Non-bleeding Patients Research Articles

Prognostic analysis of gastrointestinal stromal tumors complicated with gastrointestinal bleeding

To study the relationship between clinicopathological characteristics, prognosis and gastrointestinal bleeding in primary gastrointestinal stromal tumors (GIST). The clinicopathological and follow-up data of 200 patients with gastrointestinal stromal tumors treated in our hospital from April 2008 to December 2014 were retrospectively reviewed. The correlation of gastrointestinal bleeding with gastrointestinal stromal tumor clinicopathological characteristics and prognosis were analyzed. The 200 GIST patients were divided into two groups according to the bleeding in the digestive tract, including 57 gastrointestinal bleeding patients and 143 non-bleeding patients. The mean tumor diameter was 6.5 cm (range 1.8-22 cm) in the bleeding group and 2.5 cm (range 0.4-18 cm) in the non-bleeding group (P<0.05). Of the 57 bleeding patients, 31 located in the stomach, 25 in the small intestine, and one had colorectal bleeding. Fifty patients had mitotic index (MI) ≤ 5/50 HPF, other 6 patients ranged between 5 and 10/50 HPF and one patient had MI >10/50 HPF. Six GIST patients were complicated with tumor rapture. But in the non-bleeding group, 125 patients had gastric GIST, 8 in the small intestine, one colorectum, and 9 had esophageal or other GIST. 141 patients had MI ≤5/50 HPF, 1 patients ranged between 5 and 10/50 HPF and one patient had MI >10/50 HPF. Only 1 GIST patients was complicated with tumor rapture. The gastrointestinal bleeding was closely associated with tumor size, mitotic index, tumor location, risk classifications, tumor rapture and tumor recurrence (P<0.05 for all). The 3-year and 5-year survival rates of the 200 patients were 96.5% and 86.8%, respectively. 16 patients developed recurrence or metastasis, and 11 died of GIST. The 5-year survival rate of patients with gastrointestinal bleeding was 76.2%, significantly lower than that of patients without gastrointestinal bleeding (91.6%, P<0.05). GIST patients complicated with gastrointestinal bleeding have poor prognosis, and attention should be paid to stratifying patients for therapy.

Outcome of liver transplantation in patients with hereditary bleeding disorders: a single centre UK experience.

Patients with hereditary bleeding disorders who have developed end-stage liver disease as a consequence of hepatitis C infection (HCV) acquired from factor concentrates prior to the introduction of viral inactivation continue to be referred for liver transplantation. A retrospective review of case notes and electronic records was performed on all patients with bleeding disorders who have undergone liver transplantation at the University Hospital Birmingham (UHB). Between 1990 and 2014, 35 liver transplants have been performed in 33 patients with hereditary bleeding disorders. The indication for transplantation was mainly end-stage liver disease secondary to HCV. Five patients had human immunodeficiency virus (HIV) co-infection. No excess mortality due to bleeding occurred in the peri or postoperative period. Median overall survival post transplant is 9.7years. Overall survival rates at 1, 3 and 5years are 90%, 72% and 64% respectively. The predominant cause of mortality was liver failure secondary to either recurrent HCV or recurrent hepatocellular carcinoma (HCC). The median overall survival in patients with HIV co-infection is shorter than in those with mono-infection but this is not statistically significant. Patients with a pre-existing HCC had a statistically significant shorter survival (2.4years vs. 13.6years, P=0.007). Liver transplantation has become an accepted treatment option for patients with hereditary bleeding disorders and HCV associated end-stage liver disease with survival rates similar to non-bleeding disorder patients.

Preventable Complications Driving Rising Costs in Management of Patients with Critical Limb Ischemia

This study aimed to identify factors that drive increasing health-care costs associated with the management of critical limb ischemia in elective inpatients. Patients with a primary diagnosis code of critical limb ischemia (CLI) were identified from the 2001-2011 Nationwide Inpatient Sample. Demographics, CLI management, comorbidities, complications (bleeding, surgical site infection [SSI]), length of stay, and median in-hospital costs were reviewed. Statistical analysis was completed using Students' t-test and Mann-Kendall trend analysis. Costs are reported in 2011 US dollars corrected using the consumer price index. From 2001 to 2011, there were a total of 451,823 patients who underwent open elective revascularization as inpatients for CLI. Costs to treat CLI increased by 63% ($12,560 in 2001 to $20,517 in 2011, P<0.001 in trend analysis). Endovascular interventions were 20% more expensive compared with open surgery ($19,566 vs. $16,337, P<0.001). Age, gender, and insurance status did not affect the cost of care. From 2001 to 2011, the number of patient comorbidities (7.56-12.40) and percentage of endovascular cases (13.4% to 27.4%) increased, accounting for a 6% annual increase in total cost despite decreased median length of stay (6 to 5days). Patients who developed SSI had total costs 83% greater than patients without SSIs ($30,949 vs. $16,939; P<0.001). Patients who developed bleeding complications had total costs 41% greater than nonbleeding patients ($23,779 vs. $16,821, P<0.001). Overall, there was a 32% reduction in SSI rates but unchanged rates of bleeding complications during this period. The cost of CLI treatment is increasing and driven by rising endovascular use, SSI, and bleeding in the in-patient population. Further efforts to reduce complications in this patient population may contribute to a reduction in health care-associated costs of treating CLI.

Mathematical model and calculation to predict the effect of prophylactic plasma transfusion on change in international normalized ratio in critically ill patients with coagulopathy.

Plasma transfusion is often used prophylactically in patients with coagulopathy. However, the doses transfused may not be adequate to normalize hemostatic tests, which are commonly used as surrogate markers in practice. Currently, there is no reliable way to predict the posttransfusion international normalized ratio (INR) after plasma transfusion. Therefore, our aim was to develop and validate a formula that can reliably estimate post-plasma transfusion INR. A compartmental model was developed using demographic (sex, height, weight) and laboratory variables (hematocrit [Hct], INRinitial , and plasma volume transfused). The formula was validated using a data set from a multicenter trial conducted between May 2010 and June 2013 in critically ill, nonbleeding patients with coagulopathy, receiving prophylactic plasma transfusions. INR was measured just before and immediately after plasma transfusion. Initial plasma volume is calculated using the patient's Hct and blood volume (derived from Nadler's formula). The estimated immediate posttransfusion INR is then calculated as [Formula: see text] There was a significant agreement between the model predictions and the actual INR measurements after transfusion. A total of 83% of the predictions were within the acceptable range of variation. Furthermore, there was no proportional difference or systemic bias between the predictions and the actual INR measurements. This mathematical formula estimates posttransfusion INR after a certain volume of plasma transfusion with a good predictive ability. This formula, which only requires basic demographic and laboratory variables, may help the physicians to determine the volume of plasma required for a specific target INR in stable, nonbleeding patients.

North American Cooperative Group Members' Patterns of Blood Products Transfusion for Patients with Acute Leukemia

Background. Transfusion of blood products is an integral component of the management of patients with acute leukemias. However, high-quality evidence and clinical trial data to support specific practices of blood product transfusion in this population are limited. We hypothesized that there is wide variation in blood product transfusion practices among providers in North America who manage patients with acute leukemia.Methods. A 30-question web-based survey about transfusion practices was emailed to members of the Eastern Cooperative Oncology Group (ECOG)-ACRIN Cancer Research Group, Alliance for Clinical Trials in Oncology (Alliance), and the Southwest Oncology Group (SWOG), and the Cancer Trials Support Unit (CTSU) on 7/6/2015 with 4 subsequent weekly reminders. The distribution list included 9,859 recipients, of whom at least 741 were providers who treated patients with acute leukemia. Responses were anonymous, and the survey distribution was approved by the respective cooperative group chairs. Descriptive statistics were used to analyze the data.Results. Of 254 responses received, 113 were excluded as they were returned by recipients not directly treating patients with acute leukemia. Another 30 responses were excluded due to incomplete data, leaving 111 responses (43.7%) eligible for the primary analysis. Of those, 109 responders were from North America representing 83 institutions in 33 states and the province of Ontario. Eighty-four of the included responders (75.7%) were physicians, and 44 (39.6%) were females. Median age of responders was 44 years (range, 26-76). A hemoglobin (Hb) level of ≤7 g/dL was the most commonly used threshold (44%) for red blood cell (RBCs) transfusions to asymptomatic stable hospitalized patients, followed closely by 8 g/dL (38%) (Figure 1). In the outpatient setting, the most commonly reported threshold was 8 gm/dL (49%) (Figure 1). Most providers reported that they "always" use leukocyte-reduced (93%) and irradiated (79%) RBCs. A platelet level of 10,000/µL was the threshold for platelet transfusions in the stable non-bleeding hospitalized patients cited by the majority of responders (76%) (Figure 2). This platelet level remained the most common threshold for platelet transfusions for non-bleeding patients in the outpatient setting (49%), although 31% of responders reported a higher threshold of 20,000/µL. A preference for single-donor apheresis platelets was reported by 81% respondents, and 57% use these products exclusively. Most providers (70%) reported always using irradiated platelets. With respect to cryoprecipitate and plasma infusions, nearly half of the respondents reported a threshold fibrinogen level of 100 mg/dL as a trigger for administering a product to a stable non-bleeding patient (Figure 3). The most commonly reported platelet threshold for performing a bone marrow biopsy (BMB) was 10,000/μL (69% of responders), followed by 20,000 (21%), 50,000 (6%), and 30,000 (4%). Therapeutic anticoagulation was held by most responders (80%) before performing a BMB. Most responders (73%) reported a platelet level of 50,000/µL as the lowest level for performing a lumbar puncture (LP) without prophylactic platelet transfusion.Conclusions. This survey demonstrates wide variability in blood product transfusion patterns among providers who treat patients with acute leukemias. A platelet level of 10,000/µL is the most common trigger for platelet transfusions for stable non-bleeding patients in both inpatient and outpatient settings. This, along with a platelet threshold of 50,000/µL for performing an LP, appear to be most widely accepted practices. Our findings emphasize the need to obtain high-quality data to develop consensus evidence-based guidelines for transfusion practices in acute leukemia with the goal of limiting unnecessary transfusions without compromising patient outcomes. [Display omitted] [Display omitted] [Display omitted] DisclosuresSekeres:TetraLogic: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Steensma:Onconova: Consultancy; Incyte: Consultancy; Amgen: Consultancy; Celgene: Consultancy. Prebet:CELGENE: Research Funding. Komrokji:Celgene: Consultancy, Research Funding; Incite: Consultancy; Novartis: Speakers Bureau; GSK: Research Funding. Stone:Merck: Consultancy; AROG: Consultancy; Celgene: Consultancy; Sunesis: Consultancy, Other: DSMB for clinical trial; Abbvie: Consultancy; Novartis: Research Funding; Juno: Consultancy; Amgen: Consultancy; Roche/Genetech: Consultancy; Celator: Consultancy; Agios: Consultancy; Karyopharm: Consultancy; Pfizer: Consultancy. Erba:GlycoMimetics; Janssen: Other: Data Safety & Monitoring Committees; Sunesis; Pfizer; Daiichi Sankyo; Ariad: Consultancy; Millennium/Takeda; Celator; Astellas: Research Funding; Seattle Genetics; Amgen: Consultancy, Research Funding; Novartis; Incyte; Celgene: Consultancy, Patents & Royalties. Barbarotta:Celgene, BMS, Novartis: Speakers Bureau. Gore:Celgene: Consultancy, Honoraria, Research Funding.

Defects in Primary Hemostasis and Acquired Von Willebrand Disease As Cause of Bleeding in Patients with Multiple Myeloma

Introduction. Paraproteinemia has been associated with both thromboembolic and bleeding complications. Previous retrospective analyses and case reports report on a direct correlation of serum immunoglobulin levels (especially IgM and IgA) with critical bleeding events. Underlying mechanisms include interference with platelet function, immune thrombocytopenia, clotting factor deficiencies, and acquired von Willebrand disease (AVWD).Methods. Laboratory data, including qualitative and quantitative analyses of von Willebrand Factor (vWF), collagen binding assay (CBA) and PFA-100 closure time from 132 patients with diagnosis of multiple myeloma between 2003 and 2015 were retrieved, and cases were retrospectively evaluated for bleeding complications. Coagulation abnormalities were correlated with clinical history and disease parameters.Results. 70 out of 132 patients (53%) displayed bleeding complications including multiple hematomas (n=41), epistaxis (n=10), or perioperative bleeding (n=9). Bleeding vs. non-bleeding patients showed no differences regarding age, gender, previous chemotherapy, or immunoglobulin isotypes. Special coagulation lab results of patients with bleeding events are shown in table 1.Table 1Pathological coag labs in 70 patients with bleedingNormalAbnormalSensitivity(95% CI)Specificity(95% CI)PPV*(95% CI)NPV*(95% CI)PLT (<50x103/µl)7000100.47 (0.38-0.56)PT, aPTT6820.06 (0.02-0.1)0.95 (0.85-0.99)0.57 (0.2-0.88)0.47 (0.38-0.56)vWF:Ag or RCoF6460.09 (0.04-0.18)0.95 (0.86-0.99)0.67 (0.3-0.9)0.48 (0.39-0.9)PFA-10027430.61 (0.49-0.73)0.97 (0.88-0.99)0.96 (0.84-99)0.69 (0.58-0.78)CBA/vWF45250.35 (0.25-0.48)0.98 (0.9-0.99)0.96 (0.78-1)0.58 (0.48-0.67)PFA-100 or CBA/vWF52180.74 (0.62-0.84)0.95 (0.86-0.99)0.94 (0.84-1)0.76 (0.65-0.85)*PPV = positive predictive value, NPV = negative predictive valueSerum free light-chain, but not complete Ig paraprotein levels were significantly associated with bleeding events (p<0.001), prolonged PFA-100 closure time (p<0.001), and pathological CBA/vWF-ratio (p<0.05).Conclusions. Bleeding events were most commonly due to defects of primary hemostasis. Global coagulation tests as well as vWF:Ag and RCo were insufficient in predicting bleeding. When the results of both PFA-100 and CBA/vWF-ratio were considered, 74% of the bleeding patients could be detected. We suggest that both PFA-100 and CBA/vWF-ratio should be determined in patients with multiple myeloma and signs of bleeding in order to rule out AVWD with sufficient sensitivity. Serum free light-chain levels were correlated with hemorrhage and detectable AVWD. Therefore, free Ig light-chains may play a role in the pathophysiology of bleeding. DisclosuresWeisel:Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Travel Support, Research Funding; Noxxon: Consultancy; Onyx: Consultancy, Honoraria; Novartis: Other: Travel Support; Celgene: Consultancy, Honoraria, Other: Travel Support, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel Support; BMS: Consultancy, Honoraria, Other: Travel Support.

Cost of Bleeding in Trauma and Complex Cardiac Surgery

PurposeTrauma and complex cardiac surgery are associated with a high risk of bleeding complications. The difference in costs between patients who require bleeding control measures and those who do not is poorly understood. Our goal was to assess the cost of care and outcomes for patients in these settings. MethodsPatients >18 years of age, who were discharged between January 2010 and December 2012, were retrospectively identified in the Premier Hospital Database based on International Classification of Disease, Ninth Revision codes. These patients were categorized as having received blood products (“bleeding patients”) or not (“nonbleeding patients”). Patients with costs and length of stay (LOS) of zero were excluded. Differences in treatment costs and outcomes were assessed using univariate analysis and multivariate modeling. FindingsBleeding trauma patients (n = 8800) had a 150% higher total cost of care (P < 0.001; 146% after excluding costs of agents used for bleeding control, P < 0.001), an 81.3% longer hospital LOS (P < 0.001), and a 65.2% longer intensive care unit (ICU) LOS (P < 0.001) than nonbleeding patients (n = 53,727). Bleeding complex cardiac surgery patients (n = 82,832) had a 133.2% higher total cost of care (P < 0.001; 128.7% after excluding costs of agents used for bleeding control, P < 0.001), a 155.6% longer hospital LOS (P < 0.001), and an 89.3% longer ICU LOS (P < 0.001) than nonbleeding patients (n = 380,902). ImplicationsTrauma and cardiac surgery patients who experienced bleeding and received allogeneic blood product transfusions had significantly worse outcomes, including longer LOS, greater inpatient mortality, and higher costs of care (even when excluding costs of agents used for bleeding control) than those who did not.

Prothrombin complex concentrate for reversal of vitamin K antagonist treatment in bleeding and non-bleeding patients.

Treatment with vitamin K antagonists is associated with increased morbidity and mortality. Reversal therapy with prothrombin complex concentrate (PCC) is used increasingly and is recommended in the treatment of patients with bleeding complications undertaking surgical interventions, as well as patients at high risk of bleeding. Evidence is lacking regarding indication, dosing, efficacy and safety. We assessed the benefits and harms of PCC compared with fresh frozen plasma in the acute medical and surgical setting involving vitamin K antagonist-treated bleeding and non-bleeding patients. We investigated various outcomes and predefined subgroups and performed sensitivity analysis. We examined risks of bias and applied trial sequential analyses (TSA) to examine the level of evidence, and we prepared a 'Risk of bias' table to test the quality of the evidence. We searched the following databases from inception to 1 May 2013: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (Ovid SP); EMBASE (Ovid SP); International Web of Science; Latin American and Caribbean Health Sciences Literature (LILACS) (via BIREME); the Chinese Biomedical Literature Database; advanced Google and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We applied a systematic and sensitive search strategy to identify relevant randomized clinical trials and imposed no language or date restrictions. We adapted our MEDLINE search strategy for searches in all other databases. We reran the search in October 2014 and found one potential new study of interest. We added this study to a list of 'Studies awaiting classification', and we will incorporate this study into the formal review findings at the time of the review update. We included randomized controlled trials (RCTs), irrespective of publication status, date of publication, blinding status, outcomes published or language. We contacted investigators and study authors to request relevant data. Three review authors independently abstracted data and resolved disagreements by discussion. Our primary outcome measures were 'overall mortality longest follow-up' and 'overall 28-day mortality'. We performed subgroup analyses to assess the effects of PCC in adults in terms of various clinical and physiological outcomes. We presented pooled estimates of the effects of interventions on dichotomous outcomes as risk ratios (RRs), and on continuous outcomes as mean differences (MDs), with 95% confidence intervals (CIs). We assessed risk of bias by assessing trial methodological components and risk of random error through TSA. We included four RCTs with a total of 453 participants and determined that none of these trials had overall low risk of bias. We found six ongoing trials from which we were unable to retrieve further data. Three trials provided data on mortality. Meta-analysis showed no statistical effect on overall mortality (RR 0.93, 95% CI 0.37 to 2.33; very low quality of evidence). We were unable to associate use of PCC with the number of complications probably related to the intervention (RR 0.92, 95% CI 0.78 to 1.09; very low quality of evidence). Lack of transfusion data and apparent differences in study design prevented review authors from finding a beneficial effect of PCC in reducing the volume of fresh frozen plasma (FFP) transfused to reverse the effect of vitamin K antagonist treatment. The number of new occurrences of transfusion of red blood cells (RBCs) did not seem to be associated with the use of PCC (RR 1.08, 95% CI 0.82 to 1.43; very low quality of evidence). Still, the included studies demonstrate the possibility of equally reversing vitamin K-induced coagulopathy using PCC without the need for transfusion of FFP. No effect on other predefined outcomes was observed. In the four included RCTs, use of prothrombin complex concentrate does not appear to reduce mortality or transfusion requirements but demonstrates the possibility of reversing vitamin K-induced coagulopathy without the need for transfusion of fresh frozen plasma. All included trials have high risk of bias and are underpowered to detect mortality, benefit or harm. Clinical and statistical heterogeneity is high, and definitions of clinically important outcomes such as adverse events are highly dissimilar between trials. Only weak observational evidence currently supports the use of PCC in vitamin K antagonist-treated bleeding and non-bleeding patients, and the current systematic review of RCTs does not support the routine use of PCC over FFP. Additional high-quality research is urgently needed.

The impact of thrombin generation and rotation thromboelastometry on assessment of severity of factor XI deficiency

The phenotype of bleeding in patients with severe FXI deficiency is unpredictable and unlike other bleeding disorders, it is not directly correlated with levels of FXI. In this study we analyzed whether the global coagulation assays can serve as a clinical tool in predicting bleeding tendency in patients with severe FXI deficiency undergoing surgery, taking into account the large inter-individual variability of FXI levels and genotypes. Thrombin generation (TG) was measured in 39 platelet-poor plasma with or without tissue factor (TF) and in the presence or absence of corn trypsin inhibitor (CTI). Rotation thromboelastometry (ROTEM) was performed with fresh whole blood of 26 patients applying NATEM and INTEM tests. TG induced by recalcification can distinguish between bleeding and non-bleeding patients with severe FXI deficiency particularly among those with FXI activity of 2–20IU/dl. The addition of TF or TF and CTI to the TG assay masked the ability to differentiate between XI activity, genotype as well as bleeding and non-bleeding patients. ROTEM assays failed to distinguish bleeding from non-bleeding patients but could do so between different FXI activity levels and genotypes. In conclusion, in the current study we found a sensitive tool to distinguish between bleeding and non-bleeding patients. In order to recommend TG as a predictive tool for treatment tailoring, a larger patient group is required.

Early fibrinogen degradation coagulopathy: A predictive factor of parenchymal hematomas in cerebral rt-PA thrombolysis

Background and purposeThe purpose of this study was to systematically determine the correlations between the post-thrombolytic changes of hemostasis parameters and the occurrence of early intracerebral hemorrhage (ICH). MethodsIn 72 consecutive patients with cerebral infarcts treated with rt-PA, plasma levels of fibrinogen, plasminogen, alpha2-antiplasmin, factor XIII, fibrin(ogen) degradation products (FDPs) and d-Dimers were measured at baseline, 2 and 24h after thrombolysis. Correlations were studied between the hemostasis events and early (less than 24h) hemorrhagic infarcts (HIs) or parenchymatous hematomas (PH). ResultsOf 72 patients, 6 patients (8.3%) had early PHs, 11 (15.3%) had early HIs, and 55 (76.4%) had no bleeding. Early HIs were not linked to any hemostasis parameter at any time. Univariate comparison of patients having early PHs with non-bleeding patients showed hemostasis abnormalities at 2h: high FDP (p=0.01), high Log FDP (p=0.01), low fibrinogen (p=0.01), and low Log fibrinogen (p=0.01). Logistic regression adjusted for age, NIHSS and diabetes confirmed these 2hour predictors: Log FDP (OR: 7.50; CI: 1.26 to 44.61, p=0.03), and Log fibrinogen (OR: 19.32; CI: 1.81 to 205.98, p=0.01). The decrease in fibrinogen less than 2g/L multiplies the odds of early PH by a factor 12.82. ConclusionAn early fibrinogen degradation coagulopathy involving an increase of FDP and a massive consumption of circulating fibrinogen is predictive of early parenchymal hematomas, indicating the occurrence of a particularly intense lysis of circulating fibrinogen. These results, if confirmed by future studies, suggest that early assays of fibrinogen and FDP may be useful in predicting the risk of post-thrombolytic intracerebral hematoma.

Effect of proton-pump inhibitors on the risk of lower gastrointestinal bleeding associated with NSAIDs, aspirin, clopidogrel, and warfarin

We investigated the effects of proton-pump inhibitors (PPIs) on lower gastrointestinal bleeding (LGIB) and of their interactions with nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, clopidogrel, and warfarin on LGIB risk. We prospectively studied 355 patients emergently hospitalized for LGIB and 8,221 nonbleeding patients. All patients underwent colonoscopy. Smoking, alcohol drinking, drug exposure, and the Charlson comorbidity index score were assessed before colonoscopy. Adjusted odds ratios (AOR) of LGIB were estimated. LGIB was significantly associated with older age, higher comorbidity index, and NSAID, aspirin, clopidogrel, or warfarin use. PPI use was significantly associated with older age, male sex, being a current alcohol drinker, higher comorbidity index, and NSAID, aspirin, clopidogrel, warfarin, acetaminophen, or corticosteroid use. Multivariate analysis adjusted by the confounding factors revealed LGIB was not significantly associated with PPI use (AOR 0.87; 95 % confidence interval 0.68-1.13; p = 0.311), or specifically with omeprazole (AOR 1.18; p = 0.408), esomeprazole (AOR 0.76; p = 0.432), lansoprazole (AOR 0.93; p = 0.669), or rabeprazole (AOR 0.63; p = 0.140). In the interaction model, no significant interactions were observed between PPIs and NSAIDs (AOR 1.40; p = 0.293), aspirin (AOR 1.09; p = 0.767), clopidogrel (AOR 0.99, p = 0.985), or warfarin (AOR 1.52; p = 0.398). This large case-control study demonstrated that PPI use did not lead to an increased risk of LGIB, regardless of the type of PPI used. Further, LGIB risk was not affected by PPI use, irrespective of concomitant therapy with NSAIDs, low-dose aspirin, clopidogrel, or warfarin.

Bleeding phenotype and correlation with factor XI (FXI) activity in congenital FXI deficiency: results of a retrospective study from a single centre.

Bleeding phenotype in factor XI (FXI)-deficient patients is variable, and not related to baseline FXI:Act. Aims of our study were to describe the characteristics and the management of surgery and deliveries in FXI-deficient patients, and to investigate the relationship between the haemorrhagic phenotype and the baseline FXI:Act. Ninety-five patients were diagnosed and followed in our centre for a median follow-up of 0.9years (0.1-36.2); median FXI:Act of all patients: 38% (0.5-69%). Fifty-six patients (59%) experienced bleeding episodes not surgery-related. Prior to diagnosis, 64 patients underwent 132 surgeries, and after diagnosis, 23 patients underwent 36 surgeries. Globally 26 of 168 surgeries were prophylactically treated, whereas 142 of 168 were not. As regard as surgeries performed without prophylaxis, 30 bleeding events (21%) occurred in 21 patients. At diagnosis, the median FXI:Act of bleeding and non-bleeding patients was 28% and 37%, respectively, without statistically significant difference between the two groups (P=0.26). As regard as surgeries performed under prophylactic treatment just 1 bleeding event occurred. Prior to diagnosis, 31 spontaneous deliveries (SD) and eight caesarian sections (CS) were performed without prophylaxis: 4 postpartum haemorrhages (10.5%) occurred (patients FXI:Act: 2%, 6%, 27%, 52.3% respectively). After diagnosis, four SD and five CS were performed with prophylaxis: no postpartum haemorrhages occurred. We confirm the wide bleeding phenotype variability in FXI-deficient patients, not related to the baseline FXI:Act levels. We highlight the importance of performing a correct diagnosis andfollow-up, because a good management of prophylactic treatment, dramatically reduces the bleeding rate in case of surgery or deliveries.

Detecting Bleeding Risk in Patients Taking Vitamin K Antagonists Using Thrombin Generation Tests

Introduction:During the last 50 years vitamin K antagonists (VKAs) have been widely used for the primary prevention of thromboembolism in patients with atrial fibrillation, or for the secondary prevention in patients with a history of venous thromboembolism. The most prevalent adverse effect of anticoagulant therapy is an increased risk of bleeding. Annually approximately 1-4% of patients treated with VKAs suffer from major bleeding episodes.In the past several attempts have been made to predict the bleeding risk for these patients. Among the methods used at this moment are clinical decision scores, of which the HAS-BLED score is the most common one. Up to this point there are no laboratory methods available to predict patients at risk for bleeding. Thrombin generation (TG) tests have been shown to provide an intermediate phenotype for thrombosis. Additionally, TG has the capacity to detect the anticoagulant effect of many, if not all, anticoagulants, including VKAs. This method was only applicable in plasma, but recently this TG test has been introduced in whole blood (WB). With this study we aimed to investigate whether TG, in plasma or WB, could detect bleeding in patients taking VKAs.Materials & methods:Blood samples were collected in citrate tubes from 129 patients taking VKAs for over 3 months, who were older than 18 years of age and followed over time for bleeding episodes. The patients signed informed consent forms and the study was approved by the local medical ethical committee. TG was determined in WB, platelet rich plasma (PRP) and platelet poor plasma (PPP) by means of calibrated automated thrombinography (CAT). Tissue factor was used as a trigger at a final concentration of 1 pM in WB and PRP and at both 1 pM and 5 pM with 4µM phospholipids in PPP. Hematocrit and the hemoglobin concentration were determined in WB. The PPP of the patients was used to define the International normalized ratio (INR).Results:In our study the average INR value of all patients was 2.95 (± 0.92 (SD)). Twenty six patients (20.2 %) suffered from 44 clinically relevant bleeding episodes during a mean follow-up of 15.5 months.Applying TG in PPP and PRP we found no differences in either endogenous thrombin potential (ETP), an indication for the total amount of thrombin that can be converted, nor peak height (the highest amount of active thrombin present during coagulation). Interestingly, when we applied TG in whole blood, so including the blood cells, we found a significantly lower ETP (p < 0.01) and peak (p < 0.05) in the patients that suffered from bleeding (median: 182.5 nM.min and 23.9 nM, respectively) compared to patients that did not bleed (median: 256.2 nM.min and 39.1 nM). When examining the INR, hematocrit and hemoglobin levels, no significant differences were detected. A receiver operating curve (ROC) was constructed for the ETP and peak (figure 1). By determining the area under the curve (AUC) of the ROC we found that the ETP and peak are significantly (p < 0.05) associated with the tendency to bleed (ETP, AUC: 0.700; peak, AUC: 0.642). This compares favorably with the AUC reported for the HAS-BLED score related to clinically relevant bleeding in patients on VKAs (0.60).Conclusions:The TG test in whole blood was only recently developed and this is the first study implementing it to test patients using VKAs. In our study TG measured in WB proved to be the first laboratory test that is able to detect patients at risk of bleeding when treated with VKAs. The INR and plasma TG (CAT-based method), on the other hand, did not discriminate between bleeding and non-bleeding patients. For WB TG, based on the AUC of the ROC, the ETP and peak in WB have a predictive value for bleeding in patients taking VKAs superior over the currently used HAS-BLED score. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Indications for platelet transfusion in patients with thrombocytopenia.

Platelet transfusion has become a progressively more common and important therapeutic procedure in managing thrombocytopenic patients. Nevertheless, this therapy continues to evolve. Most platelet products are transfused into non-bleeding thrombocytopenic patients. The transfusion “trigger” or threshold for transfusion of these patients is now generally accepted to be 10,000/μL based on the results of a number of studies. However, it is important to emphasise that this “trigger” value generally applies to uncomplicated patients or those who are not febrile, have no infection, or are not being treated with a drug known to damage platelets. Importantly, even with a platelet “trigger” level established at 10,000/μL, platelet transfusion therapy must be individualised to the patient and the clinical situation. As noted above, fever and infection may be correlated with a greater risk of bleeding, but in addition, minor episodes of bleeding may also increase the subsequent risk of clinically significant bleeding; even haemoglobin concentration may play a role in determining bleeding risk. Finally, although prophylactic platelet transfusion is commonly used in the care of thrombocytopenic patients, therapeutic platelet transfusion may represent a reasonable option in managing the bleeding risk of some thrombocytopenic patients. Certainly in the studies by Wandt et al.26,27 and Stanworth et al.28 the use of therapeutic platelet transfusion resulted in an increased bleeding risk. However, in certain populations of patients, the bleeding seen in the therapeutic transfusion programme is generally mild (WHO bleeding category 2 or less). Nevertheless, the studies have repeatedly highlighted the importance of tailoring platelet transfusions to the clinical needs of each patient. While clinical guidelines for platelet transfusion therapy are reasonably well established, a review of the literature clearly indicates that platelet transfusions must be guided by the population of patients under consideration, the clinical conditions of the patients, and perhaps even the resources of the transfusing facility and its ability to respond rapidly to patients’ transfusion needs.

Red blood cell transfusion practices in two surgical intensive care units: a mixed methods assessment of barriers to evidence-based practice.

Despite evidence supporting restrictive red blood cell (RBC) transfusion thresholds and the associated clinical practice guidelines, clinical practice has been slow to change in the intensive care unit (ICU). Our aim was to identify barriers to conservative transfusion practice adherence. A mixed-methods study involving observation of prescriber (i.e., physicians, physician assistants, nurse practitioners) and bedside nurse daily bedside rounds, provider survey, and medical record abstraction was conducted in one cardiac surgical ICU (CSICU) and one surgical ICU (SICU) in an academic hospital in Baltimore, Maryland. Of 52 patient encounters observed during bedside rounds, 38 (73%) involved patients without evidence of active bleeding or cardiac ischemia. Surveys were completed by 52 (93%) of the 56 providers participating in rounds. Prescribers in the CSICU and SICU (87 and 90%, respectively) indicated the ideal pretransfusion hemoglobin (Hb) to be not more than 7 g/dL in nonbleeding and/or nonischemic patients compared to a minority of nurses (8% [p = 0.002] and 42% [p = 0.015], respectively). Prescribers and nurses in both ICUs overestimated the typical pretransfusion Hb in their units (CSICU, p < 0.001; SICU, p = 0.019). During rounds, providers infrequently explicitly discussed Hb monitoring or transfusion thresholds (33%) despite most (60%) reporting significant variation in transfusion thresholds between individual prescribers. Our study identified several provider and system barriers to evidence-based transfusion practices including knowledge differences, overly optimistic estimates of current practice, and heterogeneous transfusion practice in each ICU. Further work is necessary to develop targeted interventions to improve evidence-based RBC transfusion practices.

Acute transfusion reactions at a national referral hospital in Uganda: a prospective study.

Very little has been published about acute transfusion reactions (ATRs) in developing countries. This study was undertaken to determine the incidence, type, imputability, severity, and possible associated factors of ATRs observed in a university-affiliated hospital in Uganda. We prospectively followed the transfusion of blood units issued over a 7-week period from the hospital blood bank during regular working hours to nonbleeding patients. For each transfusion, we recorded the patient's status before, during, at the end of, and 4 hours after transfusion. Three physicians independently reviewed all reports of suspected ATRs and related hospital charts. Using predefined criteria, the presence, type, imputability, and severity of ATRs were adjudicated by consensus of two of three physicians. Factors potentially associated with ATRs were analyzed for statistical significance. A total of 507 transfusions were analyzed. Fifty-three acute transfusion events were recorded and 49 of 53 or 9.6% of the 507 transfusions were confirmed to be ATRs by physician consensus: 24 febrile, seven allergic, five hypertensive, three hypotensive, three transfusion-associated circulatory overload, two acute hemolytic, and five others. Imputability of ATRs was definite, probable, or possible in 45 of 49 ATRs (92% of ATRs or 8.9% of transfusions) and judged to be severe in nine of 45. No significant associated factors were identified. Our findings suggest that ATRs may occur more commonly in resource-limited settings than in high-income countries. Although some reactions are unavoidable, improved surveillance of transfusions and implementation of transfusion guidelines could improve the safety of transfusions in these settings.

International survey on plasma transfusion practices in critically ill children

Studies have shown heterogeneity in red blood cell transfusion practices. Although plasma transfusion is common in intensive care, there are no data on plasma transfusion practices in pediatric critical care units. A scenario-based survey was sent to 718 pediatric critical care physicians working in Europe, North America, Australia, and New Zealand. Respondents were asked to report their decisions regarding plasma transfusion practice with respect to four scenarios: pneumonia, septic shock, traumatic brain injury (TBI), and postoperative care after a Tetralogy of Fallot correction. The response rate was 187 of 718 (26%); half of the responders worked in North America. The proportion of physicians who transfused plasma to nonbleeding patients, solely based on abnormal international normalized ratio (INR), varied from 66% for pneumonia to 84% for TBI (p < 0.001). In such nonbleeding patients, the median INR threshold that would trigger plasma transfusion was 2.5 for pneumonia and septic shock patients and 2.0 for TBI and the cardiac postoperative patients (p < 0.001). Minor bleeding, minor surgery, insertion of a femoral line, hypotension, abnormal activated partial thromboplastin time, thrombocytopenia, and anemia levels were important determinants of plasma transfusion, whereas none of the respondents' demographic characteristics were important. More than two-thirds of responding pediatric critical care physicians prescribe plasma transfusions for nonbleeding critically ill children. Additionally, there is a significant variation in transfusion practice patterns with respect to plasma transfusion thresholds.

Effect of Helicobacter pylori infection on esophagogastric variceal bleeding in patients with liver cirrhosis and portal hypertension

Bleeding from esophageal and gastric varices is a fatal event in patients with liver cirrhosis and portal hypertension. However, the effects of Helicobacter pylori (H. pylori) infection on esophagogastric variceal bleeding are not known. The present study was aimed to elucidate the role of H. pylori infection in esophagogastric variceal bleeding. The subjects were 196 cirrhotic patients who were admitted to the Kurume University Hospital to treat their esophagogastric varices consisted of 95 with acute bleeding and 101 with nonbleeding but high risk of bleeding. For the diagnosis of H. pylori infection, a (13) C-urea breath test was used, and serum pepsinogen (PG) I and II levels and the PG I/II ratio were also measured. Esophagogastric variceal bleeding was seen in 34.9% (n = 30) of the H. pylori-infected patients (n = 86) and in 59.1% (n = 65) of the noninfected patients (n = 110) (P < 0.0007). There was no significant difference in the infection rate between the bleeding sites of the esophagus and the stomach. The serum PG I and II levels and the PG I/II ratio were 65.6 ng/dL, 14.7 ng/dL, and 4.4, respectively, for the bleeding patients (n = 95), and 43.7 ng/dL, 17.7 ng/dL, and 3.1 for the nonbleeding patients (n = 101). Thus, the nonbleeding patients had significantly higher rate of H. pylori infection and lower acid secretion than bleeding patients (0.001). In addition, multivariate logistic regression analysis showed a significant negative association between H. pylori infection and esophagogastric variceal bleeding. These results suggest that H. pylori infection has a protective effect against esophagogastric variceal bleeding through the induction of gastric mucosal atrophy and concomitant hypoacidity.

Therapeutic and prophylactic ethanol lock therapy in patients with bleeding disorders

Obtaining a reliable venous access is a limiting factor for early initiation of clotting factor prophylaxis and immune tolerance induction. To circumvent this issue, central venous access devices (CVADs) are increasingly being used. Catheter-related infections (CRIs) remain the primary complication of insertion of CVAD. Thus, newer strategies for treatment and prevention of CRI are needed. Ethanol lock therapy (ELT) has been used to treat and prevent CRI in non-bleeding disorder patients. The aim of this study was to assess the efficacy of ELT in treating and preventing CRI in bleeding disorder patients. The medical charts of patients with bleeding disorders who underwent ELT for antimicrobial resistant CRIs were reviewed and data were analysed. ELT was effective in catheter salvage in 87% of patients with antimicrobial resistant CRI by a wide variety of pathogens. Prophylactic therapy with ethanol lock was associated with catheter dysfunction especially in mediports. ELT should be considered prior to removal of catheters in bleeding disorder patients with resistant CRIs. Further studies are needed for using prophylactic ethanol lock in prevention of CRIs in bleeding disorder patients.

Multiphase CT Enterography Evaluation of Small-Bowel Vascular Lesions

By use of multiphase CT enterography (CTE), small-bowel vascular lesions associated with gastrointestinal bleeding can be classified into three categories--angioectasias, arterial lesions, and venous abnormalities--on the basis of common morphology and enhancement patterns. This article will review the unique patterns of enhancement and lesion morphology seen on multiphase CTE and how those findings enable detection and characterization of specific lesions in many cases. Because of the high prevalence in nonbleeding patients and frequent multiplicity of angioectasias, determining the clinical benefit from their detection by multiphase CTE and endoscopy is problematic. Although arterial lesions are less commonly encountered clinically, their detection is critically important because of a high risk of life-threatening bleeding. Along with wireless capsule endoscopy and balloon-assisted endoscopy, multiphase CTE is a useful tool for the evaluation of patients with obscure gastrointestinal bleeding due to small-bowel vascular lesions.