Clinical correlates of plasma antithrombin and protein C levels in patients with pre-eclampsia and eclampsia in Sokoto, Northwest Nigeria

Background: Hypertensive disorders of pregnancy complicate 17% of pregnancies in Sokoto, Nigeria with pre-eclampsia and eclampsia accounting for 6% and 4.29% respectively. Pre-eclampsia and eclampsia stand out as major causes of poor pregnancy outcomes with eclampsia contributing 46% of adolescent maternal mortality in Sokoto. These disorders increase risk of venous thromboembolism, DIC, placental abruption, IUGR, premature delivery and recurrent pregnancy loss. The roles of antithrombin and protein C in disease severity and outcomes of pregnancies in pre-eclampsia/eclampsia are subject of recent researches albeit with conflicting findings. The aim of the study was to determine the plasma antithrombin and protein C levels of pre-eclampsia and eclampsia in Sokoto with a view to assessing any relationship with clinical severity and pregnancy outcomes.Methods: Prospective comparative study involving 31 each of pregnant women with pre-eclampsia, eclampsia and normotensive pregnancy. Plasma antithrombin and protein C levels were determined via kinetic method using S4 Nortek semi-automated coagulometer. Data analysis was performed using SPSS version 21.0. Results: The mean plasma antithrombin and protein C levels for eclampsia, pre-eclampsia and normotensive pregnancy were (61.17±9.13 and 60.00±5.76) vs (71.24±13.15 and 71.06±6.16) vs (85.54±8.77 and 89.64±7.61) respectively; p=0.0001. Severe pre-eclampsia when compared with mild pre-eclampsia had lower antithrombin (70.21±13.58 vs 73.74±12.43; p=0.507) and protein C (70.52±6.27 vs 72.40±6.00; p=0.451) levels respectively, though without statistical significance. Pre-eclampsia with low plasma antithrombin levels had increased risk of preterm delivery when age, gravidity and booking status were factored (OR, 1.2, 95% CI 0.035 to 0.348, p=0.017).Conclusions: Lower plasma antithrombin and protein C levels were found with eclampsia and severe pre-eclampsia suggesting consumptive depletion of anticoagulants with disease progression. Women with pre-eclampsia and low plasma antithrombin levels were found to have increased odds of having preterm delivery when age, gravidity and booking status were considered.

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Contribution of the Cystathionine β-Synthase Gene (844ins68) Polymorphism to the Risk of Early-onset Venous and Arterial Occlusive Disease and of Fasting Hyperhomocysteinemia

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614070 ◽

2000 ◽

Vol 84 (10) ◽

pp. 576-582 ◽

Cited By ~ 38

Author(s):

Raffaella de Franchis ◽

Isabella Fermo ◽

Giuseppina Mazzola ◽

Gianfranco Sebastio ◽

Giovanni Di Minno ◽

...

Keyword(s):

Early Onset ◽

Gene Polymorphisms ◽

Protein C ◽

Methylenetetrahydrofolate Reductase ◽

Statistical Significance ◽

Activated Protein C ◽

Mthfr Gene ◽

Occlusive Disease ◽

Activated Protein C Resistance ◽

Increased Risk

SummaryThe frequency of the heterozygous 844ins68 mutation of the cystathionine β-synthase (CBS) gene and of its association with the homozygous C677T transition of the methylenetetrahydrofolate reductase (MTHFR) gene, plasma fasting tHcy, folate and vitamin B12 levels were evaluated in 309 consecutive patients with objectively diagnosed early-onset venous (n = 200) or arterial thromboembolic disease (n = 109) recruited over 25 months in Milan (North Italy) and Naples (South Italy). The above gene polymorphisms were also evaluated in a population of 787 unmatched controls, 204 of whom – similar to patients for age- and sex-distribution – had fasting tHcy, vitamins and activated protein C resistance measured in their plasma.Moderate fasting hyperhomocysteinemia was detected in 15.5% of patients and in 5.9% of 204 controls (Mantel-Haenszel OR after stratification for type of occlusive disease and gender: 2.88; 1.48–5.32). The frequencies of the 677TT mutation of the MTHFR gene and of the heterozygous 844ins68 insertion of the CBS gene were not significantly different in the patient (19.4% and 6.9%) and the control population (16.5% and 7.8%), but the association of the two gene polymorphisms – found in 3.9% of patients and in 1.1% of controls – was significantly associated with an increased risk of venous or arterial occlusive diseases (RR = 3.63; 1.48–8.91). The MTHFR 677TT mutation (RR: 6.92; 3.86–12.4) and its association with the 844ins68 insertion (RR: 21.9; 8.35–57.4), but not the isolated insertion (RR: 0.71), were more frequent in patients and controls with fasting hyperhomocysteinemia than in normohomocysteinemic subjects, irrespective of the type of occlusive disease (venous or arterial). When adjusted for determinants of hyperhomocysteinemia in the patient and the control populations (generalized linear model), fasting tHcy levels were significantly higher in subjects with association of the two gene abnormalities (24.2 ± 3.8 µmol/L) than in subjects with the MTHFR 677TT mutation only (14.0 ± 5.8 µmol/L, p = 0.004). Activated protein C resistance was significantly more prevalent in venous patients (9.9%) than in controls (3.9%, OR = 2.69; 1.08–6.88). Six of 21 venous patients with APCresistance also had hyperhomocysteinemia (RR = 5.04; 0.68–37.6), but isolated fasting hyperhomocysteinemia retained statistical significance for the association with venous occlusive disease (RR = 2.84; 1.34–6.01).Heterozygosity for the 844ins68 mutation of the CBS gene is not per se a risk factor for premature arterial and/or venous occlusive diseases. However, when detected in combination with thermolabile MTHFR, it increases by almost 4-fold the risk of occlusive diseases (arterial and/or venous), by increasing the risk and the degree of fasting hyperhomocysteinemia.

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Ultrasonography of the uterine cervix and preterm delivery

Fetal and Maternal Medicine Review ◽

10.1017/s0965539599000121 ◽

1999 ◽

Vol 11 (1) ◽

pp. 7-16

Author(s):

Vilho Hiilesmaa ◽

Pekka Taipale

Keyword(s):

Preterm Delivery ◽

Premature Birth ◽

Clinical History ◽

Premature Delivery ◽

Perinatal Morbidity ◽

Second Trimester ◽

Uterine Contractions ◽

The Past ◽

Increased Risk ◽

Digital Evaluation

The incidence of premature delivery (at less than 37 completed weeks) has been stable at between 5–10% of deliveries over the past 20 years despite intensive research in this field. Preterm delivery is a major cause of perinatal morbidity and mortality. The identification of women at increased risk for this condition has traditionally been based on clinical history (e.g. previous premature birth or second-trimester miscarriage), digital evaluation of the cervix and the occurrence of uterine contractions.

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HIV infected women: does use of antenatal antiretroviral therapy increase risk of premature delivery?

Weekly releases (1997–2007) ◽

10.2807/esw.06.26.01937-en ◽

2002 ◽

Vol 6 (26) ◽

Author(s):

C Thorne ◽

S Fiore ◽

M L Newell

Keyword(s):

United States ◽

Antiretroviral Therapy ◽

Combination Therapy ◽

Protease Inhibitor ◽

The United States ◽

Premature Delivery ◽

Apparent Contradiction ◽

Increased Risk ◽

Increase Risk ◽

Hiv Women

Data from the United States (US) were presented recently suggesting antiretroviral therapy (ART) during pregnancy in HIV women was not associated with an increased risk of prematurity (1). These findings contradict earlier findings from Europe which demonstrated a small but significant increased risk of premature delivery with use of combination therapy, especially when including a protease inhibitor (PI), and in particular when started before or in early pregnancy (2). But differences in populations and methodology applied could explain much of this apparent contradiction. Clinicians caring for HIV infected women should be aware of these findings.

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Management and Outcomes of Appendectomy during Pregnancy

The American Surgeon ◽

10.1177/000313481708301018 ◽

2017 ◽

Vol 83 (10) ◽

pp. 1103-1107 ◽

Cited By ~ 4

Author(s):

Roy P. Won ◽

Scott Friedlander ◽

Steven L. Lee

Keyword(s):

Length Of Stay ◽

Pregnant Women ◽

Preterm Delivery ◽

Management Practices ◽

Surgical Intervention ◽

Negative Appendectomy ◽

Increased Risk ◽

Increase Risk ◽

Inpatient Database ◽

Surgical Admission

Acute appendicitis is a common nonobstetric indication for surgical intervention during pregnancy with serious potential complications for the mother and fetus. The aim of this study was to evaluate the presentation, management practices, outcomes, and costs of appendectomy during pregnancy. We did a retrospective analysis of 62,118 nonincidental appendectomies performed in women (age 15–45 years) identified from the California State Inpatient Database (2005–2011). Primary outcomes included diagnosis or type of appendicitis, use of laparoscopy, morbidity, length of stay, and cost. Pregnant women were less likely to undergo laparoscopy (OR = 0.51, P < 0.01). Pregnancy had no effect on perforation rates, but was associated with higher rates of negative appendectomy (OR = 9.29, P < 0.01). Pregnancy was not associated with nonpregnancy-related complications after appendectomy. Pregnant women had longer length of stay (RR = 1.07, P < 0.01) but similar costs. Appendectomy did increase risk of preterm delivery at the time of surgical admission (19.5 vs 8.8%, P < 0.01). However, once discharged, there was no difference in rates of preterm delivery (9.1 vs 8.9%, P = 0.23). Pregnant women had higher rates of negative appendectomy with lower rates of laparoscopy. Despite these differences, there was no difference in nonpregnancy-related morbidity and cost. Appendectomy did increase risk of preterm birth, but the increased risk normalized over time.

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Perinatal complications and maximising lamb survival in an adolescent paradigm characterised by premature delivery and low birthweight

PLoS ONE ◽

10.1371/journal.pone.0259890 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0259890

Author(s):

Jacqueline M. Wallace ◽

Paul O. Shepherd ◽

John S. Milne ◽

Raymond P. Aitken

Keyword(s):

Preterm Delivery ◽

Low Birthweight ◽

Neonatal Morbidity ◽

Supplementary Feeding ◽

Premature Delivery ◽

Control Group ◽

Gestation Length ◽

Perinatal Complications ◽

Very Preterm ◽

Increased Risk

The competition for nutrients in overnourished and still-growing adolescent sheep negatively impacts gestation length, colostrum supply and lamb birthweight, all of which may affect neonatal morbidity and survival to weaning. Herein perinatal complications and the requirement for supplementary feeding were analysed in relation to gestational-intake, and the degree of premature delivery and prenatal growth-restriction exhibited. Pregnancies were established by embryo transfer and the mean/standard deviation (SD) gestation length and birthweight of the optimally-fed control group (n = 100) was used to define early delivery and reduced birthweight categories (1.5 and 3.0 SDs below the control mean for each aspect). Control lambs were largely delivered at term (94%), and had a normal birthweight (92%), while very preterm (≤139days, 18.5%) and preterm delivery (140-142days, 54.8%), extremely low birthweight (ELBW; females ≤2838g and males ≤3216g, 21.1%) and low birthweight (LBW; females 2839 to ≤4001g and males 3217 to ≤4372g, 32.2%), were common in the overnourished group (n = 270, P<0.001). Accordingly, overnourished dams were more likely to lamb without assistance while the incidence of major dystocia was greater in controls. Initial lamb vigour at birth was independent of gestational-intake, delivery or birthweight category but both ELBW and very premature lambs required more assistance with feeding in the first 24h postnatal, primarily reflecting low colostrum availability. Indeed, relative to normal, ELBW lambs had a greater risk of experiencing mismothering, and enhanced likelihood of requiring supplementary feeding throughout the neonatal period (P<0.001). ELBW lambs also had a greater possibility of respiratory issues at birth (P<0.01) and renal complications (P<0.001), while very preterm delivery was associated with an increased risk of gastrointestinal tract problems (P<0.01). In spite of these complications, all-cause mortality was low (5.4%) suggesting that our proactive neonatal care regime can overcome many of the issues associated with extreme prematurity and low birthweight.

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Severe Arterial Cerebral Thrombosis in a Patient with Protein S Deficiency (Moderately Reduced Total and Markedly Reduced Free Protein S): A Family Study

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646544 ◽

1989 ◽

Vol 61 (01) ◽

pp. 144-147 ◽

Cited By ~ 47

Author(s):

A Girolami ◽

P Simioni ◽

A R Lazzaro ◽

I Cordiano

Keyword(s):

Arterial Thrombosis ◽

Protein C ◽

Protein S ◽

Protein S Deficiency ◽

Protein C Deficiency ◽

Free Protein ◽

Her Family ◽

S Deficiency ◽

Increased Risk ◽

Patient Reported

SummaryDeficiency of protein S has been associated with an increased risk of thrombotic disease as already shown for protein C deficiency. Deficiencies of any of these two proteins predispose to venous thrombosis but have been only rarely associated with arterial thrombosis.In this study we describe a case of severe cerebral arterial thrombosis in a 44-year old woman with protein S deficiency. The defect was characterized by moderately reduced levels of total and markedly reduced levels of free protein S. C4b-bp level was normal. Protein C, AT III and routine coagulation tests were within the normal limits.In her family two other members showed the same defect. All the affected members had venous thrombotic manifestations, two of them at a relatively young age. No other risk factors for thrombotic episodes were present in the family members. The patient reported was treated with ASA and dipyridamole and so far there were no relapses.

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Elevated Levels of Prothrombin Activation Fragment 1+2 in Plasma from Patients with Heterozygous Arg506 to Gin Mutation in the Factor V Gene (APC-Resistance) and/or Inherited Protein S Deficiency

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650259 ◽

1996 ◽

Vol 75 (02) ◽

pp. 270-274 ◽

Cited By ~ 57

Author(s):

Benget Zöller ◽

Johan Holm ◽

Peter Svensson ◽

Björn Dahlbäck

Keyword(s):

Plasma Concentration ◽

Protein C ◽

Protein S ◽

Factor V ◽

Protein S Deficiency ◽

Apc Resistance ◽

S Deficiency ◽

Increased Risk ◽

Factor V Gene ◽

V Gene

SummaryInherited resistance to activated protein C (APC-resistance), caused by a point mutation in the factor V gene leading to replacement of Arg(R)506 with a Gin (Q), and inherited protein S deficiency are associated with functional impairment of the protein C anticoagulant system, yielding lifelong hypercoagulability and increased risk of thrombosis. APC-resistance is often an additional genetic risk factor in thrombosis-prone protein S deficient families. The plasma concentration of prothrombin fragment 1+2 (F1+2), which is a marker of hyper-coagulable states, was measured in 205 members of 34 thrombosis-prone families harbouring the Arg506 to Gin mutation (APC-resistance) and/or inherited protein S deficiency. The plasma concentration of F1+2 was significantly higher both in 38 individuals carrying the FV:Q506 mutation in heterozygous state (1.7 ± 0.7 nM; mean ± SD) and in 48 protein S deficient cases (1.9 ± 0.9 nM), than in 100 unaffected relatives (1.3 ±0.5 nM). Warfarin therapy decreased the F1+2 levels, even in those four patients who had combined defects (0.5 ± 0.3 nM). Our results agree with the hypothesis that individuals with APC-resistance or protein S deficiency have an imbalance between pro- and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state.

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Plasma Fibrin Stabilising Factor (F. S. F.) Activity in Normal Subjects and Patients with Chronic Liver Disease

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653516 ◽

1969 ◽

Vol 21 (01) ◽

pp. 134-143 ◽

Cited By ~ 9

Author(s):

W. D Walls ◽

M. S Losowsky

Keyword(s):

Liver Disease ◽

Chronic Liver Disease ◽

Clinical Improvement ◽

Quantitative Estimation ◽

Kinetic Method ◽

Normal Subjects ◽

Chronic Liver ◽

Clinical Severity ◽

Plasma Fibrinogen ◽

Normal Range

SummaryA kinetic method for the quantitative estimation of plasma F.S.F. activity is described and discussed.This method was applied to normal subjects and to patients with chronic liver disease. The plasma F.S.F. activity was uninfluenced by either sex or age, and the normal range has been defined.A significant decrease in plasma F.S.F. activity was observed in patients with chronic liver disease. Subnormal levels of activity were found in 25% of such patients but were unrelated to episodes of abnormal haemorrhage. Plasma F.S.F. activity tended to be lower in patients with disease of greater clinical severity. In 2 patients showing clinical improvement there was an increase in plasma F. S. F. activity.It was confirmed that plasma fibrinogen levels increase with age.

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Percutaneous Coronary Intervention in Patients with Diabetes and Multivessel or Left Main Disease – a Review

Interventional Cardiology Review ◽

10.15420/icr.2012.7.1.37 ◽

2012 ◽

Vol 7 (1) ◽

pp. 37

Author(s):

Donald E Cutlip ◽

Keyword(s):

Percutaneous Coronary Intervention ◽

Coronary Artery ◽

Statistical Significance ◽

Bare Metal Stents ◽

Coronary Intervention ◽

Metal Stents ◽

Increased Risk ◽

Percutaneous Coronary ◽

Patients With Diabetes ◽

The Impact

Coronary artery disease in patients with diabetes is frequently a diffuse process with multivessel involvement and is associated with increased risk for myocardial infarction and death. The role of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with diabetes and multivessel disease who require revascularisation has been debated and remains uncertain. The debate has been continued mainly because of the question to what degree an increased risk for in-stent restenosis among patients with diabetes contributes to other late adverse outcomes. This article reviews outcomes from early trials of balloon angioplasty versus CABG through later trials of bare-metal stents versus CABG and more recent data with drug-eluting stents as the comparator. Although not all studies have been powered to show statistical significance, the results have been generally consistent with a mortality benefit for CABG versus PCI, despite differential risks for restenosis with the various PCI approaches. The review also considers the impact of mammary artery grafting of the left anterior descending artery and individual case selection on these results, and proposes an algorithm for selection of patients in whom PCI remains a reasonable strategy.

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COVID-19 and Its Symptoms’ Panoply: A Case-Control Study of 919 Suspected Cases in Locked-Down Ovar, Portugal

Portuguese Journal of Public Health ◽

10.1159/000514925 ◽

2021 ◽

pp. 1-8

Author(s):

Regina Sá ◽

Tiago Pinho-Bandeira ◽

Guilherme Queiroz ◽

Joana Matos ◽

João Duarte Ferreira ◽

...

Keyword(s):

Large Scale ◽

Case Control Study ◽

Statistical Significance ◽

Case Control ◽

Case Definition ◽

Suspected Case ◽

Risk Characteristics ◽

Increased Risk ◽

Wide Range ◽

Control Study

Background: Ovar was the first Portuguese municipality to declare active community transmission of SARS-CoV-2, with total lockdown decreed on March 17, 2020. This context provided conditions for a large-scale testing strategy, allowing a referral system considering other symptoms besides the ones that were part of the case definition (fever, cough, and dyspnea). This study aims to identify other symptoms associated with COVID-19 since it may clarify the pre-test probability of the occurrence of the disease. Methods: This case-control study uses primary care registers between March 29 and May 10, 2020 in Ovar municipality. Pre-test clinical and exposure-risk characteristics, reported by physicians, were collected through a form, and linked with their laboratory result. Results: The study population included a total of 919 patients, of whom 226 (24.6%) were COVID-19 cases and 693 were negative for SARS-CoV-2. Only 27.1% of the patients reporting contact with a confirmed or suspected case tested positive. In the multivariate analysis, statistical significance was obtained for headaches (OR 0.558), odynophagia (OR 0.273), anosmia (OR 2.360), and other symptoms (OR 2.157). The interaction of anosmia and odynophagia appeared as possibly relevant with a borderline statistically significant OR of 3.375. Conclusion: COVID-19 has a wide range of symptoms. Of the myriad described, the present study highlights anosmia itself and calls for additional studies on the interaction between anosmia and odynophagia. Headaches and odynophagia by themselves are not associated with an increased risk for the disease. These findings may help clinicians in deciding when to test, especially when other diseases with similar symptoms are more prevalent, namely in winter.

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