A Case of PNH with Abdominal Pain, AKI and Hemolytic Anemia

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disorder affecting 1 to 10 people per million. With an associated 10-year mortality, PNH is a life-threatening disorder where the complement system of the body's innate immune system prematurely lyses red blood cells. It can be characterized by a number of clinical features, the most common being hemolytic anemia, pancytopenia, and thrombosis. 45 year old African American male presented with a chief complaint of shortness of breath x 2-3 days. Reports associated dry, nonproductive cough, congestion, myalgias onset one week prior. He was taking two tablets of Advil daily since symptom onset. He has a past medical history of right sided BKA after motor vehicle accident and currently uses a prosthetic leg. No other significant past medical history noted. On ED admission, the patient was febrile to 103.2F, tachycardic to 110 beats per minute, tachypneic to 26 breaths per minute, and normotensive to 128/64. On physical exam, there was conjunctival pallor, no scleral icterus, and right BKA. The remainder of the physical exam was unremarkable. Labs on admission were notable for anemia (Hgb 3.9, baseline of 9.2, 2 years prior), AKI (Cr 7.3, baseline of 0.9), elevated LDH 2336, and low Haptoglobin <10. Platelet count WNL throughout admission however there was a drop from 242 to 180 between Day 1 and 2 of admission. Peripheral smear did not show schistocytes however ADAMTS13 sent per heme/onc consult. Anemia improved to Hgb 7.6 on Day 3 of admission status post 4 units packed red blood cell transfusion. Workup for hemolytic anemia with AKI was pursued: Direct Coombs test negative, PNH screen sent. SPEP and UPEP unremarkable. On Day 6 of admission, flow cytometry showed evidence of PNH clone upon analysis of RBCs, granulocytes, and monocytes. AKI was attributed to ATN s/t heme-pigment deposition vs NSAID use and Cr trended down to 2.9 prior to discharge. On day 7 of admission, patient developed severe abdominal pain, not associated with fevers, chills, nausea, vomiting, or diarrhea. Pain moderately improved with Norco, ultrasound imaging was negative, and unable to CTA given renal function. Pt was started empirically on therapeutic anticoagulation with Lovenox, as the literature reports a high incidence of venous and/or arterial thrombosis in PNH w/granulocyte count >50% (89.8% in this patient). Patient was discharged the next day with close outpatient hematology follow-up with plan to start eculizumab. Given patient's presentation of fever, symptomatic anemia, and AKI the differential diagnosis included: hemoglobinopathies, red cell membrane disorders, PNH, DIC, TTP, HUS, AIHA, and infections such as malaria or HIV. It was difficult to identify PNH as the cause in this patient on ED presentation as there was no reported urine discoloration. Though classified as an acquired disorder through mutation of a gene on the X chromosome, it occurs in equal distribution among men and women. PNH specifically occurs through the mutation of a gene involved in the synthesis of glycosylphosphatidylinositol (GPI), an anchor protein for complement regulatory proteins that prevent complement-induced hemolysis of red blood cells. The resulting GPI deficiency leads to the unregulated formation of complement attack complexes that damage the cell membrane causing them to lyse. This intravascular hemolysis is seen as decreased levels of Hgb and hemoglobinuria that leads to elevated levels of LDH as seen with this patient. The degree of hemolysis and PNH clone size can increase risk of thrombosis, the leading cause of death in patients with PNH. Strong indicators for the start of PNH therapy are severe anemia, thrombosis, renal dysfunction, and dyspnea. The typical management of PNH in patients with thrombosis is shown in this case as the patient is put on therapeutic anticoagulation and plans for eculizumab, a monoclonal antibody that is a complement inhibitor used to prevent hemolysis. This PNH therapy will likely be administered lifelong and decrease the need for RBC transfusions as well as decrease thromboembolic rate. If the patient is unresponsive to eculizumab they become a strong candidate for allogeneic stem transplantation. This patient meets the popular standard for starting primary prophylaxis for management of thrombosis with a PNH clone size >50%.