HEMOLYTIC ANEMIA IMMUNE

1. Drug-Related Hemolysis 2. Alloimmune Hemolysis
– – – – – Hemolytic Transfusion Reaction Hemolytic Disease of the Newborn Warm autoimmune hemolysis Cold autoimmune hemolysis Paroxismal cold hemoglobinuria

3. Autoimmune Hemolysis

IMMUNE HEMOLYSIS Drug-Related

• Immune Complex Mechanism
– Quinidine, Quinine, Isoniazid

• “Haptenic” Immune Mechanism
– Penicillins, Cephalosporins

• True Autoimmune Mechanism
– Methyldopa, L-DOPA, Procaineamide, Ibuprofen

Autoimmune hemolytic anemia
• RBCs react with autoantibody (IgG or IgM) +/-complement→ premature destruction • The Coombs antiglobulin test is the major diagnostic tool • Direct Coombs test: anti- IgG or anti- C3 antisera to agglutinate the RBC • Indirect Coombs test; the patient serum is incubated with normal RBCs

Autoimmune Hemolytic Anemia Warm Type
• Most common AIHA, moderate to severe hemolytic anemia • 80% of cases involve IgG class auto-Antibody at body temperature • Specifiticy for patient proteic RBC antigens • Fix complement only to level of C3 • Fc receptors/C3b recognized by macrophages • Frequently hemolysis has an acute onset with increased reticulocytes and spherocytes (indicating extra-vascular hemolysis) • Hemolysis primarily extravascular • Idiopathic or 70% associated with other illnesses (LES, LLC, NHL, HL)

Coombs Test - Direct
• Looks for immunoglobulin &/or complement of surface of red blood cell (normally neither found on RBC surface) • Coombs reagent - combination of anti-human immunoglobulin & anti-human complement • Mixed with patient’s red cells; if immunoglobulin or complement are on surface, Coombs reagent will link cells together and cause agglutination of RBCs

Coombs Test - Indirect
• Looks for anti-red blood cell antibodies in the patient’s serum, using a panel of red cells with known surface antigens

• Combine patient’s serum with cells from a panel of RBC’s with known antigens
• Add Coombs’ reagent to this mixture • If anti-RBC antigens are in serum, agglutination occurs

WARM Auto Antibodies on Laboratory Testing
Direct Antiglobulin Test Positive in the following combinations: 1. ~ 67% have both IgG and C’ coating 2. ~ 20% have IgG only coating 3. ~ 3% have C’ only coating • ABO Grouping - usually not a problem

• Rh Typing - can be a problem with IgG coated red blood cells.

Treatment
• • • • • • • Prednisolone 1mg/kgc/d 1-2 weeks, Azathioprine, cyclophosphamide Splenectomy-selected cases Rituximab (anti CD20 ) Ig(iv) 0.4g/kg/d x 5d Folic acid 5mg/d Treat underlying disease (if secondary)

AUTOIMMUNE HEMOLYSIS Cold Type • • • • Most commonly IgM mediated Antibodies bind best at 30º or lower Fix entire complement cascade Leads to formation of membrane attack complex, which leads to RBC lysis in vasculature • Typically only complement found on cells (Direct Cooms test) • 90% associated with other illnesses

Cold Hemagglutinin Disease Chronic: Often seen in elderly patients Tends to be associated with Lymphoma, CLL, Waldenstroms macroglobulinemia Increased Erythrocyte Sedimentation Rate (ESR) Raynaud’s syndrome, acrocyanosis and hemoglobinuria seen during cold weather Severity depend on antibody titer, thermal amplitude (2330), environmental temperature

• • • • •

Cold Hemagglutinin Disease Acute/Transient • Often secondary to lymphoproliferative disease (lymphoma) or Mycoplasma pneumonia infections (anti-I specificity) • Also seen in patients with Infectious Mononucleosis with anti-i specificity. • Transient: When infectious process is complete auto antibodies fade.

Direct Antiglobulin Test (DAT) • Positive with cold auto antibodies • Only Complement (C3 components) is present because these are IgM antibodies

Treatment
• • • • • • Keep warm Corticosteroids-little value Chlorambucil or cyclophosphamide Plasma exchange Splenectomy occasional useful If blood transfusion requaired-use in line blood warmer

Selection Of Blood For Transfusion MUST KNOW if there is an underlying unexpected clinically significant allo antibody. • Transfusion of patients with WAIHA is usually NOT recommended. Why? • Transfused cells are usually destroyed as rapidly as the patients own cells. • When transfusion is unavoidable, usually must transfuse with Least Incompatible Blood. • Patient is generally transfused with small volumes, to maintain O2 carrying capacity, until hemolysis diminishes or other therapy can effect a more lasting benefit.

Forward ABO Grouping
• If cells are heavily coated with auto-antibody, they may spontaneously agglutinate on forward grouping.

How is this corrected?
• Pre-warming all reagents and patient samples. • In extreme cases may need to chloroquin treat patient red cells to remove autoantibody from cell surface.

Cold Hemagglutinin Disease Paroxysmal Cold Hemoglobinuria • Auto-Antibody with anti-P specificity (P Blood Group) – Antibody is a Biphasic IgG class antibody that binds complement at cold temperatures and lyses red cells at warm temperatures • Donath-Landstiener test is confirmatory for PCH

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