In hemolytic paroxysmal nocturnal hemoglobinuria (PNH) patients, hemoglobin levels are typically maintained by transfusions, without which severe anemia can occur. The terminal complement inhibitor eculizumab was previously shown to effectively control intravascular hemolysis and the need for transfusions in PNH patients. We now report on compassionate use of eculizumab in a severely anemic Jehovah’s Witness PNH patient. RF is a 61 year old Hispanic woman with a 10 year history of PNH and s/p nephrectomy. In Jan 2004 she was hospitalized for a severe hemolytic paroxysm with jaundice, weakness, lower abdominal pain, vomiting, hemoglobinuria, LDH of 15,000 IU/L, hemoglobin (Hgb) of 5–6 g/dL, and 40–50,000/mm3 platelets. Flow cytometry showed 41% RBC and 70% granulocyte PNH clone sizes. To her prednisone (80 mg qd), Procrit 40,000 U thrice per week and coumadin 2.5 mg qd were added. In Feb, she improved somewhat after high dose IVIG but remained icteric and had a bed-chair existence. In mid-March, her Hgb was 5.1 g/dL, LDH 5000 IU/L, and haptoglobin <26 mg/dL. Walking 5–10 feet resulted in shortness of breath and tachycardia. From Apr through Oct she generally stabilized with chronic fatigue, a bed-chair existence, LDH in the 3–4000’s IU/L, and 80–100,000 platelets/mm3; prednisone was now 20 mg qd. Her Hgb decreased from 5–7 g/dL through mid Jul, to 4–6 g/dL through Oct. She then worsened during a febrile illness: Hgb dropped to 3.6 g/dL. An investigator sponsored IND was granted by the FDA and the local Institutional Review Board approved the single patient open label trial; the patient was consented for use of eculizumab. Eculizumab therapy (600 mg/week for four weeks, then 900 mg on week 5 and every other week thereafter) was initiated on Nov 2 at which time she had severe hemoglobinuria, Hgb of 4.1 g/dL, LDH of 4326 IU/L, haptoglobin of <26 mg/dL and reticulocyte count of 250,000; she was bed-wheel chair bound, using supplemental O2. One week after the first dose, she noted clear urine, her Hgb rose almost 2 g to 5.4 g/dL, LDH dropped to 1019 IU/L, haptoglobin increased to 46 mg/dL, and she was no longer icteric. She was now able to walk short distances. At two weeks her LDH was 473 IU/L. Within a month was able to walk several blocks without difficulty. After 6 weeks of eculizumab therapy, her Hgb had risen to 9.3 g/dL and her LDH was in the normal range. Flow cytometry in Jan 2005 showed a 95% PNH RBC clone size. Her Procrit was converted to Aranesp. From Jan to early Mar her Hgb ranged from 8.1 to 9.1 g/dL with LDH remaining in the normal range; in Mar her Hgb dropped to 6.5 g/dL but without hemoglobinuria or intravascular hemolysis (LDH remained < 250 IU/L), and PNH RBC clone size was 90%. There was no evidence of GI blood loss. Though fatigued, she was still able to perform her normal daily routines. In Apr she was hospitalized with a Klebsiella UTI with a Hgb of 3.7 g/dL, but recovered to 6.6–8.0 g/dL after the resolution of the infection and initiation of IV iron supplementation. Currently, she is on Aranesp 300 mcg q2wk, prednisone 15 mg qd, oral and IV iron, folate, and 900 mg eculizumab q2wk. Her LDH is normal and Hgb is 8 g/dL. She has no hemoglobinuria, feels well, performs her daily routines and is “leading a normal life”. This case report demonstrates that intravascular hemolysis can cause severe anemia in PNH, and that eculizumab can rapidly improve Hgb through resolution of hemolysis and protection of the PNH RBC clone.

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