The impact of two whole blood inline filters on markers of coagulation, complement and cell activation.

BACKGROUND AND OBJECTIVES: There exists a current lack of information about the impact of different inline filters, used for the leucoreduction of whole blood (WB), on the levels of clotting factors and markers of coagulation, complement and cell activation in plasma. Only a few small comparisons of different types of WB inline filters have been published to date. MATERIALS AND METHODS: This study compared two plasma types of 200 units each. Both study groups were derived from WB, inline-filtered and held for 2 h at 20 degrees between donation and filtration. Then, 200 units (Group A) were filtered using a positively charged polyester filter (Baxter RZ2000) and the other 200 units (Group B) were filtered using an uncharged polyester filter (Fresenius). After filtration, both groups were analysed for fibrinogen, factors V and VIII:C (FV and FVIII:C, respectively), immunoglobulin G (IgG), residual leucocytes and platelets, and markers of coagulation, complement and cell activation. Predonation plasma samples from CPDA1-anticoagulated blood were obtained from 100 different individuals and served as controls. RESULTS: WB inline filtration did not influence fibrinogen, FV, FVIII:C or IgG levels. Neither filter induced thrombin or fibrin formation. The charged filter caused substantial complement activation and neutrophil elastase and platelet factor 4 release. In contrast, the plasma filtered through the uncharged filter showed markedly lower levels of C3a-desArg, C5a, neutrophil elastase and platelet factor 4, and moderately reduced levels of prothrombin fragments 1+2 and D-dimer, compared with controls. CONCLUSIONS: Filter type has a significant impact on the quality of plasma derived from WB filtered through inline filtration systems. Some filters produce substantial coagulation and complement activation and cell release, while others appear to reduce the plasma levels of activation markers. The clinical significance of these findings remains to be determined.

Prevalence of human parvovirus B19 in blood donors as determined by a haemagglutination assay and verified by the polymerase chain reaction.

BACKGROUND AND OBJECTIVES: Transmission of human parvovirus B19 (PV B19) by transfusion of blood and blood products is well documented. Although PV B19 infection is connected with severe complications in some recipients, donor screening is not yet mandatory. In this study the prevalence of PV B19, as detected by a haemagglutination assay (the Human PV B19 Antigen-Test), was assessed. In addition, the persistence of B19 DNA and the serological status of blood donors was also assessed. The specificity and utility of the Human PV B19 Antigen-Test for donor screening was investigated and compared with other screening strategies. MATERIALS AND METHODS: The prevalence of PV B19 viraemia was assessed in 28 972 donations from 15,660 remunerated donors by means of the haemagglutination assay. Reactive results were confirmed by the polymerase chain reaction (PCR). RESULTS: Overall, 255 donations gave reactive or indeterminate results in the screening assay. Four donations/donors detected by the haemagglutination assay were confirmed as positive for B19 DNA by PCR. Therefore, a frequency was detected of 1:7243 B19-positive donations and 1:3915 positive donors. Specificity was determined to be 99.1%. Follow-up showed the persistence of viraemia in low concentrations for prolonged time-periods. CONCLUSION: Blood donations with a high level of human PV B19 viraemia can be detected by the haemagglutination assay, which is rapid and easy to perform. The presence of neutralizing antibody may inhibit specific haemagglutination.

Screening of blood donations by hepatitis C virus polymerase chain reaction (HCV-PCR) improves safety of blood products by window period reduction.

Introduction of the nucleic acid amplification technique (NAT) as a screening test for blood donors to detect HCV RNA became mandatory on 1 April 1999. Few automated commercial systems are available for HCV RNA detection at the moment. The Cobas Amplicor HCV 2.0 System is able to perform fully automated amplification and detection of nucleic acids. A concentration of 98 IU HCV RNA/ml can be detected by the Cobas Amplicor HCV 2.0 System (n = 233, in 100% of the cases). With a pool size of 40 donor samples, the guidelines of the Paul-Ehrlich-Institute concerning sensitivity (5,000 IU HCV RNA per mL in a single donation) were followed. One whole blood donation was identified as HCV-RNA positive (anti-HCV IgG negative, GPT < 30 U/L) during a period of 5 months. No false positive test results could be observed. The internal control and the run control are primarily helpful to monitor methodological problems.

Routine HCV PCR screening of blood donations to identify early HCV infection in blood donors lacking antibodies to HCV.

BACKGROUND: Detection of early hepatitis C infection of blood donors is still a major problem for blood transfusion. Common anti-HCV screening assays show differences in sensitivity and specificity. The often mild symptoms of acute hepatitis C also cause difficulties in the identification of early HCV infection. The feasibility and efficacy of routine screening of blood donations for HCV RNA were investigated. STUDY DESIGN AND METHODS: Blood donations (n = 251,737) were screened for HCV RNA over 4 years. RNA extraction, amplification, and detection were done by two commercial HCV PCR kits (HCV Cobas Amplicor and HCV Cobas Amplicor 2.0, Roche Diagnostics). Screening was done by pool testing with a maximum pool size of 40 serum samples. RESULTS: Three donations out of 251,737 were HCV RNA positive and anti-HCV negative. ALT levels of these donations were 271, 32, and 10 U per L. The HCV infection of a fourth HCV RNA-positive donor could not be identified by routine, second-generation HCV EIA (Abbott Diagnostika). In this case, two previous donations were also HCV RNA positive, and three second-generation test systems (Abbott) could not detect anti-HCV, whereas third-generation anti-HCV screening assays detected antibody with different sensitivity. The first HCV RNA-positive donation was identified only by the HCV ELISA 3.0 (Ortho Diagnostic Systems). The results of confirmatory assays like RIBA HCV 3.0 (Ortho) and Matrix (Abbott) indicate a restricted immune response to NS3 only. CONCLUSION: HCV RNA detection by PCR can be carried out routinely in blood donor screening without significant delay of release of the components. The residual risk of transmission can be reduced by identification of early infection, which can lead to an improved safety of blood components. RNA screening can also be advantageous in cases of incomplete or lack of antibody response to HCV.

Comparison of intermittent- and continuous-flow cell separators for the collection of autologous peripheral blood progenitor cells in patients with hematologic malignancies.

BACKGROUND: The transplantation of autologous peripheral blood progenitor cells (PBPCs) after high-dose chemotherapy is a valuable therapy for patients with hematologic and solid malignancies. Several methods are used for harvesting PBPCs. The efficiency of intermittent- and continuous-flow blood cell separators in collecting progenitor cells from the blood of patients undergoing myeloablative treatment for cancer was compared. STUDY DESIGN AND METHODS: PBPC components (n = 133) were obtained from 72 patients by leukapheresis with continuous-flow machines (Spectra, COBE; CS 3000 Plus, Baxter) and with an intermittent-flow machine (MCS 3P, Haemonetics). The data were analyzed retrospectively. Blood samples obtained from the patients before leukapheresis and samples of the leukapheresis components themselves were analyzed for their content of RBCs, WBCs, platelets, and CD34+ cells. RESULTS: The Spectra processed more than twice the blood volume in the shortest time (15 L in 178 min), whereas the Baxter CS 3000 Plus (10 L in 185 min) and the MCS 3P (4.8 L in 239 min) processed significantly smaller volumes in a longer time. The mean ACD consumption was 403 mL with the MCS 3P, 900 mL with the CS 3000 Plus, and 1000 mL with the Spectra. The product volumes were 50 mL (CS 3000 Plus), 69 mL (MCS 3P), and 166 mL (Spectra). In all groups, differences in the preapheresis hemograms were not significant, but the Spectra group had fewer CD34+ cells than the other groups. Despite this, the differences in the number of CD34+ cells in the leukapheresis components of all groups were without statistical significance. In the Spectra group, the collection of MNCs of 104 percent and CD34+ cells of 154 percent was significantly more efficient than that in the MCS 3P group (42.2% and 56%, respectively) or the CS 3000 Plus group (50.8% and 47.15%) as related to the patients' blood volume. CONCLUSION: PBPC collection can be performed successfully with continuous-flow and intermittent-flow blood cell separators. The Spectra had the best recovery of CD34+ cells within the shortest time. Leukapheresis with the MCS 3P is indicated if only a single venous access is available.

Prenatal diagnosis of body stalk anomaly at 9 weeks of gestation. Case report.

We report on a case of embryonic anomaly detected at 9 + 5 gestational weeks. The lower part of the embryo was located in the coelomic cavity. Lower extremities could not be depicted. The abdominal wall showed the appearance of omphalocoele. After termination of pregnancy at 10 weeks, autopsy confirmed the anomaly of the lower embryonic parts consistent with the diagnosis of body stalk anomaly. To our knowledge, this is the first observation of this condition before 10 gestational weeks.

Clinical variability of Larsen syndrome: diagnosis in a father after sonographic detection of a severely affected fetus.

Larsen syndrome shows a broad spectrum of clinical manifestation ranging from a lethal form of the disorder to a mild clinical expression with absence of major diagnostic features. Here we show that even intrafamilial manifestation may vary extremely to the point that Larsen syndrome in a father has been diagnosed only by typical sonographic features in an affected fetus.

[Hepatocellular carcinoma as a rare cause of excessive rise in alpha-fetoprotein in pregnancy]. / Hepatozelluläres Karzinom als seltene Ursache einer exzessiven Erhöhung des Alpha-Fetoprotein in der Schwangerschaft.

OBJECTIVE: Elevation of alphafetoprotein in pregnancy warrants a thorough diagnostic workup. In most cases, no pathologic result in the fetus will be obtained. CASE REPORT: A case report is presented on a hepatocellular carcinoma (HCC) during pregnancy, in which a massive increase of alpha-fetoprotein (AFP) was found during a routine screening for neural tube defects in the 17th week of gestation. The amniocentesis revealed a normal AFP value in the amniotic fluid. Liver sonography in the 21st week of gestation showed a 5 cm tumor, which was interpreted as nodular focal hyperplasia. In the control sonography in the 32nd week of gestation, there was a growth to 12 cm. The subsequently performed magnetic resonance imaging (MRI) and fine needle aspiration led to the diagnosis of a HCC. Delivery was performed in the 34th week of gestation by cesarean section followed by surgical therapy of the HCC. CONCLUSIONS: Unexplained cases of alphafetoproteinelevation in pregnancy can be caused by maternal disease and should prompt a directed amnamnestic and diagnostic search for maternal causes. Nuclear magnetic resonance beyond the first trimester of gestation can help to clarify the diagnosis in liver tumors.

Acute onset of blindness during labor: report of a case of transient cortical blindness in association with HELLP syndrome.

The coincidence of HELLP syndrome and cortical blindness is an uncommon but very dramatic event, for the patient as well as the obstetrician. This report describes the first case of HELLP-syndrome-associated cortical blindness occuring suddenly in the third stage of labour. There were only modest correlates of cortical blindness in cerebral CT, MRI and angiography findings, but no signs of a posterior leucoencephalopathy syndrome. Mother and baby were discharged from hospital to outpatient care in good health on the 12th day.

Hyperemesis in late pregnancy--should we think of cancer? A case report.

Gastric cancer is unusual during pregnancy. The diagnosis may be delayed because specific symptoms are similar to typical pregnancy associated complaints. Our therapeutic management with palliative chemotherapy and later gastrectomy differs from other known cases, where surgical resection has been the treatment of choice. Surgery appears to have no influence on the prognosis of gastric cancer patients with hepatic metastases.

Congenital cystic adenomatoid malformation of the lung and fetal hydrops--a case with favourable outcome.

We present a case of congenital cystic adenomatoid malformation of the lung (CCAM) diagnosed at 23 weeks of gestation with concomitant fetal hydrops. The sonographical picture of CCAM disappeared in the third trimester of pregnancy and fetal hydrops resolved under medication with digitalis to the mother. The neonate showed mild dyspnea; the prenatal diagnosis of CCAM was confirmed by chest X-ray and computed tomography. The affected lung segments were dissected at 5 days of age. The diagnosis of CCAM type III was confirmed histologically.

Prenatal diagnosis of a lethal multiple pterygium syndrome type II. Case report.

Advances in ultrasound technology and sonographer's experience lead to the description of many rare syndromes and malformations through prenatal diagnosis. Diaphragmatic hernia is a rather common malformation but can be an indicator of different syndromes. We report the prenatal diagnosis of lethal multiple pterygium syndrome type II which has been established in the 34th week of pregnancy. The sonographically detectable symptoms consisted of polyhydramnios, hygroma colli, diaphragmatic hernia, scoliosis, short forearms, hypokinesia of the fetus and pterygia over the large joints. Labour was induced in the 34th week of pregnancy; the neonate died shortly after vaginal delivery as a result of the pulmonary hypoplasia. A multidisciplinary approach in prenatal assessment may help to clarify difficult diagnostic problems and may be of direct benefit for the pregnant patient.

Diagnostic dilemma with elevated level of alpha-fetoprotein in an undiagnosed twin pregnancy with a small discordant holoacardius acephalus.

We report a case of a patient who had highly elevated levels of alpha-fetoprotein when she was first examined and a positive acetylcholinesterase test result in amniotic fluid. Despite repeated ultrasonographic screening, pathologic findings were not detected and the holoacardius acephalus twin was not identified. After termination of pregnancy the histopathologic findings demonstrated a twin pregnancy with a holoacardius acephalus.

Combined partial trisomy 3p/monosomy 5p resulting in sonographic abnormalities.

We report here a case of partial trisomy of the short arm of chromosome 3 combined with partial monosomy 5p due to malsegregation of a balanced maternal translocation t(3;5). The newborn demonstrated esophageal atresia and complex cerebral malformations. Conspicuous sonographic findings offering the chance of prenatal detection included polyhydramnios without visualization of the stomach, as well as a single umbilical artery. The child died 8 days postpartum.

[Notch in the umbilical artery Doppler profile in umbilical cord compression in a twin]. / Der Notch im Nabelarteriendopplerprofil bei Nabelschnurkompression eines Zwillings.

Monoamniotic twins have a mortality rate of up to 50%, mainly due to umbilical cord accidents, e.g. true knots. Because of the rarity of monoamniotic twin gestation, few data are presently available on the optimal management of these gestations. Some authors recommend delivery at 32 weeks of gestation, while others state that the risk of cord accidents declines with advancing gestational age, thus questioning the usefulness of routine delivery at 32 weeks. It is possible nowadays to obtain an impression of the fetal blood supply by Doppler sonography. In our case, Doppler sonographic evaluation showed a notch in the umbilical artery in the twin, who later developed a pathological CTG requiring delivery at 28 weeks of gestation. Both fetuses are liveborn and developed normally. Our case shows that a notch in the umbilical artery could be an indication of umbilical cord compression and that attention should be paid to it in monoamniotic twin gestation.

Feto-feto-fetal triplet transfusion syndrome (FFFTTS).

We report a case of feto-feto-fetal-transfusion-syndrome (FFFTS) in a spontaneous monochorionic triamniotic triplet pregnancy primarily diagnosed at 17 weeks of gestation. During the course of pregnancy, sequentially two triplets appeared as donor. Symptoms of a recipient (polyhydramnios, tricuspid valve insufficiency, and ascites) were present in the third triplet. The second of the donor twins died in utero at 25 weeks. At 27 weeks, a cesarean section was performed mainly due to pre-eclampsia. The first donor triplet developed normally, whereas the recipient showed periventricular leucomalacia and neurological impairment.

[Angiogenesis of human breast cancers: neovascularization in xenotransplants and oxygenation in situ in patients]. / Angiogenese von menschlichen Mammakarzinomen: Neo-Vaskularisation in Xenotransplantaten und Oxygenierung in situ bei Patientinnen.

OBJECTIVE: Recent reports have shown that vascularization of breast cancers is an independent prognostic parameter. Tumor growth and neovascularization were investigated in xenotransplants of breast cancers and tissue oxygenation was measured in patients with breast tumors. METHODS: Tumor cells of the breast cancer MX-1 were implanted intradermally in 40 nude mice. Tumor growth and neovascularization were quantified microscopically. Tissue oxygenation was determined in 66 patients with breast tumors using the pO2-histography technique. RESULTS AND CONCLUSION: The angiogenesis begins prior to tumor growth, is insufficient and leads to chaotic blood flow. This results in a heterogeneity of tissue oxygenation in breast cancers. Oxygenation at the tumor periphery appears to be of prognostic importance for clinical outcome of breast cancer.

Oxygenation of mammary tumors as evaluated by ultrasound-guided computerized-pO2-histography.

The average pO2 in breast carcinomas in situ is significantly lower than that in the normal breast tissue. The mean pO2 value for benign breast tumors is significantly higher than that of the breast cancers but lies significantly lower than the corresponding normal breast. No significant differences are found in the mean pO2 values when comparing cancers of different stages and histology. A decrease in the mean pO2 value is measured from the periphery to the center of the breast tumors investigated. The average pO2 values for pre- and postmenopausal patients differ significantly. The described method provides a reliable assessment of tissue pO2 in situ with a minimum of discomfort. Due to extensive inter tumor heterogeneity, prediction of pO2 values for tumors of same stage and same histology is not possible, so that measurement of individual tumor is mandatory for determining therapy response.