Bone Marrow Embolism Research Articles

Nachweis von Markembolien wÄhrend Oberschenkelmarknagelungen mittels transösophagealer Echokardiographie

Cardiopulmonary complications are known in intramedullary nailing, especially of the femur. Transesophageal echocardiography now allow intraoperative detection of embolized bone-marrow, recognizable as reflecting particles in the right atrium. In intramedullary nailing of a femoral fracture with a closed distal fragment bone-marrow embolism was detectable in the right atrium during reaming of the medullary canal. This technique should permit further research on the pathophysiology of pulmonary alterations during intramedullary nailing and also testing the effectiveness of pressure-relief in the medullary canal as proposed by drilling a bone-hole.

Bone marrow embolism following cryosurgery of bone: An experimental study

Cryosurgery is commonly used in medicine for treatment of benign and malignant lesions. We had clinical and experimental data indicating that cryosurgery of intact bone could cause bone marrow intravasation and embolism, i.e., particles of bone marrow entering extraosseous veins and occluding pulmonary vasculature. This study was designed to investigate the pathogenesis of bone marrow intravasation and embolism after cryosurgery. Three hypotheses on the pathogenesis of bone marrow intravasation were tested using a model of cryosurgical continuity lesion in rats and rabbits. Influence of physical and circulatory factors were excluded supporting a mechanical-biological hypothesis; the intravasation of bone marrow after cryosurgery of bone is caused by an increased intramedullary pressure. The increased intramedullary pressure is due to edema in the medullary cavity caused by cryosurgical damage to cell membranes. It is demonstrated that the bone marrow intravasates can embolize to the lungs causing respiratory insufficiency. This can be a serious complication following cryosurgery of intact bone. Prophylactic decompression of the medullary cavity can possibly prevent the rise in intramedullary pressure and thus intravasation and embolisation of bone marrow after cryosurgery of intact bone.

Effect of Heparin on Increased Pulmonary Microvascular Permeability after Bone Marrow Embolism in Awake Sheep

We examined the alterations in pulmonary transvascular fluid and protein exchange after intravenous infusion of fat emboli, i.e., bone marrow suspension (BMS) in awake sheep prepared with chronic lung lymph fistulas and compared these changes with those observed in sheep pretreated with heparin. The BMS injection (0.2 ml/kg) over 15 min caused rapid, but transient, increases (p less than 0.05) in mean pulmonary artery pressure and pulmonary vascular resistance. These increases were accompanied by significant increases in the lymph concentrations of thromboxane B2 and 6-keto-PGF1 alpha. Pulmonary lymph flow increased by 3.9-fold (+/- 0.8) over baseline by 120 min after BMS with no change in the lymph-to-plasma protein concentration ratio (L/P ratio). Heparin pretreatment (700 U/kg) enhanced the BMS-induced increases in pulmonary artery pressure and pulmonary vascular resistance. Thromboxane B2 concentrations in the lymph increased, whereas there was no change in the concentration of 6-keto-PGF1 alpha. Lung lymph flow increased 4-fold (+/- 1.0) over baseline by 120 min after BMS without a change in L/P ratio. Changes in lung vascular permeability were evaluated by elevating pulmonary microvascular pressure (left atrial balloon catheter inflation) at 120 min after BMS. Lung lymph flow increased 7-fold (+/- 1.1) from baseline, whereas the L/P ratio decreased to a mean value of 0.48 +/- 0.03. The protein reflection coefficient (sigma = 1 - L/P ratio) decreased from a control mean of 0.69 +/- 0.02 to 0.52 +/- 0.03 after the BMS challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

PATHOLOGY OF EXPERIMENTAL PULMONARY BONE MARROW EMBOLISM

The author investigated the morphogenesis of pulmonary arteriosclerosis in rabbits at 2 days to 3 months after the infusion of sliced fresh allogeneic bone marrow (500 mg) into the marginal ear vein of 87 rabbits. After 2 to 7 days, granulation tissue was formed in the embolized bone marrow, and new endothelial cells appeared on the surface resulting in recanalization. By 2 weeks, embolized bone marrow developed into fibrous and fibro‐fatty plaques in the arterial wall. Moreover, from 4 weeks on, smooth muscle cells and elastic fibers proliferated in the emboli just beneath the new endothelial lining. The intima of non‐embolized small arteries showed circumferential fibroelastosis, as the result of arteritis and followed by proliferation of medial smooth muscle cells, with narrowing of vascular lumen. The medial smooth muscle cells play an important role in the morphogenesis of pulmonary arteriosclerosis in bone marrow embolism. Pulmonary arterial pressure gradually increased 1 month as well as 3 months after the infusion. It Is considered that narrowing of the vascular lumen resulted from post‐embolic pulmonary arteriosclerosis may produce persistent pulmonary hypertension.

Lung lymph flow after bone marrow injection into goats was reduced by indomethacin.

We examined the pulmonary response to bone marrow embolism in untreated and indomethacin-treated goats. Pulmonary arterial pressure increased by 15 cmH2O after bone marrow infusion, reaching a peak of 37.2 then stabilizing at greater than 30 cmH2O in the control group. In the treated group it increased by 4.3 cmH2O from a base line of 18.5 cmH2O but had returned to base line by 6 h. Lymph flow increased in the control group from a base line of 7.3 ml/h to a peak of 22.4 ml/h and remained near that level. It increased from a base line of 6.4 ml/h to a peak of 9.8 ml/h in the treated group and remained close to that value. The lymph-to-plasma protein ratio was little changed throughout the experiment. Cardiac output decreased by 1.2 l/min in the control group but was unchanged from base line in the treated group. Systemic arterial pressure was similar in both groups of animals. We conclude that indomethacin prevents the pulmonary hypertension seen after bone marrow infusion and protects against some of the increased permeability.

Is pain crisis a cause of death in sickle cell disease?

It has been a matter of controversy as to whether patients with sickle cell disease die of crisis or merely in crisis. The authors reviewed the 74 patients with sickle cell disease autopsied at The Johns Hopkins Hospital. From clinical review, there were 20 (27%) who died with pain crisis, 51 (69%) who died without pain crisis, and 3 (4%) for whom documentation was insufficient. On pathology review, death was attributable to infection in 19 (26%), uremia in 9 (12%), sequestration crisis in 9 (12%), necrotic bone marrow emboli in 7 (9%), and miscellaneous causes in 14 (19%); in 16 (22%) patients no cause of death could be identified. Death was explained in 47/51 (92%) patients without pain crisis; but only in 11/20 (55%, P less than 0.01) patients dying in pain crisis. The disproportionately large number of patients dying in pain crisis with an unexplained cause of death suggests that pain crisis may account for the death of some patients with sickle cell disease.

Bone Marrow Emboli Versus Fat Emboli as the Cause of Unexpected Death

Thromboemboli were found diffusely throughout the pulmonary vasculature system of a 76-year-old white female who died unexpectedly 3 days following injury and repair of a left hip intracapsular fracture. A diffuse chronic nonspecific myocarditis with marked fat atrophy, an acute myocardial infarct of the posterior left ventricular papillary muscle, and an acute right lower lobe bronchopneumonia are believed to be the cause of death.

PATHOLOGY OF EXPERIMENTAL PULMONARY BONE MARROW EMBOLISM

In order to investigate the initial lesions of pulmonary bone marrow embolism and its pathogenesis, the author studied the pulmonary changes of 70 rabbits during a 24‐hour period after the Infusion of 500 mg of fresh allogeneic bone marrow into the marginal ear veins. After 30 minutes, leukostasis was observed in the non‐embolized small arteries. After 2 hours, leukostasis increased and by 5 to 10 hours, it reached a maximum, still decreased considerably after 24 hours. In the perivascular connective tissue, edema and inflammatory cell infiltration had occurred as a result of Increased vascular permeability due to leukostasis. Fifteen minutes after intravenous administration of a single shot of indomethacln (5 mg/kg), the Infusion of allogeneic bone marrow was performed. Five hours after the infusion, the suppression of pulmonary vascular leukostasis and interstitial edema were observed. The effect of drugs on morphological changes, however, is extremely small in the group pre‐treated with diphenhydramine hydrochloride (3 mg/kg). The author concluded that the mechanical Injury of vascular endothelial cells by emboli and the accumulation of leukocytes in the pulmonary vessels may play an important role in the pathogenesis of the initial change of pulmonary bone marrow embolism. It is also suggested that the embolized bone marrow in the small arteries and vasculitis may lead to arteriosclerosis in the future.

Pathogenesis of circulatory reactions triggered by nervous reflexes during the implantation of bone cements.

Circulatory and respiratory reactions during the implantation of joint endoprostheses have been observed for years. The components of the bone cements used for anchoring (methyl methacrylate monomer) or the outpour of bone marrow substances from the affected bone marrow cavity are thought to be chiefly responsible for these effects. However, our previous investigations demonstrated unambiguously that reactions of this type can be attributed to direct nervous-reflex mechanisms triggered by the pressure rise in the medullary canal, and that, in addition, bone marrow embolism plays a part in serious circulatory incidents. The investigations on which the present paper is based have confirmed the mechanism of circulatory reactions triggered by direct nervous reflex and have shown once again that the release of cement monomers is not of any significance, at least not in animal experiments. In regard of the characteristics of these reflex processes, it has been possible to show by both surgical and pharmacologic interventions in the vegetative nervous system, performed before and during pressure experiments, that these reflex processes are caused not so much by an increase of the vagus tone as by a central inhibition of the sympathicus. Neither administrations of atropine nor bilateral cervical vagotomy are able to prevent the reactions. This was only possible under the influence of a ganglion blocker.

Pulmonary fat and bone marrow embolism in aircraft accident victims

On 28 November 1979, an Air New Zealand DC10 aircraft crashed into Mt Erebus, Antarctica with the loss of 257 passengers and crew. Postmortem examinations were carried out on 231 victims in Auckland, 4641 kilometres north of the crash site, and lung tissue was present in 205 cases. Pulmonary fat emboli were present in 134 cases (65%), pulmonary bone marrow emboli in 60 (29%) and pulmonary edema in 76 cases (37%). Clear relationships were demonstrated, firstly between the extent of fat and bone marrow embolism, secondly between the extent of fat and bone marrow embolism and the presence of pulmonary edema, and thirdly between the extent of fat and bone marrow embolism and the extent of cardiovascular damage. It was apparent that death had occurred immediately following impact, and the extent of fat and bone marrow embolism varied inversely with the severity of the injuries found. The most severely injured victims were those seated in the rear cabin of the aircraft suggesting that this was the site of impact with the ground. Our studies show that pulmonary fat embolism occurs very rapidly after severe injury and is followed by increasing numbers of fat and bone marrow emboli depending on the nature of the mortal injuries.

Role of intravascular coagulation and granulocytes in lung vascular injury after bone marrow embolism.

Role of intravascular coagulation and granulocytes in lung vascular injury after bone marrow embolism.

Occurrence of pulmonary fat and bone marrow embolism.

The lungs of 136 persons dying as a result of road traffic accidents were studied retrospectively for the presence of fat and bone marrow emboli. Comparable investigations were made in 54 cases of acute myocardial failure reported to the medicolegal authorities and in 50 cases of fatal drug overdose. A further 50 cases of myocardial failure dying in hospital were studied for the presence of bone marrow embolism only. It was considered that despite occurrence of an occasional anomalous case, both fat and bone marrow emboli are related to injury but that the incidence and severity of bone marrow embolism in particular depends greatly upon the conditions of the accidental death. The occurrence of pulmonary embolic phenomena in cases of natural death was attributed to resuscitative measures rather than the underlying condition. The results indicated that the medicolegal significance attached to the findings should, by themselves, be limited to the positive identification of injuries sustained before or at the time of death in the individual case.

Pulmonary fat and bone marrow embolism in aircraft accident victims

On 28 November 1979, an Air New Zealand DC10 aircraft on a scenic flight to Antarctica crashed with the loss of 257 passengers and crew. Postmortem examinations were carried out on 231 of the victims, and lung tissue was present in 205 of these. Twelve blocks of lung tissue from each victim were examined, 6 for the presence of fat emboli and 6 for bone marrow emboli. Pulmonary fat emboli were present in 65% of the victims, and pulmonary bone marrow emboli were seen in 29% of the victims. Pulmonary oedema was seen in 36% of the victims. There was a positive correlation between the presence of pulmonary oedema and the severity of fat and bone marrow embolism, all of which varied inversely with the severity of injury. On 28 November 1979, an Air New Zealand DC10 aircraft on a scenic flight to Antarctica crashed with the loss of 257 passengers and crew. Postmortem examinations were carried out on 231 of the victims, and lung tissue was present in 205 of these. Twelve blocks of lung tissue from each victim were examined, 6 for the presence of fat emboli and 6 for bone marrow emboli. Pulmonary fat emboli were present in 65% of the victims, and pulmonary bone marrow emboli were seen in 29% of the victims. Pulmonary oedema was seen in 36% of the victims. There was a positive correlation between the presence of pulmonary oedema and the severity of fat and bone marrow embolism, all of which varied inversely with the severity of injury.

PULMONARY BONE MARROW EMBOLISM: A REVIEW OF 350 NECROPSY CASES

Of a total of 350 necrospy cases, 71 were instances of pulmonary bone marrow embolism. The number of emboli did not vary significantly depending on whether the destruction of bone marrow was observed or not. However, the size of emboli and the number of nucleated cells increased in cases in which the destruction of bone marrows was observed. In other words, when the bones and bone marrows were destroyed to some extent, the size of emboli increased. In contrast with this, the number of emboli did not vary significantly depending on the magnitude of the destruction of bones and bone marrows. Of a total of 62 cases of which clinical histories were available, 60 were instances in which cardiac massage was carried out. The numbers and sizes of emboli varied significantly depending on whether cardiac massage was carried out or not. In other words, the number of bone marrow emboli was significantly high in cases in which cardiac massage was carried out. We suggested that cardiac massage was the most important of all predisposing factors of bone marrow embolism.

Unusual cardiac, renal and pulmonary involvement in Gaucher's disease: Interstitial glucocerebroside accumulation, pulmonary hypertension and fatal bone marrow embolization

A 25 year old black woman who had manifestations of Gaucher's disease since one year of age is described. This patient had clinically significant cardiac, renal and pulmonary involvement with Gaucher's disease. Interstitial infiltration of the myocardium by Gaucher cells caused decreased left ventricular compliance and decreased cardiac output. In the kidney, Gaucher cells were present in the mesangium of the glomeruli and the interstitium of the cortex. Also, electron dense, intramembranous granular deposits were seen in glomeruli on electron microscopy. The pulmonary findings included pulmonary arterial hypertension, accentuated basilar deposition of glucocerebroside in the interstitium of alveolar septums and fatal bone marrow embolization.

STROKE SYNDROME IN SICKLE CELL DISEASE (SCD)

To delineate the natural progression of cerebral vascular accidents in SCD and to determine the resultant structural and functional defects we investigated 29 patients (27 SS, 2 SC) who sustained strokes. Subarachnoid or intra-cerebral hemorrhage and bone marrow embolism occurred in 9 patients ages 14-35 years. Cerebral infarction occurred in 20 (19 SS, 1 SC) with a modal age of onset of 5 years. We were able to evaluate 14 long term survivors who were observed for a mean period of 9.4 years following the initial stroke. 10 (71%) had 1 or more recurrences with a mean interstroke interval of 28 months. Residual functional impairment was noted in all 14. Computerized axial tomography on 9 showed areas of low density and ventricular dilatation indicating structural brain damage. These patients were not treated with a transfusion program. Their clinical course indicates that evaluation of such therapy requires long periods of observation.

Fatal Bone-Marrow Pulmonary Emboli in Multiple Myeloma

Letters1 March 1977Fatal Bone-Marrow Pulmonary Emboli in Multiple MyelomaPATRICK J. MCCARTHY, M.D., BARRY M. SHMOOKLER, M.D., LAWRENCE E. PIERCE, M.D., F.A.C.P.PATRICK J. MCCARTHY, M.D.Search for more papers by this author, BARRY M. SHMOOKLER, M.D.Search for more papers by this author, LAWRENCE E. PIERCE, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-3-317 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptBone-marrow pulmonary embolism may, on occasion, be a primary or contributory cause of death (1). A sudden fatal outcome after pulmonary bone-marrow embolization in a patient with multiple myeloma was reported by Knoblich and Kreiner (2), but to our knowledge, no additional instances have been published. This report describes a patient with refractory multiple myeloma complicated by poorly understood recurrent dyspneic episodes with hypoxia. The basis for these episodes became apparent at postmortem examination that showed bilateral multiple embolic myelomatous bone-marrow particles occluding primarily medium and smaller branches of the pulmonary artery.A 67-year-old black man was admitted to the...

Pulmonary Embolism by Hepatic Tissue After External Cardiac Massage

To the Editor.— A 45-year-old woman who had been anephric by surgery and on hemodialysis three times a week for three years had a terminal respiratory arrest. She received external cardiac massage for one hour, but could not be resuscitated. Autopsy revealed a fracture of T6, right hemothorax, left ventricular hypertrophy, and pericarditis. The liver was unremarkable on gross examination. However, microscopic examination revealed pulmonary embolism by hepatic tissue, along with bone marrow and fat emboli (Fig 1 and 2). We speculate that external cardiac massage was instrumental in producing pulmonary embolism by hepatic tissue. To our knowledge, all previously reported cases of pulmonary embolism by hepatic tissue were caused by catastrophic traumatic injuries.1,2

Fat embolism in forensic pathology

The subject of fat embolism must be taken in conjunction with bone marrow embolism and can be considered on anatomical and on clinical grounds. From the forensic aspect, the incidental finding is of major importance as the discovery of pulmonary fat or bone marrow embolism at autopsy should be proof of bone injury having been sustained in life. This hypothesis has been tested by studying 400 aviation fatalities with fracture. The overall incidence of pulmonary fat embolism was 63% (37% of significant degree) and of bone marrow embolism 33%. The occurrence of both was directly associated with an intact cardiovascular system and with the time taken to die but was inversely related to the degree of bone injury. Fat embolism was found to be a more sensitive index of ante-mortem trauma but bone marrow embolism is a more specific marker of fracture. When correlated with carboxyhaemoglobin levels in those persons exposed to fire, a small number of anomalous cases of embolism of both positive and negative nature were observed. Provided this possibility, and the effect of attempted resuscitation, is taken into account, the use of pulmonary fat embolism as an indicator of ante-mortem trauma is a most valuable tool in forensic pathology. Pulmonary fat embolism is unlikely to be fatal. When the hydrostatic effect of arteriolar blockage results in capillary involvement, the occasionally fatal condition of systemic embolism develops. This is of forensic importance in so far as it must raise the possibility of novus actus interveniens.

PULMONARY BONE MARROW EMBOLISM

Bone marrow embolism (BME) was found in 80 out of 507 consecutive autopsies (15.7 per cent). BME was associated with accident in more than 50 per cent and with cardiac disease in approximately 25 per cent of the cases. Mechanisms for the production of BME other than fracture must be sought since 8 per cent of the cases did not have any bone involvement. BME should not be considered proof of antecedent intravital trauma and pulmonary BME did not appear to have any clinical significance.