Bone Marrow Embolism Research Articles

Femoral Nailing in a Porcine Model Causes Bone Marrow Emboli in the Lungs and Systemic Emboli in the Heart and Brain.

Shaft fractures of the femur are commonly treated with intramedullary nailing, which can release bone marrow emboli into the bloodstream. Emboli can travel to the lungs, impairing gas exchange and causing inflammation. Occasionally, emboli traverse from the pulmonary to the systemic circulation, hindering perfusion and resulting in injuries such as heart and brain infarctions, known as fat embolism syndrome. We studied the extent of systemic bone marrow embolization in a pig model. Twelve anesthetized pigs underwent bilateral intramedullary nailing of the femur, while 3 animals served as sham controls. Monitoring included transesophageal echocardiography (TEE), pulse oximetry, electrocardiography, arterial blood pressure measurement, and blood gas and troponin-I analysis. After surgery, animals were monitored for 240 minutes before euthanasia. Post mortem, the heart, lungs, and brain were biopsied. Bone marrow emboli were found in the heart and lungs of all 12 of the pigs that underwent intramedullary nailing and in the brains of 11 of them. No emboli were found in the sham group. The pigs subjected to intramedullary nailing exhibited significant hypoxia (PaO2/FiO2 ratio, 410 mm Hg [95% confidence interval (CI), 310 to 510) compared with the sham group (594 mm Hg [95% CI, 528 to 660]). The nailing group exhibited ST-segment alterations consistent with myocardial ischemia and a significant increase in the troponin-I level compared with the sham group (1,580 ng/L [95% CI, 0 to 3,456] versus 241 ng/L [95% CI, 0 to 625] at the 240-minute time point; p = 0.005). TEE detected emboli in the right ventricular outflow tract, but not systemically, in the nailing group. Bilateral intramedullary nailing caused bone marrow emboli in the lungs and systemic emboli in the heart and brain in this pig model. The observed clinical manifestations were consistent with coronary and pulmonary emboli. TEE detected pulmonary but not systemic embolization. Femoral intramedullary nailing in humans is likely to result in embolization as described in our pig model. Focused monitoring is necessary for detection of fat embolism syndrome. Absence of visual emboli in the left ventricle on TEE does not exclude the occurrence of systemic bone marrow emboli.

Femoral nailing associated with bone marrow emboli in pigs induced a specific increase in blood IL-6 and broad inflammatory responses in the heart and lungs.

Bone marrow embolization may complicate orthopedic surgery, potentially causing fat embolism syndrome. The inflammatory potential of bone marrow emboli is unclear. We aimed to investigate the inflammatory response to femoral intramedullary nailing, specifically the systemic inflammatory effects in plasma, and local tissue responses. Additionally, the plasma response was compared to that following intravenous injection of autologous bone marrow. Twelve pigs underwent femoral nailing (previously shown to have fat emboli in lung and heart), four received intravenous bone marrow, and four served as sham controls. Blood samples were collected hourly and tissue samples postmortem. Additionally, we incubated bone marrow and blood, separately and in combination, from six pigs in vitro. Complement activation was detected by C3a and the terminal C5b-9 complement complex (TCC), and the cytokines TNF, IL-1β, IL-6 and IL-10 as well as the thrombin-antithrombin complexes (TAT) were all measured using enzyme-immunoassays. After nailing, plasma IL-6 rose 21-fold, compared to a 4-fold rise in sham (p=0.0004). No plasma differences in the rest of the inflammatory markers were noted across groups. However, nailing yielded 2-3-times higher C3a, TCC, TNF, IL-1β and IL-10 in lung tissue compared to sham (p<0.0001-0.03). Similarly, heart tissue exhibited 2-times higher TCC and IL-1β compared to sham (p<0.0001-0.03). Intravenous bone marrow yielded 8-times higher TAT than sham at 30 minutes (p<0.0001). In vitro, incubation of bone marrow for four hours resulted in 95-times higher IL-6 compared to whole blood (p=0.03). A selective increase in plasma IL-6 was observed following femoral nailing, whereas lung and heart tissues revealed a broad local inflammatory response not reflected systemically. In vitro experiments may imply bone marrow to be the primary IL-6 source.

Comment on: "Bone marrow embolism: should it result from traumatic bone lesions? a histopathological human autopsy study".

Farid et al., described how 8 of 11 cases of Bone Marrow Embolism were found to be non-traumatic. In our research group we found several shortcomings in the methodology, and within our own Institute we could not replicate the results.

Bone marrow embolism: should it result from traumatic bone lesions? A histopathological human autopsy study

Bone marrow embolism (BME) is likely a consequence of fractures in which pulmonary vessels are the most affected. However, some cases of BME were reported in the absence of trauma. Thus, a traumatic injury might not be necessary for developing BME. This study discusses BME cases in patients without signs of fractures or blunt trauma. The discussion addresses various possible mechanisms for the appearance of BME. Options include cancer in which bone marrow metastasis is a suggestive cause. Another proposal is the chemical theory where bone marrow fats are released via lipoprotein lipase in a pro-inflammatory state, resulting in vascular/pulmonary obstruction. Other cases discussed in this study are hypovolemic shock and drug-abuse related BME. All autopsy cases with BME were included regardless of the cause of death for a period of 2 years. Autopsies involved complete dissection with the macroscopic evaluation of the affected organs, including the heart, lungs, and brain. Tissues were also prepared for microscopic examination. Of the 11 cases, eight showed non-traumatic BME (72%). These findings conflict with theories in the literature that BME most commonly occurs after fractures or trauma. One of the eight cases exhibited mucinous carcinoma; one is presented with hepatocellular carcinoma; and two cases showed severe congestion. Lastly, one case was found to be associated with each of the following conditions: liposuction, drug abuse, pulmonary hypertension, and heart failure. Each case suggests a different pathophysiology for developing BME, yet the exact mechanisms are not fully understood. Further study of non-traumatic associated BME is recommended.

Post-Trauma Combined Pulmonary Fat and Bone Embolism: Literature Review with Case Presentation

Following an accident in the workplace, a man received deep wounds in his left groin and left lower limb caused by plow blades. An external examination was carried out showing multiple, large, and deep slash injuries of the scrotal region, the left groin, and the left thigh. A complete autopsy was performed. The gross examination of the lungs showed edema and congestion, with some areas of parenchymal contusion and wide emphysema. The left femur showed complete, comminuted, displaced, and exposed fracture of its diaphyseal tract. Histopathological analysis was then carried out, showing unusual abnormalities in both lungs, with numerous endovascular drop-shaped fat globules with surrounding hematopoietic marrow that were mixed with small bone particles. The other organs did not show any signs that could explain the death. Given macroscopic and histopathological elements, the cause of death was ultimately identified as a traumatic shock with a high hemorrhagic component combined with pulmonary bone marrow and bone embolism. This paper aims to outline a rare case of post-trauma combined bone and bone marrow embolism. This occurrence is scantly described in the literature and should be considered in major trauma deaths. Therefore, in such cases, an accurate histopathological analysis should be mandatory to identify the correct cause of death and evaluate a possible medical liability.

Bone marrow emboli following bone marrow procedure: A possible complication.

Bone marrow emboli following bone marrow procedure: A possible complication.

Pulmonary embolism at autopsy in cancer patients

BackgroundPulmonary embolism (PE) is a potentially fatal disease, but data on the incidence of fatal PE in cancer patients are scant. ObjectiveWe sought to estimate the proportion of cancer patients with PE at autopsy. MethodsFor this retrospective cohort study, all autopsy reports of cancer patients were retrieved from PALGA: Dutch Pathology Registry and used for data extraction. The primary outcome was PE at time of autopsy, defined as any clot obstructing a pulmonary artery. The secondary outcome was venous thromboembolism, defined as the composite of thrombotic PE, deep vein thrombosis, splanchnic vein thrombosis, or internal jugular vein thrombosis. ResultsA total of 9571 cancer patients were included. In 1191 (12.4%; 95% confidence interval [CI], 11.8‐13.1) patients, one or more PE events were observed at autopsy, of whom 1074 (90.2%) had a thrombotic embolism, 168 (14.1%) a tumor embolism, 9 (0.8%) a septic embolism, 7 (0.6%) a fat tissue embolism, and 3 (0.3%) a bone marrow embolism. Among patients with PE for whom the cause of death was specified in the autopsy report, death was considered PE‐related in 642 patients (66.7%), which was 6.7% of the total study population. Venous thromboembolism was observed in 1223 (12.8%; 95% CI, 12.1‐13.5) patients. ConclusionThe proportion of PE in cancer patients at autopsy is substantial. Although the study population is not representative for the total cancer population, it suggests that PE is an important disease complication in cancer patients.

Description, Staging and Quantification of Pulmonary Artery Angiophagy in a Large Animal Model of Chronic Thromboembolic Pulmonary Hypertension.

Angiophagy has been described as a non-fibrinolytic mechanism of pulmonary artery (PA) patency restoration after distal (<50 µm in diameter) pulmonary embolism in mice. We hypothesized that angiophagy could achieve muscularized PA patency restoration after pulmonary embolism in piglets and humans. Angiophagy was defined by pathological assessment as the moving of an embolic specimen from the lumen to the interstitium according to three stages in a pig model of chronic thromboembolic pulmonary hypertension (CTEPH) 6 to 10 weeks after embolization with enbucrilate: the embolic specimen is (I) covered by endothelial cells, (II) covered by endothelial cells and smooth muscle cells, and (III) located in the adventitia. In animals, we observed the three stages of the pulmonary angiophagy of enbucrilate emboli in <300 µm PA. Stages II and III were observed in 300 to 1000 μm PA, and only Stage I was observed in larger-diameter PA (>1000 μm). In lung samples from patients with histories of pulmonary embolisms, we observed PA angiophagy stigma for embolic specimens derived from blood clots and from bone marrow emboli. This study provides an original pathological description and staging of PA angiophagy in a large animal model of CTEPH and in humans after pulmonary embolism.

Analysis of cardiopulmonary findings in COVID-19 fatalities: High incidence of pulmonary artery thrombi and acute suppurative bronchopneumonia

Since its recognition in December 2019, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread globally causing a pandemic that represents the greatest medical challenge in decades. The aim of the study was to evaluate the spectrum of cardiopulmonary pathology of COVID-19 based on (non-minimal invasive) autopsies performed on 14 COVID-19 decedents. Bilateral diffuse alveolar damage (DAD) was found in all patients. Superimposed acute bronchopneumonia was present in 11 of 14 (78.6%) patients and was considered the major cause of death in 2 patients. A key finding was the presence of thrombotic/thromboembolic vascular occlusions. We classified 5 types of pulmonary thrombi: 1. capillary microthrombi (11/14, 78.6%); 2. partially organized thrombi in mid-sized pulmonary arteries with complete vessel occlusion; 3. non-organized thrombi in mid-sized pulmonary arteries that did not completely fill out the vessel lumen and probably represented thromboemboli rather than thrombosis; 4. bone marrow emboli (1/14, 7.1%); and 5. septic pulmonary thromboemboli (1/14, 7.1%). Pulmonary thrombi in mid-sized arteries were noted in 5 of 14 (35.7%) patients, causing pulmonary infarction and/or pulmonary hemorrhage. All patients had evidence of chronic cardiac disease, including myocardial hypertrophy (13/14, 92.9%), mild to marked coronary artery atherosclerosis (14/14, 100%) and focal myocardial fibrosis (3/14, 21.4%). Acute myocardial infarction was found as concurrent cause of death in 3 (21.4%) patients, and significant cardiac hypertrophy (heart weight 750 g) was present in 1 (7.1%) patient with ATTR-positive cardiac amyloidosis. The autopsy findings confirm that COVID-19 is a systemic disease, with major involvement of the lungs, that increases the risk of cardiac and vascular complications including acute myocardial injury and thrombotic/thromboembolic events. Secondary acute bronchopneumonia is a common complication in patients with COVID-19 and may be the major cause of death.

Sickle cell disease related cerebral fat embolism: Characterizing the clinical syndrome

To characterize the clinical syndrome of sickle cell disease (SCD) related cerebral fat embolism syndrome (CFES) SCD-related CFES results from bonemarrow embolism in the absence of trauma and except for a few single case reports, its clinico-imaging spectrum has not been fully characterized. Twelve SCD patients (6 women and 6 men, aged 28.4±9.9 years), were evaluated for neurological complications such as altered sensorium (n=12) and seizures (n=2) in the setting of acute chest syndrome, fever and no preceding trauma (n=12). Laboratory findings included high CRP (11 out of 11 tested) and thrombocytopenia (n=12), normal CSF findings (n=2 out of 2 tested). EEG showed non-specific diffuse slowing in 9 out of 10 cases and occasional left temporal spike discharges (n=1). Cerebral PET scan obtained in a single case showed globally reduced glucose uptake. Lipid laden macrophages were demonstrated in the broncho-alveolar lavage in two cases. CFES was diagnosed based on the characteristic finding of multiple cerebral microbleeds in the splenium and subcortical location on susceptibility weighted imaging (SWI). Our patients received exchange transfusion, antibiotics, ventilatory assistance (n=12) and anticonvulsant (n=2). One patient died, while the others survived with variable functional disability. In SCD patients presenting with acute chest syndrome, altered mental status and fever, the presence of thrombocytopenia and high CRP provides important clue to the possibility of CFES. The diagnosis is confirmed with SWI MRI that usually demonstrates multiple microbleeds in the splenium and subcortical areas. SCD-related CFES carries considerable short-term morbidity and occasional mortality.

Perinatal Maternal Mortality in Sickle Cell Anemia: Two Case Reports and Review of the Literature

As outcomes of patients with sickle cell anemia improve and survival into adulthood with good quality of life and expectation of long-term survival becomes more common, challenges have developed, including issues related to reproduction. Pregnancy is frequently complicated in patients with sickle cell anemia with mortality up to 4.0%. Here we report maternal perinatal mortality in two women with sickle cell anemia who died post-partum due to acute chest syndrome (ACS), caused by bone marrow fat embolism and review the literature pertinent to this subject. Patient A was a 28-year-old woman with sickle cell anemia with multiple complications. At 30 weeks’ gestation she developed hemolysis associated with poor placental function necessitating delivery by C-section. The fetus was delivered successfully but she died due to multi organ failure after delivery. Autopsy showed pulmonary and amniotic fluid embolization. Patient B was a 37-year-old woman with uncomplicated sickle cell anemia who presented with pre term labor and crisis, then ACS and fetal distress. The infant was delivered successfully but the patient died after cardiovascular collapse. Autopsy results showed fat and bone marrow embolization as the cause of death. Pregnancy continues to be high risk for patients with sickle cell anemia including those with mild disease. Maternal perinatal mortality could be unpredictable due to serious complications of sickle cell disease. More studies to assess maternal perinatal mortality are needed.

Myélolipome hépatique : une entité rare, à propos d’un cas et revue de la littérature

Hepatic myelolipoma is a rare entity with only 17 cases described in the literature. A 73mm right liver mass was fortuitously discovered in a 55-year-old man. The biopsy showed normal hepatic tissue adjacent to a normal medular like hematopoïetic tissue, showing trilieage hematopoieses, including myeloid cells, erythroid cells and megakaryocytic cells. The diagnosis of hepatic myelolipoma was proposed. This benign tumor was initially described in adrenal gland, which is the most common topography. No malignancy or bleeding complication has been described in its hepatical location. The diagnosis is histological due to non-specific radiological presentation; it allows to avoid a surgical treatment in relation to its excellent prognosis. The etiology is not well established; but some hypotheses are discussed: adrenal or medullar heterotopia, bone marrow embolism, myeloïd metaplasia.

A Simple and Easy Intramedullary Lavage Method to Prevent Embolism During and After Reamed Long Bone Nailing.

Reaming of the long bones is widely practiced because it allows for improved healing and early mobilization in patients needing surgical debridement of bone tissue. The insertion of reamed intramedullary nails can cause complications such as bone necrosis, cortical blood supply damage, and fat or bone marrow embolism. We describe a novel way to limit the amount of material in the canal before nail insertion to limit the chances of embolism.

A Case Report for a Mortality Following Kyphoplasty: Suggested Method of Prevention

Study design: A case report and review of literature. Objective: To discuss the implementation of a bilateral cannula venting technique to prevent perioperative mortality and morbidity related to kyphoplasty. Summary of background data: Several authors have suggested various recommendations for techniques to lower complications related to kyphoplasty, such as specific cement types, consistencies, volumes, and intravertebral pressures. However, there are few commentaries regarding venting during kyphoplasty as a method to reduce complications, such as embolism. Methods: A 69-year-old male suffered acute cardiac decompensation and arrest during a kyphoplasty procedure, ultimately resulting in his death. Results: Autopsy report from the coroner’s office revealed the cause of death as a pulmonary fat and bone marrow embolism. In response to this event, the attending physician and his partners began venting during the kyphoplasty procedure, using a bilateral cannula technique. Conclusion: The bilateral venting modification has been adopted as the standard of practice with the senior author and his local colleagues. Since implementing this technique, the group of surgeons has successfully performed over 1000 kyphoplasty surgeries without any resulting in perioperative mortality or morbidity.

Pulmonary emboli of bone marrow associated with femoral fracture in a calf

ABSTRACTAn eight-month-old Holstein bullock with a history of recumbency and swelling of the proximal right extremity was necropsied. Gross lesions included a complete fracture in the proximal third of the right femur and multifocal haemorrhages of the surrounding soft tissues. Histologically, there was massive bone marrow emboli of varying sizes located in the pulmonary arterial branches. The emboli were osmium tetroxide, factor VIII-related antigen and myeloid-histiocyte antigen positives, consistent with fat and haematopoietic cells of bone marrow origin. No gross or microscopic abnormalities were detected elsewhere.

Akciğerde Yağ Embolisine Bağlı Ölüm Olgu Sunumu

Yağ embolisi, genellikle ciddi travma veya cerrahi girişim sonrası kemik iliğinden ya da yumuşak dokulardan yağ damlacıklarının serbestleşip sistemik dolaşıma geçmesidir. Gençlerde daha çok uzun kemik kırıklarından sonra, yaşlılarda ise kalça kırığı sonrası gelişmektedir. Genellikle travmadan 24-48 saat sonra ortaya çıkan klinik tablo, hafif olabileceği gibi solunum yetmezliği ve ölüme kadar ilerleyebilir. Sunulan olgu; 84 yaşında kadın olup, araç dışı trafik kazası nedeni ile sol kolda ve sol pelvik bölgede ağrı yakınmalarıyla hastaneye başvurmuştur. Ortopedi konsültasyonunda; sol omuz çıkığı, sol humerus suprakondiler kırığı ve sol ramus pubis kırığı nedeniyle kapalı redüksiyon uygulanarak taburcu edilmiş ve kazadan yaklaşık üç saat sonra evinde öldüğü bildirilmiştir. Şüpheli ölüm olarak değerlendirilen adli olguya yapılan otopside; akciğer kesitlerinde yer yer köpüklü hemorajik özellikli sıvı çıkışı, sol omuz çıkığı, sol humerus suprakondiler kırığı ve sol ramus pubiste deplase kırık hattı görüldü. Postmortem histopatolojik incelemede; akciğerlerde interstisiyel kapiller lümenlerde evre IV yağ embolisi ve orta çaplı pulmoner damarlarda yaygın kemik iliği embolizasyonu tespit edildi. Olayın öyküsü, tıbbi belgelerin içeriği, otopsideki makroskopik ve histopatolojik inceleme verilerine göre, kişinin ölümünün araç dışı trafik kazası sonrası genel beden travmasına bağlı ekstremite kırıklarıyla birlikte akciğerde yağ embolisi sonucunda geliştiği belirlendi.Travma ile oluşan kemik kırıkları sonrası yağ embolisi oluşumunu önlemek için, kırıkların erken fiksasyonu ve immobilizasyonu önemlidir. Bu olgularının takip ve tedavisinde dikkatli olunması, tıbbi uygulama hatalarının önlenmesi yönünden de önem taşımaktadır. Ayrıca trafik kazası ile kemik kırıkları tespit edilen ve şüpheli ölüm olarak değerlendirilen olgularda otopsi ve postmortem histopatolojik incelemenin tanıyı belirlemede katkısı olduğu açıktır.Anahtar Kelimeler: Yağ embolisi, travma, adli tıp, otopsi, şüpheli ölüm.

The impact of pulmonary bone component embolism: an autopsy study

AimsPulmonary bone marrow embolism (BME) and pulmonary bone fragment embolism (BFE) are two types of non-thrombotic pulmonary embolism (NTPE). While BME can be found consistently in autopsies, BFE is a...

Bone marrow necrosis and fat embolism: an autopsy report of a severe complication of hemoglobin SC disease

Sickle Cell Disease encompasses a group of disorders related with the hemoglobin S and other hemoglobin genotypes. The clinical manifestation and the severity of symptoms are dependent on the specific genotype. In this setting, homozygous genotype (HbSS) presents an early onset of symptoms and a low expectancy of lifetime. However, the SC genotype (HbSC), which apparently shows a less severe clinical course, may exhibit the same complications of HbSS. These complications are usually manifested late in the course of life, when compared with the HbSS patients. It is noteworthy that HbSC may present a normal hematocrit, and therefore stays unknown until the first complication, that may be disastrous. The authors report a case of an African-Descendant woman, aging 65 years, with no previous diagnosis of anemia who sought medical attention because of a thoracic back pain followed by fever and altered mental status. The clinical picture deteriorated very fast with multiple organ failure and death. The autopsy findings concluded by generalized vaso-occlusive crisis, bone marrow necrosis and bone marrow and fat embolism, mainly to the lungs and kidney. The authors call attention for the knowledge of this severe life threatening complication, mainly in a country with a high Afro-Descendant population.

Is Resistance Futile?

Is Resistance Futile?

Fatal fat embolism syndrome in a case of isolated L1 vertebral fracture-dislocation

Although fat embolism syndrome is a well-known complication of fractures of the long bones or pelvis, fat embolism syndrome occurring subsequent to fracture of the lumbar spine is rare. We report a fatal case of fat embolism syndrome characterized by fat and bone marrow embolism that occurred 36 h after an isolated fracture-dislocation of the L1 vertebra. A postmortem examination was performed and pathological finding demonstrated fat and bone marrow tissue which were disseminated in the bilateral pulmonary arteries. We need to be aware of the possibility of fat embolism syndrome as a complication of spinal fractures, including isolated vertebral body fractures.