scan detection of bone marrow infarcts in sickle cell disorders
TRANSCRIPT
Bone marrow infarction is a common cornplication of sickle cell crisis, yet is seldomproved before autopsy. Bone marrow scanningnow provides an atraumatic method of earlierconfirmation. We have studied 29 patients with
sickle cell disorders using scans of ssmTc-sulfurcolloid to demonstrate the distribution of reticuloendothelial activity within the bone marrow.All patients with S-S pattern showed increasedmarrow activity with expansion to the longbones and skull. Patients with S-C and S-Thalhad less expansion of the marrow. Three groupsof patients were studied. Group 1 was scannedwhile asymptomatic and had no crises duringthis study. In 8 out of 17 patients in this group,regions of decreased marrow uptake were notedwhich were considered due to previous infarclion with subsequent fibrosis.
Group 2 was comprised of two patients whowere scanned while asymptomatic and then during crisis. These scans showed no change fromthe previous baseline studies. We interpretedthis to indicate that no infarcts had occurredduring crisis.
Group 3 patients were scanned first duringcrises and then at subsequent intervals. Six outof ten patients in this group had areas of decreased activity on bonç marrow scans corresponding to focal pain in the same area whichwere thought to suggest bone marrow infarction.Four of these patients repopulated their marrow in 3, 4, 6, and 12 months. One case is reported in detail. We conclude that the bonemarrow scan is useful for detecting the presence of bone marrow infarction and in follow
ing the course of healing and complications.
In 193 1 Brittingham (1 ) reported the first autopsyevidence of a complication in sickle cell diseasewhich we now know to be associated with bone
marrow infarction. Autopsy of a young black womanrevealed cerebral fat embolism but the source ofthe embolism was not elucidated. Since then similarreports have appeared in the literature (2—10)wherepatients with sickle cell disease died after a stormycourse and at autopsy extensive bone marrow infarctions were found. Radiocolloid scanning nowmakes possible an atraumatic demonstration of marrow reticuloendothelial activity. In this report, wepresent the results of marrow scanning in 29 pa.tients with sickle cell disease studied to evaluatebetter the phenomenon of bone marrow infarction.
METHOD
Following the intravenous injection of 15 mCi ofs9mTc_sulfur colloid (1 1 ) , simultaneous anterior andposterior views of the reticuloendothelial systemwere made by scanning the total body. Areas of special interest were subsequently rescanned for closerscrutiny.
PATIENTS
On the basis of clinical findings and biochemicalanalysis, each of 29 patients was diagnosed as havingsickle cell anemia (5-5) or sickle cell disorders (S-Cor S-Thal). All had had multiple crises in the past.There were three subgroups:
Group 1: Seventeen were studied during an asymptomatic period for a baseline scan and had no crisisduring the remainder of the study.
Group 2: Two were scanned while asymptomaticand then were rescanned after crisis.
Group 3: Ten patients were first scanned duringcrisis and lacked a baseline study. Patients in this
Received Feb. 8, 1974; revision accepted June 18, 1974.For reprints contact: A. Alavi, Dept. of Radiology, Hos
pital of the University of Pennsylvania, Philadelphia, Pa.19104.
* Present address: Dept. of Medicine, Bryn Mawr Hospital, Bryn Mawr, Pa.
t Presentaddress:OncologicHospital,Philadelphia,Pa.
Volume 15,Number 11 1003
SCAN DETECTION OF BONE MARROW INFARCTS
IN SICKLE CELL DISORDERS
Abass Alavi, James P. Bond,* David E. KuhI, and Richard H. Creecht
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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ALAVI, BOND, KUHL, AND CREECH
tomatic periods and later during crisis and showedno changein the pattern of reticuloendothelialuptake to suggest bone marrow infarction.
One of these patients showed focal areas of decreased uptake in his original study and stayed unchanged in the study performed during crisis. Weinterpreted this as fibrotic areas due to previousinfarctions.
Group 3: Of ten patients studied immediately aftercrisis,sixshowedevidenceofrecentinfarction.Thefocal regions suspicious of infarction in the scanwere tender on palpation and in two patients necroticmarrow was aspirated from the regions of decreaseduptake noted on the scans.
The six patients with evidence of bone marrowinfarct in Group 3 were scanned at various intervalslater. Four patients showed repopulation of the marrow, seen as near-normal uptake of ssmTc@sulfur colbid in the areas of defect on previous scans, at 3,4, 6, and 12 monthsafter first detectionof the infarct. In one patient bone biopsy of posterior iliaccrest confirmed repopulation seen on bone marrowscans. We did not attempt to aspirate marrow insome patients because of a difficult location of thelesion.
DISCUSSION
The scanning results in this study lend support tothe impression of previous investigators that bonemarrow infarction is common in sickle cell disorders (9) . More than half of this group of sicklecell patients had evidence of marrow infarction atsome time in their course. Some of these areas weresymptomatic and clearly related to a painful crisiswhereas others were clinically silent. Necrotic marrow was aspirated from these areas in two patients.
With extensive infarction the normal structure ofbone marrow is deranged and immature myeloidand erythroid cells may appear in the peripheralblood. The necrotic region may serve as a nidus forinfection. Massive infarction usually produces radiographic evidence of sclerosis and coarse trabecularchanges and the infarcted region may be the site ofa pathologic fracture (24) . The complications areillustrated in the following case.
RB, a 33-year-old black man known to have sicklecell anemia (Hgb-S 94.6% ) since age 19, wasadmitted complaining of severe pleuritic chest painand significant discomfort in his lower back, righthip, knees, and right jaw. On physical examination,he was in severe distress with a fever of 102°F to104°F. There was pressure tenderness over thesternum and over most of his pelvic bones. Laboratory data revealed mild leukocytosis with a normaldifferential and 8 % nucleated red blood cells. Because of a pulmonary infiltrate, he was treated with
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FIG. 1. (A)Bonemarrowscaninsicklecellanemiawithexpansion of marrow to skull and long bones, and symmetricuptake inlong bones. (B) Bone marrow scan in sickle-thalassemia: lessexpansion of marrow to long bones and moderate degree ofsplenomegaly. (C) Patient with sickle cell anemia studied duringasymptomatic period showed areas of decreased uptake in bothlower extremities indicating probably fibrosis after previous infarction (arrows).
subgroup were scanned a few days to 2 weeks afterthe onset of crisis and those with suspected evidenceof infarctionwere followedby subsequentscansatintervals.
RESULTS
In normal adults bone marrow is located mainlyin the axial bones (spine, pelvis, ribs, and scapulas)and the proximal portion of both femora and humeri(12—16). Reticuloendothelial activity as imaged inthe bone with 1'1'@'Tc-sulfur colloid corresponds generally to erythroblastic activity (17—21).
In patients with sickle cell disorders we saw expansion of the marrow to the long bones and theskull (Fig. 1A) . This redistribution is nonspecificand can be seen in any chronic hemolytic state(22,23) since it is related to bone marrow stimulation compensating for peripheral destruction of red
bloodcells.The expansionishomogeneousandsymmetric.
In S-C or S-ThaI patients, the activity in the longbones was less than that seen in patients with homozygous sickle cell anemia.
Group I : Of 17 patients studied during an asymptomatic period, 8 showed focal areas of decreasedmarrow uptake which probably represents fibrosis
due to previous infarction (Fig. lC) . All of these17 patients had multiple crises in the past with sig
nificant bone and joint pain.Group 2: Two patients were studied during asymp
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BONE MARROW INFARCTS IN SICKLE CELL DISORDERS
obtained 6 and 7 days after the onset of crisis fromthe sternum, right iliac crest, and posterior iliac spine.All specimens had a peculiar putrid odor whenaspirated and were interpreted as necrotic marrow(Fig. 2). A bone marrow scan was performed onthe thirteenth day (Fig. 3A) . There was increaseduptake interpreted as marrow expansion in thegreater trochanters, right distal femur, and proximaltibia and fibulas. There were local defects of uptakeinterpreted as marrow infarcts in the skull, vertebralcolumn, pelvis, and distal femora.
Fourteen days after the onset of crisis, bone marrow aspirated from right proximal tibia showederythroid hyperplasia, left shift in myeloid series,and adequate megakaryocytes. The result of testswhich proved the viability of the cells in the tibiaand death of the cells in the sternum are given inTable 1.
At 1 month the patient developed osteomyelitis
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FIG.3. (A)Scansdone13daysafteradmission of Patient RB revealed lack ofuptake in skull (top), patchy uptake inpelvis and spine, (middle), and lowerfemora (lower). We had no explanationfor uptake of @mTc-sulfurcolloid in lungs.[cf. with Fig 1(A) to appreciate betterdefects in bone marrow distribution]. (B)Scans repeated after 3'h monthsrevealedstill patchy uptake but somewhat improved in above.describedareas. (C) Scansdone 3 years later showed almost complete repopulation of pelvis bone marrowwith some improvement in other areas.
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POSTBVolume 15, Number 11 1005
F1G.2. Necroticbonemarrowaspiratedfromsternumat 6days. Most cells are unidentifiable with indistinct cell borders andpyknoticnuclei.
2 million units of penicillin per day for the first 2weeks of hospitalization. By the sixth day of hospitalization his peripheral blood examination revealed1—2myeloblasts, 2—5myelocytes, 1—6metamyelocytes as well as 44—53% nucleated red blood cells/100 white blood cells. Bone marrow aspirates were
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ALAVI, BOND, KUHL, AND CREECH
Rtproximal tibia Sternum
Necrotic, with pyknotic nuclei surroundedby purple cytoplasmic globules. Onlyviable cells were polys, lymphs, andmacrophages with abundant cytoplasmicinclusion
Marrow morphology Megaloblastic erythroid hyperplasia,left shift in WBC, adequate mega.karyocytes
Nucleated cell count 32.4 X i0@ cells/mm'
24/300 cells were positive
14.1 X 1O@cells/mm'
107/300 cells were positive, most of thenonstained cells were polys and macrophages.
Trypan blue; (viable cells exclude this dye)
Residual counts from ‘°mTcin 2 cc of 53,614 cpmaspirated marrow, 19 hr after mmTcgiven to patient (background 3—5cpm).
2,500 cpm
phate) on the same patient showed increased uptakein the same region confirming the suspected asepticnecrosis of the left hip. We interpreted this to mdicate reactive bone formation around the necroticarea demonstrated by Cameron utilizing 85Sr bonescintimetry (26).
We conclude that the bone marrow scan is usefulfor detecting the presence of bone marrow infarctionin sickle cell crisis and in following the course ofhealing and complications.
ACKNOWLEDGMENTS
The authors thank the nuclear medicine technologist stafffor their technical assistance and Carol Wicker and JaneTurnier for their secretarial help. This project was supported by USPHS Training Grant 2T01 GM-01762-06.
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BONE MARROW INFARCTS IN SICKLE CELL DISORDERS
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Volume 15, Number 11 1007
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1974;15:1003-1007.J Nucl Med. Abass Alavi, James P. Bond, David E. Kuhl and Richard H. Creech Scan Detection of Bone Marrow Infarcts in Sickle Cell Disorders
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