Case

A 73-year-old man with a prior diagnosis of chronic immune thrombocytopenic purpura (ITP) and intermittent steroid treatment presents to the emergency room with a two-day history of scleral icterus and a one-day history of dark-colored urine. Pertinent positives on his review of systems include lethargy, decreased urine output, decreased appetite, non-bilious non-bloody emesis, and shortness of breath. He denied chest pain, sick contacts, orthopnea, lower extremity swelling, abdominal pain, hemoptysis, vision changes, weakness, or diarrhea. He denied any aggravating or alleviating factors for his symptoms. His family history was negative for any bleeding disorders. He reported no alcohol, tobacco, or intravenous drug use.

On examination, the patient was alert and oriented, and his vitals included a temperature of 36.8 Cº, blood pressure 135/70 mm Hg, heart rate 116 bpm, and an oxygen saturation 83% on 10L nonrebreather mask. He had scleral icterus with no hepatomegaly, splenomegaly, or lymphadenopathy noted. Cardiopulmonary examination was notable for a faint S1, S2 but no adventitious breath sounds noted. Pertinent labs included a hemoglobin of 9 g/dL, hematocrit of 27%, Aspartate aminotransferase (AST) was 3017 U/L, alanine aminotransferase (ALT) 2712 U/L, blood urea nitrogen (BUN) 74 mg/dL, creatinine 3.6 mg/dL, total bilirubin 72.4 mg/dL, direct bilirubin 41.8 mg/dL, indirect bilirubin 30.6 mg/dL, mean corpuscular volume (MCV) 106 fL, Direct anti-globulin test was negative, and his peripheral smear revealed no schistocytes. Chest x-ray showed no acute cardiopulmonary abnormality. Computed tomography scan of the abdomen and pelvis and a right upper quadrant ultrasound were unrevealing.

The medicine team consulted gastroenterology and hematology due to the significant acute liver injury noted above and the concern for hemolytic anemia based on the high indirect bilirubin level. Additional lab work would later show lactate dehydrogenase 5,417 U/L, international normalized ratio of 1.7, acetaminophen level < 10, urine drug screen negative, positive HBsAg, positive HbcAb IgG, positive HbcAb IgM, and a non-reactive HBV surface antibody. HIV, Hep A total and IgM ab, HCV Ab, HDV Ab, anti-smooth muscle antibody, and CMV Ab were all negative, ferritin < 7500 ng/mL. G6PD level was 60 (low), consistent with G6PD hemolytic anemia triggered by acute HBV infection. The patient received entecavir for treatment of his acute HBV infection. He had clinical improvement in his respiratory status with antiviral treatment and normalization of his liver chemistry studies. With supportive care, the patient improved and he was discharged home with follow-up appointments to gastroenterology and hematology.

Discussion

Glucose-6-phosphate dehydrogenase (G6PD) deficiency affects upwards of 400 million people worldwide.1 Due to the X-linked nature of the disorder, men are affected more often than women. The defective G6PD enzyme can lead to premature breakdown of red blood cells in the setting of reactive oxygen species. Many patients with G6PD deficiency remain asymptomatic in the absence of triggers. When triggers occur, patients with G6PD deficiency often experience fever, icterus, dark urine, fatigue, tachypnea, and tachycardia. Some of the most common triggers include infections, antibiotics (such as trimethoprim-sulfamethoxazole, nitrofurantoin, ciprofloxacin, chloramphenicol), antimalarial medications, aspirin, quinidine, fava beans, and naphthalene, a chemical found in mothballs.

Infections, including viral hepatitis, may precipitate mild hemolytic anemia. However, an additional underlying disease process (such as G6PD) requires consideration when severe hemolytic anemia is present. Entecavir, a selective inhibitor of hepatitis B virus replication, has shown to be well tolerated and beneficial in the treatment of hepatitis B-associated acute liver failure and can be considered in G6PD deficient patients with severe hemolysis precipitated by acute HBV.2,3 This clinical case was unique in that this is the first reported case of severe hemolysis and renal failure precipitated by acute HBV in an undiagnosed G6PD deficient patient. SGIM members should always consider G6PD deficiency as a cause of unexplained hemolytic anemia, especially in patients with newly diagnosed hepatitis. Moreover, prompt consultation with gastroenterology and hematology can lead to better clinical outcomes.

References

  1. Richardson SR, O’Malley GF.Glucose-6-Phosphate Dehydro-genase Deficiency. 2022 Sep 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. PMID: 29262208.
  2. De Socio GV, Mercuri A, Di Candilo F, et al. Entecavir to treat severe acute hepatitis B. Scand J Infect Dis. 2009;41:703–704. doi:10.1080/00365540903062705.
  3. Jochum C, Gieseler RK, Gawlista I, et al. Hepatitis B-associated acute liver failure:immediate treatment with entecavir inhibits hepatitis Bvirus replication and potentially its sequelae. Digestion. 2009;80: 235–40. doi:10.1159/000236009.

Issue

Topic

Clinical Practice, SGIM

Author Descriptions

Dr. Hundman (chundman@uthsc.edu) is a third-year internal medicine-pediatrics resident at the University of Tennessee Health Science Center in Memphis (UTHSC), TN. Dr. Jackson (cjacks67@uthsc.edu) is an assistant dean of student affairs at the UTHSC College of Medicine, associate professor of medicine at The University of Tennessee Health Science Center (UTHSC), and associate program director at UTHSC Internal Medicine Residency, Memphis, TN.

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