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Background: Immune hemolytic anemia has been associated with the administration of various antibiotics, including cephalosporins. Presented here is a patient who developed severe acute hemolysis while receiving ceftizoxime (Ceftizox, Fujisawa USA), a third-generation cephalosporin. This is the fourth reported case of hemolysis in association with ceftizoxime. In the previous cases, ceftizoxime was shown to induce hemolysis by the immune-complex mechanism. However, in one of those reports, the concentration of drug used to treat the target RBCs in vitro may not have been optimal.Case Report: The patient's antemortem blood samples were analyzed retrospectively for drug-dependent antibodies by the drug-adsorption and immune-complex methods. Antibody class and titer were evaluated.Results: The patient's sample agglutinated RBCs coated with ceftizoxime as well as uncoated RBCs in the presence of ceftizoxime. The antibodies to ceftizoxime were IgM and IgG.Conclusion: This is the first report on both the immune-complex and drug-adsorption mechanisms of ceftizoxime-induced hemolysis. The differential diagnosis of a falling Hct in a patient receiving antibiotics should include drug-related hemolysis; once this diagnosis is considered, management includes the appropriate serologic workup, immediate cessation of the implicated drugs, and possible transfusion support. [ABSTRACT FROM AUTHOR]

In men with classical Fabry disease (alpha-galactosidase A [alpha-Gal A] deficiency), kidney failure occurs as early as the second decade of life. In contrast, men with the mild "cardiac variant" have late-onset cardiac involvement and proteinuria but usually do not have renal failure. To investigate the nature of renal involvement in the cardiac variant of Fabry disease, the renal function and morphology were assessed in a 75-year-old affected man. He had mild congestive heart failure, a reduced left ventricular ejection fraction, and hypercholesterolemia but lacked the classical Fabry disease manifestations, including angiokeratoma, acroparesthesias, corneal and lenticular opacities, and hypohidrosis. At age 75 years, he had significant proteinuria, and mildly decreased renal function (serum creatinine, 1.8 mg/dL [159 micromol/L]), presumably secondary to hypertensive arteriosclerosis. He had about 4% residual alpha-Gal A activity in leukocytes, and mutation analysis identified the N215S missense mutation, the common lesion in cardiac variants. Histologic and ultrastructural studies of kidney tissue showed that lysosomal glycosphingolipid deposition was extensive in podocytes, rare in tubular epithelial cells, and absent in mesangial, interstitial, and vascular endothelial and smooth muscle cells. This cardiac variant serves as an "experiment of nature" showing that the residual alpha-Gal A activity precludes glycosphingolipid deposition in the renal endothelial and other cells that lead to early renal failure in classically affected men, whereas marked podocyte accumulation is associated with proteinuria and possibly late-onset renal dysfunction. These findings have important implications for the renal effectiveness of enzyme replacement therapy in classically affected patients and for the aggressive treatment of proteinuria in Fabry disease.

Platelet accumulation in glomerular capillaries (GC) and peritubular capillaries (PC) has pathogenetic importance in antibody-mediated hyperacute renal allograft rejection. CD61 is expressed constitutively by platelets, by platelet microparticles arising from platelet activation, and is readily detectable by immunohistochemistry. This study examined the immunohistochemical localization of CD61 in acute humoral rejection (AHR) of renal allografts to explore the relationship of platelet accumulation to antibody-mediated rejection. Two observers graded the extent of CD61 staining in PC and GC from 0 (none) to 2+ (>50%) in 15 renal allograft biopsy specimens with AHR and compared these with tissues from allografts with acute cellular rejection (ACR) (n = 23); acute calcineurin inhibitor toxicity (ACIT) (n = 21) with thrombotic microangiopathy (TMA) (n = 11) and tubular toxicity only (n = 10); acute tubular necrosis (ATN) (n = 16); acute renal vein thrombosis (RVT) (n = 4); and histologically unremarkable native kidneys (n = 26). Selected tissues were examined by electron microscopy and stained for CD34 by immunohistochemistry. Histologically unremarkable native kidney tissues had CD61 only in scattered small lumenal granules in GC and PC. Mural and occlusive lumenal CD61 deposits (>0.5+) were observed in 13 of 13 (100%) allograft tissues with GC thrombi due to AHR (1) and ACIT TMA (9) and RVT (3). Twenty-seven of 66 allografts (40.9%) without glomerular thrombi had >0.5+ GC CD61 in AHR (60%), ACR (26%), tubular ACIT (60%), and ATN (44%). More than trace (>0.5+) PC mural and lumenal CD61 deposits were seen only in AHR (53.3%) and ACR (30%). PC CD61 correlated with interstitial hemorrhage (r = 0.64), neutrophilic capillaritis (r = 0.47), and interstitial inflammation (r = 0.47) (P <0.001 for each). PC CD61 was observed in 11 of 11 foci of necrosis due to AHR, RVT, and ischemia. In AHR, capillaries with CD61 deposits had few platelets, numerous microvesicles and membrane fragments, severe endothelial injury seen on electron microscopy, and reduced capillary CD34 expression. CD61 detection by immunohistochemistry revealed products of capillary platelet activation in allograft biopsy specimens without light microscopic thrombi. Observations in this study suggest that intracapillary platelet activation occurs in response to graft capillary injury from many causes and may not be specific for antibody-mediated rejection.