Cause:Autoimmune in 1 of several different ways (see below) via drugs, cold agglutinins, idiopathic immune globulins

Pathophys:

Types:

• Autoimmune: perhaps spontaneously, eg, in SLE, perhaps induced by unknown agents
• Drug induced: methyldopa (antibodies are vs Rh antigens, 20% have positive Coombs after 5-mo rx, dose-related but much lesser % of hemolysis because of coincident RES impairment—Nejm 1985;313:596), procainamide (20%—Nejm 1984;311:809)
• Hapten type: drug or virus (Nejm 1971;284:1250) attaches to rbc and antibody is directed vs this combination; eg, penicillin, esp high-dose iv (Nejm 1972;287:1322)
• "Innocent bystander": agent/drug loosely attaches to rbc, antibody + C' attaches to rbc antigen-agent combination, agent/drug falls off leaving antibody + C'-coated rbc, which is then picked up and lysed by RES rather than intravascularly; occasionally similar coincident platelet injury; eg, penicillin (ibid), tetracycline (ibid), cephalothins (Ann IM 1977;86:64), quinine, quinidine, sulfas (Nejm 1970;283:900)
• Cold agglutinin disease: usually IgM, unlike above, which are usually IgG (Ann IM 1987;106:238)

Sx:of anemia

Si:Splenomegaly, jaundice

Drug types resolve with drug withdrawal; others respond to rx of primary disease, splenectomy, and steroids

Pulmonary emboli are most common cause of death; infections

Lab:

Chem:Bilirubin increased

Hem:Smear shows spherocytes, "too many to be congenital spherocytosis"; retics increased; Coombs often positive, though can be negative if antibody pulled off rbc by test serum; anti-C'3 Coombs positive; in innocent bystander type, increased osmotic fragility; IgG coating of rbc, 35-200 molecules/rbc too few to give positive Coombs but can be detected (Nejm 1971;285:254), debate about what number is significant and what false-pos/neg rate at each level, may be useful to follow autoimmune and drug-induced types

Rx:Steroids (often relapse on moderate doses); cyclophosphamide (Nejm 1976;295:1522); androgens like danazol 600-800 mg qd until better, then 200-400 mg qd maintenance (Ann IM 1985;102:298)

Splenectomy, 50% permanent remission, though Coombs may remain positive; takes 3 wk to help, unlike rbc-defective hemolytic anemias, probably because needs time for antibody levels to diminish