Paroxysmal nocturnal hemoglobinuria

Aplastic anemia is an acquired or inherited hematopoietic stem cell disorder that produces pancytopenia with a hypocellular, fatty bone marrow and no dysplasia, blasts, or fibrosis. Diagnosis rests on marrow biopsy showing less than 25% cellularity with severity graded by the Camitta criteria, and treatment is allogeneic stem cell transplantation for young fit patients with a matched donor or antithymocyte globulin plus cyclosporine and eltrombopag for everyone else.

Hemolytic anemia is premature red cell destruction confirmed by a high reticulocyte count and LDH with low haptoglobin and high indirect bilirubin. The approach then classifies disease by smear findings and a direct antiglobulin test, separating immune from non-immune and inherited from acquired causes to direct treatment.

Autoimmune hemolytic anemia is antibody-mediated red cell destruction confirmed by a positive direct antiglobulin (Coombs) test, split into warm IgG disease with splenic clearance and spherocytes and cold agglutinin IgM disease with complement-mediated agglutination worse in the cold. Warm disease is treated with glucocorticoids first and cold agglutinin disease with cold avoidance and rituximab, and roughly half have an identifiable secondary cause that must be sought and treated.

Myelodysplastic syndromes are clonal stem cell disorders producing ineffective hematopoiesis: a dysplastic, usually hypercellular bone marrow with peripheral cytopenias and a variable risk of transformation to acute myeloid leukemia. Diagnosis requires bone marrow biopsy showing dysplasia after excluding reversible mimics, risk is stratified with the IPSS-R, and treatment ranges from supportive transfusions and lenalidomide in lower-risk disease to hypomethylating agents and allogeneic transplant, the only cure, in higher-risk disease.

Thrombotic thrombocytopenic purpura is a thrombotic microangiopathy caused by severe ADAMTS13 deficiency that lets ultralarge von Willebrand factor multimers drive platelet microthrombi; the key dyad of microangiopathic hemolytic anemia plus thrombocytopenia without another cause mandates the PLASMIC score, an ADAMTS13 activity and inhibitor level, and emergent plasma exchange started before results return.

Hemolytic uremic syndrome is a thrombotic microangiopathy defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, most often triggered in children by Shiga toxin-producing Escherichia coli O157:H7 after bloody diarrhea. Diagnosis rests on schistocytes with a negative Coombs test plus a normal ADAMTS13 level to exclude TTP, and typical STEC-HUS is managed supportively while antibiotics and antimotility agents are avoided, whereas complement-mediated atypical HUS requires eculizumab.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy that leaves red cells unable to buffer oxidative stress, producing episodic intravascular hemolysis with bite cells and Heinz bodies after infection, fava beans, or oxidant drugs. Diagnosis rests on a G6PD enzyme activity assay that can be falsely normal during the acute episode and must be repeated 2 to 3 months later, while management centers on trigger avoidance, supportive care, and transfusion for severe hemolysis.

Hereditary spherocytosis is an inherited red cell membrane defect, usually autosomal dominant, that produces rigid spherocytes trapped and destroyed in the spleen. It presents with anemia, jaundice, splenomegaly, and pigment gallstones, is diagnosed by spherocytes with elevated MCHC and a negative direct antiglobulin test, and is confirmed by eosin-5-maleimide binding or osmotic fragility testing, with folic acid and splenectomy as the mainstays of treatment.