History

Fact Explanation
Palpitations, dyspnea, angina, and weakness. When haemolysis is severe and the increased production of RBC cannot compensate for the loss,symptoms of anemia appears.[1][2]
Colicky abdominal pain. Warm type AIHA mainly produce extravascular haemolysis therefore there is a higher chance of gallstone formation.[1][2]
Dark colored urine. In haemolysis unconjugated bilirubin levels are raised and when these excrete in the urine it gives a darker colour.[1][2]
Yellowish discoloration of the sclera. In hemolysis both unconjugated and the conjugated bilirubin fraction is increased therefore sclera and the mucous membranes appear yellowish.[1][2]
Any history of loss of weight,night sweats Chronic lymphocytic leukaemia, hodgkin's lymphoma can secondarily cause AIHA. [1] [2]
Drug use Drugs such as methyldopa, penicillin,cephalosporins,NSAIDS,quinine,interferon can secondarily cause warm type autoimmune haemolytic anemia.[1][2]
History of SLE SLE can also a known causative factor for AIHA.[1][2]
References
  1. CROWTHER M., CHAN Y. L. T., GARBETT I. K., LIM W., VICKERS M. A., CROWTHER M. A.. Evidence-based focused review of the treatment of idiopathic warm immune hemolytic anemia in adults. Blood [online] December, 118(15):4036-4040 [viewed 22 July 2014] Available from: doi:10.1182/blood-2011-05-347708
  2. DHALIWAL G, CORNETT PA, TIERNEY LM JR. Hemolytic anemia. Am Fam Physician [online] 2004 Jun 1, 69(11):2599-606 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15202694

Examination

Fact Explanation
Pallor Due to the reduction of oxygenated haemoglobin level which caused by haemolysis.[1]
Tachypnoea,tachycardia As a compensatory mechanism to low tissue oxygenation respiratory rate and the heart rate increases.[1]
Signs of heart faliure such as ankle oedema,elevated JVP,pulmonary oedema In patients who had prior cardiovascular diseases,with severe anemia they develop high output cardiac failure.[1]
Right sided abdominal tenderness Extravascular haemolysis induce bilirubin gall stone formation.[1]
Jaundice Due to haemolysis unconjugated and the conjugated bilirubin levels are elevated these deposit in the sclera and mucous membranes and appear yellowish.[1]
Splenomegaly In warm type AIHA mainly RBC haemolysis occurs extravascularly therefore splenomegaly appears.If AIHA is secondary to a lymphoproliferative disorder splenomegaly can be detected[1]
Lymphadenopathy If lymphoma is the cause for this warm type AIHA lymphadenopathy may be detected during examination.[1]
References
  1. DHALIWAL G, CORNETT PA, TIERNEY LM JR. Hemolytic anemia. Am Fam Physician [online] 2004 Jun 1, 69(11):2599-606 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15202694

Differential Diagnoses

Fact Explanation
Cold type autoimmune haemolytic anemia This can be differentiated from warm type AIHA by detecting haemoglobin and haemosiderin in the urine.[1]
Malaria Malaria can be diagnosed by thin and thick blood smears in the presence of malaria parasites.[1]
Drug-induced hemolysis In the history recent drug use is present.[1]
Major ABO blood group incompatibility In the history a recent blood transfusion is noted.However DAT is positive similarly in AIHA.[1]
paroxysmal nocturnal hemoglobinuria. This causes intravascular haemolysis therefore haemoglobinuria is present.And since it's a non immune haemolytic anemia DAT is negative.[1]
Thalassemia Thalassemia will be a chronic disease and diagnosis can be done by high performance liquid chromatography(HPLC)[1]
Sickle cell disease This will be a chronic disease with diagnosis can be easily done with the blood picture detecting sickle cells.[1]
Hereditary spherocytosis/Hereditary elliptocytosis Peripheral blood smear may detect spherocytes similar to AIHA,but here DAT will be negative.[1]
Mechanical haemolysis Blood smear will detect fragmented RBC with a history of prosthetic cardiac valves,haemolytic uraemic syndrome.TTP and etc.[1]
References
  1. DHALIWAL G, CORNETT PA, TIERNEY LM JR. Hemolytic anemia. Am Fam Physician [online] 2004 Jun 1, 69(11):2599-606 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15202694

Investigations - for Diagnosis

Fact Explanation
Complete blood cell count To see the involvement of other cell lines to exclude pancytopenia and to detect increased reticulocyte count which is seen as a compensation for haemolysis.[1]
Peripheral blood smear In warm type autoimmune hemolytic anemia (AIHA) peripheral smear may demonstrate spherocytes.A similar blood picture will be seen in congenital spherocytosis too.[1]
Serum lactate dehydrogenase(LDH) study Elevation of LDH is sensitive but not specific for hemolysis since LDH can be released from the liver, neoplastic cells or other damaged organs (ie.e myocardium)[1]
Serum haptoglobin In warm type AIHA haptoglobin level is normal. A decrease in level is more likely in intravascular hemolysis.[1]
Indirect bilirubin level Unconjugated bilirubin is a criterion for hemolysis, With hemolysis, indirect bilirubin level is usually less than 3 mg/dL.[1]
Direct antiglobulin test(DAT) or Coombs test This test demonstrates the presence of antibodies or complement on the surface of red blood cells and is the hallmark of autoimmune hemolysis. The patient's red blood cells are mixed with rabbit or mouse antibodies against human IgG or C3. Agglutination of the patient's antibody- or complement-coated red blood cells by anti-IgG or anti-C3 serum constitutes a positive test DAT result is usually positive in AIHA but it may occasionally be negative. 5-10% of AIHAs consists of DAT negative type . The polybrene test and immunoradiometric assay (IRMA) for red blood cell–bound IgG is used to detect DAT-negative AIHA.[1]
Abdominal ultrasound scan In extravascular haemolysis to detect splenomegaly this investigation is done.In addition abdominal lympnodes could be detected if a lymphoma is suspected as a cause for this AIHA.[1]
References
  1. DHALIWAL G, CORNETT PA, TIERNEY LM JR. Hemolytic anemia. Am Fam Physician [online] 2004 Jun 1, 69(11):2599-606 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15202694

Investigations - Fitness for Management

Fact Explanation
Chest radiography To detect any evidence of heart failure as a result of anemia.[1]
Electrocardiography To detect any evidence of heart failure as a result of anemia.[1]
References
  1. DHALIWAL G, CORNETT PA, TIERNEY LM JR. Hemolytic anemia. Am Fam Physician [online] 2004 Jun 1, 69(11):2599-606 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15202694

Investigations - Followup

Fact Explanation
Complete blood cell count During treatment once in 2-4 weeks to see the response by the increasing level of RBC count and the hemoglobin level[1]
References
  1. DHALIWAL G, CORNETT PA, TIERNEY LM JR. Hemolytic anemia. Am Fam Physician [online] 2004 Jun 1, 69(11):2599-606 [viewed 27 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15202694

Management - General Measures

Fact Explanation
Blood transfusions Many patients with severe hemolysis have detectable plasma antibody(pan agglutinins) hence, it may be impossible to find compatible blood for these patients. In this case, if clinically indicated, incompatible blood can be transfused if the laboratory takes special care to ensure it is ABO and Rh compatible. It has been reported that blood transfusion may adversely affect the patient by introducing more alloimmune antigens that further activate the immune system. Still transfusion therapy is still an important supportive measure in patients whose anemia has put them at risk of serious complications or death. Corticosteroid therapy, initiated with the blood transfusion,may suppress the immune destruction of the transfused red cells.[1][2]
Withholding the offending drug If there is any suspicion that the AIHA is due to a certain drug,it should be stopped immediately.[1]
References
  1. CROWTHER M., CHAN Y. L. T., GARBETT I. K., LIM W., VICKERS M. A., CROWTHER M. A.. Evidence-based focused review of the treatment of idiopathic warm immune hemolytic anemia in adults. Blood [online] December, 118(15):4036-4040 [viewed 22 July 2014] Available from: doi:10.1182/blood-2011-05-347708
  2. LECHNER K., JAGER U.. How I treat autoimmune hemolytic anemias in adults. Blood [online] December, 116(11):1831-1838 [viewed 22 July 2014] Available from: doi:10.1182/blood-2010-03-259325

Management - Specific Treatments

Fact Explanation
Steroid therapy Treatment with high-dose steroids, usually in the form of prednisone at 1–1.5 mg/kg/day, is initiated once the diagnosis of WAHA has been confirmed. The median time of response is 7–10 days. The mechanism of action of steroid therapy include: suppression of red cell clearance by the reticuloendothelial system;downregulation of the number of FcR inhibition of the release of lysosomal enzymes by macrophages; and suppression of autoantibody production. When hematologic improvement is seen, the dose of steroid should be gradually tapered over the next several months to minimize the side-effects of long-term steroid therapy. In 60–70% of patients, complete remission can be achieved, but for some patients, maintenance therapy is required. Among these patients, 50% may relapse and further treatment with higher doses of steroid therapy may be beneficial. If there is a non response to steroid by the end of the first 3 weeks, continued therapy with steroid alone is usually ineffective. Up to 40% of patients with WAHA become either steroid-dependent or steroid-resistant.[1][2]
Splenectomy Splenectomy is effective in about half of patients with WAHA.Splenectomy removes the major site of antigen presentation and, in turn, reduces antibody production.With the advance of laparoscopic splenectomy, the incidence of severe surgical complications has been reduced. The major long-term complication of splenectomy is infection, particularly of encapsulated organisms. Therefore, all patients undergoing splenectomy should receive vaccine immunization against Streptococcus pneumoniae, Meningococcus and possibly Haemophilus influenzae.[1][2]
Immunosuppressive therapy Immunosuppressive therapies, including vinca alkaloids,azathioprine and cyclophosphamide, have been reported to be beneficial in the treatment of WAHA, although the therapeutic effect may be delayed for 3–6 months after the initiation of treatment. In a small case series, the response rate was reported to be about 50%.Patients who do experience a clinical response to this therapy may require maintenance therapy for up to 12 months to induce remission. Rituximab seems highly effective and relatively safe in adults with steroid-resistant or steroid-dependent warm type AIHA.[1][2][3]
Danazol A recent study has suggested that Danazol may induce long-lasting remission in patients with refractory WAHA. The possible mechanisms include reduction in red cell bound C3d immunomodulation by alteration of T-cell subsets and reduction of FcR in the reticuloendothelial system.Side-effects from Danazol include virilization effects and dose-dependant hepatic toxicity.[1][2]
References
  1. CROWTHER M., CHAN Y. L. T., GARBETT I. K., LIM W., VICKERS M. A., CROWTHER M. A.. Evidence-based focused review of the treatment of idiopathic warm immune hemolytic anemia in adults. Blood [online] December, 118(15):4036-4040 [viewed 22 July 2014] Available from: doi:10.1182/blood-2011-05-347708
  2. LECHNER K., JAGER U.. How I treat autoimmune hemolytic anemias in adults. Blood [online] December, 116(11):1831-1838 [viewed 22 July 2014] Available from: doi:10.1182/blood-2010-03-259325
  3. BUSSONE GUILLAUME, RIBEIRO EMMANUEL, DECHARTRES AGNèS, VIALLARD JEAN-FRANçOIS, BONNOTTE BERNARD, FAIN OLIVIER, GODEAU BERTRAND, MICHEL MARC. Efficacy and safety of rituximab in adults' warm antibody autoimmune haemolytic anemia: Retrospective analysis of 27 cases. Am. J. Hematol. [online] 2009 March, 84(3):153-157 [viewed 27 July 2014] Available from: doi:10.1002/ajh.21341