Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII

In 2018, Refacto AFR, a B-domain-deleted third-generation FVIII concentrate, became our preferential product. After the introduction, the development of inhibitors was prospectively monitored; retrospectively, we sought for risk factors in the patients who developed a de-novo inhibitor. Over a period of 15 months, 4/19 adult patients with non-severe haemophilia who were treated on demand for surgery, developed high titer antibodies to FVIII after administration of Refacto AFR; 5/52 mostly severe patients on prophylaxis, developed an inhibitor (3 ≥ 0.1 BU; 1 &gt; 0.6 BU, 1 high titre) after they switched to Refacto AFR; all were children &lt;14 years of age and with &gt;100 exposure days, none related to surgery or intensive treatment; all received KovaltryR before. In conclusion: inhibitors were encountered in on demand patients and previously treated prophylaxis patients; this observation might be a coincidental finding, but also risk factors like genotype and surgery and/or that Refacto AFR is more immunogenic should be considered. For the patients on prophylaxis we hypothesize that loss of tolerance by preceding KovaltryR might have contributed to inhibitor development.</p

Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII

In 2018, Refacto AFR, a B-domain-deleted third-generation FVIII concentrate, became our preferential product. After the introduction, the development of inhibitors was prospectively monitored; retrospectively, we sought for risk factors in the patients who developed a de-novo inhibitor. Over a period of 15 months, 4/19 adult patients with non-severe haemophilia who were treated on demand for surgery, developed high titer antibodies to FVIII after administration of Refacto AFR; 5/52 mostly severe patients on prophylaxis, developed an inhibitor (3 ≥ 0.1 BU; 1 &gt; 0.6 BU, 1 high titre) after they switched to Refacto AFR; all were children &lt;14 years of age and with &gt;100 exposure days, none related to surgery or intensive treatment; all received KovaltryR before. In conclusion: inhibitors were encountered in on demand patients and previously treated prophylaxis patients; this observation might be a coincidental finding, but also risk factors like genotype and surgery and/or that Refacto AFR is more immunogenic should be considered. For the patients on prophylaxis we hypothesize that loss of tolerance by preceding KovaltryR might have contributed to inhibitor development.</p

Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII

In 2018, Refacto AFR, a B-domain-deleted third-generation FVIII concentrate, became our preferential product. After the introduction, the development of inhibitors was prospectively monitored; retrospectively, we sought for risk factors in the patients who developed a de-novo inhibitor. Over a period of 15 months, 4/19 adult patients with non-severe haemophilia who were treated on demand for surgery, developed high titer antibodies to FVIII after administration of Refacto AFR; 5/52 mostly severe patients on prophylaxis, developed an inhibitor (3 ≥ 0.1 BU; 1 &gt; 0.6 BU, 1 high titre) after they switched to Refacto AFR; all were children &lt;14 years of age and with &gt;100 exposure days, none related to surgery or intensive treatment; all received KovaltryR before. In conclusion: inhibitors were encountered in on demand patients and previously treated prophylaxis patients; this observation might be a coincidental finding, but also risk factors like genotype and surgery and/or that Refacto AFR is more immunogenic should be considered. For the patients on prophylaxis we hypothesize that loss of tolerance by preceding KovaltryR might have contributed to inhibitor development.</p

Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII

In 2018, Refacto AFR, a B-domain-deleted third-generation FVIII concentrate, became our preferential product. After the introduction, the development of inhibitors was prospectively monitored; retrospectively, we sought for risk factors in the patients who developed a de-novo inhibitor. Over a period of 15 months, 4/19 adult patients with non-severe haemophilia who were treated on demand for surgery, developed high titer antibodies to FVIII after administration of Refacto AFR; 5/52 mostly severe patients on prophylaxis, developed an inhibitor (3 ≥ 0.1 BU; 1 &gt; 0.6 BU, 1 high titre) after they switched to Refacto AFR; all were children &lt;14 years of age and with &gt;100 exposure days, none related to surgery or intensive treatment; all received KovaltryR before. In conclusion: inhibitors were encountered in on demand patients and previously treated prophylaxis patients; this observation might be a coincidental finding, but also risk factors like genotype and surgery and/or that Refacto AFR is more immunogenic should be considered. For the patients on prophylaxis we hypothesize that loss of tolerance by preceding KovaltryR might have contributed to inhibitor development.</p

Occurrence of FVIII Inhibitors in Hemophilia A Patients Following an Institutional Switch to a Third Generation B-Domain-Deleted FVIII

In 2018, Refacto AFR, a B-domain-deleted third-generation FVIII concentrate, became our preferential product. After the introduction, the development of inhibitors was prospectively monitored; retrospectively, we sought for risk factors in the patients who developed a de-novo inhibitor. Over a period of 15 months, 4/19 adult patients with non-severe haemophilia who were treated on demand for surgery, developed high titer antibodies to FVIII after administration of Refacto AFR; 5/52 mostly severe patients on prophylaxis, developed an inhibitor (3 ≥ 0.1 BU; 1 &gt; 0.6 BU, 1 high titre) after they switched to Refacto AFR; all were children &lt;14 years of age and with &gt;100 exposure days, none related to surgery or intensive treatment; all received KovaltryR before. In conclusion: inhibitors were encountered in on demand patients and previously treated prophylaxis patients; this observation might be a coincidental finding, but also risk factors like genotype and surgery and/or that Refacto AFR is more immunogenic should be considered. For the patients on prophylaxis we hypothesize that loss of tolerance by preceding KovaltryR might have contributed to inhibitor development.</p

The limitation of genetic testing in diagnosing patients suspected for congenital platelet defects

Thrombosis and Hemostasi

Modified Use of a Dynamic Bite Opener—Treatment and Prevention of Trismus in a Child with Head and Neck Cancer: A Case Report

Trismus may be a complication arising during or after treatment of patients with head and neck cancer. Treatment of trismus is difficult, making prevention very important. To prevent and treat trismus in a patient with a nasopharyngeal tumor, the Contract-Relax-Antagonist-Contract (CRAC) technique was applied, with the aid of a custom-made dynamic bite opener (DBO). The CRAC technique in combination with the DBO, as a therapy/prevention program for trismus, is not referred to in the literature. The combination of CRAC and DBO appeared to be a gentle and effective method well tolerated by the patient

Paraneoplastic manifestations in children

Paraneoplastic manifestations are signs and symptoms observed in patients with cancer, distant from the tumour or its metastases and not caused by invasion, obstruction or bulk mass. In children with cancer, paraneoplastic manifestations are rare and distinct from those observed in adults. Knowledge about paraneoplastic manifestations can be of great clinical importance because they may be the presenting sign of a tumour or its recurrence and hence facilitate early diagnosis. In contrast, they sometimes mask the symptoms of a tumour and cause diagnostic delay. In this review, paraneoplastic manifestations in children are described, including hypercalcaemia, Cushing syndrome, precocious puberty, opsoclonus/myoclonus, acquired von Willebrand disease, watery diarrhoea syndrome, and hypertension. The mechanisms causing these manifestations are also discussed