Factor VIII levels and the risk of pre-eclampsia, HELLP syndrome, pregnancy related hypertension and severe intrauterine growth retardation

OBJECTIVE: Recently, acquired as well as genetic prothrombotic factors are associated with thrombotic events. These factors have also been related to conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome and severe intrauterine growth restriction (IUGR). The aim of this study was to determine whether elevated factor VIII levels are associated with uteroplacental insufficiency, in particular pre-eclampsia, HELLP syndrome or pregnancy-induced hypertension and intrauterine growth retardation. METHODS: Plasma samples of 75 women with a history of pregnancy complicated by pre-eclampsia, HELLP syndrome, pregnancy induced hypertension or intrauterine growth restriction were tested for factor VIII:C (FVIII:C) levels at a minimum of 10 weeks post-partum. Laboratory results were compared to factor VIII:C levels found in a healthy control group of 272 women. RESULTS: Mean factor VIII:C levels were similar at 123 IU/dl in both the patient group and the controls. In a logistic regression model, after adjusting for age and blood group, no effect of factor VIII:C levels on the risk of pregnancy complications was observed, with the exception of IUGR with (OR 2.9, CI 1.0-8.7) or without hypertension (OR 2.0, CI 0.7-6.4). CONCLUSION: If the elevated level of factor VIII would be the sole factor responsible for the increased risk observed, one would expect to find an effect of blood group on risk as well (blood group being an important determinant of FVIII:C). While no such effect could be shown a causal relationship between elevated levels of factor VIII and conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome, pregnancy-induced hypertension and IUGR is not very likely.     

Maternal thrombophilias are not associated with early pregnancy loss

We investigated the association between inherited and acquired maternal thrombophilias and adverse pregnancy events. A cohort of 491 patients with a history of adverse pregnancy outcomes was evaluated for activated protein C resistance, factor V Leiden and prothrombin G20210A mutations, hyperhomocysteinemia, deficiencies of antithrombin, protein C and S and both anticardiolipin antibodies and lupus anticoagulants. The study had an 80% power to detect a 15% difference in the prevalence of thrombophilia for 1(st) trimester loss. In our high-risk cohort the presence of 1 maternal thrombophilia or more than one thrombophilia were found to be protective of recurrent losses at < 10 weeks (1 thrombophilia: OR: 0.55, 95% CI: 0.33-0.92; > 1 thrombophilia: OR: 0.48, 95%CI:0.29-0.78). In contrast, the presence of maternal thrombophilia(s) was modestly associated with an increased risk of losses > 10 weeks (1 thrombophilia: OR:1.76, 95%CI: 1.05-2.94, >1 thrombophilia: OR:1.66, 95%CI:1.03-2.68). Women who experienced only euploid losses were not more likely to have an identified thrombophilia than women who experienced only aneuploid losses (OR 1.03; 0.38-2.75). The presence of maternal thrombophilia was associated with an increased risk of fetal loss after 14 weeks, fetal growth restriction, abruption and preeclampsia. There was a significant "dose-dependent" increase in the risk of abruption (OR:3.60, 95%CI: 1.43-9.09) and preeclampsia (OR:3.21, 95%CI:1.20-8.58). In conclusion, these data indicate maternal thrombophilias are not associated with pregnancy wastage prior to 10 weeks of gestation.     

Effect of thrombophylaxis on uterine and fetal circulation in pregnant women with a history of pregnancy complications

PURPOSE: The aim of this study was to investigate the effect of thromboprophylactic therapy on fetal and maternal Doppler flow parameters in pregnant women with severe complications in previous pregnancies and evidence of acquired or congenital thrombophilia in the current pregnancy. METHODS: Sixty-five patients with a history of recurrent abortions, intrauterine fetal death, intrauterine growth restriction (IUGR), and severe early-onset preeclampsia were tested for the presence of acquired or congenital thrombophilia. Those with positive findings were prescribed low-dose aspirin plus low-molecular-weight heparin (LMWH) (enoxaparin); the remainder received low-dose aspirin only. A Doppler flow study was performed before and after treatment and in the third trimester of pregnancy. RESULTS: Of the 65 pregnancies, four ended in spontaneous abortion and were excluded from the analysis. Of the 61 women with completed pregnancies, 37 (61%) had evidence of acquired or congenital thrombophilia: 22 (36%) protein S deficiency; 1 (2%) protein C deficiency; 2 (3%) activated protein C resistance (APC-R); 2 (3%) IgG for antiphospholipid antibodies; 1 (2%) circulating anticoagulant; and 9 (15%) a combined defect. This group showed a significant decrease in mean uterine artery pulsatility index (PI) before and after treatment (1.32+/-0.36 vs. 1.04+/-0.23, P=.006), whereas the remaining 24 patients treated with low-dose aspirin only had nonsignificant changes. Pearson's correlation test yielded no correlations of the pregnancy outcome parameters with Doppler flow values in the umbilical or uterine arteries. CONCLUSIONS: Thromboprophylactic therapy transiently improves maternal circulation parameters in patients with thrombophilia at risk of fetal loss and other severe complications of pregnancy, but not in correlation with their pregnancy outcome. Therefore, Doppler examination of maternofetal circulation in the second trimester is not predictive of pregnancy outcome.     

The association between antiphospholipid antibodies and placenta mediated complications: a systematic review and meta-analysis

Background

The association between antiphospholipid antibodies (APLA) and placenta mediated pregnancy complications (pre-eclampsia, intrauterine growth restriction (IUGR), late fetal loss and placental abruption) remains controversial.

Methods

We performed a systematic review of published case-control, cohort and cross sectional studies (MEDLINE (1975 to 2009), EMBASE 16 (1980 to 2009) and all EBM Reviews (2009)) to evaluate the association between APLA and placenta mediated complications in untreated women without autoimmune diseases.

Results

Our search strategy identified 1207 potentially relevant studies. Twenty eight were included in the final analysis. LA was associated with pre-eclampsia (OR 2.34; 95%CI 1.18-4.64), IUGR (OR 4.65 95% CI 1.29-16.71) and late fetal loss (OR 4.73; 95%CI 1.08-20.81) amongst case-control studies and only with late fetal loss (OR 10.59 95% CI 1.87-59.88) amongst cohort studies. ACA were associated with pre-eclampsia (OR 1.52; 95%CI 1.05-2.20) and late fetal loss (OR 4.29; 95% CI 1.34-13.68) amongst case-control studies and only late fetal loss (OR 8.85 95% CI 1.84-42.50) amongst cohort studies. Finally, anti-B2 GP1 antibodies showed associations with pre-eclampsia (OR 19.14, 95% CI 6.34-57.77), IUGR (OR 20.03; 95%CI 4.59-87.43) and late fetal loss (OR 23.46, 95% CI 1.21-455.01) in two cohort studies.

Conclusion

APLAs appear to be associated with late fetal losses. However, the association between APLAs and other placenta mediated complications is inconsistent. LA is most strongly and consistently associated with placenta mediated complications. There are currently insufficient data to support a significant link between anti-B2 GP1 antibodies and pregnancy morbidity.     

Thrombophilia and stroke

Thrombophilia is defined as an enhanced tendency to form intravascular thrombi, which may be arterial or venous. Of the inherited thrombophilias, factor V Leiden and the prothrombin 20210 mutation have been associated with stroke, but this association is statistically significant only in children and adults under age 40. The risk of stroke in persons with these mutations is substantially increased by concomitant exposure to oral contraceptives. Hyperhomocystinemia is a major risk factor for stroke as well as Alzheimer's disease; persons with deficiencies of vitamin B12 or folic acid are especially vulnerable to these complications. Of the acquired thrombophilias, the antiphospholipid antibody syndrome is strongly associated with transient ischemic attacks, cerebral infarction, Sneddon syndrome, and dementia. The diagnosis of thrombophilia should be considered in stroke patients who are young, have a family history of thrombosis, suffer venous dural sinus thrombosis, or have recurrent strokes.     

Microparticles and pregnancy complications

Microparticles (MPs) are shed from cell membranes of a variety of cells, promote thrombus formation, mediate pro-inflammatory effects and may cause endothelial dysfunction. Normal pregnancy is characterized by increased levels of MPs compared to non-pregnant healthy women but the prevalence, cell origin and the role of MPs in pregnancy-related complications remain controversial. Normal pregnancy is an acquired hyper-coagulable state due to an increase in procoagulants and decrease in natural anticoagulants. Pregnancy-related complications such as preeclampsia, intrauterine fetal growth restriction (IUGR) and fetal loss are associated with placental dysfunction and may cause significant maternal and fetal morbidity and mortality. This article highlights the role of microparticles in maternal placental crosstalk and the interplay between microparticles, thrombosis and pregnancy complications.     

Thrombophilias and adverse pregnancy outcome - A confounded problem!

It was the objective of this study to analyse the influence of confounders, such as ethnicity, severity of illness and method of testing, in articles concerning the still moot relationship of thrombophilias to adverse pregnancy outcome (APO). Relevant case-control studies were identified using Medline and EMBASE databases between 1966 and 2006. Search terms were recurrent fetal loss, intrauterine fetal death, preeclampsia, HELLP-syndrome, eclampsia, fetal growth restriction, abruptio placentae, combined with maternal thrombophilias. Data was extracted from the articles per subgroup of APO regardless of confounder. These subgroups were tested if they fulfilled the heterogeneity testing criterion (I(2) > 35%) to weigh the influence of the confounder. Confounders were selected and examined with Mantel-Haenszel method. Increased thrombophilia prevalence was confirmed in most adverse pregnancy outcomes. Ethnicity, genetic testing only and severity of illness were confounders in the various forms of APO. Stronger relationships between factor V Leiden and severity of disease were found in 2(nd) and 3(rd) trimester than 1(st) trimester recurrent fetal loss, in preeclampsia with: blood pressure > or =160/110 mmHg than > or =140/90 mmHg; proteinuria > or =5 grams per day than <5 grams; onset before than after 28 weeks, in fetal growth restriction <3(rd) percentile than <5(th), than <10(th), and in earlier occurrence of abruptio placentae than 3(rd) trimester. In conclusion, reports on the prevalence of maternal thrombophilias and APO are influenced by various confounders, which are not always appropriately analysed. The differences we have identified reflect the differential impact of these confounders. These data emphasise the importance of more uniform research.     

Nonsynonymous mutations in three anticoagulant genes in Japanese patients with adverse pregnancy outcomes

Background

Hereditary thrombophilias may associate with uteroplacental thrombosis leading to adverse pregnancy outcomes. The present study was conducted to reveal the frequency of the low-frequency thrombophilic protein S K196E mutation, as well as the frequency of very rare nonsynonymous mutations in protein S, protein C, and antithrombin genes, in patients with adverse pregnancy outcomes.

Patients and methods

We enrolled 330 Japanese patients with adverse pregnancy outcomes and divided them into 233 patients with two or more miscarriages and 114 patients with fetal growth restriction (FGR) and/or intrauterine fetal death (IUFD); 17 patients belonged to both groups. We sequenced the entire coding regions of three anticoagulant genes in all 330 patients.

Results

We found that protein S K196E mutation was identified in 4 out of 233 patients with recurrent miscarriage and in 2 out of 114 patients with FGR and/or IUFD. The frequencies of this mutation in these patient groups were not different from that in a Japanese general population. Very rare nonsynonymous mutations were identified in 3.3% (11 out of 330) of patients with adverse pregnancy outcomes.

Conclusions

Although the low-frequency protein S K196E mutation can increase the risk for venous thromboembolism, it did not increase the risk for adverse pregnancy outcomes even in Japanese.     

Blood group AB and factor V Leiden as risk factors for pre-eclampsia: A population-based nested case-control study

IntroductionPre-eclampsia is an important cause of maternal morbidity and mortality. Its etiology is still unknown. Clinical symptoms correlate with activation of coagulation and inherited thrombophilia has been associated with pre-eclampsia. ABO blood group has been associated with thrombotic disorders and pre-eclampsia.We assessed ABO blood group, seven thrombophilia associated polymorphisms, and anti-beta2-glycoprotein I antibodies as risk factors for pre-eclampsia.Materials and methodsWe performed a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers and medical records were reviewed. We studied 248 cases fulfilling strict criteria for pre-eclampsia and 679 controls. Severe pre-eclampsia, early pre-eclampsia, and pre-eclampsia with intra-uterine growth restriction (IUGR) were analyzed separately.ResultsBlood group AB increased the risk for pre-eclampsia as a whole (OR 2.1, 95% CI 1.3-3.5), and in the three subgroups (OR 2.3, 3.8, 3.4; 95% CI 1.3-3.9, 2.0-7.1, 1.6-7.1). FV Leiden increased the risk as a whole (OR 1.7, 95% CI 0.8-3.9), and in the three subgroups, although not statistically significantly. Anti-beta2-glycoprotein I antibodies were not associated with pre-eclampsia. High body mass index, diabetes, first pregnancy, and twin pregnancy increased the risk from 1.5-fold to 8.2-fold.ConclusionsOur results confirm and extend the prior observation of blood group AB being a risk factor for pre-eclampsia. ABO blood group is known from all pregnant women. The value of blood group as risk factor for pre-eclampsia should be further assessed in prospective studies. In this study, FV Leiden was not statistically significant risk factor.     

Interaction of heritable and estrogen-induced thrombophilia: possible etiologies for ischemic optic neuropathy and ischemic stroke

Our specific aim was to assess how thrombophilic exogenous estrogens interacted with heritable thrombophilias leading to non-arteritic ischemic optic neuropathy (NAION) and ischemic stroke. Coagulation measures were performed in a 74 year old patient and her immediate family. The proband had a 47 year history of 9 previous thrombotic episodes, and developed unilateral NAION 4 years after starting estrogen replacement therapy (ERT). The proband was heterozygous for two thrombophilic gene mutations (G20210A prothrombin gene, platelet glycoprotein IIIa P1A1/A2 polymorphism), and homozygous for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Of 238 normal controls, none had these 3 gene mutations together. The proband's mother and brother had deep venous thrombosis (DVT). The proband's brother, sister, nephew, daughter, and two granddaughters were homozygous for the C677T MTHFR mutation. The proband's brother was heterozygous for the G20210A prothrombin gene mutation. The proband's niece was heterozygous for the G20210A prothrombin gene mutation, homozygous for the C677T MTHFR mutation, homozygous for the hypofibrinolytic 4G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene, and heterozygous for the platelet glycoprotein IIIa P1A1/A2 polymorphism. Of 238 normal controls, none had the niece's combination of 4 gene mutations. When ERT-mediated thrombophilia was superimposed on the proband's heritable thrombophilias, unilateral ischemic optic neuropathy developed, her tenth thrombotic event over a 5 decade period. When estrogen-progestin oral contraceptives were given to the proband's niece, she had an ischemic stroke at age 22. Exogenous estrogen-mediated thrombophilia superimposed on heritable thrombophilia and hypofibrinolysis is associated with arterial and venous thrombi, and appears to be a preventable, and potentially reversible etiology for ischemic optic neuropathy and ischemic stroke.     

The management of thrombosis in pregnancy: role of low-molecular-weight heparin

Fatal pulmonary embolism remains the most common cause of mortality among pregnant women in many Western countries. The physiological changes of pregnancy produce a hypercoagulable state that increases the risk of venous thromboembolism (VTE). Women with inherited or acquired thrombophilias are at particularly high risk of VTE during pregnancy, and thromboprophylaxis may be advisable in some cases. Thrombophilia is also associated with complications of pregnancy, including fetal loss, pre-eclampsia, intra-uterine growth restriction, and placental abruption. The antithrombotic agents available for the prevention and treatment of VTE during pregnancy, and pregnancy complications, include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH) and aspirin. Vitamin K antagonists are contra-indicated in pregnancy. Low-dose aspirin may have a role in the prevention of some pregnancy complications, although its safety in early and late pregnancy is uncertain. The efficacy and safety of LMWHs have been demonstrated for the prevention and treatment of VTE in pregnancy. These agents are increasingly being used in place of UFH, which is associated with a higher incidence of side effects compared with LMWH, in addition to the need for regular laboratory monitoring. Evidence is also emerging to support the use of LMWH in the prevention of recurrent fetal loss, although further trials are needed to explore the role of LMWHs in this indication and in the prevention of other complications of pregnancy.     

Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin

Inherited 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 (> or =3 losses in 1st, > or =2 losses in 2nd and > or =1 loss in 3rd trimester) who were found to harbor thrombophilia. Twenty-seven 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 mild-bleeding episode were noticed during enoxaparin therapy. Enoxaparin is safe and effective in prevention of pregnancy loss in women with inherited and acquired thrombophilia.     

Thrombophilic abnormalities and recurrence of venous thromboembolism in patients treated with standardized anticoagulant treatment

INTRODUCTION: Whether patients with hereditary or acquired thrombophilia have an increased risk for recurrence of venous thromboembolism (deep vein thrombosis and/or pulmonary embolism) is still controversial. The aim of this study was to evaluate the incidence of recurrence of venous thromboembolism in patients with and without thrombophilic abnormalities treated with standardized anticoagulant treatment. MATERIAL AND METHODS: Database was from a prospective multicenter randomized study aimed at evaluating the long-term clinical benefit of extending to 1 year the 3-month oral anticoagulant treatment after a first episode of idiopathic proximal deep vein thrombosis. The screening for thrombophilia included antithrombin, protein C, protein S deficiencies, resistance to activated protein C and/or factor V R506Q mutation, the mutation 20210GA of the prothrombin gene, hyperhomocysteinemia and antiphospholipid antibodies. The diagnosis of venous thromboembolism recurrence was done by objective tests and adjudicated by a panel unaware of the results of the thrombophilia screening. RESULTS: A screening for thrombophilic abnormalities was performed in 195 patients. Twenty of 57 (35.1%) thrombophilic patients experienced a recurrence of venous thromboembolism as compared with 29 of 138 (21.0%) patients without thrombophilia (HR=1.78, 95% CI 1.002-3.140, p=0.046). The difference in VTE recurrence between patients with and without thrombophilia was accounted for by those who received 3 months of oral anticoagulation (HR=3.21, 95% CI 1.349-7.616, p=0.008). No difference between thrombophilic and non-thrombophilic patients was observed in the time interval from the index episode to recurrent venous thromboembolism (29.1+/-23.9 and 30.6+/-19.8 months, respectively). CONCLUSIONS: Thrombophilic abnormalities are associated with an increased risk of venous thromboembolism recurrence. The role of thrombophilia in the long-term management of venous thromboembolism should be addressed in prospective management studies.     

Thrombophilia and pregnancy loss

A large body of evidence obtained during the past 6 years suggests a significant role for inherited thrombophilia in the development of gestational vascular complications. While the majority of women with thrombophilia will have an uneventful gestation, case-control studies have demonstrated that thrombophilia is more prevalent in cohorts of women with pregnancy loss early onset preeclampsia, placental abruption, and severe intrauterine growth retardation (IUGR).Placental pathological findings in women with thrombophilia are hallmarked by thrombosis and fibrin deposition potentially to a greater degree than in normal pregnancy. Preliminary case-control studies suggest a benefit for prophylaxis with low molecular weight heparins (LMWH), and prospective randomized trials are in progress to define whether LMWH are effective in preventing pregnancy loss in women with thrombophilia and previous fetal wastage.     

Thrombophilia in children with venous thromboembolic disease

Venous thromboembolic events (VTEs) in children are usually associated with underlying clinical conditions such as central venous line, cancer and cardiac diseases. The objective of this review is to present the importance of thrombophilia to the occurrence of childhood VTE. The reported prevalence of thrombophilia in children with VTE varies extremely between 10% and 78% in different registries. The variation in the reported prevalence most probably reflects differences in the clinical characteristics of the children studied and differences in study designs. The initial management of children with thrombophilia and VTE is similar to those individuals who do not have a specific inherited thrombophilic risk factor, except in the rare events of homozygous deficiencies of prothrombotic coagulation proteins. The impact of thrombophilic markers on long-term therapy and outcome of children with VTE has not been completely clarified. According to the current guidelines for thrombophilia, all children with VTE should be tested for a full panel of genetic and acquired prothrombotic traits. However, re-evaluation of co-morbid risk factors other than thrombophilic markers and careful consideration of the prognostic value of thrombophilic markers might help to change future attitude from the rigidity of current guidelines to more rational schemes.     

Thrombophilia, thrombosis and pregnancy

The risk of venous thromboembolism (VTE) in pregnancy is 0.05-1.8%, six times greater than in the non-pregnant state, and pulmonary embolism remains the most common cause of maternal death. Maternal age, previous history of VTE, Caesarean section and the presence of thrombophilia, significantly increase the risk of VTE. Acquired or hereditary thrombophilia occur in almost two-thirds of women presenting with recurrent miscarriages, pre-eclampsia, intrauterine growth restriction, abruptio placentae, or stillbirth, which are associated with microvascular thrombosis in placental blood vessels. Women with VTE during pregnancy and especially those with thrombophilia require individualized management, based on the type of defect, the family history and the presence of additional risk factors. These factors are important in determining the dose and duration of antithrombotic therapy during pregnancy and the puerperium, and the thromboprophylactic strategy for future pregnancies. Oral anticoagulants are now seldom used during pregnancy because of their significant side effects. Low-molecular-weight heparins (LMWHs) are increasingly replacing unfractionated heparin in the prevention and treatment of VTE during pregnancy. LMWHs have also been shown to be effective in improving the outcome of pregnancy in women with previous obstetric complications.     

Thrombophilia and pregnancy complications

The implications of currently available data on the association of gestational vascular complications with thrombophilia are presented in this consensus report. Screening is recommended for women with the following previous complications: fetal loss including three or more first trimester loss, two or more second trimester loss, or any stillbirth; early, severe or recurrent preeclampsia and severe intrauterine growth restriction. Maternal antithrombotic therapy is currently evaluated in women with thrombophilia and previous complications.     

Thrombophilic dimension of Budd chiari syndrome and portal venous thrombosis--a concise review

Budd chiari syndrome (BCS) is characterized by venous outflow obstruction either at hepatic veins or inferior vena cava, while portal vein thrombosis (PVT) is the consequence of thrombotic occlusion in the extrahepatic venous system. The aetiology of both these disorders is complicated wherein genetic, acquired and local factors interact in the pathogenesis. Among the inherited thrombophilia, factor V Leiden mutation has shown stronger association with BCS than PVT while the converse is true for prothrombin G20210A mutation. Very few studies are available on the role of fibrinolytic potential or the single nucleotide polymorphisms (SNPs) of fibrinolysis proteins, in both BCS and PVT. Among the acquired thrombophilia, myeloproliferative disorders (MPD) are the most frequent cause, while antiphospholipid antibodies (APA) and hyperhomocysteinemia have not shown very strong association with BCS and PVT. Oral contraceptives, infection, chronic inflammatory diseases like Behcets syndrome, inflammatory bowel disease, tumors, paroxysmal nocturnal hemoglobinuria (PNH), pregnancy, puerperium, poor nutrition are some of the other acquired and local risk factors associated with both these disorders. There exists a clear geographical variation both in the clinical manifestation and the underlying aetiology. Almost all the studies have proved that a multifactorial aetiology is the requisite for the manifestation. Evaluation of an extensive thrombophilia profile is essential for optimal management of patients which is further justified with the availability of specific treatment options for at least some thrombophilia markers.     

Unselected women with elevated levels of factor VIII:C or homocysteine are not at increased risk for obstetric complications

Acquired and hereditary thrombophilias are associated with obstetric complications such as (pre-)eclampsia, HELLP syndrome and fetal loss. Our objective was to assess the risk of obstetric complications in women with elevated levels of FVIII:C or hyperhomocysteinemia, as compared with their relatives who had normal FVIII:C or homocysteine levels. From a large family study of patients with venous thromboembolism or premature atherosclerosis and elevated levels of FVIII:C or hyperhomocysteinemia (propositi), the obstetric histories of female first degree relatives, who had been pregnant at least once, were studied. Levels of FVIII:C and homocysteine (both fasting and post-methionine loading) were determined. The number of obstetric complications was calculated and compared in women with normal and elevated levels of FVIII:C, and normal and elevated levels of homocysteine. Women with elevated levels of FVIII:C had a 15.4% risk for toxicosis, preeclampsia, or HELLP syndrome and a 23.9% for fetal loss. This was not statistically different from women with normal levels of FVIII:C. Women with hyperhomocysteinemia tended to have a lower risk for toxicosis, pre-eclampsia, or HELLP syndrome (8.0%, RR 0.6, 95% CI 0.2-1.7) and fetal loss (22.0%, RR 0.8, 95% CI 0.5-1.5) as compared to relatives with normal levels, although these differences did not reach statistical significance. If the analysis was limited to comparing extremes, the results did not materially differ. Unselected women with elevated plasma levels of FVIII:C or hyperhomocysteinemia are not at increased risk for obstetric complications as compared to their relatives with normal levels.     

Thrombophilien bei Patienten mit ischämischem Schlaganfall

Patients with ischemic stroke are sometimes found to have an underlying inherited (deficiency of protein C, protein S, antithrombin III, activated protein C resistance, prothrombin gene mutation, hyperhomocysteinemia) or acquired thrombophilia (lupus anticoagulant and anticardiolipin antibodies, hyperhomocysteinemia). Patient selection for thrombophilia screening is, therefore, a frequent question in managing patients with ischemic stroke. In this review we discuss patient selection and timing for laboratory tests for thrombophilia screening in stroke patients based on a literature review and we calculated overall costs per year in Germany for testing patients older than 18 years with an ischemic stroke of undetermined cause. As there is a lack of studies comparing anticoagulation with antiplatelet therapy in patients with diagnosed thrombophilia, laboratory screening for thrombophilia even in a selected group of patients with cryptogenic ischemic stroke remains of questionable value at present. An exception appears to be testing for lupus anticoagulant and anticardiolipin antibodies in younger patients with suspected antiphospholipid syndrome (two positive test results necessary), because anticoagulation seems to be superior to aspirin in patients with antiphospholipid syndrome.