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Biomedical subjects

P Hellstern

Publications and source records attributed to P Hellstern.

At least 37 records · Page 2Linked to original sources
PubMed1998

In vitro characterization of solvent/detergent-treated human plasma and of quarantine fresh frozen plasma.

BACKGROUND AND OBJECTIVES: Plasma pools, solvent/detergent(S/D)-treated plasma produced from plasma pools, and single donor fresh frozen plasma that had been quarantined for at least 6 months (QFFP) differ in their composition regarding clotting factors, inhibitors and other important plasma proteins. There are poor data concerning stability of important clotting factors after thawing of frozen plasma units. MATERIALS AND METHODS: 12 plasma pools, 12 batches of S/D plasma produced from these respective plasma pools, and 12 units of QFFP were extensively analysed. The stability of fibrinogen and factors V, VII, and VIII after thawing, storage at room temperature and at +4 degrees C was also examined. RESULTS: We extensively analysed plasma pools before and after solvent/detergent treatment as well as quarantined single donor plasma units for parameters of coagulation and fibrinolysis. After the S/D step, all clotting factor activities and the activities of most inhibitors and other plasma proteins were in the normal range in all batches. Protein S and plasmin inhibitor activities decreased by 35% and 76%, respectively. S/D treatment partly activated factor VII (FVII). However, there were no marked increases of other markers of activated hemostasis. The interindividual variations of all proteins analysed were significantly lower in the S/D plasmas than in the single donor plasma units. An 8-hour storage lead to a marked decrease of FVIII activity, whereas there was no significant influence on fibrinogen and factors V and VII. CONCLUSIONS: There are no critical reductions of the activities of clotting factors, inhibitors, and other important plasma proteins due to S/D treatment. Efficacy and safety of S/D plasma is not hampered by reduced activities of protein S and plasmin inhibitor. Dosage calculation and the evaluation of clinical response is simplified by usage of the more standardized S/D plasma compared to QFFP.

Blood Preservation↗
PubMed1998

Transferrin receptor assay and zinc protoporphyrin as markers of iron-deficient erythropoiesis in end-stage renal disease patients.

To evaluate storage iron deficiency and iron-deficient erythropoiesis we determined, in a cross-sectional study of 95 patients mainly including end-stage renal disease patients (ESRD) with (32) and without rh-EPO therapy (55), the following parameters: hemoglobin, mean corpuscular red cell volume, ferritin, transferrin saturation (TS), zinc protoporphyrin (ZPP) and soluble transferrin receptor (TfR). In the dialysis group the percentage of positive samples with each marker of tissue iron supply defined as TS < 20%, ZPP > 40 mumol/mol Heme and TfR > 3.05 microgram/ml was as follows: TS 43.7% and 32.2% at a diagnostic threshold level of < 16%, ZPP 33.3% and TfR 17.2%. Manifest storage iron deficiency defined as ferritin < 30 ng/ml was observed in 5.7% of the samples while the mean ferritin concentration of the rh-Epo treated dialysis patients was 509.3 ng/ml compared to 262.5 ng/ml in the group without rh-EPO therapy. These data reflect a generous iron substitution in our series taking a TS < 20% as an intervention criterion. Looking at the different results of the three markers the best correspondence was found between ZPP and TfR resulting in a weak positive correlation (+0.64). In conclusion, we found quite different results with different assays when evaluating endogenous iron availability in our series of mainly ESRD patients in a cross-sectional study. Because a gold-standard is not defined further firm conclusions cannot be drawn from this type of study. The adequacy of the different parameters of iron metabolism including threshold levels and, consequently, the decision and route of iron substitution deserve an evaluation in a longitudinal study to characterize the best marker or marker combination in this setting.

Adult↗
PubMed1998

Thromboembolic complications associated with the use of prothrombin complex and factor IX concentrates.

In 1994, shortly after a heat-treated prothrombin complex concentrate (PCC) had been withdrawn from the German market due to transmission of hepatitis B, the license of another brand was withdrawn, due to 3 acute fatalities associated with the use of this product. We report on the clinical data of altogether 5 patients, who died during a 3 month period in Germany after having received this brand of PCC. All patients had surgery, acquired deficiencies of coagulation factors, and underlying diseases predisposing for thrombosis or disseminated intravascular coagulation. PCC was administered for the prevention of bleeding. In three patients, a drug interaction of PCC with aprotinin may also have played a role. Several points, however, are suspicious of a major causative effect of the respective product, (a) the close temporal correlation between administration of the drug and the subsequent clinical as well as laboratory deterioration, (b) the accumulation of these adverse events in a short period of time, when the use and market share of this brand increased due to the shortage of other products, and (c) laboratory abnormalities of this brand which have been consistently observed in several in vitro studies.

Adult↗
PubMed1997

Measurement of factor VII and of activated factor VII in healthy individuals and in prothrombin complex concentrates.

We established reference ranges for factor VII clotting activity (FVII:C), factor VII amidolytic activity (FVII:AM), and activated factor VII (FVIIa) in 102 healthy individuals. The reference ranges were 65-160 U/100 ml, 70-165 U/100 ml, and 30-170 mU/ml, respectively (2.5 and 97.5 percentiles). Freezing and thawing of the plasma samples had no influence on the assay results. Due to the small sample size, the results were not influenced by gender, age, smoking habits, and oral contraceptive use. The plasma levels of FVII:C, FVII:AM, and FVIIa were significantly correlated with each other. The significant correlation between FVIIa and FVII:AM indicates that FVIIa is not completely independent of circulating FVII mass. There was also a significant, though weak, correlation between FVIIa and FVII:C/FVII:AM ratios. Sixteen batches of prothrombin complex concentrates (PCC) from 3 manufacturers were also analysed. FVIIa could be detected in all preparations, with considerable variations from batch to batch. In contrast to the results obtained in plasma from normal individuals, there was a close correlation between FVIIa and FVII:C/FVII:AM ratios. The preparations could be characterized by their FVII and FVIIa potencies and by their FVII:C/FVII:AM ratios. In PCC, FVII:C was very strongly correlated with FVIIa, whereas no significant correlation was observed between FVII:AM and FVII:C and between FVII:AM and FVIIa, respectively. These results demonstrate that the FVII:C assay used is sensitive for detecting FVIIa. Thus, we cannot confirm that FVIIa sensitivity of one-stage clotting assays for FVII:C is low when a rabbit thromboplastin and a non-adsorbed FVII-deficient plasma is used.

Adolescent↗
PubMed1997

Factor VII and activated-factor-VII content of prothrombin complex concentrates. The PCC Study Group.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the potencies of factor VII (FVII) and of activated FVII (FVIIa) in prothrombin complex concentrates (PCC). MATERIALS AND METHODS: We examined 56 lots of PCC from 5 manufacturers. Three brands were licensed preparations, and 1 product series had been involved in thromboembolic complications. FVII and FVIIa were measured using a two-stage amidolytic assay and a specific clotting assay, respectively. We also quantified FVII clotting activity by a one-stage assay reflecting a mixture of FVII zymogen and FVIIa. RESULTS: All PCC contained substantial amounts of FVII, and FVIIa could be detected in all lots. There were marked differences between manufacturers and some significant variabilities between batches. The two lots involved in thromboembolic events contained considerably more FVIIa than the PCC still licensed. The lowest FVIIa potencies were observed in an experimental product series, indicating that PCC can be produced without activation of FVII during the manufacturing process. CONCLUSION: FVIIa is present in all PCC containing FVII. High FVIIa potencies may contribute to the thrombogenic potential of these preparations, and determination of FVIIa potencies should be included in the in vitro characterization of PCC.

Blood Coagulation Tests↗
PubMed1995

The effects of two phasic oral contraceptives on hemostasis and platelet function.

OBJECTIVE: To compare the effects on hemostatic parameters of a combiphasic oral contraceptive containing desogestrel and ethinyl estradiol (DSG/EE) and a triphasic oral contraceptive containing levonorgestrel and ethinyl estradiol (LNG/EE). METHODS: In an open-label, randomized, group-comparative study in 10 healthy volunteers per treatment group, the effects on parameters of coagulation, anticoagulation, fibrinolysis, antifibrinolysis and platelet function were determined at baseline, after three treatment cycles, and after a post-treatment cycle. Changes from baseline were analyzed using a paired t-test, whereas between-group differences were analyzed by means of an analysis of co-variance. RESULTS: Both OC preparations induced modest changes of some coagulation, anticoagulation, fibrinolysis and antifibrinolysis parameters, although all mean values remained within the normal range. No significant effects were observed with either OC with respect to platelet function. Statistically significant differences between the two preparations could occasionally e observed: the concentrations of antithrombin II (AT-III) and Factor VII were higher with the DSG/EE preparation than with LNG/EE preparation at the end of treatment and AT-III activity, AT-III concentration, Factor X concentration, and plasminogen activity were higher with DSG/EE than with LNG/EE in the post-treatment cycle. CONCLUSIONS: Combiphasic DSG/EE and triphasic LNG/EE, both OCs with a comparable amount of EE per cycle, had no clinically significant effect on the overall hemostatic balance.

Blood Coagulation↗
PubMed1994

Clinical experience with the viral safety of immunoglobulins.

Preparations of intramuscular immunoglobulins (IMIGs) have not been reported to transmit viral disease since the inclusion of third-generation tests screening donor blood for hepatitis B virus. IMIGs and intravenous immunoglobulins (IVIGs) have never been a source of transmission of human immunodeficiency viruses. One episode of hepatitis B transmission by IVIGs caused by the addition of contaminated material during the manufacturing process, has been reported. Between 1983 and 1994 there were at least 17 reports of transmission of non-A, non-B hepatitis or [transaminitis' connected with the application of six IVIG preparations. These preparations were produced without including a validated virus-inactivation method in the manufacturing process. Careful analysis of these accidents demonstrates that minimization of virus contamination of source plasma, guarantee of good manufacturing practice, as well as application of an accepted virus-inactivation procedure are essential requirements for the production of safe immunoglobulin preparations.

Consumer Product Safety↗
PubMed1994

Detection of primary HIV infection by a second-generation HIV(p24) antigen test.

We studied the course of a primary HIV infection in a 54-year-old woman. Probably the source of infection was sexual intercourse, since other risks, such as i.v. drug use, acupuncture and transfusion were excluded. On admission she presented with fever, a maculopapular rash, and moderate enlargement of nuchal lymph nodes. At that time the anti-HIV 1,2 enzyme immunoassay was negative. However, the HIV-p24 Ag test, which was performed in every HIV screening in our laboratory, was positive. The suspicion of an acute HIV infection was supported by a positive HIV-cDNA-PCR and confirmed by Western blot after seroconversion. As additional finding, the blood smear showed abnormal white cell differential count, indicating viral infection. Aminotransferases were slightly increased, and antibodies to hepatitis B surface and core antigens demonstrated former hepatitis B infection. It is concluded that in this case the HIV-p24 Ag test proved its suitability for early diagnosis of an acute HIV infection. In case of testing blood donors, none of the compulsory serological screening methods would have detected the HIV infection.

AIDS Serodiagnosis↗
PubMed1993

Inactivation of viruses in fresh-frozen plasma.

Methylene blue (MB) or solvent/detergent (SD) treatment is used for the inactivation of lipid-enveloped viruses in plasma. One important characteristic of the SD treatment is the necessity to pool plasma from different donors, thus inducing the risk of spreading infectious particles. MB treatment can be applied to single-donor plasma, causing no greater infectious risk than conventional fresh-frozen plasma (FFP). However, the virucidal efficacy of the SD method regarding HIV, HBV and HCV has been significantly better examined and proven than the MB treatment. Most of the therapeutic constituents of both plasma products are well maintained; coagulation factors decrease by roughly 5-20%. SD treatment reduces protein S and alpha 2-antiplasmin by approximately 40%, whereas MB treatment leads to a significant photooxidative alteration of fibrinogen with a disturbance of fibrin polymerization. As current studies show, the use of either plasma product is obviously not limited by acute or chronic toxicity. Several studies are in progress to evaluate the relevance of alterations in FFP quality which may affect the clinical efficacy of virus-inactivated plasma.

Antiviral Agents↗
PubMed1993

Prospective study on efficacy and tolerability of solvent/detergent-treated plasma in intensive care unit patients.

Thirty patients who were postoperatively admitted to the intensive care unit had to be treated because of disseminated intravascular coagulation and/or coagulopathy resulting from blood volume dilution or loss. These patients received a single dose of solvent/detergent-treated plasma (Octaplas). No other blood products were administered 6 h prior to and 1 h after completion of the plasma infusion. Coagulation analyses were performed before and 10-60 min after plasma administration. Prothrombin time, fibrinogen, antithrombin III, and systolic blood pressure improved significantly due to plasma therapy. Activated partial thromboplastin time and platelet count also improved, but the differences were not significant. During the observation period, no side effects occurred. The subjectively assessed hemostatic effect was good.

Aged↗
PubMed1992

Manufacture and in vitro characterization of a solvent/detergent-treated human plasma.

We have developed a modified solvent/detergent (S/D) treatment to inactivate viruses in human plasma using 1% w/w final concentration of tri(n-butyl) phosphate (TNBP) and Triton X-100 and an incubation period of 4 h at 30 degrees C. The procedure inactivates > or = 10(6) chimpanzee-infectious doses (CID50) of HBV, > or = 10(5) CID50 of HCV, and > or = 10(6.2) tissue culture infectious doses (TCID50) of HIV. After virus inactivation, eleven plasma batches were lyophilized and 12 batches were deep-frozen until further use. The batches were characterized by extensive laboratory tests including measurement of clotting factors I-XIII, von Willebrand factor, plasminogen, inhibitors of blood coagulation and fibrinolysis, and other clinically important plasma proteins. All parameters were determined before and after S/D treatment. Twelve conventional single donor plasma units served as control. There were no marked losses of activities of clotting factors, antithrombin III, protein C, plasminogen, and C1-esterase inhibitor due to treatment. After the S/D step, the levels of these parameters were within the normal range in all batches. The same holds true for total protein, immunoglobulins, albumin, complement factors C3 and C4, haptoglobin, hemopexin, caeruloplasmin, alpha 1-antitrypsin, and pH. Protein S and alpha 2-antiplasmin activities decreased by about 50% and were frequently found to be slightly below the lower limit of the respective normal range after treatment. The interindividual variations of all proteins analysed were significantly lower than in the single donor plasma units. The S/D procedure did not lead to increases of markers indicating activation of hemostasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiviral Agents↗
PubMed1990

[Subcutaneous injection of desmopressin (DDAVP) for increasing factor VIII and von Willebrand factor in plasmapheresis].

Desmopressin (DDAVP) is an effective tool for increasing factor VIII (FVIII)/von Willebrand factor (vWF) in normal subjects and in patients with haemophilia A and von Willebrand's disease. There are a few studies utilizing DDAVP to increase the FVIII/vWF yield in plasmapheresis donors. In these studies, DDAVP was given either by intranasal administration or intravenous infusion. The aim of our pilot study was to investigate the subcutaneous (s.c.) injection of DDAVP in combination with double bag plasmapheresis. 8 donors with blood group A and 5 with O were given 0.4 micrograms/kg body weight DDAVP as a s.c. injection 30 min prior to the first donation. FVIII increased 3.7 and ristocetin cofactor 2.5 the initial value in the donors. In the plasma bags, a 3 (1st bag) and 3.5 (2nd bag) fold higher FVIII level was found, when compared with baseline levels. There was only a mild decrease of blood pressure, and serious adverse effects were not observed. Our data suggest that s.c. DDAVP may be more effective and especially suited for increasing FVIII/vWF yield in plasmapheresis donors.

Blood Donors↗
PubMed1990

[Hemostatic therapy in a patient with acquired von Willebrand disease and Waldenström disease with plasmapheresis and DDAVP].

A 73-year old patient suffering from IgM-paraproteinemia, plasma hyperviscosity, and acquired v. Willebrand's disease developed two consecutive bleeding episodes. He was treated by double-bag plasmapheresis and double-bag plasmapheresis combined with DDAVP. This combined therapy was superior to plasmapheresis alone, since bleeding ultimately stopped and did not reoccur. Thus, labour and expense of large volume plasma exchange and the costs of F VIII therapy could be prevented.

Aged↗
PubMed1989

Effects of long-distance running on iron metabolism and hematological parameters.

In 110 well-trained participants of a 1000-km running competition lasting for 20 days hematological parameters, iron metabolism, and their respective changes during the race were investigated. Thirty-nine men and 11 women were accustomed to wholesome vegetarian food (lacto-ovovegetarian), 52 men and 8 women consumed a conventional western diet. In each group 50% of the runners finished the race. Before the competition started red blood cell count, hematocrit, and hemoglobin were on average below the values observed in the normal population in all groups. Both male and female runners consuming the wholesome diet showed significantly lower ferritin values than those on a western diet. During the first days of the competition hemolysis occurred leading to increased serum concentrations of bilirubin and iron and decreased haptoglobin levels. Hb concentrations showed a constant decrease during the race. Serum ferritin concentration rose about twofold within the first days and then decreased again without reaching pre-race levels. Serum iron concentrations showed a significant decrease between days 3 and 6. Iron loss was caused by hematuria (25% of all urines tested), gastrointestinal blood loss (10% of all stool specimens tested), and by sweating (4.5 micrograms iron/dl sweat). Our results suggest that especially in female long-distance runners it may be difficult to supply sufficient quantities of iron with the diet.

Adult↗
PubMed1989

Subcutaneous injection of desmopressin (DDAVP): evaluation of a new, more concentrated preparation.

A more concentrated desmopressin (DDAVP) preparation (40 micrograms/ml), which required small injection volumes (less than 1 ml), was studied in a double-blind trial in 10 healthy volunteers, 12 patients with haemophilia A, and 8 patients with uraemic bleeding. DDAVP was administered by subcutaneous injection at a dose of 0.4 micrograms/kg body weight. In healthy subjects, peak levels of DDAVP ranging from 480 to 638 pg/ml were reached 1 h after the subcutaneous injection and DDAVP was eliminated with a mean half-life of 3.1 h. DDAVP produced a 2.5-fold (3.0-fold) increase of factor VIII:C (factor VIII:Ag) and a 1.9-fold (2.2-fold) increase of von Willebrand factor:Ag (ristocetin cofactor) over baseline levels. Additionally, a 2.1-fold increase of tissue-type plasminogen activator antigen was observed. Factor VIII and von Willebrand factor were rapidly eliminated with a half-life ranging from 1.3 to 5.7 h and from 1.1 to 11.4 h, respectively. In haemophilia A patients, DDAVP produced a 2.3-fold increase of factor VIII:C 1 h after the injection. DDAVP was given on 8 occasions for management of bleeding, and only in 1 patient did a wound haematoma (after herniotomia) occur. In 7 of the 8 patients with uraemia the bleeding time shortened, and in all patients an increase of platelet retention and a decrease of platelet count was observed (p less than 0.05). No serious local or systemic untoward side effects were observed.

Adult↗
PubMed1988

In vivo recovery and half-life time of a steam-treated factor IX concentrate in hemophilia B patients. The influence of reagents and standards.

Factor IX (FIX) recovery and half-life was measured in ten hemophilia B patients under standardized conditions. Each patient received a steam-treated high-purity factor IX concentrate at a dose of 19-39 U/kg body weight. FIX activity was determined using a one-stage assay, which was calibrated against the international concentrate standard (reagents from Immuno, Heidelberg). The in vivo recovery ranged from 24% to 53% (mean value 37.7%) and the half-disappearance time (HDT) from 8-30 h (mean 16.7 h). In four of the ten patients, the distribution and elimination half-lives were estimated and ranged from 0.3 h to 3.9 h (mean 1.4 h) and from 28.6 h to 39.7 h (mean 33.1 h), respectively. In six patients FIX was redetermined using a different FIX deficient plasma and a plasma standard (reagents from Merz & Dade, Munich, FRG). Recoveries and HDT based on the results obtained with this method were significantly higher (68.2% vs 39.7%; p less than 0.05), and longer (14.8 h vs 10.6 h; p less than 0.05), respectively. FIX activity was also measured by both assay systems in 100 healthy subjects (50 males, 50 females). The reagents from Immuno yielded a mean value of 0.77 U/ml, while the mean FIX activity utilizing standards and reagents from Merz & Dade was 1.11 U/ml (p less than 0.000001). The coefficient of correlation between the FIX activity measurements, as determined in 100 healthy subjects and 6 hemophilia B patients using the different test systems, was r = 0.9 (N = 159; y = 0.08 +/- 1.3* chi; p less than 0.001). Our data suggest that recovery and HDT of factor IX concentrate strongly depend on the assay and calibration conditions and that an international FIX activity plasma standard is urgently required.

Adolescent↗
PubMed1988

Platelet aggregation, rheological parameters and blood glucose profiles in diabetic children (type I) treated with human and porcine insulin.

In a three-year bicentric cross-sectional investigation on type I diabetic children between six and eighteen years of age, blood sugar profiles and spontaneous thrombocyte aggregation were assessed besides anamnestic and clinical data. In the children treated with human insulin raised spontaneous thrombocyte aggregation was significantly more frequent than in those treated with porcine insulin. At the same time blood sugar fluctuation from day to day measured between seven and nine a.m. tended to be raised in the children treated with human insulin; the fluctuation in the diurnal profile measured for fourteen days was indeed very much greater. Since the two groups were comparable as to sex distribution, age, duration of disease, quality of compensation, application and dose of insulin, the greater fluctuation of blood sugar in the children treated with human insulin appears to be the cause for the raised spontaneous thrombocyte aggregation.

Adolescent↗