Hemolytic anemia- Warm and Cold

Hemolytic anemia 

Initial work up for hemolytic anemia:

1. CBC, retic count, haptoglobin, peripheral smear ( spherocytes/ RBC agglutination, nucleated RBC), urinanalysis, LDH. Ig M causes direct agglutination, spherocytes in warm AIHA

2. DAT Coomb's, Cold agglutinin titer

3. CT CAP

4. Bone marrow biopsy, SPEP IFE, Total immunoglobulins, flow cytometry

5. ANA, hx of rheum disorders

6. HIV, Hep B, C, mycoplasma Ab, EBV

7.C3, C4

8. Drug history, UDS when indicated

9. Consider work up and coverage for infections if fever

Symptoms:

- dizziness, fatigue, abd pain, fever, jaundice

Exam: 

-pallor, icterus, adenopathy, hepatosplenomegaly ( depending on underlying cause)

Reaction pattern of DAT

Ig G alone or Ig G +C3--> drug induced, warm AIHA

Complement alone: 4 possiblities-->

1. CAD ( anti I antigen with MGUS)
2. Warm AIHA with low titer Ig G or IG A bound to RBC--> get Super Coomb's
3. Paroxysmal cold hemoglobinuria( Donath Landsteiner Ab which is Ig G against P antigen, but fixes complement)
4. Drug induced--> immune complex/ternary

Drug induced HA DAT patterns

1. Hapten ( drug dependent, ex PCN): Ig G
2. Ternary complex ( also drug dependent, ex 3rd gen cephalosporin): C3
3. True autoantibody ( not drug dependent, ex methyldopa): Ig G+ C3

Reticulocytopenia in AIHA

- folate def

-bone marrow infiltration from malignancy

-intercurrent infection

What does not work in cold AIHA: steroids, splenectomy, IVIG

Life threatening cold AIHA--> plasmapheresis to remove the IG M antibody

Discussion:

1. Warm AIHA :For patients with mild to moderate hemolysis, the recommended dose is prednisone 1 to 2 mg/kg per day for three days. Patients with severe hemolysis typically receive a high dose of steroids, such as methylprednisolone 250 to 1,000 mg per day for three days. Up to 80% of patients respond to steroids, typically within four to seven days of therapy initiation.

2. If a patient’s disease has not responded within three weeks of therapy, pt has refractory disease. 

3. For patients whose disease does not respond to steroids within two to three weeks, the next option is a course of rituximab, typically 375 mg/m2 for four weeks, which usually induces responses in 80% of patients and long-term remissions in about 60% to 70%. Rituximab is rarely used up front because it takes about a month to work while steroids begin to work within days. Patients who relapse can subsequently be treated successfully with additional courses of rituximab.

4. If severe hemolysis can use high-dose intravenous Ig. 

5. PRBC transfusion if brisk hemolysis. Patients with severe disease, particularly in cases of brisk hemolysis and precipitous anemia, may require RBC transfusions, which can be lifesaving.t RBC transfusions are discouraged for the average patient with wAIHA, but are important in some cases and not contraindicated.

6. Refractory to steroids and rituxan: approximately 25% of patients whose disease does not respond to rituximab, splenectomy is a possible treatment option for patients who are eligible. If a splenectomy does not produce the desired response, or if a patient is too medically sick to undergo surgery, additional therapy options include immunosuppressive drugs such as azathioprine, cyclosporine, bortezomib, and daratumumab.

7. Steroid dependent: use low dose prednisone maintenance

Treatment:

• Blood transfusion for severe anemia (usually with inappropriate reticulocyte response)

• For drug-induced warm antibody hemolytic anemia, drug withdrawal and sometimes IV immune globulin

• For idiopathic warm antibody hemolytic anemia, corticosteroids and, in refractory cases, rituximab, IV immune globulin, immunosuppression (eg, with azathioprine, mycophenolate mofetil, or cyclophosphamide), or splenectomy

• For cold agglutinin disease, avoidance of cold and treatment of underlying disorder. Splenectomy is usually of no value, and immunosuppressants have only modest effectiveness.

• For PCH, avoidance of cold, immunosuppressants, and treatment of syphilis if present. In children, this disease is often self-resolving. Splenectomy is of no value. Treatment of concomitant syphilis may cure PCH.

Blood transfusion is the most important treatment for patients who have symptoms and who rapidly develop severe, life-threatening anemia. In this situation, transfusion should never be withheld due to lack of "compatible" units. In general, patients who have not had a previous blood transfusion or been pregnant are at low risk for hemolysis of ABO-compatible blood. Even if transfused cells are hemolyzed, blood transfusion can be life-saving until more definitive therapy can be done. Erythropoietin may be given if the reticulocyte response is inadequate.

Reference: Merck Manual