Type II Hypersensitivity Reactions: Six Clinical Examples
Type II hypersensitivity reactions are antibody-mediated cytotoxic reactions where IgG or IgM antibodies target cell surface antigens, leading to cell destruction through complement activation, antibody-dependent cellular cytotoxicity, or interference with cellular function. 1
Six Classic Examples of Type II Hypersensitivity
1. Hemolytic Anemia
- Drug-induced or autoimmune hemolytic anemia occurs when antibodies bind to red blood cell surface antigens, triggering complement-mediated lysis or phagocytic destruction 1
- Antibiotics (particularly penicillins and cephalosporins) can induce hemolytic anemia as a Type II reaction 1
- Clinical presentation includes jaundice, fatigue, dark urine, and laboratory findings of elevated indirect bilirubin and reticulocytosis 2
2. Thrombocytopenia
- Antibody-mediated destruction of platelets leads to low platelet counts and bleeding risk 1
- Drug-induced thrombocytopenia can occur with antibiotics (particularly trimethoprim/sulfamethoxazole), where antibodies target platelet surface antigens 1
- Manifests as petechiae, purpura, mucosal bleeding, or more severe hemorrhage depending on platelet count 1
3. Blood Transfusion Reactions
- Acute hemolytic transfusion reactions occur when recipient antibodies (typically ABO incompatibility) attack donor red blood cells 1
- Presents with fever, chills, back pain, hemoglobinuria, hypotension, and potential acute kidney injury within minutes to hours of transfusion 3
- Represents a medical emergency requiring immediate cessation of transfusion and supportive care 3
4. Hemolytic Disease of the Fetus and Newborn (HDFN)
- Maternal IgG antibodies (anti-D, anti-K, anti-Kp(a), or other blood group antibodies) cross the placenta and destroy fetal red blood cells expressing paternal antigens 4, 5
- Anti-K and anti-Kp(a) are particularly severe because they not only destroy red blood cells but also suppress fetal erythropoiesis, causing profound anemia disproportionate to antibody titer 4, 5
- Clinical manifestations range from mild jaundice to severe hydrops fetalis, requiring intrauterine transfusions or early delivery 5
5. Drug-Induced Neutropenia/Agranulocytosis
- Antibodies target neutrophil surface antigens, leading to their destruction and severe immunosuppression 1
- Minocycline and trimethoprim/sulfamethoxazole are notable culprits, with agranulocytosis representing a rare but life-threatening complication 1
- Presents with severe infections, fever, and absolute neutrophil count typically <500 cells/μL 1
6. Thrombocytopenic Purpura
- Anaphylactoid purpura represents antibody-mediated platelet destruction with associated purpuric skin lesions 1
- Tetracyclines and other antibiotics can trigger this Type II reaction through hapten-mediated antibody formation against platelet antigens 1
- Distinguished from Type III reactions by direct antibody binding to platelets rather than immune complex deposition 6
Key Mechanistic Features
- Timing: Type II reactions typically develop hours to days after exposure, distinguishing them from immediate Type I reactions 7, 3
- Antibody types: Predominantly IgG or IgM antibodies that fix complement and activate cytotoxic mechanisms 1, 6
- Cell destruction mechanisms: Include complement-mediated lysis, antibody-dependent cellular cytotoxicity (ADCC), and opsonization leading to phagocytosis 6
- Diagnostic approach: Direct antiglobulin test (Coombs test) for hemolytic anemia, platelet antibody testing for thrombocytopenia, and blood type/crossmatch for transfusion reactions 4, 5
Critical Clinical Pitfall
Hematuria in the setting of suspected anaphylaxis should raise suspicion for concurrent Type II hypersensitivity with hemolytic anemia or thrombocytopenia, requiring immediate laboratory evaluation including complete blood count, peripheral smear, and direct antiglobulin testing. 3 This represents a distinct pathophysiologic process from Type I anaphylaxis and requires specific monitoring for end-organ damage from hemolysis or bleeding 3