Reduction In Bleeding Rate Research Articles

Safe and Successful Surgical Outcome in Persons with Hemophilia A with and without Inhibitors Treated with Emicizumab: A Large, Single Center, Real-World Experience.

Emicizumab is a humanized recombinant bispecific antibody, bridging together activated factor IX (FIXa) and factor X (FX), thus mimicking the activity of FVIII in vivo. Emicizumab is designed for long-term prophylaxis in patients with severe hemophilia A with and without inhibitors. This approach provides constant protection, with significant reduction in bleeding rate and improved quality of life. However, protection provided by emicizumab is not absolute, and clotting factor concentrates (FVIII, rFVIIa, aPCC) may be necessary for post-traumatic bleeding or surgery, with a potential thrombotic risk or difficulty in preventing bleeding. Real world evidence is still scanty, especially for managing major surgery. In this study, 75 surgeries were managed in 28 patients (27 major procedures in 15 patients and 48 minor procedures in 20 patients. In 17 patients without inhibitors, 30 minor surgeries were carried out by using FVIII in 5, with only a bleeding event, which was successfully treated with FVIII concentrate. Six major surgeries were uneventfully performed with FVIII concentrate. Eleven PWHA and high-titer inhibitors underwent 39 surgical procedures (18 minor and 21 major surgeries). Minor surgeries were mostly performed without prophylaxis with rFVIIa, with only a single bleeding complication. All 21 major surgeries were covered with a homogeneous protocol using rFVIIa. In four instances, bleeding complications occurred, treated with rFVIIa. Of them, a single patient only failed to respond and died because of an uncontrollable bleeding from a large ruptured retroperitoneal pseudotumor. Surgery in patients with emicizumab can be safely carried out with the use of appropriate replacement therapy protocols.

Nonreplacement therapy for hemophilia in low-income countries: experience from a prospective study in Ivory Coast

BackgroundHemophilia management has fundamentally evolved over the last decades with the development of ground-breaking therapies. Because of their mode of action and biochemical properties, these innovative therapies that are available in developed countries could be readily implemented among people from low-income countries who are either not or inadequately treated with clotting factor concentrates (CFCs). ObjectivesWe aimed at evaluating the impact of prophylaxis with emicizumab, a bispecific monoclonal antibody mimicking the FVIII activity administered subcutaneously, among boys with severe hemophilia A (HA) from the Ivory Coast, where access to CFCs is limited to humanitarian aid. MethodsWe prospectively collected data on the implementation and outcomes of prophylaxis with emicizumab, in 33 Ivorian boys aged 2 to 13 years with severe HA (with and without inhibitors). Bleeds, CFC consumption, quality of life and satisfaction of the patients and their parents were assessed. ResultsOverall, 12 months after initiating emicizumab, a 99% reduction in bleeding rates was observed, with a raise from 18% to 100% of boys having zero spontaneous joint bleeds. Three boys required a single FVIII infusion following a traumatic bleed. Health-related quality of life measures significantly improved, and perception of treatment efficacy was positively rated in children and parents. Acceptance, tolerance, and adherence were excellent. Emicizumab was instrumental in successfully implementing uninterrupted, highly efficacious, and well-tolerated prophylaxis in 72% of the Ivorian children aged ≤ 13 years identified with severe hemophilia A. ConclusionThese data illustrate how innovative and disruptive nonreplacement therapies that are already accessible in developed countries could potentially provide equity in care by profoundly and rapidly modifying hemophilia burden with a magnified impact in low-income countries.

Immune Tolerance Induction (ITI) with a pdFVIII/VWF Concentrate (octanate) in 100 Patients in the Observational ITI (ObsITI) Study.

Background Immune tolerance induction (ITI) with repeated factor VIII (FVIII) administration is the only strategy proven to eradicate inhibitors. The observational ITI study is evaluating ITI with a range of FVIII products. Methods This subgroup analysis reports prospective interim data for patients treated with a plasma-derived, von Willebrand factor-stabilized FVIII concentrate (pdFVIII/VWF, octanate). Complete success (CS) of ITI required achievement of three criteria: inhibitor titer < 0.6 BU/mL; FVIII recovery ≥ 66%; FVIII half-life ≥6 hours. Partial success (PS) required achievement of two criteria and partial response (PR) one. ITI success was defined as CS or PS. Data were analyzed for patients who achieved CS, had 36 months' observation, or failed ITI. Results One-hundred prospectively enrolled patients were included in the analysis; 91 had poor prognosis factors for ITI success. The mean (standard deviation) daily ITI dose was 116.4 (61.1) IU FVIII/kg in 14 low responders (< 5 BU/mL) and 173.7 (112.0) IU FVIII/kg in 86 high responders (≥ 5 BU/mL). Inhibitor titers < 0.6 BU/mL were achieved in 71% of patients in a median of 4.01 months, accompanied by a 93% reduction in bleeding rate. ITI success was achieved by 70% of patients and 56 of 72 (78%) primary (first-line) ITI patients. PR was achieved by 5 patients; ITI failed in 25 patients. PS and CS were achieved in a median of 5.55 and 11.25 months, respectively. Conclusions ITI with pdFVIII/VWF led to rapid eradication of FVIII inhibitors, normalization of FVIII pharmacokinetics in the majority of patients, and a significant reduction in bleeding rates.

Increased staple loading pressures and reduced staple heights in laparoscopic sleeve gastrectomy reduce intraoperative bleeding

BackgroundIn laparoscopic sleeve gastrectomy, tissue thickness and closed staple height of the staple cartridge determine the pressure applied to the tissue. Prior studies have suggested 8 g/mm2 to be ideal to minimize leaks or bleeding. MethodsWe evaluated the relationship between staple loading pressure applied to gastric tissue and bleeding rate prospectively with a novel tissue measuring device and video-recorded operative findings for 116 patients undergoing laparoscopic sleeve gastrectomy performed by 2 surgeons at a single institution. Stapling protocol 1 was used for 64 cases, defined as standard practice, typically using green-blue-blue-blue Ethicon staple cartridges. Stapling protocol 2 was defined as blue-blue-white-white or gold-blue-white-white. ResultsTissue thickness measurements from 39 cases and staple load selection showed that surgeons preferred a median staple loading pressure of 15 g/mm2. Tissue thickness measurements at 15 g/mm2 had a mean of 1.86 mm at the antrum, 1.71 mm at the body, and 1.15 mm at the fundus, all significantly thinner than tissue thickness at 8 g/mm2. For each 10 g/mm2 increase in minimum pressure and maximum pressure value within each cartridge zone, there was a reduction in bleeding rate by 59.8% and 38.7%, respectively. Compared with stapling protocol 1, stapling protocol 2 had a lower intraoperative bleeding rate (90.2% vs 70.7%; P < .0001), usage of preventive hemostatic techniques (100% vs 10%; P < .0001), and hemostatic treatments (66% vs 46%; P = .04). In the 30-day postoperative period, there was 1 bleed in stapling protocol 1; there were no leaks. ConclusionOur data suggest using shorter closed staple heights to exert higher staple loading pressures decreases intraoperative bleeding rates in laparoscopic sleeve gastrectomy.

Concizumab Subcutaneous Prophylaxis Improves Health-Related Quality-of-Life Measures in Patients with Congenital Hemophilia with Inhibitors: Phase 2 Trial Results

Introduction Concizumab is an anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody in clinical development for the subcutaneous prophylactic treatment of hemophilia patients. We present exploratory analyses assessing the impact of concizumab prophylaxis on health-related quality-of-life (HRQoL) in hemophilia A and B with inhibitor (HAwI/HBwI) patients compared with recombinant activated factor VII (rFVIIa) on-demand treatment in a phase 2 trial (NCT03196284; explorer4). HRQoL is impaired in patients with hemophilia relative to the general population and this impairment is more pronounced among patients with inhibitors, including HBwI patients for whom treatment options are particularly limited. Methods HAwI and HBwI patients were randomized 2:1 to concizumab prophylaxis (n=17) or rFVIIa on demand (recombinant activated factor VII; n=9). Patients completed the 36-item Short Form Health Survey (SF-36v2; 4-week recall) questionnaire at baseline and at the end of the main phase of the trial (24 weeks). Scoring was conducted according to the SF-36v2 scoring software (version 5.0). The change in SF-36v2 scores after treatment onset from baseline to Week 24 was analyzed with an analysis of covariance (ANCOVA model) with regimen as factor and baseline score as a covariate. Improvement in SF-36v2 scores was assessed at both group and individual patient level. At group level, SF-36v2 score improvement was assessed based on minimally important difference (MID) criteria as recommended by the SF-36v2 manual (3rd edition; 2013) (Table 1). A responder analysis was also conducted to identify the proportion of patients who had an improvement in the Physical Component Summary (PCS) in terms of meeting the recommended individual level response threshold of 3.4 points (established based on the 2009 United States general population norms; SF-36v2 manual). Results Overall, improved HRQoL was observed in patients receiving concizumab prophylaxis as reflected by improvements (higher scores) in all SF-36v2 domain scores. At a group level, the difference in improvement from baseline for concizumab prophylaxis vs rFVIIa on-demand for the PCS score met the MID criterion (Table 1), as did the difference in improvement from baseline for the following SF-36v2 domains: Social Functioning, Vitality Score, Health Perception, Bodily Pain and Physical Functioning (Table 2). This difference in improvement between the two groups was not statistically significant, as the study was not powered to show significance for this endpoint. In addition, a larger percentage of patients on concizumab prophylaxis achieved an improvement that met or exceeded the response threshold on the PCS score scale compared with patients receiving rFVIIa on-demand treatment. Conclusions Hemophilia patients have been reported to have a worse HRQoL than members of the general population, particularly in relation to physical activity and pain. In results from the concizumab phase 2 explorer4 trial presented here, HAwI and HBwI patients on concizumab prophylaxis reported higher values for change from baseline in all SF-36v2 domain scores compared with patients receiving rFVIIa on demand after 24 weeks of treatment, indicating better functional health and well-being. A reduction in bleeding rate in these patients is likely to have a positive effect on physical function and reduce pain. In explorer4, there was a 78% reduction in the estimated annualized bleeding rate (ABR) among patients on concizumab prophylaxis vs those on rFVIIa on-demand treatment (Shapiro et al., ASH 2019; abstract submitted). The larger reduction in ABR observed with concizumab subcutaneous prophylaxis may have contributed to the larger improvement in HRQoL relative to the rFVIIa on-demand treatment arm. The potential beneficial effect of concizumab prophylaxis on HRQoL in all hemophilia patients will be investigated further in the phase 3 trials. Disclosures Lee: Novo Nordisk A/S: Employment. Cepo:Novo Nordisk A/S: Employment. Porstmann:Novo Nordisk Health Care AG: Employment, Honoraria.

Transradial Retrieval of Broken Catheter After Complex PCI- A Nightmare

Transradial access has now a days become a standard of care for percutaneous coronary angiography &amp; intervention. This approach has demonstrated significant reduction in bleeding rate, length of hospital stay and improvement in clinical outcomes when compared to the traditional TF approach. However this novel approach may lead to severe catheter kinking &amp; twisting and further manipulation may require unraveling the catheter and avoiding complication. The fracture of a guide catheter is an uncommon complication during percutaneous coronary intervention (PCI). It sometimes occurs during engagement of the right coronary ostium, when there is excessive twisting of the guide catheter. An interesting case of complete fracture of a 6 Fr Ikari guide catheter in the brachial artery during transradial coronary intervention is presented.&#x0D; Ibrahim Card Med J 2018; 8 (1&amp;2): 66-70

Abstract 36: Direct Oral Anticoagulant Underdosing Increases Rates of Stroke and Myocardial Infarction With No Reduction in Bleeding Rate

Introduction: Direct oral anticoagulants (DOACs) reduce the risk of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients. The off-label prescription of lower dose DOACs is very common and usually represents an attempt to mitigate bleeding risk. Data regarding the effects of off-label DOAC lower dose on patient outcomes is limited. We evaluated the effectiveness and safety of off-label lower dose DOAC therapy in NVAF patients treated in routine clinical practice. Hypothesis: Off-label lower dose DOAC use is associated with higher risk of mortality, stroke and myocardial infarction (MI) and is not associated with a reduced bleeding rate. Methods: We identified all newly diagnosed NVAF patients initiating DOAC therapy in Clalit Health Services from 2011 to 2016. Effectiveness was defined as a composite of all-cause mortality, stroke and MI and safety was defined as bleeding requiring hospitalization. Patients were followed until May 15,2017 or until occurrence of an outcome event. The DOAC dose was determined based on electronic drug dispensing records. We compared the outcomes in patients treated with DOACs at per-label standard dose with those treated with off-label lower dose. Hazard ratios (HR) were adjusted for 21 variables, including socio-economic factors, co-morbidities and concomitant medications using multivariate regression. Results: During the study period 3,395 patients were treated with DOACs at per-label standard dose and 2,438 patients were treated with an off-label lower dose. Adjusted HR for the composite of mortality, stroke and MI in patients treated with off-label lower dose was 1.38 (95% CI: 1.13- 1.69, P=0.001), and for bleeding 1.34 (95% CI: 0.92-1.95, P=NS). Conclusions: In this cohort of NVAF patients treated in routine clinical practice, off-label lower dose of DOACs was associated with a higher risk of mortality, stroke and myocardial infarction and was not associated with a reduced bleeding rate. Our findings provide further support for encouraging adherence to the per-label dosage of DOAC therapy.

Pre-Analysis for Hemostatic Effect of Bypassing Agents in Hemophilia a Patients with Inhibitors Under the Emicizumab Prophylaxis By Global Assays

Introduction: Emicizumab (Emi) is an anti-factor (F)IXa/FX bispecific antibody that mimics FVIIIa cofactor function. The clinical trials on Emi prophylaxis for hemophilia A patients with inhibitor (HA-Inh) demonstrated marked reduction in bleeding rates. However, Emi at clinically relevant plasma concentrations (~50 mg/ml) corresponding to ~15% of FVIII equivalent activity may not provide enough hemostasis at severe bleeding or major surgical intervention. In these circumstances, additional infusions of bypassing agents (BPAs) may be needed for hemostatic management. In the HAVEN 1 study, thrombotic events/ thrombotic microangiopathy occurred in Emi-treated HA-Inh receiving consecutive infusions of aPCC in higher doses. After these reports, guidance was provided to avoid the use of aPCC as first choice during Emi prophylaxis. If aPCC is the only available BPA, use of the lowest dose expected to achieve hemostasis with the initial dose ≦50 U/kg was recommended. To further support these recommendations, more investigation is required for the use of BPAs under Emi prophylaxis. Objective: We examined the coagulation effects by spiking BPAs to whole blood or plasma samples from Emi-treated HA. Methods: Samples from eight Emi-treated HA-Inh and two hemophilia A patients without inhibitors (HA-Inh(-)) in phase 1/2 and HAVEN 1 were tested. The Emi doses were 0.3-3.0 mg/kg/w or 1.5 mg/kg/w, respectively. Either aPCC or rFVIIa was spiked to patients' whole bloods or plasmas, and assessed by rotational thromboelastometry (ROTEM; Ca2+ trigger) and clot waveform analysis (CWA; ellagic acid/tissue factor-mixed trigger; Nogami, JTH2018). Furthermore, samples in Emi-treated HA-Inh of phase 1/2 (n=1) or HAVEN 2 (n=2) receiving BPAs infusion for hemostatic management were assessed by both assays. Results and Discussion: The baseline levels, before spiking BPAs, in ROTEM parameters, such as clot time (CT) and clot formation time (CFT), of Emi-treated HA were 1,380/521sec(s) (reference range 762-1,127/207-511s), respectively. Spiking aPCC markedly shortened CT/CFT to 167/81.5s and 148/78.0s at 0.65 and 1.3 U/mL corresponding to 50 and 100 U/kg infusion, respectively. Even at 0.13 U/mL (10 U/kg), CT/CFT shortened to 290/92.6s, which was shorter than that of reference range. Its effect was dose-dependent. Spiking rFVIIa also improved CT/CFT to 726/179s, 551/141s at 32.3 and 112 μg/mL (90 and 270 μg/kg). In CWA, the baseline levels of adjusted-|min1| (ad|min1|), indicative of maximum coagulation velocity, in Emi-treated HA were 5.53 (normal control 7.98±0.24). Ad|min1| was improved to 6.48 and 8.04 by spiking aPCC (10 and 100 U/kg), or 7.11 and 7.12 by spiking rFVIIa (90 and 270 μg/kg), respectively. For rFVIIa its effect was not dose-dependent. According to the investigation for in vivo effect by BPAs infusion in a total of 9 treatment events of Emi-treated HA-Inh, CT/CFT (1,812/553s) was improved to 1,151/346s, of which was within normal range. Ad|min1| (5.7) was improved to 6.6 30 min(m) after aPCC infusion (44-74 U/kg). By rFVIIa infusion (90-119 μg/kg), CT/CFT (1,962/758s) improved to 912/207s, and ad|min1| (4.9) also improved to 6.5 30m after infusion, of which improvement remained within normal range. The hemostasis effects were clinically satisfying and no thrombosis occurred in all cases. The ROTEM parameters by spiking aPCC were apparently hypercoagulant relative to those by infusion at same dose, supporting our previous report (Furukawa JTH2015). The shortening effect on the ROTEM parameters by spiking aPCC 100 U/kg in Emi-untreated HA seemed to be similar to that by spiking aPCC 10 U/kg in Emi-treated HA. In addition, ad|min1| by spiking aPCC 10 U/kg with Emi also improved as well as ~100 U/kg without Emi in our previous report (Nogami JTH2018). Taken together, it is suggested that the hemostatic effect of aPCC infusion (10 U/kg) to Emi-treated HA could be comparable to that of 100 U/kg to Emi-untreated HA-Inh, though there is a limitation to predicting the hemostatic effect of aPCC in a clinical setting from these ex vivo results. Conclusion: Spiking tests in Emi-treated HA-Inh by ROTEM and CWA are useful to evaluate clinical coagulation potentials and dose finding of BPAs in Emi-treated HA receiving BPAs. Additionally, under Emi prophylaxis, a lower dose of aPCC infusion might be a possible option to treat breakthrough bleed in Emi-treated HA-Inh. DisclosuresFurukawa:CSL Behring: Research Funding. Nogami:Bayer: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria, Research Funding; Novo Nordisk: Consultancy, Honoraria, Research Funding; Sysmex: Consultancy, Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Anti-FIXa/X bispecific antibodies, Research Funding, Speakers Bureau. Matsumoto:Shire Japan Co. Ltd: Research Funding. Kasai:Chugai Pharmaceutical Co., Ltd: Employment. Shima:F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees; Chugai Pharmaceutical Co., Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Anti-FIXa/X bispecific antibodies , Research Funding, Speakers Bureau.

US-accelerated catheter-directed thrombolysis for the treatment of deep venous thrombosis

We aimed to evaluate the efficacy and feasibility of ultrasonography (US)-accelerated catheter-directed thrombolysis for the treatment of deep venous thrombosis. A total of 26 patients with deep venous thrombosis were prospectively selected for thrombolysis. Overall, 80.8% of the occlusions were in the lower extremities, and 19.2% were in the upper extremities. US-accelerated catheter-directed thrombolysis was performed using a recombinant human tissue plasminogen activator (alteplase), which was delivered using the EKOS EkoSonic® Endovascular System (EKOS Corporation, Bothell, Washington, USA). Postprocedure venography was repeated after the treatment, which included angioplasty and stenting if stenosis was present. Thrombolysis was successful in 92.3% (24/26) of the patients, with complete clot lysis in 14 patients and partial clot lysis in nine patients. The mean symptom duration was 54.9±51 days (range, 6-183 days), and the mean thrombolysis infusion time was 25.3±5.3 hours (range, 16-39 hours). Pulmonary embolism was not observed; however, there were three cases of bleeding at the catheter insertion site. In three patients, the underlying lesions were successfully treated with balloon angioplasty and stent insertion. Two patients developed early recurrent thrombosis due to residual venous obstruction. US-accelerated thrombolysis was demonstrated to be a safe and efficacious treatment for deep venous thrombosis in this study. The addition of US reduces the total infusion time and increases the incidence of complete lysis with a reduction in bleeding rates. Residual venous obstruction should be treated by angioplasty and stent insertion to prevent early rethrombosis.

Ultrasound-accelerated Thrombolysis for the Treatment of Deep Vein Thrombosis: Initial Clinical Experience

To evaluate the success of lysis and clinical outcomes in patients treated with ultrasound (US)-accelerated thrombolysis for deep vein thrombosis (DVT). Forty-seven patients with 53 cases of DVT were treated with US-accelerated thrombolysis at eight centers in the United States. Sixty percent of the occlusions were in the lower extremity, 36% were in the upper extremity, and 4% were hepatic. The clot was acute (< or =14 days) in 47% of cases, subacute (15-28 d) in 8%, chronic (>28 d) in 17%, acute-on-chronic in 17%, and not specified in 11%. Patients were treated with urokinase (UK), tissue plasminogen activator (tPA), recombinant plasminogen activator (rPA), or tenecteplase. Complete lysis (> or =90%) was seen in 37 of 53 cases (70%) and overall lysis (complete plus partial) was seen in 48 (91%). No lysis occurred in five cases (9%), four of which were chronic. The median thrombolysis infusion time was 22.0 hours. Major complications (hematoma at site of earlier surgery) occurred in only two patients (3.8%), with no incidence of intracranial or retroperitoneal hemorrhage. US-accelerated thrombolysis exhibited comparable or better lysis with a lower average drug dose and shorter median treatment times than reported in the National Venous Registry and a more recently published study of standard catheter-directed thrombolysis. US-accelerated thrombolysis was shown to be a safe and efficacious treatment for DVT in this multicenter experience. The addition of US reduces total infusion time and provides a greater incidence of complete lysis with a reduction in bleeding rates.

The potential clinical and economic outcomes of pharmacogenetics-oriented management of warfarin therapy – a decision analysis

Variant cytochrome P450 (CYP) 2C9 genotypes are associated with low maintenance dose requirement of warfarin therapy and increased risk of major bleeding events. The objective of the present study was to evaluate the potential clinical and economic outcomes of using CYP2C9 genotype data to guide the management of anticoagulation therapy and to identify influential factors affecting the cost-effectiveness of this treatment scheme. A decision tree was designed to simulate, over 12 months, the clinical and economic outcomes of patients newly started on warfarin associated with two alternatives: (1) no genotyping (non-genotyped group) and (2) CYP2C9 genotyping prior to initiation of warfarin therapy (genotyped group). Non-genotyped group patients would receive standard care of an anticoagulation clinic (AC). In the genotyped group, patients with at least one variant CYP2C9 allele would receive intensified anticoagulation service. Most of the clinical probabilities were derived from literature. The direct medical costs were estimated from the Diagnosis-Related Group charges and from literature. The total number of events and the direct medical cost per 100 patient-years in the genotyped and non-geno-typed groups were 9.58 and USD155,700, and, 10.48 and USD 150,500, respectively. The marginal cost per additional major bleeding averted in the genotyped group was USD 5,778. The model was sensitive to the variation of the cost and reduction of bleeding rate in the intensified anticoagulation service. In conclusion, the pharmacogenetics-oriented management of warfarin therapy is potentially more effective in preventing bleeding with a marginal cost. The cost-effectiveness of this treatment scheme depends on the relative cost and effectiveness of a pharmacogenetics-oriented intensified anticoagulation service comparing to the standard AC care.

The influence of ground granulated blastfurnace slag (GGBS) additions and time delay on the bleeding of concrete

Bleed tests were performed in accordance with ASTM C232-92 on concretes in which up to 85% of the cement was replaced with ground granulated blastfurnace slag (GGBS) obtained from a number of different sources. The time at which the bleed test was started was varied from 30 to 120 min to simulate site conditions. The addition of up to 55% slag increased the bleed capacity by 30% (compared to the plain Portland cement (OPC) mix) but had little effect on bleed rate. Increasing the slag content to 85% had no further significant effect on bleeding. The source of slag was also found to have little effect on the bleeding but comparisons made with results from 10 years ago suggest that now the present day slags have a much less marked effect on bleeding probably because they are ground finer. Delaying the start of the bleed test from 30 to 120 min reduced the bleed capacity of the OPC mix by more than 55% compared with 32% for the slag mixes. The reduction in bleed rate was similar for all mixes at about 45%.

Sclerotherapy in noncirrhotic portal fibrosis.

Endoscopic sclerotherapy has emerged as an effective and safe mode of treatment for long-term management of esophageal varices due to cirrhosis of liver and extrahepatic portal venous obstruction. There are few studies that have evaluated the role of sclerotherapy in the management of esophageal varices in patients with noncirrhotic portal fibrosis (NCPF). We report our results of long-term sclerotherapy in patients with NCPF. Seventy-two consecutive patients (men 29, women 43; age 32.9 +/- 11.8 years) with recurrent variceal bleeding due to NCPF were entered into the sclerotherapy program. Forty-eight patients received intravariceal absolute alcohol and 24 patients received intravariceal sodium tetradecyl sulfate (STD). Variceal obliteration was achieved in 65 (90.3%) patients with a mean of 5.7 +/- 3.0 (range 1-14) sessions. These patients were followed-up for a mean of 21.4 +/- 20.4 (range 1-96) months. Thirteen (17.3%) patients had episodes of upper gastrointestinal bleeding during sclerotherapy. Rebleed after obliteration was seen in 6 (9.2%) patients. Sclerotherapy was associated with a significant reduction in bleeding rate (bleeds per month per patient) during sclerotherapy and after obliteration of varices as compared to presclerotherapy period (P < 0.000001 for both). Recurrence of esophageal varices after obliteration was seen in 9 (13.9%) patients with reobliteration of varices in five patients in whom sclerotherapy was attempted. Complications including esophageal ulcer and stricture formation were seen in 18 (25%) and 4 (5.6%) patients respectively; strictures were restricted to patients who received absolute alcohol. Two (2.77%) patients died of massive upper gastrointestinal bleed during follow-up. We conclude that sclerotherapy is an effective and safe modality in the prevention of variceal bleeds in patients with NCPF.

Long term results of treatment of vascular malformations of the gastrointestinal tract by neodymium Yag laser photocoagulation.

The effect of Yag laser photocoagulation on the course of bleeding of gastrointestinal vascular malformations was studied in 59 patients, with a total of 482 lesions. The lesions were located in the upper gastrointestinal tract alone in 25 patients, in the lower tract alone in 31 patients and in both the lower and the upper gastrointestinal tract in three patients. In the month before laser therapy the number of bleeding episodes averaged 1.09 +/- 0.6 (SD) per patient (n = 57) and the transfusion requirements 2.4 +/- 2.6 red blood cells units per patient, while in the month after treatment the bleeding incidence averaged 0.16 +/- 0.5 and the transfusion requirements 0.21 +/- 0.8 (both p less than 0.001). Long term results were analysed considering for each patient an equally long pretreatment and follow up period. After a mean follow up period of 11.5 months (1-48 months), 17 of the 57 patients available for follow up rebled. The reduction of the bleeding rate was statistically significant at one, six, 12, and 18 months of follow up, while transfusion rate was significantly decreased at one, six, and 12 months. The results were disappointing in patients with Osler-Weber-Rendu (n = 4) and in patients with angiomas associated with Von Willebrand's disease (n = 3), who all rebled. In angiodysplasia the treatment was successful in 82% of the 49 patients. The more numerous the lesions, the less effective the reduction in bleeding rate by laser treatment was. Histological studies showed that the haemostatic effect of Yag laser photocoagulation was obtained by destruction of the lesion. Rebleeding was due to lesions missed at the first treatment, incompletely treated lesions and recurrence of new lesions. In two patients a free caecal perforation necessitated a right hemicolectomy. In both patients numerous or very large lesions had been treated in the caecum.