804:. In a population-based clinical study of primary CAD in Norway, the prevalence was found to be 16 per million in habitants and the incidence rate 1 per million inhabitants per year. Little is known about possible geographic variations. Median age of CAD patients was 76 years and median age at onset of symptoms was approximately 67 years. The male/female ratio has been reported to be 0.5–0.6 which is not very different from a male/female ratio of 0.72 in an age-matched general population. The frequency of auto-immune disorders other than CAD does probably not differ from what is to be expected in an elderly population with some female predominance. as about 12.5 years from diagnosis and median age at death was 82 years, which implies a life expectancy in these patients similar to that of an age-matched general population. More than 90% of patients with primary CAD have Cold-induced circulatory symptoms ranging from moderate acrocyanosis to severe Raynaud phenomena precipitated even by very slight cold exposure.
42:
813:
each. The auto antibodies responsible for hemagglutination at low temperatures, cold agglutinins (CA), may be found in the sera of healthy subjects as well as in patients with AIHA of the cold reactive types. CA bind to erythrocyte surface antigens at a temperature optimum of 0–4 °C. In contrast to polyclonal CA in healthy individuals, monoclonal CA often have a high-thermal amplitude, which contributes to their pathogenicity at temperatures approaching 37 °C.
705:(an antibody that selectively reduces specific types of immune cells) is effective in about 60% of cases of severe cold agglutinin disease. Medical researchers have found the response to rituximab is seen on average within 1 to 2 months of treatment and the effect of the treatment lasts for about 1 to 2 years. Rituximab may be used after a second and even a third relapse, however the success rate is less. Combined treatment with rituximab and
1859:
1030:
816:
Binding of CA causes agglutination of erythrocytes and the antigen–antibody complex induces complement (C) activation and hemolysis. Essential clinical manifestations of primary CAD are hemolytic anemia and cold-induced circulatory symptoms. Exact estimates of the severity of anemia and the frequency
812:
Cold hemagglutination was first reported by
Landsteiner in 1903 and found to occur in human beings in 1918. The association of cold hemagglutination with hemolysis was described in 1937 by Rosenthal and Corten. During the 1960s, Dacie and Schubothe published systematic descriptions of 16 CAD patients
689:
The treatment of cold agglutinin disease depends on many factors including the severity of the condition, the signs and symptoms present in each person, and the underlying cause. For example, in those affected by secondary cold agglutinin disease, it is important to diagnose and treat the underlying
96:
Cold agglutinin disease can be primary (unknown cause) or secondary, due to an underlying condition such as an infection, another autoimmune disease, or certain cancers. Treatment depends on many factors including the severity of the condition, the signs and symptoms present in each person, and the
92:
When affected people's blood is exposed to cold temperatures (32 °F (0 °C; 273 K) to 50 °F (10 °C; 283 K)), certain proteins that normally attack bacteria (IgM antibodies) attach themselves to red blood cells and bind them together into clumps (agglutination). This
742:
The long-term outlook (prognosis) for people with cold agglutinin disease varies based on many factors including the severity of the condition, the signs and symptoms present in each person and the underlying cause. For example, people with cold agglutinin disease caused by bacterial or viral
743:
infections tend to have an excellent prognosis; in these cases, the symptoms typically disappear within 6 months after the infection has resolved. Mild to moderate primary (unknown cause) cold agglutinin disease can also be associated with a good prognosis if excessive exposure to the
585:
If the complement response is insufficient to form membrane attack complexes, then extravascular lysis will be favored over intravascular red blood cell lysis. In lieu of the membrane attack complex, complement proteins (particularly C3b and C4b) are deposited on red blood cells. This
709:
has resulted in higher response rates (76% of cases) and longer periods of remissions (on average, 6.5 years). However the combined treatment may include serious side effects so is presently only recommended when rituximab has not worked alone. Finally,
763:
Cold agglutinin disease most commonly affects adults who are of middle age and older. Some studies also report a slight bias in favor of females in the incidence of cold agglutinin disease, particularly in older populations. People with
578:, an effector of the complement cascade. In the formation of the membrane attack complex, several complement proteins are inserted into the red blood cell membrane, forming pores that lead to membrane instability and intravascular
534:
which means that multiple environmental factors and genes likely interact to predispose a person to developing the condition. However, no disease-causing genes have been identified and no familial cases have been reported.
120:(destruction of red blood cells, causing low levels of red blood cells). However, the number of symptoms and severity of symptoms may depend on how severe the anemia is. Signs and symptoms of hemolytic anemia may include:
2556:
2541:
2035:
Berentsen, S; Ulvestad, E; Langholm, R; Beiske, K; Hjorth-Hansen, H; Ghanima, W; Sørbø, JH; Tjønnfjord, GE (2006). "Primary chronic cold agglutinin disease: a population based clinical study of 86 patients".
529:
Cold agglutinin disease is not an inherited condition. It is designated as either primary (unknown cause) or secondary (associated with or caused by another condition). In some cases, cold agglutinin may be
112:
months. Symptoms may arise suddenly leading to abrupt onset of severe anemia and hemoglobinuria or develop more gradually and insidiously in the background without patient's consciousness and precaution.
380:
376:
2162:
Dacie, J. (1992). "Auto-immune haemolytic anaemia (AIHA): Cold antibody syndromes I: Idiopathic types: Clinical presentation and haematological and serological findings.". In Dacie, J. (ed.).
632:
A diagnosis of cold agglutinin disease may be made after several types of tests are performed by a health care provider. In some cases, the diagnosis is first suspected by chance if a routine
718:, however its effect is only short term. Removing the spleen is not recommended for cold agglutinin disease. In addition, because severe cold agglutinin disease requires very high doses of
1078:
Dacie, J. V.; Crookston, J. H.; Christenson, W. N. (1957). "'Incomplete' Cold
Antibodies: Role of Complement in Sensitization to Antiglobulin Serum by Potentially Haemolytic Antibodies".
1983:
Genty, I; Michel, M; Hermine, O; Schaeffer, A; Godeau, B; Rochant, H (2002). "[Characteristics of autoimmune hemolytic anemia in adults: retrospective analysis of 83 cases]".
1714:
Berentsen, Sigbjørn; Ulvestad, Elling; Gjertsen, Bjørn Tore; Hjorth-Hansen, Henrik; Langholm, Ruth; Knutsen, Håvar; Ghanima, Waleed; Shammas, Fuad Victor; Tjønnfjord, Geir E. (2004).
218:
In people with secondary CAD (associated with another underlying condition), there may be additional signs and symptoms depending on the condition present. For example:
531:
108:
Symptoms of cold agglutinin disease (CAD) are often triggered or made worse by cold temperatures or a viral infection. Therefore, symptoms generally are worse during
550:
At body temperatures of 28–31 °C, such as those encountered during winter months, and occasionally at body temperatures of 37 °C, antibodies (generally
1704:
Dacie J. The auto-immune haemolytic anaemias: Introduction. In: Dacie J, editor. The haemolytic anaemias. vol. 3. London: Churchill
Livingstone; 1992. pp. 1–5.
725:
Several possible therapies have been reported in a few case reports to have successfully treated people who are not responding to the treatments listed above.
2143:
Rosenthal F, Corten M. Über das Phänomen der Auto-hämagglutination und über die
Eigenscaften der Kältehämagglutinine. Folia Haematol (Leipzig) 1937;58:64–90.
694:. People with few symptoms and/or mild anemia may not require any specific treatment. These cases are often managed by simply avoiding exposure to the cold.
547:
under 64 at 4 °C). In individuals with cold agglutinin disease, these antibodies are in much higher concentrations (titers over 1000 at 4 °C).
1016:
1816:
1132:
932:
881:
1539:
644:(from symptoms and/or blood tests). A person may also be physically examined for spleen or liver enlargement. An antiglobulin test (called the
332:
Cold agglutinin disease can be either primary (unknown cause) or secondary (a result of another pathology/ caused by an underlying condition).
543:
All individuals have circulating antibodies directed against red blood cells, but their concentrations are often too low to trigger disease (
1465:
Ma ecka, A.; Troen, G.; Tierens, A.; Ostlie, I.; Ma ecki, J.; Randen, U.; Berentsen, S.; Tjonnfjord, G. E.; Delabie, J. M. A. (2016-05-19).
2787:
567:
2453:
Nydegger, UE; Kazatchkine, MD; Miescher, PA (1991). "Immunopathologic and clinical features of hemolytic anemia due to cold agglutinins".
625:. Detection of antibodies in serum of the patient (still circulating in the blood, that have not yet formed any complexes with RBC) is an
2992:
1532:"Cold Agglutinin Disease Workup: Approach Considerations, Complete Blood Cell Count and Peripheral Smear, Reticulocytes and Spherocytes"
3143:
2645:
3178:
3095:
2917:
2125:
Landsteiner K. Über
Beziehungen zwischen dem Blutserum und den Körperzellen. Münchener medizinische Wochenschrift. 1903;50:1812–1814.
846:
93:
eventually causes red blood cells to be prematurely destroyed (hemolysis) leading to anemia and other associated signs and symptoms.
2987:
1840:
2927:
831:
2171:
714:, which involves filtering blood to remove antibodies, may be useful in acute hemolytic crisis and before surgery requiring
2804:
1467:"Immunoglobulin heavy and light chain gene features are correlated with primary cold agglutinin disease onset and activity"
2959:
3173:
1381:
Berentsen, Sigbjørn; Randen, Ulla; Tjønnfjord, Geir E. (2015). "Cold
Agglutinin-Mediated Autoimmune Hemolytic Anemia".
1158:
Berentsen, Sigbjørn; Randen, Ulla; Tjønnfjord, Geir E. (2015). "Cold
Agglutinin-Mediated Autoimmune Hemolytic Anemia".
2134:
Clough MC, Richter IM. A study of an auto-agglutinin occurring in human serum. Johns
Hopkins Hosp Bull. 1918;29:86–93.
355:
Primary cold agglutinin disease occurs after the fifth decade of life and peaks prevalence in a person's 70s and 80s.
2968:
2939:
1716:"Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients"
728:
However more studies need to be performed before the safety and effectiveness of these therapies can be determined.
89:, specifically one in which antibodies bind red blood cells only at low body temperatures, typically 28–31 °C.
2999:
2871:
491:
2076:
Ulvestad, E; Berentsen, S; Bø, K; Shammas, FV (1999), "Clinical immunology of chronic cold agglutinin disease.",
192:. These may occur because the heart has to work harder to make sure the body gets enough healthy red blood cells.
2932:
2638:
841:
836:
2953:
2861:
1003:
1001:
999:
997:
995:
993:
991:
989:
987:
985:
983:
981:
979:
977:
975:
973:
971:
969:
3026:
2978:
967:
965:
963:
961:
959:
957:
955:
953:
951:
949:
722:(levels not considered safe), corticosteroid treatment is no longer a recommended treatment in severe cases.
690:
condition which may include certain types of cancer; bacterial, viral, or parasitic infections; and/or other
895:
3168:
2883:
769:
487:
476:
349:
1124:
1048:
1008:
946:
871:
3035:
2909:
2773:
2728:
924:
801:
777:
613:. Those with secondary agglutinin disease may also present with an underlying disease, often autoimmune.
383:
predominantly caused by infection or lymphoproliferative disorders. In adults, this is typically due to:
86:
1618:
73:
and autoantibodies that are also active at temperatures below 30 °C (86 °F), directed against
2973:
2799:
2900:
2890:
2878:
2631:
621:
Detection of antibodies (cold or warm) and /or complement system on RBC from the patient is a direct
66:
41:
2866:
2571:
2367:
RØRVIK, K (1954). "The syndrome of high-titre cold haemagglutination; a survey and a case report".
1928:"Primary chronic cold agglutinin disease: An update on pathogenesis, clinical features and therapy"
1285:"Primary chronic cold agglutinin disease: An update on pathogenesis, clinical features and therapy"
765:
395:
1760:
Barcellini, Wilma (2015-07-31). "Current treatment strategies in autoimmune hemolytic disorders".
776:
are more susceptible to this condition. Cold agglutinin disease represents an estimated 16–32% of
3071:
575:
78:
2410:
Kirschfink, M; Knoblauch, K; Roelcke, D (1994). "Activation of complement by cold agglutinins".
3062:
2723:
2324:
Zilow, G; Kirschfink, M; Roelcke, D (1994). "Red cell destruction in cold agglutinin disease".
1531:
626:
3042:
2809:
220:
1877:
204:. These symptoms result from slow or poor circulation and can range from mild to disabling.
3052:
3047:
2855:
2741:
1647:"The role of complement in the clearance of cold agglutinin-sensitized erythrocytes in man"
773:
633:
507:
387:
282:
225:
201:
800:
In single-center series, primary CAD has been found to account for 13–15% of the cases of
8:
3101:
2846:
2654:
2560:
1204:
902:
826:
457:
652:. In people with cold agglutinin disease, the Coombs test is almost always positive for
3133:
3106:
2711:
2380:
2109:
2089:
1960:
1927:
1793:
1594:
1561:
1499:
1466:
1317:
1284:
1103:
1091:
691:
472:
419:
341:
229:
212:
62:
2565:
1996:
1679:
1646:
919:
917:
915:
3138:
3128:
3087:
3082:
3077:
3018:
2850:
2839:
2829:
2763:
2746:
2737:
2719:
2681:
2582:
2505:
2497:
2470:
2462:
2435:
2427:
2392:
2384:
2349:
2341:
2306:
2298:
2260:
2252:
2211:
2203:
2167:
2101:
2093:
2053:
2045:
2008:
2000:
1965:
1947:
1785:
1777:
1737:
1684:
1666:
1599:
1581:
1504:
1486:
1447:
1439:
1398:
1363:
1322:
1304:
1265:
1257:
1183:
1175:
1095:
1060:
571:
563:
372:
263:
196:
Many people with CAD also experience pain and bluish coloring of the hands and feet (
30:
2113:
2030:
2028:
2026:
2024:
2022:
1797:
1107:
2834:
2819:
2758:
2419:
2376:
2333:
2290:
2247:
2242:
2230:
2085:
1992:
1955:
1939:
1769:
1727:
1674:
1658:
1589:
1573:
1494:
1478:
1429:
1390:
1353:
1312:
1296:
1247:
1167:
1087:
912:
653:
641:
610:
570:). Binding of antibodies to red blood cells activates the classical pathway of the
495:
258:
117:
2611:
1773:
3013:
2576:
2019:
1817:"clinical-features-and-treatment-of-autoimmune-hemolytic-anemia-cold-agglutinins"
1482:
1434:
1417:
1342:"Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia"
1252:
1235:
719:
506:
In children, cold agglutinin disease is often secondary to an infection, such as
465:
423:
415:
307:
2071:
2069:
2067:
1921:
1919:
1917:
3030:
2658:
2166:. Vol. 3 (3rd ed.). London, UK: Churchill Livingstone. pp. 1–5.
1915:
1913:
1911:
1909:
1907:
1905:
1903:
1901:
1899:
1897:
1732:
1715:
1577:
1458:
1358:
1341:
785:
755:
generally have a poor prognosis due to the nature of the underlying condition.
711:
640:) of the red blood cells. In most cases, the diagnosis is based on evidence of
574:. If the complement response is sufficient, red blood cells are damaged by the
555:
544:
499:
375:. It is a result of an underlying condition potentially associated with either
368:
74:
2623:
2587:
2550:
2294:
1943:
1394:
1300:
1276:
1229:
1227:
1225:
1171:
1153:
1151:
1149:
817:
of cold-induced symptoms, however, have not been provided until recent years.
734:(Enjaymo) was approved for medical use in the United States in February 2022.
3162:
2501:
2466:
2431:
2388:
2345:
2302:
2256:
2207:
2097:
2064:
2049:
2004:
1976:
1951:
1863:
1781:
1670:
1585:
1490:
1443:
1308:
1261:
1179:
1034:
789:
781:
748:
637:
514:
345:
189:
2446:
1894:
609:
Individuals with cold agglutinin disease present with signs and symptoms of
2673:
2509:
2403:
2396:
2264:
2105:
2057:
2012:
1969:
1789:
1741:
1603:
1508:
1451:
1402:
1367:
1326:
1269:
1222:
1187:
1146:
1099:
1064:
587:
559:
364:
321:
302:
248:
208:
197:
185:
181:
59:
2474:
2439:
2353:
2310:
2215:
2824:
2782:
1878:"Cold Agglutinin Disease: Practice Essentials, Pathophysiology, Etiology"
1688:
1205:"Cold Agglutinin Disease: Practice Essentials, Pathophysiology, Etiology"
780:, whose annual incidence is estimated to be between 1/35,000-1/80,000 in
715:
706:
645:
622:
451:
403:
2533:
1640:
1638:
16:
Blood disorder in which cold sensitive antibodies target red blood cells
2793:
2317:
731:
439:
391:
243:
207:
Other signs and symptoms of CAD may include enlargement of the spleen (
177:
159:
149:
35:
2423:
2337:
1926:
Berentsen, Sigbjørn; Beiske, Klaus; Tjønnfjord, Geir E. (2007-07-21).
1713:
1662:
1409:
1283:
Berentsen, Sigbjørn; Beiske, Klaus; Tjønnfjord, Geir E. (2007-07-21).
1234:
Swiecicki, Paul L.; Hegerova, Livia T.; Gertz, Morie A. (2013-08-15).
1013:
Genetic and Rare
Diseases Information Center (GARD) – an NCATS Program
2606:
2281:
Olesen, H. (1966). "Thermodynamics of the Cold
Agglutinin Reaction".
1635:
907:
702:
698:
683:
591:
579:
447:
431:
287:
144:
131:
675:
No cold drinks; all drinks should be at room temperature (or above).
65:
characterized by the presence of high concentrations of circulating
876:
649:
648:) may be performed to determine the presence of a specific type of
483:
399:
316:
297:
292:
171:
167:
154:
136:
1862:
This article incorporates text from this source, which is in the
1033:
This article incorporates text from this source, which is in the
461:
435:
408:
253:
125:
1869:
2702:
2545:
2034:
752:
599:
312:
268:
109:
1755:
1753:
1751:
1416:
Swiecicki, P. L.; Hegerova, L. T.; Gertz, M. A. (2013-06-11).
582:(destruction of the red blood cell within the blood vessels).
2283:
Scandinavian Journal of Clinical and Laboratory Investigation
2235:
Hematology. American Society of Hematology. Education Program
603:
595:
427:
224:
infection (the most common cause of secondary CAD) may cause
82:
1841:"FDA approves treatment for adults with rare type of anemia"
2452:
2189:
2187:
2185:
2183:
1982:
1748:
1657:(4). American Society for Clinical Investigation: 942–949.
1477:(9). Ferrata Storti Foundation (Haematologica): e361–e364.
1199:
1197:
744:
2409:
2075:
1526:
1524:
1522:
1520:
1518:
792:, more than 60% of whom develop cold agglutinins disease.
1925:
1464:
1380:
1282:
1157:
1077:
747:
is avoided. Those with cold agglutinin disease caused by
657:
551:
518:
443:
70:
2180:
1875:
1194:
2276:
2274:
2194:
Schubothe, H (1966). "The cold hemagglutinin disease".
1515:
678:
Requires heater to maintain temperature in cold places.
2323:
1415:
1233:
228:. Various infections or cancers may cause enlarged or
2481:
100:
Cold agglutinin disease was first described in 1957.
2523:
2271:
2222:
1645:
Jaffe, C J; Atkinson, J P; Frank, M M (1976-10-01).
795:
358:
1339:
1644:
335:
1340:Berentsen, Sigbjørn; Tjønnfjord, Geir E. (2012).
562:on the surface of red blood cells (typically the
3160:
2360:
1428:(7). American Society of Hematology: 1114–1121.
2653:
1833:
1619:"What are complex or multifactorial disorders?"
1119:
1117:
929:NORD (National Organization for Rare Disorders)
363:Secondary cold agglutinin syndrome occurs when
176:Heart problems such as an irregular heartbeat (
2488:Gertz, MA (2006), "Cold agglutinin disease.",
1610:
1560:Baines, Andrea C.; Brodsky, Robert A. (2017).
2639:
1559:
2788:Glucose-6-phosphate dehydrogenase deficiency
2241:(1). American Society of Hematology: 19–23.
1707:
1383:Hematology/Oncology Clinics of North America
1160:Hematology/Oncology Clinics of North America
1114:
606:, a process termed extravascular hemolysis.
590:enhances the clearance of red blood cell by
2672:
1811:
1809:
1807:
1071:
1040:
3144:Hereditary persistence of fetal hemoglobin
2646:
2632:
1759:
866:
864:
862:
701:, medical interventions may be necessary.
371:, rendering them subject to attack by the
40:
3096:Mean corpuscular hemoglobin concentration
2918:Warm antibody autoimmune hemolytic anemia
2412:Infusionstherapie und Transfusionsmedizin
2326:Infusionstherapie und Transfusionsmedizin
2246:
2193:
1959:
1731:
1678:
1616:
1593:
1498:
1433:
1357:
1316:
1251:
847:Warm antibody autoimmune hemolytic anemia
211:) and mottled discoloration of the skin (
2157:
2155:
2153:
2151:
2149:
1804:
340:The primary form is caused by excessive
2128:
1876:Salman Abdullah Aljubran (2019-02-02).
1617:Reference, Genetics Home (2019-02-05).
859:
381:polyclonal cold-reacting autoantibodies
377:monoclonal cold-reacting autoantibodies
3161:
2366:
2280:
2137:
116:Most people with CAD have symptoms of
2701:
2627:
2487:
2228:
2161:
2146:
2119:
1700:
1698:
1651:The Journal of Clinical Investigation
1046:
103:
2805:triosephosphate isomerase deficiency
236:80–99% of people have these symptoms
2960:paroxysmal nocturnal hemoglobinuria
2928:Donath–Landsteiner hemolytic anemia
2908:
1932:Hematology (Amsterdam, Netherlands)
1125:"Orphanet: Cold agglutinin disease"
832:Donath–Landsteiner hemolytic anemia
275:5–29% of people have these symptoms
13:
2381:10.1111/j.0954-6820.1954.tb01722.x
2090:10.1111/j.1600-0609.1999.tb01887.x
1938:(5). Informa UK Limited: 361–370.
1768:(5). Informa UK Limited: 681–691.
1695:
1092:10.1111/j.1365-2141.1957.tb05773.x
925:"Anemia, Hemolytic, Cold Antibody"
538:
14:
3190:
2969:Microangiopathic hemolytic anemia
2940:Mixed autoimmune hemolytic anemia
2519:
1845:U.S. Food and Drug Administration
636:(CBC) detects abnormal clumping (
627:indirect Coombs antiglobulin test
482:Certain types of cancers such as
359:Secondary cold agglutinin disease
3179:Cold autoimmune hemolytic anemia
3000:Hemolytic disease of the newborn
1857:
1028:
2289:(1). Informa UK Limited: 1–15.
2078:European Journal of Haematology
1553:
1542:from the original on 2017-10-06
1374:
1333:
1135:from the original on 2015-10-06
1019:from the original on 2018-11-23
935:from the original on 2017-02-21
884:from the original on 2015-10-06
796:Primary cold agglutinin disease
758:
336:Primary cold agglutinin disease
2933:Paroxysmal cold hemoglobinuria
2248:10.1182/asheducation-2006.1.19
1080:British Journal of Haematology
842:Paroxysmal cold hemoglobinuria
837:List of hematologic conditions
788:. In patients with infectious
672:Treat the underlying lymphoma.
524:
1:
1997:10.1016/S0248-8663(02)00688-4
1774:10.1586/17474086.2015.1073105
852:
492:Waldenström macroglobulinemia
2884:Southeast Asian ovalocytosis
2872:Minkowski–Chauffard syndrome
1985:La Revue de Médecine Interne
1483:10.3324/haematol.2016.146126
1435:10.1182/blood-2013-02-474437
1253:10.1182/blood-2013-02-474437
770:lymphoproliferative diseases
737:
663:
616:
488:chronic lymphocytic leukemia
477:systemic lupus erythematosus
350:lymphoproliferative disorder
7:
2229:Gertz, M. A. (2006-01-01).
1762:Expert Review of Hematology
1166:(3). Elsevier BV: 455–471.
820:
778:autoimmune hemolytic anemia
87:autoimmune hemolytic anemia
10:
3195:
2993:Drug-induced nonautoimmune
2974:Thrombotic microangiopathy
2800:pyruvate kinase deficiency
1733:10.1182/blood-2003-10-3597
1578:10.1016/j.blre.2017.02.003
1359:10.1016/j.blre.2012.01.002
807:
348:, characterized by clonal
3174:Acquired hemolytic anemia
3121:
3061:
3012:
2979:Hemolytic–uremic syndrome
2899:
2891:Hereditary stomatocytosis
2879:Hereditary elliptocytosis
2772:
2757:
2710:
2694:
2665:
2597:
2527:
2295:10.3109/00365516609065601
2231:"Cold Hemolytic Syndrome"
1944:10.1080/10245330701445392
1418:"Cold agglutinin disease"
1395:10.1016/j.hoc.2015.01.002
1301:10.1080/10245330701445392
1236:"Cold agglutinin disease"
1172:10.1016/j.hoc.2015.01.002
1049:"Cold agglutinin disease"
1009:"Cold agglutinin disease"
872:"Cold agglutinin disease"
67:cold sensitive antibodies
29:
24:
2867:Hereditary spherocytosis
2369:Acta Medica Scandinavica
766:infectious mononucleosis
623:Coombs antiglobulin test
327:
164:Pain in the back or legs
3072:Mean corpuscular volume
3036:Diamond–Blackfan anemia
2988:Drug-induced autoimmune
2923:Cold agglutinin disease
2729:Plummer–Vinson syndrome
2164:The Haemolytic Anaemias
1623:Genetics Home Reference
1047:Gertz, Moric A (2006).
903:Cold Agglutinin Disease
576:membrane attack complex
52:Cold agglutinin disease
25:Cold agglutinin disease
2724:Iron-deficiency anemia
2455:Seminars in Hematology
2196:Seminars in Hematology
3043:Pure red cell aplasia
2810:hexokinase deficiency
396:Legionnaires' disease
221:Mycoplasma pneumoniae
3048:Sideroblastic anemia
2856:Hemoglobin C disease
2742:Megaloblastic anemia
1562:"Complementopathies"
774:mycoplasma pneumonia
751:or certain types of
686:has been described.
634:complete blood count
458:Parasitic infections
388:Bacterial infections
283:Abnormal urine color
226:respiratory symptoms
3169:Autoimmune diseases
2847:Sickle cell disease
827:Cold shock response
697:In severe cases of
669:Avoid cold weather.
473:autoimmune diseases
230:swollen lymph nodes
141:Cold hands and feet
3134:Sulfhemoglobinemia
2598:External resources
1882:Medscape Reference
1536:Medscape Reference
1209:Medscape Reference
692:autoimmune disease
420:Epstein-Barr virus
342:cell proliferation
213:livedo reticularis
104:Signs and symptoms
97:underlying cause.
85:. It is a form of
77:, causing them to
63:autoimmune disease
3156:
3155:
3152:
3151:
3139:Reticulocytopenia
3129:Methemoglobinemia
3117:
3116:
3008:
3007:
2948:
2947:
2747:Pernicious anemia
2690:
2689:
2682:Polycythemia vera
2621:
2620:
2424:10.1159/000223020
2338:10.1159/000223021
2173:978-0-443-03502-9
1847:. 4 February 2022
1663:10.1172/jci108547
572:complement system
373:complement system
264:Muscular weakness
202:Raynaud's disease
49:
48:
19:Medical condition
3186:
2906:
2905:
2820:hemoglobinopathy
2770:
2769:
2708:
2707:
2699:
2698:
2670:
2669:
2648:
2641:
2634:
2625:
2624:
2525:
2524:
2513:
2512:
2485:
2479:
2478:
2450:
2444:
2443:
2407:
2401:
2400:
2364:
2358:
2357:
2321:
2315:
2314:
2278:
2269:
2268:
2250:
2226:
2220:
2219:
2191:
2178:
2177:
2159:
2144:
2141:
2135:
2132:
2126:
2123:
2117:
2116:
2073:
2062:
2061:
2032:
2017:
2016:
1980:
1974:
1973:
1963:
1923:
1892:
1891:
1889:
1888:
1873:
1867:
1861:
1860:
1856:
1854:
1852:
1837:
1831:
1830:
1828:
1827:
1813:
1802:
1801:
1757:
1746:
1745:
1735:
1711:
1705:
1702:
1693:
1692:
1682:
1642:
1633:
1632:
1630:
1629:
1614:
1608:
1607:
1597:
1557:
1551:
1550:
1548:
1547:
1528:
1513:
1512:
1502:
1462:
1456:
1455:
1437:
1413:
1407:
1406:
1378:
1372:
1371:
1361:
1337:
1331:
1330:
1320:
1280:
1274:
1273:
1255:
1246:(7): 1114–1121.
1231:
1220:
1219:
1217:
1216:
1201:
1192:
1191:
1155:
1144:
1143:
1141:
1140:
1121:
1112:
1111:
1075:
1069:
1068:
1044:
1038:
1032:
1031:
1027:
1025:
1024:
1005:
944:
943:
941:
940:
921:
910:
899:
893:
892:
890:
889:
868:
654:immunoglobulin M
642:hemolytic anemia
611:hemolytic anemia
496:multiple myeloma
416:Viral infections
259:Hemolytic anemia
118:hemolytic anemia
45:
44:
22:
21:
3194:
3193:
3189:
3188:
3187:
3185:
3184:
3183:
3159:
3158:
3157:
3148:
3113:
3057:
3016:
3004:
2944:
2895:
2761:
2753:
2686:
2661:
2659:red blood cells
2652:
2622:
2617:
2616:
2593:
2592:
2536:
2522:
2517:
2516:
2486:
2482:
2451:
2447:
2408:
2404:
2365:
2361:
2322:
2318:
2279:
2272:
2227:
2223:
2192:
2181:
2174:
2160:
2147:
2142:
2138:
2133:
2129:
2124:
2120:
2074:
2065:
2033:
2020:
1981:
1977:
1924:
1895:
1886:
1884:
1874:
1870:
1858:
1850:
1848:
1839:
1838:
1834:
1825:
1823:
1815:
1814:
1805:
1758:
1749:
1712:
1708:
1703:
1696:
1643:
1636:
1627:
1625:
1615:
1611:
1558:
1554:
1545:
1543:
1530:
1529:
1516:
1463:
1459:
1414:
1410:
1379:
1375:
1338:
1334:
1281:
1277:
1232:
1223:
1214:
1212:
1203:
1202:
1195:
1156:
1147:
1138:
1136:
1123:
1122:
1115:
1076:
1072:
1045:
1041:
1029:
1022:
1020:
1007:
1006:
947:
938:
936:
923:
922:
913:
900:
896:
887:
885:
870:
869:
860:
855:
823:
810:
798:
761:
740:
720:corticosteroids
682:Treatment with
666:
619:
541:
539:Pathophysiology
527:
466:trypanosomiasis
424:cytomegalovirus
369:red blood cells
361:
338:
330:
308:Lymphadenopathy
106:
75:red blood cells
39:
20:
17:
12:
11:
5:
3192:
3182:
3181:
3176:
3171:
3154:
3153:
3150:
3149:
3147:
3146:
3141:
3136:
3131:
3125:
3123:
3119:
3118:
3115:
3114:
3112:
3111:
3110:
3109:
3104:
3092:
3091:
3090:
3085:
3080:
3067:
3065:
3059:
3058:
3056:
3055:
3050:
3045:
3038:
3033:
3031:Fanconi anemia
3024:
3022:
3010:
3009:
3006:
3005:
3003:
3002:
2996:
2995:
2990:
2984:
2983:
2982:
2981:
2971:
2965:
2964:
2963:
2962:
2949:
2946:
2945:
2943:
2942:
2937:
2936:
2935:
2925:
2920:
2914:
2912:
2903:
2897:
2896:
2894:
2893:
2888:
2887:
2886:
2876:
2875:
2874:
2858:
2853:
2844:
2843:
2842:
2837:
2832:
2815:
2814:
2813:
2812:
2807:
2802:
2790:
2778:
2776:
2767:
2755:
2754:
2752:
2751:
2750:
2749:
2734:
2733:
2732:
2731:
2716:
2714:
2705:
2696:
2692:
2691:
2688:
2687:
2685:
2684:
2678:
2676:
2667:
2663:
2662:
2651:
2650:
2643:
2636:
2628:
2619:
2618:
2615:
2614:
2602:
2601:
2599:
2595:
2594:
2591:
2590:
2579:
2568:
2553:
2537:
2532:
2531:
2529:
2528:Classification
2521:
2520:External links
2518:
2515:
2514:
2480:
2445:
2402:
2375:(4): 299–308.
2359:
2316:
2270:
2221:
2179:
2172:
2145:
2136:
2127:
2118:
2063:
2018:
1975:
1893:
1868:
1832:
1803:
1747:
1706:
1694:
1634:
1609:
1572:(4): 213–223.
1552:
1538:. 2019-02-02.
1514:
1457:
1408:
1373:
1332:
1295:(5): 361–370.
1275:
1221:
1193:
1145:
1131:. 2019-02-08.
1113:
1070:
1039:
1015:. 2019-01-24.
945:
931:. 2004-10-28.
911:
894:
857:
856:
854:
851:
850:
849:
844:
839:
834:
829:
822:
819:
809:
806:
797:
794:
786:Western Europe
760:
757:
739:
736:
712:plasmapheresis
680:
679:
676:
673:
670:
665:
662:
618:
615:
556:polysaccharide
554:) bind to the
540:
537:
532:multifactorial
526:
523:
504:
503:
500:Kaposi sarcoma
480:
469:
455:
413:
365:autoantibodies
360:
357:
337:
334:
329:
326:
325:
324:
319:
310:
305:
300:
295:
290:
285:
279:
278:
276:
272:
271:
266:
261:
256:
251:
246:
240:
239:
237:
194:
193:
186:enlarged heart
174:
165:
162:
157:
152:
147:
142:
139:
134:
129:
105:
102:
47:
46:
33:
27:
26:
18:
15:
9:
6:
4:
3:
2:
3191:
3180:
3177:
3175:
3172:
3170:
3167:
3166:
3164:
3145:
3142:
3140:
3137:
3135:
3132:
3130:
3127:
3126:
3124:
3120:
3108:
3105:
3103:
3100:
3099:
3098:
3097:
3093:
3089:
3086:
3084:
3081:
3079:
3076:
3075:
3074:
3073:
3069:
3068:
3066:
3064:
3060:
3054:
3053:Myelophthisic
3051:
3049:
3046:
3044:
3040:
3039:
3037:
3034:
3032:
3028:
3025:
3023:
3020:
3015:
3011:
3001:
2998:
2997:
2994:
2991:
2989:
2986:
2985:
2980:
2977:
2976:
2975:
2972:
2970:
2967:
2966:
2961:
2958:
2957:
2956:
2955:
2951:
2950:
2941:
2938:
2934:
2931:
2930:
2929:
2926:
2924:
2921:
2919:
2916:
2915:
2913:
2911:
2907:
2904:
2902:
2898:
2892:
2889:
2885:
2882:
2881:
2880:
2877:
2873:
2870:
2869:
2868:
2865:
2863:
2859:
2857:
2854:
2852:
2848:
2845:
2841:
2838:
2836:
2833:
2831:
2828:
2827:
2826:
2823:
2821:
2817:
2816:
2811:
2808:
2806:
2803:
2801:
2798:
2797:
2796:
2795:
2791:
2789:
2786:
2784:
2780:
2779:
2777:
2775:
2771:
2768:
2765:
2760:
2756:
2748:
2745:
2744:
2743:
2739:
2736:
2735:
2730:
2727:
2726:
2725:
2721:
2718:
2717:
2715:
2713:
2709:
2706:
2704:
2700:
2697:
2693:
2683:
2680:
2679:
2677:
2675:
2671:
2668:
2664:
2660:
2656:
2649:
2644:
2642:
2637:
2635:
2630:
2629:
2626:
2613:
2609:
2608:
2604:
2603:
2600:
2596:
2589:
2585:
2584:
2580:
2578:
2574:
2573:
2569:
2567:
2563:
2562:
2558:
2554:
2552:
2548:
2547:
2543:
2539:
2538:
2535:
2530:
2526:
2511:
2507:
2503:
2499:
2496:(4): 439–41,
2495:
2491:
2490:Haematologica
2484:
2476:
2472:
2468:
2464:
2460:
2456:
2449:
2441:
2437:
2433:
2429:
2425:
2421:
2417:
2413:
2406:
2398:
2394:
2390:
2386:
2382:
2378:
2374:
2370:
2363:
2355:
2351:
2347:
2343:
2339:
2335:
2331:
2327:
2320:
2312:
2308:
2304:
2300:
2296:
2292:
2288:
2284:
2277:
2275:
2266:
2262:
2258:
2254:
2249:
2244:
2240:
2236:
2232:
2225:
2217:
2213:
2209:
2205:
2201:
2197:
2190:
2188:
2186:
2184:
2175:
2169:
2165:
2158:
2156:
2154:
2152:
2150:
2140:
2131:
2122:
2115:
2111:
2107:
2103:
2099:
2095:
2091:
2087:
2084:(4): 259–66,
2083:
2079:
2072:
2070:
2068:
2059:
2055:
2051:
2047:
2043:
2039:
2038:Haematologica
2031:
2029:
2027:
2025:
2023:
2014:
2010:
2006:
2002:
1998:
1994:
1991:(11): 901–9.
1990:
1987:(in French).
1986:
1979:
1971:
1967:
1962:
1957:
1953:
1949:
1945:
1941:
1937:
1933:
1929:
1922:
1920:
1918:
1916:
1914:
1912:
1910:
1908:
1906:
1904:
1902:
1900:
1898:
1883:
1879:
1872:
1865:
1864:public domain
1846:
1842:
1836:
1822:
1818:
1812:
1810:
1808:
1799:
1795:
1791:
1787:
1783:
1779:
1775:
1771:
1767:
1763:
1756:
1754:
1752:
1743:
1739:
1734:
1729:
1726:(8): 2925–8.
1725:
1721:
1717:
1710:
1701:
1699:
1690:
1686:
1681:
1676:
1672:
1668:
1664:
1660:
1656:
1652:
1648:
1641:
1639:
1624:
1620:
1613:
1605:
1601:
1596:
1591:
1587:
1583:
1579:
1575:
1571:
1567:
1566:Blood Reviews
1563:
1556:
1541:
1537:
1533:
1527:
1525:
1523:
1521:
1519:
1510:
1506:
1501:
1496:
1492:
1488:
1484:
1480:
1476:
1472:
1471:Haematologica
1468:
1461:
1453:
1449:
1445:
1441:
1436:
1431:
1427:
1423:
1419:
1412:
1404:
1400:
1396:
1392:
1389:(3): 455–71.
1388:
1384:
1377:
1369:
1365:
1360:
1355:
1352:(3): 107–15.
1351:
1347:
1346:Blood Reviews
1343:
1336:
1328:
1324:
1319:
1314:
1310:
1306:
1302:
1298:
1294:
1290:
1286:
1279:
1271:
1267:
1263:
1259:
1254:
1249:
1245:
1241:
1237:
1230:
1228:
1226:
1210:
1206:
1200:
1198:
1189:
1185:
1181:
1177:
1173:
1169:
1165:
1161:
1154:
1152:
1150:
1134:
1130:
1126:
1120:
1118:
1109:
1105:
1101:
1097:
1093:
1089:
1085:
1081:
1074:
1066:
1062:
1059:(4): 439–41.
1058:
1054:
1053:Haematologica
1050:
1043:
1036:
1035:public domain
1018:
1014:
1010:
1004:
1002:
1000:
998:
996:
994:
992:
990:
988:
986:
984:
982:
980:
978:
976:
974:
972:
970:
968:
966:
964:
962:
960:
958:
956:
954:
952:
950:
934:
930:
926:
920:
918:
916:
909:
905:
904:
898:
883:
879:
878:
873:
867:
865:
863:
858:
848:
845:
843:
840:
838:
835:
833:
830:
828:
825:
824:
818:
814:
805:
803:
793:
791:
790:mononucleosis
787:
783:
782:North America
779:
775:
771:
767:
756:
754:
750:
749:HIV infection
746:
735:
733:
729:
726:
723:
721:
717:
713:
708:
704:
700:
695:
693:
687:
685:
677:
674:
671:
668:
667:
661:
659:
655:
651:
647:
643:
639:
638:agglutination
635:
630:
628:
624:
614:
612:
607:
605:
601:
597:
593:
589:
583:
581:
577:
573:
569:
565:
561:
560:glycoproteins
557:
553:
548:
546:
536:
533:
522:
520:
516:
515:mononucleosis
512:
510:
501:
497:
493:
489:
485:
481:
478:
474:
470:
467:
463:
459:
456:
453:
449:
445:
441:
437:
433:
429:
425:
421:
417:
414:
411:
410:
405:
401:
397:
393:
389:
386:
385:
384:
382:
378:
374:
370:
366:
356:
353:
351:
347:
346:B lymphocytes
343:
333:
323:
320:
318:
314:
311:
309:
306:
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3102:normochromic
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2674:Polycythemia
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588:opsonization
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322:Splenomegaly
303:Hepatomegaly
249:Autoimmunity
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209:splenomegaly
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198:acrocyanosis
195:
182:heart murmur
115:
107:
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81:and undergo
55:
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3107:hypochromic
3063:Blood tests
2825:Thalassemia
2783:enzymopathy
2712:Nutritional
716:hypothermia
707:fludarabine
646:Coombs test
525:Inheritance
452:hepatitis C
404:listeriosis
124:Tiredness (
79:agglutinate
3163:Categories
3088:macrocytic
3083:microcytic
3078:normocytic
3041:Acquired:
3027:Hereditary
2794:glycolysis
2774:Hereditary
2583:DiseasesDB
1887:2019-02-11
1851:6 February
1826:2019-02-09
1628:2019-02-10
1546:2019-02-09
1289:Hematology
1215:2019-02-09
1139:2019-02-09
1023:2019-02-09
939:2019-02-09
888:2019-02-09
853:References
732:Sutimlimab
592:phagocytes
568:Pr antigen
558:region of
509:Mycoplasma
440:adenovirus
392:mycoplasma
244:Arthralgia
178:arrhythmia
160:Chest pain
150:Dark urine
69:, usually
36:Hematology
2759:Hemolytic
2607:eMedicine
2502:0390-6078
2467:0037-1963
2432:1019-8466
2389:0001-6101
2346:1019-8466
2303:0036-5513
2257:1520-4391
2208:0037-1963
2098:0902-4441
2050:0390-6078
2005:0248-8663
1952:1607-8454
1782:1747-4086
1671:0021-9738
1586:0268-960X
1491:0390-6078
1444:0006-4971
1309:1607-8454
1262:0006-4971
1180:0889-8588
908:eMedicine
738:Prognosis
703:Rituximab
699:hemolysis
684:rituximab
664:Treatment
617:Diagnosis
580:hemolysis
564:I antigen
511:pneumonia
448:influenza
432:varicella
288:Back pain
145:Pale skin
137:Headaches
132:Dizziness
31:Specialty
3017:(mostly
3014:Aplastic
2954:membrane
2901:Acquired
2862:membrane
2762:(mostly
2655:Diseases
2510:16585009
2397:13157944
2265:17124034
2114:34579070
2106:10530415
2058:16585012
2013:12481390
1970:17891600
1821:UpToDate
1798:27741019
1790:26343892
1742:15070665
1604:28215731
1540:Archived
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1452:23757733
1403:26043385
1368:22330255
1327:17891600
1270:23757733
1188:26043385
1133:Archived
1129:Orphanet
1108:38159450
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1017:Archived
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882:Archived
877:Orphanet
821:See also
650:antibody
484:lymphoma
475:such as
460:such as
400:syphilis
390:such as
367:bind to
317:vomiting
298:Headache
293:Diarrhea
172:diarrhea
168:Vomiting
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