scholarly journals Cold Agglutinin Disease Transfusion Practices in the United States: An Electronic Medical Record-Based Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3690-3690
Author(s):  
Jun Su ◽  
Rajeshwari Punekar ◽  
Jaime Morales Arias ◽  
Nisha Jain
Keyword(s):  
Medical Record ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Index Date ◽  
Cold Agglutinin ◽  
Cold Agglutinin Disease ◽  
Employment Equity ◽  
Medical Activity ◽  
Equity Ownership ◽  
Rbc Transfusion

Introduction Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia (AIHA) accounting for 20% of all cases, with no approved therapies and limited management options for patients. CAD is characterized by immunoglobulin M-mediated erythrocyte agglutination, which triggers activation of the classical complement pathway leading to hemolysis and subsequent anemia. Red blood cell (RBC) transfusions are used as a supportive treatment in CAD to temporarily alleviate anemia, although the transfusion practices are variable among providers treating patients with CAD. Recent RBC transfusion guidelines from the AABB (formerly the American Association of Blood Banks) recommend that transfusions be administered with a restrictive threshold in most clinical scenarios (ie, transfusion is not indicated until hemoglobin [Hb] reaches 7-8 g/dL and/or patients exhibit anemia-related symptoms) to avoid associated complications such as acute reactions, alloantibody development, and hemochromatosis (Carson et al, JAMA, 2016; Carson et al, N Engl J Med, 2017). Because of the dearth of information available regarding trends in RBC transfusion practices among US hematologists, the objective of this longitudinal, retrospective, observational assessment of an electronic medical record database was to evaluate transfusion practices applied to patients with CAD in the US. Methods Patients were retrospectively identified from Optum® de-identified Electronic Health Record (EHR) dataset. Adult patients with ≥1 AIHA-related medical encounter between January 2007 and September 2018 (study period) and ≥3 mentions of CAD-related terms from physician notes ("cold agglutinin disease," "cold autoimmune hemolytic anemia," or "cold agglutinin hemoglobinuria") were included (Broome et al, Blood, 2017). The index date for each patient was the date of first mention of CAD during the study period. The baseline period was defined as the interval from the start of medical activity in the EHR database or study period (whichever occurred later) to the index date, and the follow-up period was defined as the interval from the index date to the end of the study period, end of medical activity, or death (whichever occurred earlier). The study sample was categorized into 2 study groups, the transfusion group (patients with CAD with ≥1 RBC transfusion after the index date) and the non-transfusion group (patients with CAD without any transfusions during the study period). Patients were further grouped based on the following Hb levels (g/dL): <8, ≥8 to ≤10, and >10 to ≤12. The closest Hb level prior to the most recent transfusion (within the prior 15 days and the lowest level) was used for the transfusion group and the lowest Hb level during the study period was used for the non-transfusion group. Descriptive statistics included mean, standard deviation, and median values for continuous variables and frequency (n and percent) for categorical variables. No adjustment was made for this descriptive analysis. Results A total of 903 patients with CAD were identified from the Optum EHR database; most patients were white (n=760 [84%]) and female (n=560 [62%]). Baseline demographics and clinical characteristics of each group can be found in the Table. Of the patients with CAD, 548 (61%) did not receive transfusions and 355 (39%) received ≥1 RBC transfusion. Among patients with CAD who received transfusions, 84% (n=297) had ≥2 RBC transfusions. Out of the 903 patients with CAD, 864 had Hb levels reported and 752 had Hb levels ≤12 g/dL. Forty-four percent (n=329/752) of those CAD patients received ≥1 RBC transfusion. When separated by Hb levels, 18% of patients with Hb >10 to ≤12 g/dL (n=19/108); 41% (n=88/216) of patients with Hb ≥8 to ≤10 g/dL; and 52% (n=222/428) of patients with Hb <8 g/dL received ≥1 RBC transfusion. Of the 423 (56%) patients with CAD and Hb levels ≤12 g/dL who did not receive RBC transfusions, 21% (n=89/423) had Hb levels >10 to ≤12 g/dL; 30% (n=128/423) had Hb levels ≥8 to ≤10 g/dL; and 49% (n=206/423) had Hb levels <8 g/dL. Conclusions Overall, patients with CAD are not a heavily transfused population. Even in those with a significantly decreased Hb (<8 g/dL), approximately half of them (49%) did not receive RBC transfusions. This suggests that the use of transfusions in patients with CAD may not reflect disease severity. Further prospective studies are needed to fully understand the impact of transfusions on patients with CAD. Disclosures Su: Sanofi Genzyme: Employment, Equity Ownership. Punekar:Sanofi: Employment, Equity Ownership. Morales Arias:Sanofi: Employment, Equity Ownership. Jain:Sanofi Genzyme: Employment, Equity Ownership.

scholarly journals Mortality Among Patients with Cold Agglutinin Disease in the United States: An Electronic Health Record (EHR)-Based Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4790-4790
Author(s):  
Quentin A. Hill ◽  
Rajeshwari Punekar ◽  
Jaime Morales Arias ◽  
Catherine M Broome ◽  
Jun Su
Keyword(s):  
Mortality Rate ◽  
Research Funding ◽  
Index Date ◽  
Cold Agglutinin ◽  
Control Cohort ◽  
Cold Agglutinin Disease ◽  
Employment Equity ◽  
Equity Ownership ◽  
And Control

Introduction Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia (AIHA). It is characterized by both IgM-mediated agglutination of erythrocytes and hemolysis mediated by activation of the classical complement pathway. Recent studies have shown an increased risk of thromboembolic events (TE) in CAD patients. In addition, a recent analysis using the Danish National Patient Registry demonstrated a significant increase in mortality for CAD patients compared with matched individuals from the general population in Denmark (Bylsma et al, HemaSphere, 2018). Mortality among CAD patients has not been assessed in a US population. This study evaluated mortality risk in the largest cohort of CAD patients in the US. Methods Patients were retrospectively identified from the Optum® de-identified EHR dataset. Between January 2007 and September 2018 (study period), patients with ≥1 AIHA-related medical encounter and ≥3 mentions from physician notes of CAD-related terms ("cold agglutinin disease," "cold autoimmune hemolytic anemia," or "cold agglutinin hemoglobinuria") were included in the CAD cohort ("case"). For this cohort, the first mention of CAD terms was set as the index date. Patients without an AIHA-related medical encounter were included in the non-CAD cohort ("control"). For the control cohort, the index date was assigned based on the average occurrence of index date in the CAD population for the duration in the EHR database. For both cohorts, the baseline period was defined as the interval from the start of the medical activity in the EHR database or study period (whichever occurs later) to the index date, and the follow-up period was defined as the interval from the index date to the end of the study period, the end of medical activity, or death (whichever occurs earlier). The case and control cohorts were matched by age, gender, race, region, index year, and follow-up period using 1:5 nearest neighbor matching. Both cohorts were stratified according to the presence or absence of ≥1 TE during the study period. Mortality rate per 100,000 patients was calculated as the number of patients who died in each cohort divided by the number of patients in each cohort, from 2007 to 2018, multiplied by 100,000. Mortality rate was compared between matched cohorts using a Poisson test. An independent t-test was used to compare age at death between matched CAD and control groups; and time to death (starting from the index date) was analyzed using Kaplan-Meier curves and compared between matched cohorts using log-rank P test. Results In total, 651 CAD patients and 3,255 matched non-CAD controls were identified. Of these, 35% (n=228) of CAD patients and 20% (n=641) of non-CAD patients experienced ≥1 TE (P<0.001). Median age at index date for both cohorts was 72 years. Most patients were female (CAD 64%; non-CAD 65%) and Caucasian (CAD 85%; non-CAD 85%). Median follow-up duration was 42 months for the CAD cohort and 51 months for the control cohort. Mean (standard deviation [SD]) Elixhauser Comorbidity Index Score was 8.0 (4.9) for CAD patients and 4.5 (4.1) for matched controls. The overall mortality rate was significantly higher for the CAD cohort than the matched-control cohort (CAD: 17,512 vs non-CAD: 11,306; P<0.001). For patients that experienced ≥1 TE during the study period, the mortality rate in the CAD cohort was 23,684 compared with 15,913 in the matched-control cohort (P<0.001; Table 1). During the study period, 114 CAD patients and 368 matched non-CAD patients died. The mean (SD) age at death in the CAD cohort (77 [12] years) was lower compared with the matched controls (82 [8] years; P<0.001). For patients with ≥1 TE, mean (SD) age at death was 77 (13) years vs 82 (7) years for the CAD and control cohorts, respectively (P<0.001; Table 1). A Kaplan-Meier analysis demonstrated a significantly decreased survival probability among CAD patients compared with matched controls (P<0.001; Figure 1). In addition, CAD patients with ≥1 TE also had a significant decrease in survival when compared with matched controls with ≥1 TE (P<0.001). Conclusions CAD patients in the US have an increased mortality risk compared with a matched non-CAD population. The associated increased TE risk observed among CAD patients may be a contributing factor to this mortality. Further studies are needed to better define this association and elucidate other potential contributors to mortality in these patients. Disclosures Hill: Apellis: Honoraria; Novartis: Speakers Bureau; Bioverativ, a Sanofi company: Honoraria; Alexion: Research Funding. Punekar:Sanofi: Employment, Equity Ownership. Morales Arias:Sanofi: Employment, Equity Ownership. Broome:Cellphire: Research Funding; Alexion: Honoraria, Research Funding; Sanofi Genzyme: Honoraria, Research Funding; Incyte: Research Funding; Rigel: Research Funding. Su:Sanofi Genzyme: Employment, Equity Ownership.

TNT009 Prevents Erythrocyte C3 Fragment Opsonization and Rescues Reticulocytes from Destruction in Patients with Cold Agglutinin Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 94-94
Author(s):  
Sandip Panicker ◽  
Christa Drucker ◽  
Sami Hussain ◽  
Graham C Parry ◽  
James C Gilbert ◽  
...  
Keyword(s):  
Complement Activation ◽  
Cold Agglutinin ◽  
Therapeutic Effects ◽  
Cold Agglutinin Disease ◽  
Serum Samples ◽  
Employment Equity ◽  
Equity Ownership ◽  
Baseline Levels ◽  
Pre Treatment

Abstract Autoantibody mediated classical complement pathway (CP) activation has been hypothesized to drive hemolytic anemia in cold agglutinin disease (CAD) patients. Red blood cell (RBC) destruction is believed to occur as a result of C3 opsonin mediated extravascular hemolysis in the liver. We recently reported that TNT009, a humanized monoclonal antibody targeting the CP specific serine protease C1s, rapidly restores hemoglobin levels in severely anemic CAD patients. Here we describe the pharmacodynamic changes in the complement profile of patients to provide a mechanistic understanding of the hematological responses and therapeutic benefit observed following TNT009 treatment. In a Phase 1b trial, we enrolled 5 female CAD patients with severe anemia, one of whom had a lymphoplasmacytic lymphoma with >70% bone marrow infiltration and no measurable CP activity prior to dosing. This patient did not respond to TNT009 while on study and will be omitted from subsequent analyses. Patients were given an initial 10 mg/kg test dose of TNT009 on Day 1, followed by four weekly doses of 60 mg/kg on Day 2 or Day 5. Patients were followed for 4 weeks following the last dose (washout). Plasma and serum samples were collected throughout the study to measure TNT009 concentrations and to monitor serological markers of anemia and hemolysis. Additionally, futhan-containing plasma samples were collected to assess the levels of CP specific components including C1s, C1s-C1INH, and C1q by ELISA. RBCs were collected to monitor cell surface complement deposition (C3 fragments) via flow cytometry. Finally, C4 levels and an ELISA-based readout of CP activity were examined as measures of the pharmacodynamic effect of TNT009. Baseline levels of circulating C4 were either low or undetectable in CAD patients. Accordingly, serum CP activity was reduced compared to normal human serum samples. Following the first 60 mg/kg TNT009 dose, CP activity was immediately and completely inhibited within 15 minutes of dosing in all patients and remained inhibited for 3 weeks after the last dose. During this period of inhibition, C4 levels rose from a median circulating concentration of <90 mcg/mL (range: <70 - 145) to 251 mcg/mL (range: 238 - 353; p < .001). Plasma C1s levels, on the other hand, decreased from a median plasma concentration of 53.3 mcg/mL (range: 49.4 - 60.3) to a nadir of <3.13 mcg/mL, the lower limit of quantification (LLOQ), (p < .001). Similarly, C1s-C1INH decreased from a median value of 4.5 mcg/mL (range: 4.2 - 5.3) to a nadir of <0.16 mcg/mL (LLOQ; p < .001). Notably, circulating plasma C1q levels were unaffected. Classical pathway inhibition led to a significant increase in reticulocytes in all patients by, on average, 69% within 24 hours of dosing (p < .05). Interestingly, within 1 week after the first TNT009 dose, reticulocyte counts returned to pre-treatment levels and continued to decrease throughout the study, as expected when hemoglobin normalizes. Similarly, within 24 hours of the first dose of TNT009, bilirubin levels dropped from a median value of 2.1 mg/dL (range 1.6 - 3.8) to 0.7 mg/dL (range 0.6 - 1.2), resulting in an average reduction of 66% from baseline levels (p < .05) and returning to pre-treatment levels following washout. Finally, we monitored in vivo complement activation by staining for C3 fragment deposition on RBCs. In general, we observed a gradual reduction in the percentage of C3 fragment positive RBCs over the course of the study from a median value of 49% (range: 37 - 81) to 29% (range: 20 - 38) before washout of TNT009. The decrease in opsonized RBCs was concomitant with the rise in hemoglobin (example shown in Figure 1). Figure 1: Elevation of hemoglobin is associated with a decrease in C3 fragment coated erythrocytes Here we report that TNT009 administration depletes circulating C1s and immediately halts in vivo CP activity, normalizing plasma C4 levels in CAD patients. The abrupt increase in reticulocyte count within 24 hours of dosing suggests that cold agglutinin mediated complement activation affects reticulocyte survival, preventing their maturation into erythrocytes. The observed reduction in C3 opsonized RBCs suggests that TNT009 ameliorates anemia by preventing complement mediated hepatic RBC sequestration, supported by the immediate normalization of circulating bilirubin levels. These results provide a mechanistic interpretation of the therapeutic effects of TNT009 in CAD patients. Figure 1. Figure 1. Disclosures Panicker: True North Therapeutics, Inc.: Employment, Equity Ownership. Hussain:True North Therapeutics, Inc.: Employment, Equity Ownership. Parry:Truenorth Therapeutics, Inc.: Employment, Equity Ownership. Gilbert:Truenorth Therapeutics, Inc.: Employment, Equity Ownership. Jaeger:Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses.

scholarly journals The Immunomodulatory Effect and Clinical Efficacy of Daratumumab in a Patient With Cold Agglutinin Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna Zaninoni ◽  
Juri A. Giannotta ◽  
Anna Gallì ◽  
Rosangela Artuso ◽  
Paola Bianchi ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Plasma Cell ◽  
Clinical Efficacy ◽  
Lupus Erythematosus ◽  
Autoimmune Hemolytic Anemia ◽  
Plasma Cells ◽  
Proteasome Inhibitors ◽  
Immunomodulatory Effect ◽  
Cold Agglutinin ◽  
Cold Agglutinin Disease

Daratumumab is a monoclonal antibody directed against the transmembrane glycoprotein CD38 expressed on plasma cells and lymphoplasmocytes, with a proven efficacy in multiple myeloma. Here we show its clinical efficacy in a patient with cold agglutinin disease (CAD) relapsed after multiple lines of therapy. CAD is caused by cold reactive autoantibodies that induce complement mediated hemolysis and peripheral circulatory symptoms. The disease is also characterized by the presence of monoclonal IgM gammopathy and of a lymphoid bone marrow infiltration that benefits from B-cell targeting therapies (i.e., rituximab) but also from plasma cell directed therapies, such as proteasome inhibitors. In the patient described, we also show that daratumumab therapy influenced the dynamics of several immunoregulatory cytokine levels (IL-6, IL-10, IL-17, IFN-γ, TNF-α, TGF-β) indicating an immunomodulatory effect of the drug beyond plasma cell depletion. In addition, we provide a literature review on the use of daratumumab in autoimmune conditions, including multi-treated and refractory patients with autoimmune hemolytic anemia (both CAD and warm forms), Evans syndrome (association of autoimmune hemolytic anemia and immune thrombocytopenia) and non-hematologic autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis.

scholarly journals Effective Treatment of Cold Agglutinin Disease/Cold Agglutinin Syndrome with Ibrutinib: An International Case Series

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Marit Jalink ◽  
Sigbjørn Berentsen ◽  
Jorge J. Castillo ◽  
Steven Treon ◽  
Bruno Fattizzo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Hemolytic Anemia ◽  
Median Duration ◽  
Autoimmune Hemolytic Anemia ◽  
Research Funding ◽  
Cold Agglutinin ◽  
Cold Agglutinin Disease ◽  
Btk Inhibitor

Background In cold agglutinin mediated autoimmune hemolytic anemia (cAIHA), anti-red blood cell autoantibodies lead to complement-mediated hemolysis with or without symptoms of acrocyanosis after exposure at low temperatures. cAIHA can be divided into cold agglutinin disease (primary CAD) and cold agglutinin syndrome (CAS). The latter is secondary to diseases such as B-cell malignancies including CLL, infections or autoimmune disorders. In primary CAD, more than 90% of patients have a monoclonal IgM (mostly low level) and often a small bone marrow B-cell clone. There is no approved treatment. For patients with significant hemolytic anemia or acrocyanosis despite thermal protection, rituximab is the most accepted first line treatment with an overall response rate of 50% and median duration of response &lt;1 year. Cytotoxic combinations such as rituximab-bendamustine produce more sustained remissions, although with concerns for long-term adverse effects and stem cell toxicity. Studies involving complement inhibitors are showing promising results on hemolysis, although cold induced peripheral symptoms (IgM mediated rather than complement-mediated) will not improve. Recent international guidelines on cAIHA suggest treatment with the Bruton tyrosine kinase (BTK)-inhibitor ibrutinib in refractory patients with cAIHA (Jäger et al Blood Rev 2020). Indeed, the underlying pathophysiology of cAIHA suggest that BTK inhibition could be effective. Aims To evaluate the efficacy of ibrutinib on anemia, hemolysis and acrocyanosis in patients with cold agglutinin-mediated AIHA (CAD/CAS). Methods An international retrospective study was undertaken of cAIHA patients (CAD/CAS) treated with BTK inhibition using a preformed questionnaire. For eligible patients, laboratory and clinical data regarding underlying disease, bone marrow pathology, hemolytic parameters and patient-reported acrocyanosis were collected at diagnosis, 30 days, 3 months, 6 months and 12 months and last date of follow up. Hemoglobin (Hb) response was considered none (NR), partial (PR, &gt;2 g/dL Hb increase or &gt;10g/dL) or complete (CR, &gt;12g/dL). Adverse events were graded according to the Common Terminology Criteria, version-5.0 (2017). Results So far, 10 patients with cAIHA treated with a BTK-inhibitor (all involving ibrutinib) could be included in the study. Patients were followed from April 2014 until June 2020 at 5 centers (Italy (2), Norway, The United Kingdom and The United States). Median duration of follow up was 20 months (1-74 months). The main findings are summarized in table 1. The indication to start treatment was cAIHA based in all but 1 case (CLL). Median previous number of therapies was 2. All patients had a complement-mediated hemolytic anemia, 7 were transfusion-dependent, and 7 reported symptoms of acrocyanosis at the initiation of ibrutinib. After initiation of ibrutinib, all patients showed an improvement in hemoglobin (Median rise: 4.4 g/dL) resulting in 1 PR and 9 CR. All 7 transfusion-dependent patients became transfusion independent (5 within 30 days). In all but 1 patient, markers of hemolysis (LDH, bilirubin) improved after initiation of ibrutinib (see Figure 1). All 7 patients with acrocyanosis reported clear clinical improvement, with complete resolution of symptoms in 5. There was 1 adverse event (grade 1 bleeding). Data collection is still ongoing and future updates are expected. Conclusion Data show that ibrutinib is effective in the treatment of cAIHA with a notable and brisk improvement of both the hemolytic anemia as well as the cold induced peripheral symptoms. Although preliminary, these promising data support further research of BTK-inhibitor based treatment of cAIHA (CAD/CAS) in a prospective study. Disclosures Berentsen: Alexion, Apellis, Bioverativ and Janssen-Cilag: Other: Travel grants ; Alexion, Apellis, Bioverativ, Janssen-Cilag, True North Therapeutics: Honoraria; Apellis, Bioverativ, Momenta Pharmaceuticals and True North Therapeutics: Consultancy; Mundipharma: Research Funding. Castillo:TG Therapeutics: Research Funding; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Kymera: Consultancy; Abbvie: Research Funding; Janssen: Consultancy, Research Funding. Treon:Bristol-Meyer-Squibb: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding. D'Sa:Sanofi: Honoraria; BeiGene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. OffLabel Disclosure: BTK-inhibitors (ibrutinib/acalabrutinib) are not yet indicated for the use in (primairy) cold autoimmune hemolytic anemia (cAIHA). However it is indicated for use in Waldenstrom macroglobulinemia (WM) and chronic lymphatic leukemia (CLL). Here we report retrospective data on a cohort of cases treated with ibrutinib for cAIHA mostly secondary to WM or CLL.

scholarly journals Rituximab Use in Warm and Cold Autoimmune Hemolytic Anemia

2020 ◽  
Vol 9 (12) ◽  
pp. 4034
Author(s):  
Irina Murakhovskaya
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Blood Cells ◽  
Rare Condition ◽  
Cold Agglutinin ◽  
Toxicity Profile ◽  
Cold Agglutinin Disease ◽  
First Line ◽  
Hematologic Disorder

Autoimmune hemolytic anemia is a rare condition characterized by destruction of red blood cells with and without involvement of complement. It is associated with significant morbidity and mortality. In warm autoimmune hemolytic anemia, less than 50% of patients remain in long-term remission following initial steroid therapy and subsequent therapies are required. Cold agglutinin disease is a clonal hematologic disorder that requires therapy in the majority of patients and responds poorly to steroids and alkylators. Rituximab has a favorable toxicity profile and has demonstrated efficacy in autoimmune hemolytic anemia in first-line as well as relapsed settings. Rituximab is the preferred therapy for steroid refractory warm autoimmune hemolytic anemia (wAIHA) and as part of the first- and second-line treatment of cold agglutinin disease. This article reviews the mechanism of action of rituximab and the current literature on its role in the management of primary and secondary warm autoimmune hemolytic anemia and cold agglutinin disease.

scholarly journals Postoperative Recurrence of Invasive Thymoma with Cold Agglutinin Disease and Autoimmune Hemolytic Anemia

2016 ◽  
Vol 55 (18) ◽  
pp. 2685-2689 ◽  
Author(s):  
Taro Yoneda ◽  
Hayato Koba ◽  
Kota Tanimura ◽  
Naohiko Ogawa ◽  
Satoshi Watanabe ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Postoperative Recurrence ◽  
Cold Agglutinin ◽  
Invasive Thymoma ◽  
Cold Agglutinin Disease

scholarly journals Rituximab use in Warm and Cold Autoimmune Hemolytic Anemia

2020 ◽  
Author(s):  
Irina Murakhovskaya
Keyword(s):  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Blood Cells ◽  
Rare Condition ◽  
Cold Agglutinin ◽  
Toxicity Profile ◽  
Cold Agglutinin Disease ◽  
First Line ◽  
Hematologic Disorder

Autoimmune hemolytic anemia is a rare condition characterized by destruction of red blood cells with and without involvement of complement. It is associated with significant morbidity and mortality. In warm autoimmune hemolytic anemia less than 50% of patients remain in a long-term remission following initial steroid therapy and subsequent therapies are required. Cold agglutinin disease is a clonal hematologic disorder which requires therapy in majority of patients and responds poorly to steroids and alkylators. Rituximab has a favorable toxicity profile and has demonstrated efficacy in autoimmune hemolytic anemia in first line as well as relapsed setting. Rituximab is the preferred therapy for steroid refractory wAIHA and as part of the first- and second-line treatment of cold agglutinin disease. This article reviews the mechanism of action of the rituximab and current literature its role in management of primary and secondary warm autoimmune hemolytic anemia and cold agglutinin disease.

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