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Biomedical subjects

M Hellgren

Publications and source records attributed to M Hellgren.

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↗

Inverse association between plasma homocysteine, sulphonylurea exposure and physical activity: a community-based sample of type 2 diabetes patients in the Skaraborg hypertension and diabetes project.

AIM: This study aimed to investigate levels of Homocysteine (tHcy) and folate in a population-based sample of patients with type 2 diabetes. In particular, the study explored modifiable determinants such as treatment for diabetes, life style, glucose control and kidney function. PATIENTS AND METHODS: In a community-based surveillance of patients with type 2 diabetes, 196 men and 191 women were consecutively identified in primary care and characterized by cardiovascular disease (CVD) risk factors focusing on components in the metabolic syndrome. For categorical associations plasma tHcy was dichotomized using the upper 10 percentiles of the distribution. RESULTS: Treatment with sulphonylurea was associated with lower serum levels of tHcy compared to those on diet alone. The association was confined to women [odds ratio 0.14; confidence interval 0.03-0.8] and remained significant when differences in factors related to the metabolic syndrome, life style and previous CVD were accounted for, but was lost when adjusted for HbA1c. There was an inverse dose-related association between physical activity and plasma levels of tHcy (men p = 0.006, women p = 0.034), and a positive association with serum levels of creatinine (men p = 0.004, women p < 0.001). CONCLUSIONS: The association with physical activity might be one contributing explanation for its well-known protective effect on cardiovascular disease. The over risk for vascular complications in diabetic patients with kidney disease may be partially explained by high levels of tHcy and should be further explored. Prospective studies are particularly needed on various treatment for type 2 diabetes and tHcy to explore possible implications for clinical procedures and for public health.

Aged↗

The oral direct thrombin inhibitor, ximelagatran, an alternative for anticoagulant treatment during the puerperium and lactation.

OBJECTIVE: To determine the excretion of the oral direct thrombin inhibitor (oral DTI), ximelagatran, and its active form, melagatran, in human milk, and to thus evaluate the potential exposure of breastfed infants to melagatran. DESIGN: An open, single dose, single centre study. SETTING: Department of Antenatal Care, Primary Health Care South Bohuslän and Institute for the Health of Women and Children, Göteborg University, Sweden. SAMPLE: Seven healthy Caucasian breastfeeding women who were at least two months postpartum were studied. METHODS: The concentrations of ximelagatran, its two intermediates, and melagatran were determined using liquid chromatography-mass spectrometry, with the limit of quantification of 2 nmol L(-1) for human milk and 10 nmol L(-1) for plasma concentrations. MAIN OUTCOME MEASURES: Concentrations of ximelagatran, its intermediates and melagatran were measured in breast milk over 72 hours, and in plasma over 12 hours, after a single oral 36 mg dose of ximelagatran. RESULTS: Neither ximelagatran nor its intermediates were detected in human breast milk. Only trace amounts of melagatran were detected. The mean cumulative amount of melagatran excreted into breast milk over the 72-hour period after dosing with oral ximelagatran was 0.00091% of the administered dose of ximelagatran. Ximelagatran was well tolerated, with no clinically relevant changes in laboratory variables or vital signs. CONCLUSIONS: Trace levels of melagatran are excreted in human breast milk following administration of the oral DTI ximelagatran. The exposure of breastfed infants to melagatran appears to be low and is therefore unlikely to be of clinical concern.

Administration, Oral↗

Fluticasone propionate aqueous nasal spray in pregnancy rhinitis.

Pregnancy rhinitis is a common condition with longstanding nasal congestion; troublesome for the mother, possibly also affecting the fetus. There is need for a safe, effective treatment. Nasal corticosteroids, indisputable in other types of rhinitis, have not been evaluated in pregnancy rhinitis. In this placebo-controlled, randomized, double-blind study with parallel groups, we evaluated the effect of 8 weeks of treatment with fluticasone propionate aqueous nasal spray in 53 women with pregnancy rhinitis. Daily symptom scores and nasal peak expiratory flow, as well as acoustic rhinometry before and after treatment, did not show any difference between the groups. Placebo resulted in 6/27 responders, compared with 5/26 for active treatment. There was no detectable influence on maternal cortisol as measured by morning S-cortisol and overnight 12-h-U-cortisol, or any difference in ultrasound measures of fetal growth or pregnancy outcome. Altogether, our study indicates no significant effects of the treatment described here.

Administration, Intranasal↗

Sonoclot signature during normal pregnancy.

OBJECTIVE: The Sonoclot analyser provides global measurement of haemostasis, including plasma coagulation, platelet function and fibrinolysis. Benefits of its use in cardiovascular and hepatic surgery are well-documented and it may be useful in managing obstetric complications. The aim of this study was to determine ranges of the Sonoclot variables for normal pregnancy. DESIGN: Prospective and longitudinal study. SETTING: Antenatal outpatient clinic, university hospital. PATIENTS: Forty-seven healthy women were studied; forty-two completed normal pregnancies and gave birth to healthy infants. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Sonoclot signatures were performed at 10-15, 32-34 and 38-40 weeks of gestation and at 8 weeks postpartum. Haemoglobin concentration, haematocrit, platelet count, fibrinogen and activated partial thromboplastin time (APTT) were analysed with normal results. Sonact time and peak time were significantly decreased and clot rate and secondary rate were significantly increased during pregnancy compared with 8 weeks postpartum, indicating hypercoagulability. There were no significant changes in these variables during pregnancy. There were no changes in peak amplitude and downward rate. A significant correlation was found between sonact time and APTT, and between clot rate and APTT. CONCLUSIONS: We found the Sonoclot analyser simple to handle and the signatures easy to interpret. The ranges for the Sonoclot variables apply throughout pregnancy. The ranges for sonact time, clot rate, secondary rate and peak time during pregnancy differed from the ranges at 8 weeks postpartum.

Adult↗

The incidence of pregnancy rhinitis.

The purpose of this study was to define the cumulative incidence of pregnancy rhinitis, and to study whether smoking, asthma, hayfever or month of conception are risk factors. A questionnaire was delivered during 1 year in 10 antenatal care centers in one Swedish county. Questions were asked by midwives on the ordinary check-up visits throughout pregnancy. Five centers with response rates of 70% or more, including 599 women, were evaluated. The cumulative incidence of pregnancy rhinitis was 22%. Smokers had a significantly increased incidence with a relative risk enhancement of 69%, whereas hayfever, asthma, and month of conception had no statistically significant influence on incidence. Pregnancy rhinitis was shown to appear at any time during gestation.

Adolescent↗

APC resistance and other haemostatic variables during pregnancy and puerperium.

Forty-eight healthy pregnant women were studied prospectively and longitudinally. Blood sampling was performed at 10-15, 23-25, 32-34 and 38-40 weeks of gestation, within one week and at eight weeks postpartum. Classic and modified activated protein C ratio decreased as pregnancy progressed. In the third trimester 92% of the ratios measured with the classic test were above the lower reference level whereas all modified test ratios were normal. Slight activation of blood coagulation was shown with increased levels of prothrombin fragment 1+2, soluble fibrin and D-dimer. Fibrinogen, factor VIII and plasminogen activator inhibitor type I and type 2 increased. Protein S and tissue plasminogen activator activity decreased. Protein C remained unchanged. No correlation was found between the decrease in classic APC ratio and changes in factor VIII, fibrinogen, protein S, prothrombin fragment 1+2 or soluble fibrin, nor between the increase in soluble fibrin and changes in prothrombin fragment 1+2, fibrinogen and D-dimer.

Activated Protein C Resistance↗

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↗

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↗

Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives.

OBJECTIVE: Inherited resistance to activate protein C, which is caused by a single factor V gene mutation, is a frequent risk factor for thrombosis. The purpose of this study was to determine the prevalence of activated protein C resistance in women with thromboembolic complications that had occurred in connection with pregnancy or use of oral contraceptives. STUDY DESIGN: Activated protein C resistance was analyzed in women with previous thromboembolic complications in connection with pregnancy (n = 34) or oral contraceptives (n = 28), in healthy fertile women (n = 57), and in women during normal pregnancy (n = 18). Results of the activated protein C resistance test were expressed as activated protein C ratios, values < 2 indicating activated protein C resistance. RESULTS: Activated protein C resistance was found in almost 60% of women with thromboembolic complications during pregnancy and in around 30% of women with thromboembolic complications during treatment with oral contraceptives. In nonpregnant controls approximately 10% had activated protein C resistance. In normal pregnancy activated protein C ratios were similar to those of normal controls. CONCLUSIONS: Activated protein C resistance, which is caused by a genetic defect in the factor V gene, was found to be highly prevalent in women with a history of thromboembolic complications during pregnancy. The gene defect is common in the general population, and the results evoke the question whether it would be reasonable to perform general screening for activated protein C resistance early during pregnancy or before prescription of oral contraceptives.

Adolescent↗

Calcium homeostasis in pregnancy during long-term heparin treatment.

OBJECTIVE: To investigate the effect of subcutaneous heparin treatment on calcium homeostasis in pregnancy. DESIGN: A longitudinal case-control observational study. SETTING: Department of Obstetrics and Gynaecology, Karolinska Hospital, Stockholm, Sweden. SUBJECTS: 36 pregnant women with previously verified thromboembolic complications and 23 healthy pregnant control women similar in age, parity, weight, and smoking habit. INTERVENTIONS: Thromboprophylaxis during pregnancy and 6 weeks post partum was given with subcutaneous heparin twice daily to the 36 women with a history of thromboembolic complications, 16 received an average dose of 24,500 IU/day and 20 a mean dose of 17,300 IU/day. Venous blood and urine samples were obtained every 4 weeks. MAIN OUTCOME MEASURES: Serum concentrations of total calcium, ionized calcium, calcitonin and urinary calcium. RESULTS: Women on high-dose heparin treatment showed significantly higher concentrations of total and ionized calcium and of calcitonin in serum and significantly lower concentrations of calcium in urine than did 23 normal pregnant controls. The differences were most pronounced in the third trimester. The results obtained in the low-dose heparin group were between those in the high-dose and the control groups. At 8 weeks postpartum there were no significant differences between the heparin-treated women and the controls. No significant differences were found during pregnancy in haematocrit, liver or renal function, serum levels of albumin, phosphate, magnesium, alkaline phosphatase, parathyroid hormone or urinary cyclic AMP. CONCLUSIONS: Heparin treatment during pregnancy results in changes in calcium homeostasis and a dose-dependent response is suggested.

Adult↗

Osteopenia in pregnancy during long-term heparin treatment: a radiological study post partum.

Osteopenia, sometimes with compression fractures of the spine, is a side-effect of long-term heparin treatment. The frequency is unknown. In this study, 70 women were given subcutaneous heparin as therapy for, or prophylaxis against, thromboembolism during pregnancy. All, except two, were examined by X-ray of the spine and hip first week post partum. The duration of treatment and the dosage of heparin varied. There were 12 (17%) with obvious osteopenia, including two women with multiple fractures of the spine (3%). Re-examination 6-12 months post partum showed that the changes were reversible in most cases. Another 18 women were examined about three years after heparin treatment during pregnancy. No obvious osteopenia was found among them or in a control group of 30 women examined in the first week post partum. The degree of osteopenia was not correlated with either the heparin dose or the duration of treatment. Women treated with heparin in consecutive pregnancies do not seem to have an increased risk of osteopenia.

Adult↗

Haemostatic changes during continuous oestradiol-progestogen treatment of postmenopausal women.

To identify changes in haemostatic balance during continuous oestradiol-progestogen treatment, 60 postmenopausal women with climacteric complaints, mean age 55.4 years (range 44-68) were randomly allocated to receive one of four hormone replacement regimens for one year. All four formulations were administered daily and continuously, each contained 2 mg of 17 beta-oestradiol in combination with either norethisterone acetate, 1 mg (group A) or 0.5 mg (group B) or megestrol acetate, 5 mg (group C) or 2.5 mg (group D). No significant changes occurred during treatment within or between the groups in platelet count, fibrinogen and 2-antiplasmin. Activated partial thromboplastin time was shortened (P less than 0.05) in group D and a decline in factor VII activity and antigen (P less than 0.001) and in ATIII activity (P less than 0.05) was noted in group A. Protein C tended to decline in all treatment groups but statistically significant changes were noted only in groups A and C. Two women developed crural thrombosis during the observation period.

Adult↗

Metabolic effects of continuous estradiol-progestin therapy in postmenopausal women.

Sixty postmenopausal women with climacteric complaints were randomly allocated to four treatment groups. Without interruption, each patient was given one tablet daily containing 2 mg 17 beta-estradiol along with either norethisterone acetate 1 mg and 0.5 mg or megestrol acetate 5 mg and 2.5 mg. Blood samples were obtained before treatment and then after 1, 4, and 12 months of treatment. Serum was analyzed for cholesterol and triglycerides in serum and for cholesterol in the ultracentrifugally separated lipoprotein fractions of very low-density lipoproteins, low-density lipoproteins, and high-density lipoproteins. Significant reductions of serum cholesterol were found in all treatment groups except for that given 2.5 mg megestrol acetate. After 1 and 4 months of treatment, low-density lipoprotein cholesterol decreased 7-22%, whereas high-density lipoprotein cholesterol was reduced by 2-16% in the four groups. No significant differences could be demonstrated among the groups in low-density lipoprotein cholesterol or high-density lipoprotein cholesterol during treatment, as assessed by analysis of variance. Thus, cholesterol metabolism was equally influenced by both progestin types. Accordingly, the clinical efficacy and acceptance would decide the preparation to be advocated for women in need of hormone replacement therapy.

Adult↗