Thrombophilia and its impact on pregnancy

2008 ◽  
Vol 28 (03) ◽  
pp. 130-134 ◽  
Author(s):  
I. Pabinger
Keyword(s):  
Risk Factors ◽  
Molecular Weight ◽  
Pregnancy Outcome ◽  
Prospective Studies ◽  
Pregnancy Complications ◽  
Low Molecular Weight Heparin ◽  
Pregnancy Loss ◽  
Factor V Leiden ◽  
Low Molecular Weight ◽  
Increased Risk

SummaryIn recent years thrombophilia has gained much attention as a risk factor for pregnancy complications. Whereas there is an established correlation between antiphospholipid-antibodies and pregnancy loss, data for other risk factors of thrombosis are less well established. Data suggest associations with antithrombin deficiency, hyperhomocysteinemia and also with factor V Leiden, prothrombin G20210A variation and protein S-deficiency. The association of thrombophilia with pre-eclampsia is still under discussion. A limited number of prospective studies did not reveal an increased risk for pregnancy complications in unselected women with thrombosis risk factors. In a single study low molecular weight heparin seemed to have a positive effect on pregnancy outcome after previous single or recurrent abortions. Experience in prevention of pre-eclampsia by administration of prophylactic heparin is very limited. Data on pregnancy complications in women with known heritable thrombophilia or a history of thrombosis are inconsistent as well. These women usually have a favourable pregnancy outcome. Conclusion: Thrombophilia screening might be justified in women with pregnancy loss. Treatment with low molecular weight heparin might be considered for those with pregnancy loss and thrombophilia. Further prospective studies and controlled interventional trials are urgently needed.

scholarly journals POS0737 LOW PRECONCEPTIONAL COMPLEMENT LEVEL IS RELATED WITH ADVERSE OBSTETRIC OUTCOME IN A MULTICENTRIC COHORT OF PREGNANCY IN PATIENTS WITH APS AND APL POSITIVITY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 619.2-620
Author(s):  
D. Lini ◽  
C. Nalli ◽  
L. Andreoli ◽  
F. Crisafulli ◽  
M. Fredi ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Complement Activation ◽  
Pregnancy Complications ◽  
Antiphospholipid Antibodies ◽  
Pregnancy Loss ◽  
Adverse Pregnancy Outcome ◽  
Obstetric Outcome ◽  
Complement Level ◽  
Increased Risk ◽  
Adverse Pregnancy

Background:The role of complement in the antiphospholipid (aPL) related pathology has been widely studied in animal models. Antiphospholipid antibodies can induce fetal loss in experimental animals but mice deficient in specific complement components (C4, C3, C5) appear somehow protected. In addition, in pregnant mice injected with aPL, antibody deposition has been found at decidual level causing focal necrosis, apoptosis and neutrophil infiltrates and supporting aPL pathogenetic potential. On the other hand, human studies did find hypocomplementemia associated to pregnancy complications in patients with obstetric antiphospholipid syndrome (APS). These results, however, are not unanimously confirmed and, in addition, some studies only show increased levels of complement activation products (i.e. Bb) and not decreased levels of C3 and/or C4. A recently study focusing on complement level in early pregnancy and before pregnancy showed a significant correlation with pregnancy complications and loss in a large cohort of primary APS.Objectives:To investigate if the simple detection of low C3 and/or C4 could be considered a risk factor for adverse pregnancy outcome in APS and aPL carriers pregnancies.Methods:We performed a multicentric study including patients from 10 Italian and 1 Russian Centers. Data on pregnancies in women with primary APS (n=434) and asymptomatic carriers with persistently positive aPL but not fulfilling clinical criteria for APS (n=218) were retrospectively collected. Serum C3 and C4 levels were evaluated by nephelometry; hypocomplementemia was defined by local laboratory reference values. Statistical analysis was performed using GraphPad.Results:Preconceptional complement levels and gestational outcome were available for 107 (25%) pregnancies in APS out of 434 and for 196 (90%) pregnancies in aPL carriers women out of 218. In pregnancies with low preconceptional C3 and/or C4, a significantly higher prevalence of pregnancy losses was observed (p=0.019). A subgroup analysis focusing on triple aPL positive patients was also performed. Preconceptional low C3 and/or C4 levels were found to be associated with an increased rate of pregnancy loss (p = 0.027) in this subgroup also. Otherwise, adverse pregnancy outcomes in single or double aPL positive women were not related to preconception complement levels (p = 0.44) (Table 1). Of note, all the pregnancy losses in the triple positive group occurred in patients treated with low dose aspirin and low molecular weight heparin from the time of positive pregnancy test.Conclusion:Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of adverse outcome. This has been seen only in in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss. test positivity.References:[1]De Carolis S, et al. Complementemia and obstetric outcome in pregnancy with antiphospholipid syndrome. Lupus (2012) 21:776–8.[2]Kim MY, et al. Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies. Ann Rheum Dis (2018) 77:549–55.[3]Fredi M, et al. Risk Factors for Adverse Maternal and Fetal Outcomes in Women With Confirmed aPL Positivity: Results From a Multicenter Study of 283 Pregnancies. Front Immunol. 2018 May 7;9:864.Triple aPL positivitySingle or double aPL positivityGestational outcomeLow C3/C4 (n=49)Normal C3/C4(n=17)pLow C3/C4 (n=57)Normal C3/C4(n=165)pTerm live birth (>37w)15 (31%)6 (35%)ns34 (60%)110 (67%)nsPreterm live birth (≤37w)22 (45%)11 (65%)ns15 (26%)38 (23%)nsPregnancy losses (abortion and miscarriages)12 (24%)0 (0%)0.0278 (14%) 17 (10%)nsDisclosure of Interests:None declared

Thrombin generation and low-molecular-weight heparin prophylaxis in pregnant women with thrombophilia

2015 ◽  
Vol 113 (02) ◽  
pp. 283-289 ◽  
Author(s):  
Anna Selmeczi ◽  
Rachel E. J. Roach ◽  
Csaba Móré ◽  
Zoltán Batta ◽  
Jolán Hársfalvi ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Pregnant Women ◽  
Low Molecular Weight Heparin ◽  
Thrombin Generation ◽  
Factor Xa ◽  
Peak Effect ◽  
Low Molecular Weight ◽  
Endogenous Thrombin Potential ◽  
Increased Risk ◽  
Optimal Approach

SummaryPregnancy is associated with increased risk of venous thromboembolism, especially in the presence of thrombophilia. However, there is no consensus on the optimal approach for thromboprophylaxis in this population. Recent evidence suggests that thrombin generation correlates with the overall procoagulant state of the plasma. Our aim was to evaluate thrombin generation in a prospective cohort of thrombophilic pregnant women, and investigate the effectiveness of low-molecular- weight heparin (LMWH) prophylaxis in pregnancy. Women with severe (n=8), mild (n=47) and no (n=15) thrombophilia were followed throughout their pregnancies. Thrombin generation was evaluated in each trimester as well as five days and eight weeks postpartum (as a reference category). In women undergoing LMWH prophylaxis, thrombin generation and anti-Factor-Xa activity were measured just before and 4 hours after administration (peak effect). Thrombin generation was determined using Technothrombin TGA assay system. For the analysis, median peak thrombin and endogenous thrombin potential were used. Peak thrombin and endogenous thrombin potential were increased during pregnancy compared to the non-pregnant state with the highest results in the severe thrombophilia group. In women receiving LMWH prophylaxis a decrease was observed in thrombin generation at peak effect but over the progression of pregnancy the extent of this decrease reduced in a stepwise fashion. Our results show that thrombin generation demonstrates the hypercoagulable state in thrombophilic pregnancies. In addition, we found the effect of LMWH prophylaxis to progressively decrease with advancing stages of pregnancy.

Gestational Outcome in Thrombophilic Women with Recurrent Pregnancy Loss Treated by Enoxaparin

2000 ◽  
Vol 83 (05) ◽  
pp. 693-697 ◽  
Author(s):  
R. Hoffman ◽  
Z. Blumenfeld ◽  
Z. Weiner ◽  
J. S. Younis ◽  
B. Brenner
Keyword(s):  
Molecular Weight ◽  
Live Birth ◽  
Antithrombotic Therapy ◽  
Low Molecular Weight Heparin ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Living Child ◽  
Low Molecular Weight ◽  
Single Living ◽  
Acquired Thrombophilia

SummaryInherited and acquired thrombophilia are associated with recurrent pregnancy loss (RPL). We have evaluated the efficacy and safety of the low molecular weight heparin enoxaparin in 50 women, (mean age 26 ± 3 years) with RPL (>3 losses in 1st, >2 losses in 2nd and >1 loss in 3rd trimester) who were found to harbor thrombophilia. Twentyseven had a solitary thrombophilic defect, and twenty-three women had combined thrombophilic defects: 17 – two defects and 6 – three defects. Following diagnosis of thrombophilia, sixty-one subsequent pregnancies were treated with the low molecular weight heparin enoxaparin throughout gestation until 4 weeks after delivery. Dosage was 40 mg/day in women with solitary defect and 80 mg/day in combined defects. Aspirin, 75 mg daily was given in addition to enoxaparin to women with antiphospholipid syndrome. Forty-six out of 61 (75%) gestations treated by enoxaparin resulted in live birth compared to only 38/193 (20%) of the untreated pregnancies in these 50 women prior to diagnosis of thrombophilia (p <0.00001). In 23 women without a single living child following 82 untreated gestations, antithrombotic therapy resulted in 26/31 (84%) successful deliveries (p <0.0001). In 20 women with a prior living child, antithrombotic therapy improved successful delivery from 33/86 (38%) to 20/21 (95%) (p <0.0001). Enoxaparin dose of 40 mg/day resulted in live birth in 24/35 (69%) of gestations, compared to 19/23 (83%) gestations in women treated with 80 mg/day (p = 0.37). Only one thrombotic episode and one mildbleeding episode were noticed during enoxaparin therapy. Enoxaparin is safe and effective in prevention of pregnancy loss in women with inherited and acquired thrombophilia.

scholarly journals Evaluation and Management of Women who Have Experienced Stillbirth in Their Previous Pregnancies

2019 ◽  
pp. 1
Author(s):  
Erdem Fadiloglu ◽  
Atakan Tanacan ◽  
Canan Unal ◽  
Mehmet Sinan Beksac
Keyword(s):  
Risk Factors ◽  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Low Dose ◽  
Methylenetetrahydrofolate Reductase ◽  
Post Partum ◽  
Subsequent Pregnancy ◽  
Low Molecular Weight ◽  
Mthfr Polymorphisms ◽  
The Mean

<p><strong>Objective:</strong> To evaluate the subsequent pregnancy outcomes of women who have experienced unexplained stillbirth in their previous gestations.</p><p><strong>Study Design:</strong> This retrospective cohort consisted of 14 pregnancies who had stillbirth (without known risk factors) in their previous pregnancies. These patients had been included in a special preconceptional care program to be evaluated in terms of etiological risk factors for stillbirth. At least one of the risk factors, such as methylenetetrahydrofolate reductase (MTHFR) polymorphisms, hereditary thrombophilias and autoimmune problems, were defined in this study population. After detection of pregnancy, the patients were administered low-dose low-molecular-weight heparin (LMWH) (enoxaparin, 1×2000 Anti-XA IU/0.2 mL/day), low-dose salicylic acid (100 mg/day) and low-dose corticosteroid (methylprednisolone, 1×4 mg/day orally) in necessary cases.</p><p><strong>Results:</strong> Out of 14 pregnancies, 4 (28.5%) ended up with miscarriages at 9, 11, 11 and 15 gestational weeks, respectively. The remaining 10 pregnancies ended up with alive deliveries. The mean gestational week at birth was 36.4±0.51, while the mean birthweight was 2882±381.01 g. Out of 10 pregnancies, only one was diagnosed as IUGR. Only two newborn necessitated hospitalization in the neonatal intensive care unit (NICU) due to respiratory problems. Both newborns were discharged from the NICU without any further complication at the post-partum 5th day. </p><p><strong>Conclusion:</strong> Patients with a prior stillbirth should be screened for MTHFR polymorphisms, autoimmune problems and hereditary thrombophilias, especially in case of absence of any etiological factor. Management of these patients with low-dose aspirin, low-dose low molecular weight heparin and corticosteroids seemed to be beneficial for increasing live birth rates and avoiding obstetric complications.</p>

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