Hemolytic Anemias Flashcards
Describe how a DAT works
Testing if patient RBCs have IgG and/or C3 antibodies bound to their surface. If they do, when adding IgG and C3 specific Abs, the cells will agglutinate.
5 examples of DAT+ hemolysis
Warm AIHA
CAD
PNH and PCH
Transfusion reactions
Drug induced hemolysis
6 Examples of DAT- hemolysis
DAT-negative AIHA (1-10%)
Hemoglobinopathies
Enzymopathies
MAHA
Toxins
IgA or IgM dependent hemolysis
Most common DAT result in warm AIHA?
IgG+
C3+
describe pathophysiology of warm AIHA
Patients have a panagglutinating IgG antibody directed against a common antigen on RBC surface (like Rh and others). These bind at body temperature, causing enhanced destruction of Ab-coated RBCs by macrophages in the spleen
First line Treatment for warm AIHA
Steroids. Takes 7-25 days to respond, and 75-80% of patients respond. Very slow taper
Second line therapy for warm AIHA (5)
Rituximab
Splenectomy
IVIG
MMF
Sirolimus
Patients with warm AIHA secondary to autoimmune lymphoproliferative syndrome (ALPS) have a high response rate to what treatment?
Sirolimus
Pathophysiology of Cold Agglutinin disease
IgM antibodies directed against RBCs I antigen that are active below body temperature. Causing RBC agglutination and extravascular hemolysis.
In secondary cold AIHA. What are the two most common infections?
Mycoplasma
Mono (EBV)
Patient with hemolytic anemia, livedo reticularis. Smear shows RBC agglutination. DAT is +C3 but negative for IgG. Most likely diagnosis and test to confirm?
Cold agglutinin disease (cold AIHA)
Thermal amplitude test
What is a clinically significant result on thermal amplitude test for cold AIHA?
1:64 or greater
Management of cold AIHA
Avoid cold
Transfuse as needed
Plasmapheresis for severe cases
Benda + Ritux if associated with underlying B cell disorder
Sutimlimab
What is the indication for sutimlimab?
In cold AIHA, useful for temporizing patients requiring transfusions for severe symptoms or those who can’t take immunosuppression, or refractory to immunosuppression, or those that require rapid action to improve symptoms and relieve transfusion burden
Pathophysiology of PCH
Immune mediated intravascular hemolytic anemia because of IgG that binds RBC P antigen in a cold environment and fixes complement.
Mechanism of action of sutimlimab?
Targets C1s protein, a protease that activates the classic complement pathway. Treats the anemia, hemolysis, and fatigue of cold AIHA, but doesn’t get rid of the cold agglutinin
You see a patient present with nausea, vomiting, back pain, weakness, dark urine, and evidence of hemolytic anemia. They had a viral URI about 10 days prior. DAT shows IgG negative and C3 positive. What is the test to confirm the most likely diagnosis?
Donath Landsteiner test: AutoAb taht binds to RBCs and fixes complement at cold temperatures and dissociates upon warming.
Diagnosis is PCH
Treatment for PCH
Typically self-limited
Supportive care for acute episodes
Avoid cold
If there is no rapid recovery, can offer steroids or rituximab
Pathophysiology of PNH
PIG-A mutation seen in a pluripotent stem cell causing the lack of GPI anchors in that cell, meaning complement inhibitory proteins CD55 and CD59 are not present.
This mutation is not sufficient for PNH, this clone needs to undergo expansion. Then there is a complement driven hemolytic anemia
Aside from hemolytic anemia, what are other clinical features seen in PNH?
Dark/red urine
bone marrow failure
Thrombosis, typically in unusual sites (highest risk with PNH cells >50%)
Smooth muscle dystonia (vascular constriction, pHTN)
First line Treatment for PNH
Eculizumab, Ravulizumab
Mechanism of action of Eculizumab and Ravulizumab
C5 complement inhibtor. Inhibitrs the terminal complement pathway, blocking intravascular hemolysis, doesn’t treat bone marrow failure or extravascular hemolysis
Second line therapy for PNH after eculizumab or ravulizumab
Pegcetacoplan (C3 inhibitor)
Iptacopan (factor B inhibitor)
What treatment was approved in 2024 for PNH to be used in addition to eculizumab or ravulizumab?
Danicopan