Recurrent Bleeding Episodes Research Articles

Feeding and Draining Vessel Ligation with Sclerotherapy of High Flow Arteriovenous Malformations in the Head and Neck

Feeding and Draining Vessel Ligation with Sclerotherapy of High Flow Arteriovenous Malformations in the Head and Neck

Adverse perinatal and neonatal outcomes in patients with chronic abruption-oligohydramnios sequence.

Chronic abruption-oligohydramnios sequence (CAOS) is a clinical condition with lasting vaginal bleeding and oligohydramnios because of chronic placental abruption, which seems to cause preterm labor and neonatal chronic lung disease (CLD). This prompted us to explore the correlation between perinatal/neonatal outcomes and CAOS. Patients with suspected risk of abortion with recurrent vaginal bleeding were divided into CAOS and non-CAOS groups, and we compared the perinatal/neonatal outcomes between these two groups. To examine the impact of chorioamnionitis (CAM) on the prognosis of CAOS, we also compared outcomes between the CAOS group and gestational-age-matched preterm labor due to CAM (CAM group). In the CAOS and non-CAOS groups, initial vaginal bleeding was seen at the first trimester. However, its duration was significantly longer in the CAOS group. Additionally, neonatal birthweight was lower, and small-for-gestational-age (SGA) incidence was higher in the CAOS group. CLD was observed in most infants from CAOS patients. In the comparison between CAOS and CAM groups, birthweight was lower and SGA incidence was higher in the CAOS group. Moreover, CLD incidence and neonatal mortality were significantly higher, despite the lower incidence of severe CAM in the CAOS group. Finally, multivariate analysis demonstrated that duration of bleeding was a significant predictive factor for CAOS. Our observations demonstrated that patients with CAOS were a high-risk group for poor perinatal/neonatal outcomes. Moreover, episodes of recurrent and prolonged uterine bleeding were predictive factors for CAOS. During the first trimester, prolonged bleeding is an important sign as one symptom of CAOS.

Dose escalation of low molecular weight heparin in patients with recurrent cancer-associated thrombosis

IntroductionPatients with cancer-associated thrombosis are at a high risk of developing recurrent events despite anticoagulant therapy. Escalation of the dose of low molecular weight heparin (LMWH) has been suggested as a potential treatment option to manage these patients. We sought to confirm the benefit and risk of this management strategy in patients with recurrent cancer-associated thrombosis. Material and MethodsA retrospective cohort study of consecutive cancer outpatients seen for management of a symptomatic recurrent cancer-associated thrombosis while on anticoagulation was undertaken. Objectively confirmed episodes of recurrent thrombosis were treated with either dose escalation of LMWH or initiation of therapeutic dose of LMWH in patients already anticoagulated with LMWH or vitamin K antagonist (VKA) respectively. Included patients were followed for a minimum of 3months after the index recurrent event. ResultsFifty-five cancer patients with a recurrent venous thromboembolism (VTE) despite anticoagulation were included. At the time of the recurrence, 89% of patients were on LMWH. The median time between the initial cancer-associated thrombosis to the index recurrent event was 2.3months (range 0.1 to 30.4months). Four patients (7.3%; 95% CI: 2.0 to 17.6%) had a second recurrent VTE during the 3-month follow-up period. Three patients (5.5%; 95% CI 1.1 to 15.1%) had major bleeding complications after dose escalation of LMWH. There were no recurrent fatal VTE or major bleeding episodes. ConclusionEscalating the dose of LMWH seems effective and safe for managing patients with recurrent cancer-associated thrombosis despite anticoagulant therapy.

Over-the-scope clip placement is effective rescue therapy for severe acute upper gastrointestinal bleeding.

Background and study aim: The novel over-the-scope clip (OTSC) allows for excellent apposition of tissue, potentially permitting hemostasis to be achieved in various types of gastrointestinal lesions. This study aimed to evaluate the usefulness and safety of OTSCs for endoscopic hemostasis in patients with upper gastrointestinal bleeding in whom traditional endoscopic methods had failed. Patients and methods: A retrospective case series of all patients who underwent placement of an OTSC for severe recurrent upper gastrointestinal bleeding over a 14-month period was studied. Outcome data for the procedure included achievement of primary hemostasis, episodes of recurrent bleeding, and complications. Results: Twelve consecutive patients (67 % men; mean age 59, range 29 – 86) with ongoing upper gastrointestinal bleeding despite previous endoscopic management were included. They had a mean ASA score of 3 (range 2 – 4), a mean hemoglobin of 7.2 g/dL (range 5.2 – 9.1), and shock was present in 75 % of patients. They had all received packed red blood cells (mean 5.1 units, range 2 – 12). The etiology of bleeding was: duodenal ulcer (n = 6), gastric ulcer (n = 2) Dieulafoy lesion (n = 2), anastomotic ulceration (n = 1), Mallory – Weiss tear (n = 1). Hemostasis was achieved in all patients. Rebleeding occurred in two patients 1 day and 7 days after OTSC placement. There were no complications associated with OTSC application. Conclusions: OTSC use represents an effective, easily performed, and safe endoscopic therapy for various causes of severe acute gastrointestinal bleeding when conventional endoscopic techniques have failed. This therapy should be added to the armamentarium of therapeutic endoscopists.

Blue Rubber Bleb Nevus Syndrome as a Cause of Lower Digestive Bleeding

Introduction. Blue rubber bleb nevus syndrome is a rare disorder that is characterized by multiple recurrent vascular malformations that involve the skin and the gastrointestinal tract. The disease can present chronic anemia and severe episodes of gastrointestinal bleeding. Case Report. A 41-year-old man was admitted with recurrent episodes of lower gastrointestinal bleeding and anemia that had worsened over the last 3 months. The physical examination showed soft, diffuse, compressible, bluish nodules on all of the skin surfaces of the body. A biopsy from one of these skin lesions allowed a histological diagnosis of cavernous hemangioma. He submitted to a colonoscopy, which showed hemorrhoids and a plane vascular lesion mainly located on the right colon with recent signs of bleeding; this lesion was treated by local excision and sclerosis. The pathological study of the colon specimens also reflected the presence of cavernous hemangioma. The cutaneous hemangiomas and the presence of colonic venous malformations were compatible with blue rubber bleb nevus syndrome. The patient presented a favorable follow-up with clinical control of the anemia and without relapse of the gastrointestinal bleeding two years after the procedure. Conclusion. Although rarely diagnosed, blue rubber bleb nevus syndrome may be responsible for lower digestive bleeding.

Guidelines of management of musculoskeletal complications of hemophilia

Hemophilia is an X-linked heritable coagulopathy with an overall prevalence of approximately 1 in 10,000 individuals. The most common form is factor VIII deficiency (hemophilia A), which comprises approximately 80% of cases. Factor IX deficiency (hemophilia B), comprises approximately 20% of cases. In patients with hemophilia, regular replacement therapy with clotting factor concentrates (prophylaxis) is effective in preventing recurrent bleeding episodes into joints and muscles. However, despite this success, intra-articular and intramuscular bleeding is still a major clinical manifestation of the disease. Bleeding most commonly occurs in the knees, elbows, and ankles, and is often evident from early childhood. The pathogenesis of hemophilic arthropathy is multifactorial, with changes occurring in the synovium, bone, cartilage and blood vessels. Recurrent joint bleeding causes synovial proliferation and inflammation (hemophilic synovitis) that contribute to end-stage degeneration (hemophilic arthropathy); with pain and limitation of motion severely affecting patients' quality of life. The author conducted a comprehensive review and synthesis of the relevant literature. The author reviewed all compiled reports from computerized searches. Searches were limited to English-language sources and human subjects. Literature citations were generally restricted to published manuscripts appearing in journals listed in Index Medicus and reflected literature published up to July 1, 2013. The aim of this updated paper is to provide comprehensive and timely evidence-based guidelines and recommendations on the treatments of damaged joint among hemophilia patient. Further recommendations included the control of risk factors, interventional approaches for treatment of hemophilia, the use of bypassing factors for the inhibitors, and preventing recurrent bleeding especially in high-risk populations are provided. Prophylaxis by replacement of the missing factor in patients with hemophilia is the optimal way to prevent the occurrence of haemarthrosis and thereby the onset of arthropathy, provided that it is started early in life. Dosing should be individualized and increased in case of bleeding. Prevention of bleeding episodes through early treatment will prevent accumulation of blood in joint and the subsequent inflammation and potential hemophilic arthropathy. Treatment must be maintained until bleeding remission and patients have recovered as much of their ROM and muscular strength as possible. Clinical evaluation of the joints, gait, motion, muscle tone, functional level of disability, pain, and swelling, as well as imaging techniques, must be performed to assist in the diagnosis of chronic synovitis and to guide treatment decisions. The first step to treating synovitis, refractory to medical treatment, is the use of synovectomies, non-surgical or surgical interventions. In many cases, joint deformities have to be treated by open orthopaedic surgery. State-of-the-art treatment of patients with hemophilia requires a multidisciplinary team. Level of evidence: Level III (Systematic Literature review).

Risk of recurrence and long-term outcomes after colonic diverticular bleeding

Diverticular disease is one of the most common causes of acute lower gastrointestinal bleeding. We aimed to evaluate the natural history, follow-up, and risk factors associated with re-bleeding (recurrence) in patients with colonic diverticular bleeding. We reviewed patients with proven colonic diverticular hemorrhage from September 1993 to June 2012 at our institution. Recurrence was the main outcome measure. We identified 78 out of 95 patients with proven diverticular bleed who were treated non-operatively and were followed up for a median of 57.1 months. Thirty-seven (47 %) of these patients with a median age of 67 years developed recurrent diverticular bleed after a median time of 8.1 months. The bleeding originated from the left colon in 78 (83 %) out of 95 patients in the first bleeding episode and 31(84 %) out of 37 patients during the recurrent bleeding episode. Thirty-six patients (97 %) with recurrent diverticular bleed required surgical intervention. Old age at the time of initial bleeding was associated with recurrence (p = 0.001). Patients with diverticulitis (p < 0.0001), peripheral vascular (p = 0.01), and chronic renal diseases (p = 0.047) were found to have an increased risk for recurrent colonic diverticular bleed. We only had one perioperative mortality due to postoperative sepsis. All other mortalities were not directly associated with surgery. Patients with a history of colonic diverticular bleed are prone to recur shortly thereafter. Certain risk factors including increased age, documented diverticulitis, history of peripheral vascular disease, and chronic renal failure may predispose to recurrence.

Abstract 18136: Mechanical Circulatory Support for Failing Systemic Right Ventricle - A Viable Bridging Strategy to Transplant?

BACKGROUND: The morphological right ventricle in the systemic position is associated with late failure and cardiac transplantation becomes the only treatment option. In the face of declining heart donor, the role of left ventricular assist device (VAD) as a bridge to transplant is well established. However, there is only scarce experience of supporting failing systemic right ventricle (RV). METHODS: Between 1989 and 2013, a total of 21 adult patients (age 18 years and above) had heart transplant in our institution for systemic RV failure. Since our inception case to support failing systemic RV mechanically in 2009, a total of six adult patients (5 males, mean age 36 years; 4 post atrial switch, 2 ccTGA) had been supported (5 Heartware and 1 Berlin Heart). Concomitant systemic atrioventricular surgery was required in two patients. Indications for systemic RV-VAD were (i) bridge to transplant (n=2) (group BTT) and (ii) bridge to further decision in the presence of high transpulmonary gradient and/or high PRA (n=4) (group BTD). RESULTS: Early mortality (&lt; 30 days) was 16.7% (n=1). One further patient died in-hospital following non-cardiac procedure (day 62). Overall, median ICU stay was 6 days (range 5-8 days). Four patients were discharged home: three patients reported significant improvement in functional capacity and serial TPGs assessment showed significant improvement. In group BTT, 1 was transplanted (at day 313 post-VAD). In group BTD, 1 patient was transplanted (day 685), one has on-going support (currently 375 days), and one died (day 232, sepsis and multi-organ failure). Three patients (50%) had cerebrovascular events (3, 4, 15 months post-VAD) with satisfactory recovery and one had recurrent bleeding episodes. One patient required further surgery (aortic valve replacement and device replacement due to thrombosis). Survival at transplant was 100% for those with VAD (n=2) (vs 89.5% for those without VAD support, n=17/19). CONCLUSION: The use of ventricular assist device to support failing systemic RV is a viable strategy to bridge for transplant or further assessment. Neurological event, albeit with satisfactory recovery, remains a significant morbidity.

Concomittant Acquired Von Willebrand Disease and Acquired Factor V Deficiency Causing a Severe Bleeding Diathesis Due To Multiple Myeloma With Amyloidosis

Background Acquired coagulopathies are a common problem in Hematology, and are most often due either to medication effect, liver disease, or consumption. Among the uncommon causes of acquired coagulopathy, inhibitory auto-antibodies may develop, either in the setting of autoimmune diseases, in the setting of lymphoproliferative disorders, or as isolated inhibitory immunoglobulins. Uncommonly, the adsorption of coagulation factors from the circulation into the tissues by extracellular deposition of pathologic amyloid results in an acquired factor deficiency, due to clearance of factor from the circulation that exceeds the body's ability to produce factor. When amyoidosis does cause a coagulapathy, it is most often the result of the adsorption of Factor X by the amyloid protein, resulting in an acquired Factor X deficiency. However, there are rare reports of amyloidosis being associated with other factor deficiencies. We report a case of amyloidosis that was associated with a severe bleeding diathesis, with the etiology of the bleeding disorder being due to both acquired Factor V deficiency and concomitant acquired von Willebrand Disease. Case Report A previously healthy 51-year-old gentleman presented to an outside medical center for evaluation and management of recurrent bleeding episodes. The patient had a prior medical history significant only for right ankle trauma in the year 2005, following which he underwent a total of 4 surgical procedures; there was no excessive bleeding complicating the patient's surgeries. He was then in his usual state of health until September, 2012 when he developed onset of severe abdominal pain and was admitted to the outside facility. Following hospitalization for several months at the outside facility, he was admitted to our institution. Physical examination was remarkable for extensive ecchymoses, and for splenomegaly to 18 cm. span by exam, confirmed by imaging. CT scan showed multiple peri-caval and periaortic nodes present up to 1.7 cm in size, with shotty inguinal lymph nodes. A complete blood count showed White blood count 21,600, hemoglobin 8.0 g/dL, hematocrit 24%, platelet count 370,000, Hepatic function studies and renal function studies, as well as electrolytes, were normal on admission. Coagulation studies revealed Prothrombin Time prolonged at 16.8 seconds (normal &lt; 12.7), aPTT prolonged at 44. Mixing patient plasma with equal volume normal plasma corrected both the PT and aPTT. Detailed factor assays showed markedly decreased Factor V activity of 27%; Ristocetin Cofactor activity was markedly decreased at 49%, but von Willebrand antigen was elevated at 213%. Multimer analysis was consistent with Type II vWD (see figure 1). The patient received fresh frozen plasma and Humate P, with transient correction of the bleeding diathesis. This permitted inguinal lymph node biopsy, which documented AL amyloidosis. Extraction of the protein from the lymph node documented AL lambda light chain amyloid (see figure 2). Marrow biopsy documented IgG lambda multiple myeloma. The patient was treated using Bortezumib plus Dexamethasone, and achieved a complete remission, with normalization of the coagulation parameters and factor levels over the following several months. His bleeding diathesis has fully resolved, and Karnofsky performance status improved to 100%. Conclusion Although there are several case reports of acquired von Willebrand disease on the basis of amyloidosis, and several case reports of acquired Factor V deficiency on the basis of amyloidosis, this appears to be the first reported case of both acquired vWD and acquired Factor V deficiency on the basis of amyloidosis. Disclosures: No relevant conflicts of interest to declare.

Acquired Von Willebrand Disease – To Treat Or Not To Treat The Inhibitor?

Introduction Acquired von Willebrand disease is a relatively rare but possibly under diagnosed bleeding disorder. The etiology is multifactorial, including underlying malignancy, drugs, valvular heart disease, mechanical cardiac assist devices, autoimmune diseases and infections. The disorder is characterized by mucocutaneous bleeding presenting in adulthood with no prior history or family history of bleeding tendency. Materials and Methods A retrospective chart review was performed on patients with a diagnosis of acquired von Willebrand disease over a period of 15 years. We identified 10 patients with this diagnosis in the absence of valvular heart disease or the presence of a mechanical cardiac assist device. The initial presentation along with demographic features, co-morbidities, laboratory values at the time of initial presentation and subsequent follow up, treatment of bleeding episodes and cause of death were noted. Results The mean age at diagnosis was 56.5 years with range of 39-75 years. Males and females were equally affected. One patient each had aortic valve stenosis and hypothyroidism, both of which were treated and not felt to be responsible for the diagnosis of acquired von Willebrand disease. Six of ten patients had an underlying myelo / lymphoproliferative disorder while two had a remote history of cured high grade colon cancer. Most of the patients presented with mucocutneous bleeding including easy bruising, epistaxis, gingival bleeding, and GI bleeding. Post procedural urinary tract bleeding was the presenting sign in two patients and one patient presented with spontaneous intracranial hemorrhage. All but two patients presented with ristocetin cofactor activity of &lt;10% and factor VIII and von Willebrand antigen levels in the range of 4-31% and 10-23% respectively. Multimer patterns were either severely reduced high molecular weight multimers or decreased multimers with normal distribution. For all patients, the presenting lab values remained unchanged at follow up even over several years (up to 12 in our series), including in those who received treatment for the underlying myelo / lyphoproliferative disorder. Treatment to control bleeding included DDAVP, IVIg, factor VIII/VWF concentrates, rituximab, plasma exchange, and recombinant factor VIIa, all with varying degrees of success. Six of ten patients did experience recurrent bleeding episodes and two ultimately died of uncontrolled GI bleeding. Discussion Acquired von Willebrand disease is a rare entity, typically presenting with severely decreased factor levels, and often associated with significant morbidity and potential mortality. Although some patients experience recurrent and refractory bleeding, others may survive for more than 10 years without major complications with this condition. As reported previously in literature, most of the cases in our series were also associated with underlying myelo / lymphoproliferative disorders. In two of our patients the development of acquired von Willebrand disease preceded the diagnosis of a lymphoproliferative disorder by 3-4 years, suggesting that close monitoring for future development of these disorders is warranted. In contrast to previous reports, treatment of the underlying myelo / lymphoprolifertive disorder did not lead to improvement in the bleeding episodes or lab values in any of our patients that were treated (5/6). In acquired hemophilia, approximately 80% of patients experience significant bleeding, and mortality has been quoted in the range of 8-22%. Thus, treatment usually includes an attempt to eradicate the inhibitor with immune suppression. In our series, 60% of the patients experienced recurrent and refractory bleeding, and mortality was also 20%, suggesting that a similar approach should be considered in those with acquired von Willebrand disease. Disclosures: No relevant conflicts of interest to declare.

Treatment of Pediatric Pyogenic Granulomas Using β‐Adrenergic Receptor Antagonists

Propranolol and timolol are nonselective ß-adrenergic antagonists that induce peripheral vasoconstriction and affect angiogenic cytokines. Oral and topical ß-blocker therapy has become the de facto first-line treatment for complicated infantile hemangiomas because of its superior efficacy and tolerability. Pyogenic granulomas or lobular capillary hemangiomas are common acquired vascular tumors accounting for 0.5% of all skin nodules in children. Although they are benign vascular proliferations, treatment is often sought because of recurrent episodes of bleeding and for cosmetic considerations. Numerous treatment options are available, but recurrence rates are high. Noninvasive methods of treatment are being sought, particularly for young children. Herein we report a series of seven cases of cutaneous and mucosal pyogenic granulomas treated successfully using oral or topical ß-blockers.

Acquired haemophilia A in an elderly patient: A case report

Background: Acquired haemophilia A is a rare condition that can have potentially life-threatening consequences. We report a case of acquired haemophilia A in an elderly patient who had presented to hospital with recurrent bleeding episodes. Case presentation: A 73year old female nursing home resident with advanced dementia and previous stroke was admitted with bilateral arm swelling and bruising. She had also been experiencing recurrent vaginal bleeding and had recent admissions under the Gynaecology team where no cause was found for the bleeding.

Cholecystoduodenal Fistula: A Rare Cause of Massive Upper GI Bleeding

Introduction: Rare complications of gallbladder disease include fistula formation, which can lead to further complications including pneumobilia, recurrent cholangitis, Mirizzi's, Bouveret's and gallstone ileus. Due to their rarity and the variability in which it manifests, a high degree of suspicion must be present at the start to reduce morbidity and mortality. We present a case of a cholecystoduodneal fistula that presented with massive upper GI bleeding. Case Report: A 75-year-old female patient with a history of myelodysplastic syndrome, coronary artery disease, GERD, urinary incontinence, and hypertension presented to the ED with weakness and vomiting for 1 day, with fevers and altered mental status. In the ED, the patient's vitals were temperature of 104 F, BP 94/52, and HR 102. Initial labs were significant for a white blood cell count of 24,700 and a Hb of 7.1 g/dL. In the ED, the patient experienced an episode of 200 mL of hematemesis and bright red blood per rectum. The patient was hypotensive to 80/40 with positive orthostatics. Intravenous fluids and 5 units of pRBC were given and her blood pressure improved to 115/59. An urgent EGD was performed and showed old blood in the fundus with no source for the bleeding. On day two, the patient had a recurrent episode of massive hematemesis. A repeat EGD showed bubbles emanating from the papilla, with normal gastric mucosa. A CT and MRCP were ordered showing pneumobilia with air extending to the duodenal bulb and the presence of multiple gallstones. The findings were compatible with persistent cholecystoduodenal fistula and a decompressed gallbladder. Blood cultures confirmed gram negative sepsis. The patient was treated with IV vancomycin and zosyn, improved clinically and discharged in stable condition with no more recurrent bleeding episodes. Despite recommendations, surgery was not performed. One year later, the patient returned to the ED with a several day history of weakness, decreased appetite, and weight loss. The patient's labs were significant for a white blood cell count of 15,630, an AST of 225 IU/L, ALT of 207 IU/L, and alkaline phosphatase of 697 IU/L. CT scan and MRI of abdomen and pelvis revealed an approximately 4.7-cm mass with biliary obstruction at the level of the porta hepatis, with obliteration of the previous choledocystoduodenal fistula. Biopsies confirmed gallbladder carcinoma, and a subsequent ERCP was performed with successful palliative biliary stenting. Discussion: In cases of unexplained massive upper GI Bleeding, careful inspection of the papilla may help rule out hemobilia. In this case, the diagnosis of hemobilia helped lead to the immediate treatment and management of a complicated cholecystoduodenal fistula. Disclosure - Dr. David Lee: CSL Behring: consultant: speaker bureau for a symposium.

CMV Colitis: Bright Red Bleeding per Rectum as Primary Clinical Manifestation

Introduction: Cytomegalovirus (CMV) gastrointestinal disease is an uncommon but serious complication of acquired immunedeficiency syndrome (AIDS). Recently, the incidence of CMV gastrointestinal disease has decreased substantially since the advent of highly active anti-retroviral therapy (HAART).Figure: Colonoscopy showing large ulcers at the hepatic flexure.Case: A 62-year-old male with history of HIV on HAART was sent from a nursing home for evaluation of respiratory distress with oxygen saturation of 89% on room air. On admission, the patient was noted to have supratherapeutic INR of 4.7. The patient was on warfarin for DVT. He was also found to have an acute drop in hematocrit with no obvious source of bleeding. He received packed red blood cells. He also received vitamin K to reverse coagulopathy. While in the hospital, the patient had recurrent episodes of bright red bleeding per rectum. Despite reversing coagulopathy and multiple packed red blood cell transfusions, he became hypotensive. He was transferred to ICU, where he continued to bleed. Colonoscopy was performed. The bowel preparation was suboptimal. The source of bleeding could not be identifi ed. The patient stopped bleeding spontaneously, and was later transferred to the general medical floor. The patient later had another episode of rectal bleeding. A Bleeding scan showed bleeding originating from the mid-ascending colon. A repeat colonoscopy was performed, which showed colitis with large ulcers at the hepatic flexure. The differential diagnoses that were considered at that point were Ischemia, lymphoma, MAI, amoeba and CMV. Biopsies were obtained and sent to pathology. CMV by PCR came back as 79700 copies/ml. Histopathology showed evidence of CMV colitis. The patient was treated with Ganciclovir 5 mg/kg IV every 12 hrs x 2 weeks, then 5 mg/kg once daily. He improved clinically and was discharged to the nursing home on Valaganciclovir 900 mg orally twice daily, followed by 900 mg once a day, until CD4 count becomes more than 100. Conclusion: This is a rare case of CMV colitis with gastrointestinal bleeding as the primary and only clinical manifestation.Figure: Histopathology: colonic mucosa showing giant cells with pleomorphic basophilic inclusion bodies (Owl's eyes)and inflammatory cells.

An Unusual Case of the Hiccups and the Blues: Blue Rubber Bleb Nevus Syndrome

Introduction: Persistent hiccups or singultus are quite bothersome but seldom a reason for consultation. Gastrointestinal etiologies are related mainly to esophageal or gastric causes (1). Here we describe the first known case of blue rubber bleb nevus syndrome (BRBNS) leading to persistent hiccups and its subsequent treatment. Case Presentation: A 47-year-old male presented with persistent hiccups associated with nausea and vomiting for the past 6 days. Medical history was significant for recurrent GI bleeding episodes from arteriovenous malformations in the esophagus and sigmoid colon. On physical examination, multiple scattered small flat blue nevi were noted on the face, oral mucosa, chest, extremities, and soles. Neurologic exam revealed no obvious focal deficits with specifically no hearing deficits or vertigo and a narrow-based gait. Initial labs were unremarkable with Hgb of 12.5 mg/dL and normal levels of electrolytes, liver function tests, and lipase. A CT scan of the chest demonstrated a long segment of nodular circumferential esophageal thickening. MRI did not reveal any local phrenic nerve compression. An EUS depicted hypertrophied thickened vascular esophageal mucosa in the upper third of the esophagus with no endoscopic evidence of GERD or gastric distention. Fine needle aspiration was performed of the thickened wall but was unremarkable. After excluding CNS causes, cardiothoracic surgery consultation was obtained, but given the history of known esophageal vascular ectasias, medical management was deemed appropriate. The patient was treated symptomatically with chlorpromazine, phenergan, and baclofen. Chlorpromazine was subsequently held secondary to pancytopenia. His hiccups eventually resolved with scheduled metoclopramide and baclofen (2). He continues to follow up in our clinic for surveillance endoscopies. Summary: BRBNS is a rare condition characterized by hemangiomas in the skin, GI tract, and rarely other viscera. Most common clinical presentation is GI bleeding (3). There is suggestion of chromosome 9p involvement with a tyrosine kinase receptor mutation leading to inherited or de novo mutations (2). Differential diagnoses include Sturge-Weber, Von-Hippel Lindau, and Cobb's disease. Current treatment is aimed at surveillance and management of complications. Esophageal causes of persistent hiccups include GERD, esophageal stents, and local nerve compression have been described before (1,4). In the absence of these, we propose that the extraluminal vascular ectasias caused nerve compression and stimulation of the proximal esophageal mechanoreceptors leading to the persistent hiccups.

ARC syndrome in preterm baby

A preterm female infant born of 32 weeks gestational age was presenting with musculoskeletal abnormalities, and cholestasis that later on resolved. Later on, she developed renal tubular acidosis (RTA), poor weight gain, unexplained intermittent fever and recurrent spontaneous bleeding episodes. ARC is an acronym that stands for arthrogryposis, renal dysfunction and cholestasis. ARC syndrome is a rare disorder that is difficult to diagnose and is associated with poor outcomes. We present a case of ARC syndrome in an infant with a history of failure to thrive, early cholestasis and RTA. There are many unique features about this case that should add to our understanding of this genetic condition. To our knowledge this is the first identified case of ARC syndrome in a preterm infant. Although the specific mutation found in our patient has not been reported previously, the type and location of this mutation is consistent with our genetic understanding of this disorder.

Role of postmenopausal bleeding pattern and women's age in the prediction of endometrial cancer

Women with postmenopausal bleeding should be evaluated efficiently to exclude endometrial carcinoma. To estimate the risk of endometrial cancer using individual case characteristics among women with postmenopausal bleeding in whom the endometrial thickness is >4 mm. Women with postmenopausal bleeding underwent clinical evaluation followed by transvaginal ultrasonography and endometrial biopsy. Clinical evaluation included age, body mass index, duration of menopause, number of bleeding episodes and amount of bleeding. This study included 142 women, and endometrial carcinoma was found in 18 (12.7%). Older age, higher body mass index, longer duration of menopause, longer lasting bleeding episodes, higher amount of bleeding and recurrent bleeding episodes were the clinical characteristics associated with endometrial cancer. However, multivariate analysis revealed >55 years of age during postmenopausal bleeding, history of recurrent bleeding episodes and bleeding exceeding 5 pads per day in each episode as significant parameters, which predicted the presence of endometrial cancer among women with postmenopausal bleeding. Prompt evaluation is required in women with postmenopausal bleeding to exclude endometrial cancer. Transvaginal ultrasonography is a reasonable first-line approach, and invasive sampling is required when ultrasonographic endometrial thickness is above 4 mm. However, about 90% of women with postmenopausal bleeding will finally be found to have a nonmalignant condition. Therefore, women who are at increased cancer risk should further be distinguished. This may be achieved using individual patient characteristics that result in a more accurate evaluation strategy with lower rates of unnecessary invasive procedures.

Hematidrosis

Hematidrosis is an extremely rare clinical entity characterized by recurrent episodes of skin bleeding mixed with sweat. We report a case of hematidrosis in a 10 year old girl where detailed laboratory and histopathological investigation revealed no abnormality. The girl was successfully treated with propranolol with no recurrence of bleeding over a follow-up of 3 months.

Results of the WIRK prospective, non‐interventional observational study of recombinant activated factor VII (rFVIIa) in patients with congenital haemophilia with inhibitors and other bleeding disorders

Recombinant activated factor VII (rFVIIa) has been available for the treatment of acute bleeding and for prevention of bleeding during surgery and invasive procedures in patients with congenital haemophilia with inhibitors (CHwI) and acquired haemophilia since 1996. The study objective was to assess the efficacy and safety of rFVIIa in patients with CHwI, acquired haemophilia, congenital FVII deficiency and Glanzmann's thrombasthenia, in a real-life clinical setting. There were no specific inclusion or exclusion criteria; participation was offered to all German haemophilia centres known to use rFVIIa to treat patients with the above indications. Data on rFVIIa use and efficacy for the treatment of acute bleeding episodes and invasive procedures were recorded. Adverse drug reactions and recurrent bleeding episodes were also monitored. In total, 64 patients (50.0% women) received rFVIIa treatment. Patients experienced 281 evaluable bleeding episodes and underwent 44 invasive procedures. In 252 of 281 (89.7%) bleeding episodes, a stop (66.5%) or a significant reduction (23.1%) in bleeding was observed. No bleeding complications were reported for 42 of 44 (95.5%) invasive procedures covered with rFVIIa. A clear positive association was observed between early initiation of rFVIIa treatment for acute bleeding and efficacy. The total cumulative dose and number of injections were 468.3 ± 545.8 μg kg(-1) and 3.6 ± 4.6 respectively. No drug-related adverse events were reported. rFVIIa use in Germany provided effective haemostatic cover without associated adverse events in the management of acute bleeds and invasive procedures across a range of bleeding disorders.

Potential usefulness of thrombopoietin receptor agonists in haemophiliacs with thrombocytopaenia due to chronic liver disease

New thrombopoietin receptor agonists (TPO-RA) eltrombopag and romiplostin were initially used for refractory immune thrombocytopaenic purpura, but more recently reported experience shows that they may also be applied to patients with thrombocytopaenia secondary to hepatitis C virus (HCV)-related chronic liver disease (CLD) in certain clinical situations; in haemophilic patients these drugs are always part of a therapeutic approach involving other haemostatic resources required to cover the joint congenital and acquired bleeding diathesis found in these patients. Platelet count elevation before invasive procedures or surgery or prior to and during antiviral therapy involving interferon are the main clinical applications of these drugs; they might also be useful in cases with advanced CLD and severe thrombocytopaenia in order to prevent recurrent bleeding episodes (namely articular and muscular in haemophilic individuals) or reduce bleeding risk in patients with multiple haemorrhagic risk factors. Long-term prophylactic treatment with factor concentrates in such cases is mandatory. There have been some reports of portal or splanchnic thromboses in patients on TPO-RA with CLD, especially in cases undergoing invasive procedures who reach platelet counts at least 200×10/l and often with additional risk factors for thrombosis. For this reason, and although haemophilic patients have an important protection against thrombosis, platelet counts should ideally be maintained between 50 and 100×10/l with dose adjustments carried out as required and initial doses of eltrombopag in patients with moderate or severe CLD, especially in prolonged treatments, should be reduced to 25 g once daily. These new drugs can be a useful adjuvant tool in patients with thrombocytopaenia secondary to CLD.