Diagnosis, Management and Prevention of Acute Hemolytic Anemia in Infants, Children and Adolescents

CPGL Source

Recommendation

QOE

SOR

Diagnosis Questions

1.1   What is the initial laboratory panel for infants, children and adolescents presenting with AHA?

AIEOP 2017

First level testing includes

•      Hemoglobin Level, red cell indices and morphology on peripheral smear

•      Reticulocyte count

•      WBC and platelet count

•      Indices of hemolysis (indirect bilirubin, LDH)

•      Urine analysis

•      Direct and indirect antibody test (Coombs test)

•      Blood group

Low

BSH 2017

•      Liver transaminases and kidney function (blood urea and serum creatinine) 

Low

Conditional

1.2   What is the best timing and test to diagnose G6PD deficiency in infants, children and adolescents presenting with AHA?

BSH 2020

•      If G6PD assay was done during a hemolytic episode of unknown cause, re-assay is warranted to ensure the diagnosis of G6PD deficiency is not missed.

Low

Strong

•      A normal G6PD activity during a hemolytic episode should be repeated after 2 months in absence of clinical and laboratory evidence of hemolysis.

Low*

BSH 2020

•      G6PD can be diagnosed with a quantitative spectrophotometric analysis or, more commonly, by a rapid fluorescent spot test.

Low

Strong

BSH 2020

•      Do not rely on screening tests for female patients.

•      Measure G6PD activity by quantitative spectrophotometric assay directly.

Low

Strong

BSH 2020

•      Quantitative assay must be carried out if the screening test is abnormal or borderline

Low

Strong

BSH 2020

•      The final G6PD activity should be interpreted in the lights of the reticulocyte count measured on the same sample

Low

Strong

BSH 2020

•      Samples with very low mean corpuscular hemoglobin (MCH) may give G6PD activity levels above the expected value

Low

Strong

1.3   What are the indications of G6PD testing?

BSH 2020

•      Favism (hemolysis with fava beans intake)

•      Hemolysis associated with “oxidant” drugs (Table in implementation tools) or infection

•      Red-cell morphology (Basket cells/ positive Heinz body stain)

•      Hemoglobinuria

•      Hemolysis with previous history of neonatal pallor/jaundice

Low

1.4   What is the best test to diagnose AIHA in infants, children and adolescents presenting with AHA?

BSH 2017

•      At a minimum, the DAT should include monospecific anti-IgG and anti-C3d

Low

Strong

BSH 2017

•      Investigation of DAT-negative hemolysis:

-        In patients with unexplained hemolysis and a negative screening DAT, retest with a column agglutination DAT method that includes monospecific anti-IgG, anti-IgA and anti-C3d

-        If also negative, consider preparing and investigating a red cell eluate.

Intermediate

Low

Strong

1.5   What are the additional tests before starting treatment in patients with AIHA?

BSH 2017

AIOEP 2017

•      Immunological markers

-        ANA, Anti DNA, C3, Antiphospholipid

-        Total serum immunoglobulins

-        CD markers and double negative α/β T cells if hepatosplenomegaly

•      Bone marrow aspiration is only recommended in the presence of another associated cytopenia or persistent reticulocytopenia or on suspicion of neoplasia or myelodysplasia.

High

Low

Strong

1.6. What is the initial laboratory panel for patients with suspected post diarrheal hemolytic uremic syndrome?

Bagga et al 2019

•      Complete blood count (hemoglobin <10 g/dl, hematocrit <30%, platelet count <150,000/μl)

•      Peripheral smear (fragmented red cells - schistocytes ≥ 2%)

•      Lactate dehydrogenase (LDH > 450 IU/l)

•      Haptoglobin (undetectable)

•       Kidney function tests (increased serum creatinine by 50% over baseline level)

Low**

Management Questions

2.1   What is the emergency treatment for AHA?

BSH 2017

•             If anemia is life threatening, transfuse with ABO, Rh and K matched red cells.

Low

Strong

2.2   When is Packed red cells indicated in AHA?

Sub-question: volume/ precautions needed?

BSH 2017

•      Transfusion can be avoided in hemodynamically stable patients with regular monitoring until no evidence of hemolysis.

•      Transfuse if

-  Hb < 5 g/dl

-  Hb is < 7g/dl with cardiac decompensation

Low

GPS

Conditional

BSH 2017

•      Consider the use of a blood warmer for transfusion in patients with cold AIHA (CHAD, mixed AIHA and PCH)

Low

Conditional

AIEOP 2017

•      Dose: 3-5 ml/Kg of packed RBCs fully compatible ABO, Rh, K, leucodepleted filtered blood. Transfuse slowly over 4 hours

Low

2.3   What is the medical treatment
What are the criteria of adequate /good response to treatment in infants, children, and adolescents with AIHA?

BSH 2017

•      First line therapy is prednisolone 1-2 mg/kg/day

Intermediate

Strong

BSH 2017

•      Second line therapy should be considered if:

-      No response to steroids after 3 weeks

-      Relapse during or after steroid reduction

And Refer to Hematologist

Low

Conditional

BSH 2017

•      Consider IVIg or plasma exchange for severe or life-threatening anemia

Low

Conditional

BSH 2017

•      Patients with AIHA should receive folic acid supplementation

Low

Strong

BSH 2017

•      All patients should receive oral calcium and vitamin D supplements while taking corticosteroids (typically 1200–1500 mg calcium and 800–1000 units vitamin D)

High

Strong

2.4 For follow up after discharge, what are the laboratory tests needed in patients with G6PD and AIHA?

BSH 2020

•      Follow up by CBC and reticulocyte count every 2-4 weeks when indicated by treating physician.

•      G6PD enzyme assay should be tested after complete recovery of the hemolytic attack and patient discharge.

Low

Strong

Prevention Questions

3.1   What are the drugs to be avoided and the dietary modifications required to prevent the occurrence of AHA in patients with G6PD deficiency?

AFP 2005

•      Patients with G6PD deficiency should avoid exposure to oxidant drugs and ingestion of fava beans.

•      Patients with suspected G6PD deficiency should avoid exposure to oxidant drugs and ingestion of fava beans till diagnosis.

Low

Strong

3.2   For prevention of HUS, when is empiric antibacterial treatment indicated for children with bloody diarrhea?

IDSA 2017

Antimicrobial therapy should be avoided in children with infections attributed to certain strain of STEC that produce Shiga toxin 2 (or if the toxin genotype is unknown)

Intermediate

Strong

IDSA 2017

In immunocompetent children, empiric antimicrobial therapy for bloody diarrhea while waiting for results of investigations is not recommended, except for:

·      Infants <3 months of age with suspicion of a bacterial etiology.

·      Ill immunocompetent children with fever, abdominal pain, bloody diarrhea, and bacillary dysentery presumptively due to Shigella.

·      People who have recently travelled internationally with body temperatures ≥38.5°C and/or signs of sepsis.

Low

Low

Strong

Conditional