To the editor:

Lactate dehydrogenase (LDH) is one of the enzymes of the glycolytic pathway that catalyzes the conversion of pyruvate to lactate with concurrent conversion of NADH to NAD+. It is a ubiquitous enzyme found in all tissues. Serum LDH exists in 5 separable isoenzymes numbered 1-5 according to their electrophoretic mobility.1  The distribution of the 5 isoenzymes is not uniform across body tissues. LDH1 and LDH2 are found primarily in RBCs and heart muscle; LDH3 is highest in the lungs; LDH4 is highest in the kidneys, placenta, and pancreas; and LDH5 is highest in skeletal muscle and liver.2  The routine determination of serum LDH includes all of its isoenzymes.

Along with reticulocyte count, indirect bilirubin level, and serum haptoglobin, LDH has been used as a marker of hemolysis. Serum LDH is usually elevated in sickle cell anemia in the steady state (SS).3  During painful vasoocclusive crises (VOCs), the LDH may increase further in some patients because of hyperhemolysis, as shown by RBC survival studies.4  However, the increase in LDH during VOCs is not always because of hemolysis. Neely et al found that the increase in serum LDH was not correlated with plasma Hb level, indicating that the source of LDH is not secondary to hemolysis but rather to tissue damage, most likely BM infarction.1 

A prospective descriptive cohort study in children showed that the LDH level increases significantly during VOCs compared with steady-state values and that there is a significant positive correlation between LDH levels and the severity of pain but not between LDH and Hb.5  Moreover, elevated LDH levels at admission for VOCs were associated with severe outcome, including death and worsening clinical state requiring transfer to the intensive care unit, in adult patients with sickle cell disease (SCD).6 

A retrospective review of 40 patients with SS between the ages of 5 and 19 years determined correlates of microalbuminuria and proteinuria including age, sex, height, body mass index, serum creatinine, Hb level, fetal Hb, LDH level, reticulocyte count, blood pressure, history of blood transfusion, history of hydroxyurea, and history of splenectomy. The prevalence of microalbuminuria and proteinuria among the patients studied was 15% and 5%, respectively. Univariate and multivariate analyses showed a significant correlation between LDH level and microalbuminuria and proteinuria.7  Kato et al reported an association between hemolysis and clinical subphenotypes of SCD, including pulmonary hypertension (PH), but the diagnosis of hemolysis was based on LDH levels.8  Conversely, Ataga et al reported a significant correlation between PH and microalbuminuria, but no correlation with parameters of hemolysis.9 

These data suggest that it is the LDH level that is most likely associated with PH and microalbuminuria irrespective of the severity of hemolysis. However, unless the association between hemolysis and PH and other complications of SCD is proven by RBC survival studies, this remains a hypothesis. Elevated levels of serum LDH are a marker of nonspecific tissue damage. The clinical picture and the level of LDH isoenzymes may provide clues to its source.

Authorship

Conflict-of-interest disclosure: The author declares no competing financial interests.

Correspondence: Samir K. Ballas, MD, FACP, Cardeza Foundation, 1020 Locust St, Philadelphia, PA 19107; e-mail: samir.ballas@jefferson.edu.

References

References
1
Neely
 
CL
Wajima
 
T
Kraus
 
AP
Diggs
 
LW
Barreras
 
L
Lactic acid dehydrogenase activity and plasma hemoglobin elevations in sickle cell disease.
Am J Clin Pathol
1969
, vol. 
52
 
2
(pg. 
167
-
169
)
2
Pincus
 
MR
Abraham
 
NZ
Carty
 
RP
McPherson
 
RA
Pincus
 
MR
Clinical enzymology.
Henry's Diagnosis and Management by Laboratory Methods
2011
22nd Ed
Philadelphia, PA
Elsevier Saunders
(pg. 
273
-
275
)
3
Karayalcin
 
G
Lanzkowsky
 
P
Kari
 
AB
Serum alpha-hydroxybutyrate dehydrogenase levels in children with sickle cell disease.
Am J Pediatr Hematol Oncol
1981
, vol. 
3
 
2
(pg. 
169
-
171
)
4
Ballas
 
SK
Marcolina
 
MJ
Hyperhemolysis during the evolution of uncomplicated acute painful episodes in patients with sickle cell anemia.
Transfusion
2006
, vol. 
46
 
1
(pg. 
105
-
110
)
5
Najim
 
OA
Hassan
 
MK
Lactate dehydrogenase and severity of pain in children with sickle cell disease.
Acta Haematol
2011
, vol. 
126
 
3
(pg. 
157
-
162
)
6
Stankovic Stojanovic
 
K
Steichen
 
O
Lefevre
 
G
, et al. 
High lactate dehydrogenase levels at admission for painful vaso-occlusive crisis is associated with severe outcome in adult SCD patients [published online ahead of print August 8, 2012].
Clin Biochem
 
7
Gurkan
 
S
Scarponi
 
KJ
Hotchkiss
 
H
Savage
 
B
Drachtman
 
R
Lactate dehydrogenase as a predictor of kidney involvement in patients with sickle cell anemia.
Pediatr Nephrol
2010
, vol. 
25
 
10
(pg. 
2123
-
2127
)
8
Kato
 
GJ
Gladwin
 
MT
Steinberg
 
MH
Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes.
Blood Rev
2007
, vol. 
21
 
1
(pg. 
37
-
47
)
9
Ataga
 
KI
Brittain
 
JE
Moore
 
D
, et al. 
Urinary albumin excretion is associated with pulmonary hypertension in sickle cell disease: potential role of soluble fms-like tyrosine kinase-1.
Eur J Haematol
2010
, vol. 
85
 
3
(pg. 
257
-
263
)