Cold Agglutinin Disease
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Cold agglutinin disease is a rare form of autoimmune hemolytic anemia caused by cold-reacting autoantibodies. Autoantibodies that bind to the erythrocyte membrane leading to premature erythrocyte destruction (hemolysis) characterize autoimmune hemolytic anemia. (See Pathophysiology and Etiology.) Peripheral blood smears may reveal clumps of red blood cells (RBCs). See the image below.
A common complaint among patients with cold agglutinin disease is painful fingers and toes with purplish discoloration associated with cold exposure. In chronic cold agglutinin disease, the patient is more symptomatic during the colder months. See Presentation.
Autoimmune hemolytic anemia is classified as primary or secondary and is subclassified according to autoantibody type. Primary cold agglutinin disease is characterized by a clonal lymphoproliferative disorder. [1, 2] Secondary cold agglutinin syndrome results from a systemic disease—infection or malignancy. [3]
In 90% of cases, the autoantibody in cold agglutinin disease is immunoglobulin M (IgM); rarely, it may involve monoclonal immunoglobulin G (IgG), immunoglobulin A (IgA), or λ light chain restriction. In contrast, warm autoimmune hemolytic anemia predominantly involves IgG. [1] Donath-Landsteiner hemolytic anemia is also caused by a cold-reacting immunoglobulin, but most cases are due to polyclonal IgG. [1]
Another autoimmune hemolytic anemia syndrome associated with cold-reacting autoantibodies is paroxysmal cold hemoglobinuria, which involves the IgG Donath-Landsteiner (D-L) antibody. Unlike cold agglutinin disease, in which affected RBCs are removed via extravascular phagocytosis, paroxysmal cold hemoglobinuria involves intravascular hemolysis. (See DDx.)
Primary cold agglutinin disease is usually associated with monoclonal cold-reacting autoantibodies. Primary cold agglutinin disease is chronic and occurs after the fifth decade of life, with a peak incidence in the seventh and eighth decades. (See Epidemiology.)
Secondary cold agglutinin disease may be associated with either monoclonal or polyclonal cold-reacting autoantibodies. It predominantly is caused by infection and lymphoproliferative disorders. Monoclonal secondary disease is usually chronic, occurring in adults. Polyclonal secondary cold agglutinin disease, which occurs in children and young adults, is usually transient. (See Etiology and Prognosis.)
Idiopathic cold agglutinin disease is usually benign, and most patients need only take protective measures against cold temperatures. Case studies report benefit from treatment with rituximab or the complement inhibitor eculizumab. RBC transfusion is indicated in severe, acute disease. Glucocorticoids are generally not useful in IgM-induced cold agglutinin disease but may occasionally work in selected patients. The presence of an associated malignancy requires specific therapy. See Treatment and Medication.
Cold agglutinins, or cold autoantibodies, occur naturally in nearly all individuals. These natural cold autoantibodies occur at low titers, less than 1:64 measured at 4°C, and have no activity at higher temperatures. Pathologic cold agglutinins occur at titers over 1:1000 and react at 28-31°C and sometimes at 37°C.
Cold agglutinin disease usually results from the production of a specific IgM antibody directed against the I/i antigens (precursors of the ABH and Lewis blood group substances) on red blood cells (RBCs). Cold agglutinins commonly have variable heavy-chain regions encoded by VH, with a distinct idiotype identified by the 9G4 rat murine monoclonal antibody. [4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20]
Because the I antigen is not activated until after birth, anti-i autoantibodies predominantly agglutinate neonatal RBCs, and anti-I autoantibodies predominantly agglutinate adult RBCs.
The 9G4 idiotope is localized to the V4-34 encoded portion of the variable region. [21] It is found on cold agglutinin-producing malignant lymphoid cells in the bone marrow in persons with lymphoproliferative disorders, on a small proportion of normal lymphoid cells, and in the spleen of a 15-week-old fetus. In contrast, the cold agglutinins found in healthy individuals, those with no clinical symptoms, are often derived from a variable segment other than the V4-34 portion. [22, 23]
The VH genes appear to regulate not only the production of cold agglutinins, but also the formation of normal antibodies to other carbohydrate antigens, both sharing the same fundamental mechanism of production. The I/i antigen analogues are present on human lymphocytes, neutrophils, and monocytes and in human saliva, milk, and amniotic fluid. Thus, in disease states, the finding of a clone of B cells producing this antibody may be the result of expansion of a normal clone that is specific for the production of an immunoglobulin with these properties. Autoimmune and lymphoproliferative disorders can also be associated with the production of cold agglutinins.
In vitro studies have shown that human monoclonal antibodies encoded by the V4-34 gene segment not only have cold agglutinin properties but also exhibit multireactivity. This is in contrast to the generally monospecific I/i reactivity of sera from patients with cold agglutinin disease. [18]
The hemolytic anemia associated with monoclonal cold agglutinins is typically more serious than that associated with polyclonal cold agglutinins. The monoclonal form is usually chronic, whereas the polyclonal form is often limited. [24]
Some polyclonal IgM cold agglutinins arise in association with infections with Mycoplasma pneumoniae, infectious mononucleosis, influenza B, and human immunodeficiency virus (HIV), as well as with other infections. (Cold agglutinins develop in more than 60% of patients with infectious mononucleosis, but hemolytic anemia is rare.)
Cytomegalovirus (CMV), rubella virus, varicella-zoster virus (VZV), parvovirus B19, and Chlamydia psittaci have also been implicated. [25]
In the case of infectious mononucleosis, hemolysis tends to develop 1-2 weeks after the onset of illness, but it may occur simultaneously or up to 2 months after onset. [25] Furthermore, increased expression of I/i antigens have been described on hemoglobin SS (HbSS) erythrocytes, which suggests that such patients may have increased susceptibility to cold-mediated hemolysis. [26]
In its classic presentation, with hemolytic anemia and Raynaud syndrome, cold agglutinin disease is usually idiopathic. As with most autoimmune diseases of a chronic nature, stimulated B lymphocytes begin to produce pathogenic antibodies against an antigen that is normally present in human tissue. In cold agglutinin disease, the antibody is an IgM, usually monoclonal, with kappa (κ) or lambda (λ) light chains. In chronic cold agglutinin disease, the antibody is usually directed against the I antigen on the membrane of normal adult RBCs.
Uncommonly, the antibody may be directed against only the i antigen found on fetal cord blood RBCs, which lack the mature I antigen; this has been reported in association with infectious mononucleosis. [27]
In a study of 78 patients, κ light-chain specificity was found in the majority of patients with chronic cold agglutinin disease or Waldenström macroglobulinemia, whereas two thirds of cold agglutinins found in patients with lymphomas had λ light-chain specificity. The type of light chain appears to correlate with the antigen specificity of the cold agglutinin. Fifty-eight percent of IgM/κ (usually κIII variable region subgroup) was anti-I, but 75% of IgM/λ had other antigen specificities. [11]
Antigen specificities of cold agglutinins other than the I/i system that have been described include those against Pr, M, P, and Lud and anti-Gd, anti-Fl, and anti-Sa. [7, 10, 13] Exclusive occurrence of κ chains has also been shown with some cold agglutinins. [6] Thus, benign and malignant cold agglutinins exhibit differences in their light chains and their specificities toward membrane antigens.
In vivo, the IgM antibody attaches to RBCs and causes them to agglutinate at temperatures below 37°C and maximally at 0-5°C, resulting in impaired blood flow to the digits, nose, and ears (ie, areas more likely to have colder temperatures [in the 30°C range]) when exposed to the cold.
Fixation of the C3 component of complement to the RBC by the cold agglutinin usually occurs in vivo at higher temperatures than those required by the IgM cold agglutinin to attach to the RBC, but it is generally less than 31°C. When the IgM/C3b-coated RBC circulates to warmer tissues, the IgM dissociates, leaving complement C3b on the original RBC.
The dissociated IgM cold agglutinin can then bind to another RBC at lower temperatures. Fixation of complement results in C3b and/or C4b components on the RBC membrane, which may lead to phagocytosis by macrophages in the reticuloendothelial system, particularly in the liver, where the macrophages have specific complement receptors. With time, the C3b components are converted enzymatically to C3dg, which is not recognized by macrophage receptors.
In chronic cold agglutinin disease, complement tends to be depleted. Thus, the hemolysis is self-controlled, and anemia may be only mild or moderate, because these C3dg-coated RBCs are no longer capable of reacting with the IgM antibody in the cold, the C3dg-coated RBCs are not recognized by the macrophages, and low complement levels become rate limiting.
Temporary increases in complement levels, as can occur with intercurrent febrile illnesses, can increase hemolysis. Lytic components of complement C5-C9 generally do not form on these cells, and intravascular hemolysis by complement is less likely to occur. [15] Hemolysis develops acutely following M pneumoniae infections and lasts approximately 1-3 weeks. Subclinical mild hemolysis with reticulocytosis may also occur, and the results of a direct Coombs test may be weakly positive, especially with M pneumoniae infections.
A review of Mayo Clinic patients with cold agglutinin disease identified underlying hematologic diseases in 69 of 89 patients (76%). Monoclonal gammopathy of undetermined significance (MGUS) constituted 42 cases. The other hematologic disorders were lymphoproliferative disorders: macroglobulinemia, chronic lymphocytic lymphoma, other lymphomas (including low-grade B-cell and diffuse large B-cell lymphoma), and cutaneous T-cell lymphoma. [1]
Monoclonal cold agglutinin IgM antibodies found in patients with lymphoma are the product of the abnormal clone. Progression of an idiopathic cold agglutinin disease to malignant lymphoma may occur in some cases; thus, affected patients require close, long-term follow-up, with obvious therapeutic implications. [27, 13] One study of 86 patients in Norway showed clonal light-chain predominance in 90% of patients, evidence of lymphoplasmacytic lymphoma in 50% of patients, and lymphoma of any type in 76% of patients overall. [1]
Hemolysis due to cold agglutinins can sometimes be accompanied by a warm antibody (IgG), resulting in a mixed autoimmune hemolytic anemia, [27, 12] that is, cold agglutinin syndrome and warm antibody autoimmune hemolysis, with the direct antiglobulin (direct Coombs) test results positive for the presence of IgG and complement on the surface of the sensitized RBC.
In mixed antibody syndromes, the IgG and IgM antibody components can be separated. The cold autoantibodies reactive at temperatures of 30°C or higher often show blood group specificity to the adult I antigen, whereas the warm autoantibodies are not directed against this system. A combination of cold agglutinins and cryoglobulins has also been reported with an IgM/κ monoclonal antibody, with specificity to the Pr2 antigen system. [19]
The presence of biphasic hemolysins implicates more severe disease. Biphasic hemolysins bind to RBCs at low temperatures and activate complement to produce in vitro hemolysis at warmer temperatures (37°C), whereas monophasic hemolysins bind to RBCs and activate complement at the same temperature. [28]
Data have confirmed an immunomodulatory/immunosuppressive role of the naturally occurring anti-F(ab’)2 antibodies in the production of cold agglutinins, with an inverse correlation between the titers of IgG-anti-F(ab’)2 and cold agglutinins. [17] This inverse correlation was found only in patients with anti-I/i and in the presence of a monoclonal lymphocyte population.
Several factors play a role in determining the ability of a cold agglutinin to induce an active hemolytic anemia. [4, 1] These include the following:
Cold agglutinins develop in more than 60% of patients with infectious mononucleosis, but hemolytic anemia is rare.
Classic chronic cold agglutinin disease is idiopathic, associated with symptoms and signs in relation to cold exposure. Causes of the monoclonal secondary disease include the following:
B-cell neoplasms – Waldenström macroglobulinemia, lymphoma, chronic lymphoid leukemia, myeloma [29]
Nonhematologic neoplasms
Causes of polyclonal secondary cold agglutinin disease include the following:
Mycoplasma infections – M pneumoniae [30]
Viral infections – Infectious mononucleosis due to Epstein-Barr virus (EBV) or CMV
Viral infections, other – Mumps, varicella, rubella, adenovirus, HIV, influenza, hepatitis C
Bacterial infections – Legionnaire disease, syphilis, listeriosis, Escherichia coli
Parasitic infections – Malaria, trypanosomiasis
Transient acute hemolysis may occur secondary to certain infectious diseases, such as M pneumoniae infection and infectious mononucleosis (eg, EBV). Other viral infections, such as influenza, HIV, CMV, rubella, varicella, and mumps, have also been reported to be associated with a hemolytic anemia due to cold agglutinins. Associated illnesses also include subacute bacterial endocarditis, syphilis, and malaria. The development of a febrile illness in a patient with chronic cold agglutinin disease may also accelerate hemolysis.
Cold agglutinins are seen in CANOMAD syndrome (chronic ataxic neuropathy ophthalmoplegia M-protein agglutination disialosyl antibodies). This syndrome is described by gait and upper-limb ataxia; cranial nerve involvement with external ophthalmoplegia; and the presence of cold agglutinins, IgM paraprotein, and anti-disialosyl antibodies. [31] The neurologic and hematologic symptoms have been seen to respond to rituximab. [32]
Lymphoproliferative and autoimmune diseases, myeloma, Kaposi sarcoma, and angioimmunoblastic lymphoma may occasionally be associated with the production of cold agglutinins. An idea of associated disease distribution was provided by a study of 78 patients with persistent cold agglutinins. Among these patients, 31 had lymphoma, 13 had Waldenström macroglobulinemia, 6 had chronic lymphoid leukemia, and 28 had chronic idiopathic cold agglutinin disease. [11]
A case of cold agglutinin–induced hemolytic anemia has been described in association with an aggressive natural killer cell (NK-cell) leukemia. [33] Nonhematologic malignancies can occasionally be associated with a high-titer cold agglutinin–induced hemolytic anemia. [9, 34]
Cytogenetic studies in patients with cold agglutinin disease have revealed the presence of trisomy 3 and trisomy 12. Translocation (8;22) has also been reported in association with cold agglutinin disease. [1, 35, 36]
Cold agglutinin–mediated hemolytic anemia has been described in patients after living-donor liver transplantation treated with tacrolimus and after bone marrow transplantation with cyclosporine treatments. It is postulated that such calcineurin inhibitors, which selectively affect T-cell function and spare B-lymphocytes, may interfere with the deletion of autoreactive T-cell clones, resulting in autoimmune disease. [37, 38, 39]
Cold agglutinin disease has been described in patients with sclerodermic features, with the degree of anemia being associated with increasing disease activity of the patient’s systemic sclerosis. This may suggest a close association between systemic rheumatic disease and autoimmune hematologic abnormalities. [40]
Hyperreactive malarial splenomegaly (HMS) is an immunopathologic complication of recurrent malarial infection. Patients with HMS develop splenomegaly, acquired clinical immunity to malaria, high serum concentrations of anti-Plasmodium antibodies, and high titers of IgM, with a complement-fixing IgM that acts as a cold agglutinin. [41]
Diphtheria-pertussis-tetanus (DPT) vaccination has been implicated in the development of autoimmune hemolytic anemia caused by IgM autoantibody with a high thermal range. A total of 6 cases have been reported; 2 followed the initial vaccination and 4 followed the second or third vaccinations. [23, 42, 43, 44, 45]
Equestrian perniosis is a rare cause of persistent elevated titers of cold agglutinins. [20] Also rarely, the first manifestations of cold agglutinin disease can develop when a patient is subjected to hypothermia for cardiopulmonary bypass surgery. [14]
The development of cold agglutinin syndrome is relatively uncommon, at least in the classic chronic form. Various reports state that 7-25% of cases of autoimmune hemolytic anemia are cold agglutinin mediated. Thus, while the incidence of cold and warm autoimmune hemolytic anemia (combined) is approximately 1 in 80,000, the incidence of cold agglutinin disease is approximately 1 in 300,000. Among autoimmune hemolytic anemias, cold agglutinin disease is the second most common cause, after warm autoantibody–induced immune hemolysis.
Data regarding the incidence of cold agglutinin disease are lacking. Frequency figures listed for the United States probably also apply to Canada and the United Kingdom.
In general, no predilection for either sex is noted, although some report a female predilection in older populations. Autoimmune hemolytic anemia appears to be more common in male children and female adolescents. [5, 27]
Only rarely do Infants and children develop chronic cold agglutinin disease, although Mycoplasma pneumoniae and infectious mononucleosis are diseases of young persons. Chronic cold agglutinin disease typically affects adults who are of middle age and older, with an average age of older than 60 years and peaking in the seventh and eighth decades of life. Although found in persons of all age groups, mixed autoimmune hemolysis is also more frequent in later life.
Cold agglutinin disease may be associated with an excellent long-term prognosis if it is secondary to M pneumonia or viral infections that are, in themselves, self-limited. In children and young adults, acute hemolysis lasts 1-3 weeks; evidence of cold agglutinins disappears within 6 months.
Patients with the mildly to moderately severe primary (idiopathic) variety of cold agglutinin disease are expected to have a good long-term prognosis if excessive exposure to cold is avoided and with close medical surveillance for complications or progression to lymphoma.
The nature of the antigenic specificity of the cold agglutinin, as when it is directed against the Pr antigen system, may be associated with greater severity of disease.
Cold agglutinin disease associated with HIV infection may have a relatively poor prognosis due to the nature of the underlying disease. The same applies to cases associated with lymphoma, with the prognosis dependent on remission of the underlying malignancy.
Complications of cold agglutinin disease include the following:
Brisk hemolysis due to cold exposure
Ischemic complications at exposed sites due to prolonged cold exposure
Other symptoms related to severe anemia
Infrequently, development of malignant disease during follow-up care of a patient with idiopathic chronic cold agglutinin disease
Shock or congestive heart failure, resulting from severe hemolysis and anemia
Peripheral gangrene and, rarely, fatalities after inadvertent and perhaps prolonged exposure to the cold
Transfusions for life-threatening symptoms due to severe anemia require prewarming and the use of washed RBCs (not cold). In general, autoimmune hemolytic anemia has a mortality rate of 10%.
A study by Kamesaki et al indicated that the clinical characteristics of patients with autoimmune hemolytic anemia who have a positive direct Coombs test (direct antiglobulin test [DAT]) differ from those of patients with this type of anemia and a negative DAT. The report used data from 216 patients with autoimmune hemolytic anemia, including 154 who were DAT negative and 62 who were DAT positive. [46]
The investigators found that patients who were DAT negative tended to have milder anemia and hemolysis than did patients who were DAT positive and that they needed significantly lower steroid doses during maintenance treatment. The 2 groups of patients were found to have an equally good response to steroids. Survival at 1-year follow-up for each group was comparable to that of the other.
It is essential to educate patients with chronic cold agglutinin disease about the importance of keeping all body parts warm at all times and avoiding cooling of body parts. Appropriate clothing is necessary in cold environments, and avoidance of cold foods and working in cold storage areas is also important.
Patients must comprehend the importance of their daily folic acid intake, which supplies a needed hematinic. Folic acid could easily become a rate-limiting hematinic in a patient with a chronic hemolytic process.
Teach patients to watch for signs of anemia, such as dyspnea, palpitations, and pallor, and to observe for signs of hemolysis, such as jaundice and dark urine.
For patient education information, see Anemia.
Swiecicki PL, Hegerova LT, Gertz MA. Cold agglutinin disease. Blood. 2013 Aug 15. 122 (7):1114-21. [Medline]. [Full Text].
Małecka A, Trøen G, Tierens A, Østlie I, Małecki J, Randen U, et al. Immunoglobulin heavy and light chain gene features are correlated with primary cold agglutinin disease onset and activity. Haematologica. 2016 May 19. [Medline].
Berentsen S, Randen U, Tjønnfjord GE. Cold agglutinin-mediated autoimmune hemolytic anemia. Hematol Oncol Clin North Am. 2015 Jun. 29 (3):455-71. [Medline].
Rosse WF, Adams JP. The variability of hemolysis in the cold agglutinin syndrome. Blood. 1980 Sep. 56(3):409-16. [Medline]. [Full Text].
Dacie J, The auto-immune haemolytic anaemias. The Haemolytic Anaemias. 3rd ed. Edinburgh, United Kingdom: Churchill Livingstone; 1992. Vol 3.: 210-362.
Harboe M, van Furth R, Schubothe H, Lind K, Evans RS. Exclusive occurrence of K chains in isolated cold haemagglutinins. Scand J Haematol. 1965. 2(3):259-66. [Medline].
Angevine CD, Andersen BR, Barnett EV. A cold agglutinin of the IgA class. J Immunol. 1966 Apr. 96(4):578-86. [Medline].
Garratty G, Petz LD, Hoops JK. The correlation of cold agglutinin titrations in saline and albumin with haemolytic anaemia. Br J Haematol. 1977 Apr. 35(4):587-95. [Medline].
Wortman J, Rosse W, Logue G. Cold agglutinin autoimmune hemolytic anemia in nonhematologic malignancies. Am J Hematol. 1979. 6(3):275-83. [Medline].
Roelcke D. The Lud cold agglutinin: a further antibody recognizing N-acetylneuraminic acid-determined antigens not fully expressed at birth. Vox Sang. 1981 Nov-Dec. 41(5-6):316-8. [Medline].
Crisp D, Pruzanski W. B-cell neoplasms with homogeneous cold-reacting antibodies (cold agglutinins). Am J Med. 1982 Jun. 72(6):915-22. [Medline].
Sokol RJ, Hewitt S, Stamps BK. Autoimmune hemolysis: mixed warm and cold antibody type. Acta Haematol. 1983. 69(4):266-74. [Medline].
Roelcke D. Reaction of anti-Gd, anti-Fl and anti-Sa cold agglutinins with p erythrocytes. Vox Sang. 1984. 46(3):161-4. [Medline].
Agarwal SK, Ghosh PK, Gupta D. Cardiac surgery and cold-reactive proteins. Ann Thorac Surg. 1995 Oct. 60(4):1143-50. [Medline].
Packman CH, Leddy JP. Cryopathic hemolytic syndromes. Beutler E, Lichtman M, Coller B, Kippst, eds. Williams Hematology. 5th ed. New York, NY: McGraw-Hill; 1995. 685-91.
Jacobs A. Cold agglutinin hemolysis responding to fludarabine therapy. Am J Hematol. 1996 Dec. 53(4):279-80. [Medline].
Terness P, Kirschfink M, Navolan D, et al. Inverse correlation between IgG-antihinge region and antierythrocyte autoantibody in chronic benign and malignant cold agglutination. J Clin Immunol. 1997 May. 17(3):220-7. [Medline].
Thorpe SJ, Turner CE, Stevenson FK, et al. Human monoclonal antibodies encoded by the V4-34 gene segment show cold agglutinin activity and variable multireactivity which correlates with the predicted charge of the heavy-chain variable region. Immunology. 1998 Jan. 93(1):129-36. [Medline]. [Full Text].
Ciejka JZ, Cook EB, Lawler D, et al. Severe cold agglutinin disease and cryoglobulinemia secondary to a monoclonal anti-Pr2 IgM lambda cryoagglutinin. Clin Exp Rheumatol. 1999 Mar-Apr. 17(2):227-31. [Medline].
De Silva BD, McLaren K, Doherty VR. Equestrian perniosis associated with cold agglutinins: a novel finding. Clin Exp Dermatol. 2000 Jun. 25(4):285-8. [Medline].
Potter KN. Molecular characterization of cold agglutinins. Transfus Sci. 2000 Feb-Apr. 22(1-2):113-9. [Medline].
Jefferies LC, Carchidi CM, Silberstein LE. Naturally occurring anti-i/I cold agglutinins may be encoded by different VH3 genes as well as the VH4.21 gene segment. J Clin Invest. 1993 Dec. 92(6):2821-33. [Medline]. [Full Text].
Berentsen S, Beiske K, Tjonnfjord GE. Primary chronic cold agglutinin disease: an update on pathogenesis, clinical features and therapy. Hematology. 2007 Oct. 12(5):361-70. [Medline]. [Full Text].
Gertz MA. Management of cold haemolytic syndrome. Br J Haematol. 2007 Aug. 138(4):422-9. [Medline].
McNicholl FP. Clinical syndromes associated with cold agglutinins. Transfus Sci. 2000 Feb-Apr. 22(1-2):125-33. [Medline].
Maniatis A, Papayannopoulou T, Bertles JF. Fetal characteristics of erythrocytes in sickle cell anemia: an immunofluorescence study of individual cells. Blood. 1979 Jul. 54(1):159-68. [Medline]. [Full Text].
Sokol RJ, Booker DJ, Stamps R. Erythropoiesis: Paroxysmal Cold Haemoglobinuria: A Clinico-Pathological Study of Patients with a Positive Donath-Landsteiner Test. Hematology. 1999. 4 (2):137-164. [Medline].
Sokol RJ, Booker DJ, Stamps R, Walewska R. Cold haemagglutinin disease: clinical significance of serum haemolysins. Clin Lab Haematol. 2000 Dec. 22(6):337-44. [Medline].
Maura F, Visco C, Falisi E, Reda G, Fabris S, Agnelli L, et al. B-cell receptor configuration and adverse cytogenetics are associated with autoimmune hemolytic anemia in chronic lymphocytic leukemia. Am J Hematol. 2012 Sep 26. [Medline].
Khan FY, A yassin M. Mycoplasma pneumoniae associated with severe autoimmune hemolytic anemia: case report and literature review. Braz J Infect Dis. 2009 Feb. 13(1):77-9. [Medline].
Delval A, Stojkovic T, Vermersch P. Relapsing sensorimotor neuropathy with ophthalmoplegia, antidisialosyl antibodies, and extramembranous glomerulonephritis. Muscle Nerve. 2006 Feb. 33(2):274-7. [Medline].
Siddiqui K, Cahalane E, Keogan M, Hardiman O. Chronic ataxic neuropathy with cold agglutinins: atypical phenotype and response to anti-CD20 antibodies. Neurology. 2003 Nov 11. 61(9):1307-8. [Medline].
Skorupa A, Chaudhary UB, Lazarchick J. Cold agglutinin induced autoimmune hemolytic anemia and NK-cell leukemia: a new association. Am J Hematol. 2007 Jul. 82(7):668-71. [Medline]. [Full Text].
Cao L, Kaiser P, Gustin D, Hoffman R, Feldman L. Cold agglutinin disease in a patient with uterine sarcoma. Am J Med Sci. 2000 Nov. 320(5):352-4. [Medline].
Michaux L, Dierlamm J, Wlodarska L, et al. Trisomy 3q11-q29 is recurrently observed in B-cell non-Hodgkin’s lymphomas associated with cold agglutinin syndrome. Ann Hematol. 1998 May. 76(5):201-4. [Medline].
Chng WJ, Chen J, Lim S, et al. Translocation (8;22) in cold agglutinin disease associated with B-cell lymphoma. Cancer Genet Cytogenet. 2004 Jul 1. 152(1):66-9. [Medline].
Kitamura T, Mizuta K, Kawarasaki H, Sugawara Y, Makuuchi M. Severe hemolytic anemia related to production of cold agglutinins following living donor liver transplantation: a case report. Transplant Proc. 2003 Feb. 35(1):399-400. [Medline].
Tamura T, Kanamori H, Yamazaki E, et al. Cold agglutinin disease following allogeneic bone marrow transplantation. Bone Marrow Transplant. 1994 Mar. 13(3):321-3. [Medline].
Thomson AW, Bonham CA, Zeevi A. Mode of action of tacrolimus (FK506): molecular and cellular mechanisms. Ther Drug Monit. 1995 Dec. 17(6):584-91. [Medline].
Oshima M, Maeda H, Morimoto K, Doi M, Kuwabara M. Low-titer cold agglutinin disease with systemic sclerosis. Intern Med. 2004 Feb. 43(2):139-42. [Medline]. [Full Text].
Torres JR, Villegas L, Perez H, et al. Low-grade parasitaemias and cold agglutinins in patients with hyper-reactive malarious splenomegaly and acute haemolysis. Ann Trop Med Parasitol. 2003 Mar. 97(2):125-30. [Medline].
Johnson ST, McFarland JG, Kelly KJ, Casper JT, Gottschall JL. Transfusion support with RBCs from an Mk homozygote in a case of autoimmune hemolytic anemia following diphtheria-pertussis-tetanus vaccination. Transfusion. 2002 May. 42(5):567-71. [Medline].
Gunduz Gedikoglu A, Cantez T. Haemolytic-anaemia relapses after immunisation and pertussis. Lancet. 1967 Oct 21. 2(7521):894-5. [Medline].
Zupanska B, Lawkowicz W, Gorska B, et al. Autoimmune haemolytic anaemia in children. Br J Haematol. 1976 Nov. 34(3):511-20. [Medline].
Haneberg B, Matre R, Winsnes R, et al. Acute hemolytic anemia related to diphtheria-pertussis-tetanus vaccination. Acta Paediatr Scand. 1978 May. 67(3):345-50. [Medline].
Kamesaki T, Toyotsuji T, Kajii E. Characterization of direct antiglobulin test-negative autoimmune hemolytic anemia: A study of 154 cases. Am J Hematol. 2012 Oct 25. [Medline].
Berentsen S. How I manage patients with cold agglutinin disease. Br J Haematol. 2018 May. 181 (3):320-330. [Medline].
Hoppe B, Gaedicke G, Kiesewetter H, Salama AR. Response to intravenous immunoglobulin G in an infant with immunoglobulin A-associated autoimmune haemolytic anaemia. Vox Sang. 2004 Feb. 86(2):151-3. [Medline].
Roy-Burman A, Glader BE. Resolution of severe Donath-Landsteiner autoimmune hemolytic anemia temporally associated with institution of plasmapheresis. Crit Care Med. 2002 Apr. 30(4):931-4. [Medline].
Teachey DT, Felix CA. Development of cold agglutinin autoimmune hemolytic anemia during treatment for pediatric acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2005 Jul. 27(7):397-9. [Medline].
Giulino LB, Bussel JB, Neufeld EJ. Treatment with rituximab in benign and malignant hematologic disorders in children. J Pediatr. 2007 Apr. 150(4):338-44, 344.e1. [Medline]. [Full Text].
Webster D, Ritchie B, Mant MJ. Prompt response to rituximab of severe hemolytic anemia with both cold and warm autoantibodies. Am J Hematol. 2004 Apr. 75(4):258-9. [Medline]. [Full Text].
Berentsen S, Ulvestad E, Tjonnfjord GE. B-lymphocytes as targets for therapy in chronic cold agglutinin disease. Cardiovasc Hematol Disord Drug Targets. 2007 Sep. 7(3):219-27. [Medline].
Berentsen S, Randen U, Vagan AM, Hjorth-Hansen H, Vik A, Dalgaard J. High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease. Blood. 2010 Oct 28. 116(17):3180-4. [Medline].
Shapiro R, Chin-Yee I, Lam S. Eculizumab as a bridge to immunosuppressive therapy in severe cold agglutinin disease of anti-Pr specificity. Clin Case Rep. 2015 Nov. 3 (11):942-4. [Medline].
Alexander Röth, Martin Bommer, Andreas Hüttmann, et al. Complement Inhibition with Eculizumab in Patients with Cold Agglutinin Disease (CAD): Results from a Prospective Phase II Trial (DECADE Trial). Blood. 2015 Dec 06. 126:274.
Sandip Panicker, Graham C. Parry, Michael Fillitz, et al. TNT009, a monoclonal antibody inhibitor of C1s, induces a rapid and complete remission of anemia in primary cold agglutinin disease patients. Immunobiology. 2016 Oct 01. 221:1170-1171.
Inaba H, Geiger TL, Lasater OE, Wang WC. A case of hemoglobin SC disease with cold agglutinin-induced hemolysis. Am J Hematol. 2005 Jan. 78(1):37-40. [Medline]. [Full Text].
Batalias L, Trakakis E, Loghis C, et al. Autoimmune hemolytic anemia caused by cold agglutinins in a young pregnant woman. J Matern Fetal Neonatal Med. 2006 Apr. 19(4):251-3. [Medline].
Atkinson VP, Soeding P, Horne G, Tatoulis J. Cold agglutinins in cardiac surgery: management of myocardial protection and cardiopulmonary bypass. Ann Thorac Surg. 2008 Jan. 85(1):310-1. [Medline].
Aoki A, Kay GL, Zubiate P, Ruggio J, Kay JH. Cardiac operation without hypothermia for the patient with cold agglutinin. Chest. 1993 Nov. 104(5):1627-9. [Medline].
Barbara DW, Mauermann WJ, Neal JR, Abel MD, Schaff HV, Winters JL. Cold agglutinins in patients undergoing cardiac surgery requiring cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2013 Sep. 146(3):668-80. [Medline].
Hippe E, Jensen KB, Olesen H, Lind K, Thomsen PE. Chlorambucil treatment of patients with cold agglutinin syndrome. Blood. 1970 Jan. 35(1):68-72. [Medline]. [Full Text].
O’Connor BM, Clifford JS, Lawrence WD, Logue GL. Alpha-interferon for severe cold agglutinin disease. Ann Intern Med. 1989 Aug 1. 111(3):255-6. [Medline].
Shi J, Rose EL, Singh A, Hussain S, Stagliano NE, Parry GC, et al. TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins. Blood. 2014 Jun 26. 123 (26):4015-22. [Medline].
Risitano AM, Marotta S. Therapeutic complement inhibition in complement-mediated hemolytic anemias: Past, present and future. Semin Immunol. 2016 Jun. 28 (3):223-40. [Medline].
Bartko J, Schoergenhofer C, Schwameis M, Firbas C, Beliveau M, Chang C, et al. A Randomized, First-in-Human, Healthy Volunteer Trial of sutimlimab, a Humanized Antibody for the Specific Inhibition of the Classical Complement Pathway. Clin Pharmacol Ther. 2018 May 8. 88 (12):1715, 1722-3. [Medline].
Salman Abdullah Aljubran, MD Allergist and Immunologist, Associate Director of FARE Center of Excellence, Children’s Mercy Hospitals and Clinics; Assistant Professor of Medicine and Pediatrics, Division of Allergy, Asthma and Immunology, University of Missouri-Kansas City School of Medicine
Salman Abdullah Aljubran, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American Medical Association, Clinical Immunology Society
Disclosure: Nothing to disclose.
Richard F Lockey, MD University Distinguished Health Professor, Professor of Medicine, Pediatrics and Public Health, Joy McCann Culverhouse Chair in Allergy and Immunology, University of South Florida College of Medicine; Director, Division of Allergy and Immunology, James A Haley Veterans’ Hospital
Richard F Lockey, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Allergy Asthma and Immunology, American Association for the Advancement of Science, American College of Occupational and Environmental Medicine, American College of Chest Physicians, American College of Physicians, American Medical Association, Florida Medical Association
Disclosure: Nothing to disclose.
Michael A Kaliner, MD Clinical Professor of Medicine, George Washington University School of Medicine; Medical Director, Institute for Asthma and Allergy
Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, Association of American Physicians
Disclosure: Nothing to disclose.
Nicolas A Camilo, MD Consulting Staff, Mountain States Tumor Institute, Division of Pediatric Hematology-Oncology, St Luke’s Regional Medical Center
Disclosure: Nothing to disclose.
Max J Coppes, MD, PhD, MBA Senior Vice President, Center for Cancer and Blood Disorders, Children’s National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.
Gary D Crouch, MD Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Associate Professor, Uniformed Services University of the Health Sciences
Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology
Disclosure: Nothing to disclose.
Sharon Georgy, MD Resident Physician, Department of Internal Medicine, University of South Florida College of Medicine
Sharon Georgy, MD is a member of the following medical societies: Phi Beta Kappa
Disclosure: Nothing to disclose.
James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children’s Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center
James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.
Gary R Jones, MD Associate Medical Director, Clinical Development, Berlex Laboratories
Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.
Jeffrey Lee Kishiyama, MD Assistant Clinical Professor of Medicine, University of California, San Francisco, School of Medicine; Consulting Staff, Allergy and Asthma Associates of Santa Clara Valley Research Center
Disclosure: Nothing to disclose.
Thomas W Loew, MD Director, Clinical Associate Professor of Pediatrics, Pediatric Hematology/Oncology Subspecialty Training Program, University of Iowa Hospitals and Clinics
Disclosure: Nothing to disclose.
Rajalaxmi McKenna, MD, FACP Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.
Harry L Messmore, Jr, MD Professor, Department of Medicine, Division of Hematology/Oncology, Loyola University Stritch School of Medicine
Harry L Messmore, Jr, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Angiology, American College of Physicians, American Heart Association, American Society of Hematology, and Phi Beta Kappa
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Cold Agglutinin Disease
Research & References of Cold Agglutinin Disease|A&C Accounting And Tax Services
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