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 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 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 <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, >2 g/dL Hb increase or >10g/dL) or complete (CR, >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 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.

Unusually Severe Course of Autoimmune Hemolytic Anemia / Cold Agglutinin Disease: A Case Report

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S165-S165
Author(s):  
M M Yilmaz ◽  
Y Tanhehco
Keyword(s):  
Case Report ◽  
Plasma Exchange ◽  
Hemolytic Anemia ◽  
Autoimmune Hemolytic Anemia ◽  
Middle Lobe ◽  
Cold Agglutinin ◽  
Upper Respiratory Tract ◽  
Cold Agglutinin Disease ◽  
Cell Surface Antigens ◽  
Short Period

Abstract Introduction/Objective Autoimmune hemolytic anemia (AIHA) is a group of disorders with limited epidemiological and clinical data, characterized by hemolysis due to autoantibodies against red blood cell surface antigens. Cold agglutinins account for about 25% of all AIHA, which can agglutinate erythrocytes at 0-4 °C. Cold agglutinin disease (CAD) is a self limited disease and usually does not cause significant hemolysis. Here, we report a case with an unusually severe course for secondary CAD and role of plasma exchange in the management. Methods A 53-year-old male patient with no known past medical history presented to the emergency department with shortness of breath and syncope after a week of upper respiratory tract infection symptoms. The patient became profoundly anemic (presented with 8.1 g/dL hemoglobin level and progressively decline to 4.2 g/dL) in a short period of time. Upon initial evaluation, his peripheral blood smear demonstrated clumps of RBCs. Direct anti-globulin testing was negative for IgG but positive for C3 which is consistent with CAD. A respiratory PCR panel detected Rhinovirus. Mycoplasma and EBV IgM were negative. Additionally, chest X-ray showed right middle lobe pneumonia that was treated with antibiotics. Patient received multiple transfusions of pre-warmed pRBCS and showed initial improvement but eventually went into respiratory failure and cardiac arrest with return of spontaneous circulation after 8 minutes of CPR. Subsequently, plasma exchange was started. Only after intiation of plasma exchange, the patient’s ongoing hemolysis was stabilized. Conclusion This case report presents a patient with unexpectedly rapid and severe hemolysis from secondary cold agglutinin disease. Interestingly, the case appeared not to be caused by EBV or Mycoplasma pneumonia infection but Rhinovirus. Further studies confirmed patient had no autoimmune disorder or lymphoid malignancy that may had initiated secondary CAD. On the management aspect, pre-warmed RBC transfusions were not sufficient to stabilize the patient’s condition. Plasma exchange was able to control ongoing hemolysis within 2 sessions successfully.

scholarly journals Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia in Association with Antiphospholipid Syndrome

2021 ◽  
pp. 1-4
Author(s):  
Ram Gelman ◽  
Fadi Kharouf ◽  
Yuval Ishay ◽  
Alexander Gural
Keyword(s):  
Hemolytic Anemia ◽  
Antiphospholipid Syndrome ◽  
Complement Activation ◽  
Autoimmune Hemolytic Anemia ◽  
Cold Agglutinin ◽  
Primary Antiphospholipid Syndrome ◽  
Unique Case ◽  
Hematologic Disorders ◽  
Clear Association ◽  
Immune Mediated

Antiphospholipid syndrome and cold agglutinin-mediated autoimmune hemolytic anemia are 2 distinct immune-mediated hematologic disorders. While no clear association exists between these 2 entities, complement activation is known to occur in both of them. Herein, we report a unique case of cold agglutinin hemolytic anemia in a patient with a known primary antiphospholipid syndrome.

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