Definition

Hemolytic uremic syndrome (HUS) is a clinical triad of acute renal failure (serum creatinine > 1.6 mg/dl), microangiopathic hemolytic anemia (hematocrit < 25%), and thrombocytopenia (platelet count < 100,000 cells/ml) (Lesesne et al., 1989).

Pathophysiology

The most common chemotherapy agent to cause HUS is mitomycin-C, which can cause a thrombotic microangiopathic process with endothelial cell injury and the development of platelet aggregatory immune complexes (Zakarija & Bennett, 2005). Mitomycin-C also can cause direct damage to the kidney vascular endothelial cells and inhibit prostacyclin production, resulting in promoted platelet aggregation and microthrombi formation, predominately in the kidney vasculature, leading to renal failure (Wu et al., 1997).

Risk Factors

Agents implicated in the pathogenesis of HUS include mitomycin-C, cyclosporine, quinine, ticlopidine, bleomycin, cisplatin, fluorouracil, gemcitabine, alpha interferon, and fludarabine (Muller et al., 2005; Pisoni, Ruggenenti, & Remuzzi, 2001; Wu et al., 1997). A total cumulative dose of 40-60 mg of mitomycin-C increases the risk of HUS. The syndrome usually occurs four to eight weeks after completion of therapy.

Clinical Findings

The most common presenting symptoms of HUS include anorexia, weight gain, weakness, fatigue, jaundice, dyspnea, and neurologic issues. Patients may experience anxiety or feelings of impending doom. A dry cough may be present in patients who present with concurrent pulmonary edema.

Differential Diagnosis

Initially, HUS may appear to be from severe anemia or thrombocytopenia. Hemolytic anemia or disseminated intravascular coagulation can present with similar clinical features. Acute renal failure from dehydration may be suspected. Laboratory values will confirm HUS.

Treatment

Blood product transfusions often will cause an exacerbation of HUS and induce noncardiogenic pulmonary edema within a few hours of transfusion. Erythropoietin-stimulating agents have been found to be useful in restoring red blood cells without the use of transfusions (Catalano, Gianesini, & Fabbian, 2002).

Plasma therapy every day to every other day, according to the patient's hematologic parameters, can remove circulating immune complexes. The procedure usually normalizes the blood count but rarely reverses renal insufficiency. Renal dialysis is eventually necessary to reduce serum creatinine.

Immunoperfusion has been a promising treatment. Plasmapheresis is performed with the reinfusion of plasma over a column of staphylococcal protein-A. After the patient undergoes immunoabsorption, plasma is reinfused. Splenectomy, bilateral nephrectomy, and kidney transplantation may be options for patients with severe renal impairment.

Nursing Implications

Strict monitoring of patients' renal function and complete blood count for anemia and thrombocytopenia during mitomycin-C administration is important. Urinalysis is useful in detecting hematuria and proteinuria. Patients must continue to be monitored for several months following completion of therapy because HUS may occur at any time. Nurses should monitor and document the cumulative dose of mitomycin-C and consideration should be given to hold further mitomycin-C when the cumulative dose of 40-60 mg is reached.

Nurses should monitor patients for fever, chills, nausea, and vomiting during plasmapheresis and provide supportive care as needed. Thrombocytopenic precautions should be instituted when platelets are less than 50,000 cells/ml to minimize the occurrence of bleeding. Educating patients and families about interventions that can minimize the effects of anemia may be helpful to reduce anemia-induced symptoms.

References

Catalano, C., Gianesini, C., & Fabbian, F. (2002). Erythropoietin is beneficial in mitomycin-induced hemolytic-uremic syndrome. Nephron, 91(2), 324-326.

Lesesne, J.B., Rothschild, N., Erickson, B., Korec, S., Sisk, R., Keller, J., et al. (1989). Cancer-associated hemolytic-uremic syndrome: Analysis of 85 cases from a national registry. Journal of Clinical Oncology, 7(6), 781-789.

Muller, S., Schutt, P., Bojko, P., Nowrousian, M.R., Hense, J., Seeber, S., et al. (2005). Hemolytic uremic syndrome following prolonged gemcitabine therapy: A report of four cases from a single institution. Annals of Hematology, 84(9), 621-622.

Pisoni, R., Ruggenenti, P., & Remuzzi, G. (2001). Drug-induced thrombotic microangiopathy. Drug Safety, 24(7), 491-501.

Wu, D.C., Liu, J.M., Chen, Y.M., Yang, S., Liu, S.M., Chen, L.T., et al. (1997). Mitomycin-C induced hemolytic uremic syndrome: A case report and literature review. Japanese Journal of Clinical Oncology, 27(2), 115-118.

Zakarija, A., & Bennett, C. (2005). Drug-induced thrombotic microangiopathy. Seminars in Thrombosis and Hemostasis, 31(5), 681-690.

Dawn Camp-Sorrell, MSN, FNP, AOCN[R]