PubMed Health⌕ Search

Biomedical subjects

K Bremme

Publications and source records attributed to K Bremme.

At least 19 recordsLinked to original sources

Preanalytical conditions that affect coagulation testing, including hormonal status and therapy.

Preanalytical conditions, be they due to the individual's physiologic state or to exogenous factors, can affect coagulation factors, in either a transient or a persistent manner, and need to be considered in laboratory testing. These conditions include physical and mental stress, diurnal variation, hormone levels and posture at the time of blood drawing. While testing of these factors has not been exhaustive and some results are conflicting, guidelines for testing conditions can be given.

Anticoagulants↗

Treatment with combined oral contraceptives induces a rise in serum C-reactive protein in the absence of a general inflammatory response.

BACKGROUND: The role of inflammation in the pathogenesis of cardiovascular disease is well established. C-reactive protein (CRP) is the strongest independent predictor of myocardial infarction and stroke in women. Recent studies have indicated that CRP levels are raised during use of combined oral contraceptives (COCs). OBJECTIVES: The aim of the study was to investigate the effect of COCs on serum CRP levels and to indicate the underlying mechanisms of an expected increase. METHOD: In a prospective randomized cross over-study 35 women used two different preparations of COC, one second and one third generation. Serum levels of CRP, serum amyloid A (SAA), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), antibodies against oxidized LDL, insulin and insulin-like growth factor-I (IGF-I) along with insulin-like growth factor binding protein-1 (IGFBP-1) and IGFBP-3 were analyzed before and during the two treatments. E-selectin, von Willebrand factor and factor VIII concentrations in plasma were also measured. RESULTS: A rise in serum CRP was observed during both treatments; the median level increased from 0.45 mg L(-1) at baseline to 1.48 mg L(-1) with second generation and to 2.02 mg L(-1) with third generation COC. The serum levels of SAA increased slightly during treatment with the third generation COC. IL-6 and TNFalpha were unaffected by treatment. Both preparations lowered IGF-I and raised IGFBP-1 and IGFBP-3 concentrations. CONCLUSION: The raised serum CRP concentration during treatment with COCs appears to be related to a direct effect on hepatocyte CRP synthesis and does not reflect IL-6 mediated inflammation, endothelial activation or induction of insulin resistance.

Adolescent↗

Ro52, Ro60 and La IgG autoantibody levels and Ro52 IgG subclass profiles longitudinally throughout pregnancy in congenital heart block risk pregnancies.

Congenital heart block occurs in fetuses of Ro/SSA and La/SSB positive women. To investigate the stability of maternal autoantibody levels during pregnancy, we followed Ro52, Ro60 and La autoantibody IgG level variation and Ro52 subclass profiles longitudinally in selected congenital heart block risk pregnancies. Serum samples were obtained from 12 Ro/La positive women diagnosed with a systemic rheumatic disease and followed on average 60 months (range two to 84) which included 13 pregnancies. Seven children were affected by neonatal lupus, whereof four developed complete congenital heart block. Serum was also collected from the babies at birth. Ro52, Ro60 and La IgG as well as subclass antibodies were analysed by ELISA using recombinant antigens. Six Ro/La negative rheumatic patients were included as controls for antibody levels during pregnancy. Ro52, Ro60 and La IgG levels decreased progressively from early to late pregnancy, significantly for Ro52 and Ro60 (P < 0.01). No peaks or persistent elevation of antibody levels were noted in any of the CHB risk pregnancies. Ro52 IgG1 antibody levels were significantly higher than IgG2 (P < 0.01), IgG3 (P < 0.01) and IgG4 (P < 0.05) levels in the mothers during pregnancy. Ro52 IgG1 and IgG4 levels decreased significantly from early to late pregnancy (P = 0.02), while levels of IgG2 and IgG3 were low and the decrease was not significant. All IgG subclasses were transferred to the children. We conclude that maternal levels of Ro52, Ro60 and La autoantibodies tended rather to decrease than to increase during pregnancy.

Adult↗

Sex hormone--binding globulin--a surrogate marker for the prothrombotic effects of combined oral contraceptives.

OBJECTIVE: The purpose of this study was to investigate the plausibility of serum sex hormone-binding globulin (SHBG) concentration as a risk marker for venous thromboembolism (VTE) during use of combined oral contraceptives (COC). Study design This was a prospective, randomized cross-over study. Thirty-five women were treated with COCs containing the same amount of ethinyl estradiol and either levonorgestrel (LNG/EE) or desogestrel (DG/EE). Serum SHBG and markers of hemostasis were determined before and after 2 months on each treatment. RESULTS: SHBG increased significantly with both preparations. Treatment with DG/EE caused more pronounced prothrombotic changes in hemostatic parameters than LNG/EE. With both treatment regimens, there was a significant correlation between changes in resistance to activated protein C (APCr) and changes in plasma SHBG. CONCLUSION: The correlation between SHBG and the well-established risk factor APCr might indicate the usefulness of SHBG as a risk marker for VTE during COC treatment.

Adolescent↗

Antibodies against platelet-activating factor and platelet-activating factor-like lipids are raised in women with primary recurrent abortion.

OBJECTIVE: The purpose of this study was to determine the antibody levels against platelet-activating factor (PAF), PAF-like lipids lysophosphatidylcholine (LPC), cardiolipin (CL), and oxidized low-density lipoprotein (LDL) in recurrent abortion. STUDY DESIGN: Eigthy-five women with a history of at least 3 recurrent spontaneous abortions (55 women with primary abortion [31.4+/-5.1 years old]; 30 women with secondary abortion [33+/-4.5 years old]) were compared with 48 age-matched control subjects (33+/-4.4 years old) who had delivered without complications. Antibodies were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Antibodies against PAF and antibodies against oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC) were raised significantly in the group with primary abortion, as compared to control subjects (P<.05) and not significantly higher than in secondary abortion; antibodies against oxidized LDL, LPC, or CL levels did not differ between groups. CONCLUSION: Antibodies against platelet-activating factor and antibodies against platelet-activating factor-like lipid oxPAPC are associated with primary recurrent abortion and may function as novel disease markers. Whether these antibodies also are pathogenic (eg, by interacting with endothelial cells in placenta or by interfering with platelet-activating factor during embryonal development) remains to be shown.

Abortion, Habitual↗

Increased hemostasis potential persists in women with previous thromboembolism with or without APC resistance.

BACKGROUND: Activated thrombin generation and depressed fibrinolysis due to the presence of activated protein C (APC) resistance with or without factor (F)V Leiden mutation are associated with development of deep venous thrombosis (DVT). OBJECTIVE: A better understanding of the mechanism behind the risk of recurrence of DVT, using our new, recently developed assay of overall hemostasis potential (OHP). PATIENTS AND METHODS: Levels of OHP, as well as APC resistance and FV Leiden mutation, were determined in 88 women (cases) who had previously experienced DVT in connection with pregnancy, and in 25 young healthy individuals (controls). Clotting time and clot lysis time were also investigated. RESULTS: OHP levels in the patients were increased compared with the controls. In the cases with APC resistance and the Leiden mutation this imbalance in hemostasis potential was more severe than in those without. The group with the more severe imbalance had shorter clotting times and longer clot lysis times. CONCLUSIONS: A procoagulant state perseveres in patients with a history of pregnancy-related DVT, even after the symptomatic phase is over. The mechanisms behind such an imbalance in overall hemostasis are enhanced thrombin generation and depressed fibrinolysis. These findings may underscore the need for thromboprophylaxis to prevent recurrence of thromboembolism in risk situations.

Activated Protein C Resistance↗

The assay of overall haemostasis potential used to monitor the low molecular mass (weight) heparin, dalteparin, treatment in pregnant women with previous thromboembolism.

The present study aimed to assess whether the determination of overall haemostasis potential (OHP) in plasma is powerful enough to monitor the prophylactic effect of low molecular mass heparin (dalteparin, Fragmin) in patients with increased risk of thromboembolitic events. In five pregnant women who had a history of deep venous thrombosis, OHPs were kinetically investigated in gestation weeks 32-35 twice during 24 h (before injection and after 1, 2, 4, 6, 8, 10, 12, 14, 16 and 24 h). Levels of anti-activated factor X (anti-FXa), reflecting dalteparin activity, as well as prothrombin fragments 1 + 2 (F1 + 2) and soluble fibrin, were also measured. In converse relation to changes of anti-FXa, OHPs decreased reaching the lowest level between 2 and 8 h after the injection, and then rose again, returning to the levels around those before the administration. There were no significant variations in concentrations of F1 + 2 and soluble fibrin during the observation course. These findings indicate that the OHP assay can monitor the alteration of haemostatic balance under the dalteparin influence while anti-FXa only shows the activity of the drug present in plasma. Additionally, analyses of thrombin generation markers are not useful to screen immediate changes in the haemostatic system after dalteparin injection.

Adult↗

Does thrombin activatable fibrinolysis inhibitor (TAFI) contribute to impairment of fibrinolysis in patients with preeclampsia and/or intrauterine fetal growth retardation?

Thrombin Activatable Fibrinolysis Inhibitor (TAFI) is a relatively recently described glycoprotein (MM 55 KDa) that can be converted into its active form by the thrombin/thrombomodulin complex and potentially inhibits fibrinolysis. Since it represents a link between coagulation and fibrinolysis, TAFI can be expected to play a part in various clinical conditions associated with a thrombotic tendency. Preeclampsia (PE) and intrauterine fetal growth retardation (IUFGR) are fairly common complications of pregnancy that are characterized by hemostatic abnormalities. TAFI antigen and its influence on hemostasis was investigated in 46 women with PE and/or IUFGR and in 16 normal pregnancies. We found a significant decrease of TAFI antigen in the patient group. Using the recently described method Overall Hemostatic Potential (OHP) in plasma we measured clot lysis time (CLT) and overall fibrinolytic potential (OFP). We found that CLT is prolonged and OFP decreased in patients with PE and/or IUFGR. Since OFP did not increase after addition of the specific inhibitor of TAFI (potato tuber carboxypeptidase inhibitor), it seems that TAFI does not contribute to the impairment of fibrinolysis in these patients. Since serum albumin was decreased together with presence of proteinuria and aminotransferases were increased in the patients, it seems that one explanation for the decrease in TAFI could be reduced hepatic synthesis and an increased loss in urine. It an be speculated that this mechanism can prevent more serious thrombotic complications in patients with PE and/or IUFGR.

Adult↗

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↗

Fibronectin is a marker for organ involvement and may reflect the severity of preeclampsia.

OBJECTIVE: We have studied whether plasma fibronectin is related to a rise in blood pressure during normal pregnancy, whether it can be used for the early prediction of preeclampsia, and whether plasma fibronectin is a marker for organ involvement in preeclampsia. STUDY DESIGN: Two hundred twenty-eight healthy pregnant nullipara women were examined prospectively during pregnancy. Analyses of fibronectin in plasma were performed in pregnancy weeks 16, 24, 28, 32, and 36. During the same period, 177 patients with suspected preeclampsia and/or intrauterine growth retardation (IUGR) were tested for plasma fibronectin, mainly in the third trimester. RESULTS: In the normal population of pregnant women (n=222/228), fibronectin levels were 0.35 +/- 0.06 g/L in pregnancy week 16 and 0.43 +/- 0.12 g/L in week 36. These levels showed a positive correlation to blood pressure elevation during pregnancy (r=0.21, p=0.006). The six patients in this group (n=6/228) who later developed preeclampsia had higher fibronectin values 0.42 +/- 0.07 g/L already in week 16 (p=0.023). In the population of women with suspected preeclampsia (preeclampsia, n=129; IUGR alone, n=17; hypertension or proteinuria during pregnancy, n=31), fibronectin values were significantly higher, 0.75 +/- 0.27 g/L than in the normal population. Patients with preeclampsia and laboratory signs of organ involvement (n=56) showed significantly higher fibronectin values (0.85 +/- 0.27 g/L) compared to preeclampsia without organ involvement (n=73) [0.76 +/- 0.22 g/L (p=0.03)]. CONCLUSION: Our data show that fibronectin is related to blood pressure in pregnancy. Fibronectin values in women who develop preeclampsia are elevated already in pregnancy week 16 and were higher in those with laboratory signs of organ involvement.

Adolescent↗

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↗

Hypercoagulation in surgical postmenopausal women having hormone replacement with overdose estradiol.

A benefit of estradiol replacement preventing coronary heart disease (CHD) after menopause has been suggested by clinical investigations. In the department of gynecology at our hospital, we met by chance eight senior women who were hysterectomized due to different benign gynecological disorders. Acting on their own, they took a daily dose of estradiol valerate as high as 8-50 mg for 3 years, in comparison with 1-2 mg used in routine hormonal replacement therapy. We were interested to assess whether the overdose estrogen disturbs the hemostatic function, thus losing the favorable effect on CHD occurrence. Plasma levels of some procoagulants/anticoagulants were assayed in the eight women with replacement therapy and the results were compared with those of seven age-matched senior women and of 14 young healthy women with normal menstrual cycles. Using a new laboratory method recently developed by us, the overall hemostatic potential, shown as a single parameter (Abs-sum), was also determined. Results showed that high-dose estradiol activated coagulation and depressed fibrinolysis, leading to the net effect of elevated overall hemostatic potential. Thus, the overdose estradiol replacement may not be beneficial in preventing CHD after menopause, or it may even increase the risk due to the hypercoagulable state induced therefrom.

Adult↗

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↗

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↗

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↗