Hemolytic anemia resident survival guide

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Hemolytic anemia
Resident Survival Guide
Overview
Causes
FIRE
Diagnosis
Treatment
Do's
Don'ts


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sanjana Nethagani, M.B.B.S.[2]

Synonyms and Keywords: : RBC destruction, Hemolysis

Overview

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.

Causes

Life threatening causes[1][2][3]

Other causes[4]

For a complete list of hemolytic anemia causes click here

Diagnosis

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.

 
 
 
 
 
 
 
 
 
 
 
 
Characterize the symptoms:
Weakness
Shortness of breath
Jaundice
Lethargy
Chest pain and reduced exercise tolerance
Pica
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Examine the patient:
Tachypnea
❑ Cold and clammy skin
Hypotension
❑ HEENT signs:


❑ Cardiovascular exam:


❑ Abdominal exam:


❑ Skin exam:

  • Pallor of nail beds, palmar creases
  • Bronze skin colour in case of repeated transfusions
  • Leg ulcers

Fever and neurological signs are seen in TTP
Hemoglobinuria in some cases
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initial workup for hemolysis:
❑ Indirect bilirubin
❑ serum haptoglobin
Lactate dehydrogenase level
Reticulocyte count
Urinalysis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No laboratory evidence of hemolysis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Degmacytes
 
Normal cell morphology
 
Spherocytes
 
Elliptocytes
 
Shistocytes
 
Sickle shaped cells
 
Hypochromic, microcytic cells
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
G6PD deficiency
 
Family history
❑ Drug history
❑ Recent infections
 
 
 
 
 
 
 
 
Sickle cell disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
H/o exercise, exertion, trauma or surgery?
 
 
 
 
 
Beta thalassemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Negative
 
Positive
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CD55/59
 
❑ Drug induced hemolytic anemia
❑ Autoimmune disease
 
❑Exercise induced hemolysis
Prosthetic heart valve
❑Severe aortic stenosis
 
Microangiopathic hemolytic anemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Positive
 
 
 
Negative
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-eclampsia and eclampsia
 
Recent diarrhea
 
 
Decreased ADAMTS13 activity
 
 
 
 
 
Paroxysmal nocturnal hemoglobinuria
 
 
 
Hereditary spherocytosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HELLP syndrome
 
Hemolytic uremic syndrome
 
 
Thrombotic thrombocytopenic purpura
 

Treatment

  • The treatment of hemolytic anemia depends on the cause of anemia.[5][6][7]
  • Treatment plan is summarized in the algorithm below based on the 2017 guidelines published by the British Society of Hematology and[8] and the 2020 recommendations by the First International Consensus Group.[9]
 
 
 
 
 
 
 
 
 
 
 
 
 
History
  • Fatigue
  • Dyspnea
  • Lightheadedness

Physical examination

  • Pallor
  • Icterus
  • Cold, clammy skin
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Peripheral blood smear findings
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bite cells
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Oxidative stress like
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment of acute attacks
  • Blood transfusion
  • Hemodialysis
  • Long term measures

    • Avoidance of trigger foods and drugs
    • Splenectomy- spleen is the site of destruction of RBCs
    • Avoid aspirin as it reduces the lifecycle of RBCs
    • Vaccination against common trigger infections such as Hepatitis A& B
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Positive
    Treatment of drug induced hemolytic anemia includes removal of offending agent
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Treatment for hereditary spherocytosis
    • Currently there is no cure for hereditary spherocytosis
    • Acute attacks of hemolytic anemia are treated with blood transfusions
    • Splenectomy is indicated in severe cases
    • Post-splenectomy, patients are vaccinated against influenza, capsulated bacteria such as S. pneumonia and meningococcus
    • Cholecystectomy is indicated in patients with pigment gallstones
     
     
     
     
     
    Alloimmunisation treatment

    Causes: ABO incompatible or Rh incompatible transfusion

     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    Warm type AIHA
     
     
     
    Cold type AIHA
  • Avoid cold exposure
  • Rituximab in severe or recurrent disease
  • Treat underlying infection
  •  
     
     
     
     
     
     
     
     
    Thrombotic thrombocytopenic purpura
    • Transfusion is contraindicated
    • Plasmapheresis is treatment of choice
    • Fresh frozen plasma can be given if plasmapheresis is not available
    • Corticosteroids are given concomitantly
    • Rituximab is emerging as a therapy when plasma exchange and corticosteroids fail
    • Refractory TTP is treated with immunosuppressive agents such as cyclophosphamide and vincristine
    • Caplacizumab is another treatment option but it is associated with excess bleeding

    Hemolytic uremic syndrome

    Disseminated intravascular coagulation

    HELLP syndrome

    • Immediate delivery of the baby
    • Corticosteroids may be used

    Malignant hypertension

    Paroxysmal nocturnal hemoglobinuria

    Do's

    • Folic acid supplementation for all patients with hemolytic anemia[10].
    • Erythropoietin decreases the need for transfusions, especially in children and patients with recurrent disease.[11]
    • 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.[12]
    • 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.[13]
    • Treat iron overload with chelation therapy.
    • Discontinue trigger medications such as penicillin or sulfa drugs.

    Don'ts

    • Do not transfuse blood in TTP/HUS as it increases risk of thrombosis.[14]
    • Corticosteroids must not be stopped abruptly. A tapered approach must be followed.

    References

    1. Phillips J, Henderson AC (2018). "Hemolytic Anemia: Evaluation and Differential Diagnosis". Am Fam Physician. 98 (6): 354–361. PMID 30215915.
    2. 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.
    3. Morishita E (2015). "[Diagnosis and treatment of microangiopathic hemolytic anemia]". Rinsho Ketsueki. 56 (7): 795–806. doi:10.11406/rinketsu.56.795. PMID 26251142.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    11. 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.
    12. 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.
    13. 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.
    14. 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.