A Rare Case of von Willebrand Disease Presenting as Hemolacria and Literature Review.

Hemolacria is a rare condition that causes a person to produce tears that are partially composed of blood. It can be a presenting feature of certain ocular and systemic conditions. Here, the authors describe an interesting case of a 12-year-old boy with an underlying beta-thalassemia trait, who presented with a 2-day history of bilateral blood-stained tears, and an episode of epistaxis. Ocular examination was normal, and syringing showed no nasolacrimal duct blockage. Systemic examination was unremarkable. Laboratory investigations confirmed type 2 von Willebrand disease. Management of hemolacria remains a clinical challenge given the rare occurrence of the disease. In this case report, the authors discuss the differential diagnosis and management approach to hemolacria.

Interleukin-6 and Tumor Growth Factor-ß are Risk Factors for Idiopathic Epistaxis.

OBJECTIVE: To evaluate the serum levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, tumor growth factor (TGF)-ß, endothelin, and immunoglobulin (Ig)E in patients with idiopathic epistaxis, compared with healthy control individuals. METHODS: Serum levels of IL-6, IL-8, TNF-α, TGF-ß, endothelin, and IgE were evaluated in 110 patients with idiopathic epistaxis and 100 healthy controls using the enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Serum levels of IL-6 (P <.001) and TGF-ß (P = .001) were significantly increased in patients with idiopathic epistaxis, compared with controls. TNF-α serum levels were significantly increased in male patients, compared with female patients (P = .053). We observed decreased antihistamine levels and increased expression of TGF-ß (P = .02) and TNF-α (P = .02), respectively. CONCLUSIONS: IL-6 and TGF-ß appear to participate in the pathogenesis of idiopathic epistaxis. TNF-α may be considered a risk factor for male patients in developing epistaxis. Antihistamines may inhibit angiogenesis by decreasing expression of TGF-ß and increasing expression of TNF-α.

A self-controlled comparative clinical trial to explore the effectiveness of three topical hemostatic agents for stopping severe epistaxis in pediatrics with inherited coagulopathies.

OBJECTIVE: The aim of this study was to assess the effectiveness of localized treatments to persistently stop epistaxis in patients with inherited bleeding disorders. METHODS: In a self-controlled comparative clinical trial, to offer the best solution to stop epistaxis at home (within 10 minutes), patients with inherited bleeding disorders were treated using three different topical hemostatic agents, including Tranexamic acid impregnated tampon, EpiCell tampon prepared from oxidized regenerated cellulose pad, and ChitoHem tampon (reinforced with chitosan). The results of using these different products on three groups of randomly selected patients were ultimately compared using the χ(2) and Fisher's exact test statistics. RESULTS: A total of 31 patients, 5 females and 26 males with a mean age of 5.6 years, were included in the study. Twenty-three patients had Glanzmann disease, four had von-Willebrand disease, two had Bernard soulier syndrome, two had activated factor VII deficiency, and one patient had impaired secretion of adenosine deaminase. The study exhibited that statistically there was no significant difference between EpiCell tampon and Tranexamic acid impregnated tampon treatments with respect to the hemostasis duration. However, ChitoHem tampon was more efficient than Tranexamic acid impregnated tampon (P value <0.001) and EpiCell tampon (P value < 0.05). CONCLUSION: ChitoHem tampon, the chitosan-reinforced product, was the best therapy solution to stop epistaxis. We recommend further research on the use of other hemostatic agents for localized bleeding in patients with inherited bleeding disorders.

Nasal hemophilic pseudotumor: favorable response to radiotherapy.

Hemophilic pseudotumors are rare but dangerous complications of Hemophilia. We hereby report a 3-year-old boy with Hemophilia B, presenting with nasal pseudotumor, showing favorable response to radiotherapy after unsuccessful treatment with factor IX replacement therapy. The diagnosis and treatment of this rare condition is also reviewed.

Acquired von Willebrand syndrome in a patient with monoclonal gammopathy of undetermined significance.

Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that typically presents as mucocutaneous bleeding in individuals with no personal or family history of bleeding disorder. Here we present a case in which a patient presented with profound epistaxis and was found to have AVWS in the setting of monoclonal gammopathy of undetermined significance (MGUS).

Predictors of bleeding disorders in children with epistaxis: value of preoperative tests and clinical screening.

OBJECTIVE: To identify prevalence of previously undiagnosed bleeding disorders in children with severe epistaxis who failed medical therapy requiring intraoperative nasal cautery. STUDY DESIGN: Retrospective chart review 10/15/2006-12/31/2010. SETTING: Single provider outpatient otolaryngology clinic. INCLUSION CRITERIA: children (<19 years) with epistaxis referred to otolaryngology, no known bleeding disorder, failed medical therapy and received surgical nasal cautery. DATA COLLECTED: duration/severity of epistaxis, bleeding history, family history of bleeding. A screening CBC, PT and PTT were performed on all patients. RESULTS: Of 248 subjects referred for epistaxis, 47(19%) met inclusion criteria (mean age 9.2±0.5 years; 61.7% male). 31.9% (15/47) had abnormal coagulation studies but on repeat testing only 2 patients had persistent coagulation abnormalities. 15 patients were referred to hematology, 5 were diagnosed with a bleeding disorder (3 - type 1 von Willebrand's disease, 1 - platelet aggregation disorder, 1 - mild factor VII deficiency). Out of the entire cohort 10.6% (5/47) had a bleeding diathesis. Clinical predictive factors for having a bleeding diathesis were explored and included previous emergency room visits for epistaxis (p=0.04). A trend was found in those presenting with epistaxis at a younger age (p=0.07). CONCLUSION: Children with recurrent epistaxis despite medical therapy are at higher risk of having a bleeding disorder. In this highly selected group of patients 10.6% (5/47) were found to have a bleeding disorder. Screening coagulation studies (PT, PTT) only revealed 20% (1/5) of patients with a bleeding disorder. Only a subsequent comprehensive hematology evaluation revealed the diagnosis in the majority of patients.

A retrospective analysis of low dose, intranasal injected bevacizumab (Avastin) in hereditary haemorrhagic telangiectasia.

The constantly recurring epistaxis means a great reduction of quality of life for patients with hereditary haemorrhagic telangiectasia (HHT). As yet, an ideal treatment has not been found. Vascular endothelial growth factor (VEGF) has been described as a possible new therapy. In particular, the success of submucosal doses <100 mg has not been analysed before. We injected bevacizumab (Avastin) submucosally in addition to Nd:YAG laser therapy. Doses <7.5 mg were used. To investigate the effect of these additional injections in comparison to laser therapy alone, a retrospective analysis was done. For this purpose a standardized patient questionnaire was completed, which included recording the patients' Epistaxis Severity Score (ESS) before and after the antibody treatment. Besides, patient files were analysed to collect objective data like haemoglobin levels and the number of blood transfusions needed. Data for eleven patients could be analysed. A significant improvement in the ESS resulting from additional bevacizumab therapy was observed (p < 0.01). In particular, the frequency of epistaxis (p = 0.011), duration of epistaxis (p < 0.01), severity of epistaxis (p < 0.01) and the need for acute medical treatment (p = 0.014) decreased significantly. The haemoglobin levels increased significantly (p = 0.011) and the number of blood transfusions declined. There were no side effects caused by the antibody treatment. Additional injections of a low dose of bevacizumab seem to be superior to Nd:YAG laser therapy alone. These results justify further studies.

Semiología en otorrinolaringología / Semiology in otolaryngology

La patología otorrinolaringológica (ORL) es una de las principales causas de consulta en pediatría y su exploración semiológica exige una serie de habilidades en la técnica, además de paciencia por parte del explorador, con el fin que ésta no sea una experiencia negativa para el paciente. Se debe realizar la valoración de ORLcon el niño en brazos de la madre, recordando cada uno de los pasos en semiología. En la presente revisión, se evaluarán aspectos de la anamnesis en ORL, anatomía básica así como de la exploración física de la oreja, los oídos, la nariz, los senos paranasales, la boca, la faringe y el cuello.

Otolaryngology pathology (OTL) is one of the main causes of pediatric and semiologic exploration requires a range of skills in the art, as well as patience from the browser, so it is not a negative experience for the patient . PtÑ assessment should be conducted with the child in mother's arms, remembering every one of the steps in semiology. In the present review, we evaluated aspects of OTL history.

Hemorrhagic symptoms and bleeding risk in obligatory carriers of type 3 von Willebrand disease in southern Iran.

The objective of the present study was to compare old and new bleeding scores in patients with type-3 von Willebrand disease (vWD), obligatory carriers and normal controls, and to compare the ability of bleeding scores vs. clinical and laboratory data to predict bleeding after surgery. We identified 15 patients from 12 families who had type 3 vWD. Normal controls were matched to carriers by sex and age. Two physician-administered standardized questionnaires were used to evaluate old and new bleeding symptoms. Scores for old symptoms were the same in carriers and control participants (median score 0.00 vs. 0.00, P < 0.001), and patients with vWD had a significantly higher bleeding score than carriers (median 10.00 vs. 0.00, P < 0.001). Scores for new symptoms were higher in carriers than in control participants (median score -1.00 vs. -2.00, P < 0.001), and patients had a significantly higher bleeding score than carriers (median 14.00 vs. -1.00, P < 0.001). The clinical situations associated with increased bleeding risk (old symptoms) in patients with type 3 vWD compared to obligatory carriers were epistaxis [odds ratio (OR) = 175.5; 95% confidence interval (CI) 14.55-2116.69; P < 0.001], cutaneous symptoms (OR = 108; 95% CI 10.16-1147.39; P < 0.001) and hemarthrosis (OR = 19.5%; 95% CI 4.32-156.46; P < 0.001). The clinical situations associated with increased bleeding risk according to scores for new symptoms in patients with type 3 vWD compared to obligatory carriers were epistaxis (OR = 175.5; 95% CI 14.55-2116.69; P < 0.001), cutaneous symptoms (OR = 52; 95% CI 7.65-353.09; P < 0.001) and bleeding from minor wounds (OR = 74.25; 95% CI 7.43-741.118; P < 0.001). The three groups differed significantly in the severity of epistaxis and cutaneous bleeding according to scores for new and old symptoms. The new bleeding score was more reliable than the old bleeding score in predicting bleeding after invasive procedure.

[The significance of bleeding disorders in patients with epistaxis]. / Stellenwert von Gerinnungsstörungen bei Patienten mit Epistaxis.

BACKGROUND: Epistaxis can have a variety of different local or systemic causes. It is the cardinal symptom of von Willebrand disease (VWD), the most frequent congenital bleeding disorder with a prevalence of approximately 1%. The usual routine coagulation screening tests (PT, APTT, platelet count) are not sufficient to diagnose VWD, factor XIII (FXIII)-deficiency or platelet dysfunction. METHOD: A prospective study was conducted implementing enhanced coagulation screening for bleeding disorders in a total of 100 inpatients admitted for epistaxis. RESULTS: A bleeding disorder was found in 13%. In eight patients VWD was diagnosed, in six patients FXIII-deficiency was found, and in one patient both. CONCLUSION: The prevalence of bleeding disorders in patients with epistaxis is higher than in the general population. Epistaxis can be the primary symptom of chronic inflammatory disease or malignant disease. A thorough anamnesis is necessary and in cases of doubt additional testing for underlying disorders is recommended.

Routine clotting screen has no role in the management of epistaxis: reiterating the point.

Objective of the study is to investigate the role of clotting screen in adult patients presenting with epistaxis. The study is a prospective case series done in a teaching hospital in the Northeast of Scotland. Prospective data was collected for 100 consecutive patients with epistaxis admitted to the Department of Otolaryngology over 1 year (2006-2007 August). The demographics, co-morbidities, long-term medications and blood test results were noted for these patients. A retrospective audit of all patients attending the Emergency Department (ED) with epistaxis during the same study period was also performed. The following were measured: frequency of clotting screen performed in patients with epistaxis; the treatment modifying effect of clotting screen results. Of the 100 admitted patients, 45 were male and 55 were female. The majority of them had more than two co-morbidities such as hypertension, ischaemic heart disease and atrial fibrillation. Forty-seven patients were on aspirin, 19 on warfarin and 12 patients on clopidogrel. A clotting screen was done for 80 patients but only 2 patients (2.5%) had an abnormal INR. A total of 356 patients presented to the ED with epistaxis. Of 356 patients, 138 (39%) had their clotting screen checked. Of 138 patients, 42 (30%) were on warfarin. Only 7 patients (7/138 = 5%) had an abnormal result. Our data suggests that routine clotting screen check does not alter the epistaxis management in patients with no risk factors or with stable warfarin dosage. Therefore, routine clotting screen in patients with epistaxis without relevant risk factors is not an evidence-based practice.

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.

Severe aortic valve stenosis and nosebleed.

Aortic valve stenosis is known to be associated with loss of high molecular von Willebrand multimers. This can lead to gastrointestinal bleeding in patients with gastrointestinal angiodysplasia, the Heyde syndrome. Here we present a case of anaemia and severe epistaxis associated with acquired von Willebrand syndrome. Gastrointestinal endoscopy revealed no bleeding source. Calcifying aortic stenosis was confirmed by echocardiography. Loss of high molecular weight multimers of von Willebrand factor in our patient was shown by immunoblot analysis. If severe epistaxis occurs in the context of symptomatic aortic valve stenosis, it might be an additional reason to recommend valve replacement surgery to the patient.

[The analysis of plasma Urokinase-type plasminogen activator and Urokinase-type plasminogen activator receptor which unknown factor nosebleed patients].

OBJECTIVE: To investigate the pathogenesis of unknown nosebleed patients. METHOD: The ELISA test were used to detected plasma Urokinase-type plasminogen activator (uPA) and Urokinase-type plasminogen activator receptor (uPAR) level in 19 cases unknown factor nosebleed patients and 36 health persons. RESULT: The results showed uPAR and uPA level in nosebleed group (before treatment) uPAR (0.14 +/- 0.04) microg/L, uPA (0.24 +/- 0.09) microg/L; (after treatment) uPAR (0.08 +/- 0.02) microg/L, uPA (0.18 +/- 0.07) microg/L. And normal group uPAR (0.07 +/- 0.03) microg/L, uPA (0.17 +/- 0.05) microg/L. The uPAR and uPA level in nosebleed group before treatment is higher than that in normal group (P <0.05). There is no significant difference between nosebleed group after treatment and normal group (P>0.05). CONCLUSION: The reasons of uPAR and uPA level high in unknown factor nosebleed patients were not clear, maybe relation to vascular endothelial cell, smooth muscle cell and neutrophil-monocytic release more uPAR and uPA. So uPAR and uPA density of nostril accumulation is more high in its microenvironment, that fibrinolytic system activated increase and result in its hyperactivity, and happened nosebleed when blood be in hypocoagulable state.

Anesthetic management of juvenile nasopharyngeal angiofibroma resection.

OBJECTIVE: To evaluate the anesthetic implications of the surgical resection of juvenile nasopharyngeal angiofibroma (JNA). DESIGN: Retrospective study. SETTING: University-affiliated community hospital. PARTICIPANTS: Ten patients undergoing resection of JNA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from the records of 10 patients undergoing resection of JNA were reviewed and analyzed with regard to demographics, history of the disease, characteristics of the tumor, surgical resection techniques, and anesthetic management. Patients were age 11 to 29 years. All had nasal obstruction as presenting symptom. There was no intracranial invasion. Eight tumors were resected via a lateral rhinotomy and 2 endoscopically (after embolization of the tumor's feeding vessels). Duration of surgery was 6 +/- 1 hours for rhinotomy and 6 and 6.5 hours for the 2 endoscopic resections. Anesthesia was induced in a rapid-sequence manner. Arterial and central venous catheters were placed in all patients. Mean arterial pressure was targeted to 55 to 65 mmHg by using increasing concentrations of isoflurane. The estimated blood loss was 4,800 +/- 1,600 mL and blood replacement was 3,200 +/- 1,400 mL in the first group. The 2 other patients lost 600 mL and 1,500 mL. Blood replacement in this group was 0 and 700 mL respectively. No mortality or major morbidity occurred. CONCLUSION: Resection of JNA should be considered a major procedure with many anesthetic challenges. Isoflurane may be employed to provide deliberate hypotension.

Vascular endothelial growth factor serum levels are elevated in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a genetic angiodysplasia affecting multiple organs. Two genes involved in the transduction of TGF-beta signalling are responsible for HHT. An additional role for vascular endothelial growth factor (VEGF) has been proposed. Serum VEGF, which has been evaluated in several diseases characterized by aberrant angiogenesis, has never been measured in patients with HHT. AIMS: To evaluate VEGF serum levels in HHT patients as compared to normal subjects. MATERIALS AND METHODS: 32 HHT patients (age 47.7 +/- 16.7 years) and a control group of 37 healthy subjects (age 48.2 +/- 15.5 years) were entered in the study. Each patient underwent serum VEGF dosage using a commercial ELISA specific for the human molecule. RESULTS: The serum level of VEGF in HHT patients was 196.3 +/- 103.2 pg/ml, while it was 152.0 +/- 84.1 pg/ml in the control group. Statistical analysis showed that serum VEGF was significantly higher in HHT patients than in the controls (p < 0.031). CONCLUSIONS: According to a study performed in a murine model, persistence of the activation phase of angiogenesis might be responsible for an increased production of several angiogenic factors, in particular VEGF, in HHT. Our work is the first to suggest an increased expression of VEGF in the serum of subjects with HHT in agreement with the stimulation of VEGF synthesis proposed in the murine model.

Clinical and laboratory features of 178 children with recurrent epistaxis.

PURPOSE: To determine the clinical and laboratory features of 178 children referred for the evaluation of recurrent epistaxis to an outpatient hematology clinic in a university medical center. PATIENTS AND METHODS: Medical records of 3681 outpatient pediatric hematology referrals were retrospectively review, and 178 children with recurrent epistaxis from 1985 to 1999 were identified. Historic (other bleeding symptoms: gingival bleeding, easy bruising, menorrhagia, and gross blood in the urine or stool: duration and severity of the epistaxis episodes; and family history of bleeding) and laboratory (complete blood count and coagulation tests) data were analyzed. RESULTS: There were 103 boys and 75 girls with a median age of 84 months (range 15-219 months). Sixty-seven percent (n = 119) did not have a coagulopathy diagnosed and 33% (n = 59) did. The diagnoses included von Willebrand disease in 33, platelet aggregation disorders in 10, thrombocytopenia in seven, mild factor VIII deficiency in three, Bernard-Soulier syndrome in two, factor VII deficiency in one, factor IX deficiency in one, and factor XI deficiency in one, and coagulation inhibitor in one. Of the historic data, only a family history of bleeding was predictive of diagnosing a coagulopathy (P = 0.023). The duration and severity of the epistaxis and the presence of other bleeding symptoms had no predictive value. Children with a coagulopathy diagnosed had a longer median partial thromboplastin time (PTT) (33.1 vs. 30.5 seconds; P = 0.012). CONCLUSIONS: One-third of children presenting with recurrent epistaxis have a diagnosable coagulopathy. A positive family history and a prolonged PPT are useful predictive data.