Autoimmune Hemolytic Anemia - Warm type - Clinicals, Diagnosis, and Management

Hematology

Clinicals - 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. Palpitations, dyspnea, angina, and weakness.
When haemolysis is severe and the increased production of RBC cannot compensate for the loss,symptoms of anemia appears.
Colicky abdominal pain. Warm type AIHA mainly produce extravascular haemolysis therefore there is a higher chance of gallstone formation. Colicky abdominal pain.
Warm type AIHA mainly produce extravascular haemolysis therefore there is a higher chance of gallstone formation.
Dark colored urine. In haemolysis unconjugated bilirubin levels are raised and when these excrete in the urine it gives a darker colour. Dark colored urine.
In haemolysis unconjugated bilirubin levels are raised and when these excrete in the urine it gives a darker colour.
Yellowish discoloration of the sclera. In hemolysis both unconjugated and the conjugated bilirubin fraction is increased therefore sclera and the mucous membranes appear yellowish. Yellowish discoloration of the sclera.
In hemolysis both unconjugated and the conjugated bilirubin fraction is increased therefore sclera and the mucous membranes appear yellowish.
Any history of loss of weight,night sweats Chronic lymphocytic leukaemia, hodgkin's lymphoma can secondarily cause AIHA. Any history of loss of weight,night sweats
Chronic lymphocytic leukaemia, hodgkin's lymphoma can secondarily cause AIHA.
Drug use Drugs such as methyldopa, penicillin,cephalosporins,NSAIDS,quinine,interferon can secondarily cause warm type autoimmune haemolytic anemia. Drug use
Drugs such as methyldopa, penicillin,cephalosporins,NSAIDS,quinine,interferon can secondarily cause warm type autoimmune haemolytic anemia.
History of SLE SLE can also a known causative factor for AIHA. History of SLE
SLE can also a known causative factor for AIHA.

Clinicals - Examination

Fact Explanation
Pallor Due to the reduction of oxygenated haemoglobin level which caused by haemolysis. Pallor
Due to the reduction of oxygenated haemoglobin level which caused by haemolysis.
Tachypnoea,tachycardia As a compensatory mechanism to low tissue oxygenation respiratory rate and the heart rate increases. Tachypnoea,tachycardia
As a compensatory mechanism to low tissue oxygenation respiratory rate and the heart rate increases.
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. 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.
Right sided abdominal tenderness Extravascular haemolysis induce bilirubin gall stone formation. Right sided abdominal tenderness
Extravascular haemolysis induce bilirubin gall stone formation.
Jaundice Due to haemolysis unconjugated and the conjugated bilirubin levels are elevated these deposit in the sclera and mucous membranes and appear yellowish. Jaundice
Due to haemolysis unconjugated and the conjugated bilirubin levels are elevated these deposit in the sclera and mucous membranes and appear yellowish.
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 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
Lymphadenopathy If lymphoma is the cause for this warm type AIHA lymphadenopathy may be detected during examination. Lymphadenopathy
If lymphoma is the cause for this warm type AIHA lymphadenopathy may be detected during examination.

Investigations - 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. 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.
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. 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.
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) 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)
Serum haptoglobin In warm type AIHA haptoglobin level is normal. A decrease in level is more likely in intravascular hemolysis. Serum haptoglobin
In warm type AIHA haptoglobin level is normal. A decrease in level is more likely in intravascular hemolysis.
Indirect bilirubin level Unconjugated bilirubin is a criterion for hemolysis, With hemolysis, indirect bilirubin level is usually less than 3 mg/dL. Indirect bilirubin level
Unconjugated bilirubin is a criterion for hemolysis, With hemolysis, indirect bilirubin level is usually less than 3 mg/dL.
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.
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.
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. 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.

Investigations - Management

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 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
Chest radiography To detect any evidence of heart failure as a result of anemia. Chest radiography
To detect any evidence of heart failure as a result of anemia.
Electrocardiography To detect any evidence of heart failure as a result of anemia. Electrocardiography
To detect any evidence of heart failure as a result of anemia.

Management - Supportive

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.
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.
Withholding the offending drug If there is any suspicion that the AIHA is due to a certain drug,it should be stopped immediately. Withholding the offending drug
If there is any suspicion that the AIHA is due to a certain drug,it should be stopped immediately.

Management - Specific

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.
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.
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.
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.
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.
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.
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.
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.

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