Abstract 3315

Background:

Acquired von Willebrand syndrome (AVWS) is a frequent cause of bleeding in patients with severe aortic stenosis (AS). The goals of this study were to understand the incidence and patterns of bleeding in patients with various degree of AS and identify predictors for bleeding.

Methods:

Ninety-one patients (59 men, median age 79 years) with mild, moderate or severe aortic stenosis (AS) (n=64) or heart valve replacement (n=27) were studied. Clinically significant bleeding was determined based on the 2008 NHLBI VWD diagnostic guideline (Haemophilia. 2008, 14(2):171–232). We recorded blood counts, vital signs, mean gradient, peak aortic velocity, aortic valve area (AVA) and valve area index (AVAi), time velocity integral ratio (TVI ratio), VWF antigen (VWF:Ag), VWF activity by latex immunoturbidity assay (VWF:Lx), VWF multimer analysis, and closure times of platelet function analysis ADP and epinephrine cartridges (PFA–CADP and –CEPI). VWF high molecular weight multimer (HMWM) losses were graded as normal/mild or severe when compared to pooled plasma samples from normal donors. Associations with bleeding tendency were explored using single variable and multivariable logistic regression models.

Results:

Of the 91 patients, 29 (32%) were taking warfarin, and 55 (60%) were taking aspirin. None received a thienopyridine. Clinically significant bleeding was seen in 27 (30%) patients with gastrointestinal (GI) bleeding being most common (n=13). Nine patients who bled required hospitalization. Bleeding tendency was more common in patients with a severe loss of HMWM (OR=3.18, 95% CI: 1.06–9.71, P=0.039) and in patients with AS-associated symptoms (OR=3.02, 95% CI: 1.14–8.24, P=0.027). No other echocardiographic, laboratory, or clinical features demonstrated a statistically significant association with bleeding tendency.

Conclusion:

The incidence of clinically significant bleeding in this population was about 30% with GI being the most common site. Bleeding tendency was associated with severe HMWM loss and AS-associated symptoms. This study underscores the importance of acquisition of a history of bleeding, cardiac symptoms, and VWF multimer analysis in clinical management of AS patients.

Table:

Predictors of bleeding among all patients (N=91)

Single variable analysisMultivariable analysis
VariableOR (95% CI)P-valueOR (95% CI)P-value
Gender (male) 0.46 (0.18–1.15) 0.095 0.41 (0.15–1.07) 0.069 
Age (years) 0.89 (0.61–1.32) 0.55 0.81 (0.54–1.22) 0.30 
Patient type (AS vs. valve replacement) 1.30 (0.49–3.76) 0.61 0.82 (0.27–2.56) 0.72 
Aortic stenosis related symptoms 3.44 (1.35–9.17) 0.011 3.02 (1.14–8.24) 0.027 
Current use of warfarin 1.10 (0.41–2.84) 0.85 1.74 (0.60–5.11) 0.31 
Current use of aspirin 1.16 (0.47–3.01) 0.75 1.06 (0.41–2.83) 0.91 
GFR (60 vs. <60) 0.93 (0.36–2.50) 0.88 0.79 (0.29–2.19) 0.64 
Atrial fibrillation 0.80 (0.29–2.09) 0.66 1.10 (0.38–3.10) 0.86 
Left ventricular hypertrophy 0.83 (0.29–2.26) 0.73 0.67 (0.21–1.91) 0.47 
Platelet (100 units) 0.84 (0.37–1.80) 0.66 0.72 (0.30–1.60) 0.43 
Hemoglobin (1 unit) 0.79 (0.58–1.05) 0.10 0.78 (0.57–1.06) 0.12 
Peak velocity  0.68  0.68 
<3 m/sec (mild) 1.00 (reference)  1.00 (reference)  
3-4 m/sec (moderate) 0.93 (0.29–2.95)  0.80 (0.24–2.58)  
>4 m/sec (severe) 1.47 (0.51–4.33)  0.51 (0.10–2.13)  
Mean Gradient  0.35  0.20 
<25 mmHg (mild) 1.00 (reference)  1.00 (reference)  
25-40 mmHg (moderate) 0.38 (0.08–1.37)  0.41 (0.09–1.53)  
>40 mmHg (severe) 1.00 (0.36–2.70)  0.30 (0.04–1.25)  
Aortic Valve Area  0.97  0.58 
1.5 (mild) 1.00 (reference)  1.00 (reference)  
1.0-1.5 (moderate) 0.89 (0.28–2.97)  0.81 (0.24–2.76)  
<1.0 (severe) 1.01 (0.33–3.24)  0.50 (0.12–1.87)  
TVI Ratio  0.83  0.59 
>0.35 (mild) 1.00 (reference)  1.00 (reference)  
0.25-0.35 (moderate) 0.77 (0.22–2.47)  0.79 (0.23–2.60)  
<0.25 (severe) 1.10 (0.39–3.13)  0.51 (0.12–1.77)  
AVA Index  0.65  0.23 
>0.84 (mild) 1.00 (reference)  1.00 (reference)  
0.60-0.84 (moderate) 1.78 (0.53–6.36)  1.82 (0.53–6.63)  
<0.60 (severe) 1.31 (0.43–4.31)  0.58 (0.13–2.28)  
vWF Ratio (Ltx/Ag), % = 0.8) 2.16 (0.63–7.28) 0.21 1.30 (0.32–4.92) 0.70 
PFA collagenADP closure time (% ≥ 121) 2.01 (0.80-5.08) 0.14 1.18 (0.37–3.54) 0.77 
Severe loss of HMW multimers 3.60 (1.26–10.53) 0.017 3.60 (1.26–10.53) 0.017 
Single variable analysisMultivariable analysis
VariableOR (95% CI)P-valueOR (95% CI)P-value
Gender (male) 0.46 (0.18–1.15) 0.095 0.41 (0.15–1.07) 0.069 
Age (years) 0.89 (0.61–1.32) 0.55 0.81 (0.54–1.22) 0.30 
Patient type (AS vs. valve replacement) 1.30 (0.49–3.76) 0.61 0.82 (0.27–2.56) 0.72 
Aortic stenosis related symptoms 3.44 (1.35–9.17) 0.011 3.02 (1.14–8.24) 0.027 
Current use of warfarin 1.10 (0.41–2.84) 0.85 1.74 (0.60–5.11) 0.31 
Current use of aspirin 1.16 (0.47–3.01) 0.75 1.06 (0.41–2.83) 0.91 
GFR (60 vs. <60) 0.93 (0.36–2.50) 0.88 0.79 (0.29–2.19) 0.64 
Atrial fibrillation 0.80 (0.29–2.09) 0.66 1.10 (0.38–3.10) 0.86 
Left ventricular hypertrophy 0.83 (0.29–2.26) 0.73 0.67 (0.21–1.91) 0.47 
Platelet (100 units) 0.84 (0.37–1.80) 0.66 0.72 (0.30–1.60) 0.43 
Hemoglobin (1 unit) 0.79 (0.58–1.05) 0.10 0.78 (0.57–1.06) 0.12 
Peak velocity  0.68  0.68 
<3 m/sec (mild) 1.00 (reference)  1.00 (reference)  
3-4 m/sec (moderate) 0.93 (0.29–2.95)  0.80 (0.24–2.58)  
>4 m/sec (severe) 1.47 (0.51–4.33)  0.51 (0.10–2.13)  
Mean Gradient  0.35  0.20 
<25 mmHg (mild) 1.00 (reference)  1.00 (reference)  
25-40 mmHg (moderate) 0.38 (0.08–1.37)  0.41 (0.09–1.53)  
>40 mmHg (severe) 1.00 (0.36–2.70)  0.30 (0.04–1.25)  
Aortic Valve Area  0.97  0.58 
1.5 (mild) 1.00 (reference)  1.00 (reference)  
1.0-1.5 (moderate) 0.89 (0.28–2.97)  0.81 (0.24–2.76)  
<1.0 (severe) 1.01 (0.33–3.24)  0.50 (0.12–1.87)  
TVI Ratio  0.83  0.59 
>0.35 (mild) 1.00 (reference)  1.00 (reference)  
0.25-0.35 (moderate) 0.77 (0.22–2.47)  0.79 (0.23–2.60)  
<0.25 (severe) 1.10 (0.39–3.13)  0.51 (0.12–1.77)  
AVA Index  0.65  0.23 
>0.84 (mild) 1.00 (reference)  1.00 (reference)  
0.60-0.84 (moderate) 1.78 (0.53–6.36)  1.82 (0.53–6.63)  
<0.60 (severe) 1.31 (0.43–4.31)  0.58 (0.13–2.28)  
vWF Ratio (Ltx/Ag), % = 0.8) 2.16 (0.63–7.28) 0.21 1.30 (0.32–4.92) 0.70 
PFA collagenADP closure time (% ≥ 121) 2.01 (0.80-5.08) 0.14 1.18 (0.37–3.54) 0.77 
Severe loss of HMW multimers 3.60 (1.26–10.53) 0.017 3.60 (1.26–10.53) 0.017 

OR = odds ratio; CI = confidence interval. P-values result from logistic regression analysis. * Multivariable models are adjusted for severe loss of HMW multimers.

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Disclosures:

No relevant conflicts of interest to declare.

Topics:
aortic valve stenosis, hemorrhage, bleeding diathesis, aspirin, von willebrand factor multimer assay, warfarin, antigens, atrial fibrillation, echocardiography, epinephrine

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Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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