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Peripheral blood smear – An expeditious test in the preliminary diagnosis of bone marrow embolism in a case of multiple fractures: A case report


1 Department of Pathology, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India
2 Department of Surgical Gastroenterology, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India

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Date of Submission21-Apr-2021
Date of Decision20-Jan-2022
Date of Acceptance27-Jan-2022
Date of Web Publication07-Jun-2022
 

   Abstract 


Bone marrow embolism is known to occur after fractures of long bones such as the femur and pelvis. We report a case of multiple fractures in a 32-year-old female patient, demonstrating bone marrow elements in the peripheral blood as early as 2 hours after trauma. This is the first case being reported with an ante-mortem demonstration of circulating marrow emboli in the peripheral blood, while the previously reported cases have demonstrated the emboli in post-mortem examination. A careful correlation of the clinical history of trauma, hematology auto-analyzer results, and the presence of bone marrow particles and fat globules in peripheral blood helped in arriving at the diagnosis of fat embolism in our case irrefutably.

Keywords: Bone marrow embolism, fracture, peripheral blood


How to cite this URL:
Rajashekar RB, Suchitha S, Shetty MS, Gowda AP. Peripheral blood smear – An expeditious test in the preliminary diagnosis of bone marrow embolism in a case of multiple fractures: A case report. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Feb 5]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=346841





   Introduction Top


Fat embolism was first clinically diagnosed in a patient of comminuted fracture of the femur by Ernst von Bergmann in the year 1873.[1] Fat embolism refers to the presence of fat globules, sometimes with the associated bone marrow in circulation after long bone fractures or rarely in soft-tissue trauma. Fat embolism syndrome (FES) is the term applied to the minority of patients who become clinically symptomatic.[2] FES is known to present 12–72 hours after trauma with a classic triad of respiratory changes, neurological abnormalities, and petechial rash.[2],[3],[4] The diagnosis of fat embolism remains non-specific even with the available criteria,[1],[4] requiring more objective evidence.


   Case Report Top


A 32-year-old lady who had suffered high impact abdominal and orthopedic injuries after being struck by a vehicle was brought to the emergency. The time of accident was around 8 pm; the patient was conscious with tachycardia (98 bpm) and hypotension (80/40 mm hg). The complete hemogram sent as a part of initial work-up at around 9.30 pm showed hemoglobin of 11 gm/dl, a total white blood cell (WBC) count of 19,960/cumm, and a platelet count of 43,000/cumm. The six-part analyzer showed flags of abnormal scattergram, left shift, nucleated red blood cells (RBCs) (14/100 WBCs), and lipid particles. The differential WBC counts were not displayed [Figure 1]a. The ethylenediaminetetraacetic acid (EDTA) anti-coagulated blood examined on a petridish showed numerous fat globules [Figure 1]b. Peripheral blood smear showed numerous bone marrow particles with hematopoietic cells and megakaryocytes admixed with adipocytes. Scattered megakaryocytes, erythroblasts, and myeloid precursors were seen in different parts of the smear, suggestive of bone marrow embolism [Figure 1]c, [Figure 1]d, [Figure 2]a, [Figure 2]b, and [Figure 2]c. Urine microscopy showed plenty of red blood cells. A diagnosis of bone marrow embolism was made.
Figure 1: (a) Auto-analyzer result displaying flags of left shift, nRBCs, and lipid particles with no differential WBC count. (b) EDTA anti-coagulated peripheral blood showing numerous fat globules. (c) Peripheral blood smear with marrow particles at the tail. The inset shows marrow particles with adipocytes and megakaryocytes (Leishman stain, whole slide scan). (d) Hematopoetic cells with adipocytes and megakaryocytes (Leishman stain, x200)

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Figure 2: (a-c) Different foci of peripheral smear showing megakaryocytes (a), myelocytes, (b) and nucleated RBCs (c) (Leishman stain, x400). (d and e) X-ray-right hip-anteroposterior view (d) and MSCT (multi-slice computed tomography) of pelvis-coronal MPR (multi-planar reconstruction) (e) showing the communited fracture of the upper end of shaft of the right femur and right iliac bone with displacement of fracture fragments

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Her blood gas analysis showed a low pH of 7.09, an increased PCo2 of 49 mmHg, and a low Po2 of 17.2 mmHg with low O2 saturation of 15.6%, suggesting metabolic acidosis with severe hypoxia. Serum amylase of 262 U/L and lipase of 176 U/L were elevated. The X-ray of the right hip showed fractures of the femur and iliac bone [Figure 2]d. However, the chest X-ray was normal. Computed Tomography (CT) of the abdomen and pelvis showed a comminuted displaced fracture shaft of the right femur and pelvic bone [Figure 2]e. The patient also had fractures of transverse processes of L1, L2, and L3 vertebra. Internal injuries comprised laceration of the liver and spleen with moderate hemoperitoneum. The patient was planned for laparotomy to repair the splenic and liver injuries.

However, the hemoglobin dropped to 5 gm/dl with tachycardia (122 bpm) and progressive hypoxemia. Despite maximum dual inotrope support, she developed bradycardia, had cardiac arrest by 11 am, and expired. The cause of death was attributed to fat embolism syndrome.


   Discussion Top


Fat embolism is known to occur in 90% of individuals with severe skeletal trauma.[2],[3] Fat embolism syndrome is reported in 5–30% cases of fractures. It lacks universal criteria for diagnosis, posing a diagnostic challenge while treating patients of orthopedic trauma.[1] Fat embolism has been described in around 33% of patients with bilateral femoral fractures.[4] A few cases have been reported after vertebral fractures.[5],[6] Our case had fractures of the femur, pelvis, and vertebra, increasing the likelihood of fat embolism.

FES is characterized by pulmonary insufficiency, neurologic impairment, anemia, and thrombocytopenia.[2],[7] Pathogenesis of fat embolism syndrome has been explained by mechanical and biochemical theories.[2],[4],[5] The fat from the disrupted bone marrow is forced into torn venules in areas of fractures with the highest incidence in the case of marrow-containing bones such as the pelvis and femur.[1],[4] This is possibly because the disrupted venules in the bone marrow remain tethered open by their osseous attachments allowing the marrow contents to enter the venous circulation and travel to the lung.[4] This theory might explain the immediate (within 2 hours of trauma) demonstration of marrow emboli in peripheral blood in our case. Although the development of fat embolism takes 12–72 hours, there are rare reports of rapid onset of fat embolism similar to our case.[8] The biochemical theory proposes the production of toxic metabolites from the degraded fat emboli in plasma to free fatty acids.[1],[3],[4]

Among the various diagnostic criteria, Gurd's criteria are the most accepted for the diagnosis of fat embolism syndrome comprising petechiae, hypoxemia (PaO2 <60 mm Hg), and central nervous system depression as major criteria. The minor criteria described include tachycardia, pyrexia >39°C, retinal change, a sudden drop in hematocrits/platelets, a high erythrocyte sedimentation rate, and fat globules in sputum. The diagnosis requires at least one major and four minor criteria.[7],[9] Lindeque's criteria are based on respiratory features alone,[4],[9] while Schonfeld's criteria require a score of 5 for diagnosis including petechiae, chest X-ray changes, hypoxemia, fever, tachycardia, and tachypnoea.[4],[9] Other minor features of fat embolism include pyrexia, tachycardia, retinal exudates (Purtscher's retinopathy), coagulation abnormalities, and renal changes such as oliguria, lipiduria, hematuria, or proteinuria. Elevated serum lipase has also been reported in a few cases as seen in our case.[4]

The demonstration of fat globules has been suggested with the use of Sudan or Oil Red O staining on the cytological samples of urine, blood, and sputum.[1],[4] Although diffuse lung infiltrates can be seen with progression of respiratory insufficiency, the chest X-ray is often normal initially as in our case.[4],[10] However, all the above-described criteria vary in their sensitivity and specificity, causing a delay in diagnosis and patient management.

The investigation results of the present case satisfied one major criterion (hypoxemia) and three minor criteria including tachycardia (122 bpm), a drop in hemoglobin (5 gm/dl), and thrombocytopenia (43,000/cumm). The fat globules and marrow particles were demonstrated in the peripheral blood sample within 2 hours of trauma proving it to be fatal resulting in her death soon after 15 hours of trauma. Although hematuria was noted in the urine sample, fat globules could not be demonstrated.

Auto-analyzer flags obtained by the six-part analyzer were useful clues in identifying the lipid particles in the blood sample and the nucleated RBCs (erythroblasts). The display of abnormal scattergram with left shift indicated the myeloid precursors, and hence, a differential WBC count was not obtained. A vigilant peripheral blood examination demonstrated the marrow cells with fat globules in Leishman stained smear along with visible fat globules in the anti-coagulated blood sample.

Fat globules have been demonstrated in the blood of 50% of orthopedic trauma patients without evidence of FES.[4] The microscopic demonstration of fat requires specialized techniques of frozen sections and special stains for fat.[2] Nevertheless, neither of them were necessary in our case as the marrow elements were demonstrable in the peripheral blood. Bone marrow emboli have been demonstrated in the pulmonary vasculature of patients with FES on post-mortem examination,[5],[6],[7],[8] but none of them have documented evidence of ante-mortem demonstration of circulating bone marrow elements in peripheral blood.

In the absence of specific tests or criteria for the diagnosis of FES, a swift and simple test of examining the peripheral blood for marrow elements in the immediate post-trauma period of 2–3 hours might prove to be an invaluable tool in arriving at a specific diagnosis of fat embolism in cases of multiple fractures, even before the development of classic signs and symptoms of FES and the associated complications. It might alleviate the need of other investigations to arrive at the diagnosis, although not listed in the accepted diagnostic criteria. The utility of flags generated by the auto-analyzer cannot be under-estimated. It is important not to limit our observations to the defined criteria alone. This is the first case of ante-mortem demonstration of bone marrow emboli in peripheral blood to the best of our knowledge.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Uransilp N, Muengtaweepongsa S, Chanalithichai N, Tammachote N. Fat embolism syndrome: A case report and review literature. Case Rep Med 2018;2018:1479850.  Back to cited text no. 1
    
2.
Hemodynamic disorders, thromboembolic disease, and shock. In Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier Saunders; 2020. p. 131-2.  Back to cited text no. 2
    
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Sudulagunta SR, Kumbhat M, Sodalagunta MB, Nataraju AS, Sepehrar M, Raja SK. Fat embolism syndrome: Case report. J Neurol Res 2016;6:114-7.  Back to cited text no. 3
    
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Gupta A, Reilly CS. Fat embolism. Continuing Education in Anaesthesia, Critical Care & Pain 2007;7:148-51.  Back to cited text no. 4
    
5.
Lastra RR, Saldanha V, Balasubramanian M, Handal J. Fatal fat embolism in isolated vertebral compression fracture. Eur Spine J 2010;19(Suppl 2):S200-2.  Back to cited text no. 5
    
6.
Papi L, Gori F, Turco S. Fat embolism as fatal complication of vertebral fractures. Arch Clin Med Case Rep 2020;4:91-6.  Back to cited text no. 6
    
7.
Selvi SK, Kar R, Vadivelan M, Subrahmanyam DK. A fatal case of bone marrow embolism of unknown cause masquerading clinically as dengue shock syndrome. Indian J Pathol Microbiol 2012;55:572-3.  Back to cited text no. 7
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8.
Kurian CP, Shetty S, Rani S, Shetty M, Shetty V. Rapid onset of fatal fat embolism in a case of lynching. J South India Medicolegal Assoc 2020;12:121-3.  Back to cited text no. 8
    
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Lama SM, Raja SB. Post Traumatic Fat Embolism Syndrome: A Case Report. ARC J Anesthesiol 2019;4:19-23.  Back to cited text no. 9
    
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Kwiatt ME, Seamon MJ. Fat embolism syndrome. Int J Crit Illn Inj Sci 2013;3:64-8.  Back to cited text no. 10
[PUBMED]  [Full text]  

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Correspondence Address:
Rajalakshmi B Rajashekar,
Rajashekar, Department of Pathology, JSS Medical College, JSS Academy of Higher education and Research, Mysuru, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_394_21



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