| 1. |
- Blomqvist, Fredrik Lennart Rune, 1947, et al.
(författare)
-
Platelet aggregation in healthy women during normal pregnancy - a longitudinal study.
- 2019
-
Ingår i: Platelets. - : Informa UK Limited. - 1369-1635 .- 0953-7104. ; 30:4, s. 438-444
-
Tidskriftsartikel (refereegranskat)abstract
- Increased platelet activation is involved in obstetric complications such as preeclampsia and intrauterine growth retardation. It is of interest to study platelet aggregation during pregnancy, since increased aggregation theoretically could be a mechanism associated with placenta-mediated complications, which possibly could be prevented by drugs inhibiting platelet aggregation. There are, however, few robust studies describing platelet aggregation during normal pregnancy. The present longitudinal study was performed in order to study platelet aggregation during normal pregnancy resulting in a healthy child, during the puerperium and in nonpregnant, fertile women. Healthy, nonsmoking, pregnant women (n=104), aged under 39years and with BMI <35, were followed during pregnancy and postpartum. Twenty-seven nonpregnant, non-puerperal, fertile women were studied for comparison. Platelet aggregation was determined with multiple electrode impedance aggregometry and analyzed at inclusion, 4 times during pregnancy and after at least 3 months postpartum. Platelet aggregation postpartum was compared with gestational weeks 8-15 and 37-40, respectively, and with nonpregnant, fertile women. Hemoglobin, leucocyte count, platelet count, prothrombin time, and activated partial thromboplastin time were determined at inclusion in order to verify normal hemostasis. Activation of platelets by arachidonic acid, adenosine diphosphate (ADP), and thrombin receptor activating peptide (trap-6) resulted in less aggregation during pregnancy, compared with postpartum (p<0.03-<0.001). Platelet aggregation following activation by collagen was unchanged. A minor increase in aggregation as pregnancy continued was found related to ADP (p<0.021). Positive correlations were found between platelet counts and platelet aggregation. Postpartum platelet aggregation after activation with arachidonic acid, collagen, and trap-6 was lower than in the non-puerperal fertile state. Other hemostatic analyses were normal. In conclusion, there is a minor decrease in platelet aggregation after activation with arachidonic acid, trap-6, and ADP, measured with multiple electrode impedance aggregometry during normal pregnancy resulting in healthy babies, compared with the postpartum period. The small changes in platelet aggregation may be a consequence of a minor decrease in platelet count and probably lack clinical significance under normal conditions. Interindividual variations at certain time-points are substantial, which limits the usefulness of the multiple electrode impedance aggregometry for determining minor changes in platelet function.
|
|
| 2. |
- Blomqvist, Lennart, 1947, et al.
(författare)
-
Acetylsalicylic acid does not prevent first-trimester unexplained recurrent pregnancy loss: A randomized controlled trial
- 2018
-
Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349. ; 97:11, s. 1365-1372
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Recurrent pregnancy loss occurs in about 1% of fertile couples. Without proper evidence for an effect, different treatments have been used when no etiological factor has been detected. The present trial is the first randomized trial to compare 75 mg acetylsalicylic acid with placebo for women with recurrent pregnancy loss. Material and methods: This randomized, double-blind, placebo-controlled trial was conducted at a single center between 2008 and 2015. Recurrent pregnancy loss was defined as at least 3 consecutive first-trimester miscarriages within the couple. Women < 40 years old with a body mass index < 35 kg/m(2) were eligible if the workup was negative. Randomization was through a third party, who manufactured and delivered the study drugs, and occurred when fetal heartbeat was detected, to either 75 mg acetylsalicylic acid or placebo; 200 women in each group. Group allocation was concealed until all the study participants had a pregnancy outcome registered. All women attended the same control program. Primary outcome was live birth. Statistical analyses were according to intention-to-treat. Results: All 400 women completed the follow up. Live birth rate was 83.0% (n=166) and 85.5% (n=171) for the acetylsalicylic acid and placebo groups, respectively (P=0.58). The difference was -2.5% (95% CI -10.1% to 5.1%). The risk ratio was 0.97 (95% CI 0.89-1.06). Conclusions: Treatment with acetylsalicylic acid did not prevent recurrent miscarriage in women with at least three consecutive miscarriages in the first trimester, of unknown reasons and in the same relationship. The fertility prognosis is very good, the live birth rate being > 80% with or without acetylsalicylic acid.
|
|
| 3. |
- Blomqvist, Lennart, 1947, et al.
(författare)
-
Arachidonic acid-induced platelet aggregation and acetylsalicylic acid treatment during pregnancy in women with recurrent miscarriage, a post hoc study
- 2022
-
Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 33:2, s. 278-284
-
Tidskriftsartikel (refereegranskat)abstract
- In this post hoc study, arachidonic acid (AA)-induced platelet aggregation during pregnancy with and without acetylsalicylic acid (ASA) treatment was studied in 323 women with unexplained recurrent first-trimester miscarriage and in 59 healthy women with normal pregnancies. All women had normal AA-induced platelet aggregation in the non-pregnant state. Women with recurrent miscarriage were treated with 75 mg ASA or placebo daily. AA-induced platelet aggregation was measured with multiple electrode impedance aggregometry and presented in units (U), where 1 U = 10 aggregation units x minutes. There were no significant differences in platelet aggregation between placebo-treated women with recurrent miscarriage and healthy women. The mean differences were -0.7 (95%CI; -7.0; 5.6) U in the non-pregnant state, 3.8 (95%CI; -4.6; 12.2) U during the late first trimester and 1.7 (95%CI; -6.7; 10.3) U and 4.1 (95%CI; -3.9; 12.0) U during the early and late third trimester, respectively. ASA reduced platelet aggregation by median -84.0% (Q1; Q3; -89.8; -76.3), -79.9% (-84.7; -69.2) and -75.7% (-83.5; -49.5), respectively, during pregnancy. The degree of inhibition by ASA decreased during the third trimester (p < .0001). There were two (1.9%) complete non-responders to ASA and 32.1% with a partial response. The rate of subsequent miscarriage was not affected by ASA, which did not seem to influence the rate of early miscarriage if treatment was initiated when a viable pregnancy was detectable by ultrasound.
|
|
| 4. |
- Blomqvist, Lennart, 1947, et al.
(författare)
-
Preconceptual thyroid peroxidase antibody positivity in women with recurrent pregnancy losses may contribute to an increased risk for another miscarriage.
- 2023
-
Ingår i: Clinical endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 98:2, s. 259-269
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate preconceptual thyroid peroxidase antibody (TPO-ab) positivity and/or thyroid stimulating hormone (TSH) levels in the upper range of normal as risk factors for recurrent unexplained first-trimester miscarriage.A post-hoc study of a randomized trial, in which acetylsalicylic acid did not affect the risk of a new miscarriage.Women (n=483) with at least three unexplained recurrent first-trimester miscarriages investigated at a Swedish secondary referral center.The levels of TPO-ab and TSH were determined before pregnancy. The occurrence of a new first-trimester miscarriage was analyzed by logistic regression with adjustments when applicable, for age, number of previous miscarriages, obesity and the investigated covariates levels of TPO-ab and TSH.Including all first trimester miscarriages, odds ratio (OR) according to presence of TPO-ab was 1.60 (95% confidence interval [CI]; 0.99-2.57), after adjustment 1.54 (95% CI; 0.94-2.53). Very early (biochemical) pregnancy losses occurred more often in women with than without preconceptual TPO-ab (6.8% vs. 2.0%), OR 3.51 (95% CI; 1.15-10.71), after adjustment 2.91 (95% CI; 0.91-9.29). There was no association between TSH in the upper range of normal and a new miscarriage, adjusted OR 0.76 (95% CI; 0.32-1.83). A prediction model for a new miscarriage included number of previous miscarriages, woman's age and presence of TPO-ab.In women with at least three recurrent unexplained pregnancy losses, the presence of TPO-ab may contribute to an increased risk of a first-trimester miscarriage, possibly more pronounced in very early pregnancy. TSH levels 2.5-4.0 mU/L do not seem to increase the miscarriage risk.
|
|
| 5. |
- Rasmark Roepke, Emma, et al.
(författare)
-
Treatment efficacy for idiopathic recurrent pregnancy loss - a systematic review and meta-analyses
- 2018
-
Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:8, s. 921-941
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Medical treatment of women with idiopathic recurrent pregnancy loss is controversial. The objective was to assess the effects of different treatments on live birth rates and complications in women with unexplained recurrent pregnancy loss. Material and methods: We searched MEDLINE, Embase and the Cochrane Library, and identified 1415 publications. This systematic review included 21 randomized controlled trials regarding acetylsalicylic acid, low-molecular-weight heparin, progesterone, intravenous immunoglobulin or leukocyte immune therapy in women with three or more consecutive miscarriages of unknown cause. The study quality was assessed and data was extracted independently by at least two authors. Results: No significant difference in live birth rate was found when acetylsalicylic acid was compared with low-molecular-weight heparin or with placebo. Meta-analyses of low-molecular-weight heparin vs. control found no significant differences in live birth rate [risk ratio (RR) 1.47, 95% CI 0.83-2.61]. Treatment with progesterone starting in the luteal phase seemed effective in increasing live birth rate (RR 1.18, 95% CI 1.09-1.27) but not when started after conception. Intravenous immunoglobulin showed no effect on live birth rate compared with placebo (RR 1.07, 95% CI 0.91-1.26). Paternal immunization compared with autologous immunization showed a significant difference in outcome (RR 1.8, 95% CI 1.34-2.41), although the studies were small and at high risk of bias. Conclusion: The literature does not allow advice on any specific treatment for idiopathic recurrent pregnancy loss, with the exception of progesterone starting from ovulation. We suggest that any treatment for recurrent pregnancy loss should be used within the context of a randomized controlled trial.
|
|
| 6. |
- Blomqvist, Lennart, 1947
(författare)
-
Recurrent unexplained first-trimester miscarriage. Effects of acetylcalicylic acid, platelet aggregation and thyroid disease
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Recurrent unexplained first-trimester miscarriage. Effects of acetylsalicylic acid, platelet aggregation and thyroid disease. Lennart Blomqvist, Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden, 2019. Background/Aims: Recurrent pregnancy loss (RPL) occurs in 1-2% of fertile couples and about 50% of cases are unexplained. Impaired placental circulation, increased platelet aggregation, immunological factors and thyroid autoimmunity have been suggested to be involved. Other placenta-mediated complications have been reduced by inhibition of platelet aggregation with acetylsalicylic acid (ASA). The effect of ASA on RPL has been unclear. These studies aimed at investigating the effect of ASA treatment on RPL and arachidonic acid (AA)-induced platelet aggregation in women with RPL, as well as the effect of thyroid function by analyzing Thyroid Stimulating Hormone (TSH) and thyroid peroxidase antibodies (TPO-ab). Methods: Women (n=640) with at least three unexplained first-trimester miscarriages were screened for inclusion in a single-center, randomized, placebo-controlled trial (the ASA-RCT, Paper I). Four hundred women were given either 75 mg ASA or placebo daily, beginning at gestational week (gw) 6-7, when fetal heartbeat was detected by vaginal ultrasound. Treatment ended at the latest at gw 36. Treatment compliance was determined by analysis of AA-induced platelet aggregation using multiple electrode impedance aggregometry. All women underwent the same follow-up. Primary outcome was live birth rate (LBR). In order to define reference values for the multiple electrode impedance aggregometry (the Multiplate analyzer), a longitudinal study was conducted including 79 healthy, non-smoking pregnant women with normal pregnancies (Paper II). Platelet aggregation induced by AA, adenosine diphosphate (ADP), thrombin receptor activating peptide 6 (TRAP) and collagen (COL) were determined four times during pregnancy and three months postpartum. From the randomized population, 176 and 177 women, respectively, with normal AA-induced platelet aggregation before pregnancy and treated with ASA or placebo, were studied (Paper III). Platelet aggregation was determined before and during pregnancy and results in the randomized groups were compared with one another, as well as with those in the healthy controls from Paper II. From the screened and eligible population, 495 women with complete thyroid test analyses [thyroid stimulating hormone (TSH), free thyroxine (T4) and thyroid peroxidase antibodies TPO-ab] before pregnancy were included. Risk factors for a new miscarriage were studied, in particular associations with TPO-ab and TSH in the upper normal range. Results: In the ASA-RCT, all 400 randomized women completed the follow-up. LBR were 83.0% and 85.5% in the ASA and placebo groups, respectively. The mean difference was -2.5% (95% CI to -10.1% to 5.1%). The risk ratio was 0.97 (95% CI 0.89 to 1.06). In the longitudinal study of platelet aggregation during normal pregnancy, activation of platelets by AA, ADP and TRAP resulted in a minor decrease in platelet aggregation during pregnancy, compared with postpartum. COL-induced platelet aggregation was unchanged. A minor increase in platelet aggregation as pregnancy continued was found related to ADP. There were no significant differences in AA-induced platelet aggregation when placebo-treated women with RPL were compared with healthy women with normal pregnancies. ASA treatment significantly reduced platelet aggregation during pregnancy, compared with before pregnancy. Gradually increased platelet aggregation was seen in the majority of ASA-treated women as pregnancy progressed. There were only two complete non-responders to ASA. Miscarriage occurred more often in women with than without TPO-ab (25.7% vs 17.5%). There was no association between TSH in the upper normal range and a new miscarriage. Potential risk factors for a new miscarriage were age, number of previous miscarriages and presence of TPO-ab. Conclusions: ASA does not prevent a new miscarriage in women with at least three previous first-trimester miscarriages. AA-induced platelet aggregation seems to be similar in women with RPL and in healthy women with normal pregnancies. ASA, 75 mg daily, decreases AA-induced platelet aggregation in most women during pregnancy, but the effect diminishes as pregnancy progresses. TPO-ab, but not TSH in the upper normal range, may be associated with an increased risk of a new miscarriage.
|
|
| 7. |
- Torkzad, Michael R., et al.
(författare)
-
Magnetic resonance imaging and ultrasonography in diagnosis of pelvic vein thrombosis during pregnancy
- 2010
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 126:2, s. 107-112
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Pelvic deep vein thrombosis (DVT) is difficult to diagnose during pregnancy. In a two-center trial, we evaluated the agreement between ultrasonography and magnetic resonance imaging (MRI) in diagnosing the extent of DVT into the pelvic veins during pregnancy. MATERIALS AND METHODS: Pregnant women with proximal DVT were examined both with ultrasound and MRI as part of a study designed for treatment of DVT during pregnancy. Ultrasound was performed using color flow by specialist in vascular ultrasound with Doppler and compression techniques. The MRI sequences consisted of a 2D Time of Flight angiography with arterial flow suppression and maximum intensity projection reconstructions; a 3D, T1-w-prepared gradient echo sequence with fat saturation for thrombus imaging; a steady-state free precession sequence; and a Turbo-Spin-Echo. No contrast agent was used. Proportion of agreement (kappa) for detection of DVT in individual veins was measured for different ipsilateral veins and inferior vena cava. RESULTS: All 27 patients were imaged with both techniques at an average gestational age of 29 weeks (range 23-39). Three cases (11.5%) of DVT in the pelvic veins were missed on ultrasound but detected by MRI. The upper limit of the DVT was always depicted at a higher (20 cases, 65.4%) or the same level (seven cases, 34.6%) on MRI than on ultrasound. Agreement expressed as kappa was 0.33 (95% CI 0.27-0.40) demonstrating only fair agreement. In one woman the thrombus had propagated into the inferior vena cava, shown only on MRI. CONCLUSION: Our study suggests that in pregnant women there is only fair agreement between ultrasound and MRI for determination of extent of DVT into pelvic veins, with MRI showing consistently more detailed depiction of extension. Our results indicate that MRI has an important role as a complementary technique in the diagnosis of DVT during pregnancy.
|
|
