Bone Marrow Fat Embolism Research Articles

Bone marrow necrosis and fat embolism syndrome in sickle cell disease during COVID-19 infection treated successfully with sequential red cell and plasma exchange.

Fat embolism syndrome (FES) is a rare life-threatening condition that is particularly seen in milder forms of sickle cell disease (SCD). Widespread systemic fat emboli are generated in the context of extensive bone marrow necrosis. Multi-organ failure with a high morbidity and mortality may quickly develop. Infection with Parvovirus B19 is a common precipitant. Here, the authors report the case of a 35-year-old Afro-Caribbean man with HbSC disease who presented with FES having tested positive for SARS-COV-2. He rapidly became critically ill and required admission to the intensive care unit for organ support. He was treated with red cell exchange and plasma exchange and made a good recovery to leave hospital at week 7.

Causes of Death in Patients with Sickle Cell Disease from a Large Population-Based Cohort

Background Mortality rates and causes of death in children with sickle cell disease (SCD) have changed significantly over the past several decades. With ongoing improvements in standards of care, modern mortality rates and causes of death must be updated. Children's Healthcare of Atlanta (CHOA) houses one of the largest pediatric SCD programs in the country. This analysis reviews causes of death in children with SCD who were treated at CHOA between June 2010-June 2022. Methods We reviewed the CHOA's Sickle Cell Clinical Database (SCCD) for deceased patients. Demographics, SCD genotype, date and age at death, healthcare utilization, hydroxyurea (HU) use, chronic transfusion therapy (CTT), and bone marrow transplant (BMT) were obtained from the SCCD. Cause of death and history of significant comorbidities were abstracted from the medical record, death certificates and/or autopsy reports. Results A total of 4022 unique patients with SCD were seen at CHOA from June 2010- June 2022. Fifty-seven patients died during this period. All but 1 patient had been seen in the CHOA Sickle Cell Outpatient Clinic at least once. That patient received SCD care at a different institution, died from complications of a non-SCD related disease following transfer to CHOA, and was excluded from analysis. SCD-related causes accounted for 22 (39%) deaths. Acute SCD-related causes included bone marrow fat emboli, acute chest syndrome or pneumonia, cerebral hemorrhage in a person with history of stroke and moyamoya, and pulmonary hypertensive crisis. Of the infectious causes included Streptococcus pneumoniae, gram negative bacteria, unspecified streptococcal meningitis (by verbal report), and due to presumed septic shock complicated by severe anemia. Viral infections included respiratory syncytial virus, COVID-19 with severe anemia, and Parvovirus B-19 complicated by bone marrow fat emboli. Death due to complications of treatment included ceftriaxone-induced hemolysis and severe intrathoracic hemorrhage after apheresis catheter removal for treatment of ACS. BMT-associated complications included adenovirus infection after transplant with a matched unrelated donor and Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis after haploidentical transplant (see Figure 1). Non-SCD comorbidities or accidents accounted for 15 (27%) deaths. These included heart disease, advanced cancer or complications of cancer (including E. coli sepsis in a child with relapsed neuroblastoma), accidents, one due to motor vehicle accident and one drowning. Gastrointestinal causes included bleeding from undiagnosed inflammatory bowel disease and liver failure leading to coagulopathy and intracranial hemorrhage. There was a case of severe anemia related to systemic lupus erythematosus. The causes of death were unknown in the remaining 19 (34%) of individuals. Six (11%) were under 18 years of age. Five died at home or out of state and had no autopsy information, one had autopsy declined by the coroner. Of those who were 18 years of age or older, 7 (53%) were lost to follow-up, 3 (23%) had transitioned to adult care, and 3 (23%) were still being treated at CHOA. There were more deaths in the 0-2 year and 15-17 year groups, and the most among adults (n = 19, 34%). Death from congenital heart disease was more frequent in children 0-5 years old. Pneumococcal sepsis were in children 5-7 years old, after stopping penicillin and before the second Pneumovax vaccine. Other bacterial infections were evenly distributed by age. Non-infectious SCD-related deaths were more likely to occur in patients 12 years and older (n = 6, 86%) (Figure 2). Conclusions Continuing from a previous study by Lai et al. (2020) which reported the 10-year mortality rate at CHOA, this study described the causes of death of SCD patients during a 12-year period. Of direct SCD-related causes, bone marrow fat embolism was the most common and was also present in a patient who also had Parvovirus-B19 infection. Severe anemia was present in several patients at the time of death, associated with ceftriaxone-induced hemolysis, presumed septic shock, COVID-19, systemic lupus erythematosus, as well as G or intracranial hemorrhage. Patients beginning transition to adult care are at risk of becoming lost to follow-up and may experience difficulties transitioning to adult care. Future analyses will include review of regional hospital where available, and CDC's National Death Index. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Newly Diagnosed Sickle Cell Disease Complicated by AKI With Bone Marrow Necrosis and Fat Embolism Syndrome Successfully Treated With Plasma Exchange

Newly Diagnosed Sickle Cell Disease Complicated by AKI With Bone Marrow Necrosis and Fat Embolism Syndrome Successfully Treated With Plasma Exchange

28-Year-Old Man With Joint Pain

28-Year-Old Man With Joint Pain

Bone Marrow Necrosis and Fat Embolism in a Patient with Sickle Cell Crisis, a Fatal Complication

We report a case of a 56-year-old female with past medical history of sickle cell disease, atrial fibrillation and prior history of stroke. She presented to the emergency department with chief complaint of left leg pain. After few hours the pain moved to the lower and upper back.

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.

Inside Out: Bone Marrow Necrosis and Fat Embolism Complicating Sickle-β+ Thalassemia

Inside Out: Bone Marrow Necrosis and Fat Embolism Complicating Sickle-β+ Thalassemia

Sudden Death in Sickle Cell Anaemia: Report of Three Cases with Brief Review of Literature

Vaso-occlusive crisis in sickle cell anaemia is one of the commonest presentations and a leading cause of death. Death can be sudden and unexpected. Herein we present three cases of sickle cell anaemia with sudden death within 3days of hospitalisation. All the three cases presented with fever and jaundice. Two cases presented consecutively in the same year within a span of 5months while the other case had presented 2years prior to these two cases. Infection was the precipitating event in two cases and pregnancy with infection in one. One case in addition had 'right upper quadrant syndrome' and one case had 'acute chest syndrome' (ACS) due to bone marrow fat embolism. Postmortem liver biopsy of all the three cases showed dilated and congested sinusoids with sickled RBCs, kupfer cell prominence with erythrophagocytosis. Lung biopsy of case with ACS showed vessels occluded with bone marrow elements indicating bone marrow fat embolism.

地固め療法後，敗血症から骨髄壊死，脂肪塞栓症を合併し死亡した急性リンパ性白血病

地固め療法後，敗血症から骨髄壊死，脂肪塞栓症を合併し死亡した急性リンパ性白血病

Bone marrow necrosis and fat embolism syndrome in sickle cell disease: Increased susceptibility of patients with non-SS genotypes and a possible association with human parvovirus B19 infection

Fat embolism syndrome (FES) due to extensive bone marrow necrosis (BMN) in sickle cell disease (SCD) is a potentially under-diagnosed complication associated with severe morbidity and mortality. We identified 58 cases reported in the world literature to date. Typically, patients presented with a seemingly uncomplicated vaso-occlusive crisis (VOC) and subsequently deteriorated rapidly with a drop in their haemoglobin and platelets, development of respiratory failure, encephalopathy and varying degrees of involvement of other systems. Overall mortality in the reported cases was 64% but differed according to the use of transfusion and was 29%, 61% and 91% for patients receiving exchange, top-up or no transfusion respectively. Patients most at risk appear to be those with a “milder” form of SCD as 81% of patients had a genotype other than HbSS and the majority had no history of significant sickle-related complications. Human parvovirus B19 (HPV B19) infection was documented in 24% of cases.

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.

A fatal case of bone marrow embolism of unknown cause masquerading clinically as dengue shock syndrome

Bone marrow fat embolism usually occurs following multiple bone fractures, intraosseous surgical procedures, following vigorous cardiac resuscitation, ecclampsia, sickle cell anemia, malignancies, etc. We present a case of 70-year-old male who presented with fever, cough with expectoration, respiratory distress, altered sensorium, hypotension and thrombocytopenia, and diagnosed to have dengue shock syndrome and expired within 1 day of admission. Postmortem lung biopsy revealed bone marrow fat embolism.

Pulmonary fat embolism after reamed and unreamed nailing of femoral fractures

BackgroundTo determine whether reamed or unreamed intramedullary nailing of femoral fractures results in higher incidence of pulmonary fat embolism, three different methods of intramedullary nailing were compared in sheep. To analyze the presence of bone marrow fat embolism in pulmonary arteries, histological evaluation was undertaken using a quantitative computer-assisted measurement system. MethodsIn this experimental model of 27 female Swiss alpine sheep, an osteotomy of the proximal femur was conducted in each animal. Then, the animals were divided into three groups according to the method of treatment: two different reamed intramedullary nailing techniques and an unreamed nailing technique were used.In the first group “ER” (experimental reamer; n=9), the nail was inserted after reaming with an experimental reamer; in the second group “CR” (conventional reamer; n=7), the intramedullary nail was inserted after reaming with the conventional AO-reamer. In the third group “UN” (unreamed; n=8) unreamed nailing was performed. During the operation procedure intramedullary pressure was measured in the distal fragment.After sacrificing the animals, quantitative histological analyses of bone marrow fat embolism in pulmonary arteries were done using osmium tetroxide fixation and staining of the fat. ResultsThe measurement of intramedullary pressure showed significantly lower values for reamed nailing than for the unreamed technique. The quantitative histological evaluation of lung vessels concerning bone marrow fat embolism revealed a statistically significant difference between reamed and unreamed insertion of the nail: 7.77%±6.93 (ER) and 6.66%±5.61 (CR) vs. 16.25%±10.05 (UN) (p<0.05) of the assessed lung vessels were filled with fat emboli. However, no difference was found between the traditional and experimental reamer. ConclusionsIntramedullary nailing after reaming is a safe procedure with low systemic embolisation when compared to the unreamed insertion of the nail.

Cardiovascular changes after PMMA vertebroplasty in sheep: the effect of bone marrow removal using pulsed jet-lavage

Clinically, the displacement of intravertebral fat into the circulation during vertebroplasty is reported to lead to problems in elderly patients and can represent a serious complication, especially when multiple levels have to be treated. An in vitro study has shown the feasibility of removing intravertebral fat by pulsed jet-lavage prior to vertebroplasty, potentially reducing the embolization of bone marrow fat from the vertebral bodies and alleviating the cardiovascular changes elicited by pulmonary fat embolism. In this in vivo study, percutaneous vertebroplasty using polymethylmethacrylate (PMMA) was performed in three lumbar vertebrae of 11 sheep. In six sheep (lavage group), pulsed jet-lavage was performed prior to injection of PMMA compared to the control group of five sheep receiving only PMMA vertebroplasty. Invasive recording of blood pressures was performed continuously until 60 min after the last injection. Cardiac output and arterial blood gas parameters were measured at selected time points. Post mortem, the injected cement volume was measured using CT and lung biopsies were processed for assessment of intravascular fat. Pulsed jet-lavage was feasible in the in vivo setting. In the control group, the injection of PMMA resulted in pulmonary fat embolism and a sudden and significant increase in mean pulmonary arterial pressure. Pulsed jet-lavage prevented any cardiovascular changes and significantly reduced the severity of bone marrow fat embolization. Even though significantly more cement had been injected into the lavaged vertebral bodies, significantly fewer intravascular fat emboli were identified in the lung tissue. Pulsed jet-lavage prevented the cardiovascular complications after PMMA vertebroplasty in sheep and alleviated the severity of pulmonary fat embolism.

Influence of Bone Marrow Fat Embolism on Coagulation Activation in an Ovine Model of Vertebroplasty

Intraoperative cardiovascular deterioration as a result of pulmonary embolization of bone marrow fat is a potentially serious complication during vertebroplasty. The release of fatty material and thromboplastin from the bone marrow cavity during vertebroplasty may activate the coagulation cascade resulting in thrombogenesis, and pharmacological prophylaxis may therefore prevent cardiovascular complications. Thus, the effects of bone marrow fat embolism on coagulation activation during vertebroplasty were investigated with use of an animal model. Polymethylmethacrylate was injected into three lumbar vertebrae of six sheep in order to force bone marrow fat into the circulation. Invasive blood pressures and heart rate were recorded continuously until sixty minutes after the last injection. Cardiac output, arterial and mixed venous blood gas parameters, and coagulation parameters were measured at selected time-points. Postmortem lung biopsy specimens were assessed for the presence of intravascular fat. Embolization of bone marrow fat resulted in a sudden and dramatic increase in mean pulmonary arterial pressure and a decrease in mean arterial blood pressure. There were no significant changes in any coagulation parameter from before the injection to after the injection. Intravascular fat and bone marrow cells were present in all lung lobes. Injection of polymethylmethacrylate into vertebral bodies caused embolization of bone marrow fat with subsequent transient cardiovascular deterioration, but no changes in coagulation parameters were observed. Thromboembolism did not contribute to the observed cardiovascular changes.

Plasma levels of endothelin‐1 after a pulmonary embolism of bone marrow fat

During orthopedic surgery, embolization of bone marrow fat can lead to potentially fatal, intra-operative cardiovascular deterioration. Vasoactive mediators may also be released from the bone marrow and contribute to these changes. Increased plasma levels of endothelin-1 (ET-1) have been observed after pulmonary air and thrombo-embolism. The role of ET-1 in the development of acute cardiovascular deterioration as a result of bone marrow fat embolization during vertebroplasty was therefore investigated. Bone cement was injected into three lumbar vertebrae of six sheep in order to force bone marrow fat into the circulation. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output, arterial and mixed venous blood gas parameters and plasma ET-1 concentrations were measured at selected time points. Post-mortem, lung biopsies were taken for analysis of intravascular fat. Cement injections resulted in a sudden (within 1 min) and severe increase in pulmonary arterial pressure (>100%). Plasma concentrations of ET-1 started to increase after the second injection, but no significant changes were observed. Intravascular fat and bone marrow cells were present in all lung lobes. Cement injections into vertebral bodies elicited fat embolism resulting in subsequent cardiovascular changes that were characterized by an increase in pulmonary arterial pressure. Cardiovascular complications as a result of bone marrow fat embolism should thus be considered in patients undergoing vertebroplasty. No significant changes in ET-1 plasma values were observed. Thus, ET-1 did not contribute to the acute cardiovascular changes after fat embolism.

Sildenafil Prevents Cardiovascular Changes after Bone Marrow Fat Embolization in Sheep

Sudden, intraoperative cardiovascular deterioration as a result of pulmonary embolization of bone marrow fat is a potentially fatal complication during total hip and knee arthroplasty, intramedullary nailing, and spine surgery. Anesthetic management is challenging in the presence of increased right ventricular afterload due to pulmonary hypertension. Selective pulmonary vasodilation may be an appropriate prophylactic or therapeutic measure. The effect of sildenafil (phosphodiesterase inhibitor) on cardiovascular deterioration after bone marrow fat embolization was therefore investigated. Bone cement (polymethylmethacrylate) was injected into three lumbar vertebrae in 12 sheep. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output and arterial and mixed venous blood gas variables were measured at selected time points. Before the first cement injection, 6 animals received a bolus injection (0.7 mg/kg) of sildenafil, with continuous infusion (0.2 mg . kg . h) thereafter. Postmortem lung and kidney biopsies were taken for semiquantitative analysis of intravascular fat. Fat embolism was associated with a transient increase (21 +/- 7mmHg) in pulmonary arterial pressure. A transient decrease in arterial blood pressure and temporary increases in central venous pressure and dead space were also observed. No significant changes in any cardiovascular variable were observed after fat embolism in the sildenafil group. There was significantly (P < 0.05) less intravascular fat in the lungs of the sildenafil (median count of 5 emboli per microscopic view) compared with the control group (median count of 1). Administration of sildenafil prevented the acute cardiovascular complications after bone marrow fat embolism in sheep.

Lungs in Hemoglobinopathies, Erythrocyte Disorders, and Hemorrhagic Diatheses

The erythropoietic system plays a major role in tissue oxygenation because the erythrocytes are the primary carriers of oxygen in the form of oxyhemoglobin. Therefore, clinical entities such as abnormal hemoglobins, polycythemia, anemia, and significant changes in blood volume frequently produce alterations in various respiratory functions. The pulmonary manifestations can vary from mild respiratory illness to life-threatening emergencies with high mortality rates. Among the hemoglobinopathies, sickle cell disease is clinically the most important and commonly associated with serious pulmonary consequences, including acute chest syndrome, pneumonia, infarction due to in situ thrombosis, bone marrow fat embolism of pulmonary vasculature, bone marrow infarction, pulmonary hypertension, and other abnormalities. Hemoglobinopathies with high and low affinity for oxygen and other abnormal hemoglobinopathies occasionally cause clinically significant respiratory complications by interfering with normal tissue oxygenation. Acquired methemoglobinemia can cause alarming cyanosis and medical emergency. Erythrocyte disorders are associated with pulmonary complications, including pulmonary hypertension, alveolar fibrosis, and pulmonary dysfunction. Coagulation disorders, both the inherited and acquired types, have the potential to affect the respiratory system in the form of hemorrhage from the airways, lung parenchyma, or pulmonary hypertension. The following paragraphs describe the common pulmonary complications and manifestations associated with hemoglobinopathies, erythrocyte disorders, and coagulation abnormalities.

Fat embolism and related effects during reamed and unreamed intramedullary nailing in a pig model.

To determine whether reamed or unreamed femoral intramedullary nailing is more adverse to pulmonary function, the authors compared three populations of healthy pigs, analyzing the biochemical and hemodynamic effects related to fat embolism. Likewise, the authors histologically evaluated the presence of bone marrow fat embolism in lungs, heart, kidney, brain, and retina. Randomized, experimental model. Laboratory. Twenty-five male Duroc Jersey adult healthy pigs divided in three groups. Reamed and unreamed intramedullary nailing. Biochemical, hemodinamical, and histologic analysis. In the first group of ten pigs, a reamed nail was inserted; in the second group of ten specimens, the authors placed an unreamed nail; and in the third group of five animals (control), only the surgical approach was made without opening the medullary cavity. The authors did not find statistically significant differences in pulmonary function between the reamed and unreamed group in the hemodynamic, biochemical, and histopathologic parameters evaluated. The histologic analysis of the lung tissue revealed a statistically significant difference between the nailed groups and the control (P < 0.04). In this animal model, the results indicate that pulmonary changes and fat embolization during intramedullary nailing occur to the same degree in reamed and in unreamed femurs.

Intramedullary Pressure and Bone Marrow Fat Extravasation in Reamed and Unreamed Femoral Nailing

This study was designed to investigate whether intramedullary pressure and embolization of bone marrow fat are different in unreamed compared with conventional reamed femoral nailing in vivo. In a baboon model, the femoral shaft was stabilized with interlocking nailing after a midshaft osteotomy. Intramedullary pressure was measured in the distal femoral shaft fragment at the supracondylar region. Extravasation of bone marrow fat was determined by the modified Gurd test (range: 0–5) with blood samples from the vena cava inferior. Data were monitored in eight unreamed and eight reamed intramedullary femoral nailing procedures. Intramedullary pressure increased in the unreamed group to 76 ± 25 mm Hg (10.1 ± 3.3 kPa) during insertion of 7-mm nails and in the reamed group to 879 ± 44 mm Hg (117.2 ± 5.9 kPa) during reaming of the medullary cavity. Insertion of 9-mm nails after the medullary cavity had been reamed to 10 mm produced an intramedullary pressure of 254 ± 94 mm Hg (33.9 ± 12.5 kPa) (p < 0.05). Fat extravasation in the unreamed group was recorded with a score of 2.9 ± 0.4 for the Gurd test during nailing with 7-mm nails, whereas in the reamed group significantly more fat extravasation was noticed during the reaming procedures, with a score of 4.6 ± 0.1. Liberation of fat during insertion of 9-mm nails after reaming was recorded with a score of 3.5 ± 0.4. In both groups, a positive correlation of fat extravasation with the rise in intramedullary pressure was found (reamed group: rs = 0.868: unreamed group: rs = 0.698), resulting in significantly less liberation of bone marrow fat in the unreamed stabilized group than in the reamed control group (p < 0.05). The data indicate that fat embolization during nailing procedures after femoral osteotomy increases with increasing intramedullary pressure and occurs in a lesser degree in unreamed than in reamed intramedullary femoral shaft stabilization.