Educational 🧵 on autoimmune hemolytic anemias (AIHA). Not medical advice. Always open to feedback and corrections.
#medtwitter #hematology #internalmedicine #classicalhematology
#medtwitter #hematology #internalmedicine #classicalhematology
1/Immune hemolytic anemia
Broadly divided into three groups:
Autoimmune hemolytic anemia (AIHA)
Alloimmune hemolytic anemia
Drug induced immune hemolytic anemia
We will discuss AIHA in this 🧵
Broadly divided into three groups:
Autoimmune hemolytic anemia (AIHA)
Alloimmune hemolytic anemia
Drug induced immune hemolytic anemia
We will discuss AIHA in this 🧵
2/AIHA - Major categories
Warm autoimmune hemolytic anemia (WAIHA)
Cold agglutinin disease (CAD)
Paroxysmal cold hemoglobinuria (PCH)
Mixed-type AIHA
Warm autoimmune hemolytic anemia (WAIHA)
Cold agglutinin disease (CAD)
Paroxysmal cold hemoglobinuria (PCH)
Mixed-type AIHA
3/WAIHA
*Most common AIHA
*Autoantibodies react well at 37 C, and are generally IgG
*Classified as Idiopathic or secondary
*Secondary causes include heme and solid organ malignancies, autoimmune diseases, immunodeficiency disorders, viral infections
*WAIHA + ITP = Evans Syndrome
*Most common AIHA
*Autoantibodies react well at 37 C, and are generally IgG
*Classified as Idiopathic or secondary
*Secondary causes include heme and solid organ malignancies, autoimmune diseases, immunodeficiency disorders, viral infections
*WAIHA + ITP = Evans Syndrome
4/WAIHA
*Generally presents with fatigue, dizziness, dyspnea
*Can present with fever, jaundice, hepato-splenomegaly in children with viral infections where it can be life threatening
*Generally presents with fatigue, dizziness, dyspnea
*Can present with fever, jaundice, hepato-splenomegaly in children with viral infections where it can be life threatening
5/WAIHA
*Mostly IgG mediated
*Rare cases of IgA and fatal cases with warm-reacting IgM reported
*Hemolysis is predominantly extravascular
*Splenomegaly,Lymphadenopathy,renal failure fever,petechiae should prompt evaluation for underlying lymphoproliferative disorder in adults
*Mostly IgG mediated
*Rare cases of IgA and fatal cases with warm-reacting IgM reported
*Hemolysis is predominantly extravascular
*Splenomegaly,Lymphadenopathy,renal failure fever,petechiae should prompt evaluation for underlying lymphoproliferative disorder in adults
6/WAIHA
*DAT +ve in>95% of the cases
*85% have either IgG alone or both IgG and C3d+ve DAT
*10-14% have only C3d+ve DAT
*1-4% have negative DAT due to IgA or IgM being the autoantibody
*Some other technical issues can also cause a false -ve DAT
*-ve DAT does not rule out WAIHA
*DAT +ve in>95% of the cases
*85% have either IgG alone or both IgG and C3d+ve DAT
*10-14% have only C3d+ve DAT
*1-4% have negative DAT due to IgA or IgM being the autoantibody
*Some other technical issues can also cause a false -ve DAT
*-ve DAT does not rule out WAIHA
7/WAIHA - T/t
1st line - Steroids (Prednisone)
2nd line - Either splenectomy (50% success rate) or Rituximab (73% overall response rate)
3rd line - Azathioprine or cyclophosphamide
Last resort - Hematopoietic stem cell transplant
1st line - Steroids (Prednisone)
2nd line - Either splenectomy (50% success rate) or Rituximab (73% overall response rate)
3rd line - Azathioprine or cyclophosphamide
Last resort - Hematopoietic stem cell transplant
8/CAD
*15-20% cases of AIHA
*Non-pathologic cold agglutinins are commonly found in healthy individuals at 4 C, the titres are generally less than 1:64, are polyclonal, and have no reactivity above temp of 30 C
*Pathologic cold agglutinins are monoclonal and react at temp >30 C
*15-20% cases of AIHA
*Non-pathologic cold agglutinins are commonly found in healthy individuals at 4 C, the titres are generally less than 1:64, are polyclonal, and have no reactivity above temp of 30 C
*Pathologic cold agglutinins are monoclonal and react at temp >30 C
9/CAD
Thermal amplitude (TA) - temperature range at which the cold agglutinins are reactive to the RBCs
A TA near/at 37 C causes more severe symptoms
Thermal amplitude (TA) - temperature range at which the cold agglutinins are reactive to the RBCs
A TA near/at 37 C causes more severe symptoms
10/CAD - pathophysiology
Peripheral circulation -> Drop in temperature of blood -> IgM antibody bind RBC surface -> Activates classical complement pathway -> Intravascular hemolysis
Peripheral circulation -> Drop in temperature of blood -> IgM antibody bind RBC surface -> Activates classical complement pathway -> Intravascular hemolysis
11/CAD - Pathophysiology
Return to central circulation -> Warmer temperature -> IgM dissociation but C3b remains attached -> Extravascular hemolysis in hepatic macrophages
*Patients with high TA can have intravascular hemolysis in central circulation as well
Return to central circulation -> Warmer temperature -> IgM dissociation but C3b remains attached -> Extravascular hemolysis in hepatic macrophages
*Patients with high TA can have intravascular hemolysis in central circulation as well
12/CAD
Acute CAD - Polyclonal IgM with normal κ and λ chain distribution, usually secondary to Mycoplasma, infectious mono, or other viral infections
Chronic CAD - Monoclonal IgM with κ light chains, disease of elderly-can be idiopathic or secondary to lymphoproliferative disease
Acute CAD - Polyclonal IgM with normal κ and λ chain distribution, usually secondary to Mycoplasma, infectious mono, or other viral infections
Chronic CAD - Monoclonal IgM with κ light chains, disease of elderly-can be idiopathic or secondary to lymphoproliferative disease
13/CAD
*Can present with fatigue, dyspnea, pallor, acrocyanosis
*Acrocyanosis occurs due to RBC autoagglutination in vivo causing capillary stasis
*Acute CAD has abrupt, mild to severe hemolysis typically 2-3 weeks after the aforementioned infections mentioned in tweet "12/CAD"
*Can present with fatigue, dyspnea, pallor, acrocyanosis
*Acrocyanosis occurs due to RBC autoagglutination in vivo causing capillary stasis
*Acute CAD has abrupt, mild to severe hemolysis typically 2-3 weeks after the aforementioned infections mentioned in tweet "12/CAD"
14/CAD
*DAT is positive for for C3d
*A cold agglutinin test determines titres
*Titres can be as high as 1:1,000,000 at temp of 4 C
*Blood sample fold cold agglutinins should be collected and stored at temp of 37 C to avoid a falsely low titre due to binding of IgM to RBCs
*DAT is positive for for C3d
*A cold agglutinin test determines titres
*Titres can be as high as 1:1,000,000 at temp of 4 C
*Blood sample fold cold agglutinins should be collected and stored at temp of 37 C to avoid a falsely low titre due to binding of IgM to RBCs
15/CAD
*Acute CAD is generally self limiting, and titres are usually less than 1:4000
*Severe acute CAD can be treated with blood transfusion and supportive care
*Chronic CAD with mild anemia are monitored with advice to avoid cold temperatures
*Acute CAD is generally self limiting, and titres are usually less than 1:4000
*Severe acute CAD can be treated with blood transfusion and supportive care
*Chronic CAD with mild anemia are monitored with advice to avoid cold temperatures
16/CAD
*Chronic CAD with moderate to severe symptoms can be treated with *Rituximab
*Rituximab + Fludarabine
*Rituximab +Bendamusitine
*Plasmapheresis can be used in severe cases but is only a temporary measure
*Chronic CAD with moderate to severe symptoms can be treated with *Rituximab
*Rituximab + Fludarabine
*Rituximab +Bendamusitine
*Plasmapheresis can be used in severe cases but is only a temporary measure
17/CAD
*Corticosteroids and other immunosuppressants like cyclophosphamide/chlorambucil are not useful
*Splenectomy is not useful since extravascular clearance is predominantly liver mediated
*Life threatening anemia requires RBC transfusion
*Corticosteroids and other immunosuppressants like cyclophosphamide/chlorambucil are not useful
*Splenectomy is not useful since extravascular clearance is predominantly liver mediated
*Life threatening anemia requires RBC transfusion
18/PCH
*Idiopathic or secondary
*Common in children (Post respiratory viral infection), rarer in adults (Late stage syphilis)
*Median age at presentation is 5 years and accounts for 32-40% of AIHA in children
*Idiopathic or secondary
*Common in children (Post respiratory viral infection), rarer in adults (Late stage syphilis)
*Median age at presentation is 5 years and accounts for 32-40% of AIHA in children
19/PCH
*Characterized by complement binding IgG (Anti-P antibody), called Donath-Landsteiner antibody
*Anti-P antibody is biphasic (Activates C1-C4 at 4 C activates C3-C9 at 37 C), hemolysis only occurs at 37 C
*Characterized by complement binding IgG (Anti-P antibody), called Donath-Landsteiner antibody
*Anti-P antibody is biphasic (Activates C1-C4 at 4 C activates C3-C9 at 37 C), hemolysis only occurs at 37 C
20/PCH
*Fever, malaise 1-2 weeks after an URI
*DAT +ve for C3d only
*Treated with transfusion and supportive measures
*Usually has a good prognosis and is self limiting
*Fever, malaise 1-2 weeks after an URI
*DAT +ve for C3d only
*Treated with transfusion and supportive measures
*Usually has a good prognosis and is self limiting
21/PCH
*Tested with Donath-Landsteiner screening test: Two specimens - Patient test and patient control.
*Patient test - Incubated first at 4 C for 30 minutes and then at 30 C for 30 minutes
*Patient control - Incubated at 37 C for both incubations (60 minutes)
*Tested with Donath-Landsteiner screening test: Two specimens - Patient test and patient control.
*Patient test - Incubated first at 4 C for 30 minutes and then at 30 C for 30 minutes
*Patient control - Incubated at 37 C for both incubations (60 minutes)
22/PCH
*Positive if hemolysis in test sample AND no hemolysis in control sample
*Positive if hemolysis in test sample AND no hemolysis in control sample
23/Mixed-type AIHA
*Clinically significant warm as well as cold agglutinins
*IgG with optimum reactivity at 37 C and IgM with optimum reactivity at 0-10 C, but has a TA > 30 C
*Intra+Extravascular hemolysis
*DAT can be positive for IgG alone, C3d alone or both IgG AND C3d
*Clinically significant warm as well as cold agglutinins
*IgG with optimum reactivity at 37 C and IgM with optimum reactivity at 0-10 C, but has a TA > 30 C
*Intra+Extravascular hemolysis
*DAT can be positive for IgG alone, C3d alone or both IgG AND C3d
24/Reference:
Rodak's Hematology: Clinical principles and applications, 6th edition, Chapter 23 on Extrinsic Defects Leading to Increased Erythrocyte Destruction-Immune Causes. Section on Autoimmune Hemolytic Anemia, Authored by Ruth Perez, MS.
Rodak's Hematology: Clinical principles and applications, 6th edition, Chapter 23 on Extrinsic Defects Leading to Increased Erythrocyte Destruction-Immune Causes. Section on Autoimmune Hemolytic Anemia, Authored by Ruth Perez, MS.
Unroll @threadreaderapp
• • •
Missing some Tweet in this thread? You can try to
force a refresh
