Post-mortem molecular diagnosis of sickle cell disease from peripheral blood smear

Ferdane Kutlar, Dwight Mirmow, Leslie Holley, Jennifer L. Rumph, Abdullah Kutlar

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Currently in the U.S., the majority of patients with sickle cell disease (SCO) are diagnosed at birth through statewide newborn screening programs. Some patients, particularly those with less severe forms of SCO (SC,Sβ+ thalassemia) are diagnosed in adulthood either fortuitously or when they present with various complications. Here we report a case in which the diagnosis of SCO was established post-mortem. A 68 year-old African-American female was admitted to Aiken Regional Medical Center with chest, arm, and back pain. A dissecting aortic aneurysm was ruled out. Workup revealed severe cervical spinal stenosis. The patient's condition rapidly deteriorated with respiratory distress and mental status changes. Laboratory findings were significant for renal failure, elevated liver function tests, and markedly elevated LDH. Peripheral smear revealed a large number of NRBCs. Patient's cardiopulmonary status continued to deteriorate and she expired 3 days after transfer. Past medical history: hypertension, diabetes, hip replacement, and cholecystectomy. At autospy, major macroscopic findings included splenic infarction. Microscopic examination revealed sickled red cells in many organs. Fat emboli were seen diffusely in small vessels, most prominently in lungs, heart, kidney, and brain consistent with death from systemic fat embolization, most likely originating from bone marrow infarction. A Wright's stained peripheral blood smear was submitted to the Sickle Cell Center Laboratory at the Medical College of Georgia. DNA was extracted from the glass slide with a modification of the method of Schoh et al (Brit. J. Haematol., 92:140-142, 1996). -700 bp 5' globin fragment was amplified and the PCR product sequenced which revealed compound heterozygosity for the sickle mutation (GAG→GTG at codon 6) and the A→G mutation at nucleotide -29 in the TATAA box of the β-globin promoter thus establishing the diagnosis as Hb S β+ thalassemia. This case highlights two important points: First, so-called "mild" forms of SCD can cause significant morbidity and mortality. The demise of this patient, presumably with a "mild" course and no previous diagnosis of SCD, from multi-organ failure due to systemic fat embolization, serves to illustrate this point. Second, accurate molecular diagnosis can be established by relatively simple methods from a stained peripheral smear. Such studies should be undertaken as part of the post-mortem examination in cases where even a remote possibility of SCD is suspected.

Original languageEnglish (US)
Pages (from-to)19b
Issue number11 PART II
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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