From the Guidelines
The diagnostic work-up for hemolytic anemia should include a comprehensive evaluation with history and physical examination, blood chemistry, CBC, peripheral smear, LDH, haptoglobin, bilirubin, reticulocyte count, and autoimmune serology, as recommended by the American Society of Clinical Oncology clinical practice guideline 1. The workup should start with a thorough history and physical examination, considering new drugs, insect, spider, or snake bites, and include blood chemistry tests such as CBC with evidence of anemia, macrocytosis, and evidence of hemolysis on peripheral smear.
- Key laboratory tests include:
- LDH, haptoglobin, bilirubin, reticulocyte count, and free hemoglobin
- Disseminated intravascular coagulation panel, including Prothrombin Time and International Normalized Ratio (PT/INR)
- Autoimmune serology
- Paroxysmal nocturnal hemoglobinuria screening
- Direct and indirect bilirubin, direct agglutinin test, and bone marrow analysis if no obvious cause is found
- Additional evaluations should be considered, including:
- Viral/bacterial causes of hemolysis studies
- Protein electrophoresis and cryoglobulin analysis
- Work-up for bone marrow failure syndrome if refractory, including B12, folate, copper, parvovirus, iron, thyroid, and infection
- Glucose-6-phosphate dehydrogenase evaluation
- Assessment of common drug causes and methemoglobinemia This comprehensive approach, as outlined in the American Society of Clinical Oncology clinical practice guideline 1, allows for accurate diagnosis and appropriate management of hemolytic anemia, which is crucial for improving patient outcomes in terms of morbidity, mortality, and quality of life.
From the Research
Hemolytic Anemia Workup
The workup for hemolytic anemia involves several laboratory tests and examinations to determine the underlying cause of the condition.
- The laboratory evaluation of anemia begins with a complete blood count and reticulocyte count, as stated in 2.
- The anemia is then categorized as microcytic, macrocytic, or normocytic, with or without reticulocytosis.
- Examination of the peripheral smear and a small number of specific tests confirm the diagnosis, including the serum iron level, total iron-binding capacity, serum ferritin level, and hemoglobin electrophoresis 2.
- A suggested approach to the hemolytic anemias includes using the micro-Coombs' test and ektacytometry 2.
Laboratory Test Results
Laboratory test results that confirm hemolysis include:
- Reticulocytosis
- Increased lactate dehydrogenase
- Increased unconjugated bilirubin
- Decreased haptoglobin levels, as mentioned in 3 and 4.
- The direct antiglobulin test further differentiates immune causes from nonimmune causes 3 and 4.
Classification of Hemolytic Diseases
Hemolytic diseases are classified into:
- Hemoglobinopathies
- Membranopathies
- Enzymopathies
- Immune-mediated anemias
- Extrinsic nonimmune causes, including the thrombotic microangiopathies, direct trauma, infections, systemic diseases, and oxidative insults, as stated in 3.
Approach to Haemolysis
When approaching haemolytic anaemia, subdividing patients into those who are 'direct antiglobulin test (DAT) positive' (immune) or 'DAT negative' (non-immune) is a simple and clinically relevant way to start to formulate a cause for the haemolytic anaemia, as mentioned in 4.
- Immune causes of haemolytic anaemia include autoimmune haemolytic anaemia, drugs, and delayed haemolytic transfusion reactions.
- Non-immune causes include the haemoglobinopathies (such as sickle cell disease) and microangiopathic haemolytic anaemias (such as disseminated intravascular coagulation) 4.