Coombs’ test

The direct Coombs test detects the presence of antibodies on red cells, whereas the indirect test detects the presence of circulating antibodies to antigens present on red cells. 

Adverse reactions CNS Convulsions, confusion, drowsiness, myoclonus, fever Dermatologic Rash Metabolic Electrolyte imbalance Hematologic Positive Coombs test, hemolytic anemia Local Rain, thrombophlebitis Renal Acute interstitial nephritis Miscellaneous Anaphylaxis, hypersensitivity, Jarisch-Herxheimer reaction CNS Seizures, confusion, drowsiness, myoclonus, CNS stimulation Cardiovascular Myocardial depression, vasodilation, conduction disturbances Hematologic Positive Coombs test, hemolytic anemia, neutropenia Local Thrombophlebitis, sterile abscess at injection site Renal Interstitial nephritis Miscellaneous Pseudoanaphylactic reactions, hypersensitivity, Jarisch-Herxheimer reaction, serum sickness... 

A positive Coombs test and hemolytic anemia may follow the administration of which antihypertensive drug ... 

The answer is a. (Katzung, p 162.) Many drugs can cause an immunohemolytic anemia. Methyldopa may cause a positive Coombs test in as many as 20% of patients, along with hemolytic anemia. Other drugs with similar actions on red blood cells are penicillins, quinidine, procainamide, and sulfonamides. These form a stable or unstable hapten on the red cell surface, which induces an immune reaction I immunoglobulin G (IgG) antibodies] and leads to dissolution of the membrane. 

Major progress in the analytical use of antibodies occurred with the development of several fundamental techniques the ability to detect cell-bound antibody (Coombs Test, 1945) immunoprecipitation in gels (Ouchterlony, 1953) radioimmunoassay (Yalow and Berson, 1960) and monoclonal antibodies (Kohler and Milstein, 1975). These, together with a con-... 

Methyldopa has been used for approximately 15 years. The most common side effects are somnolence, hemolytic anemia (rare), appearance of a direct Coombs test (frequent), methyldopa fever and hepatotoxicity (rare). 

Positive Coombs test/Hemolytic anemia With prolonged therapy, 10% to 20% of patients develop a positive direct Coombs test, usually between 6 and 12 months of therapy. This is associated rarely with hemolytic anemia, which could lead to potentially fatal complications and is difficult to predict. Perform baseline and periodic blood counts to detect hemolytic anemia. If Coombs -positive hemolytic anemia occurs, discontinue methyidopa anemia usually remits promptly. 

Blood transfusions Should the need for transfusion arise in a patient receiving methyidopa, perform both a direct and indirect Coombs test. 

Monitoring Blood count, Coombs tests, and liver function tests are recommended before initiating therapy and at periodic intervals. Perform periodic determinations of hepatic function, particularly during the first 6 to 12 weeks of therapy or when an unexplained fever occurs. 

Drug/Lab test interactions False-positive urine glucose reactions may occur with penicillin therapy if Clinitest, Benedict s Solution, or Fehling s Solution are used. It is recommended that enzymatic glucose oxidase tests (such as Clinistix or Tes-Tape) be used. Positive Coombs tests have occurred. High urine concentrations of some penicillins may produce false-positive protein reactions (pseudoproteinuria) with the P.870... 

Perform both direct and indirect Coombs test if blood transfusion needed. If indirect Coombs test positive, interference may occur with crossmatch. Positive direct Coombs test will not interfere... 

Direct Coombs test before therapy and after 6-12 mo. If positive, rule out hemolytic anemia... 

Other important adverse effects of methyldopa are development of a positive Coombs test (occurring in 10-20% of patients undergoing therapy for longer than 12 months), which sometimes makes cross-matching blood for transfusion difficult and rarely is associated with hemolytic anemia, as well as hepatitis and drug fever. Discontinuation of the drug usually results in prompt reversal of these abnormalities. 

Mydriasis may occur and may precipitate an attack of acute glaucoma in some patients. Other reported but rare adverse effects include various blood dyscrasias a positive Coombs test with evidence of hemolysis hot flushes aggravation or precipitation of gout abnormalities of smell or taste brownish discoloration of saliva, urine, or vaginal secretions priapism and mild—usually transient—elevations of blood urea nitrogen and of serum transaminases, alkaline phosphatase, and bilirubin. 

False-positive protein reactions False-positive Coombs test... 

Adverse Reactions Diarrhea, nausea Eosinophilia, positive Coombs test, thrombocytosis, agranulocytosis, hemolytic anemia, leukopenia, thrombocytopenia, prolonged prothrombin time Elevation of hepatic enzymes Rash, anaphylactic reaction Phlebitis at injection site... 

It is unclear whether metformin caused hemolysis directly in this case or via G6PD deficiency. Two other patients have been reported with normal G6PD activity (94,95) one had a positive Coombs test (95). 

The most important diagnostic features of HS are as follows (1) congenital hemolytic anemia (2) microspherocytosis on the peripheral blood film (3) increased osmotic fragility, particularly in incubated red cells and (4) negative antiglobulin (Coombs) test. 

Laboratory tests showed that hemoglobin was 7.5 g/dL (normal range is 12-15 g/dL), and the reticulocyte count was 262 x 109/L (normal range is 50-100 X 109/L). The tests also indicated neutrophilia, a white cell count of 34 X 109/L (normal range is 4-11 x 109/L), and a platelet count of 328 X 109/L (normal range is 150-400 X 109/L). Renal function was normal. Malarial parasite screen and direct Coombs test were negative. Blood film showed nucleated red blood cells and anisocytosis with bite cells ... 

Antiphospholipid syndrome is a disorder of recurrent arterial or venous thrombosis, thrombocytopenia, hemolytic anemia, or a positive Coombs test, and in women recurrent idiopathic fetal loss, associated with raised concentrations of antiphospholipid antibodies. In systemic lupus erythematosus, the risk of this syndrome is about 40%, compared with a risk of 15% in the absence of antiphospholipid antibodies (539). However, only half of those with antiphospholipid antibodies have systemic lupus erythematosus, and the overall risk of the syndrome is about 30%. In patients who have antiphospholipid antibodies associated with chlorpromazine, there appears to be no increased risk of the syndrome. In contrast, in the primary antiphospholipid syndrome, the only clinical manifestations are the features of this syndrome. 

A 79-year-old woman who had been taking sulfasalazine for ulcerative colitis for 5 years developed a positive Coombs test and a hemoglobin of 8.2 g/dl. 

Hemolytic anemia has been reported (SEDA-10, 79) (SEDA-12, 83). A high percentage of patients taking azapropazone had a positive direct Coombs test, but this did not persist after treatment had been stopped for several weeks (SEDA-12,83). Hemolytic anemia has also been described in combination with pulmonary alveolitis, which suggests an allergic or immune reaction (3). Photosensitivity is often reported 190 reports of photosensitivity were submitted to several national drugmonitoring centers in Europe in 1985 (SEDA-10, 79) (SEDA-12, 83). 

Non-IgE-antibody-mediated immunological reactions Modification of erythrocyte surface components due to binding of beta-lactams or their metabolic products is thought to be the cause of the formation of antierythrocyte antibodies and the development of a positive Coombs test implicated in the development of immune hemolytic anemia (211). About 3% of patients receiving large doses of intravenous penicillin (10-20 million units/ day) will develop a positive direct Coombs test (212). However, only a small fraction of Coombs positive patients will develop frank hemolytic anemia (213). Antibody-coated erythrocytes are probably eliminated by the reticuloendothelial system (extravascular hemolysis) (214), or less often by complement-mediated intravascular erythrocyte destruction (215). Another mechanism implicates circulating immune complexes (anti-beta-lactam antibody/beta-lactam complexes), resulting in erythrocyte elimination by an innocent bystander mechanism (82). Similar mechanisms have been implicated in thrombocytopenia associated with beta-lactam antibiotics (216,217). 

Blanchard M, Oppliger R, Bucher U. Positiver direkter Coombs-Test bei akuten Leukamien und anderen Hamoblastosen Zusammenhang mit clavulansaurehaltigen Antibiotika [Positive direct Coombs test in acute leukemias... 

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