Cold Agglutinin Disease 3 Types of Cold Sensitive Antibodies: 1. Cold Agglutinins (CAD) 2. Donath-Landsteiner Antibodies[PCH] 3. Cryoglobulins (Vasculitic Picture) Epidemiology: • 6-7th decade • May occur in 30's • Mostly women • 15% of AIHA Primary Secondary Cold Agglutinin Disease (CAD): - Idiopathic monoclonal IgM - Possibly originate from a low-grade lymphoproliferative disorder Secondary Cold Agglutinin Syndrome (CAS): - Due to Viral infection, autoimmune disorder or lymphoid malignancy (CLL) - Monoclonal - Lymphoid Malignancy - Polyclonal - Viral Infection Clinical Presentation - Cold-Induced Circulatory Symptoms: • Livedo reticularis • Raynaud disease • Agglutination in the nose, ears, or fingers • Acrocyanosis (Cold-induced symptoms - most common presentation) • Cutaneous necrosis • Hemoglobinuria • Symptoms of anemia include fatigue, pallor, dyspnea, and poor appetite. Diagnosis: • hemolytic anemia • Cold agglutinin titer of ≥64 at 4°C • Reticulocytosis • Hyperbilirubinemia • Elevated lactate dehydrogenase • Positive Coombs testing for anti-C3d and negative anti-lgG • Compensated hemolysis • C3↓ C4↓ • +Immunoglobulin M (IgM) • Blood smear - RBC agglutination After CAD Is Established Check For: • Infections: Polyclonal IgM post infectious setting - Mycoplasma, EBV, HIV, rubella legionella, varicella, Citrobacter and influenza (younger pts) • Underlying malignancies - B-cell malignancies -> CLL (older) • Autoimmune disease (younger pts) Differential Diagnosis Monoclonal IgM Includes Disorders Such As: • IgM monoclonal gammopathy of undetermined significance (MGUS), CLL, Myeloma • Waldenström macroglobulinemia Paroxysmal Cold Hemoglobinuria (PCH): • Donath-Landsteiner (IgG) antibodies sensitize red blood cells (RBCs) at cold temperatures by fixing complement to the RBCs causing intravascular hemolysis on rewarming • Symptoms: High fevers, chills, flank pain, hemoglobinemia and passage of red-brown urine • Diagnostic Test: Donath-Landsteiner test #cold #agglutinin #disease #hemolytic #anemia #hematology #diagnosis
