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 Table of Contents  
CASE REPORT
Year : 2013  |  Volume : 4  |  Issue : 3  |  Page : 114-117

Bone marrow necrosis in sickle cell disease: A case report and review of the literature


1 Department of Hematology and Blood Bank, Theodor Bilharz Research Institute, Giza, Egypt; Prince Sultan Military Medical City, Central Military Laboratory and Blood Bank, Riyadh, Kingdom of Saudi Arabia
2 Prince Sultan Military Medical City, Central Military Laboratory and Blood Bank, Riyadh, Kingdom of Saudi Arabia
3 Department of Adult Clinical Hematology and Stem Cell Therapy, Riyadh, Kingdom of Saudi Arabia

Date of Web Publication19-Dec-2013

Correspondence Address:
Ghaleb Elyamany
Theodor Bilharz Research Institute, Egypt, Consultant Hematopathology, PO Box 7897, Riyadh 11159, Kingdom of Saudi Arabia

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1658-5127.123313

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  Abstract 

The clinicopathologic entity of bone marrow necrosis (BMN) was first reported by Wade and Stevenson in 1941. BMN is defined as necrosis of the myeloid tissues and stroma without cortical bone involvement. The pathophysiology of BMN remains unclear; however, the occlusion of microcirculation, accompanied by hypoxemia, causes damage to the cells and plays an important role. Severe BMN is rarely diagnosed in living patients. Herein, we report a rare case of severe BMN in a patient with sickle cell disease (SCD) who presented with an unusually severe vaso-occlusive crisis complicated by acute chest syndrome (ACS), pancytopenia, and disseminated intravascular coagulation. Although the clinical features are highly suggestive of BMN, the diagnosis still required a bone marrow (BM) examination because early transfusion therapy can be lifesaving. The prognosis of severe BMN seems to reflect the poor outcomes of such underlying conditions; however, the prognosis of generalized BMN is not so poor when associated with SCD.

Keywords: Bone marrow necrosis, sickle cell disease, pancytopenia


How to cite this article:
Elyamany G, Alsuhaibani O, Shaker A, Fadalla KE, Albalawi M, Al Abdulaaly A. Bone marrow necrosis in sickle cell disease: A case report and review of the literature. J Appl Hematol 2013;4:114-7

How to cite this URL:
Elyamany G, Alsuhaibani O, Shaker A, Fadalla KE, Albalawi M, Al Abdulaaly A. Bone marrow necrosis in sickle cell disease: A case report and review of the literature. J Appl Hematol [serial online] 2013 [cited 2021 Sep 25];4:114-7. Available from: https://www.jahjournal.org/text.asp?2013/4/3/114/123313


  Background Top


Bone marrow necrosis (BMN) is a relatively uncommon clinicopathologic entity. [1] It was first reported by Wade and Stevenson in 1941 in a patient with sickle cell disease (SCD). [2] BMN is defined as myeloid tissue and medullary stroma necrosis that results in an amorphous eosinophilic background, ill-defined necrotic cells, and preserved cortical bone. [3] The incidence of BMN is low. [1],[4],[5] The relative frequency varies among different reports, ranging from 0.37 to 6.5%. [6],[7]

The underlying causative diseases of BMN are diverse. Hematological malignancy is the most common cause. [1],[3],[4],[5],[8],[9] BMN has been reported to be associated with infection, sickle-cell anemia, and solid tumors, [3],[9],[10] and in rare cases, it has been reported to be associated with some cytokines and drugs, such as interferon alpha, granulocyte colony-stimulating factor, [11] all-trans retinoic acid (ATRA), and fludarabine, which are commonly used drugs in hematology-oncology practices. [12],[13],[14],[15],[16],[17] Rarer causes of BMN include anorexia nervosa, hemolytic uremic syndrome, antiphospholipid syndrome, and disseminated intravascular coagulation (DIC), which is generally associated with disseminated metastatic disease and hyperparathyroidism. [18],[19],[20],[21],[22],[23],[24],[25]

The pathophysiologic mechanism of BMN has not been clearly elicited, but a failure in microcirculation is thought to be critical. [8] This microcirculatory occlusion might result from tumor emboli, tumor compression, fibrin thrombi, or cytotoxic injury. [3] Other critical events that contribute to BMN include the toxic effects of chemotherapy, irradiation, bacterial endotoxins, tumor cell involvement in the marrow microvasculature, [23] and aberrant cytokine production, particularly of tumor necrosis factor. [26]

Patients with BMN usually present with bone pain, fever, and fatigue. [1],[10],[27] Pancytopenia, anemia, or thrombocytopenia might be present. Elevated lactate dehydrogenase (LDH), alkaline phosphatase (ALP), uric acid, and alanine transferase (ALT) levels are common. [8] Diagnoses are usually based on findings from a bone marrow (BM) aspiration and biopsy. We describe here a rare case of severe BMN associated with SCD that presented with an unusually severe vaso-occlusive crisis, complicated by acute chest syndrome (ACS), pancytopenia, and DIC.


  Case Description Top


A 23-year-old man with sickle cell anemia who was treated with hydroxyurea and folic acid, with no history of other drug intake, was admitted with severe lower and upper limbs, chest, and back pain as part of a vaso-occlusive crisis. This was complicated by shortness of breath and hypoxia. A chest computed tomography (CT) scan showed no evidence of a pulmonary embolism, but did show a pulmonary infiltrate. The patient was diagnosed with ACS and required intensive care unit (ICU) admission after being intubated. He was administered broad-spectrum antibiotics, including meropenem, azithromycin, and oseltamivir (Tamiflu), in addition to other supportive therapy. Tamiflu was later discontinued after he was found to be H1N1-negative, and the remainder of the viral profile, including parvovirus B19, the hepatitis viruses, Epstein-Barr virus (EBV), cytomegalovirus (CMV), and the human immunodeficiency virus (HIV), were negative. The patient's laboratory results are shown in [Table 1]. After admission, his condition deteriorated; ALP level increased to 1,381 U/L, while the ALT level was 37 U/L, creatinine kinase level was 594 U/L (normal range, 50-190 U/L), creatinine kinase MB level was 52 (normal range, 0-24 U/L), aspartate aminotransferase (AST) level was 119 U/L, and LDH level was 6,556 U/L. Later, he developed DIC, as indicated by the prolonged activated partial thromboplastin time of 64 s (normal range, 27-40 s) and prothrombin time of 20.7 s (normal range, 7.6-9.9 s), as well as the elevated d-dimer level of 1.2 mg/L (reference range, 0.000-0.450 mg/L), decreased fibrinogen level from 6.7 g/L at admission to 1.8 g/L (normal range, 2.0-4.0 g/L), and pancytopenia with leukoerythroblasts in the peripheral blood film. A brain CT scan was performed after the patient experienced a tonic clonic seizure, and this showed a hyperdense lesion consistent with necrotizing vasculitis that was confirmed by brain magnetic resonance imaging and a CT angiogram. A transthoracic echocardiogram showed no evidence of infective endocarditis. A transesophageal echocardiogram showed no evidence of intracardiac vegetation or thrombus. A BM aspiration and biopsy were performed, and these indicated severe marrow necrosis.
Table 1: The patient's laboratory findings


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The BM aspiration was difficult (dry tap), and the stained films of the BM imprints show blurred, faint cell outlines (necrotic cells) that appeared as a mixture of smeared cells, bare degenerating nuclei, and cell debris with increased amounts of amorphous pink background material; some intact cells were observed, but these cells had also lost their normal staining characteristics [Figure 1]. The BM biopsy revealed that the majority of hematopoietic tissue (around 80%) had been replaced by amorphous eosinophilic material and the trabecular bone had been preserved [Figure 2].
Figure 1: High-power magnification of bone marrow touch imprints, showing necrotic cells with some intact cells

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Figure 2: High-power magnification of the bone marrow trephine biopsy, showing areas of necrosis. Note the necrotic cells that appear as eosinophilic cell ghosts

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  Discussion Top


Severe BMN is rarely diagnosed in living patients, [8] but BM necrosis has been described and reported during the autopsies of many patients with SCD. [28],[29] BMN is defined as myeloid tissue and stromal necrosis without cortical bone involvement. [1],[3],[30] This differs from avascular necrosis of the bone, in which the cortical elements are usually involved, with sparing of the myeloid elements, such as in SCD. However, BMN has been reported in SCD patients in association with vaso-occlusive crises. [31] BMN ranges from localized to widespread generalized processes and is graded semiquantitatively according to the extent of necrosis evident in the BM biopsy, described by Maisel et al., as follows: [3]

  • Grade I (mild): Less than 20% of the biopsy
  • Grade II (moderate-intermediate): 20-50% of the biopsy
  • Grade III (severe-extensive): More than 50% of the biopsy.


BMN is most often observed in patients with leukemia and other malignant conditions; however, generalized BMN has also been observed in patients with SCD, in whom it is almost certainly a consequence of blood vessel occlusion. Activation of the clotting system seems to play a role in this clinical setting. Systemic fat embolism and acute multiorgan failure syndrome can also complicate BMN in patients with SCD. [31]

Our patient experienced a severe vaso-occlusive crisis accompanied by fever, high levels of serum LDH and ALP, and leukoerythroblastosis that was complicated by ACS, pancytopenia, and DIC. Despite such suggestive clinical features, a BMN diagnosis still requires a BM biopsy for early diagnosis, and transfusion therapy can be lifesaving. In our case, although BMN was severe and the patient's condition deteriorated and was complicated by serious clinical disorders, the patient recovered, which was proven by his clinical condition and improved laboratory data; this indicated that the prognosis of generalized BMN is not so poor when associated with SCD, similar to observations in other reports. [31] Our patient's presentation and laboratory findings were similar to those reported in the majority of previously reported cases. [1],[8]

Early diagnosis of BMN can prevent clinical deterioration and death because ACS, which usually complicates severe BMN in SCD patients, is the leading cause of death in SCD patients. [28],[29],[32] In adults with SCD, up to 77% of ACS episodes are the result of BM or fat emboli and require ICU management, [33] similar to that in our case. Vaso-occlusion within the pulmonary microvasculature is the basis for ACS pathophysiology. The etiologies for ACS include either vaso-occlusion triggered by infection, asthma, and hypoventilation or vaso-occlusion resulting from BM and fat emboli. [34],[35] These etiologies can occur concurrently; once intrapulmonary vaso-occlusion has been initiated, it is propagated by hypoxia, inflammation, and acidosis.


  Summary Top


Severe BMN is rarely diagnosed in living patients; however, severe BMN has also been observed in patients with SCD, where it is almost always consequent to blood vessel occlusion. Although the clinical features might be highly suggestive, BMN diagnosis still requires a BM examination, particularly in patients with SCD, as early transfusion therapy can be lifesaving. ACS, systemic fat embolism, and acute multiorgan failure syndrome can complicate BMN in patients with SCD; therefore, early diagnosis can prevent clinical deterioration and death, and the prognosis of severe BMN is not so poor when associated with SCD.

 
  References Top

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2.Wade LJ, Stevenson LD. Necrosis of bone marrow with fat embolism in sickle cell anemia. Am J Pathol 1941;17:47-54.  Back to cited text no. 2
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    Figures

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    Tables

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