55 Hemolytic Anemia resulting from Immune Injury Flashcards
The two main features of immune red blood cell (RBC) injury are
- (a) shortened RBC survival in vivo and
- (b) evidence of host antibodies reactive with autologous RBCs, most frequently demonstrated by a positive direct antiglobulin test (DAT) result, also known as the Coombs test
Most cases in adults are mediated by ___________ autoantibodies.
Warm-reactive autoantibodies
Sera of some patients with hemolytic anemia directly agglutinated saline suspensions of normal or autologous human RBCs
These serum factors, later shown to be specific antibodies (largely of the immunoglobulin [Ig] M class), were termed
Direct or saline agglutinins
The patients’ sera could mediate lysis of the test RBCs in the presence of fresh serum as a complement source.
The heat-stable factors (antibodies) necessary for in vitro complement-mediated lysis were called
Hemolysins
When the RBCs are coated chiefly with complement proteins, a positive DAT result depends on the presence of anticomplement (principally ____________) in the antiglobulin reagent.
anti-C3
Cryopathic hemolytic syndromes are caused by autoantibodies that bind RBCs optimally at temperatures less than _____°C and usually less than ______°C.
Less than 37°C and usually less than 31°C
Two major types of “cold antibody” may produce AHA:
- Cold agglutinins: cold agglutinin disease; agglutinins
- Donath-Landsteiner autoantibody: paroxysmal cold hemoglobinuria; hemolysins
Immunoglobulin OR complement system
In both cryopathic syndromes, the ____________ plays a major role in RBC injury; as such, much greater potential exists for direct intravascular hemolysis than in warm antibody–mediated AHA.
Complement system
Cold agglutinin disease pertains to patients with chronic AHA in which the autoantibody directly agglutinates human RBCs at temperatures below body temperature, maximally at __________°C.
0°C–5°C
Cold agglutinins typically are Ig_____, although occasionally they may be immunoglobulins of other isotypes.
IgM
Monoclonal or Polyclonal
The cold agglutinins in chronic cold agglutinin disease generally are__________.
Monoclonal
Most cold agglutinins have specificity for _______________of the RBC
Oligosaccharide antigens (I or i)
Viral disease associated with Donath-Landsteiner antibody
Congenital or tertiary syphilis
rare
An increasing proportion of Donath-Landsteiner autoantibody-mediated hemolytic anemias occurs as a single postviral episode in children, without recurrent attacks (paroxysms).
The prognosis for such cases is excellent.
Donath-Landsteiner hemolytic anemia
When no recognizable underlying disease is present, the AHA is termed
Primary or idiopathic
Account for approximately half of all secondary warm AHA cases
Lymphocytic malignancies, particularly chronic lymphocytic leukemia (CLL) and lymphomas
The majority of AHA cases mediated by cold agglutinins have a
Clonal lymphoproliferative disorder
Without clinical or radiologic evidence of malignancy; these are considered primary
A large proportion of patients with mixed cold and warm autoantibodies have this autoimmune disease
SLE
Infections associated with AHA mediated by cold agglutinins
Infectious mononucleosis and Mycoplasma pneumoniae
Hemolysis is rare
Rarely, in children with chickenpox
Despite the frequent occurrence of immune thrombocytopenia and positive DATs in patients infected with human immunodeficiency virus (HIV), AHA is relatively rare in these patients.
Two of the mechanisms of drug-immune hemolytic anemia that involve drug-dependent antibodies
Hapten-drug adsorption and ternary complex formation
TRUE OR FALSE
Drug-related nonimmunologic protein adsorption by RBCs may result in a positive DAT without actual RBC injury.
TRUE
Drug-related nonimmunologic protein adsorption by RBCs may result in a positive DAT without actual RBC injury.
In general, AHA is considered secondary when
(a) AHA and the underlying disease occur together with greater frequency than can be accounted for by chance alone
(b) the AHA reverses simultaneously with correction of the associated disease, or
(c) AHA and the associated disease are related by evidence of immunologic aberration
Careful follow-up of patients with primary AHA is essential because hemolytic anemia may be the presenting finding in a patient who subsequently develops overt evidence of an underlying disorder.
The most common cause of drug-induced autoantibodies
Fludarabine
Replaced α-methyldopa
In warm-antibody AHA, the autoantibodies that mediate RBC destruction are predominantly (but not exclusively) ______ globulins
IgG
Although generally transient, the positive DAT result may persist for up to _____ days in some transfusion recipients, long after any transfused RBCs have disappeared.
300 days
Drug that can induce warm-reacting IgG anti-RBC autoantibodies in otherwise normal persons
α-methyldopa
A critical difference is that the drug-associated autoantibodies subside when the drug is discontinued, suggesting that
* (a) the latent potential to form this type of anti-RBC autoantibody is present in many immunologically normal individuals, and
* (b) the steps required to generate such autoantibodies do not necessarily create a sustained autoimmune state
The approximate frequency of positive DATs in the entire population
1 in 10,000
Also the prevalence of positive DATs in normal blood donors
Almost all patients with cold agglutinin disease display _______________ whose heavy-chain variable regions are encoded by ________________
Monoclonal IgM cold agglutinins (with either anti-I or anti-i specificity)
IGHV4–34 (immunoglobulin heavy chain variable region)
TRUE OR FALSE
There is a direct relationship between the quantity of RBC-bound IgG antibody and RBC survival
FALSE
There is an inverse relationship between the quantity of RBC-bound IgG antibody and RBC survival
In wAIHA, The macrophage has surface receptors for the Fc region of IgG, with preference for the:
IgG1 and IgG3 subclasses and surface receptors for opsonic fragments of C3 (C3b and C3bi) and C4b
RBC sequestration in warm-antibody AHA occurs primarily in the
Spleen
Very large quantities of RBC-bound IgG or the concurrent presence of C3b on the RBCs may favor trapping in the liver.
A consistent and diagnostically important hallmark of AHA, and the degree correlates well with the severity of hemolysis.
Spherocytosis
TRUE OR FALSE
Direct complement-mediated hemolysis with hemoglobinuria is unusual in warm-antibody AHA, even though many warm autoantibodies fix complement.
TRUE
Direct complement-mediated hemolysis with hemoglobinuria is unusual in warm-antibody AHA, even though many warm autoantibodies fix complement.
Dahil may normal na protective mechanism ang body (CD55 and CD59)
Glycosylphosphatidylinositol-linked erythrocyte membrane proteins that limit the action of autologous complement on autoantibody-coated RBCs
- Decay-accelerating factor (DAF; CD55)
- Homologous restriction factor (HRF; CD59)
Inhibits the formation and function of cell-bound C3-converting enzyme, thus indirectly limiting formation of C5-converting enzyme
DAF
Impedes C9 binding and formation of the C5b–9 membrane attack complex
HRF
The highest temperature at which these antibodies cause detectable agglutination is termed the
Thermal amplitude
Generally, patients with cold agglutinins with higher thermal amplitudes have a greater risk for cold agglutinin disease.
The pathogenicity of a cold agglutinin depends on its ability to bind host RBCs and to activate complement. This process is called
Complement fixation
The great preponderance of cold agglutinin molecules are IgM (pentamers or hexamers)
IgM pentamers
Although in vitro agglutination of the RBCs may be maximal at 0°–5°C, complement fixation by these antibodies may occur optimally at 20°–25°C and may be significant at even higher physiologic temperatures.
TRUE OR FALSE
Pentamers fix complement and lyse RBCs more efficiently than do hexamers, suggesting that pentameric IgM plays a role in the pathogenesis of hemolysis in these patients.
FALSE
Hexamers fix complement and lyse RBCs more efficiently than do pentamers, suggesting that hexameric IgM plays a role in the pathogenesis of hemolysis in these patients.
Cold agglutinins of the____ isotype, an isotype that does not fix complement, may cause acrocyanosis but not hemolysis.
IgA isotype
A:A IgA:Acrocyanosis
Complement fixation by cold agglutinins may effect RBC injury by two major mechanisms:
(a) Direct lysis and
(b) Opsonization for hepatic and splenic macrophages
TRUE OR FALSE
Donath-Landsteiner antibody is a more potent hemolysin than cold agglutinin.
TRUE
Donath-Landsteiner antibody is a more potent hemolysin than cold agglutinin.
TRUE OR FALSE
Most of the antiglobulin-positive RBCs of patients with cold agglutinin disease are coated with C3dg
TRUE
Most of the antiglobulin-positive RBCs of patients with cold agglutinin disease are coated with C3dg
The surviving C3dg-coated RBCs circulate with a near-normal lifespan and are resistant to further uptake of cold agglutinins or complement.
However, C3dg-coated RBCs also may react in vitro with anticomplement (anti-C3) serum in the DAT.
Prototype drug Brug-induced AHA
Hapten-Drug Adsorption:
Ternary Complex Formation:
Autoantibody Binding:
Nonimmunologic Protein Adsorption:
Hapten-Drug Adsorption:Penicillin
Ternary Complex Formation: Quinidine
Autoantibody Binding: α-Methyldopa
Nonimmunologic Protein Adsorption: Cephalothin
Most individuals who receive penicillin develop ______antibodies directed against the _____________ determinant of penicillin
IgM antibodies
Benzylpenicilloyl determinant of penicillin
- This antibody plays no role in penicillin-related immune injury to RBCs
- The antibody responsible for hemolytic anemia is of the IgG class, occurs less frequently than the IgM antibody, and may be directed against the benzylpenicilloyl, or, more commonly, nonbenzylpenicilloyl determinants.
- Antibodies eluted from patients’ RBCs or present in their sera react in the indirect antiglobulin test (IAT) only against penicillin-coated RBCs.
This step is critical in distinguishing these drug-dependent antibodies from true autoantibodies.
Orher drugs: Cephalosporins, Tetracycline, tolbutamide, Carbromal
Antibodies eluted from patients’ RBCs or present in their sera react in the indirect antiglobulin test (IAT) only against penicillin-coated RBCs.
Blood cell injury is mediated by a cooperative interaction among three reactants to generate a ternary complex involving
(a) the drug (or drug metabolite in some cases)
(b) a drug-binding membrane site on the target cell
(c) antibody
Features of Ternary Complex Mechanism
- Exhibit only weak direct binding to blood cell membranes
- A relatively small dose of drug is capable of triggering destruction of blood cells
- Cellular injury appears to be mediated chiefly by complement activation at the cell surface
The cytopathic process induced by such drugs previously has been termed the innocent bystander or immune complex mechanism.
Not only of RBCs but also of platelets or granulocytes
Aside from methylodopa, other drugs that cause AHA thru Autoantibody Mechanism
- Levodopa
- Pentostatin
- Fludarabine
- Cladribine
- Immune checkpoint inhibitors
- Lenolidomide
- Efalizumab
- Tacrolimus
Features of AHA thru Autoantibody Mechanism
- DAT reaction usually is positive only for IgG
- Development of hemolytic anemia does not depend on drug dose.
- Frequently the autoantibodies are reactive with determinants of the Rh complex
Drugs probably bind to membrane antigens of cells that are relatively hemoglobin free, for example, cells at the early proerythroblast stage or RBC stroma
Risk factors for hemolysis in patients with CLL treated with the purine analogues fludarabine, pentostatin, or cladribine
- Previous therapy with a purine analogue
- High β2-microglobulin
- A positive DAT result before therapy
- Hypogammaglobulinemia
The most common offender among immune checkpoint inhibitors causing AIHA
Nivolumab
Most patients respond to glucocorticoid therapy.
Antibiotics that may induce RBC injury by the hapten mechanism, by the ternary complex mechanism, by the autoantibody mechanism and nonimmunologic protein adsorption
ALL Mechanisms
Cephalosporin
The autoantibody mechanism are more serious but apparently occur less frequently than nonimmunologic protein adsorption.
Hemolysis occurring in M. pneumoniae infections is acute in onset, typically appearing as the patient is recovering from pneumonia and coincident with peak titers of cold agglutinins.
The hemolysis is self-limited, lasting _____ weeks.
1–3 weeks
Tyep of drug-induced AHA often causes sudden, severe hemolysis with hemoglobinuria.
Hemolysis can occur after only one dose of the drug in a patient previously exposed to the drug.
Acute renal failure may accompany severe hemolysis
Ternary complex mechanism
kasi nga complement
Others exhibit mild to moderate hemolysis, with insidious onset of symptoms developing over a period of days to weeks.
Hemolytic anemia in infectious mononucleosis develops either at the onset of symptoms or within the ___________ weeks of illness.
First 3 weeks of illness
Lab features of AIHA
- Increased reticulocyte count and a positive DAT result
- Polychromasia
- Spherocytes
- RBC fragments, nucleated RBCs, and occasionally erythrophagocytosis by monocyte
- Mild leukocytosis and neutrophilia
- Reticulocyte count usually is elevated
- Hyperbilirubinemia (chiefly unconjugated)
- Urinary urobilinogen is increased
- Serum haptoglobin levels are low
- Lactate dehydrogenase (LDH) levels are elevated
Cold-antibody AHA: RBC autoagglutination
Severe immune thrombocytopenia that is associated with warm-antibody AHA
Evans syndrome
May occur de novo or as a phenomenon secondary to an autoimmune disease, lymphoma, or immunodeficiency
TRUE OR FALSE
Patients with paroxysmal cold hemoglobinuria have hematocrit levels that decrease rapidly during a paroxysm.
TRUE
Patients with paroxysmal cold hemoglobinuria have hematocrit levels that decrease rapidly during a paroxysm.
Chronic cold agglutinin disease: mild to moderate, fairly stable anemia
- During a paroxysm, leukopenia is noted early followed by leukocytosis. (also in ternary complex-mediated hemolysis)
- Complement titers frequently are depressed because of consumption of complement proteins during hemolysis.
Hemoglobinuria is encountered in rare patients with warm-antibody AHA and hyperacute hemolysis, more commonly in patients with:
- Cold agglutinin disease
- Paroxysmal cold hemoglobinuria
- Drug-induced immune hemolytic anemia mediated by the ternary complex mechanism
As a screening procedure, use of a _______________—that is, one that contains antibodies directed against human immunoglobulin and complement components (principally C3)—is customary.
“broad-spectrum” antiglobulin (Coombs) reagent
If agglutination is noted with a broad-spectrum reagent, antisera reacting selectively with IgG (the γ Coombs) or with C3 (the non-γ Coombs) are used to define the specific pattern of RBC sensitization.
Three possible major patterns of direct antiglobulin reaction in AHA and drug-induced immune hemolytic anemia exist:
(a) RBCs coated with only IgG
(b) RBCs coated with IgG and complement components
(c) RBCs coated with complement components without detectable immunoglobulin
In patterns 2 and 3, the complement components most readily detected are C3 fragments (mainly C3dg).
DAT Reaction pattern: Immunoglobulin (Ig) G alone
- Warm-antibody autoimmune hemolytic anemia (AHA)
- Drug-immune hemolytic anemia: hapten drug adsorption type or autoantibody type
DAT Reaction pattern: Complement alone
- Warm-antibody AHA with subthreshold IgG deposition
- Cold-agglutinin disease
- Paroxysmal cold hemoglobinuria
- Drug-immune hemolytic anemia: ternary complex type
DAT Reaction pattern: IgG plus
complement
- Warm-antibody AHA
- Drug-immune hemolytic anemia: autoantibody type (rare)
Major portion detected by the DAT
Autoantibody bound to the patient’s RBCs
Major portion detected by the IAT
“free” Autoantibody
TRUE OR FALSE
Patients with a positive IAT as a result of a warm-reactive autoantibody should also have a positive DAT result.
TRUE
Patients with a positive IAT as a result of a warm-reactive autoantibody should also have a positive DAT result.
Pwede both positive DAT and IAT
Patients whose RBCs are heavily coated with IgG more likely exhibit plasma autoantibody.
TRUE OR FALSE
A patient with a serum anti-RBC antibody (positive DAT result) and a negative IAT result probably have an autoimmune process.
FALSE
A patient with a serum anti-RBC antibody (positive IAT result) and a negative DAT result probably does not have an autoimmune process but rather an alloantibody stimulated by prior transfusion or pregnancy.
There are three principal causes for the negative DAT reaction:
(a) IgG or complement sensitization below the threshold of detection of commercial antiglobulin (Coombs) reagents;
(b) low-affinity IgG sensitization with loss of cell-bound antibody during the cell washing steps before the direct antiglobulin reaction; and
(c) sensitization with IgA or IgM antibodies, which many commercial DAT reagents cannot detect because they contain only anti-IgG anti-C3.
Techniques to address initial DAT-negative in clinical warm AHA
- Specialized methods (eg, anti-IgG consumption assays, automated enhanced agglutination techniques, enzyme-linked immunoassays, radioimmunoassays, flow cytometry)
- Highly concentrated RBC eluates
- Cold washing (0°–4°C) or by use of low-ionic-strength saline
The IgG subclass most commonly encountered
IgG1
The IgG subclass autoantibodies that appear to be more effective in decreasing RBC lifespan
IgG1 and IgG3
- Have greater affinity of macrophage Fc receptors
- With higher complement-fixing activity
Nearly half of all AHA patients have autoantibodies specific for epitopes on__________.
Rh proteins
Occasionally, the anti-Rh autoantibodies have anti-e, anti-E, or anti-c (or, more rarely, anti-D) specificity (Rh related)
The major target of Rh-related autoantibodies is a 32- to 34-kDa nonglycosylated polypeptide lacking on Rhnull RBCs.
This polypeptide is similar, if not identical, to the polypeptide expressing the ______ alloantigen.
Rh(e) alloantigen
Group of autoantibodies is designated non–Rh related
anti-Wrb, anti-Ena, anti-LW, anti-U, anti-Ge, anti-Sc1, or antibodies to Kell blood group antigens
Autoantibodies with non-Rh serologic specificity react with the ___________________.
- Band 3 anion transporter or
- With both band 3 and glycophorin A
Naturally occurring anti–band 3 IgG autoantibodies are found in almost all humans.
These autoantibodies may play a role in the clearance of senescent RBCs by reacting with neoantigens formed on these cells by proteolytic alteration or aggregation of band 3 proteins.
Cold agglutinins are distinguished by their ability to directly agglutinate saline-suspended human RBCs at low temperature, maximally at ________
0°C–5°C
Cold agglutinins are characteristically ______.
IgM
The DAT result is positive with anticomplement reagents.
Blood group antigens targets in Cold AHA
Mycoplasma:
Donath-Landsteiner antibodies:
idiopathic cold agglutinin disease:
Infectious mononucleosis:
Chickenpox:
Lymphoma:
Mycoplasma: Anti-I
Idiopathic cold agglutinin disease: Anti-I
Donath-Landsteiner antibodies: P blood group antigen (non-agglutinating)
Infectious mononucleosis:Anti-i
Chickenpox: anti-Pr
Lymphoma: Anti-I, Anti-i
Pr-es has Chicken pox; it’s P. Duterte; has to see small “i”M doctor and told it’s Infectious mononucleosis not chic pox
The I/i system, which are precursors of the _________blood group substances.
- I antigens are expressed strongly on adult RBCs but weakly on neonatal (cord) RBCs. The converse is true of i antigens, indicating I/i antigen expression is developmentally regulated.
ABH and Lewis
The P antigen also occurs on
Lymphocytes and skin fibroblasts
Might be related in some way to the occurrence of cold urticaria in paroxysmal cold hemoglobinuria
Coomb’s test oin Drug-Induced Immune Hemolytic Anemia
Hapten-drug adsorption mechanism:
Ternary complex mechanism:
Autoantibody:
Hapten-drug adsorption mechanism:Positive DAT reactions with anti-IgG, anti-C3d
Ternary complex mechanism: Positive DAT reactions with anticomplement serum
Autoantibody: Positive DAT reactions with anti-IgG only
React only with drug-coated RBCs
In ternary complex mechanism, the IAT reaction with anticomplement serum may be positive only if the incubation mixture permits interaction of:
(a) normal RBCs;
(b) antidrug antibody from the patient’s serum;
(c) the relevant drug, either still in the patient’s serum or added in vitro in appropriate concentration; and
(d) a source of complement, that is, fresh normal serum or the patient’s own serum if freshly obtained
Recipients of transplantations may also develop an alloimmune hemolytic anemia that mimics warm-antibody AHA.
The problem is seen in kidney, liver, or hematopoietic stem cell transplantations and usually occurs when :
An organ from a blood group O donor is transplanted into a blood group A or B recipient
Indication for RBC transfusions
- Symptomatic coronary artery disease
- Anemia with signs or symptoms of circulatory failure
Transfusion of RBCs in immune hemolytic anemia presents two difficulties:
- (a) crossmatching
- (b) the short half-life of the transfused RBCs
TRUE OR FALSE
Units that are incompatible because of the presence of autoantibody are less dangerous to transfuse than units that are incompatible because of an alloantibody.
TRUE
Units that are incompatible because of the presence of autoantibody are less dangerous to transfuse than units that are incompatible because of an alloantibody.
- Before transfusing an incompatible unit, the patient’s serum must be tested carefully for an alloantibody that could cause a severe hemolytic transfusion reaction against donor RBCs, especially in patients with a history of pregnancy, abortion, or prior transfusion.
- Packed RBCs should be administered slowly and in the case of cold hemolysis syndromes should be brought at least to room temperature.
- Monitored for signs of a hemolytic transfusion reaction
Glucocorticoids can cause dramatic cessation or marked slowing of hemolysis in about _________ of patients.
Two-thirds
20%: complete remission
10%: minimal or no response
The best responses with glucocorticoids are seen in _________________.
Idiopathic cases or in those related to SLE
Dose of steroids
Oral prednisone at an initial daily dose of 1–1.5 mg/kg
Critically ill patients with rapid hemolysis may receive: IV methylprednisolone 100–200 mg in divided doses over the first 24 hours
High doses of prednisone may be required for 10–14 days.
Therapy should not be stopped until the DAT reaction becomes negative.
Monoclonal antibody that eliminate B lymphocytes, including, presumably, those making autoantibodies to RBCs
Initially in refractory AHA either unresponsive to or relapsed after oral glucocorticoid therapy.
Rituximab
Doses:
* 375 mg/m2 weekly for 2–4 weeks intravenously
* 100 mg/m2 weekly for 4 weeks along with a short course of oral glucocorticoid
The relapse-free survival was superior for the combination of glucocorticoids and rituximab.
Primary site of RBC trapping
Spleen
Approximately _________ of AHA patients have a partial or complete remission after splenectomy.
Two-thirds
Reserved primarily for patients who do not respond to glucocorticoids or rituximab and for patients who are poor surgical risks.
Immunosuppressive therapy
- Oral cyclophosphamide 50–100 mg daily
- Oral azathioprine 2–4 mg/kg given daily
- If the patient tolerates the drug, continue treatment for at least 3 months while waiting for a response.
- Treatment with either agent increases the risk of subsequent neoplasia.
OTHERS:
* Mycophenolate mofetil
* Cyclosporin A
* High-dose cyclophosphamide 50 mg/kg ideal body weight per day for 4 consecutive days intravenously with granulocyte colony-stimulating factor support
Used to treat five patients with refractory AHA associated with CLL
Alemtuzumab
Other therapies for AIHA
- Plasma exchange or plasmapheresis- life-threatening warm IgG-mediated AHA refractory to glucocorticoids and splenectomy
- Plasma-derived C1 inhibitor concentrate: severe warm IgM-mediated AHA
- Rituximab and eculizumab: refractory warm IgM-mediated AHA
- High-dose IV γ-globulin
- Danazol
For patients with chronic compensated hemolysis, treatment with oral folate at _________ is recommended
1 mg/day
Standard first-line therapy for patients with cold agglutinin disease.
Treatment directed at B lymphocytes
* Rituximab
* Rituximab in combination with bendamustine
* Bortezomib
In patients with lymphoma, treatment of the underlying disorder usually results in control of the cold agglutinin disease.
Useful as a bridge by causing rapid cessation of hemolysis, allowing time for B cell–directed therapies to take effect
Complement-directed therapies
* Eculizumab
* Sutimlimab
It does not inhibit RBC agglutination, nor does it eliminate the symptoms caused by agglutination such as acrocyanosis and Raynaud phenomenon.
TRUE OR FALSE
Most contemporary cases of paroxysmal cold hemoglobinuria are self-limited.
TRUE
Most contemporary cases of paroxysmal cold hemoglobinuria are self-limited.
- Glucocorticoid therapy and splenectomy have not been useful.
- When paroxysmal cold hemoglobinuria is associated with syphilis, effective treatment of the infection may result in complete remission.
- Antihistaminic and adrenergic agents may relieve symptoms of cold urticaria.
Blood product for RBC transfusion in Cold AHA
Washed RBC
Avoid replenishing depleted complement components and reactivating the hemolytic process.
Treatment for drug-induced hemolytic anemia
Discontinuation of the offending drug
TRUE OR FALSE
In patients taking α-methyldopa in the absence of hemolysis, a positive DAT result has not necessarily been an indication for stopping the drug.
TRUE
In patients taking α-methyldopa in the absence of hemolysis, a positive DAT result has not necessarily been an indication for stopping the drug.
Drug-induced AHA
Glucocorticoids are generally unnecessary, and their efficacy is questionable except in:
- Immune checkpoint inhibitors
- CLL and autoimmune hemolysis caused by purine analogues
