"Children's Autoimmune Hemolytic Anemia Diagnosis and Treatment Guidelines (2021 Edition)" released!

Autoimmune hemolytic anemia (AIHA) is a collective term for a group of hemolytic anemias caused by the body's immune function disorder, the production of red blood cell autoantibodies, and the increase of red blood cell destruction through the antibody or complement pathway, which exceeds the compensatory proliferation of the red blood system of the bone marrow.
.

AIHA can occur throughout childhood, and there is no obvious ethnic difference in incidence.

In order to standardize the diagnosis and treatment of children with AIHA in my country, the National Health Commission’s Children’s Hematology Expert Committee has discussed and formulated the "Children's Autoimmune Hemolytic Anemia Diagnosis and Treatment Standards (2021 Edition)".

Let's take a look at the content of AIHA's first-line treatment and second-line treatment together! Warm antibody AIHA is usually easy to recur and presents a chronic process, which often cannot be relieved without treatment, and requires medication.

First-line treatment ➤Glucocorticoid is the first-line treatment of warm-antibody AIHA.
It is recommended to use it in the absence of contraindications to glucocorticoids.

For warm-antibody AIHA, glucocorticoids usually take effect within 24 to 48 hours, and the treatment response rate is 50% to 80%, but it is easy to relapse when the dose is reduced too quickly or suddenly stopped.

Children with paroxysmal cold hemoglobinuria (PCH) usually have self-limited hemolysis, but short-term use of glucocorticoids may be needed to reduce hemolysis and improve anemia.

In a few cases, glucocorticoids may be effective for cold agglutinin disease (CAD).

① The initial dose depends on the degree of anemia: children with severe anemia need to be hospitalized, and methylprednisolone (1 to 2) mg/kg is administered intravenously every 6 to 8 hours for the first 24 to 72 hours.

In severe cases, shock doses can also be used, such as methylprednisolone 30 mg/(kg·d), the maximum dose is 1 g/d, for 3 consecutive days; then it is changed to regular dose maintenance.

Children with mild to moderate anemia can receive oral prednisone at a dose of (1-2) mg/(kg·d), with a maximum dose of 60 mg/d.

② Decrease can be fast first and slow later: glucocorticoids are not considered until the hematocrit is greater than 30% or the HGB level is stable above 100 g/L, and the dosage will be gradually reduced within 2 to 6 months according to the patient’s tolerance.
For example, reduce 2.
5 to 10.
0 mg per month.

In the later stage, glucocorticoids should be reduced slowly until hemoglobin, reticulocyte count, lactate dehydrogenase (LDH) and haptoglobin are normal.

③ Complications need to be closely monitored during treatment: long-term use of glucocorticoids in children can cause a variety of complications, including increased body mass, impaired growth, mental and cognitive symptoms, hypertension, hyperglycemia, osteoporosis, and femoral head Necrosis and cataracts, etc.

④ Other treatments and monitoring: need to pay attention to alkalization and diuresis (hydration is not emphasized in severe anemia.

Moderate alkalinization is required for
intravascular hemolysis.
No alkalinization is required for extravascular hemolysis), cholestasis and yellowing, and attention to electrolyte balance.

Regular clinical evaluation and monitoring of hemoglobin levels, reticulocyte count, LDH and direct anti-human globulin test (DAT), the frequency of monitoring depends on the severity of the disease and treatment.

Laboratory tests are usually monitored once a week; as the clinical situation stabilizes, the interval between tests can be gradually extended.

Usually monitored for at least 1 year.

If DAT is still positive after complete remission, it is necessary to further search for secondary causes, such as Evans syndrome or systemic lupus erythematosus.

⑤ Treatment response: Expected response: Approximately 80% of patients will get an initial response after glucocorticoid therapy.

Studies have shown that most children recover their hemoglobin levels within 1 month, but 72% of children have received treatment for at least 6 months.

Relapse: AIHA patients often relapse, and 15%-40% of patients have relapses during the first 6 months to 1 year after obtaining the initial response.

Relapse treatment is usually to restart the lowest dose of prednisone that can effectively maintain the patient's remission.

Glucocorticoid dependence: Refers to patients who have frequent relapses or low-dose prednisone (≤0.
2 mg/kg daily) cannot maintain remission.

⑥ Efficacy criteria: recovery: secondary to the infection, after the primary disease is cured, AIHA is also cured.

Manifested as no clinical symptoms, no anemia, and negative DAT.

The titers of cold agglutinin were normal in patients with CAD, and cold and hot hemolysis test in patients with PCH was negative.

Complete remission: the clinical symptoms disappeared, the red blood cell count, HGB level and the percentage of reticulocytes were normal, and the serum bilirubin level was normal.

DAT is negative.

Partial relief: clinical symptoms disappeared, HGB>80 g/L, reticulocyte percentage <4%, serum bilirubin <34.
2μmol/L.

DAT is negative or still positive but the titer is significantly lower than before.

Ineffective: There are still varying degrees of anemia and hemolysis, and the laboratory has not reached the partial remission standard.

In addition, first-line treatment also includes intravenous immunoglobulin (IVIG) pulse therapy combined with glucocorticoids, which is effective against warm antibody AIHA, with a dose of 0.
4 g/(kg·d), continuous intravenous infusion for 5 days; or 1 g/(kg·d), continuous 2 d shock treatment.

For relapsed or refractory AIHA, multiple use can be considered.

IVIG is a very attractive option for adult AIHA, but most children do not respond to IVIG alone.
Even if a response occurs, the effect is usually short-lived.

Second-line treatment ➤ The following conditions require second-line treatment: patients who do not respond to glucocorticoid treatment within 1 to 2 months, and cannot tolerate the gradual reduction of glucocorticoid, and the daily maintenance dose of prednisone is> 1 mg/kg.
Glucocorticoid dependence, other contraindications or intolerance to glucocorticoid treatment, AIHA recurrence.

① Rituximab: intravenously, each dose of 375 mg/m2, once a week for 2 to 4 weeks, the response rate is 60% to 85%.

It is necessary to pay attention to allergic reactions when using rituximab.
Most of them occur at the first infusion.
Acetaminophen and antihistamines can be used to prevent them before treatment.

Serious adverse reactions include severe infusion-related reactions, reactivation of hepatitis B virus infection, severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy.

Before starting rituximab treatment, all patients should be screened for hepatitis B virus (HBV) according to local guidelines.
Children who are in the active stage of hepatitis B should not be treated with rituximab.

For patients who have a positive HBV serology test, they should consult a liver specialist before starting treatment, and they should be monitored to prevent HBV reactivation.

② Splenectomy: Splenectomy is an effective treatment for children with chronic or refractory AIHA; about 2/3 of the children have short-term improvement, usually within 2 weeks after surgery.

After splenectomy in young children, there is a risk of sepsis caused by capsular bacteria.
Therefore, children under 3 years of age should avoid splenectomy, and it is best to delay it until after 6 years of age.

Patients who are preparing for splenectomy should be immunized against Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type B at an appropriate time before surgery.

Children who have undergone splenectomy should be given prophylactic treatment with long-acting penicillin as appropriate, and the patient should be instructed to seek medical attention immediately when fever occurs.

The above content is extracted from: Medical Administration and Hospital Administration.
Standards for the diagnosis and treatment of autoimmune hemolytic anemia in children (2021 edition).
General Office of the National Health Commission.
2021.
4.
29.