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Normoblastemia after thermal injury
Normoblastemia
after Thermal Injury
W. Abe Andes, MD, Fort Sam Houston, Texas
Nucleated red blood cells (NRBC) are unknown in the circulating blood of normal persons except in utero and shortly after birth [I]. Previous studies have noted the presence of NRBC in the circulating blood in a variety of conditions. Some studies have related them to hypoxia [2,3] or electrical injury [4]. Their occurrence after burn injury has attracted little attention [5]. The present study concerns the occurrence of NRBC in a number of burned patients receiving a wide variety of treatments during a two and a half year period. Material and Methods The individuals studied consisted of 214 of the 655 patients admitted to this Institute during a thirty month period (I972 to 1975). They ranged in age from six weeks to eighty-five years, and eleven patients with NRBC were children. Patients who manifested NRBC suffered burns ranging from 5 to 98 per cent (mean, 57 per cent) of the total body surface. These burns were not different in size from those in patients without NRBC (mean, 51 per cent). Patients were initially studied because of complications, bleeding, anemia, or the possibility of preburn hematologic disease. Smears made from fresh blood were stained with Wright’s stain. Samples were taken as early as 2 hours and as late as seventy-five days post burn. Most specimens were collected during the first month after injury. Laboratory tests included nucleated cell counts and determination of hemoglobin and hematocrit using a Coulter Counter, Model S. The number of normoblasts per 100 leukocytes (Figure 1) was determined during count of 200 consecutive leukocytes with oil immersion microscopy. In some cases, normoblasts seen during low power scanning, but not during the counting procedure, were noted as <0.5 normoblasts/lOO leukocytes. (Figure 1.) Absolute numbers of NRBC were determined by using corrected leukocyte counts. Bone marrow aspirations were examined one or more times in twenty-six patients.
From the United States Army Institute of Surgical Research, Brooke Army Medical Center, Fort Sam Houston, Texas. The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. Reprint requests shoufdbe addressed to the Instituteof Surgical Research, Brooke Army Medical Center, Fort Sam Houston, Texas. Resent address: Depamnent of Medicine, Section of Hematology, Tulane University School of Medicine, 1430 Tulane Avenue. New Orleans, Louisiana 70112.
Volume 131, June 1976
Results Fifty-one of the 214 patients had peripheral NRBC at some time during hospitalization. Six of the fifty-one patients with NRBC and forty-one of the 163 patients without NRBC survived. NRBC were found from 2 hours to sixty days post injury and, surprisingly, in eleven patients on the day of injury. (Figure 1.) The presence of sepsis was not related to the occurrence of NRBC, although the most common cause of death was infection. Patients with the largest burns had NRBC most frequently. (Table I.) Absolute NRBC numbers ranged from 86 to 1,710/mm3 and up to 35 NRBC/lOO leukocytes. Patients rarely manifested leukopenia, but thrombocytopenia was occasionally present, especially during septic complications. No relation between leukocyte or platelet counts and numbers of NRBC was found. There was a general tendency for NRBC to be present for several days at a time in individual patients. Circulating normoblasts were usually orthochromatic but occasionally basophilic or polychromatophilic and Howell-Jolly bodies were absent. The degree of basophilic stippling was most often slight or absent in the 104 slides with NRBC. Reticulocytes rarely constituted more than 3 per cent of the total circulating erythrocytes [6]. Hence, little suggestion of accelerated erythropoiesis was noted. No relationship (r = 0.02) between hematocrits ranging from 10 to 56
Figure 1. The occurrence of normoblasts in the circulating blood of the seriously burned patient.
725
Andes
TABLE
I Size of Burn in Patients with Normoblastemia
Size of Burn* 0 25 50 75
to to to to
24 49 74 100
Number of Patients
Number with Normoblasts
incidence
15 90 79 30
1 21 17 12
7 23 22 40
(%I
*Per cent of total body surface area.
per cent and numbers of NRBC occurred. Evidence of hemolysis with microspherocytes but without other evidence of a microangiopathic process was noted during the first few days post burn in many patients, most commonly in those with larger burns. Bone marrow specimens were cellular to hypercellular with myeloid hyperplasia and normal to slightly decreased numbers of erythroid precursors. No evidence of infiltrative processes or dyserythropoiesis was noted. Comments NRBC in the circulating blood have been thought to be due to tissue hypoxia, a disordered marrow microenvironment due to malignant infiltration or other damage, dyserythropoiesis, or other causes. Impaired oxygenation was probably not a factor in our patients inasmuch as NRBC were present with normal or elevated hematocrit values (on admission) and normal blood gas values. Although most patients became anemic, there was no relation between hematocrit and numbers of NRBC. The appearance of the bone marrow did not suggest primary medullary disease. NRBC were not part of an accelerated erythropoietic response to the patient’s anemia in view of erythrocyte morphology, low reticulocyte counts, and bone marrow findings in spite of increased erythropoietin levels [6].
726
Thus, burn injury frequently induces a “breakdown” in the marrow-peripheral blood “barrier,” resulting in the release of NRBC into the peripheral blood. The cause of this “breakdown” is unknown, but appears different from that in patients previously noted to manifest circulating NRBC. The presence of NRBC should not imply accelerated erythropoiesis since, in fact, the reverse appears true. Investigations of other possible causes of circulating NRBC in the seriously burned patient should be conservative because of the frequency of their occurrence in these patients.
Summary The peripheral blood smears of 214 thermally injured patients studied during a thirty month period revealed a 20 per cent incidence of normoblastemia (51 patients). Nucleated red blood cells were most common in patients with the largest burns. The absolute number of normoblasts was not related to the hematocrit and was not correlated with other determinants of erythropoietic function.
References 1. B&ton CJC: Disorders of the Blood. New York, Grune & Stratton, 1969. 2. Schwartz SO, Stansbury F: Significance of nucleated red blood cells in peripheral blbod. J-Am Med Assoc 154: 1339, 1954. 3. Frumin AM, Mendell TH, Mintz SS, Novack P, Faulk AT: Nucleated red blood cells in congestive heart failure. Circulation 20: 367, 1959. 4. Rey JJ. Wolf PL: Extreme leukocytosis in accidental electric shock. Lancer 1: 16, 1968. 5. Sevitt S. Jackson D, Stone P, Baar S, Pollock A: Acute Heinzbody anemia in burned patients. Lancet 2: 471, 1973. 6. Andes- WA, Rogers PW: Inappropriate erythropoietin elevation and hyperreninemia in the thermally injured patient, p 48. Presentation and Abstract from the 17th Meeting, American Society of Hematology, Atlanta, 1974.
The American Journal of Surgery
after Thermal Injury
W. Abe Andes, MD, Fort Sam Houston, Texas
Nucleated red blood cells (NRBC) are unknown in the circulating blood of normal persons except in utero and shortly after birth [I]. Previous studies have noted the presence of NRBC in the circulating blood in a variety of conditions. Some studies have related them to hypoxia [2,3] or electrical injury [4]. Their occurrence after burn injury has attracted little attention [5]. The present study concerns the occurrence of NRBC in a number of burned patients receiving a wide variety of treatments during a two and a half year period. Material and Methods The individuals studied consisted of 214 of the 655 patients admitted to this Institute during a thirty month period (I972 to 1975). They ranged in age from six weeks to eighty-five years, and eleven patients with NRBC were children. Patients who manifested NRBC suffered burns ranging from 5 to 98 per cent (mean, 57 per cent) of the total body surface. These burns were not different in size from those in patients without NRBC (mean, 51 per cent). Patients were initially studied because of complications, bleeding, anemia, or the possibility of preburn hematologic disease. Smears made from fresh blood were stained with Wright’s stain. Samples were taken as early as 2 hours and as late as seventy-five days post burn. Most specimens were collected during the first month after injury. Laboratory tests included nucleated cell counts and determination of hemoglobin and hematocrit using a Coulter Counter, Model S. The number of normoblasts per 100 leukocytes (Figure 1) was determined during count of 200 consecutive leukocytes with oil immersion microscopy. In some cases, normoblasts seen during low power scanning, but not during the counting procedure, were noted as <0.5 normoblasts/lOO leukocytes. (Figure 1.) Absolute numbers of NRBC were determined by using corrected leukocyte counts. Bone marrow aspirations were examined one or more times in twenty-six patients.
From the United States Army Institute of Surgical Research, Brooke Army Medical Center, Fort Sam Houston, Texas. The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. Reprint requests shoufdbe addressed to the Instituteof Surgical Research, Brooke Army Medical Center, Fort Sam Houston, Texas. Resent address: Depamnent of Medicine, Section of Hematology, Tulane University School of Medicine, 1430 Tulane Avenue. New Orleans, Louisiana 70112.
Volume 131, June 1976
Results Fifty-one of the 214 patients had peripheral NRBC at some time during hospitalization. Six of the fifty-one patients with NRBC and forty-one of the 163 patients without NRBC survived. NRBC were found from 2 hours to sixty days post injury and, surprisingly, in eleven patients on the day of injury. (Figure 1.) The presence of sepsis was not related to the occurrence of NRBC, although the most common cause of death was infection. Patients with the largest burns had NRBC most frequently. (Table I.) Absolute NRBC numbers ranged from 86 to 1,710/mm3 and up to 35 NRBC/lOO leukocytes. Patients rarely manifested leukopenia, but thrombocytopenia was occasionally present, especially during septic complications. No relation between leukocyte or platelet counts and numbers of NRBC was found. There was a general tendency for NRBC to be present for several days at a time in individual patients. Circulating normoblasts were usually orthochromatic but occasionally basophilic or polychromatophilic and Howell-Jolly bodies were absent. The degree of basophilic stippling was most often slight or absent in the 104 slides with NRBC. Reticulocytes rarely constituted more than 3 per cent of the total circulating erythrocytes [6]. Hence, little suggestion of accelerated erythropoiesis was noted. No relationship (r = 0.02) between hematocrits ranging from 10 to 56
Figure 1. The occurrence of normoblasts in the circulating blood of the seriously burned patient.
725
Andes
TABLE
I Size of Burn in Patients with Normoblastemia
Size of Burn* 0 25 50 75
to to to to
24 49 74 100
Number of Patients
Number with Normoblasts
incidence
15 90 79 30
1 21 17 12
7 23 22 40
(%I
*Per cent of total body surface area.
per cent and numbers of NRBC occurred. Evidence of hemolysis with microspherocytes but without other evidence of a microangiopathic process was noted during the first few days post burn in many patients, most commonly in those with larger burns. Bone marrow specimens were cellular to hypercellular with myeloid hyperplasia and normal to slightly decreased numbers of erythroid precursors. No evidence of infiltrative processes or dyserythropoiesis was noted. Comments NRBC in the circulating blood have been thought to be due to tissue hypoxia, a disordered marrow microenvironment due to malignant infiltration or other damage, dyserythropoiesis, or other causes. Impaired oxygenation was probably not a factor in our patients inasmuch as NRBC were present with normal or elevated hematocrit values (on admission) and normal blood gas values. Although most patients became anemic, there was no relation between hematocrit and numbers of NRBC. The appearance of the bone marrow did not suggest primary medullary disease. NRBC were not part of an accelerated erythropoietic response to the patient’s anemia in view of erythrocyte morphology, low reticulocyte counts, and bone marrow findings in spite of increased erythropoietin levels [6].
726
Thus, burn injury frequently induces a “breakdown” in the marrow-peripheral blood “barrier,” resulting in the release of NRBC into the peripheral blood. The cause of this “breakdown” is unknown, but appears different from that in patients previously noted to manifest circulating NRBC. The presence of NRBC should not imply accelerated erythropoiesis since, in fact, the reverse appears true. Investigations of other possible causes of circulating NRBC in the seriously burned patient should be conservative because of the frequency of their occurrence in these patients.
Summary The peripheral blood smears of 214 thermally injured patients studied during a thirty month period revealed a 20 per cent incidence of normoblastemia (51 patients). Nucleated red blood cells were most common in patients with the largest burns. The absolute number of normoblasts was not related to the hematocrit and was not correlated with other determinants of erythropoietic function.
References 1. B&ton CJC: Disorders of the Blood. New York, Grune & Stratton, 1969. 2. Schwartz SO, Stansbury F: Significance of nucleated red blood cells in peripheral blbod. J-Am Med Assoc 154: 1339, 1954. 3. Frumin AM, Mendell TH, Mintz SS, Novack P, Faulk AT: Nucleated red blood cells in congestive heart failure. Circulation 20: 367, 1959. 4. Rey JJ. Wolf PL: Extreme leukocytosis in accidental electric shock. Lancer 1: 16, 1968. 5. Sevitt S. Jackson D, Stone P, Baar S, Pollock A: Acute Heinzbody anemia in burned patients. Lancet 2: 471, 1973. 6. Andes- WA, Rogers PW: Inappropriate erythropoietin elevation and hyperreninemia in the thermally injured patient, p 48. Presentation and Abstract from the 17th Meeting, American Society of Hematology, Atlanta, 1974.
The American Journal of Surgery