Assessing Anemia Secondary to Hemolysis in Hemodialysis Patients

Nephrology Nursing Journal, April, 2001 by Jamie Behrens

Case Study of the Anemic Patient

Nephrology nurses who assess and manage patients affected by the anemia of end-stage renal disease (ESRD) must be aware of the wide array of etiologies that can contribute to hyporesponse to Epoetin alfa. Many conditions can affect red blood cell (RBC) production, including: (a) chronic blood loss, (b) inappropriate Epoetin alfa dose, (c) iron deficiency, (d) infection, (e) inflammation, (f) secondary hyperparathyroidism, (g) autoimmune or neoplastic diseases, (h) aluminum toxicity, and (i) vitamin deficiency. All of these etiologies are well-defined contributors to decreased hemoglobin (Hb) levels. When left uncontrolled, these conditions can jeopardize the goal of maintaining Hb levels in the target range of 11 to 12 g/dL recommended by the National Kidney Foundation's Dialysis Outcome Quality Initiative (NKF-DOQI) (National Kidney Foundation, 1997).

Another etiology that can result in hyporesponse to Epoetin alfa is hemolysis--the lysing of RBCs which results in the liberation of Hb and a decline in red cell indices. Nephrology clinicians are very aware of severe or overt hemolysis, which typically manifests as thin blood the color of "cherry pop" in the extracorporeal circuit. Occult or silent hemolysis, in which the destruction of RBCs is not severe enough to result in a visible change in the appearance of blood, is more difficult to discern. This article explores the causative factors that can lead to hemolysis, with an emphasis on laboratory and clinical assessment techniques that can be used to minimize the potential impact of hemolysis.

Etiology of Hemolysis in Patients with ESRD

Physiological changes that occur during ESRD may predispose patients to hemolysis. Several studies have demonstrated an impaired antioxidant response that makes hemodialysis patients more susceptible to oxidative stress and chronic hemolysis. This enhanced sensitivity may modify RBC membranes, leading to a reduction in flexibility that decreases the ability of RBCs to pass through splenic macrophages (Taccone Gallucci, et al., 1999; Weinstein, et al., 2000; Zachee, et al, 1993;). This lack of flexibility appears to encourage earlier destruction of RBCs and may contribute to the comparatively shorter RBC lifespan that has been observed in dialysis patients (Taccone Gallucci, et al, 1999).

Compounding this predisposition to RBC fragility is the fact that dialysis patients are exposed to a wide variety of etiologies that can precipitate hemolysis. These factors can be divided into five general categories: (a) water-borne toxins in the dialysate, (b) patient-specific factors, (c) medications, (d) hypotonic or hypertonic dialysis, and (e) faulty dialysis equipment or procedures.

Water-borne toxins in the dialysate: Hemolysis in the dialysis population is most often caused by metals or other organic and inorganic substances that contaminate the water used for dialysate. One of the most common contaminants is chloramine, which is frequently used to purify water. This oxidating chemical can destroy the membranes of living cells, including RBCs. Because chloramine can diffuse across dialysis membranes, the Association for the Advancement of Medical Instrumentation (AAMI) guidelines recommend that dialysis water contain no more than 0.1 mg/L of chloramine, with total chlorine levels not to exceed 0.5 mg/L (Hudson & Arslanian, 1992). The presence of chloramine can be verified through on-site water analysis and by checking with local city authorities to determine which substances are routinely added to the water supply. Chloramine can be proactively removed by deionizers, charcoal filtration, vacuum treatment, or boiling (Kjellstrand, 1993).

Several other water-borne substances can also cause hemolysis as well. Zinc from galvanized piping has been shown to cause acute hemolysis in both home and incenter patients (Kjellstrand, 1993). Acidic water can leach copper from plumbing pipes, causing nausea, headache, chills, pancreatitis, metabolic acidosis, liver damage, and fatal hemolysis. Further, water contamination from nitrates and nitrites has been described, especially in home patients who use well water that has been contaminated by in-ground urine from domestic animals (Hudson & Arslanian, 1992; Kjellstrand, 1993).

Patient-specific factors: Hypersplenism, microangiopathic vasculitis, parvovirus, and certain infections can all contribute to hemolysis in particular patients. Hypersplenism is a rare cause of hemolysis in dialysis patients, with the diagnosis requiring concomitant hemolytic anemia, thrombocytopenia, leukopenia, splenomegaly, and a positive [sup.51]CR-RBC test (indicating increased sequestration of red cells in the spleen). If all five of these factors are present, a splenectomy is typically performed (Kjellstrand, 1993).

Microangiopathic vasculitis is diagnosed on a peripheral blood smear showing helmet cells, fragmented RBCs, and evidence of schistocytes (irregularly shaped RBCs). It has been described in a variety of disorders, including systemic lupus erythematosus, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and rejection of a kidney transplant. Infections such as hepatitis and pneumonia can cause acute hemolysis and contribute to a decrease in RBC count (Kjellstrand, 1993). There have also been case reports of hemolysis occurring with bacterial infections. In these cases, hemolysis is apparently caused by several mechanisms, including direct invasion of RBCs by bacteria or their toxins, induction of antibodies or cold agglutinins that act against RBC-wall antigens, and alteration of RBC-wall antigens to render them immunogenic (Ifudu, & Valcourt, 1999). Treatment of patient-specific contributors should be aimed at correcting or eliminating the underlying cause of hemolysis.