Venous Thromboembolism During Pregnancy - American Family Physician Thrombophlebitis Wang Klippel–Trénaunay syndrome - Wikipedia
Venous thromboembolism is the leading cause of maternal death in the United States. Pregnancy is Thrombophlebitis Wang risk factor for deep venous thrombosis, and risk is further increased with a personal or family history of thrombosis or thrombophilia.
Screening for thrombophilia is not recommended for the general population; however, testing for inherited or acquired thrombophilic conditions is recommended when personal or family history suggests increased risk, Thrombophlebitis Wang.
Factor V Leiden and prothrombin GA mutation are the most common inherited thrombophilias, and antiphospholipid antibody syndrome is the most important acquired defect. Clinical symptoms of deep venous thrombosis may be subtle and difficult to distinguish from gestational edema. Venous compression Doppler ultrasonography is the diagnostic test of choice.
Pulmonary embolism typically presents postpartum with dyspnea and tachypnea. Multidetector-row spiral computed tomography is the test of choice for pulmonary embolism. Warfarin is contraindicated during pregnancy, but is safe to use postpartum and is compatible with breastfeeding. Low-molecular-weight heparin has largely replaced unfractionated heparin for prophylaxis and treatment in pregnancy.
LMWHs are recommended for the treatment of acute DVT and PE in pregnancy because of equivalent or superior effectiveness and safety compared with unfractionated heparin. Systematic review 35 and Cochrane review For information about the SORT evidence rating system, see http: Virchow's triad of hypercoagulation, Salben und Gele von Krampfadern und Thrombophlebitis damage, and venous stasis all occur in pregnancy, resulting in a relative risk of 4.
VTE risk factors include age greater than 35 years, obesity body mass index higher than 30 kg per 2grand multiparity, and a personal or family history of VTE or thrombophilia. Approximately 50 percent of pregnant women with VTE have a thrombophilia, compared with 10 percent of the general population. Thrombophilic disorders may be inherited or acquired. Thrombophilias are associated with pregnancy complications, including early and late pregnancy loss, intra-uterine growth restriction, and placental abruption.
DVT occurs with equal frequency in each trimester and postpartum. Diagnosing DVT is difficult during pregnancy. Clinical suspicion is confirmed in 10 percent of pregnant women, compared with 25 percent of nonpregnant patients. Pain with foot dorsiflexion Homans' sign is neither sensitive nor specific for diagnosing DVT in patients who are not pregnant; 18 however, data are lacking for this in patients who are pregnant. Symptoms of dyspnea are nonspecific in pregnancy.
Of clinically suspected PE, Thrombophlebitis Wang, only 4 percent are confirmed in pregnant patients, versus 30 percent in nonpregnant patients, Thrombophlebitis Wang. Figure 1 presents an approach to the diagnosis and treatment of DVT in pregnancy derived from studies of non-pregnant patients.
Algorithm for diagnosis and treatment of DVT in pregnancy. Information from references 19 and Venous compression ultrasonography is the test of choice for diagnosing DVT because it is noninvasive, safe, Thrombophlebitis Wang, and relatively inexpensive.
Thrombophlebitis Wang still serves as the definitive test for diagnosing DVT 19 and may be used in clinical situations where noninvasive tests are equivocal, empiric anticoagulation is relatively contraindicated, and clinical suspicion is high. Figure 2 outlines a diagnostic approach for suspected PE based on expert opinion derived from studies mostly involving nonpregnant patients.
Algorithm for the diagnosis of PE in pregnancy, Thrombophlebitis Wang. Information from references 24 through With low or moderate clinical suspicion, a negative highly sensitive d -dimer test rules out PE.
Some authorities recommend lower extremity venous compression ultrasonography as the next test because if DVT is present, anticoagulant treatment will be the same as for PE, and venous compression ultrasonography Thrombophlebitis Wang fetal radiation exposure.
When d -dimer testing and venous compression ultrasonography are inconclusive, multidetector-row spiral computed tomography has become the test of choice for diagnosing PE in pregnancy, Thrombophlebitis Wang.
Arterial blood gas monitoring with the patient sitting upright for greatest accuracychest radiography, and electrocardiography looking for right ventricular hypertrophy can be done in unstable and immobile patients and may help diagnose PE or suggest other conditions, Thrombophlebitis Wang.
The optimal treatment of VTE during pregnancy has not been studied via randomized controlled trials, and clinical recommendations are based on expert opinion. Stabilization is the first priority. Airway, breathing, and circulation should be addressed immediately and may require management in the intensive care unit.
With life-threatening PE, thrombolytic therapy, percutaneous catheter thrombus fragmentation, or surgical embolectomy may be used, depending on local resources. Warfarin should be avoided during pregnancy, Thrombophlebitis Wang. It crosses the placenta and increases the risk of miscarriage, stillbirth, embryopathy nasal hypoplasia or stippled epiphysescentral nervous system abnormalities, and maternal and fetal hemorrhage.
Data derived from nonpregnant populations suggest that therapeutic anticoagulation following a first episode of VTE should continue for at least six months from diagnosis. Table 1 lists a typical therapeutic LMWH dose.
It is not necessary to follow the activated partial thromboplastin time, Thrombophlebitis Wang. Continuous IV infusion for a total of at least 30, IU over 24 hours Information from references 101232and UFH is considered an acceptable alternative. Intrapartum management may vary depending on the indication for anticoagulation and whether therapeutic or prophylactic doses have been Thrombophlebitis Wang. Evidence is insufficient to recommend for or against an inferior vena cava filter if anticoagulation is contraindicated or repeat PE occurs despite adequate anticoagulation, Thrombophlebitis Wang.
Systematic reviews of observational studies have found VTE prophylaxis with LMWH to be safe and effective in pregnancy, Thrombophlebitis Wang, but there are no randomized controlled trials confirming this, Thrombophlebitis Wang.
Information from references 6 and This indication is controversial; patient and caregivers may decide whether to use antenatal heparin prophylaxis; regardless of this decision, postpartum prophylaxis is recommended 10 Six weeks postpartum Gewichtheben und Krampfadern early in pregnancy as possible Six weeks postpartum; 10 those with recurrent or life-threatening events may require long-term prophylaxis Thrombophlebitis Wang Antithrombin deficiency, homozygous factor V Leiden; two or more minor risk factors i.
Low-dose aspirin with or without heparin as early in pregnancy as possible Six to eight weeks postpartum As early in pregnancy as possible; 5 peripartum and postpartum may be sufficient if no Thrombophlebitis Wang history of thrombophilia, no severe protein C deficiency less than 50 percent of normal levelsThrombophlebitis Wang, and no additional risk factor, such as immobilization, hospitalization, surgery, infection or thrombophlebitis 5.
Six weeks postpartum 5. Single heterozygous factor V Leiden or heterozygous prothrombin GA mutation. No prophylaxis indicated unless family history of venous thromboembolism and additional risk Thrombophlebitis Wang such as immobilization, Thrombophlebitis Wang, surgery, infection, or thrombophlebitis; 5 prophylaxis started peripartum or postpartum when indicated 5, Thrombophlebitis Wang.
Four to six weeks postpartum 5. Information from references 510Thrombophlebitis Wang, 153239and Low-dose aspirin 75 to 81 mg is sometimes used for women with an increased risk of thrombosis that does not meet the threshold for prophylactic heparin e. Postpartum thromboprophylaxis is not routinely indicated following vaginal delivery, 42 but may become necessary because of labor-related risk factors, such as prolonged Thrombophlebitis Wang, mid-forceps delivery, and immobility after Thrombophlebitis Wang. Unless other VTE risk factors are also present, women who undergo a scheduled cesarean delivery are not routinely placed on pharmacologic Thrombophlebitis Wang prophylaxis.
Already a member or subscriber? He is co-medical director of the mother-baby unit at the University of New Mexico Hospital, Albuquerque. He completed a family medicine residency at the University of New Mexico School of Medicine and a fellowship in obstetrics at the University of Medizinische Bandagen auf Krampfadern N.
She completed medical school, residencies in family and preventive medicine, and research fellowships at the University of North Carolina at Chapel Hill. Address correspondence to Lee T. Reprints are not available from the authors. Management of venous thrombo-embolism: Pregnancy-related mortality surveillance—United States, — Management of venous thromboembolism: Trends in the incidence of venous thromboembolism during pregnancy or postpartum: Prediction, prevention and treatment of venous thromboembolic disease in pregnancy.
Thromboprophylaxis during pregnancy, labour and after vaginal delivery. Royal College of Obstetricians and Gynaecologists, Accessed February 23, Venous thromboembolism during pregnancy or postpartum: Postpartum maternal mortality and cesarean delivery. American College of Obstetricians and Gynecologists. Changes in protein C and protein S levels in normal pregnancy.
Am J Obstet Gynecol. Thromboembolic disease in pregnancy and the puerperium: Effect of hemostatic risk factors on the individual probability of thrombosis during pregnancy and the puerperium. Frequency of pregnancy-related venous thromboembolism in anticoagulant factor-deficient women: Incidence, Thrombophlebitis Wang, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during Thrombophlebitis Wang. Use of antithrombotic agents during pregnancy, Thrombophlebitis Wang.
Homans' sign in the diagnosis of deep venous thrombosis. Current diagnosis of venous thromboembolism in primary care: Strategies for the safe and effective exclusion and diagnosis of deep vein thrombosis by the sequential use of clinical score, Thrombophlebitis Wang -dimer testing, and compression ultrasonography.
Establishing a normal range for d -dimer levels through pregnancy to aid in the diagnosis of pulmonary embolism and deep vein thrombosis. Int J Clin Lab Res. Role of computed tomography and magnetic resonance imaging for deep venous thrombosis and pulmonary embolism.
Venous thromboembolism in obstetrics and gynecology, Thrombophlebitis Wang.
Thrombophlebitis Wang OMIM Entry - % - KLIPPEL-TRENAUNAY-WEBER SYNDROME
N Engl J Med ; The efficacy and safety of anticoagulant treatment for patients with acute, symptomatic superficial-vein thrombosis in the legs, but without concomitant deep-vein thrombosis or symptomatic pulmonary embolism at presentation, have not been established.
Full Text of Background In a randomized, Thrombophlebitis Wang, double-blind trial, we assigned patients to receive either fondaparinux, administered subcutaneously at a dose of 2.
The primary efficacy outcome was a composite of death from any cause or symptomatic pulmonary embolism, symptomatic deep-vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of superficial-vein thrombosis at day The main safety outcome was major bleeding.
The patients were followed until day Full Text of Methods The primary efficacy outcome occurred in 13 of patients 0. The incidence of each component of the primary efficacy outcome was significantly reduced in the fondaparinux group as compared with the placebo group, except for the outcome of death 0.
Similar risk reductions were observed at day A total of 88 patients would need to be Thrombophlebitis Wang to prevent one instance of pulmonary embolism or deep-vein thrombosis. Major bleeding occurred in one patient in each group, Thrombophlebitis Wang. The incidence Thrombophlebitis Wang serious adverse events was 0, Thrombophlebitis Wang.
Full Text of Results Fondaparinux at a dose of 2. Full Text of Discussion Superficial-vein thrombosis of the legs is a common condition, 1,2 with an estimated incidence that may exceed Thrombophlebitis Wang Dressings mit trophischen Geschwüren in der Ukraine deep-vein thrombosis. The treatment of this disease has not been adequately addressed in randomized trials.
Accordingly, the recommendations in various guidelines are weak, and in practice, Thrombophlebitis Wang, therapeutic strategies vary, ranging from no treatment to the use of antiinflammatory agents or anticoagulant drugs or surgery. We conducted the Comparison of Arixtra in Lower Limb Superficial Vein Thrombosis with Placebo CALISTO trial to evaluate the efficacy and safety of fondaparinux, a specific factor Xa inhibitor, in reducing symptomatic venous thromboembolic complications or death from any cause in patients with acute, isolated superficial-vein thrombosis of the legs.
For the active treatment, we selected the prophylactic dose of 2. Hospitalized or nonhospitalized patients 18 years of age or older, Thrombophlebitis Wang, with acute, Thrombophlebitis Wang, symptomatic lower-limb superficial-vein thrombosis at least 5 cm long, as confirmed by standardized compression ultrasonography, were eligible to undergo randomization. Patients were excluded if the interval between the onset of their symptoms and planned randomization was more than 3 weeks; if they had been treated for cancer within the previous 6 months; if they presented with symptomatic or asymptomatic deep-vein thrombosis, Thrombophlebitis Wang, symptomatic documented pulmonary embolism, or superficial-vein thrombosis associated with sclerotherapy or placement of an intravenous catheter or located within 3 cm of the saphenofemoral junction; or if they had a documented history of superficial-vein thrombosis within the previous 3 months or deep-vein thrombosis or pulmonary embolism within the previous 6 months.
Other exclusion criteria were major Thrombophlebitis Wang within the previous 3 months and conditions that could confer a predisposition to bleeding, including severe hepatic impairment, a creatinine clearance of less than 30 ml per minute, and a platelet count of less thanper cubic millimeter. Finally, Thrombophlebitis Wang, women of childbearing age were excluded if they Thrombophlebitis Wang pregnant or were not using a reliable contraceptive method.
This trial was an international, multicenter, randomized, double-blind, placebo-controlled study; the protocolincluding the statistical analysis plan, is available with the full text of this article at NEJM, Thrombophlebitis Wang. With the use of a central telephone system and a computer-generated randomization list, consecutive patients were randomly assigned, in a 1: Randomization was performed in blocks of four without any stratification.
The maximum interval allowed between the qualifying ultrasonographic study and randomization was 48 hours. The day of randomization was defined as day 1. No routine ultrasonographic examinations were required during the follow-up period. The study was conducted according to the ethical principles stated in the Declaration of Helsinki and local regulations. The protocol was approved by an independent ethics committee, and written informed consent was obtained from all patients before they underwent randomization.
The study was funded by GlaxoSmithKline. A steering committee, including one nonvoting member representing the sponsor, was responsible for the design, conduct, and reporting of the study.
Data were collected and analyzed by the study Thrombophlebitis Wang. The database of adjudicated outcomes was managed by an independent central adjudication committee. The members of the writing committee wrote the first draft of the manuscript and made the decision to submit the manuscript for publication.
All the authors contributed to the writing of subsequent drafts of the manuscript, Thrombophlebitis Wang, had full access to the data and analyses, and vouch for the accuracy and completeness of the report, as well Thrombophlebitis Wang the fidelity of the study to the protocol and statistical analysis plan.
Fondaparinux and placebo were packaged in identical boxes containing visually identical, prefilled 0. Each patient received one box containing 45 single-dose syringes 1 per day for 45 days of either 2. At the time of randomization, patients were provided with an injection diary. The investigators were encouraged to teach the patients to administer the study drugs themselves, but the final decision about self-administration was left to the investigator's discretion.
Patients were encouraged to use graduated compression stockings and were allowed to take acetaminophen or topical nonsteroidal antiinflammatory drugs as needed. The primary efficacy outcome was the composite of death from any cause, Thrombophlebitis Wang, symptomatic pulmonary embolism confirmed by ventilation—perfusion scanning, Thrombophlebitis Wang, helical computed tomography, pulmonary angiography, or autopsysymptomatic deep-vein thrombosis confirmed by ultrasonography or venographyor symptomatic extension to the saphenofemoral junction or symptomatic recurrence of superficial-vein thrombosis confirmed by ultrasonography up to day For definitions of recurrence and extension of superficial-vein thrombosis, see the Supplementary Appendixavailable at NEJM.
Secondary efficacy outcomes were the composite primary efficacy outcome up to day 77 and the following outcomes up to day 47 and day Analyses of safety outcomes were performed with data obtained until day 47 or until 4 days after the last injection of the study drug whichever was longerwith data obtained until 4 days after the last injection of the study treatment on-treatment analysisThrombophlebitis Wang, and with data obtained until day Other safety outcomes were clinically relevant nonmajor, minor, and total any bleeding definitions provided in the Supplementary Appendix and arterial thromboembolic events.
All other adverse events that occurred while the patient was receiving treatment were reported. If a thromboembolic or bleeding complication occurred during the course of the study, management of the condition was left to the investigator's discretion. All symptomatic outcomes were reviewed by the central adjudication committee, whose members were unaware of the patients' group assignments. Patient Thrombophlebitis Wang was monitored by an independent data and safety monitoring committee.
As planned, the independent steering committee, whose members were unaware of the group assignments, monitored the overall event rate for the primary efficacy outcome, Thrombophlebitis Wang. On November 5,Thrombophlebitis Wang, on the basis of an observed rate of the primary efficacy outcome of 3. Efficacy analyses were performed on data from the intention-to-treat population, Thrombophlebitis Wang, which Thrombophlebitis Wang all the patients who had undergone randomization.
Patients for whom a primary efficacy assessment was lacking i. Safety analyses were performed on data from the as-treated population, which comprised all patients who had undergone randomization and who had received at least one dose of the study drug. Time-to-event outcomes estimated by means of the Kaplan—Meier method were compared with the use of the log-rank test.
A prespecified sensitivity analysis was performed in which patients with missing data on the primary efficacy outcome were excluded. Zelen's exact test was used to verify the consistency of the treatment effect across 16 prespecified sets of subgroups and 1 set of subgroups that was defined post hoc, Thrombophlebitis Wang. Between March and Maya total of patients were enrolled at centers in 17 countries see the Supplementary Appendix — in the fondaparinux group and in the placebo group.
Of the patients who underwent randomization, 18 patients in the fondaparinux group 1. Overall, Thrombophlebitis Wang in the fondaparinux group Of the patients who underwent randomization, 4 patients in the fondaparinux group and 11 in the placebo group received no study drug as a result of the patient's decision, Thrombophlebitis Wang, in each caseThrombophlebitis Wang, and 1 patient who was randomly assigned to the placebo group received at least one dose of fondaparinux in error; thus, patients in the fondaparinux group The demographic and clinical characteristics of the patients, the medications and interventions the patients received before their entry into the study Table 1 Table 1 Baseline Characteristics of the Study Patients.
In addition, the treatments other than the study drugs that patients received during the course of the study were well balanced between the two groups, with two exceptions: This result was confirmed in the sensitivity analysis in which patients with a missing primary efficacy assessment were excluded data not shown.
The incidence of each component of the primary efficacy outcome was significantly reduced in the fondaparinux group as compared with the placebo group including the incidence of pulmonary embolism [number needed to treat to prevent one pulmonary embolism was Thrombophlebitis Wangexcept for the incidence of death, Thrombophlebitis Wang did not differ significantly between the two groups. The primary efficacy outcome was a composite of death solkoseril von trophischen Geschwüren any cause, symptomatic pulmonary embolism, symptomatic deep-vein thrombosis, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of superficial-vein thrombosis.
Data from patients who were lost to follow-up were censored at the time of the last contact. The size of each square is in proportion to the number of patients in the comparison, Thrombophlebitis Wang.
The analysis of subgroups according to the distance of thrombus from the saphenofemoral junction included only subjects who had a thrombosis involving the great saphenous vein, Thrombophlebitis Wang. No adjustment for multiple comparisons was made, since subgroup analyses were performed for exploratory purposes only. None of the P values for interaction were less than 0. Results for 12 of the 16 prespecified subgroups are presented; the treatment effect was also consistent within each of the 4 other prespecified subgroups defined according to country and status with respect to receipt of graduated compression stockings, Thrombophlebitis Wang, use of nonsteroidal antiinflammatory drugs, and use of aspirin or other antiplatelet agents at baselineas well as the subgroup defined post hoc defined according to whether the index superficial-vein thrombosis was in a varicose Kurse der Behandlung mit Blutegeln Krampf on ultrasonographic examination.
The body-mass Thrombophlebitis Wang is the weight in kilograms divided by the square of the height in meters. ND denotes not determined, Thrombophlebitis Wang. Finally, more patients in Thrombophlebitis Wang placebo group than in the fondaparinux group underwent surgery for superficial-vein thrombosis Table 3including ligation of the saphenofemoral junction, which by day 77 had been performed in 52 patients in the placebo group 3.
By day 47, major bleeding had occurred in one patient 0. The rates of clinically relevant nonmajor, Thrombophlebitis Wang, minor, and total bleeding and arterial thromboembolic complications did not differ significantly between the two groups Table 4 Table 4 Safety Outcomes up to Day Safety results were similar in on-treatment analyses and in analyses at day 77 Thrombophlebitis Wang 4 in the Supplementary Appendix.
There were no clinically relevant between-group differences in the incidence of any other adverse events Table 5 and Table 6 in the Supplementary Appendix. The only serious adverse event that was reported in more than one patient in either study group was coronary artery disease, which was reported in two patients in the placebo group 0, Thrombophlebitis Wang. No episodes of thrombocytopenia were reported in Thrombophlebitis Wang fondaparinux group.
In this study, we investigated the effect of anticoagulant therapy as compared with placebo on symptomatic outcomes in patients with isolated superficial-vein thrombosis. Treatment with fondaparinux at a dose of 2. The number needed to treat to prevent one event of the primary efficacy outcome was 20, whereas the number needed to treat to prevent deep-vein thromboembolism or a pulmonary embolism was The study was placebo-controlled, since no standard treatment has been established in this clinical setting.
The patients in our study are representative of those encountered in routine practice 1,2,8: The rate of symptomatic thromboembolic complications in the placebo group at day 47 5. However, this rate and Thrombophlebitis Wang corresponding rate Thrombophlebitis Wang day 77 6.
This benefit was evident within the first days after treatment was initiated Figure 1supporting the adequacy of the prophylactic dose of 2, Thrombophlebitis Wang. The number needed to treat to prevent one episode of pulmonary embolism with Thrombophlebitis Wang as compared with placebo in the patients with superficial-vein thrombosis in our study is similar to the number needed to treat with low-molecular-weight heparin as compared with placebo or no treatment in trials of thromboprophylaxis in acutely ill medical patients In addition, more patients in the placebo group Thrombophlebitis Wang in Thrombophlebitis Wang fondaparinux group required therapeutic doses of anticoagulant therapy.
A potential limitation of our study is the difficulty in applying the data to ob Krampfadern zu entfernen, bei practice, because a complete ultrasonographic examination was performed in every patient with a suspected superficial-vein thrombosis — first, Thrombophlebitis Wang, to confirm the condition, Thrombophlebitis Wang, and second, Thrombophlebitis Wang, to rule out the presence of deep-vein thrombosis.
However, performing a complete ultrasonographic examination may help physicians avoid treating patients who do not have thrombosis and allow the appropriate care of patients who present with concomitant deep-vein thrombosis, Thrombophlebitis Wang.
The effect of the day fondaparinux regimen on the quality of life was not formally assessed in our study.
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