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Blood, Vol. 107, Issue 6, 2279-2285, March 15, 2006
Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease
Blood Kato et al.
107: 2279
Supplemental materials for: Kato et al
Files in this Data Supplement:
- Table S1. Associations with serum lactate dehydrogenase level in patients with sickle cell disease, with subgroup analysis according to hydroxyurea treatment (PDF, 113 KB) -
Compared to the group not on hydroxyurea, in patients who took hydroxyurea statistically significant correlations were not seen for LDH with haptoglobin, alkaline phosphatase, sVCAM-1 or sP-selectin. Somewhat weaker LDH correlations were found in the hydroxyurea group for reticulocyte count, and somewhat stronger LDH correlations for arginase and sE-selectin. Indicated in the table are the number of patients in each group (n) and the Spearman correlation coefficient (r). In general, hydroxyurea therapy did not significantly affect the correlations of LDH to the variables analyzed below.
- Figure S1. Interaction of gender and serum LDH level on nitric oxide resistance in 26 patients with sickle cell disease (JPG, 182 KB)
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The amount of increased forearm blood flow induced by brachial artery infusion of the nitric oxide donor sodium nitroprusside at 0.8, 1.6 and 3.2 µg/min was measured by venous occlusion strain gauge plethysmography. Males with sickle cell disease tend to demonstrate more resistance to nitric oxide than females, both in the group with (A) lower serum LDH levels (<339 IU/L) and (B) higher LDH levels (>339 IU/L)(p=0.03, ANOVA with repeated measures). (C) Although little difference was seen in vascular reactivity sodium nitroprusside among female patients with sickle cell disease, (D) males with high LDH levels (<339 IU/L) showed significantly more resistance to nitric oxide than males with low LDH levels (<339 IU/L)(p=0.03, ANOVA with repeated measures). Results are depicted as mean ± SEM.
- Figure S2. Relationship of serum LDH levels and history of vasculopathic complications (JPG, 137 KB)
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(A) The frequency distribution of 213 patients with sickle cell disease by LDH level in hundreds is indicated by the vertical bars. Dark bars indicate patients with hemoglobin SC disease (all HbSC patients had LDH values <500 IU/L), and white bars indicate all others. For comparison of the prevalence of selected sickle cell complications, data from all 213 patients are divided into three groups according to serum LDH levels. The low LDH is defined by LDH levels lower than one standard deviation below the overall mean (range 121 — 189 IU/L), mid LDH by overall mean LDH level plus or minus one standard deviation (range 190 — 511 IU/L) and high LDH higher than one standard deviation above the overall mean (range 512 — 1171 IU/L). The prevalence of pulmonary hypertension (B), leg ulcers (C), and in males, priapism (D) are also related to LDH group. Statistics are significant by chi square test for trend for all sickle cell patients for each of these three complications.
- Figure S3. Serum LDH levels remain associated with pulmonary hypertension and early mortality with exclusion of patients with HbSC disease (JPG, 115 KB)
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(A) Compared to patients without pulmonary hypertension (TRV<2.5 m/sec, n= 106), higher mean LDH values are seen with mild pulmonary hypertension TRV 2.5-2.9 m/sec, n=46) and moderate-severe pulmonary hypertension (TRV>2.9 m/sec, n=19)(p=0.0005, Kruskal-Wallis test). Error bars indicate SEM. (B) Kaplan-Meier plot of survival of patients with higher ≥ 315 IU/L) or lower (<315 IU/L) steady state LDH levels (p=0.02, logrank test).
- Figure S4. Interaction of serum LDH levels and hydroxyurea treatment (JPG, 282 KB)
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Increasing levels of steady state serum LDH are seen in patients with sickle cell disease (A) not taking hydroxyurea (for each group, n=88, 27, 15, respectively; p=0.003, Kruskal Wallis test) or (B) on hydroxyurea therapy (n=47, 20, 5; p=0.02). Bars indicate mean and SEM. (C) In patients not taking hydroxyurea, significantly worse survival is seen for those with steady state serum LDH levels <315 IU/L, compared to those with LDH ≥ 315 IU/L (p=0.04, logrank test). (D) This survival difference is narrower among patients taking hydroxyurea (p=0.2)
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