown.

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.

Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

2021 ◽  
Vol 47 (02) ◽  
pp. 192-200
Author(s):  
James S. O'Donnell
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Personalized Treatment ◽  
Treatment Plans ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThe biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD) have been studied extensively. In contrast, although accounting for the majority of VWD cases, the pathobiology underlying partial quantitative VWD has remained somewhat elusive. However, important insights have been attained following several recent cohort studies that have investigated mechanisms in patients with type 1 VWD and low von Willebrand factor (VWF), respectively. These studies have demonstrated that reduced plasma VWF levels may result from either (1) decreased VWF biosynthesis and/or secretion in endothelial cells and (2) pathological increased VWF clearance. In addition, it has become clear that some patients with only mild to moderate reductions in plasma VWF levels in the 30 to 50 IU/dL range may have significant bleeding phenotypes. Importantly in these low VWF patients, bleeding risk fails to correlate with plasma VWF levels and inheritance is typically independent of the VWF gene. Although plasma VWF levels may increase to > 50 IU/dL with progressive aging or pregnancy in these subjects, emerging data suggest that this apparent normalization in VWF levels does not necessarily equate to a complete correction in bleeding phenotype in patients with partial quantitative VWD. In this review, these recent advances in our understanding of quantitative VWD pathogenesis are discussed. Furthermore, the translational implications of these emerging findings are considered, particularly with respect to designing personalized treatment plans for VWD patients undergoing elective procedures.

scholarly journals Phage Display Broadly Identifies Inhibitor-reactive Regions in von Willebrand Factor

2021 ◽  
Author(s):  
Andrew Yee ◽  
Manhong Dai ◽  
Stacy E. Croteau ◽  
Jordan A. Shavit ◽  
Steven W. Pipe ◽  
...  
Keyword(s):  
Phage Display ◽  
Von Willebrand Factor ◽  
Gene Deletion ◽  
Von Willebrand Disease ◽  
Response To Treatment ◽  
Phage Library ◽  
Incomplete Removal ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryBackgroundCorrection of von Willebrand factor (VWF) deficiency with replacement products containing VWF can lead to the development of anti-VWF alloantibodies (i.e., VWF inhibitors) in patients with severe von Willebrand disease (VWD).ObjectiveLocate inhibitor-reactive regions within VWF using phage display.MethodsWe screened a phage library displaying random, overlapping fragments covering the full length VWF protein sequence for binding to a commercial anti-VWF antibody or to immunoglobulins from three type 3 VWD patients who developed VWF inhibitors in response to treatment with plasma-derived VWF. Immunoreactive phage clones were identified and quantified by next generation DNA sequencing (NGS).ResultsNGS markedly increased the number of phage analyzed for locating immunoreactive regions within VWF following a single round of selection and identified regions not recognized in previous reports using standard phage display methods. Extending this approach to characterize VWF inhibitors from three type 3 VWD patients (including two siblings homozygous for the same VWF gene deletion) revealed patterns of immunoreactivity distinct from the commercial antibody and between unrelated patients, though with notable areas of overlap. Alloantibody reactivity against the VWF propeptide is consistent with incomplete removal of the propeptide from plasma-derived VWF replacement products.ConclusionThese results demonstrate the utility of phage display and NGS to characterize diverse anti-VWF antibody reactivities.

Clinical cases of using coagulation factor VIII with von Willebrand factor in parturient women with type III von Willebrand disease

2020 ◽  
Author(s):  
И.В. Куртов ◽  
Е.С. Фатенкова ◽  
Н.А. Юдина ◽  
А.М. Осадчук ◽  
И.Л. Давыдкин
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
Coagulation Factor Viii ◽  
Vitro Fertilization ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

Болезнь Виллебранда (БВ) может представлять определенные трудности у рожениц с данной патологией. Приведены 2 клинических примера использования у женщин с БВ фактора VIII свертывания крови с фактором Виллебранда, показана эффективность и безопасность их применения. У одной пациентки было также показано использование фактора свертывания крови VIII с фактором Виллебранда во время экстракорпорального оплодотворения. Von Willebrand disease presents a certain hemostatic problem among parturients. This article shows the effectiveness and safety of using coagulation factor VIII with von Willebrand factor for the prevention of bleeding in childbirth in 2 patients with type 3 von Willebrand disease. In one patient, the use of coagulation factor VIII with von Willebrand factor during in vitro fertilization was also shown.

von Willebrand factor alloantibodies in type 3 von Willebrand disease

2020 ◽  
Vol 31 (1) ◽  
pp. 77-79
Author(s):  
Barbara Faganel Kotnik ◽  
Karin Strandberg ◽  
Maruša Debeljak ◽  
Lidija Kitanovski ◽  
Janez Jazbec ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

Expression and characterization of von Willebrand factor dimerization defects in different types of von Willebrand disease

Blood ◽  
2001 ◽  
Vol 97 (7) ◽  
pp. 2059-2066 ◽  
Author(s):  
Reinhard Schneppenheim ◽  
Ulrich Budde ◽  
Tobias Obser ◽  
Jacqueline Brassard ◽  
Kerstin Mainusch ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Recombinant Expression ◽  
Von Willebrand Disease ◽  
Disulfide Bonding ◽  
Amino Terminal ◽  
Carboxy Terminal ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Dimerization defects of von Willebrand factor (vWF) protomers underlie von Willebrand disease (vWD) type 2A, subtype IID (vWD 2A/IID), and corresponding mutations have been identified at the 3′ end of the vWF gene in exon 52. This study identified and expressed 2 additional mutations in this region, a homozygous defect in a patient with vWD type 3 (C2754W) and a heterozygous frameshift mutation (8566delC) in a patient with vWD type 2A, subtype IIE. Both mutations involve cysteine residues that we propose are possibly essential for dimerization. To prove this hypothesis, transient recombinant expression of each of the 2 mutations introduced in the carboxy-terminal vWF fragment II and in the complete vWF complementary DNA, respectively, were carried out in COS-7 cells and compared with expression of vWD 2A/IID mutation C2773R and the wild-type (WT) sequence in COS-7 cells. Recombinant WT vWF fragment II assembled correctly into a dimer, whereas recombinant mutant fragments were monomeric. Homozygous expression of recombinant mutant full-length vWF resulted in additional dimers, probably through disulfide bonding at the amino-terminal multimerization site, whereas recombinant WT vWF correctly assembled into multimers. Coexpression of recombinant mutant and recombinant WT vWF reproduced the multimer patterns observed in heterozygous individuals. Our results suggest that a common defect of vWF biosynthesis—lack of vWF dimerization—may cause diverse types and subtypes of vWD. We also confirmed previous studies that found that disulfide bonding at the vWF amino-terminal is independent of dimerization at the vWF carboxy-terminal.

Sign in / Sign up

Export Citation Format

Share Document