55 Hemolytic Anemia resulting from Immune Injury Flashcards
(106 cards)
1
Q
The two main features of immune red blood cell (RBC) injury are
A
- (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
2
Q
Most cases in adults are mediated by ___________ autoantibodies.
A
Warm-reactive autoantibodies
3
Q
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
A
Direct or saline agglutinins
4
Q
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
A
Hemolysins
5
Q
When the RBCs are coated chiefly with complement proteins, a positive DAT result depends on the presence of anticomplement (principally ____________) in the antiglobulin reagent.
A
anti-C3
6
Q
Cryopathic hemolytic syndromes are caused by autoantibodies that bind RBCs optimally at temperatures less than _____°C and usually less than ______°C.
A
Less than 37°C and usually less than 31°C
7
Q
Two major types of “cold antibody” may produce AHA:
A
- Cold agglutinins: cold agglutinin disease; agglutinins
- Donath-Landsteiner autoantibody: paroxysmal cold hemoglobinuria; hemolysins
8
Q
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.
A
Complement system
9
Q
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.
A
0°C–5°C
10
Q
Cold agglutinins typically are Ig_____, although occasionally they may be immunoglobulins of other isotypes.
A
IgM
11
Q
Monoclonal or Polyclonal
The cold agglutinins in chronic cold agglutinin disease generally are__________.
A
Monoclonal
12
Q
Most cold agglutinins have specificity for _______________of the RBC
A
Oligosaccharide antigens (I or i)
13
Q
Viral disease associated with Donath-Landsteiner antibody
A
Congenital or tertiary syphilis
rare
14
Q
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.
A
Donath-Landsteiner hemolytic anemia
15
Q
When no recognizable underlying disease is present, the AHA is termed
A
Primary or idiopathic
16
Q
Account for approximately half of all secondary warm AHA cases
A
Lymphocytic malignancies, particularly chronic lymphocytic leukemia (CLL) and lymphomas
17
Q
The majority of AHA cases mediated by cold agglutinins have a
A
Clonal lymphoproliferative disorder
Without clinical or radiologic evidence of malignancy; these are considered primary
18
Q
A large proportion of patients with mixed cold and warm autoantibodies have this autoimmune disease
A
SLE
19
Q
Infections associated with AHA mediated by cold agglutinins
A
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.
20
Q
Two of the mechanisms of drug-immune hemolytic anemia that involve drug-dependent antibodies
A
Hapten-drug adsorption and ternary complex formation
21
Q
TRUE OR FALSE
Drug-related nonimmunologic protein adsorption by RBCs may result in a positive DAT without actual RBC injury.
A
TRUE
Drug-related nonimmunologic protein adsorption by RBCs may result in a positive DAT without actual RBC injury.
22
Q
In general, AHA is considered secondary when
A
(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.
23
Q
The most common cause of drug-induced autoantibodies
A
Fludarabine
Replaced α-methyldopa
24
Q
In warm-antibody AHA, the autoantibodies that mediate RBC destruction are predominantly (but not exclusively) ______ globulins
A
IgG
25
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
26
Drug that can induce **warm-reacting IgG anti-RBC autoantibodies** in otherwise normal persons
α-methyldopa
## Footnote
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
27
The approximate frequency of positive DATs in the entire population
1 in 10,000
## Footnote
Also the prevalence of positive DATs in normal blood donors
28
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)
29
# 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
30
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
31
RBC sequestration in warm-antibody AHA occurs primarily in the
Spleen
## Footnote
Very large quantities of RBC-bound IgG or the concurrent presence of C3b on the RBCs may favor trapping in the **liver**.
32
A consistent and diagnostically important **hallmark of AHA,** and the degree correlates well with the severity of hemolysis.
Spherocytosis
33
# 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)
34
*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)
35
Inhibits the formation and function of cell-bound C3-converting enzyme, thus indirectly limiting formation of **C5-converting enzyme**
DAF
36
Impedes C9 binding and formation of the **C5b–9 membrane attack complex**
HRF
37
The **highest temperature** at which these antibodies cause detectable **agglutination** is termed the
Thermal amplitude
## Footnote
Generally, patients with cold agglutinins with **higher** thermal amplitudes have a **greater risk for cold agglutinin disease**.
38
The **pathogenicity** of a cold agglutinin depends on its **ability to bind host RBCs and to activate complement**. This process is called
Complement fixation
39
The great preponderance of cold agglutinin molecules are IgM (pentamers or hexamers)
IgM pentamers
## Footnote
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.
40
# 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.
41
Cold agglutinins of the____ isotype, an isotype that **does not fix complement**, may cause **acrocyanosis but not hemolysis**.
IgA isotype
| A:A IgA:Acrocyanosis
42
Complement fixation by cold agglutinins may effect RBC injury by two major mechanisms:
(a) Direct lysis and
(b) Opsonization for hepatic and splenic macrophages
43
# 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.
44
# 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
## Footnote
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.
45
# 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**
46
Most individuals who receive **penicillin** develop ______antibodies directed against the _____________ determinant of penicillin
IgM antibodies
Benzylpenicilloyl determinant of penicillin
## Footnote
* 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.*
47
This step is critical in distinguishing these drug-dependent antibodies from true autoantibodies.
## Footnote
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.
48
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
49
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
## Footnote
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**
50
Aside from **methylodopa**, other drugs that cause AHA thru **Autoantibody Mechanism**
* Levodopa
* Pentostatin
* Fludarabine
* Cladribine
* Immune checkpoint inhibitors
* Lenolidomide
* Efalizumab
* Tacrolimus
51
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**
## Footnote
Drugs probably bind to membrane antigens of cells that are relatively hemoglobin free, for example, cells at the early proerythroblast stage or RBC stroma
52
**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
53
The most common offender among immune checkpoint inhibitors causing AIHA
Nivolumab
## Footnote
Most patients respond to glucocorticoid therapy.
54
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
## Footnote
The **autoantibody** mechanism are **more serious** but apparently occur **less frequently** than nonimmunologic protein adsorption.
55
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
56
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
## Footnote
Others exhibit **mild to moderate** hemolysis, with **insidious** onset of symptoms developing over a period of days to weeks.
57
Hemolytic anemia in **infectious mononucleosis** develops either at the onset of symptoms or within the ___________ weeks of illness.
First 3 weeks of illness
58
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**
59
Severe **immune thrombocytopenia** that is associated with **warm-antibody AHA**
Evans syndrome
## Footnote
May occur de novo or as a phenomenon secondary to an autoimmune disease, lymphoma, or immunodeficiency
60
# 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
## Footnote
* 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.
61
**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
62
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
## Footnote
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.
63
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
## Footnote
In patterns 2 and 3, the complement components most readily detected are C3 fragments (mainly **C3dg**).
64
DAT Reaction pattern: **Immunoglobulin (Ig) G alone**
* Warm-antibody autoimmune hemolytic anemia (AHA)
* Drug-immune hemolytic anemia: hapten drug adsorption type or autoantibody type
65
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
66
DAT Reaction pattern: **IgG plus
complement**
* Warm-antibody AHA
* Drug-immune hemolytic anemia: autoantibody type (rare)
67
Major portion detected by the DAT
Autoantibody bound to the patient’s RBCs
68
Major portion detected by the IAT
“free” Autoantibody
69
# 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
## Footnote
Patients whose RBCs are **heavily coated with IgG** more likely exhibit **plasma autoantibody.**
70
# 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.**
71
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.
72
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
73
The IgG subclass most commonly encountered
IgG1
74
The IgG subclass autoantibodies that appear to be more effective in decreasing RBC lifespan
IgG1 and IgG3
## Footnote
* Have greater affinity of macrophage Fc receptors
* With higher complement-fixing activity
75
Nearly **half** of all AHA patients have autoantibodies specific for epitopes on__________.
Rh proteins
## Footnote
Occasionally, the anti-Rh autoantibodies have anti-e, anti-E, or anti-c (or, more rarely, anti-D) specificity **(Rh related)**
76
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
77
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
78
Autoantibodies with non-Rh serologic specificity react with the ___________________.
* Band 3 anion transporter or
* With both band 3 and glycophorin A
## Footnote
*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.
79
Cold agglutinins are distinguished by their ability to directly agglutinate saline-suspended human RBCs at low temperature, maximally at ________
0°C–5°C
80
Cold agglutinins are characteristically ______.
IgM
## Footnote
The DAT result is positive with **anticomplement** reagents.
81
# 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**
## Footnote
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
82
The **I/i system**, which are precursors of the _________blood group substances.
## Footnote
* **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
83
The P antigen also occurs on
Lymphocytes and skin fibroblasts
## Footnote
Might be related in some way to the occurrence of **cold urticaria** in paroxysmal cold hemoglobinuria
84
# 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
## Footnote
React only with drug-coated RBCs
85
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
86
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**
87
Indication for RBC transfusions
* Symptomatic coronary artery disease
* Anemia with signs or symptoms of circulatory failure
88
Transfusion of RBCs in immune hemolytic anemia presents two difficulties:
* (a) crossmatching
* (b) the short half-life of the transfused RBCs
89
# 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.
## Footnote
* 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
90
**Glucocorticoids** can cause dramatic cessation or marked slowing of hemolysis in about _________ of patients.
Two-thirds
## Footnote
20%: complete remission
10%: minimal or no response
91
The best responses with glucocorticoids are seen in _________________.
Idiopathic cases or in those related to SLE
92
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.
## Footnote
**Therapy should not be stopped until the DAT reaction becomes negative.**
93
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
## Footnote
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.
94
Primary site of RBC trapping
Spleen
95
Approximately _________ of AHA patients have a partial or complete remission after splenectomy.
Two-thirds
96
Reserved primarily for patients who **do not respond to glucocorticoids or rituximab** and for patients who are **poor surgical risks**.
Immunosuppressive therapy
## Footnote
* 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
97
Used to treat five patients with refractory AHA associated with CLL
Alemtuzumab
98
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**
99
For patients with chronic compensated hemolysis, treatment with **oral folate** at _________ is recommended
1 mg/day
100
Standard first-line therapy for patients with **cold agglutinin disease**.
**Treatment directed at B lymphocytes**
* Rituximab
* Rituximab in combination with bendamustine
* Bortezomib
## Footnote
In patients with lymphoma, treatment of the underlying disorder usually results in control of the cold agglutinin disease.
101
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
## Footnote
It **does not inhibit RBC agglutination, nor does it eliminate the symptoms** caused by agglutination such as acrocyanosis and Raynaud phenomenon.
102
# TRUE OR FALSE
Most contemporary cases of paroxysmal cold hemoglobinuria are self-limited.
TRUE
Most contemporary cases of paroxysmal cold hemoglobinuria are **self-limited**.
## Footnote
* 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**.
103
Blood product for RBC transfusion in Cold AHA
Washed RBC
## Footnote
Avoid replenishing depleted complement components and reactivating the hemolytic process.
104
Treatment for drug-induced hemolytic anemia
Discontinuation of the offending drug
105
# 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.
106
# 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
