Cold Agglutinin Disease, a rare blood disorder, is a type of autoimmune hemolytic anemia. Cold agglutinin disease, also called cold antibody disease. Cold agglutinin disease (CAD) usually develops as a result of the production of a specific IgM antibody directed against the I/i antigens (precursors of the ABH and Lewis blood group substances) on RBCs.
It is caused by the body mistakenly making antibodies (of the IgM type) against a component of red blood cells. Cold agglutinin disease is classified as primary or secondary. Primary cold agglutinin disease is usually associated with monoclonal cold-reacting autoantibodies.
Cold agglutinin disease occurs in the pediatric population but is more frequent in the elderly population.Primary cold agglutinin disease is chronic and occurs after the fifth decade of life, with a peak incidence at approximately age 70 years. Secondary cold agglutinin disease may be associated with either monoclonal or polyclonal cold-reacting autoantibodies. Secondary cold agglutinin disease is predominantly caused by infection. Secondary cold agglutinin disease in children and young adults is usually transient and is caused by infection. Secondary cold agglutinin disease primarily occurs in children and young adults.
Overall, roughly 7-25 percentage of cases of autoimmune hemolytic anemia are caused by cool agglutinins only. Symptoms of this disorder may include tiredness; anemia caused by reduced levels of circulating crimson blood cells; jaundice characterized by relentless yellowing of the rind, mucous membranes and whites of the eyes; and/or perspiration and coolness of the fingers and/or toes and spotty bluish or crimson discoloration of the rind of the fingers toes, ankles, and wrists. Cold agglutinins are seen in CANOMAD syndrome. CANOMAD syndrome is described by gait and upper-limb ataxia.
Cranial nerve involvement with external ophthalmoplegia. More than 80% of patients have evidence of hepatitis C infection. Interferon and interferon plus ribavirin have been shown to produce serologic responses. Conventional medical treatments may help relieve the symptoms of cold agglutinin disease. When vasculitis is active, corticosteroids are often required to permit healing of ulcers in the skin or to treat the membranoproliferative glomerulonephritis that is seen, thereby preventing loss of renal function. Rituximab therapy has been found to be effective in mixed cryoglobulinemia, with decreases in cryoglobulin values and improvement in complement values.
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