Management Of Thrombophilia Research Articles

Management of thrombophilia in primary care

Thrombophilia is a disorder associated with an increased tendency to thrombosis. Thrombophilia can be acquired or hereditary. Only a few of the inherited thrombophilia pre­sent a major risk of thrombosis and they should be diag­nosed when thromboembolic disease or miscar­riages occur in pregnant women. It is important to know the personal history and the family history of the patients, to look for the cause of venous or arterial throm­bo­embolism and to investigate the patients at risk in order to apply the prophylaxis and the anticoagulant treat­ment when necessary. A special attention should be given to patients with antiphospholipid syndrome, some­times requiring anticoagulation indefinitely.

Preventing thrombophilia-related complications of pregnancy: an update

Approximately half of all pregnancy-related venous thromboembolic events are associated with thrombophilia. Although the most compelling data for a link between thrombophilia and other adverse pregnancy outcomes derive from women with antiphospholipid antibodies, some studies also suggest an association between these pregnancy complications and hereditary thrombophilias. Management of thrombophilia often involves anticoagulant therapy; however, use of these agents during pregnancy is challenging. There is a paucity of high-quality studies and consequently, recommendations are based largely on extrapolation from data in nonpregnant women, in addition to observational studies and a few small randomized studies. This article will review the impact of the thrombophilias on pregnancy and its outcome, evidence for therapies aimed at the prevention of thrombophilia-related pregnancy complications, and the most recent recommendations contained in the 9th Edition of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

Assisted reproduction in a patient with Klippel-Trenaunay syndrome: management of thrombophilia and consumptive coagulopathy

Klippel-Trenaunay Syndrome (KTS) is a rare, sporadic triad of congenital malformations involving an extensive port wine stain, soft tissue or bone hypertrophy and underlying venous and/or lymphatic malformation involving an extremity. Pregnancy is known to exacerbate KTS complications and can put women at increased obstetrical risk due to deep venous thrombosis and other thromboembolic events. Here we report a case of a patient with KTS who achieved a pregnancy through in vitro fertilization (IVF) using her own eggs and a gestational surrogate in the setting of hypercoagulability and chronic consumptive coagulopathy.

Special issue of the 10th EFCC Continuous Postgraduate Course in Clinical Chemistry: “New Trends in Classification, Diagnosis and Management of Thrombophilia”, October 2010, Dubrovnik, Croatia

Special issue of the 10th EFCC Continuous Postgraduate Course in Clinical Chemistry: “New Trends in Classification, Diagnosis and Management of Thrombophilia”, October 2010, Dubrovnik, Croatia

3A.3 Management of thrombophilia in women with placental vascular complications

The hemostatic system plays an important role in the success of pregnancy and the process of implantation, and placentation. Implantation of the fertilized egg into the uterine decidua establish a contact with maternal circulation, which is crucial for the success of pregnancy. Prothrombotic state, such as thrombophilias may interfere with these processes with thrombosis, abnormal implantation and trophoblast invasion and other as yet unknown mechanisms, which may lead to placental vascular complications (PVC). The questions that should be asked are what is the prevalence of PVC, is there an association with thrombophilias, what is the rate of recurrence, and are women with pregnancy complications and/or placental thrombosis and thrombophilias candidates for anti-thrombotic therapy as certainly are those with venous and arterial thrombosis? There is increasing evidence regarding the specific association of PVC such as severe preeclampsia, fetal loss, fetal growth restriction (FGR), abruptio placentae and thrombophilias. The overall prevalence of PVC is approximately 8%, however these complications account for 75% of fetal morbidity and mortality regardless of thrombophilias. It is also evident that prior history of any of these pregnancy complications is a strong predictor of their recurrence in a subsequent pregnancy and prior poor pregnancy outcome is associated with a significantly higher risk of subsequent pregnancy outcomes. When PVC are associated with thrombophilia the recurrence rate in subsequent pregnancies may be as high as 54% (Table 1), while the type of pregnancy complications may alter.

The origins of cerebral palsy

Cerebral palsy is the most common and visible motor disability of childhood. Its aetiology remains a topic of hot debate between those who see it as a reflection of medical mismanagement of an avoidable complication and those who see its origins in the development of the fetal brain affected at many points along a causal pathway to damage. This review outlines the themes of research publications over the year 2004/2005. The review looks at recent findings relating to epidemiology, infection and inflammation, prematurity, multiple pregnancy, thrombophilias, genetics, placenta, neuroimaging and rescue therapies in cerebral palsy. Papers this year have helped clarify risk groups and identify some areas (e.g. the management of thrombophilias and the potential of induced hypothermia) with the potential to be rapidly introduced into clinical practice. In this enigmatic and multifactorial condition, however, progress remains slow. New tools such as magnetic resonance imaging are providing valuable insights into the lesions that result in cerebral palsy but the pathways to injury remain unclear. The future of cerebral palsy research lies in understanding the complex interactions of multiple factors on the road to cerebral palsy or in looking for final common pathways such as inflammation which may be amenable to manipulation.

Management of thrombophilia in pregnant women

Management of thrombophilia in pregnant women

Management of thrombophilia

It is now possible to identify acquired and hereditary risk factors in a substantial percentage of patients presenting with a venous thrombotic event. Discovery of the factor V Leiden and prothrombin G20210A mutations has greatly increased the percentage of patients in whom venous thrombosis can be attributed to hereditary thrombophilia. There is, however, considerable uncertainty as to how this information should be used in patient management. Although prolonged anticoagulation at an international normalized ratio of 2-3 is highly effective in preventing thrombotic recurrences, this benefit is partially offset by major bleeding which occurs at an average rate of 2%-3% per year. A decision as to the overall benefit of extended anticoagulation in the individual patient requires assessment of the risk of recurrence in the absence of treatment vs. the bleeding risk associated with prolonged anticoagulation. Low-intensity warfarin therapy or novel anticoagulants such as oral direct thrombin inhibitors may prove effective strategies for preventing recurrent venous thromboembolism in patients with thrombophilia.

The Management of Thrombophilia During Pregnancy: A Canadian Survey

Objective: To determine current Canadian practice patterns in the management of pregnant women with thrombophilia.Methods: Physician members of the Society of Obstetricians and Gynaecologists of Canada (SOGC) who provide obstetrical care were invited to complete a closed-ended questionnaire in which they were presented 5 clinical scenarios involving thrombophilic pregnancies and asked to give their management recommendations. The 5 scenarios presented in the survey were of a pregnant woman with (1) asymptomatic factor V Leiden (FVL), (2) asymptomatic FVL and a family history of venous thromboembolism (VTE), (3) FVL and recurrent fetal loss, (4) FVL and a previous VTE, or (5) antiphospholipid antibody syndrome and recurrent fetal loss.Results: Of the 1448 eligible SOGC members invited, 18 had moved with no forwarding address, and 662 (46.3% of the remainder) responded. The majority (65%) of the respondents were obstetricians and 51 % of them had a university-affiliated practice. In scenario 1, 26% of physicians indicated they would recommend some form of antepartum thromboprophylaxis, whereas in the remaining four scenarios, 58% to 84% would definitely recommend antepartum thromboprophylaxis.Conclusion: Most clinicians favour intervening with thromboprophylaxis in pregnant thrombophilic women rather than observing without prophylaxis. This tendency spans a wide range of clinical scenarios, despite a lack of evidence to support such decisions. This survey highlights the need to provide clinicians and women with evidence for the safety and effectiveness of prophylaxis, before these interventions become the default recommendation by clinicians caring for this prevalent group of women.

Management of Thrombophilia in Renal Transplant Patients

Renal allograft recipients with thrombophilia (a hypercoagulable state) are at higher risk for early allograft loss. Following an episode of allograft renal vein thrombosis in a patient subsequently diagnosed with protein C deficiency, we adopted universal screening for hypercoagulable risk factors. Patients with a history of a thromboembolic event underwent laboratory screening for thrombophilia. Eight patients with a defined hypercoagulable disorder or a strong clinical history of thrombosis even in the absence of hematologic abnormalities were treated with anticoagulation following renal transplantation. We reviewed the outcomes of these eight patients and all renal transplant recipients at our center who developed thrombotic complications after renal transplantation. Since the introduction of universal screening for hypercoagulable risk factors, 235 consecutive transplants were performed without allograft thrombosis. Eight patients with evidence of thrombophilia, recognized before renal transplantation, received perioperative heparin and postoperative oral anticoagulation. Two of these eight patients developed perinephric hematomas requiring evacuation, blood transfusion, and temporary withholding of anticoagulation. Of interest, two of the remaining 227 patients, not identified with thrombophilia before surgery, developed thrombotic complications after renal transplantation. A hypercoagulable disorder was subsequently documented in each. Identifying patients with thrombophilia before transplantation and defining their management presents many challenges. The risk of allograft thrombosis must be weighed against the risk of perioperative bleeding and the need for long-term anticoagulation. Recommendations for managing thrombophilia in renal transplant recipients are suggested based on our experience and review of the literature.

Thrombophilia: what's a practitioner to do?

Management of thrombophilia is an ever-changing field as new disorders are described and additional clinical experience accrues. This paper addresses three common management issues in the care of patients with thrombophilia. The first two topics are updates for common but perplexing hypercoagulable states and the last topic introduces a new option for optimal management of oral anticoagulant therapy. Dr. Jacob Rand updates and organizes the approach to patients with antiphospholipid syndrome. This syndrome is a common acquired thrombophilic state, but the diagnosis and treatment of patients remains a challenge. Dr. Rand outlines his diagnostic and treatment strategies based on the current understanding of this complicated syndrome. Dr. Barbara Konkle addresses the special concerns of managing women with thrombophilia. Hematologists are often asked to advise on the risks of hormonal therapy or pregnancy in a woman with a personal or family history of thrombosis or with an abnormal laboratory finding. Dr. Konkle reviews the available data on the risks of hormonal therapy and pregnancy in women with and without known underlying thrombophilic risk factors. In Section III, Dr. Gail Macik will discuss a new approach to warfarin management. Several instruments are now available for home prothrombin time (PT) monitoring. Self-testing and self management of warfarin are slowly emerging as reliable alternatives to traditional provider-based care and Dr. Macik reviews the instruments available and the results of studies that support this new management option.

1 Epidemiology, risk factors and prophylaxis of venous thrombo-embolism in obstetrics and gynaecology

Venous thrombo-embolism remains a major cause of mortality and morbidity following gynaecological surgery and in association with pregnancy and delivery. Specific risk factors can be identified pre-operatively and before or during pregnancy and delivery. Clinicians and units should develop guidelines for risk assessment and the implementation of specific thromboprophylactic measures in patients considered to have significant risk. The main prophylactic techniques are unfractionated and low-molecular-weight heparins and physical methods such as graduated elastic compression stockings. It should be noted that there are particular concerns with regard to the use of pharmacological thromboprophylaxis with both heparin and warfarin in pregnancy. Unfractionated heparin is associated with osteoporotic problems, allergy and heparin-induced thrombocytopenia which can cause significant thrombotic problems. Warfarin is associated with teratogenesis and the risk of bleeding in mother and fetus. Clearly, where antenatal thromboprophylaxis is to be used, the risk of the anticoagulants employed must be weighed against the potential benefits. Such assessment might be best done prior to pregnancy in order that the patient can enter pregnancy with a clear view of the potential hazards and benefits. Low-molecular-weight heparins are being increasingly used in pregnancy but it is unclear to what extent they are safer than unfractionated heparins. However, they do appear to have substantially less risk of heparin-induced thrombocytopenia and possibly less risk of heparin-induced osteoporosis. Increasingly, thrombophilia is recognized as underlying many thrombotic problems, particularly in young women, and when the events occur in association with pregnancy. In view of the complexity in the management of such patients, it is important that they be referred to a unit with specific expertise in the management of thrombophilia.

Current status on new anticoagulant and antithrombotic drugs and devices.

Several new drugs for the management of thromboembolic disorders have recently become available. Low-molecular-weight heparins are being evaluated for the prophylaxis of medical and surgical deep venous thrombosis and pulmonary embolism; for the treatment of pre-existing thrombosis; and for cases of coronary syndrome (unstable angina, myocardial infarction), thrombotic and ischemic stroke, interventional cardiology, pregnancy, cancer, and transplantation-associated thrombosis. A chemically synthesized heparin pentasaccharide, which has purely anti-factor Xa activity and does not induce thrombocytopenia, is also in clinical trial. Thrombin inhibitors, such as hirudin and argatroban, are a practical anticoagulant substitute where heparin cannot be used. They are also useful for the management of coronary syndrome and as adjunct therapy. The antiplatelet agent ticlopidine and its analogue, clopidogrel, which does not produce blood dyscrasia, are effective for the secondary prevention of thrombotic stroke and the management of combined arterial thrombotic syndromes. Glycoprotein-targeting antibodies, synthetic derivatives, and peptides (some of which are orally bioavailable) have added a new dimension to the management of arterial thrombosis and high-risk patients having angioplasty. Plasma-derived agents, such as antithrombin III, are available for the management of thrombophilia and disseminated intravascular coagulation. Compression devices and the foot pump, alone and in combination with pharmacologic agents, have been used successfully. Combination therapy using various agents in different proportions have also been found useful. Although there is much enthusiasm in this quickly developing area and clinical trials are demonstrating the antithrombotic efficacy of the new drugs, safety considerations require additional clinical validation. Long-term outcomes and costs also need to be addressed objectively.

Management of patients with thrombophilia.

In broad terms patients who have a propensity to thrombosis do so because they have a disorder of the blood (e.g. a coagulation defect or a cellular abnormality such as polycythaemia) or a defect of the vessel wall. Where enhanced coagulation is the primary cause the disorder is referred to as thrombophilia.1 In this article we review the causes, diagnosis and management of thrombophilia.

Management of thrombophilia in pregnancy

Thromboembolism remains a major cause of maternal morbidity and mortality. The incidence of thrombosis associated with pregnancy is stated to be around 0.99% 1 but is greater in women with familial or acquired thrombophilia. Around 50% of pregnancies in women with antithrombin III deficiency are complicated by thrombosis. Anticoagulation throughout pregnancy and the puerperium is recommended in women with antithrombin III deficiency. Because thrombosis is less common in women with protein C or protein S deficiency less aggressive management may be appropriate during pregnancy but anticoagulation post partum is generally recommended. The most important acquired thrombophilic abnormality is the development of antiphospholipid antibodies (‘lupus anticoagulants’). Women with these antibodies may present major problems but no clear guidelines for their management currently exist. The majority of women with a history of thrombosis have no identifiable haemostatic abnormality. Management of pregnancy in these patients depends on individual circumstances.

Guidelines on the investigation and management of thrombophilia. The British Committee for Standards in Haematology.

Guidelines on the investigation and management of thrombophilia. The British Committee for Standards in Haematology.