Management of epistaxis in patients on novel oral anticoagulation therapy.

BACKGROUND: Individuals on anticoagulation therapy are at increased risk of bleeding, including epistaxis. There is a lack of available reversal agents for novel oral anticoagulation therapy. OBJECTIVE: This paper reviews the current literature on epistaxis in the context of novel oral anticoagulation use, in order to recommend guidelines on management. METHOD: A comprehensive search of published literature was conducted to identify all relevant articles published up to April 2019. RESULTS: Patients on oral anticoagulation therapy are over-represented in individuals with epistaxis. Those on novel oral anticoagulation therapy were more likely to relapse compared to patients on classic oral anticoagulants or non-anticoagulated patients. Idarucizumab is an effective antidote for bleeding associated with dabigatran use. Recommendations for epistaxis management in patients on novel oral anticoagulation therapy are outlined. CONCLUSION: Clinicians need to be aware of the potential severity of epistaxis and the increased likelihood of recurrence. High-quality studies are required to determine the efficacy and safety of andexanet alfa and ciraparantag, as well as non-specific reversal agents.

Safety of direct oral anticoagulants in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular dysplasia resulting in visceral arteriovenous malformations and smaller mucocutaneous telangiectasia. Most patients experience recurrent nosebleeds and become anemic without iron supplementation. However, thousands may require anticoagulation for conditions such as venous thromboembolism and/or atrial fibrillation. Over decades, tolerance data has been published for almost 200 HHT-affected users of warfarin and heparins, but there are no published data for the newer direct oral anticoagulants (DOACs) in HHT. METHODS: To provide such data, a retrospective audit was conducted across the eight HHT centres of the European Reference Network for Rare Multisystemic Vascular Diseases (VASCERN), in Denmark, France, Germany, Italy, the Netherlands and the UK. RESULTS: Although HHT Centres had not specifically recommended the use of DOACs, 32 treatment episodes had been initiated by other clinicians in 28 patients reviewed at the Centres, at median age 65 years (range 30-84). Indications were for atrial fibrillation (16 treatment episodes) and venous thromboembolism (16 episodes). The 32 treatment episodes used Apixaban (n = 15), Rivaroxaban (n = 14), and Dabigatran (n = 3). HHT nosebleeds increased in severity in 24/32 treatment episodes (75%), leading to treatment discontinuation in 11 (34.4%). Treatment discontinuation was required for 4/15 (26.7%) Apixaban episodes and 7/14 (50%) Rivaroxaban episodes. By a 4 point scale of increasing severity, there was a trend for Rivaroxaban to be associated with a greater bleeding risk both including and excluding patients who had used more than one agent (age-adjusted coefficients 0.61 (95% confidence intervals 0.11, 1.20) and 0.74 (95% confidence intervals 0.12, 1.36) respectively. Associations were maintained after adjustment for gender and treatment indication. Extreme hemorrhagic responses, worse than anything experienced previously, with individual nosebleeds lasting hours requiring hospital admissions, blood transfusions and in all cases treatment discontinuation, occurred in 5/14 (35.7%) Rivaroxaban episodes compared to 3/15 (20%) Apixaban episodes and published rates of ~ 5% for warfarin and heparin. CONCLUSIONS: Currently, conventional heparin and warfarin remain first choice anticoagulants in HHT. If newer anticoagulants are considered, although study numbers are small, at this stage Apixaban appears to be associated with lesser bleeding risk than Rivaroxaban.

Endoscopic-guided coblation treatment of nasal telangiectasias in hereditary hemorrhagic telangiectasia: "How I do it".

INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease that leads to frequent epistaxis. It can have a significant impact on quality of life. Many reports exist regarding various therapies to address the epistaxis. MATERIALS AND METHODS: We presented our technique for addressing the epistaxis associated with HHT. RESULTS: Patients are treated in the operating room while they are under general anesthesia. A local anesthetic is injected sublabially, and oxymetazoline is dripped into the nose. The coblation wand is used to treat the telangiectasias. Bevacizumab is then injected into the nasal cavity bilaterally. CONCLUSION: The coblation wand, with or without adjunctive bevacizumab injection, is a technically feasible intervention for patients with HHT that all providers can perform.

Nasal powders of thalidomide for local treatment of nose bleeding in persons affected by hereditary hemorrhagic telangiectasia.

In this work nasal powder formulations of thalidomide were designed and studied to be used by persons affected by hereditary hemorrhagic telangiectasia as a complementary anti-epistaxis therapy, with the goal of sustaining the effect obtained with thalidomide oral treatment after its discontinuation for adverse effects. Three nasal powders were prepared using as carriers ß-CD or its more hydrophilic derivatives such as hydropropyl-ß-CD and sulphobutylether-ß-CD and tested with respect to technological and biopharmaceutical features after emission with active and passive nasal powder devices. For all formulated powders, improved dissolution rate was found compared to that of the raw material, making thalidomide promptly available in the nasal environment at a concentration favouring an accumulation in the mucosa. The very limited transmucosal transport measured in vitro suggests a low likelihood of significant systemic absorption. The topical action on bleeding could benefit from the poor absorption and from the fact that about 2-3% of the thalidomide applied on the nasal mucosa was accumulated within the tissue, particularly with the ß-CD nasal powder.

Comparison of microporous polysaccharide hemospheres and Ankaferd Blood Stopper in a rabbit epistaxis model.

The aim of this study was to evaluate the histopathological impact, effectiveness, and safety of two hemostatic agents, Ankaferd Blood Stopper (ABS) and microporous polysaccharide hemospheres (MPH), in an experimental rabbit epistaxis model. Rabbits were randomly assigned, using a computerized random number generator, to the following three groups of six animals: group 1 (control, irrigated with saline); group 2 (ABS-treated); and group 3 (MPH-treated). In all groups, a standardized rabbit epistaxis model was used. Hemostasis time and extent of nasal bleeding were measured to compare the hemostatic effect of ABS and MPH among groups. Septums were removed for histopathological analysis, 7 days after the procedure. ABS reduced hemostasis time to 104.2 s and amount of bleeding to 20.5 mg. MPH reduced hemostasis time to 71.7 s and amount of bleeding to 11.5 mg. Mean bleeding time in wounds administered ABS and MPH was significantly shorter compared with wounds administered isotonic saline solution (p = 0.004). ABS and MPH application decreased bleeding significantly compared with the control group (p = 0.004). Bleeding time and amount in the MPH group was significantly reduced compared with the ABS group (p = 0.013 and p = 0.004, respectively). There was no significant difference in the histopathological evaluation results between the ABS, MPH, and control groups. Our data indicate that both ABS and MPH represent safe, effective, and fast-acting hemostatic agents in the management of epistaxis. MPH was more effective than ABS in terms of hemostasis time and amount of bleeding.

The effect of thyme honey nasal spray on chronic rhinosinusitis: a double-blind randomized controlled clinical trial.

Chronic rhinosinusitis is a common disease which causes persisting inflammatory conditions of one or more sinuses. This study was designed to evaluate the effect of thyme honey nasal spray as an adjunctive medication on chronic rhinosinusitis after functional endoscopic sinus surgery. This was a randomized, placebo controlled, double-blind clinical study. 64 patients with chronic rhinosinusitis undergoing functional endoscopic sinus surgery were enrolled in this study. Patients were randomized and blinded to receive either placebo or thyme honey nasal spray in addition to the standard regimen postoperatively. Patients were visited on postoperative days 7, 30 and 60. The sino-nasal outcome test, endoscopic grading system and sinus CT-scan were scored before operation and on the day 60 after surgery. 54 patients completed the study. Significant improvement was observed in both treatment groups. There were no significant changes in SNOT-22, endoscopy and CT-scan scores between the two study groups. However, a greater reduction in endoscopic scores was shown in thyme honey group. The incidence of adverse effects was not significantly different between the groups, but synechiae formation and epistaxis were lower in treatment group. Thyme honey nasal spray seems to be a low-priced potential adjuvant remedy with excellent safety profile, to reduce inflammation and polyp formation and also fostering mucosal healing for patients suffering from chronic rhinosinusitis. However, further studies are recommended.

Topical Yunnan Baiyao administration as an adjunctive therapy for bleeding complications in adolescents with advanced cancer.

PURPOSE: Yunnan Baiyao (White Medicine from Yunnan, YNB) is a Chinese herbal medicinal powder used to stop bleeding and improve circulation in traumatic injuries. We describe the use of YNB in adolescents with cancer as an adjunct to uncontrolled bleeding in the palliative care setting. METHODS: Through a retrospective chart review of all patients receiving integrative medicine consultations at the Integrative Therapies Program at Columbia University from January 1, 2007 to January 31, 2012, we describe the outcome of patients treated with YNB for management of uncontrolled bleeding. RESULTS: Four patients were identified who received topical YNB for uncontrolled bleeding; patients included two males and two females with diagnoses of solid tumors (n = 3) and Burkitt's lymphoma (n = 1). Mean age was 15.5 years (range 15-17). Fifty percent had life-threatening bleeding from the tumor site and 50 % experienced uncontrollable epistaxis. All patients received preceding therapy with packed red blood cells and platelet transfusions, topical thrombin, and oral aminocaproic acid. Two patients used YNB in the inpatient setting, and all four patients used YNB as outpatients. In all patients, bleeding control improved with the addition of YNB to conventional hemostatic interventions. Two patients using YNB in their home reported control of bleeding episodes. There were no adverse events reported. CONCLUSIONS: YNB may be an efficacious agent for uncontrolled bleeding in conjunction with conventional hemostatic agents in adolescents with advanced cancer. It is well accepted by patients. YNB may be especially valuable in the outpatient setting to prevent the recurrence of hemorrhage.

Bevacizumab in hereditary hemorrhagic telangiectasia-associated epistaxis: effectiveness of an injection protocol based on the vascular anatomy of the nose.

OBJECTIVE/HYPOTHESIS: To evaluate the effectiveness of a standardized intranasal bevacizumab injection in treating hereditary hemorrhagic telangiectasia (HHT)-associated epistaxis. STUDY DESIGN: Prospective pilot study. METHODS: A total dose of 100 mg bevacizumab (25 mg/mL Avastin) was injected submucosally, 50 mg on each side. A total of 0.5 mL was injected in the sphenopalatine area, upper part of bony septum, upper part of the later nasal wall, and the anterior part of nasal floor. No cauterizations or laser therapy were done during or after the procedure. The hemoglobin level and grades of epistaxis were recorded before and monthly after the procedure. The IFT grading system (intensity [I], frequency [F] of epistaxis, and the amount of blood transfusion [T]) and epistaxis severity score (ESS) for hereditary hemorrhagic telangiectasia system were used. Quality of life (QoL) was evaluated before and 4 weeks after the procedure using the Short Form-36 Health Survey questionnaire, Cantril's Self-Anchoring Ladder questionnaire, and Slotosch disease-specific QoL questionnaire. RESULTS: A significant improvement was found in IFT grading (P = .007), ESS grading (P = .001), and hemoglobin level (P = .01). The QoL differences were statistically not significant. CONCLUSIONS: The four-injection site technique of intranasal administration of bevacizumab is an effective treatment option in HHT-associated epistaxis, at least on the short-term effect. Long-term and comparative studies are needed to further evaluate the significance of this treatment modality.

Prospective, randomized, controlled clinical trial of Ankaferd Blood Stopper in patients with acute anterior epistaxis.

This is a study evaluating the efficacy of Ankaferd Blood Stopper (ABS) as a hemostatic agent compared to hemostasis by phenylephrine in patients with anterior epistaxis. The study design is a prospective, randomized, controlled, nonblinded, clinical trial. In total, 49 patients were randomly seperated to receive hemostasis technique by means of either ABS wet tampon or phenylephrine impregnated gauze tampon for anterior epistaxis control. Patients were crossed over to the other technique after two unsuccessful attempts of the first technique. Measured outcomes such as number of applications, relationship of number of applications with bleeding intensity (1 = stains on napkin, 2 = soaked napkin, 3 = bowl needed), patient discomfort during hemostasis (0 = none, 9 = unbearable), and complications were assessed. Additional data were recorded for rebleeding within 7 days. 24 of the 49 patients were assigned to the new ABS group (group I) and remaining 25 were included in the standard phenylephrine group (group II). ABS was more effective than phenylephrine at control of anterior epistaxis (79.2 vs. 64%, p < 0.05). For the patients who crossed over from phenylephrine to ABS, 44.4% achieved hemostasis by ABS. ABS successfully treated all bleeding intensity 1 and 2 patients with one application (5 min). ABS patients experienced fewer rebleeding rates within 7 days compared to phenylephrine patients (8.3 vs. 20%, p < 0.05). The patients for which ABS was applied, significant differences in effective control of anterior epistaxis were observed compared to phenylephrine. ABS is effective, safe, quick, and easy alternative to the phenylephrine in patients with anterior epistaxis.

The effect of bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia.

OBJECTIVES/HYPOTHESIS: Determine the effectiveness of treating epistaxis in hereditary hemorrhagic telangiectasia (HHT) with potassium titanyl phosphate (KTP) laser cautery combined with submucosal injection of 100 mg of bevacizumab. STUDY DESIGN: Retrospective pilot study. METHODS: Bevacizumab was injected throughout the nasal cavity following KTP laser treatment in 10 patients (bevacizumab/KTP group) and compared to nine patients previously treated with KTP laser alone (KTP group). Epistaxis frequency and severity, blood transfusion requirement, intravenous iron supplementation, emergency department visit frequency, and quality of life within 1 month and 1 year pre- and postsurgery were analyzed. Benefit was defined as less than three nosebleeds per week, with less than 10 minutes to stop each nosebleed, and no blood transfusions. The pre- and postsurgery data were analyzed within and between the two groups. RESULTS: The groups were comparable in age and gender. Significant benefit was found in frequency of epistaxis (P < .05), number of blood transfusions (P = .04), disability (P = .01), and effect on social life (P = .03) 1 month pre- and postsurgery in the bevacizumab/KTP group. Eighty percent of bevacizumab/KTP group patients reported benefit in comparison to 56% in the KTP group. CONCLUSIONS: KTP laser combined with bevacizumab in HHT epistaxis is superior to KTP laser treatment alone. It significantly decreases frequency and severity of nosebleeds and blood transfusion requirements, and significantly improves work ability and quality of life.

Treatment of epistaxis in hereditary hemorrhagic telangiectasia patients by argon plasma coagulation with local anesthesia.

BACKGROUND: Recurrent epistaxis is the most common manifestation of hereditary hemorrhagic telangiectasia (HHT). The aim of this study was to determine the role and efficacy of argon plasma coagulation (APC) in the management of epistaxis caused by HHT. METHODS: From 1997 to 2004, 43 patients with diagnosed HHT were treated for recurrent epistaxis with APC in our department. RESULTS: Thirty-six patients reported substantial reduction of bleeding after treatment. Of the 18 patients who previously needed blood transfusions, 13 reported substantial reduction of bleeding after treatment and no blood transfusions were necessary. CONCLUSION: APC allows a control of epistaxis in HHT patients and guarantees a long time free from blood transfusions. This treatment modality can be performed with local anesthesia, is not invasive, is well tolerated, is inexpensive, and can be used as a first step even in patients who need to undergo several blood transfusions for their epistaxis.

Management of posterior epistaxis with the use of the fibreoptic nasolaryngoscope.

Posterior epistaxis is usually treated by repeated nasal packing and in failed situations by ligation of feeding arteries with considerable morbidity and mortality. The most logical approach should be location of the bleeding site and arrest of haemorrhage by local treatment. The exact location of the bleeding area can be identified in actively bleeding noses with the fibreoptic naso-laryngoscope and the bleeding arrested by chemical, or thermal cautery and in failed situations by using small nasal packs confined to the bleeding site. This approach to the management of posterior epistaxis is effective and reduces the duration of hospital stay. It significantly reduces the discomfort to the patient. The current practice of indiscriminate blind nasal packing in the hope of arresting nasal haemorrhage by incidental pressure on the bleeding site should be re-evaluated.

Clinical application of inhibitors of fibrinolysis.

The basic proteinase inhibitor from bovine organs, aprotinin, was first identified in 1930 and its effect on enzyme and other biological systems has since been extensively studied. Aprotinin can only be administered intravenously and has a half-life of about 2 hours. Its administration at the start of cardiopulmonary bypass surgery appears to reduce blood loss and to protect against global myocardial ischaemia. Similarly, a smaller infarct size seems to result from early administration of aprotinin within the first hour after myocardial infarction, though further studies are needed to confirm this effect. A combination of aprotinin with tranexamic acid may be effective in preventing or delaying rebleeding after rupture of an intracerebral aneurysm; the addition of aprotinin seems to decrease the incidence of delayed cerebral vasospasm and ischaemic complications which are sometimes noted when tranexamic acid alone is used. Aprotinin is also effective as adjuvant treatment in traumatic haemorrhagic shock. The recommended loading dose is 15,000 to 20,000 KIU/kg bodyweight administered as a short intravenous infusion, followed by 50,000 KIU/hour by continuous infusion. Side effects of aprotinin are very rare. Epsilon-Aminocaproic acid (EACA), p-aminomethylbenzoic acid (PAMBA) and tranexamic acid are synthetic antifibrinolytic amino acids. Saturation of the lysine binding sites of plasminogen with these inhibitors displaces plasminogen from the fibrin surface. On a molar basis tranexamic acid is at least 7 times more potent that epsilon-aminocaproic acid and twice as potent as p-aminomethylbenzoic acid. All 3 compounds are readily absorbed from the gastrointestinal tract and excreted in active form in the urine. The plasma half-life of tranexamic acid is about 80 minutes. The main indications for tranexamic acid are the prevention of excessive bleeding after tonsillectomy, prostatic surgery, and cervical conisation, and primary and IUD-induced menorrhagia. It is possible that gastric and intestinal bleeding can also be reduced as well as recurrent epistaxis. Tranexamic acid could also be useful after ocular trauma. The value of fibrinolysis inhibitors in the prevention of bleeding after tooth extraction in patients with haemophilia is well documented, as is the treatment of hereditary angioneurotic oedema. The usual dose of tranexamic acid is 0.5 to 1g (10 to 15 mg/kg bodyweight) given intravenously 2 to 3 times daily, or 1 to 1.5 g orally 3 to 4 times daily. This dose needs to be reduced in patients with renal insufficiency. The main side effects of tranexamic acid are nausea or diarrhoea.