Sickle cell anemia is caused by substitution of normal hemoglobin (HbA) by hemoglobin S (HbS). When an individual is homozygous for the mutant gene, all the hemoglobin is of the abnormal, HbS, type, and even with normal saturation of oxygen, the disorder is fully expressed (i.e., sickling deformity of all red cells and hemolytic anemia).

In the heterozygote, only a proportion of the hemoglobin is HbS (the remainder being HbA), and therefore red cell sickling and possibly hemolysis occur only when there is exposure to lowered oxygen tension. This is referred to as the sickle cell trait to differentiate it from full-blown sickle cell anemia.

Pathological synopsis

 hepatic anomalies

• chronic lobular cholestasis
• aggregation of red cells in hepatic sinusoids (perivenular zone)
• thrombi in hepatic sinusoids
• hepatic sinusoidal congestion
• hepatic sinusoids packeds with sickled red cells
• hepatic sinusoidal erythrophagocytosis
• focal liver-cell necrosis
• lobular pericellular fibrosis
• hepatic granuloma
• secondary hepatic hemosiderosis
• hepatic vein thrombosis
• crescent-shaped red cells in sinusoids and Kupffer cells
• hemosiderin and ceroid pigment in Kupffer cells
• focal nodular hyperplasia related to local ischemia
• hepatic biloma

 pulmonary hypertension

Etiology

 sickle cell anemia is the result of mutations of the beta globin gene HBB (MIM.141900) in which the mutation causes sickling of hemoglobin rather than reduced amount of beta globin which causes beta-thalassemia.

The most common cause of sickle cell anemia is Hb S, with SS disease being most prevalent in Africans.

References

 Haque AK, Gokhale S, Rampy BA, Adegboyega P, Duarte A, Saldana MJ. Pulmonary hypertension in sickle cell hemoglobinopathy: a clinicopathologic study of 20 cases. Hum Pathol. 2002 Oct;33(10):1037-43. PMID: #12395378#