Sickle Cell Disease (SCD)


Peripheral Blood Smear

The normal morphology of red blood cells (RBCs) is a biconcave disc-shape that measures between 7-8 µm in diameter. RBCs have a central pallor that spans approximately one-third of the cells diameter and lack nuclei. Intra-cytoplasmic inclusions are not observed in the normal RBC.1 In SCD, RBCs appear abnormally sickle-shaped due to the precipitation of abnormal hemoglobin S. Other abnormalities seen in the peripheral blood smear of patients with SCD include Howell-Jolly bodies, nucleated red blood cells, and target cells. 

Howell-Jolley bodies are pathognomonic for splenic dysfunction, a common state in SCD. One of the roles of the spleen under normal circumstances is to remove the nuclear remnants from RBC precursors. If the remnants persist, as seen in conditions that course with splenic dysfunction such as SCD, they appear as cytoplasmic inclusion bodies on peripheral blood smear. The nuclear fragments appear as strongly basophilic dots inside the eosinophilic RBC that resemble an RBC with a superimposed platelet. They may also be seen in other conditions such as alcoholism and systemic lupus erythematosus.2  

Target cells are bell-shaped and have a centrally located disk of hemoglobin that appears dark which is surrounded by an area of pallor. The outer rim of hemoglobin adjacent to the area of pallor is also darker giving the cell the appearance of a target. They exist when RBC contain excessive amount of cell membrane (as seen in SCD) or cholesterol (as seen in lecithin cholesterol acyl transferase deficiency.3,4 They are observed in the following circumstances: thalassemia, hepatic disease with jaundice, hemoglobin disorders, and the postsplenectomy state.3

The Spleen

Grossly, the spleen of SCD patients is usually larger in weight. On microscopic examination there are distinct differences to both the red and white pulp of SCD spleens compared to healthy spleens. Histological examination of the sleep of 7 patients who underwent total splenectomy due to SCD reveals that the white pulp is devoid of well-formed marginal zones and possess only scant lymphoid follicles. Gamna-Gandy bodies (sclero-siderotic nodules) were observed in the red pulp of all patients along with increased reticulin deposition, and a reduction in the density of CD8+ sinusoids. There was also a significant increase of SMA-positive myoid cells compared to controls. The relationship between high numbers of SMA-positive myeloid cells and sclerotic changes (marked by Gamna-Gandy) bodies suggests that these cells may play a role in the deposition of reticulin fibers and resultant fibrosis possibly due to chronic micro-vascular accidents within the red pulp.5 

The Kidneys

Progressive kidney disease is a common complication of SCD which ranges from microalbuminuria to severe renal failure. A multicenter retrospective analysis years reported the renal biopsy results 36 patients ages 4-19 years.  The most common finding was hemosiderin deposits, interstitial fibrosis with tubular atrophy (IFTA), and mesangial hypercellularity. Additionally, glomerular hypertrophy is observed in 58% of patients, focal segmental glomerulosclerosis (FSGS) was documented in 30%, and 54% of these patients also had global sclerosis in addition to FSGS. Less common findings include membranoproliferative glomerulonephritis (14%), and crescents. On electron microscopy, podocyte effacement was present in 55%, glomerular basement membrane thickening was found in 58%, mesangial deposits in 27%, and subendothelial deposits in 15%. Positive immunofluorescence was present in 65% of biopsies, but was non-specific, with staining for IgG, IgM, IgA, C3, C1q and C4.6 

References

1. Adewoyin A, Nwogoh B. PERIPHERAL BLOOD FILM – A REVIEW. Ann Ib Postgrad Med. 2014;12(2):71-79.

2. Scafidi JM, Gupta V. Histology, Howell Jolly Bodies. In: StatPearls. StatPearls Publishing; 2021. Accessed November 30, 2021. http://www.ncbi.nlm.nih.gov/books/NBK557489/

3. Lynch EC. Peripheral Blood Smear. In: Walker HK, Hall WD, Hurst JW, eds. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Butterworths; 1990. Accessed November 30, 2021. http://www.ncbi.nlm.nih.gov/books/NBK263/

4. Blood smear Information | Mount Sinai – New York. Mount Sinai Health System. Accessed November 30, 2021. https://www.mountsinai.org/health-library/tests/blood-smear

5. Pizzi M, Fuligni F, Santoro L, et al. Spleen histology in children with sickle cell disease and hereditary spherocytosis: hints on the disease pathophysiology. Hum Pathol. 2017;60:95-103. doi:10.1016/j.humpath.2016.09.028

6. Zahr RS, Yee ME, Weaver J, et al. Kidney biopsy findings in children with sickle cell disease: a Midwest Pediatric Nephrology Consortium study. Pediatr Nephrol. 2019;34(8):1435-1445. doi:10.1007/s00467-019-04237-3

Reviewed by Debjyoti Talukdar, MD, on 12/3/2021.

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