Abstract 1128

Background

Dysfunctional or mismatched prosthetic heart valves can results in high shear stress related von Willebrand factor (VWF) impairment, and clinical bleeding. This mechanism is similar to that seen in aortic stenosis patients, where gastrointestinal bleeding related to VWF multimer loss is well described (Heyde syndrome). In this study, we compared the results of VWF testing of patients with normally functioning cardiac valve prostheses, dysfunctional prosthetic valves, severe native aortic stenosis, and normal controls.

Methods

A total of 75 patients, 31 female and 44 male with a median age of 79.5 years were recruited to this study. Thirty patients had severe aortic stenosis (mean gradient > 40 mm Hg); 39 patients had normally functioning prosthetic valves, 21 aortic (AVR) and 18 mitral valves (MVR); and 6 patients had with dysfunctional valves (4 aortic and 2 mitral). Whole blood and plasma samples were drawn from patients and tested for platelet function analyzer-100 collagen ADP closure time (PFA-CADP), VWF antigen (VWF:Ag), VWF activity by latex immunoassay (VWF:Ltx), VWF multimer analysis and VWF multimer densitometry ratio of large vs medium to low molecular weight multimers (>15 mers/2–15 mers).

Results

The 6 dysfunctional prosthetic valve patients included patient-prosthesis mismatch (2) and (one each), thrombosed mechanical aortic prosthesis, torn biological aortic prosthesis, severe tissue mitral prosthetic regurgitation, and post-mitral valve repair severe mitral regurgitation. Four of six patients had clinically significant bleeding. Most aortic stenosis and all 6 prosthetic dysfunction patients had abnormal VWF multimers which is rare in normally functioning prostheses and completely absent in normal donors. VWF:Ltx/Ag was lower in AS and MVR than normal. VWF:Ltx/Ag ratio, VWF:multimer ratio and PFA-CADP were all significantly abnormal in patients with dysfunctional prosthetic valve. VWF:multimer ratios in normally functioning prostheses tended to be intermediate between normals and than those of patients with severe AS or prosthetic valve dysfunction (Table).

Table.
NormalsProsthetic DysfunctionAVRMVRSevere AS
Abnormal VWF multimers 0/21 6/6 2/21 1/18 26/30 
Multimer ratio
 >15/2–15 mers 0.24 ± 0.05 0.13 ± 0.01*† 0.17 ± 0.02* 0.19 ± 0.04* 0.13 ± 0.03*† 
PFA-100 CADP 89 ± 16 141 ± 36*† 98 ± 29 93 ± 31 181 ± 69*† 
Ltx/Ag 0.96 ± 0.11 0.71 ± 0.06*† 0.93 ± 0.09‡ 0.87 ± 0.05* 0.87 ± 0.16*† 
NormalsProsthetic DysfunctionAVRMVRSevere AS
Abnormal VWF multimers 0/21 6/6 2/21 1/18 26/30 
Multimer ratio
 >15/2–15 mers 0.24 ± 0.05 0.13 ± 0.01*† 0.17 ± 0.02* 0.19 ± 0.04* 0.13 ± 0.03*† 
PFA-100 CADP 89 ± 16 141 ± 36*† 98 ± 29 93 ± 31 181 ± 69*† 
Ltx/Ag 0.96 ± 0.11 0.71 ± 0.06*† 0.93 ± 0.09‡ 0.87 ± 0.05* 0.87 ± 0.16*† 
*

p<0.001 vs normals. † p<0.001 vs AVR+MVR. cm=NS vs normal, but p<0.02 vs mitral valve replacement.

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Conclusions

VWF testing including quantitative von Willebrand multimer analysis and PFA-CADP reliably separate dysfunctional from normally functioning cardiac prostheses, and should be considered in the evaluation of patients with cardiac prostheses, especially those who have clinically significant bleeding.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
heart valve prosthesis, mitral valve prosthetic malfunction, platelet function, von willebrand factor, prostheses, aortic valve stenosis, hemorrhage, middle east respiratory syndrome, von willebrand factor multimer assay, antigens

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2012 by The American Society of Hematology
2012
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