The patient was a 33-year-old, well-conditioned male athlete who presented to a referring hospital with a 4-day history of fatigue, lethargy, fever, chills, jaundice, dark urine, and abdominal pain. His medical history included ocular toxoplasmosis in childhood. Several years before admission, he had become acutely anemic and was successfully treated with red blood cell (RBC) transfusions and immunosuppression. He was then lost to follow-up until the onset of this illness. He took vitamins and nutritional supplements, used smokeless tobacco, and denied alcohol or drug abuse. He had recently started a job working with refrigerated and frozen food.
At the referring hospital, he was found to be severely anemic and received 4 units of RBCs before transfer to our institution. Their initial gel antibody screen was positive, but the units were deemed compatible on a prewarmed cross-match. Among other findings at the referring hospital were an unremarkable chest radiograph and the following laboratory results:
• White blood cell count: 16,200 cells/µL
• Hemoglobin: 3.6 g/dL
• Hematocrit: 10.6%
• Mean corpuscular volume: 104.7 fL
• Platelet count: 340,000 cells/µL
• Reticulocyte count: 8.4% (0.5%-2.3%)
• Haptoglobin: 6 mg/dL (36-195)
• Lactate dehydrogenase (LDH): 943 U/L (91-180)
• Aspartate aminotransferase: 100 U/L (8-33)
• Alanine aminotransferase: 35 U/L (4-36)
• Total bilirubin: 7.0 mg/dL (0.1-1.0)
• Direct bilirubin: 0.9 mg/dL (< 0.3)
• Albumin: 3.4 g/dL (3.2-4.5)
• Total protein: 7.0 g/dL (6.0-7.8)
• Sodium: 134 mEq/L (136-142)
• Potassium: 4 mEq/L (3.8-5.0)
• Chlorine: 104 mEq/L (95-103)
• Carbon dioxide: 22 mmol/L (24-30)
• Glucose: 172 mg/dL (70-110)
• Creatinine: 1.4 mg/dL (0.6-1.2)
• Blood urea nitrogen: 39 mg/dL (8-23)
• Calcium: 8.4 mg/dL (9.2-11.0)
• Magnesium: 1.9 mg/dL (1.8-3.0)
• Serum iron: 267 µg/dL (60-150)
• Total iron-binding capacity: 291 µg/dL (250-400)
• Transferrin: 208 mg/dL (215-380)
• Sedimentation rate: 119 mm/h (10-12)
• Acute hepatitis panel: negative
Upon admission to our hospital, the patient's hemoglobin level was 4.6 g/dL, and all other laboratory results were consistent with those from the referring hospital. Blood and urine cultures were negative. Peripheral smears (Figure 1) demonstrated RBC agglutinates, microspherocytes, polychromasia, and nucleated RBCs.
Figure 1. Peripheral smears on successive days. A. RBC agglutinates (blue arrows) and polychromasia (reticulocytes) (green arrows) B. Microspherocytes (black arrows). C and D. Nucleated RBCs (red arrows). All photos originally 50×. Image courtesy of Sally Davis, MT(ASCP), UKMC Hematology Laboratory
Our blood bank received 2 specimens from this patient during his admission. The results of both were similar to his previous laboratory results, which had demonstrated an autoantibody of wide thermal amplitude. The direct antiglobulin test (DAT) results were inconclusive on the first specimen because of a positive saline control, but the second specimen had an appropriately negative saline control and showed reactivity with anti-IgG and anti-C3b/-C3d.
A short cold panel including a 3-cell antibody screen, autologous control, and type O cord cells was reactive at immediate spin, 15-30 minute incubation at room temperature, and 15-30 minute incubation at 4°C. The patient's antibody screen was negative using the prewarmed technique, and of interest, in view of their brief in vivo survival, all units tested were compatible by prewarmed cross-match. Although we did not directly demonstrate the presence of IgM antibodies, given the broad range of thermal activity, the DAT results, the agglutinates, and the mixed evidence of intravascular and extravascular hemolysis, the patient most likely had a mix of IgG and IgM autoantibodies.
Because of worsening symptoms of inadequate oxygen delivery, the patient received more than 20 units of RBCs throughout his hospitalization, with no sustained increase in his hemoglobin level. Despite intensive transfusion; further laboratory evaluation; and treatment, including plasmapheresis and immunosuppression, he experienced a relentless downhill course. His mental status deteriorated daily, from lethargy through disorientation to stupor and finally coma. He began to show additional evidence of multiple system organ failure.
The patient was placed on mechanical ventilation with general anesthesia and paralysis to reduce peripheral oxygen demand. The clinical team obtained a US Food and Drug Administration (FDA) compassionate use exemption to use a hemoglobin-based oxygen carrier (HBOC) acquired from a manufacturer. No HBOC is currently approved for routine use. Despite this, the patient died of complications of intractable severe anemia following 1 week of hospitalization. The family declined autopsy.
Medscape Pathology © 2013
Cite this: Duncan C. MacIvor, Jennifer Phillips. A Fatal Case of Intractable Anemia - Medscape - Sep 25, 2013.