Cold agglutinin disease Report of a case Thomas R. Kerley, D.M.D., * Carl E. Schow, Jr., D.D.S., David R. Mulherin, D.D.S.,*** Galveston, Texas DIVISION
OF ORAL
MEDICAL
BRANCH
SURGERY,
DEPARTMENT
OF SURGERY,
THE
** and UNIVERSITY
OF TEXAS
Cold agglutinin disease is an autoimmune hemolytic anemia with varying causes. Two major types are recognized, with different clinical manifestations. Cold agglutinins are circulating antibodies capable of erythrocyte agglutination. However, the reaction is readily reversible. Treatment of the disease is variable. A case is presented to illustrate that minor oral surgical procedures are feasible, provided the proper precautions are taken.
C
old agglutinin disease is an autoimmune hemolytic anemia’ that has various causes. Two major types are recognized: transienP 3 or secondary4, 5 and chronic6 idiopathic of cold agglutinin disease syndrome.2 Chronic cold agglutinin disease is of unknown origin, with clinical manifestations of intravascular agglutination, acrocyanosis, hemolytic anemia,4 and paroxysmal hemoglobinuria on exposure to cold.’ The hemolytic anemia is usually mild, with intermittent severe crises exacerbated by exposure to cold temperatures.” s It presents as a lymphoproliferative disorder6 in the fourth to the eighth decade,” with a peak incidence at the age of 50 to 60 years.’ It may progress to classic lymphoma.’ Secondary cold agglutinin disease occurs because of an increase in cold agglutinin titers associated variously with atypical mycoplasmal pneumonia,3* 5 lymphoma, systemic lupus erythematosis, cirrhosis, colitis, pancreatitis, 4 infectious mononucleosis, mumps orchitis, and trypanos0miasis.j It is rarely associated with hemolysis.’ Cold agglutinins are circulating, completment-fixing IgM antibodies capable of agglutinating erythrocytes at temperatures below 37” C.*, 4, ’ As temperature decreases, cold agglutinin is bound to the erythrocyte surface by the Ii antigen and fixes complement.‘, ’ If sufficient complement is bound, intravascular hemolysis may occur,” ’ but usually only enough is bound to produce sequestration by the reticuloendothelial sys*Second-year Resident in Oral and Maxillofacial Surgery. **Professor and Chief of the Division of Oral and Maxillofacial Surgery. ***Third-year Resident in Oral and Maxillofacial Surgery.
0030.4220/79/070039+02$00.20/0
0
1979 The C. V. Mosby Co.
tern. The sensitized erythrocytes are bound to Kupffer’s cells in the liver sinusoids, where most are phagocytized; however, some are released back into circulation, where the cells survive normally.*~ ’ A rewarming to 37” C. results in an almost immediate total reversal by dissociation of the antigen-antibody complex.‘, 4 Treatment of cold agglutinin disease consists of treatment of any underlying disease,4 avoidance of cold42 ’ and maintenance of room temperature at 32 to 35” C. ,s transfusions,s and/or cytotoxic drugs.‘, ’ Steroids are of questionable value. Another recently proposed therapeutic tool is plasma exchange.’ CASE REPORT On June 18, 1978, a 59-year-old white man was referred to our office with the diagnosis of periodontal disease, cold agglutinin disease,and prolonged bleeding time. Clinical and radiographic examination revealed a well-developed, wellnourished white man with fourteen remaining teeth and advanced periodontal disease. The patient’s past medical history revealedthat since 1959 he had suffered acrocyanosis, paroxysmal hemoglobinuria, abdominal discomfort, and nauseaon exposure to temperatures below 6.5”F. When he donatedblood in 1974, a routine sample hemolysed on cooling. A complete history and evaluation of further testsled to the diagnosis of chronic cold agglutinin disease.From the time of his initial diagnosis until his referral to our office, the patient was placed on varying courses of chlorambucil, Cytoxan, vincristine, prednisone, and folic acid; he underwent regular plasmapheresiswith transfusions as indicated. In 1977the patient was discoveredto have a prolonged Ivy bleeding time, presumably causedby an IgM coating of the platelets interfering with surface aggregation. His current
39
40
Kerlry,
medications
consisted
vincristine caproic
(2 mg. acid
19.
tractions.
well
through
recovered
warmer, The
accomplished
acid
syrup in
and careful
without
without
for 2 days for
suture
REFERENCES I. Schubothe,
local
every
2.
anes3.
intravenous and 4.
the procedure bleeding
postoperatively
removal.
ex-
of warming
approximation
tolerated
(16 C.C. orally
I week
with consisted
postoperatively
day),
and amino-
full-mouth
administering
patient
every
4 hours).
underwent
precautions
He was maintained returned
orally
2 weeks).
every
to 32” C.,
a blood
aminocaproic
(5 mg.
and gingivoplasty
Special
of the gingiva. and
Oral Surg. July, 1979
every
the patient
preoperatively
hemolysis. patient
1978,
alveoloplasty,
suturing
acid
intravenously
in our office.
the room fluids
of folic
intravenously
(4 Cm.
On July thesia
Scholv, and Mulheritt
or
5.
on
4 hours).
The
which
was
6.
incident.
SUMMARY
Cold agglutinin disease is an autoimmune hemolytic anemia involving an antigen-antibody reaction with complement fixation upon exposure to decreased temperatures resulting in hemolysis. It may be idiopathic, or it may occur as a secondary disease entity. Treatment consists of avoidance of cold, administration of cytotoxins, treatment of underlying disease, transfusion, plasma exchange, and/or steroids. The case of a patient with long-standing chronic cold agglutinin disease who underwent a full-mouth extraction without complications has been presented.
7.
8.
9.
H.: Current Problems of Chronic Cold Hemagglutinin Disease, Ann. N. Y. Acad. Sci. 124: 484-490. 1965. Jaffe. C. J.. Atkinson, 1. P.. and Frank. M. M.: The Role of Complement in the Clearance of Cold Agglutinin-Sensitized Erythrocytes in Man, J. Clin. Invest. 58: 942-949, 1976. Jacobsen, L. B., and Longstreth. G. F.: Clinical and Immunologic Feature\ of Transient Cold Agglutinin Hemolytic Anemia, Am. J. Med. 54: 514.521, 1973. Felber, N.: Cold Agglutinin Disease. Postgad. Med. 60: 89-94, 1976. Harbor. M.: Cold Auto-agglutinin
OF ORAL
MEDICAL
BRANCH
SURGERY,
DEPARTMENT
OF SURGERY,
THE
** and UNIVERSITY
OF TEXAS
Cold agglutinin disease is an autoimmune hemolytic anemia with varying causes. Two major types are recognized, with different clinical manifestations. Cold agglutinins are circulating antibodies capable of erythrocyte agglutination. However, the reaction is readily reversible. Treatment of the disease is variable. A case is presented to illustrate that minor oral surgical procedures are feasible, provided the proper precautions are taken.
C
old agglutinin disease is an autoimmune hemolytic anemia’ that has various causes. Two major types are recognized: transienP 3 or secondary4, 5 and chronic6 idiopathic of cold agglutinin disease syndrome.2 Chronic cold agglutinin disease is of unknown origin, with clinical manifestations of intravascular agglutination, acrocyanosis, hemolytic anemia,4 and paroxysmal hemoglobinuria on exposure to cold.’ The hemolytic anemia is usually mild, with intermittent severe crises exacerbated by exposure to cold temperatures.” s It presents as a lymphoproliferative disorder6 in the fourth to the eighth decade,” with a peak incidence at the age of 50 to 60 years.’ It may progress to classic lymphoma.’ Secondary cold agglutinin disease occurs because of an increase in cold agglutinin titers associated variously with atypical mycoplasmal pneumonia,3* 5 lymphoma, systemic lupus erythematosis, cirrhosis, colitis, pancreatitis, 4 infectious mononucleosis, mumps orchitis, and trypanos0miasis.j It is rarely associated with hemolysis.’ Cold agglutinins are circulating, completment-fixing IgM antibodies capable of agglutinating erythrocytes at temperatures below 37” C.*, 4, ’ As temperature decreases, cold agglutinin is bound to the erythrocyte surface by the Ii antigen and fixes complement.‘, ’ If sufficient complement is bound, intravascular hemolysis may occur,” ’ but usually only enough is bound to produce sequestration by the reticuloendothelial sys*Second-year Resident in Oral and Maxillofacial Surgery. **Professor and Chief of the Division of Oral and Maxillofacial Surgery. ***Third-year Resident in Oral and Maxillofacial Surgery.
0030.4220/79/070039+02$00.20/0
0
1979 The C. V. Mosby Co.
tern. The sensitized erythrocytes are bound to Kupffer’s cells in the liver sinusoids, where most are phagocytized; however, some are released back into circulation, where the cells survive normally.*~ ’ A rewarming to 37” C. results in an almost immediate total reversal by dissociation of the antigen-antibody complex.‘, 4 Treatment of cold agglutinin disease consists of treatment of any underlying disease,4 avoidance of cold42 ’ and maintenance of room temperature at 32 to 35” C. ,s transfusions,s and/or cytotoxic drugs.‘, ’ Steroids are of questionable value. Another recently proposed therapeutic tool is plasma exchange.’ CASE REPORT On June 18, 1978, a 59-year-old white man was referred to our office with the diagnosis of periodontal disease, cold agglutinin disease,and prolonged bleeding time. Clinical and radiographic examination revealed a well-developed, wellnourished white man with fourteen remaining teeth and advanced periodontal disease. The patient’s past medical history revealedthat since 1959 he had suffered acrocyanosis, paroxysmal hemoglobinuria, abdominal discomfort, and nauseaon exposure to temperatures below 6.5”F. When he donatedblood in 1974, a routine sample hemolysed on cooling. A complete history and evaluation of further testsled to the diagnosis of chronic cold agglutinin disease.From the time of his initial diagnosis until his referral to our office, the patient was placed on varying courses of chlorambucil, Cytoxan, vincristine, prednisone, and folic acid; he underwent regular plasmapheresiswith transfusions as indicated. In 1977the patient was discoveredto have a prolonged Ivy bleeding time, presumably causedby an IgM coating of the platelets interfering with surface aggregation. His current
39
40
Kerlry,
medications
consisted
vincristine caproic
(2 mg. acid
19.
tractions.
well
through
recovered
warmer, The
accomplished
acid
syrup in
and careful
without
without
for 2 days for
suture
REFERENCES I. Schubothe,
local
every
2.
anes3.
intravenous and 4.
the procedure bleeding
postoperatively
removal.
ex-
of warming
approximation
tolerated
(16 C.C. orally
I week
with consisted
postoperatively
day),
and amino-
full-mouth
administering
patient
every
4 hours).
underwent
precautions
He was maintained returned
orally
2 weeks).
every
to 32” C.,
a blood
aminocaproic
(5 mg.
and gingivoplasty
Special
of the gingiva. and
Oral Surg. July, 1979
every
the patient
preoperatively
hemolysis. patient
1978,
alveoloplasty,
suturing
acid
intravenously
in our office.
the room fluids
of folic
intravenously
(4 Cm.
On July thesia
Scholv, and Mulheritt
or
5.
on
4 hours).
The
which
was
6.
incident.
SUMMARY
Cold agglutinin disease is an autoimmune hemolytic anemia involving an antigen-antibody reaction with complement fixation upon exposure to decreased temperatures resulting in hemolysis. It may be idiopathic, or it may occur as a secondary disease entity. Treatment consists of avoidance of cold, administration of cytotoxins, treatment of underlying disease, transfusion, plasma exchange, and/or steroids. The case of a patient with long-standing chronic cold agglutinin disease who underwent a full-mouth extraction without complications has been presented.
7.
8.
9.
H.: Current Problems of Chronic Cold Hemagglutinin Disease, Ann. N. Y. Acad. Sci. 124: 484-490. 1965. Jaffe. C. J.. Atkinson, 1. P.. and Frank. M. M.: The Role of Complement in the Clearance of Cold Agglutinin-Sensitized Erythrocytes in Man, J. Clin. Invest. 58: 942-949, 1976. Jacobsen, L. B., and Longstreth. G. F.: Clinical and Immunologic Feature\ of Transient Cold Agglutinin Hemolytic Anemia, Am. J. Med. 54: 514.521, 1973. Felber, N.: Cold Agglutinin Disease. Postgad. Med. 60: 89-94, 1976. Harbor. M.: Cold Auto-agglutinin
