Biomedical subjects

K Bremme

Publications and source records attributed to K Bremme.

At least 19 recordsLinked to original sources

PubMed2001

Presence of CD30(+) and CD30L(+) cells in human placenta and soluble CD30 levels in cord blood are independent of maternal atopy.

The intrauterine environment is characterized by a Th2 dominance during pregnancy, a milieu that also promotes atopic allergy. The aim of this study was to compare the presence of CD30, a molecule associated with Th2 related disorders such as atopic allergy, and its ligand (CD30L) in placenta in order to investigate if the placenta environment differs between atopic and non-atopic women. Serum concentrations of soluble CD30 (sCD30) from the mothers and their newborns were also elucidated. There were no differences in the immunohistochemical expression of CD30 and CD30L in placenta from atopic (n=28) compared with non-atopic (n=37) women. CD30 was expressed on the decidual stromal cells alone, while CD30L, previously not described in placenta, was detected on macrophage-like HLA-DR(+) cells throughout the mesenchymal chorionic villi. Serum sCD30 in atopic mothers was significantly elevated compared with serum sCD30 in non-atopic mothers (P< 0.05), while sCD30 levels in cord blood were similar in both groups independently of maternal atopic heredity. We suggest that sCD30 in cord blood and CD30 expression by decidual cells may reflect the Th2 environment surrounding the fetus, and both CD30 and CD30L could have immune regulatory functions in placenta.

Decidua↗

PubMed2001

Accumulation of low molecular mass heparin during prophylactic treatment in pregnancy.

A history of thromboembolism is associated with an increased risk of new thromboembolic events during pregnancy. Prophylaxis with heparin during pregnancy implicates long-term treatment with daily injections with either unfractionated heparin (UFH) or low molecular mass heparin (LMMH). Prolonged treatment with heparin may result in endothelial absorption and drug accumulation. In order to test this hypothesis, anti-FXa activity during pregnancy was measured in four women allergic to conventional UFH, who were treated with LMMH (dalteparin; Pharmacia). It was found that, at the commencement of treatment, it took more than 8 days to reach a steady maximum peak value, located 3 h after the given dose. One daily dosage of 5,000 IU anti-Xa resulted in a measurable level of FXa for 24 h in pregnancy week 40, compared with 17h at pregnancy week 37. The implications of an elevated anti-FXa activity during pregnancy, especially during the third trimester and at partus, are discussed. We present a reduced dose regime near term and during delivery.

Adult↗

PubMed2001

Cesarean section under epidural ropivacaine 0.75% in a parturient with severe pulmonary hypertension.

Pregnancy and delivery are a potentially lethal combination in a patient with primary pulmonary hypertension. There are controversies regarding mode of delivery. Cesarean section is considered to be associated with extensive perioperative risks. We report on a parturient with severe pulmonary hypertension who underwent a succesful semiemergent cesarean section on vital indication. Vaginal delivery was excluded since her cervix was too immature for succesful induction. This is the first reported case of its kind to receive an epidural anesthesia with ropivacaine with its potential advantage of a low cardiac toxicity. The epidural was slowly and carefully titrated to give a stable anesthesia with good quality.

Adult↗

PubMed2001

Measurement of activated protein C resistance during menstrual cycle in women with and without the Leiden mutation.

Variations in the APC ratio during the menstrual cycle were assessed in 25 women without the Leiden mutation, and 10 women who were carrier of the mutation. Blood samples were collected at four occasions during one menstrual cycle. APC ratios were measured with two APTT based plasma methods with and without factor V depleted plasma. None of the methods were able to accurately discriminate between mutated and non mutated women in all samples. Although a normalized method with factor V depleted plasma was favorable. The levels of estradiol and progesterone did not differ between mutated and non mutated women. Our findings suggest that the level of estradiol at estimated time of ovulation is of importance for the response to APC during luteal phase, since the women exhibiting the highest levels of estradiol at time for ovulation had the lowest response to APC.

Activated Protein C Resistance↗

PubMed2001

Preoperative treatment of anemic women with epoetin beta.

AIM: To compare the effects of preoperative treatment with recombinant human erythropoietin (EPO) and iron with iron only on hemoglobin levels (Hb) in anemic women prior to hysterectomy. METHODS: The study was an open-labelled randomized parallel study. Fifteen women scheduled for hysterectomy due to uterine myoma were given oral iron and EPO (NeoRecormon) 4 weeks prior to surgery (group I) and 16 women were given oral iron only (group II). RESULTS: Group I showed a significantly greater increase in mean Hb during the pre-surgery study period compared with group II (p=0.007). Two weeks postoperatively, however, there was no significant difference in mean Hb between the two groups. CONCLUSION: We found that a significantly greater increase in Hb was achieved with iron in combination with EPO, although in most cases iron only seemed to be as efficacious as iron+EPO in correcting anemia in myoma patients pre-operatively.

Administration, Oral↗

PubMed2000

Toxic and essential elements in placentas of Swedish women.

OBJECTIVES: To evaluate interactions between toxic and essential elements in the mother-fetus relationship and possible predictors of trace element concentrations in placenta and cord blood. DESIGN AND METHODS: A group of 106 Swedish women was investigated for concentrations of cadmium, lead, and several essential elements in placenta as well as cadmium, lead, zinc, and selenium in venous blood collected at gestational week (gw) 36 and umbilical cord blood. Relations between these elements and maternal and child's characteristics were examined. RESULTS: The concentrations of cadmium in placenta ranged from 10 to 170 nmol/kg, with the median value (Md) being 46 nmol/kg. Cord blood cadmium (Md of 0.19 nmol/L) was only about 10% of that in maternal blood. Smokers had significantly higher cadmium concentrations in blood (p < 0.001) and placenta (p = 0.001) than non-smokers. The median placental concentration of lead was 26 nmol/kg (range 0-630 nmol/kg). The lead levels in cord blood (Md of 54 nmol/L) were almost the same as in maternal blood. Statistically significant negative associations were found between cord blood lead, on one hand, and child's weight, length, and head circumference, on the other. The placental levels (medians and ranges) of the essential elements (micromol/kg) were 160 (120-280) for zinc, 2.4 (2.0-3.3) for selenium, 15 (10-20) for copper, 0.084 (0.02-0.32) for cobalt, 0.055 (0.03-0.12) for molybdenum, and 1.2 (0. 65-5.1) for manganese, respectively. Several of the essential elements in placenta correlated significantly with each other. Multiparous mothers had significantly lower concentrations of zinc (p = 0.002) and selenium (p = 0.049) in serum as well as zinc (p = 0. 001) and calcium (p = 0.004) in placenta than nulliparous ones. Also, cord blood zinc decreased with parity. CONCLUSIONS: The results showed that lead, but not cadmium crossed easily the placental barrier. There were no negative effects of cadmium on the zinc status. Cord blood lead, on the other hand, was a negative predictor of child's birth weight, length and head circumference, indicating that lead might have negative influence on growth in children even at very low exposure levels. There was a depletion of maternal stores of essential elements with increasing parity.

Cadmium↗

PubMed2000

Primary habitual abortions are associated with high frequency of factor V Leiden mutation.

OBJECTIVE: To analyze the prevalence of the mutation G1691A in factor V gene (Leiden mutation), of mutation C677T in the methylenetetrahydrofolate reductase (MTHFR) gene, and of polymorphism in G20210A in the prothrombin gene in women with recurrent abortions; further, to identify a subgroup at higher risk of being carriers of these mutations. DESIGN: Prospective case control evaluation. SETTING: University clinic. PATIENT(S): Eighty-four women with 3 or more consecutive miscarriages were compared with 69 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Polymerase chain reactions were performed to identify the mutations G1691A in factor V and C677T in MTHFR genes and the polymorphism G20210A in the prothrombin gene. RESULT(S): In women with primary habitual abortions, 27.8% carried the Leiden mutation. No difference was observed in the prevalence of mutation C677T in the MTHFR gene or in polymorphism G20210A in the prothrombin gene. CONCLUSION(S): The Leiden mutation may play a considerable role for women having primary recurrent abortions.

Abortion, Habitual↗

PubMed2000

Decrease in protein C inhibitor activity and acquired APC resistance during normal pregnancy.

BACKGROUND: Since protein C inhibitor (PCI) inhibits activated protein C (APC) and a number of proteases, one would expect lower concentrations of PCI in a hypercoagulable state due to increased consumption of the inhibitor. Normal pregnancy is associated with a state of activated hemostasis, where response to APC is depressed. We aimed to study whether PCI function varies during normal pregnancy, and assess the relationship between this inhibitor and acquired APC resistance. METHODS: PCI activity in plasma was tested during pregnancy and postpartum in 28 healthy pregnant women without factor V Leiden Arg(506) - Gln mutation and in 14 non-pregnant female controls. The PCI levels determined in the present study was compared to the APC ratio (APC-r), we investigated previously, in the same samples. RESULTS: The levels of PCI in the pregnant group, as compared to that in the control group (4.74 +/- 0.48), gradually decreased from the first to the third trimester, i.e., 3.30 +/- 1.31 microg/mL in week 12 (p < 0.001), 2.66 +/- 1.44 microg/mL in week 20 (p < 0.001), 1.92 +/- 1.18 microg/mL in week 28 (p < 0.001), 1.30 +/- 0.94 microg/mL in week 32 (p < 0.001) and 1.49 +/- 1.12 microg/mL in week 37 (p < 0.001). After delivery, they rose to 5.02 +/- 1.93 microg/mL, similar to that in the controls (p > 0.05). The values of APC-r showed the same tendency during gestation and postpartum. CONCLUSION: With advance of normal pregnancy, decreasing PCI function corresponds to increasing APC resistance, probably due to that activated hemostasis acts as a link connecting the two variables.

Activated Protein C Resistance↗

PubMed1999

A laboratory method for determination of overall haemostatic potential in plasma. I. Method design and preliminary results.

The aim of this study was to design a simple laboratory method that can screen the overall haemostatic potential in plasma (OHPP) when a hyper- or hypocoagulable state is present. A fibrin time curve was made via spectrophotometric registration of fibrin generation and lysis in plasma, to which exogenous thrombin and tissue type plasminogen activator was added. The area under the curve, calculated by the sum of absorbance (ABS-sum), varied in correlation to the concentrations of platelets or purified pro-/anticoagulants: tissue factor, von Willebrand factor, fibrinogen, antithrombin, plasminogen, or plasminogen activator inhibitor type 1. The ABS-sums also changed in positive relation to the haemostatic function investigated in 16 menopausal women and 14 young healthy nonpregnant women (controls). The findings imply that the ABS-sums not only offer a general information about fibrin generation and lysis in vitro, but also reflect the OHPP (i.e., final combined effects of platelet activity, coagulation, and fibrinolysis in vivo). Preliminary results were satisfactory; the levels of OHPP, expressed as the ABS-sums, were higher in normal pregnant women than in the controls, and even higher in preeclamptic patients than in pregnant women with no complications, which corresponds to the different grades of hypercoagulability in the three groups. Moreover, the level of OHPP was considerably lower in an untreated infant with von Willebrand's disease type 3 and in factor VIII- or factor IX-deficient plasma samples.

Adult↗

PubMed1999

Clinical evaluation of a solid-phase test for red cell antibody screening of pregnant women.

BACKGROUND: The aims of this study were to evaluate the results of a new solid-phase screening test for detecting atypical red cell (RBC) antibodies in a large number of pregnant women and to compare these results to the clinical outcome of the newborn. STUDY DESIGN AND METHODS: A total of 38,700 infants born in Stockholm were studied retrospectively. Of these infants, 18,500 were born to pregnant women screened with the solid-phase test. Data were collected on all newborns with a positive direct antiglobulin test (DAT) and on infants requiring an exchange transfusion or a blood transfusion. These data were correlated to the screening results for the mothers. RESULTS: Of 409 DAT-positive newborns, a serologic explanation for the positive DAT was found in 349. Three hundred four cases were due to ABO incompatibility between mother and child; 19 of these infants needed an exchange transfusion. Forty-two cases were due to unexpected maternal RBC antibodies; 11 of these infants were given an exchange transfusion. All 11 were identified before birth. Three other infants had DAT-positive tests due to ABO incompatibility and to unexpected maternal RBC antibodies. CONCLUSION: ABO incompatibility is a major indication for exchange transfusion in DAT-positive newborns. There was no evidence that the solid-phase screening test had failed to detect any clinically significant RBC antibodies. Finally, the results of this study do not indicate a need for routine screening of D+ women more than once during each pregnancy.

ABO Blood-Group System↗

PubMed1999

Can the laboratory assay of protein C activity assist in monitoring the hemostatic function in pre-eclampsia?

Published reports do not agree about whether protein C activity is non-significantly changed or decreased in a hypercoagulable state induced by pre-eclampsia without hemolysis-elevated liver enzyme/low platelet (HELLP) syndrome. In order to assess the relationship between this anticoagulant and enhanced hemostasis, levels of protein C activity, thrombin-antithrombin complexes, soluble fibrin, fibrin D-dimers and antithrombin were determined in 30 pre-eclampsia patients without the HELLP syndrome, in 22 normal pregnant women in gestational weeks 30-35, and in 13 non-pregnant controls. Levels of thrombin-antithrombin complexes, soluble fibrin and D-dimers increased (P < 0.05) whereas antithrombin decreased (P < 0.05) in patients with pre-eclampsia, compared with normal pregnant women. Levels of protein C did not differ significantly between patients with pre-eclampsia, normal pregnant women and controls (P > 0.05). The 5th and 95th percentiles of protein C levels in normal pregnant women were 0.53 and 1.30 U/ml, respectively; levels between these two values could be considered physiological. When the pre-eclampsia patients were subdivided according to these percentiles, none belonged to the subgroup with protein C < or = 5th percentile; 23% (seven of 30) fell into the subgroup with protein C > or = 95th percentile. Elevated levels of hypercoagulation markers were shown in the groups whose protein C fell within 5th-95th or > or = 95th percentiles (P < 0.05), compared with normal pregnant women. Concentrations of protein C and thrombin-antithrombin complex were significantly correlated (r = 0.69, P > 0.05) in patients with pre-eclampsia. In summary, in subjects with pre-eclampsia without the HELLP syndrome, protein C activity may be similar to that in normal pregnant women. However, such a 'physiological' anticoagulant level in association with the enhanced thrombin generation and fibrin formation does not necessarily reflect a physiological capability of coagulation. Thus, assays of protein C activity might not always assist in monitoring the hemostatic function during pre-eclamptic pregnancy.

Adult↗

PubMed1999

Haemostatic, endothelial and lipoprotein parameters and blood pressure levels in women with a history of preeclampsia.

To determine whether perturbations of haemostatic function and lipoprotein metabolism prevail long after preeclampsia and increase the risk of future coronary heart disease (CHD), we conducted a follow-up study in women with (cases, n = 25) or without (controls, n = 24) a history of preeclampsia. Blood samples were taken in the follicular and in the luteal phases of a menstrual cycle. Levels of blood pressure (BP) and proteinuria measured during the index pregnancy were included in the evaluation. Compared to control women who had undergone a normal pregnancy, the formerly preeclamptic patients had higher systolic (p <0.01) and diastolic (p <0.05) BPs and increased plasma levels of von Willebrand factor (vWF), fibrinogen, cholesterol, triglycerides and very low density lipoprotein (VLDL) (all p <0.05). The lipid, vWF, and fibrinogen levels were positively related to the degree of BP elevation but not to the degree of proteinuria during the index pregnancy. Except for the increase in vWF level, all biochemical perturbations were only present in the luteal but not in the follicular phase samples. In conclusion, persistent endothelial dysfunction with ensuing dysregulation of blood pressure, haemostatic perturbation and dyslipoproteinemia after preeclampsia may indicate a proneness to future CHD.

Adult↗

PubMed1998

Serum transferrin receptor: a specific marker of iron deficiency in pregnancy.

BACKGROUND: Current markers of iron deficiency tend to be less reliable in pregnancy. OBJECTIVE: Our aim was to study the usefulness of soluble serum transferrin receptor (sTfR) as a marker for iron deficiency during early and late gestation and to define iron status in 254 pregnant Swedish women. DESIGN: We performed a cross-sectional and longitudinal evaluation of sTfR in comparison with concentrations of serum ferritin and hemoglobin in blood collected around gestational weeks 11 and 36. RESULTS: The specificity of sTfR was 100%. The sensitivity in relation to both anemia and depleted iron stores was approximately 70%, but this figure is less reliable because of few samples. sTfR in early pregnancy was low: 11% of women had a value below the reference interval. sTfR increased significantly from early to late pregnancy even in the group of women with persisting iron stores. In late pregnancy, 14% of women developed tissue iron deficiency and 5% had iron deficiency according to a combination of all 3 markers. CONCLUSIONS: sTfR seems to be a specific and sensitive marker of iron deficiency in pregnancy and may have advantages over serum ferritin and hemoglobin. The low sTfR concentration in early gestation seems to be caused by reduced erythropoiesis, whereas the increase from early to late pregnancy reflects increased erythropoiesis, and in case of iron deficiency, also tissue iron deficiency. Further studies are needed to verify whether decreased erythropoiesis reduces the possibility of detecting iron deficiency during early gestation by sTfR.

Anemia↗

PubMed1998

Reactivity against phospholipids during pregnancy.

Antibodies against phospholipids (PLa) are often thought to be associated with the development of activated protein C (APC) resistance. In the present study, PLa were followed throughout 29 healthy pregnancies and compared to APC resistance. The level of PLa did not change during pregnancy [6.9 +/- 3.7 GPL week 12 versus 6.3 +/- 2.8 GPL week 37; 3.3 +/- 1.8 MPL versus 3.2 +/- 1.5 MPL; and lupus anticoagulant (LA) coefficient 0.99 +/- 0.11 versus 0.94 +/- 0.09], in contrast to the APC resistance, which was suppressed (0.96 +/- 0.22 versus 0.78 +/- 0.13, P < 0.05), but both parameters elevated after delivery (up to 8.7 +/- 4.2 GPL; 1.13 +/- 0.1 LA coefficient; 1.11 +/- 0.22 nAPC ratio; P < 0.05). Three women possessed PLa (1 CLa IgG +/- IgM; 1 IgG CLa +/- PSa +/- PEa; 1 PSa), no LA activity was registered. In the PLa-positive women, dynamics of the nAPC ratio during pregnancy was not related to PLa.

Activated Protein C Resistance↗

PubMed1998

A pharmacokinetic study of dalteparin (Fragmin) during late pregnancy.

Seventeen women with previously verified thromboembolism were included in a pharmacokinetic evaluation of dalteparin during the third trimester of pregnancy. The bioavailability of morning subcutaneous administration of dalteparin (crossover study) was also compared with that in the evening. Fifteen women injected themselves subcutaneously with 5000 IU and two with 2500 IU dalteparin once daily. An anti-FXa activity of 0.20-0.40 IU/ml 3 h after injection was obtained. The means +/- SD, when comparing morning and evening doses for 5000 IU, were: Cmax 0.21 +/- 0.05 and 0.20 +/- 0.05 IU anti-FXa/ml, AUC 0-24 h 1.97 +/- 0.46 and 1.93 +/- 0.55 IU x h/ml and tmax 3.71 +/- 0.89 and 4.32 +/- 1.60 h, respectively (NS). The two regimens were equivalent. A measurable anticoagulant effect was still observed 16 h after injection of 5000 IU dalteparin. The half-lives after a morning and an evening dose of 5000 IU dalteparin were 4.92 +/- 2.80 and 3.87 +/- 1.15 h, respectively (NS). There were no changes in thrombin marker levels during the two pharmacokinetic measurements.

Adult↗

PubMed1998

Production of phospholipid antibodies in selected thrombophilic women differing in genotype at the 506 site of factor V.

The composition of antibodies against phospholipids (PLa) was analysed in 54 PLa-positive thrombophilic women, different in the factor V genotype (Arg506-Gln mutation carriers, n=23; and noncarriers, n=31). The presence of antibodies against prothrombin was also studied. The incidence of cardiolipin antibodies (CLa) and lupus anticoagulant (LA) activity was similar among the carriers and noncarriers, while phosphatidylserine antibodies (PSa) were often the only PLa detected in the carriers of the mutation (7/23 vs. 2/31; chi2=5.47, p<0.05). Antibodies against prothrombin were found in 11 of 54 patients. They segregated with PSa (8/19 vs. 3/35; chi2=8.54, p<0.025), but were equally distributed between carriers and noncarriers. The analysis of nAPC-ratio in patients with different PLa showed that it was consistently lower in the mutation carriers in whom none of the PLa caused further suppression. The noncarrier group positive for LA in several assays was associated with a reduction of nAPC-ratio (0.82+/-0.25 vs. 1.12+/-0.22, p<0.05). Our findings indicate that PLa contributing to the development of APC resistance are restricted to those possessing LA activity.

Adult↗

PubMed1998

Soluble fibrin in plasma as a sign of activated coagulation in patients with pregnancy complications.

BACKGROUND: Disseminated intravascular coagulation (DIC) is a frequently observed complication in pregnant women. The laboratory diagnosis of DIC is difficult but the development in the detection of circulating soluble fibrin has improved the possibility. METHODS: A number of pregnant women (n= 175) with obstetric complications e.g. preeclampsia, hypertension, intrauterine growth retardation (IUGR) and intrahepatic cholestasis was examined for plasma soluble fibrin and subjected to some routine hemostatic tests, mainly during the third trimester of pregnancy. RESULTS: Of these patients, 57 of 175 (33%) had an elevated concentration of soluble fibrin (above 23 nmol/L) as compared with a healthy group of women sampled in the third trimester. Eighteen patients (10%) had highly increased levels, above 100 nmol/L. In comparison, none of the 23 healthy, pregnant women investigated had a value above 40 nmol/L. CONCLUSIONS: Hemostatic abnormalities, including increased concentrations of soluble fibrin, are quite frequently observed in women with obstetric complications, most likely as a sign of a systemic activation of coagulation. Although a higher concentration of plasma soluble fibrin was observed in many of the women, no clear correlation to the outcome of the pregnancy was obtained. Whether or not plasma soluble fibrin is of any value, either diagnostically or the treatment of patients with pregnancy complications, remains to be shown.

Blood Coagulation Tests↗

PubMed1998

Thromboprophylaxis with low molecular mass heparin, 'Fragmin' (dalteparin), during pregnancy--a longitudinal safety study.

Twenty-five women with previous verified thromboembolic complications were treated with delteparin (Fragmin) during pregnancy and puerperium. Women with known hereditary thrombophilia (antithrombin, protein C and protein S deficiencies) or with phospholipid antibodies were excluded. The dose at entry was calculated according to body weight and thereafter monitored by anti-FXa activity aiming at 0.20-0.40 IU/ml plasma 3 h post injection. Dalteparin or dextran was used during delivery. Twenty-two women completed the study and 14 of these could be given the same dose throughout pregnancy. There was an increased dose response postpartum. There were no thromboembolic recurrences or severe bleeding complications. The level of antithrombin activity remained normal. Our thrombosis-prone pregnant women had initially increased levels of thrombin markers but no further increase was observed during the dalteparin thromboprophylaxis. Retrospectively, three heterozygous and three homozygous individuals for the FV Leiden mutation leading to activated protein C resistance were identified. In conclusion, dalteparin could safely be used as thromboprophylaxis during pregnancy in these thrombosis-prone women. Women weighing 50-79 kg at entry could be treated with 5000 IU of dalteparin once daily during pregnancy, without monitoring. Postpartum, many of the women were given a reduced dose.

Adult↗