Medullary Microvascular Thrombosis and Injury in Sickle Hemoglobin C Disease

Abstract

Sickle cell nephropathy is a common complication in patients with sickle cell hemoglobinopathies. In these disorders, polymerization of mutated hemoglobin S results in deformation of red blood cells, which can cause endothelial cell injury in the kidney that may lead to thrombus formation when severe or manifest by multilayering of the basement membranes (glomerular and/or peritubular capillaries) in milder forms of injury. As the injury progresses, the subsequent ischemia, tubular dysfunction, and glomerular scarring can result in CKD or ESRD. Sickle cell nephropathy can occur in patients with homozygous hemoglobin SS or heterozygous hemoglobin S (hemoglobin SC, hemoglobin S/β(0)-thalassemia, and hemoglobin S/β(+)-thalassemia). Clinical manifestations resulting from hemoglobin S polymerization are often milder in patients with heterozygous hemoglobin S. These patients may not present with clinically apparent acute sickle cell crises, but these milder forms can provide a unique view of the kidney injury in sickle cell disease. Here, we report a patient with hemoglobin SC disease who showed peritubular capillary and vasa recta thrombi and capillary basement membrane alterations primarily involving the renal medulla. This patient highlights the vascular occlusion and endothelial cell injury in the medulla that contribute to sickle cell nephropathy.

Keywords: endothelial cells; peritubular capillary; renal pathology; thrombosis.

Figure 1.

Medullary thrombi with loss of PTCs. PTCs (arrowheads) in the medulla show thrombi with fragmentation of the RBCs, and there is also a notable paucity of PTCs (hematoxylin and eosin). Original magnification, ×400.

Figure 2.

Vasa recta thrombi. Vasa recta (arrowheads) contain several thrombi with an absence and distortion of the normal distribution of vasa recta in this region in the medulla (hematoxylin and eosin). Original magnification, ×400.

Figure 3.

Polymerized Hb in irregularly shaped RBCs. An RBC in a PTC of the medulla is packed full of cytoplasmic fibrils that are indicative of polymerized Hb. Original magnification, ×7900.

Figure 4.

Multilayering of PTC basement membranes in the medulla. This PTC in the medulla shows multilayering of the basement membranes, which indicates repetitive endothelial cell injury. Scale bar, 1 μm.