Hemolytic anemia
DDx:
Hemoglobinopathy - sickle cell disease, thalassemia
Hemoglobinuria
Enzyme def
ABX causing hemolytic anemia
In persons with or without G-6PD:
penicillins
cephalosporins
sulfonamides, co-trimoxazole, chloramphenicol
dapsone
INH, rifampin,
nitrofurantoin, naldixic acid.
Primaquine, fava beans, ascorbic acid >1g, vitK analogs, ASA >3g/day.
anemia, ▲ retic. count, ▲ LDH, ▲ indirect bili, ▼ haptoglobin = hemolytic anemia
Labs: CBC w diff, retic, peripheral smear, CMP, UA, DAT, indirect Coomb's test, HbEP, Heinz body stain. Thin/thick smear for Parasites-malaria, babeosis.
Intravascular hemolysis shows the following:
Abnormal peripheral smear (schistocytes, helmet cells, fragmented cells).
hemoglobinuria
hemosiderinuria
Autoimmune Hemolytic Anemia
Definition
In autoimmune hemolytic anemia autoantibody is targeted to antigens on the patient’s own red cells resulting in extravascular hemolysis.
Classification
Warm AIHA antibodies interact best with RBCs at 37°C.
Cold AIHA antibodies are most active at temperatures below 37°C.
Etiology
Warm antibody AIHA is usually caused by an IgG autoantibody. It may be idiopathic or associated with underlying malignancy like lymphoma, chronic lymphocytic leukemia, collagen vascular disorder, or drugs.
Cold antibody AIHA is typically IgM in cold agglutinin disease. The acute form often secondary to an infection (Mycoplasma, EBV), which is usually transient. The chronic form is due to paraprotein (lymphoma, CLL, Waldenstrom macroglobinemia in ~ ½ cases and is usually idiopathic in the others.
Diagnoses
Mild cases of warm antibody AIHA may present with a stable anemia and reticulocytosis. In fulminant cases RBC life span of <5 days, the anemia can be severe and compensatory erythropoiesis becomes inadequate, with a presentation of a rapidly declining hemoglobin, fever, chest pain, and dyspnea. Jaundice, icterus, and a dark urine reflect elevated indirect bilirubin from hemoglobin degradation.
In cold antibody AIHA, severe acute hemolysis may be triggered by exposure to cold ambient temperatures in some patients so that avoiding the cold is of utmost importance. The disease is otherwise generally characterized by mild anemia with intermittent exacerbation.
Diagnostic testing
Decrease in haptoglobin
Increase in LDH and bilirubin, which may not be dramatic due to extravascular hemolysis.
Positive DAT:
Warm AIHA: IgG+, C3+ or IgG +, C-
Cold AIHA: IgG-, C+
Cold agglutinin titers
Flow cytometry to rule out PNH
Peripheral smear shows spherocytes, polychromasia.
Consider workup for malignancy
Treatment
Treat underlying cause
Warm AIHA
Glucocorticoid, such as prednisone 1 mg/kg. If patients are sensitive to local glucocorticoids, response is typically seen in 7 to 10 days. When hemolysis has abated, glucocorticoids can be tapered to 2 to 3 months. Rapid steroid tapers can result in relapse. IVIG is less effective than in ITP, with response rate of about 40%. Splenectomy should be considered for steroid resistant AIHA. Rituximab, 375 mg/m2 IV wkly x 4 doses, has shown efficacy.
Idiopathic cold AIHA
Glucocorticoids and splenectomy or not efficacious. Rituximab has been demonstrated to be effective. In severe cases, plasma exchange may be used to remove offending IgM antibody (which is 80% intravascular) to control the disease while other therapies are administered.
Warm RBC transfusions to 37° C; keep the patient and room warm to prevent exacerbation of hemolysis.
RBC transfusion in AIHA
RBC transfusions may not be as effective in increasing RBC mass due to hemolysis of transfused cells. Transfuse RBC use only when patient is symptomatic orders decrees oxygen caring capacity example hemoglobin of less than 6 g per deciliter.
Autoantibodies may confound plasma antibodies screens and conventional crossmatches and therefore alloantibodies may go undetected.
Hereditary spherocytosis. The spectrin network is linked at two points to the membrane: through ankyrin to the intrinsic membrane protein band 3 and through band 4.1R to the intrinsic membrane protein glycophorin. Multiple mutations have been desribed in HS, but all serve to disrupt vertical interactions between the spectrin meshwork and one of the other intrinsic membrane proteins. The most common mutated component is ankyrin, but mutations in spectrin, band 4.1R and band 3 have also been described.
Splenectomy corrects anemia in HS, but spherocytes persist b/c defect remains. By removing the spleen, RBC sequestration in spleen and subsequent destruction of these RBCs by the macrophages in the spleen does not occur.
Splenomegaly is very common in HS, than in any other form of hemolytic anemia.
Cholelithiasis is common in 50% of patients of HS.
Clinical features in HS: anemia, jaundice, splenomegaly. Increased osmotic fragility is a characteristic finding that is helpful in Dx. Clinical course may be punctated by aplastic crisis, often triggered by parvovirus inf →→ transient cessation in RBC production.
No Tx for HS. Splenectomy is beneficial. Must consider risk of increased susceptibility (OPSS) to infection, particulary in children.
Microangiopathic Hemolytic Anemia
Definition
This is a syndrome of traumatic microangiopathic intravascular Hemolysis.
Diagnosis
MAHA is a morphologic classification in which a fragmented RBCs (schistocytes) are seen on peripheral blood smear. It is not a specific diagnoses but suggests a limited differential diagnoses.
Differential diagnoses:
Mechanical heart valves can cause RBC sheared stress, especially if the valve is dysfunctional; this may be difficult to diagnose.
Other processes that can cause RBC fragmentation and hemolysis include DIC, TTP, HUS, malignant hypertension, preeclampsia/eclampsia syndromes, vasculitis, adenocarcinoma, and improper use of blood warmers.
Labs
CBC count: Normocytic anemia with thrombocytopenia
Elevated LDH, reticulocyte count, bilirubin
Decreased haptoglobin
Peripheral smear shows schistocytes, polychromasia.
Treat the etiology.