Hemoglobin

Anemia is defined as a reduction in the number of circulating red blood cells, the hemoglobin concentration, or the volume of packed red cells (hematocrit) in the blood. In the laboratory, anemia is identified when a patient’s hemoglobin (Hb)/hematocrit (Hct) values fall below the lower end of a normal range of values for age- and sex-matched subjects. The likelihood and severity of anemia is based on the patient’s deviation from normal values. Women in their childbearing years normally have a low hemoglobin value by about 1 gm/dL than men of the same age, likely due to hormonal influences. After menopause, the gender difference virtually disappears.

In end-stage renal disease (ESRD), severe impairment of QOL may occur in as many as 31% of patients.13 Several factors contribute to poor QOL in these patients, including low hemoglobin or Hct. Anemia in patients with cancer contributes to fatigue and may reduce patients’ ability to function normally, thus reducing QOL.12,14,15 The corollary to this is that the correction of anemia is associated with improved QOL. In fact, improved hemoglobin and Hct values are associated with better scores on QOL assessments in a variety of disease states, including CKD, inflammatory bowel disease,18 rheumatoid arthritis, cancer, and HIV/AIDS.

Correction of anemia has been associated with significant improvements in cardiovascular morbidity and mortality. In patients with heart failure, the correction of mild anemia to a hemoglobin level of 12.5 g/dL is associated with functional improvement, increased left ventricular ejection fraction, improved exercise capacity, and a decline in hospitalizations.

The key to erythropoietin production is the availability of oxygen, which is transported to tissues in a form bound to the hemoglobin molecule contained within the red cells.

low hemoglobin

The fundamental stimulus for erythropoietin production is oxygen availability to the kidney. Impaired oxygen delivery to the kidney is caused by a decrease in the number of circulating red cells (anemia), impaired oxygen loading of the red cell hemoglobin or, rarely, impaired flow of red cells to the kidney because of renal artery stenosis.

Erythropoietin not only is responsible for the day-to-day regulation of erythropoiesis, but it also responds dramatically to increase red cell production in the face of an inadequate oxygen supply, thereby meeting tissue oxygen needs. When the hemoglobin concentration falls below 10 g/dL to 12 g/dL, and if kidney function is normal, plasma erythropoietin levels rise logarithmically in inverse proportion to the level of hemoglobin. Under the stimulus of erythropoietin, red blood cell production can increase four- to fivefold within 1 to 2 weeks. However, this can occur only in the presence of adequate substrates, most particularly iron. In order for this feedback system to function properly, there must be normal renal production of erythropoietin, a functioning erythroid marrow, and an adequate supply of substrates for hemoglobin synthesis. A defect in any of these key components can lead to anemia.

Guidelines from the NKF-K/DOQI recommend that an anemia work-up be initiated when the hemoglobin/Hct value declines to approximately 80% of the mean value defined for healthy, normal subgroups, as anemia is likely to be present.6 For example, in adult men and postmenopausal women with CKD, an anemia work-up should be initiated at hemoglobin ≤12.5 g/dL (Hct <37%); in premenopausal women and prepubertal CKD patients, the corresponding levels are hemoglobin ≤11 g/dL (Hct <33%).

The NKF-K/DOQI guidelines recommend that hemoglobin levels in patients with ESRD be maintained between 11 g/dL and 12 g/dL. The same target hemoglobin range (11 g/dL to 12 g/dL) has come to apply also to patients with CKD who do not have ESRD, despite a lack of studies on the long-term effects of maintaining such a hemoglobin range in this population.

A consensus on the optimal hemoglobin levels at varying stages of CKD has not been reached, but the current Centers for Medicaid and Medicare Services policy restricts reimbursement for the initiation of anemia treatment to hemoglobin ≤10 g/dL, even though evidence indicates that adverse anemia-related sequelae occur at hemoglobin ≤11 g/dL.

Low Hemoglobin

Specifically, decreasing hemoglobin was associated with increasing risk of LVH. The first study showed a 6% increase in the risk of LVH for each 1 g/dL decrease in hemoglobin.11 The second, larger study showed an even greater risk: an increase of 32% in LVH risk for each 0.5-g/dL decrease in hemoglobin (P = 0.004).2 This study identified three risk factors that contributed to the development of LVH in patients with CKD: hemoglobin concentration, systolic blood pressure, and baseline left ventricular mass index. Similarly, in patients with end-stage renal disease (ESRD) undergoing dialysis, left ventricular end-diastolic volume and left ventricular mass both were found to increase with low hemoglobin levels. Decreasing hemoglobin levels have also been associated with a greater risk of the development of de novo or recurrent heart failure and increased mortality in this population.

The incidence and prevalence of anemia in CHF patients cannot be precisely determined from existing data, but retrospective studies suggest that low hemoglobin is common in this syndrome. Patients hospitalized with CHF have been reported to have a mean hemoglobin level of approximately 12 g/dL, and it has been demonstrated that the hemoglobin level decreases as the severity of heart failure progresses.16,17 For example, a retrospective analysis of 142 patients with CHF revealed that the prevalence of a hemoglobin level <12 g/dL increased with the severity of the disease, reaching a prevalence of 79.1% in patients with New York Heart Association (NYHA) functional classification IV.20 In addition, endogenous erythropoietin levels have been shown to increase with increasing severity of CHF.