PHARMACOLOGIC MANAGEMENT OF DEEP VEIN TROMBOSIS IN PREGNANCY AND NURSING IMPLICATIONSDora AguilarIsabel BarradasLinda GuevaraLuz Luque
Deep Vein Thrombosis in Pregnancy• In pregnancy • Hypercoagulable state. • Leading cause of maternal death in the United States
Epidemiology• Incidence of DVT • Estimated at 1 in 500 – 2000 deliveries. • 75% - 80% of cases of pregnancy associated venous tromboembolism. • Most frequent on the left side lower extremity (85%).
Risk factors• Physiological pregnancy process • Virchow’s triad of hypercoagulation. • Hypercoagulable state • Vascular damage • Venous stasis• Inherited• Acquired • Antiphospholipid antibody syndrome • Pregnancy age more than 35 • Parity more than 3 • Obesity • Inmobilization • Smoking • Medical problems • Hypertension, nephrotic syndrome, sever infection • Cesarean dellivery
Pathophysiology• Hypercoagulable state. • Increased serum levels of procoagulants • II, VII, VIII, X, XII • Fibrinogen • Decreased during pregnancy • Protein S • Protein C • Decreased fibrinolytic state • Increase Serum plasminogen activator inhibitor-1 (PAI-1) • Placental activator inhibitor-2 (PAI-2)
Signs and Symptoms• Most frequent on the left side lower extremity.• Leg pain and swelling are unilateral.• Hofman’s sign • No specific for DVT diagnosis
Diagnostic• Compression ultrasonography • Lower extremity or extremities• Magnetic resonance
Algorithm for diagnosis and treatment of DVT inpregnancy
Treatment• Therapeutic anticoagulation All women with acute venous thromboembolism• Women with high risk of thrombosis Mechanical heart valve History of thrombosis Thrombophilia
Treatment• Drugs used during pregnancy or postpartum • Unfractionated heparine • Low molecular weight heparin (LMWH) • Warfarin
Treatment• Heparin Compounds • Unfractionated heparin (UFH) • Low molecular weight heparin (LMWH) • They both bind to anti-thrombine II increasing its interaction with the clotting factor X producing anticoagulant effect. • LMWH can be monitor with anti-factor Xa Levels every 1-3 months keeping them at 0.5 – 1.2 U/ml. • UFH increase interaction between anti-thrombine II and thrombine (factor II), prolonging the aPTT that is used to monitor unfractionated heparine.
Treatment• UFH and LMWH are harmless during the gestation • Does not cross the placenta • Does not cause teratogenic or toxic fetal effect. • Have shorter half-lives • Lower peak plasma concentration • High rate of clearance in pregnancy women • Augmented glomerular filtration
TreatmentAdverse effects UFH and LMWH • Osteoporosis • Heparin-induced thrombocytopenia • Calcium and Vitamin D reduce risk of osteoporosis.Advantages of LMWH •Fewer adverse effects than UFH •Fewer bleeding episodes •Lower risk of heparin-induced thrombocytopenia •Less bone mineral density loss •More predictable therapeutic response•Disadvantages of LMWH •More expensive •Longer half-life compared with UFH
Treatment• LMWH must be stopped 24 hours previous regional anesthesia or induction of labor.• LMWH can be change for UFH at 36 weeks of pregnancy and instruct to the patient to stop UFH when spontaneous labor starts.• Anticoagulation will be reassumed after 6 hours of vaginal delivery or 6 to 12 hours after cesarean.• UFH therapeutic dosage is 80 U/kg bolus intravenous • 18 U/kg/hour adjusted to aPTT of 60-80 SC • 216 U/kg /12 hr• UFH prophylactic dose is 5,000 U (1st trimester) 7,500 U (2nd trimester) 10,000 U (3rd trimester) SC twice daily.
Treatment• Warfarin • Inhibits the generation of Vit K-dependent procoagulants factors • II, VII, IX, X, protein C and S. • Associated with warfarin embriopathy when is used during the 1st semester • Nasal bone, hypoplasia, condrodysplasia puntata, congenital heart defects, agenesis of corpus callosum. • After 12 weeks of gestation, it is related with fetal bleeding and pregnancy loss. • Incidence of congenital abnormalities is 6-10% and fetal demise is 30%. • Mother with mechanical heart valves after 12 week of gestation. • More used during postpartum • Dosage is 5 -10 mg daily. It must be overlap with heparin for 5 to 7 days until get INR.
Treatment• Allergic patient • Danaparoid • Probably does not cross the placent • Has long half-life without a reversible agent • It is not available in the United States since 2002 • It is accessible in Canada and Europe • Fondaparinux • First option in patients with heparin-induced trobocitopenia • Binds to antithrombin III to facilitate its binding to factor X to inactivate it and stopping the clotting cascade. • Released intact and can keep inhibiting more factor X. • Its half-life is 17 hrs. • Cathegory B (studies in-vitro human show that does not cross placenta significantly • Profilaxis dosage is 2.5 mg SC daily • Therapeutic dosage is 5-10 mg SC daily
Nursing Implications• The “gold standard” in DVT is LMWH by SC injections. • Reduce risk of a pulmonary embolism • Reduce risk of developing another clot in the legs. •LMWH: •Has potential advantages over UFH during pregnancy. •Cause less heparin induced thrombocytopenia. •Has the potential for once-daily administration. •Lower risk of heparin-induced osteoporosis. •Coumarin: •Can cross the placenta: •Bleeding in the fetus and teratogenicity. •Embryopathy (nasal hypoplasia and/or stippled epiphyses). Trauma of delivery can lead to bleeding in the neonate.
Nursing Implications• Potential fetal complications of maternal anticoagulant therapy: • Teratogenicity • Bleeding• UFH and LMWH do not cross the placenta. • Inhibit complications. • Bleeding at the uteroplacental junction is possible.
Nursing Implications• Enoxaparin (LovenoxR) • Assess the patient for signs of bleeding and hemorrhage • Bleeding gums • Nose bleeding • Unusual bruising • Tarry stools • Hematuria • Fall in hematocrit • Fall in the blood pressure levels • Monitor for signs of hypersensitivity reactions • Chills • Fever • Urticaria • Platelets count, elevation of AST and ALT levels • Special monitoring of aPTT is not necessary
Nursing Implications• Fondaparinux (ArixtraR) • Alternative medication used in acute DVT in pregnancy. • Advise the patient to report unusual • Bleeding • Itchiness • Rash • Fever • Platelet count must be monitored on regular intervals • It may cause asymptomatic elevation of AST and ALT • Fully reversible while having no association with increased bilirubin levels
Nursing Implications• Measures recommended: • Staying active as tolerated • Wearing prescribed compression stocking to help circulation in the legs. • Warm compresses to the affected area • Elevation of the affected extremity• To reduce the risk of acute DVT when travelling: • Drink plenty of water • Do not drink alcohol (it can lead to dehydration) • Perform simple leg exercises (flexing ankles up and down) • Take short walks when in-flight.
Nursing Implications• American College of Chest Physicians (Bates et al. ACCP, 2012) recommends: • LMWH for the prevention and treatment of VTE in pregnant women instead of unfractionated heparin (Grade 1B). • For pregnant women with acute VTE, the anticoagulants will be continued for at least 6 weeks postpartum. • For a minimum duration of therapy of 3 months, compared with shorter durations of treatment (Grade 2C).
Nursing Implications • Women with criteria for antiphospholipid antibody syndrome (APLA) with three or more pregnancy losses give: • Antepartum administration of prophylactic or intermediate-dose unfractionated heparin of prophylactic LMWH combined with low-dose aspirin (75-100mg/dl) over no treatment (Grade 1B). • For women with inherited thrombophilia and history of pregnancy complications: • Eliminating antithrombotic prophylaxis (Grade 2C). • For women with two or more miscarriages but without APLA or thrombophilia: • Antithrombotic prophylaxis (Grade 1B).