Successful use of recombinant factor VIIa for management of severe menorrhagia in an adolescent with an acquired inhibitor of human thrombin

Antibodies directed against human thrombin are exceedingly rare, having only been reported in adult patients with underlying diseases. Consensus on the most appropriate management has not yet been reached. A 12-y-old girl presented with intractable menorrhagia several days after an acute infectious episode. Laboratory tests revealed disturbed clotting tests: prothrombin index 17%, activated partial thromboplastin time >150 s, thrombin time >120 s, and failure to achieve correction with a normal pooled plasma. Further studies demonstrated the presence of an antibody directed against human thrombin. Viral serology revealed a 1/128 titre for adenovirus. Massive haemorrhage was unresponsive to standard treatments, but intravenous administration of recombinant factor VIIa resulted in a successful outcome. Conclusion: This is the first report of an anti-human thrombin antibody associated with severe bleeding in a child. Recombinant factor VIIa could represent a novel therapeutic approach for such patients.     

Systemic capillary leak syndrome presenting as recurrent shock.

OBJECTIVE: To report a case of systemic capillary leak syndrome (SCLS) in a child. DESIGN: Case report. SETTING: Pediatric intensive care unit. PATIENT: A 6-yr-old girl was admitted twice to the pediatric intensive care unit, at a 10-month interval, in severe shock with important edema. RESULTS: The patient presented with acute symptoms of abdominal pain, vomiting, and syncope in the hour preceding the shock. During both episodes necessary management included aggressive intravenous fluid rehydration, mechanical ventilation, and use of inotropes/vasopressors. Suspicion of a lower limb fasciitis necessitated surgical exploration, but pathology reports were negative on both occasions revealing only subcutaneous tissue edema. The patient recovered within 24 hrs on both episodes. Investigation ruled out cardiogenic shock and septic shock due to bacterial etiology. On the first episode, a nasopharyngeal aspirate was positive for influenza A (H3N2) by both viral immunofluorescence and culture. The presumed diagnosis was toxic shock syndrome associated with influenza virus. On the second episode, all bacterial and virology cultures remained negative. Hypovolemic shock was suspected, but there was no history of dehydration, bleeding, or gastrointestinal losses (persistent vomiting or diarrhea). Noninfectious causes of hypovolemic shock with edema were ruled out, leading us to believe that she suffered from SCLS. CONCLUSIONS: Although well described in the adult literature, there have been few reports of SCLS in pediatric patients. SCLS should be considered in the differential diagnosis of recurrent hypovolemic shock without identifiable cause. The only therapeutic intervention is to obtain vascular access when initial manifestations occur and give aggressive fluid reanimation.     

Use of recombinant factor VIIa for bleeding in children with Glanzmann thrombasthenia

Glanzmann thrombasthenia is a very rare inherited platelet function disorder in which bleeding may be extremely difficult to stop. Recombinant factor VIIa is one of the alternative treatments for bleeding. The authors report here their experience with the use of factor VIIa, which may be useful for arresting bleeding in Glazmann thrombasthenia.     

Use of Recombinant Factor VIIa for Bleeding in Children with Glanzmann Thrombasthenia

Glanzmann thrombasthenia is a very rare inherited platelet function disorder in which bleeding may be extremely difficult to stop. Recombinant factor VIIa is one of the alternative treatments for bleeding. The authors report here their experience with the use of factor VIIa, which may be useful for arresting bleeding in Glazmann thrombasthenia.     

A new challenge in pediatric obesity: pediatric hyperglycemic hyperosmolar syndrome.

OBJECTIVES: To describe four adolescents with hyperglycemic hyperosmolar syndrome, an uncommon presentation of type 2 diabetes in pediatric patients. DESIGN: Case report. SETTING: Two tertiary pediatric intensive care units in university teaching hospitals. PATIENTS: Four obese adolescents with hyperglycemic hyperosmolar syndrome associated with type 2 diabetes mellitus. INTERVENTIONS: Isotonic fluid resuscitation and insulin. MEASUREMENTS AND MAIN RESULTS: Two of the four patients died. The first patient died within the first 24 hrs of hyperglycemic hyperosmolar syndrome presumably due to hypovolemic shock. The second patient, who died, developed rhabdomyolysis and multiple-system organ failure after a prolonged intensive care unit stay. The third and fourth patients were discharged from the hospital in good health. None of the patients had cerebral edema on head computed tomography, despite differences in fluid and insulin management. CONCLUSIONS: Pediatric patients with hyperglycemic hyperosmolar syndrome have a high mortality rate and may experience multiple complications such as rhabdomyolysis and hypovolemic shock. Treatment strategies to reduce mortality are unclear and warrant further investigation.     

Recombinant factor VIIa in an infant with haemophilia A and inhibitors

Post-traumatic bleeding from the gingiva in a 16-month-old boy with severe haemophilia A did not stop after treatment with factor VIII concentrate and tranexamic acid, and it was demonstrated that he had developed antibodies to factor VIII. Treatment with recombinant factor VIIa 60-90 micrograms/kg body weight four to eight times daily, together with local measures, stopped the bleeding and no complications were seen.     

儿童消化道出血的原因与应急治疗

消化道出血是危害儿童生命健康的急症,其出血原因众多,并随年龄而不同,需要合理诊断和治疗.患儿临床表现从无症状性贫血到失血性休克变化多样,因此,救治的关键是对患儿先进行快速评估、稳定和复苏,然后再做病因诊断及治疗.     

Gastrointestinal manifestations in Henoch-Schönlein purpura: a review of 261 patients

Aim: Henoch‐Schönlein purpura is an IgA‐mediated autoimmune vasculitis of children. It often presents with symptoms including purpuric rash, abdominal pain, renal involvement or arthritis. Abdominal pain is a frequent symptom in children with HSP and raises the suspicion of intussusception or perforation. We sought to evaluate abdominal pain via stool occult blood and image studies. Methods: A retrospective study of 261 patients diagnosed with Henoch‐Schönlein purpura from December 1991 to December 2001 was conducted. Image studies, including abdominal echo, abdominal CT and panendoscopy, were performed for patients who suffered from abdominal pain. Results: Of the 261 patients, 151 (58%) had abdominal pain, and 46 (17.6%) suffered either overt gastrointestinal bleeding or had positive stool occult blood. Seven patients had gross bloody stools. One acute intussusception and one bowel perforation were noted. One patient suffered from hypovolemic shock due to massive gastrointestinal bleeding. When stool occult blood was 3+ or 4+, the incidence of a positive image finding was high. Conclusion: We found that stool occult blood and image studies may be necessary regarding severe gastrointestinal involvement. Ultrasonography is an important tool when intussusception or bowel perforation is suspected. Monitoring the vital signs is important, especially in patients with massive gastrointestinal bleeding.     

Recombinant activated Factor VII as a hemostatic agent in very low birth weight preterms with gastrointestinal hemorrhage and disseminated intravascular coagulation

OBJECTIVE: Acute hemorrhage in preterm infants leads immediately to a life-threatening event because of the small circulating blood volume. The beneficial use of recombinant activated Factor VII (rFVIIa; NovoSeven, NovoNordisk, Gentofte, Denmark) as hemostatic treatment in neonates with hemorrhagic shock has been described. Necrotizing enterocolitis is a challenge in neonatology as the disease represents one of the leading causes of mortality in preterm infants. We report on the use of rFVIIa in very low birth weight (<1500 g), preterms with intestinal hemorrhage, and disseminated intravascular coagulation (DIC). DESIGN: Retrospective analysis of 5 cases. PATIENTS: Five preterm infants 相似文献   

The use of recombinant coagulation factor VIIa in uncontrolled postoperative bleeding in children undergoing cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: To assess the hemostatic efficacy of recombinant coagulation factor VIIa (rFVIIa) in the management of uncontrolled bleeding in postcardiac surgery with cardiopulmonary bypass in children. DESIGN: An open-label study. SETTING: A postoperative intensive care unit. PATIENTS: Eight consecutive pediatric patients with excessive bleeding after cardiac surgery with cardiopulmonary bypass that met the criteria for reexploration and did not respond to optimal transfusions of platelets and fresh frozen plasma. INTERVENTIONS: rFVIIa 30 microg/kg was given as a bolus injection. A higher dose of 60 microg/kg was used if a patient had preoperative coagulopathy, preoperative multiple-organ failure, or indications that required an emergency operation. The same dose was repeated 15 mins after the previous injection if the bleeding had not decreased. If the bleeding had decreased but still exceeded 10 mL/hr for body weight 5 kg, the same dose was repeated 2 hrs after the previous injection. A maximum of four doses could be given before rFVIIa was considered ineffective and a reexploration was needed. MEASUREMENTS AND MAIN RESULTS: Postoperative blood loss was estimated from the volume of chest tube drainage. rFVIIa successfully controlled bleeding and prevented reexploration in all seven patients who received treatment according to the protocol. One patient who received only one dose of rFVIIa required reexploration because a second dose was not available. No adverse events related to rFVIIa were seen. CONCLUSIONS: rFVIIa may be useful in preventing reexploration in uncontrolled postoperative bleeding in children undergoing cardiac surgery with cardiopulmonary bypass. Randomized, placebo-controlled studies are needed to confirm the safety and efficacy of rFVIIa in this clinical setting.     

Successful Use of Recombinant Factor VIIa (NovoSeven<Superscript>®</Superscript>) During Cardiac Surgery in a Pediatric Patient with Congenital Factor XI Deficiency

We report our experience with the use of recombinant activated factor VII (rFVIIa) during cardiac surgery in a 4.5-year-old boy with severe congenital FXI deficiency and a congenital heart disease. After weaning the patient from cardiopulmonary bypass, the first intravenous dose of rFVIIa (90 μg/kg) was administered. This same dosage was repeated eight more times, at 2- to 4-hour intervals postoperatively. There was no bleeding during and after surgery. rFVIIa treatment may be used successfully in children with severe FXI deficiency in major operations such as open heart surgery.     

Use of recombinant factor VIIa (rFVIIa) to control intraoperative bleeding in pediatric brain tumor patients

Surgical bleeding during the resection of brain tumors in children may be related to tumor vascularity, pathology, and location. Despite improvements in neurosurgical technique, neuroanesthesia, and blood product replacement, bleeding can be life-threatening in these surgeries. We report eight pediatric patients in whom recombinant factor VIIa (rFVIIa) was used to control intraoperative bleeding during surgical resection of pediatric brain tumors. rFVIIa should be considered as a method to control intraoperative bleeding that is unresponsive to conventional interventions. Additional studies are needed to determine optimal patient selection and drug dosing, efficacy and safety.     

Recombinant Activated Factor VII Usage in Life Threatening Hemorrhage: A Pediatric Experience

Objective  

To determine the safety and efficacy of off label usage of Recombinant activated factor VII (rFVIIa) in children with severe bleeding in non-hemophiliac children with diverse etiologies like leukemia, post hematopoietic stem cell transplantation, dengue shock syndrome and Glanzmann thrombasthenia.     

Effectiveness of activated factor VII in postoperative bleeding after cardiac surgery with extracorporeal membrane oxygenation

A 4-year-old girl suffered severe postoperative chest tube drainage bleeding after cardiac transplant surgery requiring extracorporeal membrane oxygenation. Transfusions of platelets and fresh frozen plasma failed to decrease the bleeding. At 2.5 hours a dose of 180 mcg/kg of recombinant activated Factor VII was administered. The hemorrhage decreased from 45 ml/kg/h in the first 2.5 hours to 17 ml/kg/h in the next 2.5 hours. The same dose of recombinant activated Factor VII was administered and the hemorrhage suddenly decreased to 1.5 ml/kg/h in the next 2.5 hours, with subsequent disappearance. No adverse events related to activated Factor VII were observed. Recombinant activated Factor VII may be useful in some cases of severe postoperative bleeding in children after cardiac surgery. Randomized controlled studies are needed to confirm its safety and efficacy, and to evaluate the most suitable dose.     

Pyelolithotomy in a patient with Glanzmann thrombasthenia and antiglycoprotein IIb/IIIa antibodies: the shortest possible duration of treatment with recombinant activated factor VII and platelet transfusions

Transfusion of platelet concentrates remains the first-line therapy for Glanzmann thrombasthenia in case of bleeding or preparation for surgery. However, development of antibodies to platelet glycoprotein (Gp) IIb/IIIa complex or human leukocyte antigens (HLA) is frequent and the main cause of platelet refractoriness. Recombinant activated factor VII (rFVIIa) is a potent alternative for patients with Glanzmann thrombasthenia with anti-platelet antibodies. We describe a case of Glanzmann thrombasthenia with alloantibodies to platelet Gp IIb/IIIa complex who underwent a successful pyelolithotomy operation under the coverage of recombinant activated factor VIIa and platelet transfusions.     

Are ECG abnormalities in Noonan syndrome characteristic for the syndrome?

Of all patients with Noonan syndrome, 50–90% have one or more congenital heart defects. The most frequent occurring are pulmonary stenosis (PS) and hypertrophic cardiomyopathy. The electrocardiogram (ECG) of a patient with Noonan syndrome often shows a characteristic pattern, with a left axis deviation, abnormal R/S ratio over the left precordium, and an abnormal Q wave. The objective of this study was to determine if these ECG characteristics are an independent feature of the Noonan syndrome or if they are related to the congenital heart defect. A cohort study was performed with 118 patients from two university hospitals in the United States and in The Netherlands. All patients were diagnosed with definite Noonan syndrome and had had an ECG and echocardiography. Sixty-nine patients (58%) had characteristic abnormalities of the ECG. In the patient group without a cardiac defect (n = 21), ten patients had a characteristic ECG abnormality. There was no statistical relationship between the presence of a characteristic ECG abnormality and the presence of a cardiac defect (p = 0.33). Patients with hypertrophic cardiomyopathy had more ECG abnormalities in total (p = 0.05), without correlation with a specific ECG abnormality. We conclude that the ECG features in patients with Noonan syndrome are characteristic for the syndrome and are not related to a specific cardiac defect. An ECG is very useful in the diagnosis of Noonan syndrome; every child with a Noonan phenotype should have an ECG and echocardiogram for evaluation.     

Use of recombinant factor VIIa for refractory hemorrhage during extracorporeal membrane oxygenation.

OBJECTIVE: To describe the outcome and treatment of two patients with recombinant factor VIIa (rFVIIa) for severe hemorrhage associated with extracorporeal membrane oxygenation (ECMO). DESIGN: Case report. SETTING: A 38-bed pediatric intensive care unit and 20-bed pediatric cardiac intensive care unit at a tertiary care children's hospital. Patient: Two patients with life-threatening hemorrhagic complications associated with ECMO requiring massive transfusion of blood products. INTERVENTIONS: Administration of repeated doses of rFVIIa at 90 microg/kg/dose. MEASUREMENT AND MAIN RESULTS: Patient 1 was an 11-yr-old male with a dilated cardiomyopathy who had undergone an orthotopic heart transplant treated with venoarterial ECMO postoperatively for right ventricular dysfunction. Patient 2 was a 13-yr-old male treated with venoarterial ECMO for cardiopulmonary failure from necrotizing staphylococcal pneumonia. Both patients had severe hemorrhage from the cannulation sites and thoracostomy tubes requiring massive transfusion to maintain intravascular blood volume and replace clotting factors. Both patients were treated with rFVIIa every 2-4 hrs and attained hemostasis. Patient 1 was administered three doses and Patient 2 was administered ten doses. No evidence of abnormal thrombus formation was noted in their respective ECMO circuits. CONCLUSIONS: The efficacy of rFVIIa in reducing intractable bleeding postcardiac surgery and in other coagulopathic states is being investigated. Despite theoretical concerns of thrombosis, these cases illustrate that there may be a role for the cautious use of rFVIIa in treating severe and intractable hemorrhage associated with ECMO.     

Growth hormone therapy in pre-pubertal children with Noonan syndrome: first year growth response and comparison with Turner syndrome

We studied the growth-promoting effect of treatment with recombinant human growth hormone in 23 prepubertal children with Noonan syndrome, aged between 5. 4 and 14. 3 y, and all with a height < 1. 4 SD for Tanner standards. The growth response and skeletal maturation after 1 y of recombinant human growth hormone treatment (0. 15 U/kg/day given by daily injection) in the Noonan syndrome patients was compared with the auxological changes observed in a group of 17 girls with Turner syndrome with a comparable age and height deficit who were treated with recombinant human growth hormone in a similar way. During 1 y of treatment, the mean ± SD height velocity increased by 4. 0 ± 1. 6 cm/y in the Noonan syndrome group and by 3. 6 ± 1. 3 cm/y in the Turner syndrome group. Height SDS for chronological age in the Noonan syndrome group increased by 0. 53 ± 0. 46 ( p < 0. 001). In the Noonan syndrome patients the changes in height velocity were positively related to birthweight ( r = 0. 48, p < 0. 05). The changes in height velocity or height SDS were not related to the age, height deficit or a delay in bone age maturation at start of treatment. In neither the patients with Noonan syndrome nor Turner syndrome was an acceleration of bone maturation found. We conclude that treatment with recombinant human growth hormone in pre-pubertal NS patients induces an increase in height velocity and height SDS comparable to that observed in Turner syndrome girls.     

A case of extrahepatic portal hypertension

Bleeding from the proximal part of the gastrointestinal (GI) tract is not uncommon in children. Children could present with anemia secondary to chronic occult bleeding in the gastrointestinal tract or as anemia secondary to acute exsanguinations and can present in hypovolemic shock. There are various causes of upper GI bleeding in children. A systematic approach in evaluating these children is essential so that the diagnosis is made in timely manner and appropriate management is begun early.     

Chronic subcutaneous octreotide decreases gastrointestinal blood loss in blue rubber-bleb nevus syndrome

BACKGROUND: A patient affected by blue rubber-bleb nevus syndrome had chronic gastrointestinal bleeding requiring weekly blood transfusions. Despite multiple surgical and endoscopic procedures to treat the venous malformations, the patient continued to bleed primarily from lesions in the small bowel. Therefore, this patient was treated with octreotide, a somatostatin analog known to decrease splanchnic blood flow and that is used for acute and chronic gastrointestinal bleeding. METHODS: Octreotide therapy, 5.7 microg/kg subcutaneously twice daily, was initiated, and the patient was followed up clinically. Complete blood counts, blood glucose concentration, pancreatic enzyme concentration, liver function tests, and growth hormone concentration were monitored during treatments. RESULTS: During the 4 weeks after initiation of octreotide therapy, hemoglobin concentration was maintained without the need for transfusions. Octreotide decreased the patient's monthly need for blood transfusion from 52 +/- 7 mL. kg-1. mo-1 of packed red blood cells to 23 +/- 7 mL. kg-1. mo-1. She had no detectable side effects or growth inhibition. Other medical interventions including -epsilonaminocaproic acid, nadolol, and total parenteral nutrition with bowel rest were not as effective as octreotide alone. CONCLUSION: Octreotide decreased the patient's need for blood transfusions. Possible mechanisms include altering blood flow to the gastrointestinal tract and direct effects on the venous malformations.