Impact of a product-specific reference standard for the measurement of a PEGylated rFVIII activity: the Swiss Multicentre Field Study.

INTRODUCTION: Measuring factor VIII (FVIII) activity can be challenging when it has been modified, such as when FVIII is pegylated to increase its circulating half-life. Use of a product-specific reference standard may help avoid this issue. AIM: Evaluate the impact of using a product-specific reference standard for measuring the FVIII activity of BAX 855 - a pegylated FVIII - in eight of Switzerland's main laboratories. METHODS: Factor VIII-deficient plasma, spiked with five different concentrations of BAX 855, plus a control FVIII sample, was sent to the participating laboratories. They measured FVIII activity by using either with a one-stage (OSA) or the chromogenic assay (CA) against their local or a product-specific reference standard. RESULTS: When using a local reference standard, there was an overestimation of BAX 855 activity compared to the target concentrations, both with the OSA and CA. The use of a product-specific reference standard reduced this effect: mean recovery ranged from 127.7% to 213.5% using the OSA with local reference standards, compared to 110% to 183.8% with a product-specific reference standard, and from 146.3% to 182.4% using the CA with local reference standards compared to 72.7% to 103.7% with a product-specific reference standard. CONCLUSION: In this in vitro study, the type of reference standard had a major impact on the measurement of BAX 855 activity. Evaluation was more accurate and precise when using a product-specific reference standard.

[Traumatic abruption of the placenta with disseminated intravascular coagulation]. / Traumatische plazentalösung mit disseminierter intravasaler gerinnung.

Trauma in pregnancy is infrequent and a systematic primary strategy constitutes a real challenge for the interdisciplinary team. With a high fetal mortality rate and a substantial maternal mortality rate traumatic placental abruption is a severe emergency which every anesthetist should be aware of. After hemodynamic stabilization of the mother and control of the viability of the fetus the therapy of traumatic placental abruption consists mostly of an immediate caesarean section. Coagulopathy by depletion of coagulation factors as well as disseminated intravascular coagulation (DIC) have to be expected and consequently a massive blood loss must be anticipated. Thrombelastography provides assistance for fast differential diagnosis and goal-directed treatment of the disturbed sections of the coagulation cascade.

[Differential diagnosis of absolute lymphocytosis]. / Differentialdiagnose der absoluten Lymphozytose.

The differential diagnosis of absolute lymphocytosis is variegated. In general, reactive (secondary) lymphocytosis can be well differentiated from a lymphoproliferative disease (primary lymphocytosis). Together with correspondent clinical characteristics, an absolute lymphocytosis often suggests a potential diagnosis and the further diagnostic process. Reactive lymphocytosis is usually self limiting and normalizes after cessation of the inflammatory stimulus. If a lymphoproliferative disorder is suspected further diagnostic procedures (i.e. cytometry, bone marrow examinations, biopsies of other organs if needed and molecular analyses) should be performed. If the distinction between malignant lymphoproliferation and reactive lymphocytosis cannot be done immediately, a watch and wait strategy may be implemented. In case of persistent lymphocytosis for longer than six months or occurrence of additional symptoms earlier on, diagnosis should be forced.

Acute pericarditis and pleural effusion complicating cytarabine chemotherapy.

BACKGROUND: Pericarditis is a rare but possibly severe complication of treatment of acute leukemia with cytarabine. CASE REPORT: We report a possibly cytarabine-induced acute pericarditis and pleuritis with a rapid onset. A patient with acute myelomonocytic leukemia developed an isolated pericarditis 3 weeks after the first course of chemotherapy with cytarabine and idarubicin. The second course of chemotherapy with cytarabine and amsacrine was started after clinical improvement; 3 days later an acute pericarditis with a large pericardial effusion accompanied by a left pleural effusion developed. A pericardio- and pleuracentesis was performed and the symptoms improved rapidly without reaccumulation of the fluid. The third course of chemotherapy with mitoxantrone and etoposide was completed without further cardiopulmonary complications. CONCLUSION: The differential diagnosis of pericarditis in the setting of chemotherapy with cytarabine should include cytarabine- induced pericarditis. The pathogenesis remains unclear, directly toxic and immunological mechanisms are suggested. Severe progression with massive pericardial effusion necessitating risky pericardiocentesis can occur and therefore a therapy with high-dose corticosteroids should be considered early.

Interleukin-8 expression by fetal and neonatal pulmonary cells in hyaline membrane disease and amniotic infection.

IL-8, a chemokine with striking neutrophil-activating properties, is important in the pathogenesis of various disorders of the adult lung. Little is known about its production and possible role in fetal and neonatal lung disorders. We therefore examined IL-8 expression by immunohistochemistry in lung tissue from neonates with hyaline membrane disease, from fetuses with amniotic infection, and from a fetal control group with noninflammatory diseases. In the majority of cases with hyaline membrane disease, intense IL-8 immunoreaction was seen in fetal and neonatal neutrophils and in almost half of these cases, in epithelial cells of the terminal airways as well as in the connective tissue cell compartment. In contrast, in the amniotic infection group, strong IL-8 immunostaining was almost exclusively seen in maternal aspirated neutrophils. Little or no IL-8 signal was seen in the control cases in all cell types examined. Also, no IL-8 production by fetal lung cells was detected in fetuses <18 wk of gestation. The marked presence of IL-8 in all cell types of the lung in hyaline membrane disease cases indicates a role for IL-8 in the pathobiology of hyaline membrane disease possibly similar to that in adult respiratory distress syndrome. It further suggests that the cytokine network of the fetal lung is already well developed by the second trimester of pregnancy.