Pancytopenia in
a
Patient With
Sickle Cell Anemia Kir Y. Kim, MD; Gungor Karayalcin, MD; Fred Rosner, MD; Arturo Aballi, MD
\s=b\ An 11-year-old black boy with sickle cell anemia developed profound pancytopenia during the course of his disease, but fully recovered therefrom. The patient was receiving anticonvulsant drugs for a seizure disorder secondary to a
"stroke," and, therefore, a drug-related aplasia cannot be ruled out. (Am J Dis Child 129:1195-1196, 1975)
marrow
The
crisis
aplastic
cell anemia18
in
sickle
usually represents
temporary failure of erythrocyte production. Aplastic crisis is a mis¬ nomer, since there is only an acute erythroblastopenia2 and reticulocytopenia.7 Leukopenia is quite uncom¬ mon, and thrombocytopenia is ex¬ tremely rare. The present report concerns a patient with homozygous sickle cell anemia who had profound pancytopenia during the course of his disease, but fully recovered there¬ from. The patient was receiving anti¬ convulsant drugs, and, therefore, a drug-related marrow aplasia cannot a
3
be ruled out.
Received for publication Aug 2,1974; accepted Dec 16. From the Department of Pediatrics (Drs Kim, Karayalcin, and Aballi) and Division of Hematology (Dr Rosner), Queens Hospital Center, Affiliation of the Long Island Jewish-Hillside Medical Center, Jamaica, NY; and the Health Sciences Center, State University of New York at Stony Brook (Drs Karayalcin, Rosner, and
Aballi). Reprint requests to Hematology Division, Queens Hospital Center, 82-68 164th St, Jamaica, NY 11432 (Dr Rosner).
REPORT OF A CASE An 11-year-old black boy, known to have sickle cell anemia since the age of 8 months, was hospitalized with high fever, generalized malaise, and lethargy. At 2V4 years of age, the patient suffered a cerebral thrombosis that resulted in partial aphasia, right hemiparesis, and a seizure disorder for which he was treated with anticonvulsants, most recently primidone (Mysoline) (250 mg daily), mephenytoin (Mesantoin) (200 mg daily), and
phénobarbital (128 mg daily). The patient was acutely ill, febrile, and tachypneic. Mucous membranes were pale and sclerae were slightly jaundiced. Gingivae were severely hypertrophie. There was generalized lymphadenopathy. The heart was enlarged and a loud systolic ejection murmur was heard all over the precordium. The lungs were clear to per¬ cussion and auscultation. The liver was palpable 12 cm below the right costal mar¬ gin. The spleen was not felt. There was also hemiparesis and contracture de¬ formity of the right upper and lower ex¬ tremities, with increased deep tendon reflexes. The hemoglobin level was 5.5 gm/100 ml; hematocrit value, 16%; red blood cell count, 1.6 million/cu mm; and white blood cell count, 5,600/cu mm with 53% neutrophils, 43% lymphocytes (of which half were atyp¬ ical), 2% eosinophils, and 2% plasmacytes. The reticulocyte count was 1.5%, and plate¬ let count was 208,000/cu mm. Target cells, sickle cells, and a few burr cells were seen on the peripheral blood smear. Serial blood counts are shown in the Figure. Bone marrow aspirate was extremely hypoplastic. Cultures from blood, naso-
pharynx, urine,
and stool were sterile. Results of CSF examination were within normal limits, and culture was sterile. An¬ ticonvulsant therapy was discontinued and ampicillin sodium, 1 gm daily, and folie acid, 5 mg daily, were administered. On the third day of hospitalization, the leuko¬ cyte count was 3,700/cu mm and the plate¬ let count was 137,000/cu mm. On the 18th day, the platelet nadir of 20,000/cu mm and leukocyte nadir of 1,800/cu mm were reached. Viral, fungal, and protozoal studies in blood, urine, and stool were also negative. The pancytopenia slowly reversed, so that on the 32nd hospi¬ tal day, the entire blood count was normal, except for nine nucleated erythrocytes per 100 leukocytes in the peripheral blood smear. Bone marrow aspirate now showed substantial myeloid and erythroid hyper¬
plasia.
COMMENT The most
common
symptoms of the
aplastic crisis in sickle cell anemia are fever, pain, lethargy, anorexia, weak¬ ness, nausea and vomiting, and head¬ ache. The most prominent physical findings include pallor, hepatomegaly, splenomegaly, lymphadenopathy, and signs of upper-respiratory-tract in¬ fections. The Hb level is usually less than 6 gm/100 ml and platelet and leukocyte counts are nearly always normal. Complete recovery is the rule. The reticulocyte response and usually a normoblastemia occur during the first few days after the aplastic crisis. Viral most
or
bacterial infections are the precipitating factors of
common
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sumed viral infection for which the patient was hospitalized may have been the precipitating factor for the development of pancytopenia. In hereditary spherocytosis, pan¬ cytopenia as part of an aplastic crisis is quite common. The postulated rea¬ son is that the enlarged spleen in spherocytosis sequesters not only the spherically shaped erythrocytes, but also leukocytes and thrombocytes as well. This mechanism cannot be in¬ voked in sickle cell anemia where the spleen is usually infarcted, atrophie, and nonfunctional. Whereas the aplastic crisis in sickle cell anemia is nearly always quickly (7 to 14 days) and completely rever¬ sible, pancytopenia and marrow apla¬ sia due to toxins, bacteria, viruses, allergies, or other causes are incom¬ pletely or not at all reversible, and are associated with a very high mor¬ tality (up to 85%).
Nonproprietary
Name and Trademarks of Drug
Ampicillin sodium—A lpen-N, Amcill-S, Omnipen-N. References
Day Of Hospitalization Bone Marrow
Aspiration rrrow Bone Marrow Cellulariity
1
2
3
4
5
6
tît {¡¡ !
7
8
3
16 ...22 25 30 32
10 15
t t
t t
'' •"'.''''"""'"''"i'l'ili'i'ill'I'W'IWi'i'i'W'i'i'i'iii'l'l ~M.~..JiS! J
Tx
=
I Unit Packed
Norma'
36 45 50 60
70 80
t t t t t
flWffi
'.'.'.Vl'l'l'l'l'l'l'lll'l'l'l
Hyperplasia
473, 1957.
Erythrocytes
Clinical values in patient with sickle cell anemia who
developed pancytopenia.
aplastic crisis in sickle cell disease. The term "aplastic crisis" is a mis¬ nomer, since only erythrocyte produc¬ tion temporarily ceases. In a few re¬ ported cases, mild leukopenia has also occurred. No patient with throm¬ bocytopenia has been reported. Thus, our patient is unique in that
profound pancytopenia.
an
90
he had
1. Singer A, Motulsky AG, Wile SA: Aplastic crisis in sickle cell anemia: A study of its mechanism and its relationship to other types of hemolytic crises. J Lab Clin Med 35:721-735, 1950. 2. Chernoff AI, Josephson AM: Acute erythroblastopenia in sickle-cell anemia and infectious mononucleosis. Am J Dis Child 82:310-322, 1951. 3. Miesch DC, Baxter MR, Levin WC: Acute erythroblastopenia: Pathogenesis, manifestations and management. Arch Intern Med 99:461\x=req-\
In ad¬ the of his duration dition, aplasia (three weeks) is longer than that usu¬ ally seen in the aplastic crisis of sickle cell disease. We, therefore, postulate that the anticonvulsant therapy may have played a role in the causation of the aplasia. Alternatively, the pre-
4. Megas H, Papadaki E, Constantidives B: Salmonella septicemia and aplastic crisis in a patient with sickle cell anemia. Acta Pediatr 50:517-521, 1961. JE,Parker-Williams EJ: The aplas5. MacIver tic crisis in sickle cell anemia. Lancet 1:1086\x=req-\ 1089, 1961. 6. Pierce LE, Rath CE: Evidence for folic acid deficiency in the genesis of anemia sickle cell crisis. Blood 20:19-32, 1962. 7. Charney E, Miller G: Reticulocytopenia in sickle cell disease: Aplastic episodes in the course of sickle cell disease in children. Am J Dis Child 107:450-455, 1964. 8. Diggs LW: Sickle cell crises. Am J Clin Pathol 44:1-19, 1965.
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/05/2015
a
Patient With
Sickle Cell Anemia Kir Y. Kim, MD; Gungor Karayalcin, MD; Fred Rosner, MD; Arturo Aballi, MD
\s=b\ An 11-year-old black boy with sickle cell anemia developed profound pancytopenia during the course of his disease, but fully recovered therefrom. The patient was receiving anticonvulsant drugs for a seizure disorder secondary to a
"stroke," and, therefore, a drug-related aplasia cannot be ruled out. (Am J Dis Child 129:1195-1196, 1975)
marrow
The
crisis
aplastic
cell anemia18
in
sickle
usually represents
temporary failure of erythrocyte production. Aplastic crisis is a mis¬ nomer, since there is only an acute erythroblastopenia2 and reticulocytopenia.7 Leukopenia is quite uncom¬ mon, and thrombocytopenia is ex¬ tremely rare. The present report concerns a patient with homozygous sickle cell anemia who had profound pancytopenia during the course of his disease, but fully recovered there¬ from. The patient was receiving anti¬ convulsant drugs, and, therefore, a drug-related marrow aplasia cannot a
3
be ruled out.
Received for publication Aug 2,1974; accepted Dec 16. From the Department of Pediatrics (Drs Kim, Karayalcin, and Aballi) and Division of Hematology (Dr Rosner), Queens Hospital Center, Affiliation of the Long Island Jewish-Hillside Medical Center, Jamaica, NY; and the Health Sciences Center, State University of New York at Stony Brook (Drs Karayalcin, Rosner, and
Aballi). Reprint requests to Hematology Division, Queens Hospital Center, 82-68 164th St, Jamaica, NY 11432 (Dr Rosner).
REPORT OF A CASE An 11-year-old black boy, known to have sickle cell anemia since the age of 8 months, was hospitalized with high fever, generalized malaise, and lethargy. At 2V4 years of age, the patient suffered a cerebral thrombosis that resulted in partial aphasia, right hemiparesis, and a seizure disorder for which he was treated with anticonvulsants, most recently primidone (Mysoline) (250 mg daily), mephenytoin (Mesantoin) (200 mg daily), and
phénobarbital (128 mg daily). The patient was acutely ill, febrile, and tachypneic. Mucous membranes were pale and sclerae were slightly jaundiced. Gingivae were severely hypertrophie. There was generalized lymphadenopathy. The heart was enlarged and a loud systolic ejection murmur was heard all over the precordium. The lungs were clear to per¬ cussion and auscultation. The liver was palpable 12 cm below the right costal mar¬ gin. The spleen was not felt. There was also hemiparesis and contracture de¬ formity of the right upper and lower ex¬ tremities, with increased deep tendon reflexes. The hemoglobin level was 5.5 gm/100 ml; hematocrit value, 16%; red blood cell count, 1.6 million/cu mm; and white blood cell count, 5,600/cu mm with 53% neutrophils, 43% lymphocytes (of which half were atyp¬ ical), 2% eosinophils, and 2% plasmacytes. The reticulocyte count was 1.5%, and plate¬ let count was 208,000/cu mm. Target cells, sickle cells, and a few burr cells were seen on the peripheral blood smear. Serial blood counts are shown in the Figure. Bone marrow aspirate was extremely hypoplastic. Cultures from blood, naso-
pharynx, urine,
and stool were sterile. Results of CSF examination were within normal limits, and culture was sterile. An¬ ticonvulsant therapy was discontinued and ampicillin sodium, 1 gm daily, and folie acid, 5 mg daily, were administered. On the third day of hospitalization, the leuko¬ cyte count was 3,700/cu mm and the plate¬ let count was 137,000/cu mm. On the 18th day, the platelet nadir of 20,000/cu mm and leukocyte nadir of 1,800/cu mm were reached. Viral, fungal, and protozoal studies in blood, urine, and stool were also negative. The pancytopenia slowly reversed, so that on the 32nd hospi¬ tal day, the entire blood count was normal, except for nine nucleated erythrocytes per 100 leukocytes in the peripheral blood smear. Bone marrow aspirate now showed substantial myeloid and erythroid hyper¬
plasia.
COMMENT The most
common
symptoms of the
aplastic crisis in sickle cell anemia are fever, pain, lethargy, anorexia, weak¬ ness, nausea and vomiting, and head¬ ache. The most prominent physical findings include pallor, hepatomegaly, splenomegaly, lymphadenopathy, and signs of upper-respiratory-tract in¬ fections. The Hb level is usually less than 6 gm/100 ml and platelet and leukocyte counts are nearly always normal. Complete recovery is the rule. The reticulocyte response and usually a normoblastemia occur during the first few days after the aplastic crisis. Viral most
or
bacterial infections are the precipitating factors of
common
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/05/2015
sumed viral infection for which the patient was hospitalized may have been the precipitating factor for the development of pancytopenia. In hereditary spherocytosis, pan¬ cytopenia as part of an aplastic crisis is quite common. The postulated rea¬ son is that the enlarged spleen in spherocytosis sequesters not only the spherically shaped erythrocytes, but also leukocytes and thrombocytes as well. This mechanism cannot be in¬ voked in sickle cell anemia where the spleen is usually infarcted, atrophie, and nonfunctional. Whereas the aplastic crisis in sickle cell anemia is nearly always quickly (7 to 14 days) and completely rever¬ sible, pancytopenia and marrow apla¬ sia due to toxins, bacteria, viruses, allergies, or other causes are incom¬ pletely or not at all reversible, and are associated with a very high mor¬ tality (up to 85%).
Nonproprietary
Name and Trademarks of Drug
Ampicillin sodium—A lpen-N, Amcill-S, Omnipen-N. References
Day Of Hospitalization Bone Marrow
Aspiration rrrow Bone Marrow Cellulariity
1
2
3
4
5
6
tît {¡¡ !
7
8
3
16 ...22 25 30 32
10 15
t t
t t
'' •"'.''''"""'"''"i'l'ili'i'ill'I'W'IWi'i'i'W'i'i'i'iii'l'l ~M.~..JiS! J
Tx
=
I Unit Packed
Norma'
36 45 50 60
70 80
t t t t t
flWffi
'.'.'.Vl'l'l'l'l'l'l'lll'l'l'l
Hyperplasia
473, 1957.
Erythrocytes
Clinical values in patient with sickle cell anemia who
developed pancytopenia.
aplastic crisis in sickle cell disease. The term "aplastic crisis" is a mis¬ nomer, since only erythrocyte produc¬ tion temporarily ceases. In a few re¬ ported cases, mild leukopenia has also occurred. No patient with throm¬ bocytopenia has been reported. Thus, our patient is unique in that
profound pancytopenia.
an
90
he had
1. Singer A, Motulsky AG, Wile SA: Aplastic crisis in sickle cell anemia: A study of its mechanism and its relationship to other types of hemolytic crises. J Lab Clin Med 35:721-735, 1950. 2. Chernoff AI, Josephson AM: Acute erythroblastopenia in sickle-cell anemia and infectious mononucleosis. Am J Dis Child 82:310-322, 1951. 3. Miesch DC, Baxter MR, Levin WC: Acute erythroblastopenia: Pathogenesis, manifestations and management. Arch Intern Med 99:461\x=req-\
In ad¬ the of his duration dition, aplasia (three weeks) is longer than that usu¬ ally seen in the aplastic crisis of sickle cell disease. We, therefore, postulate that the anticonvulsant therapy may have played a role in the causation of the aplasia. Alternatively, the pre-
4. Megas H, Papadaki E, Constantidives B: Salmonella septicemia and aplastic crisis in a patient with sickle cell anemia. Acta Pediatr 50:517-521, 1961. JE,Parker-Williams EJ: The aplas5. MacIver tic crisis in sickle cell anemia. Lancet 1:1086\x=req-\ 1089, 1961. 6. Pierce LE, Rath CE: Evidence for folic acid deficiency in the genesis of anemia sickle cell crisis. Blood 20:19-32, 1962. 7. Charney E, Miller G: Reticulocytopenia in sickle cell disease: Aplastic episodes in the course of sickle cell disease in children. Am J Dis Child 107:450-455, 1964. 8. Diggs LW: Sickle cell crises. Am J Clin Pathol 44:1-19, 1965.
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/05/2015
