Acquired Von Willebrand Syndrome In Mitral Valve Leak

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4657-4657
Author(s):  
Almudena Pérez-Rodríguez ◽  
Maria Joana Costa Pinto Prego de Faria ◽  
Esther Lourés Fraga ◽  
Angela Rodríguez-Trillo ◽  
José Joaquín Cuenca ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Oral Anticoagulation ◽  
Conflicts Of Interest ◽  
Relative Proportion ◽  
Von Willebrand Disease ◽  
Mitral Valve Stenosis ◽  
Bleeding Diathesis ◽  
Acquired Von Willebrand Syndrome ◽  
Von Willebrand ◽  
Valve Leak

Abstract Abstract 4657 Background Several studies have shown that between 15% to 25% of patients with severe aortic stenosis present bleeding episodes that may be attributed to an acquired von Willebrand syndrome (AVWS). Until now, to our knowledge, no association of AVWS with mitral valve disfunction has been reported. Design and Methods Four patients with mitral valve leak presented acquired abnormalities of von Willebrand factor (VWF) and a bleeding history. Two of them presented severe bleedings requiring blood transfusions. All of them were within an adequate range of oral anticoagulation. Results Prior to surgery, these patients presented an APTT prolonged and in two of them the closure time determined by the platelet function analyzer (PFA-100®) (with COL/ADP and COL/Epi) was prolonged also. Factor VIII procoagulant activity (FVIII:C), VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo) and VWF collagen binding (VWF:CB) were considerably elevated and the VWF multimers in plasma, showed a lower relative proportion of the high molecular weight VWF multimers (HMWM), to some extent similar to type 2A congenital von Willebrand disease (VWD). In two of them, the VWF:RCo/VWF:Ag or VWF: CB/VWF:Ag ratios were less than normal range (>0.7) while in the other two were normal. After surgery, FVIII:C, and VWF properties were extremely increased and the ratios VWF:RCo/VWF:Ag and VWF: CB/VWF:Ag > 0.7. After surgery, FVIII:C, VWF:Ag, VWF:RCo and VWF:CB increased considerably. The ratios were > 0.7. The PFA-100® (COL/ADP and COL/Epi) was corrected in the two patients who had it prolonged. The multimeric VWF profile were also corrected in all of them. Conclusions The present study describes acquired VWF qualitative alterations for the first time in mitral valve leak. When such alterations are important they may be associated or to contribute to a bleeding diathesis. This problem was reported previously in aortic valve stenosis in relationship with a suspected very high shear stress. This situation may be not usually present in mitral valve stenosis, but it seems that it must occur in the presence of mitral valve leak. Consequently, the AVWS should be taken into account in patients with mitral valve leak that present a bleeding diathesis, not explained by an excess of oral anticoagulation. ACKNOWLEDGEMENTS This work was supported by the Fondo de Investigación Sanitaria, F.I.S. Carlos III, Ministerio de Sanidad, Spain (FIS PI# 07/0229), and Consellería de Innovación e Industria, Xunta de Galicia (INCITE08ENA916109ES). Disclosures: No relevant conflicts of interest to declare.

The Acquired Von Willebrand Syndrome in Patients with Monoclonal IgA Proteins Is Rare but May be Clinically Severe

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2830-2830
Author(s):  
Ulrich Budde ◽  
Rita Dittmer ◽  
Sonja Schneppenheim ◽  
Tina Rausch
Keyword(s):  
Conflicts Of Interest ◽  
Lymphoproliferative Disorders ◽  
Von Willebrand Disease ◽  
Bleeding Complications ◽  
Severe Bleeding ◽  
Iliac Crest Biopsy ◽  
Acquired Von Willebrand Syndrome ◽  
Large Patient ◽  
Diagnostic Panel ◽  
Von Willebrand

Abstract During the last 10 years our laboratory diagnosed and typed 5585 different patients with inherited von Willebrand disease (VWS) and acquired von Willebrand syndrome (aVWS). Out of these 21% (1217) suffered from aVWS. With 252 patients lymphoproliferative disorders were number three in frequency (21%) after cardiovascular (43%) and myeloproliferative (27%) disorders. Out of the patients with lymphoproliferative disorders patients with a monoclonal IgA protein comprised only 3.6% (9 patients). Much more abundant were monoclonal IgG´s (71%) and IgM´s (26%). According to our data only one patient was classified as MGUS and the others suffered from myeloma. The most impressive property was the heterogeneity of their laboratory and clinical data with the exception that all patients suffered from severe bleeding complications whenever their hemostatic system was challenged by accidents or invasive procedures (even iliac crest biopsy). The VWF:Ag ranged from 0.06 – 5.60 IU/ml and only one patient had a VWF:Ag <0.5 IU/dl. The functional test (VWF:CB) ranged from 0.06 and 5.48 IU/ml again with only one patient <0.5 IU/dl. The ratio VWF:CB / VWF:Ag was below 0.8 in three patients. Thus more than 50% of the patients would remain undetected if the VWF multimers were not included in the diagnostic panel. Two patients displayed the whole set of multimers, while the others showed a mild (5) or severe (2) absence of the large multimers. The hallmark of the multimic pattern from patients with an IgA monoclonal protein was the presence of a lot of smeary material within the electrophoretic lanes diplayed in all patients. In summary aVWS in the course of lymphoproliferative disorders and monoclonal IgA proteins is clinically severe, although probably not life threatening. It remains undetected with standard VWF tests and might be therefore not as rare as detected in our large patient panel. Disclosures No relevant conflicts of interest to declare.

Abnormal Structure of von Willebrand Factor in Myeloproliferative Syndrome Is Associated to Either Thrombotic or Bleeding Diathesis

1987 ◽  
Vol 58 (02) ◽  
pp. 753-757 ◽  
Author(s):  
M F López-Fernández ◽  
C López-Berges ◽  
R Martín ◽  
A Pardo ◽  
F J Ramos ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Proteinase Inhibitors ◽  
Relative Proportion ◽  
Variable Degree ◽  
Bleeding Diathesis ◽  
Myeloproliferative Syndrome ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe multimeric and subunit patterns of plasma von Willebrand factor (vWF) were analyzed in eight patients with myeloproliferative syndrome (MS) in order to investigate the possible existence of heterogeneity in the “in vivo” proteolytic cleavage of the protein, previously observed in this entity. Six patients lacked large vWF multimers, five of them having normal bleeding times (BT) and clinically documented episodes of thrombotic origin, whereas one patient had long BT and bleeding symptoms. Seven patients showed a relative increase in the 176 kDa subunit fragment while the 189 kDa polypeptide was increased in only one. In addition, another patient (and prior to any therapy) showed the presence of a new fragment of approximately 95 kDa which disappeared after Busulfan therapy. The collection of blood from these patients with proteinase inhibitors did not correct the abnormalities.The infusion of DDAVP to two patients with abnormal vWF was accompanied by: the appearance of larger vWF multimers which disappeared rapidly from plasma; an increase in the relative proportion of the satellite bands of each multimer and a further increase of the 176 kDa fragment. These data point to some heterogeneity in the vWF abnormality present in MS which may be related in part to a variable degree of proteolysis of vWF occurring “in vivo” rather than “in vitro”, and which may be associated to either a thrombotic or a bleeding diathesis. They also suggest that despite the presence of abnormal, already proteolyzed vWF, DDAVP-enhanced proteolysis occurs in MS to a similar extent to what is described in normal individuals.

Further specificity characterization of von Willebrand factor inhibitors developed in two patients with severe von Willebrand disease

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 116-120 ◽  
Author(s):  
MF Lopez-Fernandez ◽  
R Martin ◽  
C Lopez-Berges ◽  
F Ramos ◽  
N Bosch ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Complex Structure ◽  
Relative Proportion ◽  
Von Willebrand Disease ◽  
Rabbit Antibody ◽  
Human Factor Viii ◽  
Rabbit Polyclonal Antibody ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Circulating inhibitors against von Willebrand factor (vWF) that show the properties of heterologous IgG antibodies have been described in a few patients with severe von Willebrand disease (vWD). The present study provides further characterization of inhibitors from two patients with severe vWD. Inhibitors in both, like polyclonal rabbit antibody, detected all sizes of multimers and the complex structure of each multimer from platelets and plasma of normal individuals as well as from plasma of patients with IIA, IIB, and IIC vWD. Both inhibitors and the rabbit antibody reacted mainly with the intact 225-Kd vWF subunit and the 189-H and 140-Kd fragments in contrast to monoclonal antibodies specific for vWF fragments that detected a higher relative proportion of 176-Kd fragment. Furthermore, all these antibodies recognized fragment III, although one inhibitor and rabbit polyclonal antibody reacted poorly and the other inhibitor did not react at all with reduced fragment II of vWF digested with Staphylococcus aureus V-8 protease. These data suggest that although human inhibitors from severe vWD patients may behave, to some extent, as polyclonal heterologous antibodies against native vWF, the former show striking differences in their target specificity as well as a much broader specificity than that described for human factor VIII inhibitors.

Bleeding diathesis associated with acquired von Willebrand Syndrome in three patients with chronic lymphocytic leukemia

2015 ◽  
Vol 56 (12) ◽  
pp. 3452-3454 ◽  
Author(s):  
Mona Lisa Alattar ◽  
Maria Ciccone ◽  
Mahmoud R. Gaballa ◽  
Candida Vitale ◽  
Xavier C. Badoux ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Bleeding Diathesis ◽  
Acquired Von Willebrand Syndrome ◽  
Von Willebrand

Von Willebrand factor in aortic or mitral valve stenosis and bleeding after heart valve surgery

2021 ◽  
Vol 198 ◽  
pp. 190-195
Author(s):  
Piotr Mazur ◽  
Joanna Natorska ◽  
Michał Ząbczyk ◽  
Łukasz Krzych ◽  
Radosław Litwinowicz ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Heart Valve ◽  
Von Willebrand Factor ◽  
Valve Surgery ◽  
Mitral Valve Stenosis ◽  
Heart Valve Surgery ◽  
Von Willebrand ◽  
Willebrand Factor

How I treat the acquired von Willebrand syndrome

Blood ◽  
2011 ◽  
Vol 117 (25) ◽  
pp. 6777-6785 ◽  
Author(s):  
Andreas Tiede ◽  
Jacob H. Rand ◽  
Ulrich Budde ◽  
Arnold Ganser ◽  
Augusto B. Federici
Keyword(s):  
Factor Viia ◽  
Medical Condition ◽  
Treatment Options ◽  
Von Willebrand Disease ◽  
Acquired Von Willebrand Syndrome ◽  
Functional Interference ◽  
Typical Treatment ◽  
Evidence Based Guidelines ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract The acquired von Willebrand syndrome (AVWS) is a bleeding disorder that is frequently unrecognized or is misdiagnosed as von Willebrand disease. AVWS is characterized by structural or functional defects of von Willebrand factor (VWF) that are secondary to autoimmune, lymphoproliferative or myeloproliferative, malignant, cardiovascular, or other disorders. VWF abnormalities in these disorders can result from (1) antibody-mediated clearance or functional interference, (2) adsorption to surfaces of transformed cells or platelets, or (3) increased shear stress and subsequent proteolysis. Diagnosis can be challenging as no single test is usually sufficient to prove or exclude AVWS. Furthermore, there are no evidence-based guidelines for management. Treatments of the underlying medical condition, including chemo/radiotherapy, surgery, or immunosuppressants can result in remission of AVWS, but is not always feasible and successful. Because of the heterogeneous mechanisms of AVWS, more than one therapeutic approach is often required to treat acute bleeds and for prophylaxis during invasive procedures; the treatment options include, but are not limited to, desmopressin, VWF-containing concentrates, intravenous immunoglobulin, plasmapheresis or recombinant factor VIIa. Here, we review the management of AVWS with an overview on the currently available evidence and additional considerations for typical treatment situations.

Mapping of the Binding Site within Glycoprotein Ibα for the Leukocyte Integrin Mac-1 (αMβ2).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 472-472
Author(s):  
Adam D Munday ◽  
Yuandong Peng ◽  
Yunmei Wang ◽  
Daniel I Simon ◽  
Jose A. Lopez
Keyword(s):  
Binding Site ◽  
Platelet Adhesion ◽  
Conflicts Of Interest ◽  
Peptide Binding ◽  
Von Willebrand Disease ◽  
Targeted Mutagenesis ◽  
Dimensional Structure ◽  
Monocytic Cell ◽  
Platelet Surface ◽  
Von Willebrand

Abstract Abstract 472 To maintain hemostasis, the human body uses more that 7,000 platelets/μl of blood a day; 3.5 billion platelets a day in a 70 kg adult male. Lack of fully functional platelets results in bleeding disorders such as Bernard-Soulier syndrome, Glanzmann thrombasthenia and platelet-type von Willebrand disease. It is becoming increasingly well appreciated that in addition to their hemostatic role, platelets play important roles in inflammation and wound healing. The initial step of platelet adhesion is mediated by the glycoprotein (GP) Ib-IX-V complex on the platelet surface, which binds von Willebrand factor (VWF). This interaction leads to activation of the integrin αIIbβ3, platelet arrest, and spreading and aggregation. The GPIb-IX-V complex also has a key role in inflammation, mediating a key interaction of platelets with leukocytes by binding the integrin Mac-1 (αMβ2, CD11b/CD18). This interaction mediates the firm adhesion of leukocytes on platelet thrombi, enabling their migration through the thrombus into the vessel wall. Interestingly, the insert domain (I-domain) of the αM subunit of Mac-1 has a similar 3-dimensional structure to the A1 domain of VWF. Our previous studies showed that the I-domain of Mac-1 binds the C-terminal flanking sequence of GPIbα (Phe201-Gly268), demonstrated by the ability of the anti-GPIbα monoclonal antibody AP1 to inhibit the interaction. The epitope of AP1 has been mapped to a 10-amino acid sequence spanning Arg218 to Tyr228. In the current investigation, we constructed a series of cell lines expressing mutants of human GPIbα, either by replacement of the human sequence with the corresponding dog sequence (dog GPIbα does not bind human Mac-1) or by targeted mutagenesis, and tested their ability to bind the recombinant αM I domain. TheGPIbα region Phe201–Asn223 was crucial for Mac-1 binding, with residues Arg218, Asp222 and Asn223 playing vital roles. In addition, a peptide containing the AP1 epitope (Leu214–Val229) bound αM I-domain specifically and saturably. Peptide binding was blocked by LPM19c, a monoclonal anti-αM I-domain antibody, and soluble GPIbα, and by the M2 peptide, which corresponds to the GPIbα–binding site in the αM I domain (Phe201–Lys217). Peptide binding was also blocked by an antibody against the M2 sequence. The AP1 peptide inhibited the attachment of GPIb-IX complex–expressing CHO cells to immobilized αM I domain, and the adhesion of THP-1 cells—a monocytic cell line expressing Mac-1—to immobilized GPIbα. In summary, we have defined the GPIbα sequence Arg218 to Ala224 as a critical binding site for Mac-1. Because a peptide corresponding to this region inhibits GPIbα binding to Mac-1 but blocks neither platelet adhesion to immobilized VWF nor thrombin-induced platelet aggregation, it has potential to guide the development of agents that will specifically inhibit leukocyte-platelet complexes that promote vascular inflammation. Disclosures: No relevant conflicts of interest to declare.

Hemophilia in the Peruvian Social Security System: Report of Five Centers.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4446-4446
Author(s):  
Gloria Chumpitaz ◽  
Fernando Cauvi ◽  
Juan Ramon Navarro ◽  
Karina Pedraza
Keyword(s):  
Conflicts Of Interest ◽  
Age Groups ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
Severe Illness ◽  
Factor Deficiency ◽  
Coagulation Factor Deficiency ◽  
Receive Treatment ◽  
New Diagnosis ◽  
Von Willebrand

Abstract Abstract 4446 The Hemophilia Unit of the Hematology Department of the National Hospital Edgardo Rebagliatti Martins- ESSALUD, is one of the most important Hemophilia Centers through the country, that assists patients not only in its jurisdiction but also a great amount referred from other institutions due the complexity of their treatment, like acquired inhibitor disorders as well as orthopedic and mayor cardiovascular surgeries and severe hemorrhages. The Hemophilia ESSALUD system is compounded of centers in Lima (02), Callao (01) and provinces (05) (Arequipa, Chiclayo, Trujillo, Piura and Cuzco). The range of patients with new diagnosis is about 5 to 20 patients per year. The prevalence of Hemophilia in the last 5 years, accounts 83.38% patients of the global amount with coagulation disorders. Of the 331 patients in treatment, 228 (68.8%) have Hemophilia A. Considering the classification of status severity, 12.5% patients of this group belong to mild status hemophilia, 39.47% patients to moderate status, and 41.43% to severe status. In relation to Hemophilia B, we account 48 (14.5%) patients; 5.2% corresponds to mild status, 23.68% moderate status and 52.63% severe status. The rest of the patients have other disorders of coagulation such as Von Willebrand disease and rare coagulation factor deficiency (V, VII, XI and XII). According to the age group distribution for this series, a mayor proportion of 44.68%of patients belong to the group between 16 to 35 years old. The group above 35 years accounts 30%.The age groups of 6 to 15 years old and the group of 1 to 5 year old account 16.48% and 8.51%, respectively. Finally, it is important to point out that 37.76% of our hemophiliac patients are in the group of moderate illness status and 44.14% in the group of severe illness status. All the patients receive treatment with plasma-derived coagulation factor concentrates and in some cases recombinant therapy. Children receive prophylactic treatment. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document