Hemolytic anemia: an overview

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.

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.

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.

Sickle cell disease is an autosomal recessive hemoglobinopathy caused by a beta-globin point mutation that produces hemoglobin S, which polymerizes under deoxygenation to sickle erythrocytes and drive chronic hemolysis and vaso-occlusion. Diagnosis is confirmed by hemoglobin electrophoresis or HPLC showing predominant HbS, and lifelong management centers on hydroxyurea, folic acid, penicillin prophylaxis and vaccination for functional asplenia, transcranial Doppler stroke screening, and, in severe disease, transfusion, hematopoietic stem cell transplant, or gene therapy.

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.

Paroxysmal nocturnal hemoglobinuria is an acquired clonal stem cell disorder caused by a somatic PIGA mutation that leaves blood cells unprotected from complement, producing intravascular hemolysis, unusual-site venous thrombosis, and cytopenias. Diagnosis rests on flow cytometry showing loss of the GPI-anchored proteins CD55 and CD59, and eculizumab or ravulizumab is used to block terminal complement and reduce both hemolysis and thrombotic risk, while allogeneic stem cell transplant remains the only cure.

Transfusion reactions are a spectrum of immunologic and non-immunologic complications of blood product administration, ranging from a benign febrile reaction to fatal acute hemolysis, anaphylaxis, TRALI, or septic shock. The first step for any reaction is always to stop the transfusion; the type is then distinguished by timing, hemolysis markers, and hemodynamic and respiratory pattern, and each type has a specific treatment and prevention strategy.