Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study

Combined oral contraceptives, oral hormone replacement therapy and thrombophilias are recognised risk factors for venous thromboembolism in women. The objective of this study was to assess the risk of thromboembolism among women with thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. Seven studies included pre-menopausal women on oral contraceptives and two studies included peri-menopausal women on hormone replacement therapy. For oral contraceptive use, significant associations of the risk of venous thromboembolism were found in women with factor V Leiden (OR 15.62; 95%CI 8.66 to 28.15); deficiencies of antithrombin (OR 12.60; 95%CI 1.37 to 115.79), protein C (OR 6.33; 95%CI 1.68 to 23.87), or protein S (OR 4.88; 95%CI 1.39 to 17.10), elevated levels of factor VIIIc (OR 8.80; 95%CI 4.13 to 18.75); and factor V Leiden and prothrombin G20210A (OR 7.85; 95%CI 1.65 to 37.41). For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47). Although limited by the small number of studies, the findings of this study support the presence of interaction between thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, thrombophilias with venous thromboembolism among hormone users.     

Risk of recurrence of cerebral venous and sinus thrombosis during subsequent pregnancy and puerperium

OBJECTIVE: To assess the risk of recurrence of cerebral venous and sinus thrombosis (CVST) during subsequent pregnancy and puerperium in women with previous cerebral venous occlusive disease. METHODS: The authors retrospectively studied the relapse rate of CVST and the incidence of extracerebral venous thrombosis during subsequent pregnancies in 39 women (from 125 patients with CVST) who suffered a CVST at childbearing age. RESULTS: Mean follow up was 10.25 years (range 1 to 20). Twenty two pregnancies and 19 births were observed in 14 women without evidence of either recurrence of CVST or extracerebral venous thrombosis. One pregnancy occurred during oral anticoagulation and was interrupted and two pregnancies ended with spontaneous abortions. Low dose heparin had been given during five pregnancies. CONCLUSIONS: The risk of recurrence for CVST during pregnancy seems to be low and these data do not justify a negative advice on pregnancy in women with previous CVST. Further studies are needed to evaluate the need for a prophylactic anticoagulation during pregnancy and puerperium.     

Dural puncture and activated protein C resistance: risk factors for cerebral venous sinus thrombosis

OBJECTIVES—Dural puncture is regarded asafe procedure when contraindications are carefully excluded and has sofar not been recognised as a risk factor for cerebral venous sinusthrombosis (CVST). Five patients are described with CVST after duralpuncture in the presence of additional risk factors.
METHODS—In four out of five patients completeinvestigations for thrombophilia were performed at least one monthafter withdrawal of oral anticoagulation.
RESULTS—In three out of four patients tested,activated protein C (APC) resistance due to heterozygous coagulationfactor V R506Q mutation (factor V Leiden) was found. One patient wasusing oral contraceptives as a circumstantial risk factor and three hadhad spinal anaesthesia for surgical procedures. Family history of venous thromboembolism was negative in all patients. Retrospective evaluation of 66 patients with CVST disclosed that dural puncture wasthe fourth most common risk factor (8%) possibly contributing to thrombosis.
CONCLUSION—Dural puncture may constitute anadditional risk factor for CVST especially in patients with APCresistance or surgery. In such patients a thrombophilia screen is indicated.

     

Progestin-only contraception and venous thromboembolism

Combined oral contraceptives (COC) are the most popular contraceptive method in developed countries. Since their introduction there have been numerous changes and modifications in its composition with the aim to improve safety and tolerability while maintaining contraceptive efficacy. Most of the changes have been conducted on the progestin component, since most of the combinations include ethinyl estradiol as oestrogen. One of the adverse effects of COC is the increased risk of venous thromboembolism (VTE) in two clinical forms of presentation: deep vein thrombosis or pulmonary embolism. This review details the changes in haemostasis induced by progestin-only contraceptives and the risk of VTE in women who utilize this type of contraception; the relationship with other risk factors such as thrombophilia; the interactions of these contraceptives with anticoagulant treatment and finally the eligibility criteria for the use of hormonal contraception in women with previous VTE or thrombophilia carriers.     

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.     

Epidemiology of the contraceptive pill and venous thromboembolism

Current users of combined oral contraceptives have an increased risk of venous thromboembolism. The risk appears to be higher during the first year of use and disappears rapidly once oral contraception is stopped. There is a strong interaction between hereditary defects of coagulation, combined oral contraceptive use and venous thromboembolism. Nevertheless, the routine screening of women before they use combined oral contraception is not recommended. Venous thromboembolism seems to be higher in overweight users, and after air, and possibly other forms of, travel. Both the oestrogen and progestogen content of combined oral contraceptives have been implicated in differences in venous thrombotic risk between products. Even if real, the absolute difference in risk between products is small, because the background incidence of venous thromboembolism in young women is low. All currently available combined oral contraceptives are safe. Progestogen-only oral contraceptives are not associated with an increased risk of venous thromboembolism.     

Cerebral venous and sinus thrombosis

Abstract. Cerebral venous and sinus thrombosis (CVST) can present with a variety of clinical symptoms ranging from isolated headache to deep coma. Prognosis is better than previously thought and prospective studies have reported an independent survival of more than 80% of patients. Although it may be difficult to predict recovery in an individual patient, clinical presentation on hospital admission and the results of neuroimaging investigations are—apart from the underlying condition—the most important prognostic factors. Comatose patients with intracranial haemorrhage (ICH) on admission brain scan carry the highest risk of a fatal outcome. Available treatment data from controlled trials favour the use of anticoagulation (AC) as the first-line therapy of CVST because it may reduce the risk of a fatal outcome and severe disability and does not promote ICH. A few patients deteriorate despise adequate AC which may warrant the use of more aggressive treatment modalities such as local thrombolysis. The risk of recurrence is low (< 10%) and most relapses occur within the first 12 months. Analogous to patients with extracerebral venous thrombosis, oral AC is usually continued for 3 months after idiopathic CVST and for 6–12 months in patients with inherited or acquired thrombophilia but controlled data proving the benefit of long-term AC in patients with CVST are not available.Abbreviations CVST cerebral venous and sinus thrombosis - aPTT activated partial thromboplastin time - IU international units - INR international normalized ratio - AED antiepileptic drug - ICP intracranial pressure - mOsm/kg milliosmole per kilogram     

Inherited thrombophilia as a risk factor for the development of ischemic stroke in young adults

INTRODUCTION: Several recent studies have analyzed a possible effect of thrombophilia risk factors such as factor V Leiden, the prothrombin variant (allele 20210 A), and homozygosity for thermolabile methylenetetrahydrofolate reductase (MTHFR-T) on the development of ischemic stroke (IS). In the present study, we determined the role of these prothrombotic polymorphisms in the early onset of arterial IS or cerebral venous thrombosis (CVT) in a group of young Brazilian adults of Caucasian and African descent. MATERIALS AND METHODS: We conducted a cross-sectional study of 167 survivors of IS (153 patients with arterial IS and 14 cases of CVT; 66 men: 101 women; 124 of Caucasian and 43 of African origin; median age: 32.6 years; range: 15 to 45 years) and compared the prevalence of inherited thrombophilia risk factors with a control group of 225 sex and age matched individuals of the same ethnic background. To determine the interaction with atherogenic risk factors, the following diagnoses were considered: hypertension, hyperlipoproteinemia, diabetes mellitus, smoking status and use of oral contraceptives. RESULTS: In the arterial IS group, no significant variation was found between patients and controls of Caucasian origin regarding the prevalence of factor V Leiden (P = 0.92), the prothrombin variant (P = 0.13) or homozygosity for MTHFR-T (P = 0.61). Among Brazilians of African descent, 10.3% were homozygous for MTHFR-T, which was significantly elevated, odds ratio of 5.9 (95% CI: 0.88 to 49.15). In the CVT group, two Caucasian patients (20%) were heterozygous for the prothrombin variant, odds ratio of 9.7 (95% CI: 0.95 to 89.71) and one patient was carrier of factor V Leiden (P = 0.49). No prothrombotic polymorphism was identified in patients with CVT of African descent. All women in the CVT group were in use of oral contraceptives or in the post-partum state. DISCUSSION: Inherited thrombophilia risk factors were not found to increase the risk of arterial IS among young patients of Caucasian descent. However, a potential role of homozygosity for MTHFR-T was observed in a small group of patients of African origin. The analysis of patients with CVT revealed an increased risk due to the prothrombin gene variant or oral contraceptive use. Further studies including all incoming patients with IS are necessary to evaluate the impact of inherited thrombophilia risk factors on early mortality.     

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.     

EFNS guideline on the treatment of cerebral venous and sinus thrombosis

Cerebral venous and sinus thrombosis (CVST) is a rather rare disease which accounts for <1% of all strokes. Diagnosis is still frequently overlooked or delayed due to the wide spectrum of clinical symptoms and the often subacute or lingering onset. Current therapeutic measures which are used in clinical practice include the use of anticoagulants such as dose-adjusted intravenous heparin or body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH), the use of thrombolysis, and symptomatic therapy including control of seizures and elevated intracranial pressure. We searched MEDLINE (National Library of Medicine), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Library to review the strength of evidence to support these interventions and the preparation of recommendations on the therapy of CVST based on the best available evidence. Review articles and book chapters were also included. Recommendations were reached by consensus. Where there was a lack of evidence, but consensus was clear we stated our opinion as good practice points. Patients with CVST without contraindications for anticoagulation should be treated either with body weight-adjusted subcutaneous LMWH or dose-adjusted intravenous heparin (good practice point). Concomitant intracranial haemorrhage related to CVST is not a contraindication for heparin therapy. The optimal duration of oral anticoagulation after the acute phase is unclear. Oral anticoagulation may be given for 3 months if CVST was secondary to a transient risk factor, for 6-12 months in patients with idiopathic CVST and in those with 'mild' hereditary thrombophilia. Indefinite anticoagulation (AC) should be considered in patients with two or more episodes of CVST and in those with one episode of CVST and 'severe' hereditary thrombophilia (good practice point). There is insufficient evidence to support the use of either systemic or local thrombolysis in patients with CVST. If patients deteriorate despite adequate anticoagulation and other causes of deterioration have been ruled out, thrombolysis may be a therapeutic option in selected cases, possibly in those without intracranial haemorrhage (good practice point). There are no controlled data about the risks and benefits of certain therapeutic measures to reduce an elevated intracranial pressure (with brain displacement) in patients with severe CVST. Antioedema treatment (including hyperventilation, osmotic diuretics and craniectomy) should be used as life saving interventions (good practice point).     

Cerebral Venous Sinus Thrombosis and Acute Myocardial Infarction in a Patient with PAI-1 4G/4G Homozygosity

The plasminogen activator inhibitor-1 (PAI-1) 4G/4G homozygous genotype represents a genetic thrombophilia that has been associated with enhanced risk of arterial and venous thrombotic events. The optimal anticoagulation strategy for PAI-1 4G homozygous patients is unclear. Herein we present a case of a patient with PAI-1 4G/4G homozygosity who was placed on dabigatran after developing cerebral venous sinus thrombosis (CVST), but who then suffered an acute myocardial infarction several weeks later. We seek to highlight the relationship between the PAI-1 4G/4G genotype and risk of CVST, as well as discuss our management strategy in the aftermath of dabigatran failure.     

Low-oestrogen oral contraceptives as a major risk factor for cerebral venous and sinus thrombosis: evidence from a clinical series

Cerebral venous and sinus thrombosis (CVST) is still considered a severe clinical problem that is difficult to diagnose and manage and is linked to a poor prognosis. Nonetheless, conventional cerebral angiography and magnetic resonance imaging (MRI), or more recently, MR angiography allow a more rapid and precise diagnosis, and prognosis has improved with the use of anticoagulant treatment.We report 23 cases of CVST consecutively admitted to the Institute of Neurology of the University of Parma during the period 1990-1997. In all cases diagnosis was confirmed by means of MRI or conventional angiography of brain vessels. Among the patients, 22 were female and 1 was male. In all patients, plasma levels of protein C, protein S, antithrombin III (ATIII) and antiphospholipid antibodies (APA) were evaluated. In 15 of 23 patients, the presence of factor V Leiden mutation was also determined, and found positive in 3 patients (20%). Of the 22 female patients, 15 (68%) were on low-oestrogen (containing less than 50 microg oestrogen) oral contraceptive (OC) treatment. This percentage of OC use by patients with CVST is much higher than that of the rest of the female Italian population. OC use was associated with the presence of factor V Leiden mutation in two cases, with a deficiency of protein C in 1 case and a deficiency of protein S in another.Whether low-oestrogen Ocs may induce cerebral thromboembolic events is an open matter. According to our data, it may be argued that Ocs, even if at low oestrogen content, represent a major risk factor for CVST. The use of Ocs, as is the case for systemic venous thromboembolic events, may further increase the risk of CVST in women carrying the factor V Leiden mutation or other inherited hyperthrombotic conditions.     

EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients

Background: Cerebral venous and sinus thrombosis (CVST) is a rather rare disease which accounts for <1% of all strokes. Diagnosis is still frequently overlooked or delayed as a result of the wide spectrum of clinical symptoms and the often subacute or lingering onset. Current therapeutic measures which are used in clinical practice include the use of anticoagulants such as dose‐adjusted intravenous heparin or body weight‐adjusted subcutaneous low‐molecular‐weight heparin (LMWH), the use of thrombolysis and symptomatic therapy including control of seizures and elevated intracranial pressure. Methods: We searched MEDLINE (National Library of Medicine), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Library to review the strength of evidence to support these interventions and the preparation of recommendations on the therapy of CVST based on the best available evidence. Review articles and book chapters were also included. Recommendations were reached by consensus. Where there was a lack of evidence but consensus was clear we stated our opinion as good practice points. Results and conclusions: Patients with CVST without contraindications for anticoagulation (AC) should be treated either with body weight‐adjusted subcutaneous LMWH or with dose‐adjusted intravenous heparin (level B recommendation). Concomitant intracranial haemorrhage (ICH) related to CVST is not a contraindication for heparin therapy. The optimal duration of oral anticoagulant therapy after the acute phase is unclear. Oral AC may be given for 3 months if CVST was secondary to a transient risk factor, for 6–12 months in patients with idiopathic CVST and in those with “mild” thrombophilia, such as heterozygous factor V Leiden or prothrombin G20210A mutation and high plasma levels of factor VIII. Indefinite AC should be considered in patients with recurrent episodes of CVST and in those with one episode of CVST and ‘severe’ thrombophilia, such as antithrombin, protein C or protein S deficiency, homozygous factor V Leiden or prothrombin G20210A mutation, antiphospholipid antibodies and combined abnormalities (good practice point). There is insufficient evidence to support the use of either systemic or local thrombolysis in patients with CVST. If patients deteriorate despite adequate AC and other causes of deterioration have been ruled out, thrombolysis may be a therapeutic option in selected cases, possibly in those without large ICH and threatening herniation (good practice point). There are no controlled data about the risks and benefits of certain therapeutic measures to reduce an elevated intracranial pressure (with brain displacement) in patients with severe CVST. However, in severe cases with impending herniation craniectomy can be used as a life‐saving intervention (good practice point).     

Oral contraceptives, hormone replacement therapy and thrombosis

Oral contraceptives and hormone replacement therapy are used by hundreds of millions of women worldwide. Since the early 1960s it is known that female hormones increase the risk of venous thrombosis, myocardial infarction and stroke. This risk is still present with current low-dose oral contraceptives and, even though in absolute terms the risk is small, oral contraceptives form the major cause of thrombotic disease in young women. The risk is higher during the first year of use (up to I per 1000 per year), with the use of desogestrel- or gestodene-containing oral contraceptives ("third generation progestogens") and among women with a prothrombotic predispositon. Hormone replacement therapy increases the risk of venous thrombosis, while results of randomised trials so far do not substantiate the expectation of a beneficial effect on the risk of arterial cardiovascular disease. First results are emerging that specific subgroups of women, with prothrombotic or other abnormalities, may be at risk, especially during the first years of use of hormone substitution.     

Loco-regional thrombolysis in the treatment of cerebral venous and sinus thrombosis: report of two cases

Although intravenous (i.v.) heparin is widely used as the first line treatment for cerebral venous and sinus thrombosis (CVST), the most appropriate therapy for this disease is still controversial. We report 2 cases of CVST who were successfully treated by means of loco-regional thrombolysis with urokinase. In the first case we chose this treatment instead of i.v. heparin because clinical conditions of the patient appeared critical for life on hospital admission; in the second case loco-regional thrombolysis was performed because a full-dose heparin treatment over 8 days failed to improve the clinical picture of the patient. In the literature, there are no established criteria for the use of loco-regional thrombolysis in CVST. On the basis of our own experience and few previous reports on the matter, we suggest that loco-regional thrombolysis should be considered an appropriate treatment for CVST when patients are at life risk, when an involvement of deep cerebral veins is present or when, after full heparinization, patients are doing poorly clinically.     

Prothrombin gene variant (G20210A) in a patient with cerebral venous sinus thrombosis.

We describe a 33-year-old woman, who presented with lowered consciousness level and seizures, due to cerebral venous sinus thrombosis with venous haemorrhagic infarcts. The patient. who was taking oral contraceptives, appeared to be heterozygous for a prothrombin gene variant, which is due to a G-->A transition at position 20210. This 20210A prothrombin has recently been established as an important risk factor for cerebral venous sinus thrombosis, which interacts with oral contraceptive use.     

The APC-PCI concentration as an early marker of activation of blood coagulation: A study of women on combined oral contraceptives

Background

The risk of venous tromboembolism (VTE) in women taking combined oral contraceptives (COCs) is attributed to changes in coagulation and fibrinolysis. The impact of the COCs may be greater in women with preexisting thrombophilic defects. Nevertheless most women who suffer from venous thrombosis do not have any of the well known hereditary or acquired risk factors. A simple and sensitive marker of”thrombogenicity” has not been identified.

Objectives

To investigate the effects of two different monophasic combined oral contraceptives (COCs) on the plasma concentrations of activated protein C-inhibitor of protein C ( APC-PCI) and on comparable hemostatic factors in fertile women.

Method

Forty four healthy nulliparous women with regular menstrual periods were included and randomly assigned to start with a monophasic preparation containing 30 μg ethinylestradiol and 150 μg levonogestrel (LNG/EE) or a preparation containing 30 μg ethinylestradiol and 150 ug desogestrel (DG/EE). After a wash out period of two months, treatment with the alternate preparation was initiated and continued for two more cycles.

Results

The plasma concentration of the APC-PCI complex and thrombin-antithrombin complex (TAT) increased during treatment with the two COCs. During DG/EE treatment the APC-PCI complex increased significantly more than during LNG/EE (p < 0,01).The plasma concentration of D-dimer did not increase during OC treatment.

Conclusion

The APC-PCI complex concentration, which serves as a marker for thrombin generation and indicates hypercoagulability, was increased during COC treatment compared to baseline. The method is a sufficiently sensitive marker to detect even small differences in the activation of coagulation.     

Cerebral venous thrombosis: influence of risk factors and imaging findings on prognosis

PURPOSE: To investigate imaging findings, risk factors and outcome in patients with cerebral venous thrombosis (CVT). METHODS: Records of all patients with diagnosis of CVT between 1992 and 2002 were reviewed. Patients with CNS infection and with CVT secondary to invasive procedures were excluded. Inherited and acquired thrombophilia were searched in all patients. RESULTS: Twenty-four patients (18 women, 6 men) with mean age of 29.5 years (range 3-48 years) were identified. Mean follow-up was 44 months (range 11-145 months). The most common symptoms were headache (75%), vomiting (33%) and impairment of consciousness (21%). Probable causes of CVT could be determined in 21 (88%) patients: pregnancy or puerperium in six (25%), oral contraceptive use in four (17%), head trauma in two (8%), mastoiditis in one (4%), nephrotic syndrome in one (4%), systemic disease in three (13%), and inherited thrombotic risk factors in four (17%) patients. CVT associated with pregnancy, puerperium and use of oral contraceptives had a significant better outcome than CVT caused by inherited thrombophilia or systemic disease (OR=14.4; p=0.02). CT scans were abnormal in 15 (62.5%) patients and MRI with gadolinium was abnormal in all. Those with parenchymal involvement had neurological sequelae during follow-up. All were treated with heparin followed by oral anticoagulants, and none had new or worsening of pre-existing intracerebral hemorrhage. CONCLUSION: MRI is superior to conventional CT for diagnosing CVT. Patients with parenchymal lesions, thrombophilia and antiphospholipid syndrome had greater risk to be left with neurological sequelae. Anticoagulant therapy did not predispose to further intracerebral hemorrhage.     

Paradoxical cerebral embolism: eight cases

We evaluated eight patients with possible or probable paradoxical cerebral embolism. One patient had a hemispheric transient ischemic attack; the others had infarcts. Ischemic symptoms followed a Valsalva's maneuver in three cases. Others were linked to placement of a Swan-Ganz catheter, deep venous thrombosis and pulmonary embolism, right atrial myxoma, and use of oral contraceptives. Four had no known predisposing conditions. In six patients, contrast echocardiography showed right-to-left shunting. Cardiac catheterization showed a patent foramen ovale in three patients; one had an atrial septal defect. In the clinical setting of otherwise unexplained cerebral embolism in a young patient, paradoxical cerebral embolism should be considered. Contrast echocardiography is a useful screening test for this purpose.     

Screening for thrombophilia and antithrombotic prophylaxis in pregnancy: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET)

The term thrombophilia describes an increased tendency to develop thrombosis and many laboratory markers with different strengths of association with thrombosis have been identified. The main causes of maternal mortality and morbidity in developed countries is venous thromboembolism (VTE) and obstetric complications. During pregnancy and puerperium the risk for VTE increases due to hemostatic imbalance towards a prothrombotic state, and it is further increased in women carriers of thrombophilia; recent studies have also demonstrated an association between thrombophilia and obstetric complications. These complications are, therefore, considered potentially preventable with the prophylactic administration of anticoagulant drugs, although their efficacy is not proven by data from randomized controlled trials. After a systematic comprehensive literature review and using a rigorous methodology, the expert panel formulated recommendations regarding the usefulness of screening for thrombophilia in pregnancy to identify high-risk women and for the management of antithrombotic prophyalxis. When evidence is lacking, consensus-based recommendations are provided.