Hereditary hemolytic anemias (HHAs) are a group of disorders that are characterized by hemolysis, or the abnormal destruction of red blood cells (RBCs), and are caused by intrinsic RBC abnormalities, extrinsic factors, or both.1 Some extrinsic factors include, antibody-mediated hemolysis and mechanical injury to RBCs in microangiopathic hemolytic anemias (MAHAs). Defects in hemoglobin, the RBC membrane, and RBC enzymes are some major intrinsic factors.2 Premature RBC destruction may also occur intravascularly or extravascularly in the reticuloendothelial system, primarily by the splenic and liver macrophages. HHAs often present at birth with neonatal hyperbilirubinemia, while severe cases may occur prenatally and present as fetal distress and hydrops fetalis. Cases of mild hemolytic anemia or well-compensated hemolysis may be asymptomatic until later on in childhood or even into adulthood, and generally present during an acute illness that exacerbates hemolysis.
Splenectomy can be an effective treatment for some types of hemolytic anemia and has been employed for decades in HHAs as a means of decreasing hemolysis and improving anemia. However, the authors of a new review in Pediatric Blood & Cancer point out that there have been recent advancements in the field, including improvements in diagnosis, availability of genetic testing, availability of follow-up data on the efficacy of partial splenectomy in HHA patients, and increased awareness of postsplenectomy vascular complications, such as thrombosis and pulmonary hypertension. In their review, the investigators discussed the applicability, efficacy, safety, and the choice of partial vs total splenectomy as the best strategy for the patients with HHA.
“In general, the goal would be to avoid splenectomy if at all possible due to the risks of sepsis and thrombosis,” said author Jennifer Rothman, MD, an associate professor in the division of pediatric hematology and oncology, and director of the Pediatric Comprehensive Sickle Cell Program at Duke University Medical Center in Durham, North Carolina. “Patients may require splenectomy if they have moderate-to-severe symptomatic anemia, which may require transfusions.”
Patients who develop splenomegaly, in which the spleen is painful or causes difficulty with eating, may benefit from a splenectomy. “The key message is that splenectomies are associated with significant late effects and so the decision to proceed with a splenectomy should be based on patient symptoms and not just hemoglobin level,” Dr Rothman said. “It is important to also consider the underlying genetic cause of HHA [because] some do not respond to splenectomy.”
Making a Diagnosis
An accurate diagnosis along with knowledge of the underlying pathogenesis is imperative for making treatment decisions. This can be challenging for clinicians, since the presenting signs and symptoms of hemolytic anemias are generally the same, even though the extrinsic or intrinsic factors may vary considerably. When a patient presents with hemolytic anemia or with compensated hemolysis, the authors recommend checking direct antiglobulin test (DAT or direct Coombs) and indirect antiglobulin tests as a first line of action, primarily to rule out autoimmune or alloimmune hemolytic anemia. To screen for possible MAHA, evaluation of platelet count, creatinine and a review of the blood smear for schistocytes and helmet cells should also be a priority, as these can be life threatening.
After ruling out other hemolytic anemias, HHA differential diagnosis is recommended. This includes a complete blood count (CBC) with reticulocyte count and attention to RBC indices, such as mean cellular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC). The differential diagnosis also would include reviewing blood smears from the patient. If the patient is a neonate or has recently received a blood transfusion, a review of parental blood smears is also recommended.
Other diagnostics will vary based on results from the history and smear review. Assessing glucose 6-phosphate dehydrogenase deficiency activity level, for example, would be an appropriate step for a male patient presenting with hemolytic crisis episodes with a baseline normal CBC.