Incidence Of Severe Bleeding Research Articles

Web-Based Warfarin Management (Alfalfa App) Versus Traditional Warfarin Management: Multicenter Prospective Cohort Study.

Poor anticoagulation management of warfarin may lead to patient admission, prolonged hospital stays, and even death due to anticoagulation-related adverse events. Traditional non-web-based outpatient clinics struggle to provide ideal anticoagulation management services for patients, and there is a need to explore a safer, more effective, and more convenient mode of warfarin management. This study aimed to compare differences in the quality of anticoagulation management and clinical adverse events between a web-based management model (via a smartphone app) and the conventional non-web-based outpatient management model. This study is a prospective cohort research that includes multiple national centers. Patients meeting the nadir criteria were split into a web-based management group using the Alfalfa app or a non-web-based management group with traditional outpatient management, and they were then monitored for a 6-month follow-up period to collect coagulation test results and clinical events. The effectiveness and safety of the 2 management models were assessed by the following indicators: time in therapeutic range (TTR), bleeding events, thromboembolic events, all-cause mortality events, cumulative event rates, and the distribution of the international normalized ratio (INR). This national multicenter cohort study enrolled 522 patients between June 2019 and May 2021, with 519 (99%) patients reaching the follow-up end point, including 260 (50%) in the non-web-based management group and 259 (50%) in the web-based management group. There were no observable differences in baseline characteristics between the 2 patient groups. The web-based management group had a significantly higher TTR than the non-web-based management group (82.4% vs 71.6%, P<.001), and a higher proportion of patients received effective anticoagulation management (81.2% vs 63.5%, P<.001). The incidence of minor bleeding events in the non-web-based management group was significantly higher than that in the web-based management group (12.1% vs 6.6%, P=.048). Between the 2 groups, there was no statistically significant difference in the incidence of severe bleeding and thromboembolic and all-cause death events. In addition, compared with the non-web-based management group, the web-based management group had a lower proportion of INR in the extreme subtreatment range (17.6% vs 21.3%) and severe supertreatment range (0% vs 0.8%) and a higher proportion in the treatment range (50.4% vs 43.1%), with statistical significance. Compared with traditional non-web-based outpatient management, web-based management via the Alfalfa app may be more beneficial because it can enhance patient anticoagulation management quality, lower the frequency of small bleeding events, and improve INR distribution.

Platelet inhibitor withdrawal and outcomes after coronary artery surgery: an individual patient data meta-analysis.

To evaluate the association between guideline-conforming as compared to shorter than recommended withdrawal period of P2Y12 receptor inhibitors prior to isolated on-pump coronary artery bypass grafting (CABG) and the incidence of severe bleeding and ischaemic events. Randomized controlled trials are lacking in this field. We searched PUBMED, Embase and other suitable databases for studies including patients on P2Y12 receptor inhibitors undergoing isolated CABG and reporting bleeding and postoperative ischaemic events from 2013 to March 2024. The primary outcome was incidence of Bleeding Academic Research Consortium type 4 (BARC-4) bleeding defined as any of the following: perioperative intracranial bleeding, reoperation for bleeding, transfusion of ≥5 units of red blood cells, chest tube output of ≥2 l. The secondary outcome was postoperative ischaemic events according to the Academic Research Consortium 2 Consensus Document. Patient-level data provided by each observational trial were synthesized into a single dataset and analysed using a 2-stage IPD-MA. Individual data of 4837 patients from 7 observational studies were synthesized. BARC-4 bleeding, 30-day mortality and postoperative ischaemic events occurred in 20%, 2.6% and 5.2% of patients. After adjusting for EuroSCORE II and cardiopulmonary bypass time, guideline-conforming withdrawal was associated with decreased BARC-4 bleeding risk in patients on clopidogrel [adjusted odds ratio (OR) 0.48; 95% confidence intervals (CI) 0.28-0.81; P = 0.006] and a trend towards decreased risk in patients on ticagrelor (adjusted OR 0.48; 95% CI 0.22-1.05; P = 0.067). Guideline-conforming withdrawal was not significantly associated with 30-day mortality risk (clopidogrel: adjusted OR 0.70; 95% CI 0.30-1.61; ticagrelor: adjusted OR 0.89; 95% CI 0.37-2.18) but with decreased risk of postoperative ischaemic events in patients on clopidogrel (clopidogrel: adjusted OR 0.50; 95% CI 0.30-0.82; ticagrelor: adjusted OR 0.78; 95% CI 0.45-1.37). BARC-4 bleeding was associated with 30-day mortality risk (adjusted OR 4.76; 95% CI 2.67-8.47; P < 0.001). Guideline-conforming preoperative withdrawal of ticagrelor and clopidogrel was associated with a 50% reduced BARC-4 bleeding risk when corrected for EuroSCORE II and cardiopulmonary bypass time but was not associated with increased risk of 30-day mortality or postoperative ischaemic events.

Assessment of a randomized controlled trial on the safety of pre-placing bronchial balloons in transbronchial lung cryobiopsy for diagnosing interstitial lung disease

Rationale and objectivesBleeding is a major complication of transbronchial lung cryobiopsy (TBLC), and pre-placing a bronchial balloon is one of the clinical practices used to prevent it, but with very weak evidence, which should be confirmed. This study aimed to conduct whether pre-placing a bronchial balloon in TBLC for diagnosing interstitial lung disease (ILD) is more safety.Materials and methodsIn this prospective, single-center, randomized controlled trial, patients with suspected ILD were enrolled and randomly assigned to pre-placed balloon and none-pre-placed balloon groups. The primary outcome was incidence of moderate bleeding in each group. The secondary endpoints were the incidence of severe bleeding, pneumothorax, and other procedural complications.ResultsExactly 250 patients were enrolled between August 2019 and March 2022, with 125 in each group. There were no significant differences in severe bleeding between the none-pre-placed balloon group and pre-placed balloon group (1.6% vs. 0.8%; adjusted p = 0.520), while more moderate bleeding occurred in the none-pre-placed balloon group (26.4% vs. 6.4%, adjusted p = 0.001), as well as more use of hemostatic drug (28.0% vs. 6.4%, adjusted p = 0.001). Three patients in the none-pre-placed balloon group used the bronchial balloon. More samples could be acquired in the pre-placed balloon group than in the none-pre-placed balloon group (3.8 ± 0.9 vs. 3.1 ± 0.9, p < 0.001). There were no significant differences in multidisciplinary discussion (MDD) between the two groups (89.6% vs. 91.2%, adjusted p = 0.182).ConclusionA pre-placed bronchial balloon can reduce the incidence of moderate bleeding and increase the confidence of the bronchoscopists. However, it had no effect on increasing the diagnostic rate of MDD and reducing severe bleeding.Registration number: NCT04047667 (www.clinicaltrials.gov identifier).

The bleeding risk and safety of multiple treatments by bronchoscopy in patients with central airway stenosis

Background Central airway obstruction (CAO) are common abnormality that usually needing interventional bronchoscopy, and sometimes multiple rounds of treatment. However, there were few studies explore the safety of it. Research design & methods The records of patients who underwent interventional bronchoscopy because of CAO at Respiratory department between January 1, 2010, and December 31, 2020 were revised. The patients’ clinical characteristics, information about bronchoscopy and incidence of complications were collected and analyzed. Results There were totally 1,482 bronchoscopy procedures conducted in the 733 CAO patients. And the incidence of major complications in the retreatment group was significantly lower than that in the first treatment group ((4.77% vs. 1.87%, χ2=9.78, df=1, p<0.01), so did the incidence of severe bleeding (2.46% vs. 0.40%, χ2=11.20, df=1, p<0.01). However, there was some variability between the two groups in age and anesthesia type. A short interval time, more treatment times, and general anesthesia were related to a lower incidence of hemorrhage. For patients who were previously bleeding, the incidence of hemorrhage was significantly higher than the incidence in the non-bleeding patients (42.93% vs. 16.33%, respectively; χ2=57.54, df=1, p<0.01). Conclusion For the patients with CAO, repeated interventional bronchoscopy treatment was safe, and it should be treated with discretion when retreat the patients once bleeding during previous therapeutic bronchoscopy.

Risk of bleeding after ground-level falls in elderly patients with atrial fibrillation and warfarin therapy

The aim of this study was to investigate bleeding risk in patients treated with VKAs after ground-level falls, considering the type and severity of bleeding. The study was designed as a retrospective cohort study and included a total of 204 elderly patients aged > 65 years treated for AF continuously with warfarin for more than 3 years. Data were obtained from hospital registries in Bratislava, Slovakia. A 5-year assessment of death/survival was performed to determine mortality. There was no statistically significant difference in severe bleeding (2.13 % with falls vs 2.55 % without, p = 1) and 5-year mortality (45 % and 38 % respectively, p = 0.3987) based on the presence of falls. Multivariate analysis, after adjustment for age, CHA2DS2VASc, HASBLED, stroke history, labile INR and number of falls showed that only HASBLED score was a statistically significant contributor (CI: 1.0245 - 1.0919, p = 0.0007) to severe bleeding. There was statistically significant difference in severe bleeding (18 % vs 0 %, p = 0.0132) between patients suffering from spontaneous and bleeding after falls and also when comparing individual bleeding episodes (12 % vs 1 %, p < 0.0001). There was no statistically significant difference in 5-year mortality between the two groups (43 % vs 42 % respectively, p = 0.3931). Our results show that occurrence of falls in AF patients treated with VKAs have no significant impact on the incidence of severe bleeding and 5-year mortality and that spontaneous bleeding was associated with a significantly higher risk of severe bleeding compared to bleeding after falling (Tab. 4, Ref. 30).

A Two-Step Method for Percutaneous Transhepatic Choledochoscopic Lithotomy.

Intrahepatic and extrahepatic choledocholithiasis is a challenge in the field of biliary surgery. We present our experience using a two-step percutaneous transhepatic choledochoscopic lithotomy (PTCSL) procedure to treat challenging biliary stones. We retrospectively reviewed 81 patients with intrahepatic and extrahepatic choledocholithiasis treated using this two-step PTCSL from January 2013 to January 2020, including 40 males and 41 females, with an average age of 66 years. In contrast to traditional percutaneous transhepatic cholangioscopy (PTCS), a channel was established directly through a 16F Amplatz sheath, and the stone in the channel was removed with the aid of a nephroscope. The clinical efficacy and complications of all patients were analyzed. Eighty-one patients (81/81, 100%) had their biliary stones successfully removed; 62/81 patients (76.5%) had biliary stones completely removed after the first operation; 17/81 patients (21%) underwent a second operation; 2/81 patients (2.5%) needed a third operation to completely remove the stones. The incidence of severe bleeding during the operation was 0%, and there were no deaths. The use of the two-step PTCSL method is safe and efficacious, and contributes to a better prognosis of intrahepatic and extrahepatic choledocholithiasis.

Severe Bleeding Risks of Direct Oral Anticoagulants in the Prevention and Treatment of Venous Thromboembolism: A Network Meta-Analysis of Randomised Controlled Trials

The aim of this study was to determine the severe bleeding safety of direct oral anticoagulants (DOACs) for the prevention and treatment of venous thromboembolism (VTE). PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched up to 6 January 2021. The incidence of severe bleeding (major, gastrointestinal [GI], intracranial, and fatal) was investigated. Using frequentist network meta-analysis, interventions that were not compared directly could be compared indirectly by the 95% confidence interval (CI), making the search results more intuitive. Based on surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. Thirty-one randomised controlled trials (76 641 patients) were included. For the treatment of VTE, the risk of major bleeding with apixaban was significantly lower than dabigatran (odds ratio [OR] 2.10, 95% CI 1.07 – 4.12) and edoxaban (OR 2.64, 95% CI 1.36 – 5.15). The safety of the drugs was ranked from highest to lowest as follows: major bleeding: apixaban (SUCRA 98.0), rivaroxaban (SUCRA 69.6), dabigatran (SUCRA 50.7), edoxaban (SUCRA 26.5), and vitamin K antagonists (VKAs; SUCRA 5.1); GI bleeding: apixaban (SUCRA 80.7), rivaroxaban (SUCRA 66.8), edoxaban (SUCRA 62.3), VKAs (SUCRA 34.4), and dabigatran (SUCRA 5.8); intracranial bleeding: rivaroxaban (SUCRA 74.4), edoxaban (SUCRA 70.4), dabigatran (SUCRA 58.2), apixaban (SUCRA 44.4), and VKAs (SUCRA 5.6); fatal bleeding: edoxaban (SUCRA 82.7), rivaroxaban (SUCRA 59.2), dabigatran (SUCRA 48.6), apixaban (SUCRA 43.0), and VKAs (SUCRA 16.3). For the prevention of VTE, the risk of major bleeding with apixaban was significantly lower than rivaroxaban (OR 2.14, 95% CI 1.02 – 4.52). Among the four types of bleeding, apixaban had the lowest bleeding risk among DOACs (major bleeding: SUCRA 81.6; GI bleeding: SUCRA 75.4; intracranial bleeding: SUCRA 64.1; fatal bleeding: SUCRA 73.6). For the treatment of VTE, in terms of major bleeding and GI bleeding, apixaban had the lowest bleeding risk; in terms of intracranial bleeding, rivaroxaban had the lowest bleeding risk; in terms of fatal bleeding, edoxaban had the lowest bleeding risk. For the prevention of VTE, apixaban had the lowest bleeding risk.

One-year follow-up results of atrial fibrillation patients who undergoing transcatheter aortic valve implantation

Objective: To investigate whether atrial fibrillation (AF) before transcatheter aortic valve implantation (TAVI) will affect the prognosis of patients post TAVI. Methods: This is a single center retrospective study. A total of 115 patients with severe aortic stenosis (AS) who were admitted to General Hospital of Northern Theater Command from May 2016 to November 2020 and successfully received TAVI treatment were included. According to absence or accompaniment of AF pre-TAVI, they were divided into AF group (21 cases) and non-AF group (94 cases). The patients were followed up for postoperative antithrombotic treatment and the occurrence of the net adverse clinical and cerebrovascular events (NACCE) at 12 months post TAVI, including cardiogenic death, readmission to hospital for heart failure, nonfatal myocardial infarction, ischemic stroke and severe bleeding (BARC levels 3-5). Univariate logistic regression was used to analyze the related factors of NACCE. Results: Among the 115 selected patients, age was (73.8±6.9) years, there were 63 males. And 21 cases (18.2%) were diagnosed as AFbefore TAVI. In terms of postoperative antithrombotic therapy, 48.9% (46/94) of the patients in the non-AF group received monotherapy and 47.9% (45/94) received dual antiplatelet therapy. In the AF group, 47.6% (10/21) received anticoagulants and 33.3% (7/21) received dual antiplatelet therapy. The proportion of patients in the AF group taking non-vitamin K antagonist oral anticoagulants (NOAC) was higher than that in the non-AF group (38.1% (8/21) vs. 2.1% (2/94), P<0.001). Patients in both groups were followed up to 12 months after TAVI. During the 12 months follow-up, the incidence of NACCE after TAVI was 14.3% (3/21) in the AF group, which was numerically higher than that in the non-AF group (6.4% (6/94)), but the difference was not statistically significant (P=0.441). The incidence of severe bleeding was significantly higher in the AF group than in the non-AF group (9.5% (2/21) vs. 0, P=0.032). Univariate logistic regression analysis showed that hypertension was associated with the risk of NACCE (OR=8.308, P=0.050), while AF was not associated with the risk of NACCE (P=0.235). Conclusion: The incidence of severe bleeding after TAVI is higher in patients with AF than in patients without AF prior TAVI, and there is a trend of increased risk of NACCE post TAVI in AF patients.

Percutaneous Transhepatic Choledochoscopic Lithotomy (PTCSL) is Effective for the Treatment of Intrahepatic and Extrahepatic Choledocholithiasis.

To explore percutaneous transhepatic choledochoscopic lithotomy (PTCSL) as a treatment for intrahepatic and extrahepatic choledocholithiasis. A retrospective review of 67 patients with intrahepatic and extrahepatic choledocholithiasis treated by PTCSL from January 2014 to January 2019, including 36 males and 31 females, with an average age of 66 years. During the operation, the doctor established a channel through a 16-Fr Amplatz sheath and removed the stone in the channel with the aid of nephroscope. The clinical efficacy and complications of all patients were analyzed. Sixty-seven patients (67/67, 100%) had their stones successfully removed in the first operation. Only 2 patients (2/67, 3.0%) developed mild reactive pleural effusion after the operation, and 1 patient (1/67, 1.5%) with cholangiocarcinoma after the operation. The incidence of severe bleeding during the operation was 0%. PTCSL is a minimally invasive, simple, effective and easy to repeat procedure for use in the clinic. It is an effective surgical treatment and is worthy of clinical use.

A prospective randomized trial of xylometazoline drops and epinephrine merocele nasal pack for reducing epistaxis during nasotracheal intubation.

BackgroundThe most frequent complication of nasotracheal intubation (NTI) is epistaxis. Epinephrine nasal gauze packing has been used conventionally as a pre-treatment for reducing epistaxis, but it carries a disadvantage of pain and anxiety in patients. However, xylometazoline drops are easier to administer and more convenient for patients. We aimed at comparing the effectiveness of xylometazoline drops and epinephrine merocele packing in reducing bleeding and postoperative complications in our population.MethodsOur study enrolled 120 patients in a double-blind randomized controlled trial. We randomly allocated ASA1 or 2 adult patients into 2 groups: Group X and Group E. Group X received 0.1% xylometazoline nasal drops, and epinephrine (1:10,000) merocele nasal packing was used in Group E. The primary outcome was the incidence of bleeding during NTI; the severity of bleeding, navigability, bleeding during extubation, and postoperative complications were secondary outcomes. We used IBM SPSS and Minitab software for statistical analysis, and P < 0.05 was considered statistically significant.ResultsWe analyzed the data of 110 patients: 55 in Group X and 55 in Group E. The two groups did not have different bleeding incidence (56.4% vs 60.0%; P = 0.70); however, the incidence of severe bleeding was less with xylometazoline than with epinephrine (3.63% vs 14.54%; P < 0.05). We also observed less bleeding during extubation (38.2% vs 68.5%; P < 0.05) with xylometazoline. Other secondary outcomes were akin to both groups.ConclusionThe incidence of severe and post-extubation bleeding was significantly less with xylometazoline. Hence, it may be an effective alternative for reducing the incidence and severity of epistaxis during NTI.

Bronchial arterial embolization may reduce the risk of severe bleeding in central airway obstruction due to renal cell carcinomas during bronchoscopic procedures.

Background:Hemorrhage is a life-threatening complication during bronchoscopic intervention in patients with central airway obstruction (CAO) due to metastatic renal cell carcinoma (RCC). Whether pre-bronchoscopic bronchial arterial embolization (BAE) can reduce the risk of severe bleeding in CAO patients due to metastatic RCC remains unclear.Methods:A total of 31 CAO patients due to metastatic RCC were included retrospectively and divided into a BAE group (receiving pre-bronchoscopic BAE) and non-BAE group in this study. Based on computed tomography (CT) and bronchoscopic findings, tumor debulking was used to reconstruct the airway during interventional bronchoscopy. The primary outcome was the incidence of severe bleeding during bronchoscopic procedures. Bleeding-related complications, Karnofsky performance score (KPS) and dyspnea score were also analyzed over a 1-month observation period.Results:There were no significant differences between the two groups in baseline characteristics, including patients’ features, tumor morphology under CT scannings, tumor site, and obstruction degree under bronchoscopic examination. Procedure-related bleeding occurred in all 31 patients. Pre-bronchoscopic BAE significantly reduced the incidence of moderate and major bleeding when compared with that in the non-BAE group. The incidence of poor visualization and hypoxia was also reduced significantly in the BAE group. There was no significant difference in KPS and dyspnea score between the BAE and non-BAE groups at 1 month follow up.Conclusion:Pre-bronchoscopic BAE might be a feasible option to reduce the risk of severe bleeding for CAO patients due to metastatic RCC during bronchoscopic intervention. Interventional bronchoscopy was a safe and effective procedure for CAO due to metastatic RCC. The reviews of this paper are available via the supplemental material section.

Safety of Percutaneous Biopsy for Hepatic Angiosarcoma: Results of a Multicenter Korean Survey

PurposeTo evaluate the incidence of severe bleeding and mortality associated with percutaneous biopsy for hepatic angiosarcoma in a multicenter retrospective cohort. Materials and MethodsA retrospective review of 33 patients with biopsy-proven hepatic angiosarcoma (29 male; median age, 57 y; age range, 24–96 y) was performed at seven tertiary academic hospitals between January 1998 and March 2015. The mean maximum tumor size was 5.5 cm (range, 1.7–20 cm). An 18-gauge automated cutting biopsy needle was used with a freehand technique in all patients who underwent ultrasonography-guided percutaneous core needle biopsy on an inpatient basis. The incidences of severe bleeding and procedure-related mortality were evaluated per Society of Interventional Radiology (SIR) guidelines. ResultsThere was a mean of 2.8 needle passes per patient during the procedure (range, 1–6). The overall incidence of severe bleeding events (SIR grade C/D) was 9.1% (3 of 33). Two patients were managed with blood transfusion, and one patient underwent embolization for bleeding control. No other major complications were encountered. There were no cases of mortality associated with the biopsy. ConclusionsSevere bleeding was not a frequent complication after percutaneous biopsy for hepatic angiosarcoma. The majority of bleeding complications could be controlled with conservative management.

Thrombophylaxis in Patients Undergoing Bariatric Surgery

Background: Patients undergoing bariatric surgery are at increased risk for symptomatic venous thromboembolism (VTE). Although the incidence of clinical VTE is lower than in other general and orthopedic surgical procedures, pulmonary embolism is an independent predictor of death after gastric bypass surgery. The optimal strategy for postoperative thrombophylaxis in bariatric surgery has yet to be elucidated. In 2010 our institution proposed a guideline for postoperative thrombophylaxis for bariatric surgery based on risk stratification. Patients were considered high risk if they had history of VTE or a BMI >/= 60 kg/m2 or if they had two or more of the following: age > 50, BMI >/= 50 kg/m2, male sex, recent history of smoking, obstructive sleep apnea, varicose veins, or hormone therapy within 30 days. All patients undergoing bariatric surgery received enoxaparin 40 mg SC twice daily in addition to mechanical thrombophylaxis including venodynes and compression stockings during the hospital stay. Prophylactic IVC filter insertion was not recommended. High-risk patients received an extended course of anticoagulation for 10 days after discharge.Methods: We retrospectively reviewed the medical charts of 692 patients who underwent bariatric surgery at Dartmouth-Hitchcock Medical Center from 2009 to 2014. We analyzed the incidence of VTE and bleeding complications under two different institutional thrombophylaxis protocols: an earlier protocol of VTE prophylaxis based on surgeon's preference (n = 62) and our subsequent protocol based on risk stratification (n = 630).Results: Prior to implementing our protocol the incidence of VTE and bleeding complications in patients who underwent bariatric surgery was 1.6% (1 in 62) for each. After 2010, with the implementation of extended VTE prophylaxis for high-risk patients, the incidence of postoperative VTE was 0% (0 in 630) and the incidence of postoperative bleeding was 2.7% (17 in 630). Of 17 patients who developed postoperative bleeding, 14 (82%) developed bleeding before postoperative day 3 during the hospitalization and 3 (18%) experienced delayed bleeding after hospital discharge. Of 3 patients with delayed bleeding, only 1 was on the extended thrombophylaxis protocol. Severe bleeding, defined as the need for packed red blood cell transfusions or re-operation, occurred in 1.6% (10 in 630).Conclusion: Our study demonstrates that a protocol based on risk stratification is effective at reducing the risk of symptomatic VTE in patients undergoing bariatric surgery. Although the incidence of all postoperative bleeding appears to have increased slightly after implementation of the protocol, the incidence of severe bleeding appears unchanged. As most of the post-operative bleeding events occurred during the hospitalization period, extending the length of pharmacologic thromboprophylaxis was not associated with an increase in bleeding. This study is limited by its retrospective design and the small number of patients studied prior to implementing the extended VTE prophylaxis protocol. Nevertheless, the findings are promising with respect to VTE risk reduction after bariatric surgery and suggest that prospective evaluation of the thromboprophylaxis protocol is in order. DisclosuresNo relevant conflicts of interest to declare.

Autologous blood in obstetrics: where are we going now?

In developed countries1, pregnancy-related transfusion accounts for about 6 percent of red blood cell (RBC) units transfused. This means that, for example, in the UK as a whole, approximately 70,000 units of RBC are transfused to obstetric patients each year2. The pattern of blood usage is very different in countries in which diagnostic and treatment options are more limited, with 37 percent of transfusions being given to women with obstetric emergencies1. Obstetric haemorrhage is a leading cause of maternal and perinatal mortality3. Placental abruption and placenta praevia/accreta can present as antepartum haemorrhage and are risk factors for post-partum haemorrhage (PPH). Uterine atony, inversion, retained products of conception and genital tract trauma all cause PPH and account for the majority of cases of major haemorrhage. Uterine rupture is an infrequent cause of haemorrhage and maternal death and can occur spontaneously or at the site of previous uterine surgery (caesarean section or retained placenta)3. During the triennium 2006–2008, the rate of deaths from hemorrhage in the UK was 0.39 per 100,000 maternities4. The incidence of severe bleeding in childbirth has been estimated in various surveys and is approximately one in 200 to 250 deliveries4. In developed countries treatment is generally effective with an approximate case fatality rate between 1 in 600 to 800 cases of obstetric bleeding5–7. Various blood conservation techniques can reduce exposure to allogeneic blood. These include pre-operative autologous blood donation (PABD), acute normovolaemic haemodilution (ANH) and intra-operative blood salvage (IBS). PABD may cause anaemia, does not eliminate transfusion risk, cannot be used in an emergency, is not acceptable to Jehovah’s Witnesses and should be reserved for exceptional circumstances8,9. ANH may induce anaemia and cardiac failure, cannot be used in an emergency and may have a limited role in combination with other techniques9. The use of IBS has increased substantially during the last two decades and the re-infusion of shed washed blood is commonplace in many types of surgical operations in which heavy blood loss is anticipated10,11. In this technique, blood shed at the time of surgery is collected and washed, and RBC are returned to the patient as an ongoing process (Figure 1)12,13. In skilled hands, blood salvage can be quickly set up and the final product returned to the patient within minutes of collection. In addition, this technique is also acceptable to some Jehovah’s Witnesses, provided the equipment is set up in continuity with the circulation (Figure 1)14, but consent needs to be obtained on an individual basis. Figure 1 Schematic representation of a blood salvage system with a double suction setup to reduce the possible contamination of the blood suctioned from the surgical field138. In this setup, one suction line is connected to the collection reservoir and used for ... However, the safety of IBS in obstetrics has been questioned and its introduction in this clinical arena has been delayed because of theoretical concerns stemming from the historical and ongoing dispute focused on the risk of maternal-foetal anti-Rh(D) alloimmunisation and the risk of contamination of the cell-saved blood with traces of amniotic fluid (AF)15,16. The objective of this article is to review the role of autologous blood conservation techniques in obstetrics focusing on the currently available evidence regarding IBS. An overview of current European regulatory requirements on IBS will also be provided.

Phase II–III Study of Gemtuzumab Ozogamicin Monotherapy versus Best Supportive Care in Older Patients with Newly Diagnosed AML Unfit for Intensive Chemotherapy: First Results of the EORTC-GIMEMA AML-19 Trial

Treatment of AML in the elderly remains challenging. In particular, few therapeutic options exist for patients (pts) who are not considered medically fit for intensive chemotherapy. Gemtuzumab ozogamicin (GO), a humanized anti-CD33 monoclonal antibody conjugated to calicheamicin, has demonstrated single agent efficacy in older patients with relapsed AML. In a previous trial we reported a complete response rate of 17% when the licensed dose/schedule of GO was used as frontline monotherapy for older unfit pts with AML, but excess hematologic and liver toxicity suggested changes in both dosing and scheduling to improve feasibility. The AML-19 study was designed as a sequential phase II–III trial in pts of age 61 or over with untreated AML, who could not be considered candidates for, or must have declined, conventional intensive chemotherapy. The primary objective of the phase II study was to investigate whether any of two different schedules of lower dose GO monotherapy (total delivered dose 9 mg/m2 in 2 or 3 fractions over one week) is sufficiently effective and tolerable frontline therapy to continue phase III comparison with best supportive care (BSC). Pts had to have adequate renal and hepatic function, and the WBC count had to be less than 30,000/cmm at the time of registration. Two-thirds of the pts were randomly assigned to receive a single induction course of either GO 3 mg/m2 iv on days 1, 3 and 5 (arm A), or GO 6 mg/m2 iv on day 1 and 3 mg/m2 on day 8 (arm B); the remaining third was assigned to the BSC arm. Randomization was stratified by age, performance status (PS), initial WBC, CD33 expression on marrow blasts, and Institution. Pts with no evidence of objective disease progression were eligible to receive continuation treatment with monthly outpatient infusions of GO at 2 mg/m2 for a maximum of 8 months. Primary end-point of the phase II study was clinical benefit rate (CBR) defined as the number of pts either achieving a remission (CR, CRp, PR) or maintaining a stable disease (SD) in each experimental arm. The arm associated with the highest CBR would be selected for phase III assessment, providing that it is at least 48% (Simon design). Between 06/2004 and 12/2006, 56 pts were randomized in the two experimental arms (arm A 29; arm B 27). The two arms were comparable in terms of age (arm A: median 77 yrs; arm B: median 78 yrs), PS >2 (arm A: 7%; arm B: 4%), secondary AML (arm A: 45%; arm B: 37%), and CD33 expression on ≥20% marrow blasts (arm A: 86%; arm B: 85%). In arm A, 6 pts achieved CR, 2 PR, and 3 maintained SD for an overall CBR of 38% (90% CI, 23%–55%); in arm B, 5 pts achieved CR, 1 CRp, and 11 maintained SD for an overall CBR of 63% (90% CI, 45%–78%). Most toxicities were <grade 3 in both arms and included nausea/vomiting, diarrhea, fatigue, stomatitis and transient elevations of serum transaminases and bilirubin. The rate of grade ≥3 infection was slightly higher in arm B (48% vs 31%), as was the incidence of severe bleeding (11% vs 0%). All-cause early mortality (<6 wks) occurred in 17% of pts in arm A (2 infection, 3 AML) and in 11% of pts in arm B (1 infection, 1 AML, 1 infection+AML). In summary, lower dose GO is a tolerable and active primary therapy for older AML pts who are considered unsuitable for intensive chemotherapy. The day 1+8 schedule (arm B) is associated with a more favourable efficacy profile, meeting the statistical criteria to be selected as the preferred regimen for phase III comparison with BSC. Accrual to the phase III trial is ongoing.

Abstract 3164: Combined Antithrombotic Therapy in Atrial Fibrillation. Role of different Antiplatelet Strategies

The NASPEAF trial showed that combined anticoagulant plus antiplatelet therapy was more effective than anticoagulant alone at reducing vascular events in atrial fibrillation (AF) patients. We planned both to validate this benefit during a longer follow-up of patients included in that trial and to assess the hypothesis that combination of anticoagulation plus different antiplatelets could be differently effective and/or safe in patients from that trial and new ones followed-up for at least one year. Methods: Five hundred and seventy-four AF patients were included. Anticoagulation alone therapy (INR 2.0 –3.0) was used as control group (g) 1 to compare with anticoagulation (1.9 –2.5) plus either trifusal 600 mg/d (g2), trifusal 300 mg/d (g3) or aspirin 100 mg/d (g4). Median follow-up was 50, 32, 50 and 37 months respectively. The primary outcome was a composite of ischemic/haemorrhagic stroke, systemic/coronary ischemic events and cardiovascular death. The incidence of severe bleeding was also collected. Anticoagulation was regularly controlled in dedicated units. Results: Long-term follow-up showed benefit of combined anticoagulant plus trifusal 600 mg/d vs anticoagulant alone (primary outcome 2.86% pt/years in g1 vs 1.36% in g2, P=0.014). Combined therapy using other antiplatelet strategies was less effective or safe due to higher incidence of ischemic events when using trifusal 300 mg/d (2.44% pt/years in g3 vs 0.61% in g2, P=0.031) as well as more severe bleeding events with aspirin 100 mg/d (6.60% pt/years in g4 vs 1.51% in g2, P=0.008). Groups g1, g3 and g4 had similar primary outcome (2.86% pt/years, 2.67% and 2.83% respectively). Mean INR and other anticoagulation parameters were similar in the three combined therapy groups. Non-gastric severe bleeding incidence during combined therapy with trifusal 600 mg/d (0.3% pt/years) was lower than that observed in either anticoagulant alone therapy (2.1%, P=0.012) or combined with aspirin (6.60%, P=0.008). In conclusion, long-term follow-up of the NASPEAF trial confirmed the benefit of combined antithrombotic therapy over anticoagulant alone therapy. Combined therapy with aspirin 100 mg/d instead of trifusal 600 mg/d caused higher incidence of severe bleeding.

The incidence and impact of thrombocytopenia in myelodysplastic syndromes

Thrombocytopenia and platelet dysfunction contribute to hemorrhagic complications in the myelodysplastic syndromes (MDS). Reliable data regarding the frequency and consequences of thrombocytopenia in MDS are lacking. An extensive literature review indicated that the prevalence of thrombocytopenia (platelets<100x10(9)/L) in MDS ranged from 40% to 65%; the median frequency of thrombocytopenia prior to any MDS therapy was 65% (range, 23-93%). A retrospective review of patients who were referred to the University of Texas M. D. Anderson Cancer Center (MDACC) identified 1605 of 2410 patients (67%) with thrombocytopenia at referral. Of these, 1756 patients were classified using the International Prognostic Scoring System (IPSS), and 896 patients (51%) had intermediate-2 or high-risk disease. Treatment-related thrombocytopenia was observed in studies that involved azacitidine, tipifarnib, decitabine, lenalidomide, sirolimus, and combination chemotherapy with idarubicin, cytarabine, and topotecan. The reported incidence of hemorrhagic complications in the literature ranged from 3% to 53%, and the frequency of hemorrhagic deaths ranged from 14% to 24%. At MDACC, 460 patients had a coded cause of death: hemorrhage as a contributory cause of death, 20%; hemorrhage as the only cause of death, 10%. Thrombocytopenia was common in MDS, and there was an increased prevalence in higher risk IPSS categories. Many approved and investigational MDS therapies caused or exacerbated preexisting thrombocytopenia. The incidence of severe bleeding in MDS was greater than reported in current guidelines.

The Incidence and Impact of Thrombocytopenia in Myelodysplastic Syndrome (MDS).

Background: MDS is a heterogeneous stem cell malignancy characterized by ineffective hematopoiesis and increased risk of transformation to acute myeloid leukemia. Thrombocytopenia and platelet dysfunction are recognized to contribute to hemorrhagic complications, however, reliable data regarding the frequency and consequences of thrombocytopenia in MDS are lacking.Objective: To assess thrombocytopenia in MDS based on literature and chart review.Methods: MDS literature (January 1980 to November 2005) was identified using MEDLINE, EMBASE, and Cochrane databases, society websites, and hand searches of bibliographies. In addition, a retrospective review of all patients referred to the MD Anderson Cancer Center (MDACC) with MDS since 1980 was performed.Results: A total of 85 references were identified describing clinical consequences of thrombocytopenia, n=16; efficacy and safety of MDS therapies, n=60; guidelines, n=9. Because of variable definitions of thrombocytopenia, a platelet count <100x109/L was applied as the threshold point in the literature analysis. The prevalence of thrombocytopenia in MDS ranged from 40% to 65%. Baseline thrombocytopenia rates were reported in 19/60 (32%) references; the median frequency of thrombocytopenia prior to MDS therapy was 65% (range, 23% to 93%). The MDACC database review identified 1605/2410 (67%) patients with thrombocytopenia (<100x109/L) at referral. Severe thrombocytopenia (<20x109/L) was observed in 425 (18%) patients. Using the International Prognostic Scoring System (IPSS), 399/2410 (17%) patients had intermediate-2 or high risk disease; 83% and 25% of these patients had platelet counts of <100x109/L and <20x109/L, respectively. Corresponding event frequencies decreased to 21% and 3% in patients with low or intermediate-1 risk MDS (264/2410, 11%). The reported incidence of MDS treatment-related thrombocytopenia was >50% in studies involving lenalidomide, azacitidine, or a combination of idarubicin, cytarabine and topotecan. Treatment-related thrombocytopenia was also observed in studies involving tipifarnib, linomide, decitabine, all-trans retinoic acid, and sirolimus. The reported incidence of hemorrhagic complications ranged from 3% to 53%, and the frequency of hemorrhagic deaths ranged from 14% to 24%. At MDACC, 460 patients had a coded cause of death: hemorrhage as a cause of death, 20%; hemorrhage as the only cause of death, 10%.Conclusions: Thrombocytopenia is common in MDS with a higher prevalence in higher risk IPSS categories. Many approved and investigational MDS therapies cause or exacerbate pre-existing thrombocytopenia. The incidence of severe bleeding in MDS was higher than reported in current guidelines or reviews.

Multiple Enterocolic Perforations and Their Possible Association with Prolonged Intake of Nimesulide: Report of Two Cases

Nimesulide is a selective cyclooxygenase type 2 (COX2) inhibitor that, although having the characteristic antiinflammatory effects of nonsteroidal anti-inflammatory drugs (NSAIDs), has better gastrointestinal tolerability (with less gastric and duodenal injury) than conventional nonselective cyclooxygenase inhibitors) (1). It is well known that toxicity in chronic NSAIDs users is not specific to the gastroduodenal tract. Over the past few years several reports have focused on the prevalence, clinical aspects, and pathogenesis of NSAIDs-induced adverse side effects (ASEs) on the small and large intestine, including diaphragm-like strictures, ulcerations, and perforations, associated with blood and protein loss (2‐5). The prevalence of NSAID-associated enteropathy in the upper gastroenteric tract (UGT) is approximately 20%, and among patients chronically taking NSAIDs the incidence of severe bleeding or perforation complications is 1t o2 %per year of use (6). Nevertheless, the assumption that enteropathy is mainly located in the UGT may be considered a bias, as demonstrated by retrospective, hospital-based, systemic studies showing that ASEs may sometimes have a higher prevalence in the lower gastroenteric tract (LGT) than in the UGT (7). Furthermore, a threeto-one ratio of large-versus-small bowel injuries (ulcers or perforations) was found (8). However, these intestinal complications were not reported in patients on nimesulide. A clinical survey carried out on a large population taking nimesulide gave no ev