Non-hemorrhage Group Research Articles

Xanthine Oxidase Inhibition Prevents Mesenteric Blood Flow Deficits after Resuscitated Hemorrhagic Shock by Preserving Endothelial Function

To determine the contribution of xanthine oxidase-mediated endothelial dysfunction to the blood flow deficits seen in the mesenteric circulation after resuscitated hemorrhagic shock, rats were prepared for intravital microscopic study then bled to 50% of baseline blood pressure for 60 min. Treatment animals received a 50 mg/kg bolus and a 25 mg/kg/hr infusion of the xanthine oxidase inhibitor allopurinol (allo) after shock but before resuscitation with shed blood and an equal volume of Ringer's lactate. A similarly resuscitated group (Std Res) and a nonhemorrhage group served as controls. Endothelial function was quantified at baseline, 30 min (R30), and 90 min (R90) postresuscitation as a change in mesenteric vessel diameter after topical application of acetylcholine (Ach), an endothelial-dependent vasodilator. Resuscitation restored cardiac output and blood pressure in both groups. First-order arteriolar blood flow (A1) remained depressed in the Std Res group but was restored to baseline in the group treated with allo. A1 arterioles demonstrated a 22 and a 27% reduction in ability to dilate to Ach at R30 and R90 after Std Res. V1 venules demonstrated a 39 and a 36% reduction in ability to dilate to Ach at R30 and R90 after Std Res. Endothelial-dependent vasodilation and blood flow were preserved in the group receiving Std Res plus allo. The preservation of endothelial function correlated with the restoration of microvascular blood flow postresuscitation. These data suggest that xanthine oxidase-mediated ischemia–reperfusion injury contributes to endothelial dysfunction and blood flow deficits in the mesenteric microcirculation after resuscitated hemorrhagic shock, the effect of which can be attenuated by the addition of the xanthine oxidase inhibitor allopurinol to standard resuscitation.

The Difference of Variceal Distribution in the Portal Hypertension on CT between Hemorrhagic and Nonhemorrhagic Groups

The Difference of Variceal Distribution in the Portal Hypertension on CT between Hemorrhagic and Nonhemorrhagic Groups

Gastrointestinal Hemorrhage After Acute Stroke

Although patients with critical illness or acute head injury are known to be at risk of gastrointestinal hemorrhage, there is little information concerning acute stroke. We sought to record the frequency, possible causes, and course of gastrointestinal hemorrhage in a cohort of hospitalized stroke patients. During a 36-month period we prospectively identified 613 strokes (excluding subarachnoid hemorrhage). We then retrieved the case notes, and a single observer reviewed all available records (n=607), noting any episodes of gastrointestinal hemorrhage together with details concerning the course, possible precipitating+ factors, management, and outcome. Eighteen patients (3%) experienced a gastrointestinal hemorrhage, half of which were severe. These patients were older and had suffered more severe strokes than those without any gastrointestinal bleeding. The source was identified in 5 patients; 2 had gastric ulceration, 2 duodenal ulceration, and the remaining one had esophageal/duodenal ulceration. In 17 patients, there was a potential risk factor for hemorrhage, although the odds ratios comparing the use of antithrombotic drugs in the hemorrhage and nonhemorrhage groups did not achieve statistical significance. Death during the acute admission period was more common in the 18 hemorrhage patients (odds ratio, 4.6; 95% confidence interval, 1.7 to 13.2; two-tailed P=.002, Fisher's exact test); of the 10 who died, gastrointestinal hemorrhage appeared to have been a contributing factor in 3. Our study provides a reasonably accurate estimate of the frequency of gastrointestinal hemorrhage after acute stroke. The higher frequency found in our study than the previously published data is probably due to study methodology. Older patients with more severe strokes may be at increased risk of this complication, and it may adversely affect outcome.

Use of hematocrit changes as an indicator of blood loss in adult trauma patients who receive intravenous fluids

To validate the use of changes in hematocrit as an indicator of blood loss in adult trauma patients receiving IV fluids and to identify parameters of hematocrit changes that may differentiate between patients with and without hemorrhage. A descriptive, retrospective chart review. A convenience sample of 90 adult trauma patients at an urban level I trauma center emergency department who received IV fluids for whom hematocrit measurements were available. Records were reviewed for patients with documented hematocrit readings before and after receiving 2 L of IV fluid, noting the time between hematocrit measurements. Patients were divided into groups: Group 1 consisted of 74 subjects with no hemorrhaging (< 500 ml blood loss); group 2 consisted of 16 subjects in whom hemorrhage occurred (> 500 ml of blood loss). In group 1 (nonhemorrhage group), the mean hematocrit change was -5.3%; in group 2 (hemorrhage group) the hematocrit change was -8.3%. The findings showed a statistically significant difference (p < 0.05) between the groups for both the repeat hematocrit scores and the change in hematocrit scores. On the basis of a hematocrit decrease of 5% or less, 97% of the patients would have been correctly assigned to the nonhemorrhage group. Hematocrit determinations are a valid indicator of blood loss in trauma patients receiving IV therapy. The use of repeat hematocrit readings for clinicians trying to differentiate those with significant blood loss and the effects of IV fluid administration remains limited.

Coagulation Monitoring During Extracorporeal Membrane Oxygenation: The Role of Thrombelastography

Patients undergoing extracorporeal membrane oxygenation (ECMO) are at an increased risk for developing coagulopathies due to the adverse effects of extracorporeal circulation on the hemostatic mechanism. Methods of determining causative factors of bleeding diathesis are often inconsistent and non-specific. ECMO patients require aggressive transfusion therapy with autogenic blood products to stabilize and maintain hemostasis. The present study evaluated the coagulation status of newborn patients undergoing ECMO therapy, using a viscoelastic monitor (Thrombelastograph -TEG) that measures functional aspects of clot development and stabilization. Seventeen neonatal patients undergoing ECMO for severe respiratory dysfunction were entered into this study. Serial blood samples were obtained and routine coagulation assessment including fibrinogen concentration, platelet count and ionized calcium was performed. In addition, fibrin ( ogen) degradation products (FDP), d-Dimers, antithrombin III and plasma free hemoglobin were measured. Transfusion indicators were established and total transfusion requirements recorded. TEG profiles were determined with the use of heparinase, an enzyme that degrades heparin but has little effect on other coagulation factors. The most commonly encountered complication was hemorrhaging which was diagnosed by laboratory and clinical assessment in 11 of 17 patients. Transfusion requirements (measured in ml/kg/ECMO hour) were the following: packed red blood cells - 1.34±0.5; platelets - 0.71 ±o.57; fresh frozen plasma- 0.09±0.12; cryoprecipitate 0.05 ±o.05. Thrombelastograph profiles reflected hemostatic conditions that ranged from severe coagulopathies (DIC) to hypercoagulability. Interpretation of TEG profiles identified hemostatic abnormalities in 57 of 101 profiles ( 46.5% ), with the most common etiology related to platelet dysfunction. In the non-hemorrhagic group the TEG profiles were normal in 30 of 41 (73.2%) instances, while the hemorrhagic group had 24 of60 (40%) profiles in the normal range (p&lt;.001). d-Dimers and FDP were elevated in all patients during ECMO despite maintenance of activated clotting times greater than 180 seconds. During ECMO coagulation assessment with the TEG provides useful information for the rapid diagnosis of hemorrhagic conditions, which may help guide transfusion therapy.

Changes in coagulation and fibrinolytic system after local intra-arterial thrombolysis for acute ischemic stroke.

Intracerebral hemorrhagic transformation is one of the most important complications of thrombolytic therapy for acute ischemic stroke. The relationship between changes in markers for the coagulation and fibrinolytic systems and occurrence of hemorrhagic transformation was determined after local intra-arterial thrombolytic therapy using urokinase (UK) (24 patients) or recombinant tissue plasminogen activator (t-PA) (10 patients) within 6 hours of onset. All 34 patients had no hypodensity areas on initial computed tomography scans. Plasma concentrations of fibrinogen-fibrin degradation products (FDP), fibrinogen, alpha 2-plasmin inhibitor (alpha 2-PI), plasmin-alpha 2 plasmin inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), and D-dimer were measured. Hemorrhagic transformation occurred in seven patients (21%) with complete or partial recanalization; four in the UK group and three in the t-PA group. Doses of the thrombolytic agents did not correlate with the incidence of hemorrhagic transformation. The FDP levels in the hemorrhagic transformation group treated with UK significantly increased immediately and 1 hour after the therapy. The alpha 2-PI activities decreased and PIC levels increased in both the hemorrhagic transformation and the nonhemorrhagic groups after the therapy. The TAT levels in both groups tended to be higher than the normal range, but there was no significant difference from the pretreatment levels. The D-dimer levels in the hemorrhagic transformation group were higher than those in the nonhemorrhagic group at 24 hours after the therapy. Furthermore, the D-dimer levels were significantly higher in patients with complete recanalization compared with those with none or partial recanalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral haemodynamic changes after endovascular treatment of arteriovenous malformations: evaluation by single-photon emission CT.

Cerebral haemodynamic changes in 17 patients with cerebral arteriovenous malformations (AVMs), who showed hypoperfusion on single-photon emission computed tomography (SPECT) before endovascular treatment, were studied after embolization. Nine of them had non-haemorrhagic clinical manifestations and the other eight had a history of intracranial haemorrhage. Obliteration of AVMs was nearly total in six patients and partial in eleven. New low density lesions on X-ray computed tomography (CT) developed in 3 of 6 patients after nearly total obliteration and one of 11 patients after partial obliteration. The first SPECT after embolization showed diminished hypoperfusion in 11 of 13 patients without new low density lesions and one of 4 patients with new low density lesions. Diminution of hypoperfusion was seen even in two patients who underwent SPECT study immediately after the embolization. Cerebral circulation was improved in five of eight patients with low density lesions before embolization and in nine of eleven patients after partial obliteration. Hypoperfused state in the haemorrhagic group tended to remain unchanged compared with that in the non-haemorrhagic group. The hypoperfused area was expanded after embolization in three patients with new cerebral infarction. It is important for improvement of cerebral circulation to reduce the shunt flow without causing new infarction due to the embolization itself. In one of two patients who had a hyperperfused area surrounding the AVM after embolization, an unexpected and abnormal degree of brain swelling and haemorrhage occurred at the end of the surgery 20 days after the embolization. In the other patient, total extirpation was successfully performed after confirming disappearance of hyperperfusion in the follow-up SPECT.(ABSTRACT TRUNCATED AT 250 WORDS)

The Influence of Hemodynamic and Anatomic Factors on Hemorrhage from Cerebral Arteriovenous Malformations

The physiological and anatomical aberrations that result in hemorrhage from cerebral arteriovenous malformations (AVMs) remain unclear. In an attempt to clarify which conditions may predispose to hemorrhage, we examined clinical and physiological indices on presentation groups of either hemorrhage or nonhemorrhage in a large cohort of patients (n = 449). Variables examined included AVM size, type of venous drainage, transcranial Doppler (TCD) velocities, feeding mean arterial pressure (FMAP), and draining vein pressure. TCD and pressure data were obtained before any treatment. Age (mean +/- standard deviation) at the time of presentation was 33 +/- 13 years and did not differ between groups. Patients with small (< or = 2.5 cm) AVMs presented more frequently with hemorrhage (90%) than did patients with medium (> 2.5 and < or = 5.0 cm; 52%) or large (> 5.0 cm; 50%) AVMs (P = 0.0001). The 48 of 94 AVMs (51%) with deep venous drainage were more likely to have hemorrhage (P = 0.0219) than were those with superficial drainage (24 of 73 [33%]). Deep drainage was a predictor of hemorrhage even in the subgroup of medium and large supratentorial AVMs (P = 0.005). There was no difference in draining vein pressure (n = 18) between groups (21 +/- 10 and 19 +/- 11 mm Hg, respectively; P = 0.7812). FMAP (n = 52) was higher in the hemorrhage than in the nonhemorrhage group (44 +/- 13 versus 34 +/- 10 mm Hg; P = 0.0007) but was only weakly related to the size of the lesion (largest dimension) (y = -0.74x + 40; r = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Morphological evaluation of amyloid-laden arteries in leptomeninges, cortices and subcortices in cerebral amyloid angiopathy with subcortical hemorrhage.

To investigate the relationship between cerebral amyloid angiopathy and subcortical (lobar) hemorrhage, we examined the severity of amyloid deposition in the leptomeningeal, cortical and subcortical arteries in 28 autopsied elderly patients with cerebral amyloid angiopathy with subcortical hemorrhage, deep cerebral hemorrhage or without hemorrhage. The severity was evaluated in terms of the frequency of amyloid-laden arteries and the degree of amyloid deposition within the arteries. The frequency of amyloid-laden arteries, especially among arteries over 200 microns in diameter, was higher in subcortical hemorrhage group than in the deep hemorrhage group and the non-hemorrhage group, and when the degree of amyloid deposition in the arteries was divided into four grades (none, mild, moderate or severe), the severity was higher in the subcortical hemorrhage group than in the deep cerebral hemorrhage group and the non-hemorrhage group. These results suggest that severe cerebral amyloid angiopathy is related to non-traumatic subcortical hemorrhage in elderly persons.

Recurrent bleeding after variceal hemorrhage: predictive value of portal venous duplex sonography.

Risk assessment of recurrent variceal bleeding is essential for therapeutic decisions and is usually performed by endoscopy of the upper gastrointestinal tract. We studied the value of portal venous duplex sonography in predicting subsequent variceal bleeding in patients with cirrhosis. Thirty patients with cirrhosis who received sclerotherapy because of acute variceal hemorrhage for the first time (hemorrhage group), 30 patients with cirrhosis who had no previous hemorrhage (nonhemorrhage group), and 30 control subjects were examined prospectively. With the use of portal duplex and color Doppler sonography, flow direction, flow velocity, vein diameter, and response to respiration of portal vein vessels were measured and portosystemic collaterals and thrombosis of portal vessels were visualized. The results of these measurements and imaging findings were combined into a Doppler sonoscore. At entry into the study, all patients were classified on the basis of a sonoscore as having a low (sonoscore, < 4) or a high (sonoscore, > or = 4) risk for subsequent hemorrhage. During a mean follow-up period of 2 years (range, 15-36 months), the predictive value of this Doppler sonoscore was studied. In the hemorrhage group, the prevalence of recurrent hemorrhage was 40%, despite sclerotherapy, and the mortality rate was 60%. In patients with a Doppler sonoscore of 4 or more, the prevalence of recurrent hemorrhage was 67%, whereas in patients with a score less than 4, the prevalence was only 22% (p < .02). After sclerotherapy, endoscopic criteria showed no significant correlation with the prevalence of bleeding. In the nonhemorrhage group, the prevalence of variceal hemorrhage occurring was 13%, and Doppler sonographic criteria showed no significant correlation with the prevalence of subsequent hemorrhage. We conclude that Doppler sonography, performed after the first occurrence of variceal hemorrhage, provides useful prognostic information regarding the risk of recurrent hemorrhage. If these results are confirmed, Doppler sonography may be used to select the best method of treatment.

Neurodevelopmental assessment of very low birth weight neonates: Effect of germinal matrix and intraventricular hemorrhage

During a recent 36-month interval, all neonates of ≤ 1250 gram birth weight who were admitted to our Newborn Special Care Unit and survived the first 36 postnatal hours underwent either computed tomography or echoencephalography or both for the assessment of neonatal germinal matrix hemorrhage and intraventricular hemorrhage. Seventy of the 164 long-term surviving infants experienced neonatal germinal matrix and/or intraventricular hemorrhage (GMH/IVH Group), whereas 94 infants had studies that were negative (Non-hemorrhage Group). Serial neurodevelopmental assessments were performed on 142 (87%) of the 164 long-term surviving infants; these assessments included the Bayley Scales of Infant Development at 3, 6, 12, and 18 months (corrected age) and the Stanford-Binet and Peabody Picture Vocabulary examinations at 30 months (corrected age). At 30 months (corrected age), the incidence of major neurologic abnormalities was extremely low in both the GMH/IVH and the Non-hemorrhage groups. In addition, although there were few survivors of the more severe grades of intraventricular hemorrhage, we could detect no difference between the developmental scores of the GMH/IVH and the Non-hemorrhage Group infants.

Posthemorrhagic hydrocephalus. Low incidence in very low birth weight neonates with intraventricular hemorrhage.

In addition to seizures and long-term neurodevelopmental handicaps, infants with intraventricular hemorrhage (IVH) are at risk for posthemorrhagic hydrocephalus (PHH), and the incidence of this problem in preterm infants with known IVH has been reported to vary from 25% to 74%. Over a 46-month period, 438 neonates of 1250-gm birth weight or less were admitted to this Newborn Special Care Unit, and 269 survived the first 36 postnatal hours. Of these, 265 patients underwent computerized tomography and/or cranial ultrasound scanning for evaluation of germinal matrix and/or intraventricular hemorrhage (GMH/IVH): 133 infants were found to have experienced GMH/IVH, and 27 of these died within the 1st postnatal week. Of the 95 survivors with GMH/IVH, 43 were known to have GMH only; the other 52 experienced IVH and were therefore at risk for PHH. Patients with GMH/IVH underwent repeat investigations for the development of ventriculomegaly and possible PHH. Only five patients with IVH developed PHH, defined as ventriculomegaly, elevated intracranial pressure, and increasing occipitofrontal head circumference. Serial cranial ultrasound studies of 95 other consecutively admitted patients in this birth-weight range revealed an equal incidence (45%) of low intracranial pressure ventriculomegaly in both the hemorrhage and non-hemorrhage groups, but none of them required shunting for hydrocephalus. One infant with congenital aqueductal stenosis was also identified.

FELLOW EYES OF GLAUCOMATOUS PATIENTS WITH UNIOCULAR OPTIC DISC HAEMORRHAGE

Optic disk stereophotographs and clinical data of 94 patients with uniocular disc haemorrhage were analyzed at the time the haemorrhage was present. Comparison of haemorrhagic eyes with their fellow eyes showed that such patients do not form a separate disease entity but rather present a group of patients with different types of bilateral open-angle glaucoma or suspected glaucoma in various stages of the disease progression. By multivariate analysis, notching of the neural rim was the most effective factor to increase probability of bleeding in contrast to presence of capsular glaucoma which increased probability of an eye belonging to the non-haemorrhagic group of eyes.