Hemolytic anemia resident survival guide
Resident Survival Guide
Synonyms and Keywords: : RBC destruction, Hemolysis
Anemia is defined as a decrease in red blood cell count in the body. Hemolytic anemia results from a premature destruction of RBCs. Hemolysis can be due to either extravascular or intravascular destruction of cells. It is caused by a wide variety of reasons, which include inherited diseases like thalassemia, sickle cell disease etc, infections, autoimmune conditions, bone marrow dysfunction, blood transfusions and certain drugs can also result in hemolytic anemia. The most common presenting symptoms are: fatigue, palpitations, dyspnea, tachycardia and icterus in severe cases. Diagnosis usually requires a battery of tests including, but not limited to a peripheral smear, CBC, serum LDH, bone marrow studies, etc. Treatment is directed by the specific cause and can involve bone marrow transplant, splenectomy, transfusions etc.
- ABO incompatibility
- Disseminated intravascular coagulation
- Thrombotic thrombocytopenic purpura
- Hemolytic uremic syndrome
- Pre-eclampsia and malignant hypertension
- Membrane cytoskeletal defects like hereditary spherocytosis and hereditary elliptocytosis
- Glucose 6 phosphate dehydrogenase deficiency
- Pyruvate kinase deficiency
- Sickle cell disease
- Cold agglutinin disease
- Drug induced hemolytic anemia
- Systemic lupus erythematosus
- Prosthetic heart valves
- Infectious causes such as malaria, hepatitis, CMV infection etc.
For a complete list of hemolytic anemia causes click here
The approach to diagnosis of hemolytic anemia is based on a step-wise testing strategy. Below is an algorithm summarizing the identification and laboratory diagnosis of hemolytic anemia.
Examine the patient:
❑ Cold and clammy skin
❑ HEENT signs:
❑ Fever and neurological signs are seen in TTP
❑ Hemoglobinuria in some cases
|No laboratory evidence of hemolysis|
|Degmacytes||Normal cell morphology||Spherocytes||Elliptocytes||Shistocytes||Sickle shaped cells||Hypochromic, microcytic cells|
❑ Family history
❑ Drug history
❑ Recent infections
|Sickle cell disease|
H/o exercise, exertion, trauma or surgery?
❑ Drug induced hemolytic anemia
❑ Autoimmune disease
|❑Exercise induced hemolysis|
❑Prosthetic heart valve
❑Severe aortic stenosis
|Microangiopathic hemolytic anemia|
|Pre-eclampsia and eclampsia||Recent diarrhea||Decreased ADAMTS13 activity|
|Paroxysmal nocturnal hemoglobinuria||Hereditary spherocytosis|
|HELLP syndrome||Hemolytic uremic syndrome||Thrombotic thrombocytopenic purpura|
- The treatment of hemolytic anemia depends on the cause of anemia.
- Treatment plan is summarized in the algorithm below based on the 2017 guidelines published by the British Society of Hematology and and the 2020 recommendations by the First International Consensus Group.
Peripheral blood smear findings
Treatment for hereditary spherocytosis
Cold type AIHA
Thrombotic thrombocytopenic purpura
- Folic acid supplementation for all patients with hemolytic anemia.
- Erythropoietin decreases the need for transfusions, especially in children and patients with recurrent disease.
- Oral iron supplementation must be given in patients with iron deficiency.
- Corticosteroids whenever used, must be tapered. Most patients need low dose corticosteroid as a long term maintenance therapy.
- Vaccinate against influenza and encapsulated organisms like meningococcus and Streptococcus pneumoniae to prevent OPSI in patients who have undergone splenectomy.
- Long term monitoring of hemoglobin, reticulocyte count, LDH, bilirubin level and haptoglobin is needed to track response to therapy and future episodes of hemolysis.
- Transfusions must be avoided when not needed. When absolutely necessary, blood must be typed and matched. If in an emergency situation typing and cross matching is not possible, the least incompatible blood type is used to transfuse.
- Transfusion of blood must be done at a slow rate to prevent destruction of transfused RBCs.
- Treat iron overload with chelation therapy.
- Discontinue trigger medications such as penicillin or sulfa drugs.
- Do not transfuse blood in TTP/HUS as it increases risk of thrombosis.
- Corticosteroids must not be stopped abruptly. A tapered approach must be followed.
- Phillips J, Henderson AC (2018). "Hemolytic Anemia: Evaluation and Differential Diagnosis". Am Fam Physician. 98 (6): 354–361. PMID 30215915.
- Renard D, Rosselet A (2017). "Drug-induced hemolytic anemia: Pharmacological aspects". Transfus Clin Biol. 24 (3): 110–114. doi:10.1016/j.tracli.2017.05.013. PMID 28648734.
- Morishita E (2015). "[Diagnosis and treatment of microangiopathic hemolytic anemia]". Rinsho Ketsueki. 56 (7): 795–806. doi:10.11406/rinketsu.56.795. PMID 26251142.
- Barcellini W, Bianchi P, Fermo E, Imperiali FG, Marcello AP, Vercellati C; et al. (2011). "Hereditary red cell membrane defects: diagnostic and clinical aspects". Blood Transfus. 9 (3): 274–7. doi:10.2450/2011.0086-10. PMC 3136593. PMID 21251470.
- Matsumoto M, Fujimura Y, Wada H, Kokame K, Miyakawa Y, Ueda Y; et al. (2017). "Diagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) 2017 in Japan". Int J Hematol. 106 (1): 3–15. doi:10.1007/s12185-017-2264-7. PMID 28550351.
- Bagga A, Khandelwal P, Mishra K, Thergaonkar R, Vasudevan A, Sharma J; et al. (2019). "Hemolytic uremic syndrome in a developing country: Consensus guidelines". Pediatr Nephrol. 34 (8): 1465–1482. doi:10.1007/s00467-019-04233-7. PMID 30989342.
- Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH; et al. (2014). "Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members". JAMA. 312 (10): 1033–48. doi:10.1001/jama.2014.10517. PMID 25203083.
- Kamesaki T (2019). "[Progress in diagnosis and treatment of autoimmune hemolytic anemia]". Rinsho Ketsueki. 60 (9): 1100–1107. doi:10.11406/rinketsu.60.1100. PMID 31597833.
- Jäger U, Barcellini W, Broome CM, Gertz MA, Hill A, Hill QA; et al. (2020). "Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting". Blood Rev. 41: 100648. doi:10.1016/j.blre.2019.100648. PMID 31839434.
- Azzam M, Attalla S (2019). "Serum Folate Levels in Patients with Chronic Hemolytic Anemia on Regular Folic Acid Supplementation Before and After Dose Modification". Indian Pediatr. 56 (10): 845–848. PMID 31724541.
- Tchernia G, Delhommeau F, Perrotta S, Cynober T, Bader-Meunier B, Nobili B; et al. (2000). "Recombinant erythropoietin therapy as an alternative to blood transfusions in infants with hereditary spherocytosis". Hematol J. 1 (3): 146–52. doi:10.1038/sj.thj.6200022. PMID 11920183.
- Dussadee K, Taka O, Thedsawad A, Wanachiwanawin W (2010). "Incidence and risk factors of relapses in idiopathic autoimmune hemolytic anemia". J Med Assoc Thai. 93 Suppl 1: S165–70. PMID 20364571.
- Pirenne F, Yazdanbakhsh K (2018). "How I safely transfuse patients with sickle-cell disease and manage delayed hemolytic transfusion reactions". Blood. 131 (25): 2773–2781. doi:10.1182/blood-2018-02-785964. PMC 6014354. PMID 29724898.
- Otrock ZK, Liu C, Grossman BJ (2015). "Platelet transfusion in thrombotic thrombocytopenic purpura". Vox Sang. 109 (2): 168–72. doi:10.1111/vox.12274. PMID 25900398.