DELAYED HEMOLYTIC TRANSFUSION REACTION DUE TO JKB ANTIBODIES PRESENTED WITH ASSOCIATION OF ACUTE KIDNEY INJURY THAT REQUIRED RENAL REPLACEMENT THERAPY.

Case Presentation: 73 YO female with PMH of dementia, upper GI bleed with multiple transfusions who presented 1-week post discharge for GI bleed (where she was transfused with 4 units of RBC – hgb was 9 g/dl on discharge) with fatigue, diarrhea and dark colored urine. Patient reported possible bloody diarrhea. Patient’s vital signs were stable and physical exam was prominent for pale mucous membranes, scleral icterus, and B/L lower abdominal tenderness. – Labs were remarkable for Hgb 6.5 g/dl, MCV 97 FL, platelet 93 K, BUN 48 and Cr 4.3 mg/dl (was 12/0.78 subsequently upon discharge), LDH 6450 u/l, total bilirubin 6.3 mg/dl, direct bilirubin 3 mg/dl, and normal CPK. – Blood smear showed normochromic RBCs, occasional schistocytes, anisocytosis, poikilocytosis and many acanthocytes. – Urinalysis showed large blood with no RBC’s seen. – CT abd/pelvis revealed no hydronephrosis or obstruction. Patient received 1 unit of pRBC in the ER and hgb dropped to 5.8 g/dl post transfusion with no sign of active bleeding. Also, the clinical presentation was consistent with DHTR with hemoglobinuria and AKI, but because of occasional fragmentation and AMS with patient reported possible bloody diarrhea, we could not rule out TTP. Patient was started initially on plasmapheresis, steroids with vigorous hydration and blood transfusion avoidance; but pheresis was held later with normal ADAMTS 13. Later blood work was found to be positive for Anti C, Anti E, Kell and Anti JKB Ab and c, e JkA, LeA, N, S, s Ag with most likely hemolysis due to Anti JKB Ab. Patient was diagnosed with DHTR and was started on low dose Epogen three times weekly with monitoring of the hemolysis markers. Further lab workup showed a low haptoglobin, positive indirect coombs test, negative direct coombs, normal C3 & C4 levels, ADAMTS-13 activity assay 73%, and a negative screening test for paroxysmal nocturnal hemoglobinuria. HIV, HBV and HCV were all negative. BUN/Cr continued to rise 89/8.5 mg/dl with no signs of fluid overload, but patient was started on hemodialysis later for uremic encephalopathy. EGD and colonoscopy were done and showed mild esophagitis, Schatzki ring, gastritis, healed duodenal ulcers and pan diverticulosis throughout the colon.

Discussion: In this case, the patient presented with symptoms consistent with DHTR with hemoglobinuria and AKI. However, the AKI was severe and with the presence of diarrhea; HUS was high among the differential.Because of the occasional fragmentation on blood smear and AMS in association with bloody diarrhea, we could not rule out TTP. Patient was initially started on plasmapheresis, steroids, vigorous hydration, and blood transfusion avoidance; however, pheresis was held later after ADAMTS 13 was found to be normal. Later prednisone was tapered, and patient was discharged home with outpatient dialysis.Current management of DHTR is empirical and includes supportive care, optimization of erythropoiesis, immunosuppression (steroids, intravenous immunoglobulins and rituximab) and minimizing further RBC transfusions.

Conclusions: DHTRs occur more than 24 hours and most commonly 1-2 weeks after a blood transfusion. DHTRs are determined by the presence of prior alloimmunization typically secondary to antibodies associated with the Rh and Kidd systems. It is characterized by extravascular hemolysis that is often clinically silent; and less commonly, with intravascular hemolysis. Early diagnosis of DHTR is essential to avoid additional blood transfusions which may exacerbate hemolysis and cause further drops in Hgb levels.