Unexpectedly High Prevalence of Acquired von Willebrand Syndrome in Patients with Severe Aortic Stenosis as Evaluated with a Novel Large Multimer Index

Tamura, Toshihiro; Horiuchi, Hisanori; Imai, Michitaka; Tada, Takeshi; Shiomi, Hiroki; Kuroda, Maiko; Nishimura, Shunsuke; Takahashi, Yusuke; Yoshikawa, Yusuke; Tsujimura, Akira; Amano, Masashi; Hayama, Yasufumi; Imamura, Sari; Onishi, Nobuyuki; Tamaki, Yodo; Enomoto, Soichiro; Miyake, Makoto; Kondo, Hirokazu; Kaitani, Kazuaki; Izumi, Chisato; Kimura, Takeshi; Nakagawa, Yoshihisa

doi:10.5551/jat.30809

Cited by 76 publications

(101 citation statements)

References 18 publications

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“…This finding is consistent with the recognised association of anaemia with aortic valve stenosis 1,4,[6][7][8][9][10][11]15,18,19,22 and indicates that this phenomenon is common enough to be clinically relevant, if only because of the need to exclude other causes of anaemia. This finding is consistent with the recognised association of anaemia with aortic valve stenosis 1,4,[6][7][8][9][10][11]15,18,19,22 and indicates that this phenomenon is common enough to be clinically relevant, if only because of the need to exclude other causes of anaemia.…”

Section: Discussionsupporting

confidence: 86%

“…The diagnosis of Heyde syndrome 1 may be supported by evaluation of platelet morphology and function, [12][13][14][15][16][17] estimation of levels of large von Willebrand multipliers 7,10,11,14,16,[18][19][20][21][22] and evidence of haemolysis, 12,23,24 including reticulocytes, 24,25 fragmented erythrocytes 23 and haemosiderinuria. 23,26 We propose further studies to evaluate these tests to determine whether we can identify patients with Heyde syndrome for whom other causes of anaemia need not be pursued before AVR is undertaken.…”

Section: Resultsmentioning

confidence: 99%

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Heyde syndrome revisited: anaemia and aortic stenosis

Tjahjadi

Wee

Hay

et al. 2017

Internal Medicine Journal

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Section: Discussionsupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Heyde syndrome revisited: anaemia and aortic stenosis

Tjahjadi

Wee

Hay

et al. 2017

Internal Medicine Journal

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“…This unique bleeding syndrome, called Heyde's syndrome, is identified as acquired type 2A von Willebrand syndrome (AVWS). It is characterized by the loss of high-molecular-weight (HMW) von Willebrand factor multimers (VWFMs) 4–6) . This type of AVWS was also found in patients treated with ventricular assist devices 7) and extracorporeal membrane oxygenation therapy 8) .…”

Section: Introductionmentioning

confidence: 99%

Rapid Restoration of Thrombus Formation and High-Molecular-Weight von Willebrand Factor Multimers in Patients with Severe Aortic Stenosis After Valve Replacement

Yamashita

Yano

Hayakawa

et al. 2016

JAT

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Aim: Patients with severe aortic stenosis (AS) may have bleeding episodes due to the loss of high-molecular-weight (HMW) von Willebrand factor multimers (VWFMs). The absence of HMW-VWFMs and bleeding tendency are usually corrected after aortic valve replacement (AVR). To investigate the process of VWFM recovery and symptoms in patients with severe AS, we analyzed changes in VWF antigen (VWF:Ag), ADAMTS13 activity (ADAMTS13:AC), and platelet thrombus formation under high shear stress conditions.Methods: Nine patients with severe AS undergoing AVR were analyzed.Results: Evident deficiency of HMW-VWFMs was observed in six patients before surgery, which was rapidly restored within 8 days after AVR. Median levels of VWF:Ag before surgery, on postoperative days (PODs) 1, 8, 15, and 22, and one year after AVR were 78.1%, 130%, 224%, 155%, 134%, and 142%, respectively. In contrast, ADAMTS13:AC was 50.5%, 35.5%, 25.5%, 25.1%, 30.3%, and 84.6%, respectively. Preoperative thrombus formation but not surface coverage was significantly lower than that on POD 22, which was considered as normal level in each patient. Compared with preoperative levels, thrombus volume was significantly lower on POD 1, but rapidly increased by POD 8.Conclusion: Bleeding tendency and loss of HMW-VWFMs observed in patients with severe AS before surgery was rapidly corrected after AVR. Instead, patients were in a VWF-predominant state between POD 8 and 22.

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“…Acquired VWD can be caused by a number of conditions, including aortic stenosis 24–26 or ventriculoseptal cardiac defects. 27 In elderly patients, acquired VWD can be caused by an autoantibody to VWF that causes VWF to be rapidly cleared, but VWFpp is unaffected.…”

Section: Zpmcb-vwdmentioning

confidence: 99%

What have we learned from large population studies of von Willebrand disease?

Montgomery

Flood

2016

Hematology

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Von Willebrand factor (VWF) is a critical regulator of hemostatic processes, including collagen binding, platelet adhesion, and platelet aggregation. It also serves as a carrier protein to normalize plasma factor VIII synthesis, release, and survival. While VWF protein measurements by immunoassay are reasonably comparable between institutions, the measurement of VWF ristocetin cofactor activity (VWF:RCo) has significant variability. Other tests of VWF function, including collagen binding or platelet glycoprotein IIb–IIIa binding, are not universally available, yet these functional defects may cause major bleeding even with normal VWF antigen (VWF:Ag) and VWF:RCo assays. This results in both the overdiagnosis and underdiagnosis of VWD. Newer assays of VWF function (using recombinant glycoprotein Ib rather than whole platelets) have been developed that may improve interlaboratory variability. Some of these tests are not uniformly available and may not be licensed in the United States. Large longitudinal studies of VWF in von Willebrand disease (VWD) patients are not available. Patients are sometimes diagnosed with a single diagnostic VWF panel. Plasma VWF levels increase with age, but it is not clear if this results in less bleeding or whether different normal ranges should be used to identify age-related decreases in VWF. In order to quantitatively compare bleeding symptoms in VWD patients and normal individuals, recent studies in the European Union, Canada, United Kingdom, Holland, and the United States have used semiquantitative bleeding assessment tools (BATs). Even with careful centralized testing, including functional assays of VWF, addition of a BAT does not solve all of the problems with VWD diagnosis. No matter where the line is drawn for diagnosis of VWD, VWF is still a continuous variable. Thus, VWD can be a severe hemorrhagic disease requiring frequent treatment or a mild condition that may not be clinically relevant. As will be discussed by Dr. Goodeve in her presentation, genetics has helped us to diagnose type 2 functional variants of VWD but has not been helpful for the many patients who are at the interface of normal and low VWF and carry the possible diagnosis of type 1 VWD. The he-matologist’s management of patients with reduced levels of VWF still requires both the art and science of clinical medicine.

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Unexpectedly High Prevalence of Acquired von Willebrand Syndrome in Patients with Severe Aortic Stenosis as Evaluated with a Novel Large Multimer Index

Cited by 76 publications

References 18 publications

Heyde syndrome revisited: anaemia and aortic stenosis

Heyde syndrome revisited: anaemia and aortic stenosis

Rapid Restoration of Thrombus Formation and High-Molecular-Weight von Willebrand Factor Multimers in Patients with Severe Aortic Stenosis After Valve Replacement

What have we learned from large population studies of von Willebrand disease?

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