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Pathogenesis of hemorrhage induced by bilitoxin, a hemorrhagic toxin isolated from the venom of the common cantil (Agkistrodon bilineatus bilineatus).

The pathogenesis of hemorrhage induced by the i.m. injection of the hemorrhagic toxin, bilitoxin, was studied using light and electron microscopy. White mice were injected with sublethal doses of the toxin, and tissue samples were obtained at 5 and 30 min, and 1, 3 and 24 hr after the injection. There was a good correlation between amount of toxin injected and amount of hemorrhage observed. Microscopically, hemorrhage was visible in all parts of the connective tissue surrounding muscle cells just 5 min after injection and fibrin was present both intravascularly and extravascularly. At later time periods the hemorrhage was more extensive and there was more fibrin. Many vessels were plugged with platelets. At 30 min after the injection, muscle cells appeared to be damaged having either delta lesions or disrupted myofibrils. Electron microscopy revealed damaged capillaries with ruptured endothelial cells, disrupted basal lamina and intact intercellular junctions. Thus, this hemorrhagic toxin acts rapidly to disrupt the capillary endothelium without damaging the intercellular junctions, and it also appears to damage skeletal muscle cells.

Animals↗

Lack of lung hemorrhage in humans after intraoperative transesophageal echocardiography with ultrasound exposure conditions similar to those causing lung hemorrhage in laboratory animals.

This study investigated the phenomenon of ultrasonically induced lung hemorrhage in humans. Multiple experimental laboratories have shown that diagnostic ultrasound exposure can cause hemorrhage in the lungs of laboratory animals. The left lung of 50 patients (6 women, 44 men, mean age 61 years) was observed directly by the surgeon after routine intraoperative transesophageal echocardiography was performed. From manufacturer specifications the maximum derated intensity in the sound field of the system used was 186 W/cm2, the maximum derated rarefactional acoustic pressure was 2.4 MPa, and the maximum mechanical index was 1.3. The lowest frequency used was 3.5 MHz. This exposure exceeds the threshold found for surface lung hemorrhage seen on gross observation of laboratory animals. No hemorrhage was noted on any lung surface by the surgeon on gross observation. We conclude that clinical transesophageal echocardiography, even at field levels a little greater than the reported thresholds for lung hemorrhage in laboratory animals, did not cause surface lung hemorrhage apparent on gross observation. These negative results support the conclusion that the human lung is not markedly more sensitive to ultrasound exposure than that of other mammals.

Adult↗

Firsthand clinical observations of hemorrhagic manifestations in Ebola hemorrhagic fever in Zaire.

About 5 weeks after the beginning of the outbreak of Ebola virus fever in Yambuku, Zaire, several acute cases of the disease were observed. All of those affected had the following common signs and symptoms: sudden onset of high fever, with chills, headache, myalgia, anorexia, nausea, abdominal pain, sore throat, expressionless face, and profound prostration. In some cases, on around the fifth day of the acute phase, the appearance of an exanthematous rash on the trunk announced the hemorrhagic manifestations: hemorrhagic conjunctivitis, bleeding ulcerations in the mouth and on the lips, gingival bleeding, hematemesis, and melena; epistaxis, ear bleeding, hematuria, and postpartum hemorrhages were also reported. All these hemorrhagic cases had a fatal outcome within about a week. The hemorrhagic manifestations were less severe in the cases that occurred by the end of the outbreak than in the first reported cases. Hemorrhagic manifestations were less frequent and less severe, or even absent, in the nonfatal cases (convalescents, serologically confirmed). No biologic investigation of the hemostatic impairment could be performed under the emergency conditions of this field study.

Adult↗

A new model of uncontrolled hemorrhage that allows correlation of blood pressure and hemorrhage.

OBJECTIVE: To compare hemodynamics, mortality rates, and bleeding rates at 3 severities of hemorrhage in a new model of uncontrolled intra-abdominal bleeding that uses an injury of varying severity and geometry unfavorable to thrombosis. METHODS: Ten swine were bled through a flow-monitored shunt placed between the femoral artery and the peritoneal cavity. The shunt was connected to catheters of varying diameters placed in the femoral artery to create 3 rates of hemorrhage. Blood flow through the shunt was measured with an in-line Doppler probe. Arterial pressures, cardiac output (CO), and ECGs were monitored. Survival and blood loss were calculated. RESULTS: The model successfully produced 3 hemorrhage severities. At all 3 rates of bleeding, blood flow was linearly related to mean arterial pressure, with R2 > 0.72. Bleeding was continuous in all groups. The mean numbers of minutes until death were 53, 45, and 25, respectively, at the increasing shock severities. Blood pressure (BP) and CO decreased continuously in all groups, but did so more rapidly with increasing severity of hemorrhage. CONCLUSIONS: In this model of uncontrolled hemorrhage, bleeding was continuous and linearly related to BP. The hemodynamic response to uncontrolled bleeding in this model differs markedly from those in previous wire aortotomy models where wound geometry is favorable to thrombosis. Hence, when injury geometry is favorable to thrombosis (as in aortotomy), thrombosis formation affects hemorrhage rates and hemodynamic responses.

Analysis of Variance↗

Subcortical cerebral hemorrhage with reference to vascular malformations and hypertension as causes of hemorrhage.

The authors have reviewed 80 cases of subcortical cerebral hemorrhage, in all of which intraoperative examinations during craniotomy or autopsies were performed. Cases involving trauma and aneurysm were excluded from the study. The diagnosis of subcortical hemorrhage was made by plain computed tomography in all cases. The most common cause of hemorrhage was vascular malformation (68%; 56 cases), in 20 (36%) of which angiographically occult vascular malformations were noted. Hypertension was present in 23 (29%) of 80 cases but was the cause of hemorrhage in only 9 cases (11%). Hypertension was present in 6 (30%) of 20 angiographically occult vascular malformations, all of which were in patients under 65 years. In 12 (75%) of 16 cases of angiographically occult vascular malformations, prolonged high-dose delayed-contrast computed tomography and magnetic resonance imaging were able to provide definite diagnostic information. We recommend that patients with subcortical cerebral hemorrhage, especially those under age 65, with or without hypertension, be carefully examined by prolonged high-dose delayed contrast computed tomography and magnetic resonance imaging for the presence of angiographically occult vascular malformations causing hemorrhage.

Adolescent↗

[Latent gastro-intestinal hemorrhages as symptoms of hemorrhagic syndrome in acute leukemia].

A clinicoradiologic investigation of latent gastrointestinal hemorrhages was conducted in acute leukemia patients with the use of 51Cr. A total of 26 patients suffering from varying forms of leukemia with no external hemorrhages were investigated. Latent gastrointestinal hemorrhages were detected in 50% of the patients. A definite relationship has been revealed between the hemorrhage degree and the leukemic process stage, in acute periods of the disease the volumes of gastrointestinal hemorrhages significantly exceed the permissible volumes. The authors have shown that the method of quantitative determination of latent gastrointestinal hemorrhages with the use of 51Cr, due to its accuracy and informative value, can be recommended for practical use and scientific investigations.

Acute Disease↗

Diffuse alveolar hemorrhages and hemorrhagic pleural effusion after thrombolytic therapy with streptokinase for acute myocardial infarction.

Thrombolytic therapy with streptokinase is commonly used in acute myocardial infarction and has markedly reduced morbidity and mortality from this condition. However, it can cause various hemorrhagic and immunological complications. We report a patient who developed diffuse pulmonary hemorrhages and bilateral hemorrhagic pleural effusion after thrombolytic therapy with streptokinase for acute myocardial infarction. This was recognized by a drop of hematocrit, pulmonary infiltrates, hemorrhagic pleural effusion and hypoxemia. The diagnosis was confirmed by demonstration of iron-laden macrophages (siderophages) in bronchoalveolar lavage. The patient required mechanical ventilation and recovered successfully. This combination of pulmonary hemorrhages and hemorrhagic pleural effusion following streptokinase therapy is extremely unusual and has not been reported previously.

Adult↗

[Acute preretinal hemorrhage before life threatening complications of subarachnoid hemorrhage].

BACKGROUND: To report on a patient with acute preretinal and intraretinal bleedings as first clinical signs of a life-threatening subarachnoid hemorrhage. PATIENT: A 36-year-old, so far healthy woman complained of decreased vision, which had started eight hours before. She presented herself in good general condition. Ophthalmoscopic evaluation showed intraretinal hemorrhages in both eyes and a preretinal hemorrhage in the left eye. During the examination, the patient fainted and suffered generalized seizure. Cranial computed tomography revealed a subarachnoid hemorrhage originating from an internal carotid artery aneurysm. CONCLUSION: Acute intraretinal and preretinal bleedings in apparently healthy patients can be precursors of eventually life-threatening complications of subarachnoid hemorrhages.

Adult↗

Decompressive hemicraniectomy for poor-grade aneurysmal subarachnoid hemorrhage patients with associated intracerebral hemorrhage: clinical outcome and quality of life assessment.

OBJECTIVE: Decompressive hemicraniectomy has been proposed as a potential treatment strategy in patients with poor-grade aneurysmal subarachnoid hemorrhage presenting with focal intracerebral hemorrhage causing significant mass effect. Although hemicraniectomy improves overall survival rates, the long-term quality of life (QoL) for survivors in this patient population has not been reported. METHODS: Using adjudicated outcome assessments, we compare long-term clinical outcomes and QoL between a group of patients with poor-grade aneurysmal subarachnoid hemorrhage receiving decompressive hemicraniectomy (n=12) and a control group of similar patients managed more conservatively (n=10). RESULTS: Patients receiving decompressive hemicraniectomy experienced a statistically insignificant decrease in short-term mortality compared with controls (25 versus 42%); however, long-term QoL in hemicraniectomy survivors was generally poor. Furthermore, hemicraniectomy patients did not experience an increase in mean quality-adjusted life years over control patients (2.31 versus 2.22 yr). CONCLUSION: Decompressive hemicraniectomy prolongs short-term survival in patients with poor-grade aneurysmal subarachnoid hemorrhage with associated intracerebral hemorrhage; however, this trend is not statistically significant, and the overall QoL experienced by survivors is poor. Decompressive hemicraniectomy may be indicated if performed early in a select subset of patients. On the basis of our preliminary data, large prospective studies to investigate this issue further may not be warranted.

Adult↗

Life-threatening pulmonary hemorrhage with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia.

The occurrence of significant pulmonary hemorrhage associated with pulmonary arteriovenous malformations (PAVMs) and hereditary hemorrhagic telangiectasia (HHT) and the incidence of PAVMs in family members of patients with PAVMs and HHT are poorly defined. We reviewed our experience in 143 patients with PAVMs and HHT. Eleven (8 percent) of the 143 patients with HHT and PAVMs had a history of either massive hemoptysis or of hemothorax which required hospitalization. One patient died directly related to the pulmonary hemorrhage. There were four men and seven women. Three of the seven women experienced pulmonary hemorrhage during pregnancy. Seven of the 11 families participated in screening for PAVMs. Thirty-six (80 percent) of the 45 screened family members were found to have HHT. Thirteen (36 percent) of the 36 family members with HHT were proven to have PAVMs by pulmonary angiography. Pulmonary hemorrhage due to spontaneous rupture of the PAVM is a potentially life-threatening complication that should be treated aggressively with transcatheter embolotherapy. It occurs more frequently than previously recognized in patients with PAVMs and HHT. In addition, because of the increased incidence of PAVMs in family members of patients with HHT and PAVM, screening of family members with HHT is recommended especially in women of childbearing age.

Adolescent↗

Hormonal responses to hemorrhage and their relationship to individual hemorrhagic shock susceptibility.

The effect of differences in sympathoadrenomedullary and pituitary-adrenocortical responses of individual animals to 35% hemorrhage on severity of shock induction has been studied in unanesthetized unrestrained rats by measuring plasma concentrations of adrenaline (A), noradrenaline (NA), corticosterone (CS) and adrenocorticotropin (ACTH). The responses of A, CS and ACTH were related to the decrease of blood volume and mean arterial pressure (MAP), whereas plasma NA remained unchanged. Higher susceptibility to blood loss was characterized by more pronounced hemorrhage-induced increase in blood lactate concentration and plasma enzyme activities as well as lethal outcome of hemorrhagic shock. In animals with irreversible hemorrhagic shock, enhanced catecholamine secretion and reduced ACTH release was observed. Furthermore, a revealed direct correlation between A and blood lactate concentration and plasma enzyme activities (aspartate aminotransferase, isocitric dehydrogenase, creatine kinase, lipase and glutathione-S-transferase) may indicate its possible participation in the mechanism of shock induction. In contrast, an inverse relationship of plasma CS to the indicators of shock severity was demonstrated. In conclusion, non-optimal neuroendocrine regulation of cardiovascular adjustments to hemorrhage in shock-prone animals might cause an exaggerated compensatory activation of adrenomedullary catecholamine secretion, which in turn has been shown to exert deleterious vascular and metabolic effects. The mechanisms responsible for reduced ACTH secretion in shock-prone animals remain to be established.

Adrenal Glands↗

A new method for quantitating hemorrhage induced by rattlesnake venoms: ability of polyvalent antivenom to neutralize hemorrhagic activity.

Polyvalent (Crotalidae) antivenin was tested for its ability to neutralize the hemorrhagic activity of two crotaline venoms when mixed with them prior to injection. Hemorrhage was measured by two methods. In the first method an intradermal injection of venom produced a hemorrhagic spot which was quantitated by measuring diameters. In the second method the amount of hemoglobin in a muscle extract was measured after i.m. injection of venom. The results show that both methods are useful for quantitating hemorrhage induced by Crotalus viridis viridis and Crotalus atrox venoms. Antivenin neutralized the hemorrhagic activity of 240 micrograms C. v. viridis venom and 120 micrograms C. atrox venom per 0.05 ml. The question remains, can antivenin neutralize this amount of venom when injected independently of venom.

Animals↗

Evaluation of the effect of aqueous extract of Croton urucurana Baillon (Euphorbiaceae) on the hemorrhagic activity induced by the venom of Bothrops jararaca, using new techniques to quantify hemorrhagic activity in rat skin.

Aqueous extracts of Croton urucurana (Sangra D'agua), a plant popularly considered a cicatrizant, were analyzed for anti-Bothrops jararaca venom activity. The plant extracts antagonized the hemorrhagic activity of the venom and proanthocyanidins were involved in this activity. Two new methods for the quantification of hemorrhagic activity evoked by bothropic venoms were employed. The first consists of graphic computer analysis of the hemorrhagic halo evoked in rats by dorsal intradermic administration of venom. The second method involves quantification of the hemoglobin present in the hemorrhagic halo. Based on the results, we suggest that these methods, easily implemented in the laboratory routine, allow for quantification of venom-induced hemorrhagic activity. In addition, this study demonstrates that the rich extracts of proanthocyanidins are powerful inhibitors of bothropic venom metalloproteinases.

Animals↗

Pulmonary hemorrhage syndrome associated with an autochthonous case of dengue hemorrhagic fever.

Dengue fever is a major public health problem worldwide. Dengue hemorrhagic fever, a much rarer form of the disease, occurs when a person previously infected with dengue is re-infected with a different viral serotype. In recent years the infection rates of dengue and both clinical syndromes have increased along the United States-Mexico border. We present the case of a 61-year-old Laotian female who presented with a 1-week history of fever, altered mental status, oral ulceration, and rash. The patient developed diffuse pulmonary hemorrhage and anemia requiring multiple transfusions. She eventually sustained multi-organ system failure and expired. Both the titer data and serologies were consistent with the diagnosis of dengue hemorrhagic fever. We hypothesize that this syndrome was the result of re-infection occurring within the United States. This case is also unusual in that it is the second reported in the literature of pulmonary hemorrhages associated with dengue hemorrhagic fever.

Fatal Outcome↗

Toxic products in hemorrhagic ascitic fluid generated during experimental acute hemorrhagic pancreatitis in dogs and a treatment which reduces their effect.

Toxic substances produced in hemorrhagic ascitic fluid during experimental hemorrhagic pancreatitis in dogs were investigated. An average of 394 ml of ascitic fluid was produced within 5 h after the induction of acute pancreatitis by intraductal injection of a mixture of autologous bile and trypsin. Hemorrhagic ascitic fluid was collected under sterile conditions, which was confirmed by aerobic and anaerobic culture and a Limulus test. The sterile fluid was injected intraperitoneally into mice in doses of 2 and 3 ml, and the mortality rate 72 h after injection was 66.0 and 88.4%, respectively. It contained high concentrations of pancreatic enzymes, including trypsin and esterase activity, as well as bradykinin, histamine and prostaglandin. Autopsy and histological examination of mice revealed shock with lung damage. The results suggest that hemorrhagic ascitic fluid produced in pancreatitis may be an important factor for early deaths in acute pancreatitis. When a new synthetic antiprotease (nafamstat mesilate) in a dosage of 0.2 mg was mixed with 1 ml of ascitic fluid, trypsin was not detectable, and bradykinin was reduced 1.0 ng/ml from 8.0 ng/ml, while esterase activity decreased to one tenth of its previous activity. The mortality following injection of the solution decreased to 26.7 and 80.6%, respectively. These results indicate that peritoneal lavage with a solution containing antiprotease may be an effective treatment for hemorrhagic acute pancreatitis.

Acute Disease↗

Perimesencephalic hemorrhage: a nonaneurysmal and benign form of subarachnoid hemorrhage.

We studied 28 patients with subarachnoid hemorrhage and normal angiograms. On early CT (within 5 days) in 13 cases, blood was seen mainly or only in the cisterns around the midbrain. This pattern of hemorrhage was found in only 1 of 92 patients with a ruptured aneurysm. None of the unexplained perimesencephalic hemorrhages was associated with intracerebral hematoma or intraventricular hemorrhage. The clinical features also differed from those of aneurysmal hemorrhage; loss of consciousness was rare, and after 3 months, all 13 patients had returned to normal life. The cause of this benign disorder remains elusive, but a venous or capillary source seems likely.

Humans↗

Fatty liver hemorrhagic syndrome in hens overfed a purified diet. Selected enzyme activities and liver histology in relation to liver hemorrhage and reproductive performance.

A nutritionally adequate, purified diet was developed and used in studies to characterize selected aspects of laying hens in which fatty liver hemorrhagic syndrome (FLHS) was induced by overfeeding. Hens consuming the diet ad libitum or intubated with the diet in quantities equivalent to usual daily energy intake maintained normal rates of lay, did not become obese, and did not develop liver hemorrhage. Overfed hens had a 33% incidence of FLHS, as indicated by the presence of severe liver hemorrhage score, and displayed the full range of symptoms associated with spontaneous outbreaks of FLHS, including definitive lesions of hepatic reticulin. Among four groups of hens clinically classified according to rates of liver hemorrhage and egg production, there were no differences noted in total liver fat, liver fat concentration, or final body weight. Liver hemorrhage was associated with the degree of induction of liver lipogenic accessory enzymes. Serum enzyme activities indicate that overfed hens, unlike the overfed goose, retain hepatocellular membrane integrity. Overfeeding caused altered reproductive performance in 72% of hens. Alterations included erratic laying, increased incidence of double ovulations, shell defects, follicular collapse, and oviduct involution. Pattern of lay preceding necropsy seemed to influence follicle weight at necropsy. The data presented re-emphasize the interdependence among liver, ovary, and oviduct function in the etiology of FLHS.

Animal Feed↗