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Histometric analysis of cell populations in gingiva with bleeding on probing by immunohistochemistry.

The present study was performed by immunohistochemical methods in order to morphometrically characterize and compare the composition of cellular infiltrates in human gingivae with bleeding and non-bleeding upon probing. A total of 64 gingival biopsies (33 bleeding and 31 non-bleeding gingivae) were obtained from 23 patients. Routine Hematoxylin & Eosin and immunohistochemical stains were performed following tissue preparations. On each section, three zones were histologically divided. For each zone, the percentage and histometric analysis of plasma cells, phagocytic cells, B-cells and T-cells was calculated to characterize the composition of cellular infiltrates in gingiva associated with bleeding on probing. Significant difference was found in the middle and apical zones of infiltrated connective tissue when compared with plasma cells expressed by kappa- or lambda-chain positive immunostaining between bleeding and non-bleeding gingivae. Significant difference was also found in the coronal zone when compared with phagocytic cells and B lymphocytes between bleeding and non-bleeding gingivae. It is suggested that clinical bleeding tendency of gingiva may be highly associated with histological alterations of underlying inflammatory cell populations and a complicated immunological mechanism appears to be involved.

B-Lymphocytes↗

First bleeding episode from oesophageal varices in cirrhotic patients: a prospective study of endoscopic predictive factors.

Two hundred patients affected by liver cirrhosis and oesophageal varices were studied in 9 Gastrointestinal Units in Lombardy (Northern Italy) in order to assess factors possibly related to variceal bleeding. Only patients without any previous episode of gastrointestinal bleeding were included in the prospective evaluation. For each patient demographic data, aetiology of cirrhosis, various clinical and biochemical parameters able to group patients into the three Child-Pugh Classes, endoscopic items for calculation of Beppu's and of NIEC prognostic scores were recorded on computerized cards. Patients were regularly interviewed every three months for one year and underwent an upper gastrointestinal endoscopy at enrollment, after six months and in case of bleeding. Within the twelve-month follow-up period, 29 out of the 200 patients (14%) bled and 52 out of 200 died (26%). In 16 of the 52 patients who died (59% of bleeding patients) death was directly related to gastrointestinal bleeding. Bleeding from oesophageal varices was endoscopically proven in 19/29 patients, in another 9 bleeding was classified as from unknown source and in one patient a bleeding gastric ulcer was diagnosed. Univariate analysis of all the recorded clinical, biochemical and endoscopic parameters, performed by Chi-square method and Fisher exact test showed that the presence of RWM (p < 0.001) was the only factor significantly associated to variceal bleeding within one year. Relationship between size of varices and bleeding was very close to the statistical significance but did not achieve it (p = 0.058).

Adult↗

Seasonal variation in the incidence of peptic ulcer and esophageal variceal bleeding in Taiwan.

BACKGROUND: Seasonal variation of peptic ulcer and peptic ulcer bleeding has been reported in many western countries. To investigate the seasonal variation of peptic ulcer (PU) and esophageal variceal (EV) bleeding in Taiwan, this retrospective study was conducted. METHODS: Seven hundred and forty-six cases of gastric ulcer (GU) bleeding, 777 cases of duodenal ulcer (DU) bleeding and 264 cases of EV bleeding were recruited from January 1, 1991 to December 31, 1992. Patients were sent to the Medical Emergency Room (MER) for hematemesis and/or melena. Upper gastrointestinal (UGI) endoscopic examinations were completed within 24 hours for all patients. RESULTS: Significant seasonal variation was found in the incidence of PU and EV bleeding. PU bleeding was most often seen in March and EV bleeding was most often seen in February. CONCLUSIONS: The possible mechanism for the cyclic change of PU and EV bleeding is unclear, but clearly more manpower is needed during the months of February and March for better management of the increasing number of cases of PU and EV bleeding.

Aged↗

Treatment of active gastroesophageal variceal bleeding with terlipressin or hemostatic balloon in patients with cirrhosis. A randomized controlled trial.

Gastroesophageal variceal bleeding due to portal hypertension should be treated by endoscopic sclerotherapy. This procedure, however, has some limitations. It has been established that vasoactive drugs are effective for controlling active variceal bleeding. We report the results of a randomized controlled trial comparing terlipressin to hemostatic tube (Linton-Michel tube) for the treatment of bleeding gastroesophageal varices in cirrhotic patients. Thirty-seven cirrhotic patients with a total of 40 episodes of gastroesophageal variceal bleeding were included in this trial. Patients were randomly assigned to intravenous terlipressin or Linton-Michel tube (LM tube), for 24 h. During this period, hemostasis was defined as obtaining of hemodynamic and hematocrit stabilization and/or absence of hematemesis or melena. Bleeding recurrence was assessed during a 1-month period after treatment. Twenty bleeding episodes were treated with terlipressin (Group I) and 20 with LM tube (Group II). Both groups of patients were similar in age, sex distribution, etiology of cirrhosis and degree of hepatic insufficiency. Bleeding was controlled in 70% of patients from Group I and in 95% from Group II (p < 0.05) during treatment. Bleeding recurred in 14% of patients in Group I vs. 36% in Group II 1 week following the treatment (p > 0.05) and in 16.6% in Group I vs. 83.3% in Group II 1 month after treatment (p < 0.05). Complications were more frequent in Group II than in Group I (65 vs. 15%, p < 0.05). Mortality rate was similar in both groups 1 month after treatment. In conclusion, hemostatic tubes were superior to terlipressin for the control of active gastroesophageal variceal bleeding within the first 24 h. Complications and bleeding recurrence were more frequent in patients treated by hemostatic tube within a period of 1 month after treatment. Mortality rate was similar in both groups of patients.

Adult↗

Beta-blockers for prophylaxis of bleeding from esophageal varices in cirrhotic portal hypertension. Review of the literature.

Hemorrhage from esophageal varices is a life-threatening event in patients with liver cirrhosis. About 40% to 80% of the patients surviving the first bleeding suffer from a recurrence of variceal bleeding within one year. This high recurrence rate substantially contributes to the mortality in patients with liver cirrhosis. Therefore, various treatment regimens both in primary and secondary prophylaxis were studied. Most experience in medical primary prophylaxis was collected with beta-blockers, mainly propranolol. Treating patients with esophageal varices with propranolol significantly reduces the incidence of first variceal bleeding. However, the effect on mortality is marginal, and primary prophylaxis is generally not recommended in these patients. Several studies support the hypothesis, that medical prophylaxis with beta-blockers is more effective in reducing the rate of first esophageal bleeding in patients with a high risk of hemorrhage, such as the presence of very large varices with red spots. A score to assess the individual risk of a given patient to suffer a variceal bleeding would be helpful. As long as such a score is not validated, no general rule for this treatment decision can be given. In secondary prophylaxis, both administration of beta-blockers and endoscopic therapy (sclerotherapy or ligation of the varices) are effective in significantly lowering the rate of re-bleeding. However, the effect on mortality was not significant in most studies. Several studies comparing the efficacy of medical prophylaxis and endoscopic treatment showed advantages of the endoscopic therapy with a greater reduction in recurrent bleeding episodes. However, medical prophylaxis with beta-blockers has the important advantage of being immediately effective whereas endoscopic procedures provide the best protection against recurrent bleeding after complete obliteration of the varices. Therefore, in the first weeks and months of endoscopic therapy, the additional treatment with beta-blockers may further reduce the risk of re-bleeding. Only half of all studies on this topic reported a significant advantage of such a combined therapy. Therefore, it seems reasonable to restrict this approach to patients with a high risk of re-bleeding such as patients with large sclerotherapy-derived esophageal ulcers.

Adrenergic beta-Antagonists↗

Predictive factors of variceal bleeding control by emergency sclerotherapy. Multicenter Group.

OBJECTIVES: Acute bleeding from esophageal varices is a major complication of cirrhosis. Despite the large number of published studies no predictive factors of control of bleeding have been identified. We assessed the clinical and biological factors predictive of bleeding control within the first 2 weeks after a bleeding episode in a homogeneous group of patients enrolled in a large multicenter trial, who underwent a standardized emergency sclerotherapy session. METHODS: 101 patients with cirrhosis were enrolled. All had endoscopy-proven variceal bleeding, and the interval between hematemesis or melena and emergency sclerotherapy was always less than 24 hours. A second sclerotherapy session and other methods for the prevention of rebleeding were allowed after 5 days. RESULTS: Treatment failed in 16 patients after 24 hours and in a total of 33 patients after 15 days. Three of the 17 variables included in multivariate logistic analysis were associated with failure at 24 hours: encephalopathy (P = 0.006, OR = 4.0), blood transfusion prior to sclerotherapy (P = 0.012, OR = 6.2) and previous propranolol therapy (P = 0.022, OR = 4.6). Two variables were associated with failure between 24 hours and day 15 in patients successfully controlled after 24 hours: an interval between the onset of bleeding and sclerotherapy of less than 12 hours (P = 0.010) and blood transfusion (P = 0.018). After 15 days, three variables were associated with failure in a multivariate Cox model: encephalopathy (P = 0.0025, OR = 2.3), time to sclerotherapy (P = 0.022, OR 2.3) and blood transfusion before sclerotherapy (P = 0.0005, OR = 4.0). CONCLUSION: Encephalopathy, the severity of bleeding, assessed in terms of transfusion requirements, and the time between clinically overt bleeding and sclerotherapy are the main predictive factors of failure of the control of bleeding after emergency sclerotherapy for acute bleeding from esophageal varices.

Emergencies↗

The preoperative bleeding time test lacks clinical benefit: College of American Pathologists' and American Society of Clinical Pathologists' position article.

The major conclusions of this position article are as follows: (1) In the absence of a history of a bleeding disorder, the bleeding time is not a useful predictor of the risk of hemorrhage associated with surgical procedures. (2) A normal bleeding time does not exclude the possibility of excessive hemorrhage associated with invasive procedures. (3) The bleeding time cannot be used to reliably identify patients who may have recently ingested aspirin or nonsteroidal anti-inflammatory agents or those who have a platelet defect attributable to these drugs. The best preoperative screen to predict bleeding continues to be a carefully conducted clinical history that includes family and previous dental, obstetric, surgical, traumatic injury, transfusion, and drug histories. A history suggesting a possible bleeding disorder may require further evaluation; such an evaluation may include performance of the bleeding time test, as well as a determination of the platelet count, the prothrombin time, and the activated partial thromboplastin time. In the absence of a history of excessive bleeding, the bleeding time fails as a screening test and is, therefore, not indicated as a routine preoperative test.

Anti-Inflammatory Agents, Non-Steroidal↗

The bleeding time as a preoperative screening test.

To examine the benefit of determination of the bleeding time as a preoperative screening test, the medical records of all patients who had a prolonged bleeding time during a six-month period were reviewed. At Northwestern Memorial Hospital, where the bleeding time test is part of the presurgical panel, 1,941 bleeding time determinations were performed during six months. Prolonged bleeding times were recorded in 110 preoperative patients, of whom 83 (75 percent) had bleeding risk factors, including drug ingestion, thrombocytopenia, and azotemia. In these patients, the bleeding time ranged unpredictably from 10 to more than 20 minutes. However, of the 27 patients without apparent risk factors, only two had bleeding times of more than 20 minutes. This small number probably does not justify the routine use of the test in all preoperative patients. Rather, the test should be used selectively for those subjects who, on the basis of history or laboratory evidence, are suspected of being at risk of hemorrhage. Moreover, even in these patients, prolongation of the bleeding time may not always be associated with excessive surgical blood loss.

Aspirin↗

The effect of magnesium sulfate on bleeding time in pregnancy.

OBJECTIVE: The bleeding time is one of the most commonly used diagnostic tests to evaluate platelet-related hemorrhagic disorders. Magnesium has been shown in vitro to be a platelet antiaggregant. This study was conducted to evaluate the hypothesis that magnesium sulfate has no effect on the template bleeding time. STUDY DESIGN: The study group consisted of 24 women who required magnesium sulfate in pregnancy. A blood cell count, platelet count, magnesium level, bleeding time, and mean arterial pressure were obtained before and 2 hours after magnesium sulfate infusion. Magnesium sulfate was infused beginning with a 6 gm intravenous bolus followed by 2 gm/hr. A template bleeding time was performed with a Simplate-II (Organon Teknika, Durham, N.C.) device. Two of the authors performed all the bleeding times. Data were analyzed with a paired t test and Wilcoxon rank test. RESULTS: Fifteen (63%) patients received magnesium sulfate for tocolysis or before external cephalic version and nine (37%) for preeclampsia prophylaxis. No differences were found between the normotensive and hypertensive groups regarding maternal age, gestational age, initial bleeding time, or platelet count. Analysis of the entire study group revealed a prolongation of the bleeding time after magnesium sulfate (5.7 +/- 1.8 vs 6.6 +/- 1.9 minutes, p < 0.05); a lowering of the mean arterial pressure (p < 0.05), and a rise in the magnesium level (p < 0.05). Four patients (16.7%) had a postmagnesium bleeding time > 9 minutes. CONCLUSION: Magnesium sulfate appears to prolong the bleeding time in pregnancy. The clinical significance remains to be determined.

Adult↗

Controlling bleeding from superficial wounds by the use of topical alpha adrenoreceptor agonists spray. A randomized, masked, controlled study.

In an attempt to determine whether alpha adrenergic agonists sprayed directly over the wound are able to reduce a superficial bleeding, phenylephrine (0.25%), oxymetazoline (0.05 and 0.25%) and saline (0.9%) were tested in a rat model. The study was randomized, controlled and quantitative. A total of four incisions were made in each rat, and each solution was sprayed directly on the incision according to a specific protocol. The bleeding times were measured and summed up. Biases were minimized by the fact that each rat received all four solutions, including the control, in all possible combinations. The mean bleeding time after spraying phenylephrine (0.25%) was significantly shorter than the mean bleeding time after spraying saline (1.90 +/- 0.14 min versus 4.80 +/- 0.43 min, respectively, P < 0.001) and significantly shorter than the mean bleeding time after spraying oxymetazoline (0.05 or 0.25%: 4.46 +/- 0.54 and 5.50 +/- 0.58 min, respectively, P < 0.001). No statistically significant difference was found between the mean bleeding time after spraying oxymetazoline (0.05 or 0.25%) compared with saline. We conclude that sprayed phenylephrine (0.25%) can be used for reducing superficial bleedings. This method is simple, cost-effective, does not cause further trauma to the tissue, and can be used to treat several bleedings simultaneously (especially abrasions and lacerations) with a single application, without the need for direct physical contact with the bleeding sites. The method is apparently safe, but further studies are needed to test the systemic effect of the sprayed solution.

Adrenergic alpha-Agonists↗

Bivalirudin Versus Heparin in Low and Non-Low Bleeding Risk Patients Undergoing Primary PCI for STEMI: The BRIGHT-4 Trial.

BACKGROUND: In the BRIGHT-4 trial, among 6,016 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with a radial artery approach, procedural anticoagulation with bivalirudin plus a post-PCI high-dose infusion for 2 to 4 hours reduced the 30-day primary composite outcome of all-cause death or Bleeding Academic Research Consortium (BARC) types 3 to 5 bleeding, as well as death and bleeding individually, compared with heparin monotherapy. OBJECTIVES: We sought to determine whether the benefits of bivalirudin apply principally to patients who are at low bleeding risk (LBR) as well as non-LBR. METHODS: In a prespecified analysis from BRIGHT-4, outcomes were examined by baseline bleeding risk, with LBR defined as a CRUSADE score <30. RESULTS: At baseline, 4,581 patients (76.1%) were categorized as LBR. Non-LBR patients had higher rates of the 30-day primary endpoint (8.6% vs 2.2%; HR: 4.08 [95% CI: 3.14-5.31]; P < 0.0001), driven by both greater mortality and BARC types 3 to 5 bleeding. In non-LBR patients, the primary outcome occurred in 8.1% of patients randomized to bivalirudin vs 9.2% of those randomized to heparin (difference: -1.1% [95% CI: -4.0% to 1.8%]; HR: 0.88 [95% CI: 0.62-1.26]). In LBR patients, the primary outcome occurred in 1.4% of patients randomized to bivalirudin vs 2.9% of those randomized to heparin (difference: -1.5% [95% CI: -2.3% to -0.6%]; HR: 0.49 [95% CI: 0.32-0.75]) (Pabsolute interaction = 0.81; Prelative interaction = 0.04). The effects of bivalirudin compared with heparin in reducing all-cause death were as robust in LBR patients compared with non-LBR patients (Pabsolute interaction = 0.67; Prelative interaction = 0.06). CONCLUSIONS: Among patients with STEMI undergoing primary PCI with radial artery access, procedural anticoagulation with bivalirudin plus a high-dose post-PCI infusion for 2 to 4 hours reduced the 30-day risk of all-cause death and major bleeding in patients at low bleeding risk as well as in patients at higher-risk of bleeding. (Bivalirudin With Prolonged Full Dose Infusion Versus Heparin Alone During Emergency PCI [BRIGHT-4; NCT03822975]).

Humans↗

Multicenter randomized controlled trial comparing different schedules of somatostatin in the treatment of acute variceal bleeding.

BACKGROUND/AIMS: The dose of somatostatin used for variceal bleeding (250 microg/h) is lower than that proven to effectively decrease portal pressure and azygos blood flow (500 microg/h). Moreover, i.v. somatostatin boluses have greater effects than continuous infusions. The aim of this study was to investigate whether higher doses of somatostatin and repeated boluses may increase its efficacy in controlling variceal bleeding. METHODS: A total of 174 patients with acute variceal bleeding were randomized to receive for 48 h: (A) one 250 microg bolus +250 microg/h infusion; (B) three 250 microg boluses +250 microg/h infusion; (C) three 250 microg boluses +500 microg/h infusion. RESULTS: The three schedules of somatostatin were equally effective in controlling variceal bleeding (73, 75 and 81%, respectively, NS). Multivariate analysis showed active bleeding at endoscopy (n=75) as the only predictor of failure to control bleeding. In these patients, the 500 microg/h infusion dose achieved a higher rate of control of bleeding (82 vs. 60%, P<0.05), less transfusions (3.7 +/- 2.7 vs. 2.5 +/- 2.3 UU, P=0.07) and better survival (93 vs. 70%, P<0.05) than schedules A/B. CONCLUSIONS: Somatostatin is highly effective in controlling variceal bleeding. Patients with active bleeding at emergency endoscopy may benefit from higher doses of somatostatin infusion.

Acute Disease↗

The bleeding time may be longer in children than in adults.

The bleeding time, the most frequently performed test reflecting in vivo platelet function, is the duration of blood flow from a standardized incision on the volar surface of the forearm. Normal values have been determined in adult subjects, but with the exception of neonates, data on the range of bleeding time values in pediatric patients are unavailable. Standard hematology textbooks imply that bleeding time values in children are similar to those of adults. We have reviewed our 9 years of experience with 137 children (mean age 6.5 years) who were referred for diagnostic evaluation of a bleeding disorder but whose history and physical examination were felt by us to be inconsistent with an abnormality of hemostasis. Bleeding time values in these individuals (mean 6.0 min, 95th percentile 9.0 min) were compared with those of 85 normal adult volunteers (mean 4.4 min, 95th percentile 6.5 min). The Simplate-I disposable device and vertical (perpendicular to elbow crease) incision direction were used in both groups. This difference between the pediatric and adult bleeding time values is statistically significant (p less than 0.0001). Neither age nor sex had a significant effect on the pediatric bleeding time measurements. We conclude that the bleeding time, when performed as described, is longer in children than in adults and that pediatric standards for bleeding time should be used in order to avoid a spurious diagnosis of a primary hemostatic disorder in some normal children.

Adolescent↗

Comparison of PFA-100 and bleeding time testing in pediatric patients with suspected hemorrhagic problems.

BACKGROUND: The bleeding time test is difficult to perform, standardize, and interpret in children. In this study the authors evaluated the sensitivity, specificity, and efficiency of the bleeding time test and the PFA-100 in a series of children referred for possible bleeding problems. PATIENTS AND METHODS: Between February 2000 and August 2001 patients aged more than 6 months and less than 18 years of age who were referred to the authors' institution for a hemostatic evaluation were included in the study if residual blood was available for testing on the PFA-100 instrument. Fifty-two children had platelet count, prothrombin time, partial thromboplastin time, bleeding time, and PFA-100 testing performed as well as an evaluation by a hematologist. For PFA-100 testing, 52 patients had Col/Epi measurements; adequate sample remained for Col/ADP testing on 32. Additional testing for diagnostic purposes was at the discretion of the treating physician. RESULTS: Use of the Col/Epi cartridge in the PFA-100 instrument offered 100% sensitivity and 97% specificity for detection of qualitative platelet abnormalities, compared with 37% and 88%, respectively, for bleeding time testing. For pediatric patients with von Willebrand disease, the sensitivity was 100% using the Col/Epi cartridge, compared with 17% for the bleeding time test. The sensitivities for combined qualitative platelet defects and von Willebrand disease using the Col/Epi or Col/ADP cartridges were 100% and 87%, respectively, compared with 37% for the bleeding time test. CONCLUSIONS: The PFA-100 is a more efficient test; it can replace the bleeding time test as a component of the laboratory evaluation of children with a potential bleeding problem.

Adolescent↗

Vitamin K deficiency bleeding (VKDB) in infancy. ISTH Pediatric/Perinatal Subcommittee. International Society on Thrombosis and Haemostasis.

TERMINOLOGY: Replace the term "Hemorrhagic Disease of the Newborn" (HDN) by "Vitamin K Deficiency Bleeding" (VKDB), as neonatal bleeding is often not due to VK-deficiency and VKDB may occur after the 4-week neonatal period. DEFINITION: VKDB is bleeding due to inadequate activity of VK-dependent coagulation factors (II, VII, IX, X), correctable by VK replacement. DIAGNOSIS: In a bleeding infant a prolonged PT together with a normal fibrinogen level and platelet count is almost diagnostic of VKDB; rapid correction of the PT and/or cessation of bleeding after VK administration are confirmative. WARNING SIGNS: The incidence of intracranial VKDB can be reduced by early recognition of the signs of predisposing conditions (prolonged jaundice, failure to thrive) and by prompt investigation of "warning bleeds". CLASSIFICATION: VKDB can be classified by age of onset into early (<24 h), classical (days 1-7) and late (>1 week <6 months), and by etiology into idiopathic and secondary. In secondary VKDB, in addition to breast feeding, other predisposing factors are apparent, such as poor intake or absorption of VK. VK-PROPHYLAXIS: BENEFITS: Oral and intramuscular VK (one dose of 1 mg) protect equally well against classical VKDB but intramuscular VK is more effective in preventing late VKDB. The efficacy of oral prophylaxis is increased with a triple rather than single dose and by using doses of 2 mg vitamin K rather than 1 mg. Protection from oral doses repeated daily or weekly may be as high as from i.m. VK. VK-PROPHYLAXIS: RISKS: VK is involved in carboxylation of both the coagulation proteins and a variety of other proteins. Because of potential risks associated with extremely high levels of VK and the possibility of injection injury, intramuscular VK has been questioned as the routine prophylaxis of choice. Protection against bleeding should be achievable with lower peak VK levels by using repeated (daily or weekly) small oral doses rather than by using one i.m. dose. BREAST FEEDING MOTHERS TAKING COUMARINS: Breast feeding should not be denied. Supervision by pediatrician is prudent. Weekly oral supplement of 1 mg VK to the infant and occasional monitoring of PT are advisable. CONCLUSION: VKDB as defined is a rare but serious bleeding disorder (high incidence of intracranial bleeding) which can be prevented by either one i.m. or multiple oral VK doses.

Humans↗

Hematologic changes during and after cardiopulmonary bypass and their relationship to the bleeding time and nonsurgical blood loss.

The hemostatic dysfunction induced by cardiopulmonary bypass is due, in part, to a platelet dysfunction evidenced by a postoperative extension of the bleeding time; it leads to increased postoperative blood loss and morbidity. This study, which was conducted in 85 patients undergoing cardiopulmonary bypass, was designed to characterize the hematologic changes during and after cardiopulmonary bypass and to elucidate the relationships between these changes, the extension of the bleeding time, and the magnitude of the postoperative nonsurgical blood loss. Variables were measured before, during, and 2, 24, 48, and 72 hours after cardiopulmonary bypass. Univariate and multivariate analyses were performed with either the 2-hour postbypass bleeding time or the 4-hour postbypass blood loss as the dependent variables. The reversal of the extension of the bleeding time in the postoperative period was accompanied by a significant increase in the mean platelet volume and by a significant increase in the level of thromboxane B2 measured in the blood shed from the site of the bleeding time determination. The postoperative bleeding time correlated with the postoperative blood loss, and both parameters were dependent on the duration of cardiopulmonary bypass. In addition, the postoperative bleeding time correlated with the skin temperature and the plasma level of D-dimer, while the postoperative blood loss also correlated with temperature and the plasma levels of C3. These data establish a direct relationship between the postoperative bleeding time, the postoperative blood loss, and temperature. They indicate that the reversal of the postoperative extension of the bleeding time is due in part to rewarming and to the release of larger platelets into the circulation, and they suggest that hyperfibrinolysis and complement activation may play an important role in the cardiopulmonary bypass-induced platelet dysfunction.

Bleeding Time↗

Assessment of bleeding for the evaluation of therapeutic preparations in small animal models of antibody-induced hemophilia and von Willebrand disease.

Three small animal models of bleeding are described and used to evaluate the effects of preparations intended for therapy of human bleeding disorders. We modified techniques for the assessment of bleeding to be able to reproducibly quantify blood loss and rate of blood flow in addition to the measurement of bleeding time. Temporary hemophilia was induced in a rabbit model by injection of high titer human inhibitor plasma [> or = 1000 Bethesda units (BU)/ml]. A decrease in rabbit FVIII from normal values to below the limit of detection was observed within 30 min, cuticle bleeding time changed from normal (approx. 10 min) to steady state bleeding (> 30 min), and the rate of blood flow increased from 4 to > 30 microliters blood/min. Infusion of an activated prothrombin complex concentrate, (FEIBA STIM4, Immuno) at doses between 75 and 150 U/kg normalized the rate of blood flow, while infusion of FVIII/vWF concentrate resulted in partial correction. Administration of FVIIa, both recombinant and plasma-derived, failed to correct bleeding, however. In an analogous murine model, FVIII/ vWF inhibitor plasma was obtained by immunizing goats with a purified human FVIII/vWF complex. This plasma cross-reacted with mouse vWF in vitro. Injection of the anti-FVIII/vWF inhibitor plasma into mice caused a decrease in vWF antigen, in some animals with a complete loss of vWF multimers comparable to severe von Willebrand disease. A specific anti-vWF inhibitor plasma obtained by immunization of goats with recombinant vWF was used in a further murine model, resulting in a gradual but substantial decrease in FVIII as well as in intensive bleeding. The infusion of a FVIII/vWF concentrate (IMMUNATE, IMMUNO) normalized the rate of blood flow in both murine models. The same assessment methods were used to characterize bleeding in a natural mouse model of von Willebrand disease (strain RIIIS/J). The use of quantitative techniques of assessment of blood loss and rate of blood flow appears to be a helpful tool for characterizing hemorrhagic situations and evaluating the capacity of therapeutic preparations to correct hemostatic defects.

Animals↗

Upper gastrointestinal tract bleeding in institutionalized mentally retarded adults. Primary role of esophagitis.

BACKGROUND: Upper gastrointestinal (UGI) tract bleeding is a common reason for hospitalization of mentally retarded adults. The purpose of this study was to determine the frequency and cause of and risk factors for UGI tract bleeding in institutionalized mentally retarded adults admitted to our hospital. METHODS: Case-control study, with a retrospective review of medical records. SETTING: Inner-city tertiary care hospital. PATIENTS: Mentally retarded adults who reside in one of three long-term care facilities. MEASUREMENTS: Data on demographic features, clinical features, and concurrent medical conditions were collected on mentally retarded adults admitted to our hospital for UGI tract bleeding (n = 40). Data from these patients were compared with those from a control group of mentally retarded adults admitted for nonbleeding conditions (n = 124). Endoscopic data were reviewed on the patients who bled to further clarify the causes of UGI tract bleeding. The patients who bled were compared with those who did not bleed using the chi 2 and Mann-Whitney rank sum tests. RESULTS: Upper gastrointestinal tract bleeding was the most common reason for hospitalization in this patient population. Such bleeding was most commonly caused by erosive esophagitis (70% of patients who bled). Conditions associated with an increased risk for UGI tract bleeding were hiatal hernia, reduced activity, incontinence, hypoalbuminemia, kyphoscoliosis, and spastic quadriplegia. CONCLUSIONS: Upper gastrointestinal tract bleeding is a common cause of hospitalization in mentally retarded adults and is usually due to erosive esophagitis. It is hoped that vigorous efforts to treat gastroesophageal reflux disease may reduce hospitalization in these patients.

Adult↗