Anticoagulants

Treatment of Venous Thromboembolism

• When VTE is suspected, anticoagulation with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) should be initiated until the diagnosis is excluded. Neither of these anticoagulants cross the placenta nor are secreted into breast milk; thus, there is no risk for teratogenicity or fetal hemorrhage, although bleeding at the uteroplacental junction is possible. Although UFH has been stan­dard treatment for the prevention and treatment of VTE during pregnancy, recent evidence-based clinical practice guidelines now recommend LMWH. Compression stockings and leg elevation should be used for DVT.

Weight-adjusted LMWH should be used for the treatment of VTE Advantages of LMWH include fewer bleeding complications, lower risk of heparin-induced thrombocytopenia (HIT) and osteoporosis, longer plasma half- life, and more predictable dose-response relationships. Theoretical concerns have been raised regarding once daily dosing compared to twice daily dosing (i.e., pro­phylactic or therapeutic) secondary to the increased renal clearance in pregnancy possibly prolonging trough LMWH levels. However, no comparison data of the two regimens are available. Additionally, recent data suggest daily dosing in the treatment of acute VTE is effective. Monitoring of LMWH levels remains con­troversial. LMWH cannot be monitored using activated partial thromboplastin time (aPTT), as it will likely be normal.

Anti-factor Xa activity levels may be measured 4 hours after subcutaneous injection, with a therapeutic peak goal of 0.6 to 1.0 U/mL (slightly higher if once daily dosing is used); however, frequent monitoring is not typically recommended, except at extremes of body weight. If trough levels are evaluated with therapeutic dosing (i.e., 12 hours after dosing), goal level is 0.2 to 0.4 IU/mL. Current guidelines do not provide definitive mon­itoring recommendations; however, some researchers advocate checking levels periodically (every 1 to 3 months).

  What about UFH?? Is it like rapid Test ?? UFH  is administered either IV or subcutaneously (SC). IV UFH may be a better initial therapeutic option in unstable patients (e.g.,A)  large B) PE with hypoxia or C) extensive iliofemoral disease) or D) patients with significant renal impairment (i.e., creatinine clear­ance <30 mL/min). The goal of the initial bolus dose (typically 80 U/kg) and subse­quent maintenance dosing (typically 18 U/kg/hr) is to achieve a midinterval (6 hours postinjection) therapeutic aPTT (often described as an aPTT ratio of 1.5 to 2.5 times normal). Measuring anti-factor Xa heparin levels may assist in evaluating heparin dosing (target level 0.3 to 0.7 IU/mL). Many facilities have standard protocols for heparin titration. IV treatment should be maintained in the therapeutic range for at least 5 days, and therapy may then be continued with either adjusted-dose SC heparin injections or LMWH. If maintained on UFH, the aPTT should be moni­tored every 1 to 2 weeks.

 The aPTT response to heparin in pregnant women is often attenuated secondary to elevated heparin-binding proteins and increased factor VIII and fibrinogen. The therapeutic dose may need to be adjusted. Thus, it may be dif­ficult to achieve target aPTT levels late in pregnancy. The major concerns with UFH use during pregnancy are bleeding, osteopenia, and thrombocytopenia. The risk of major bleeding with UFH is approximately 2%. Bone density reductions have been reported in 30% of patients on heparin for over 1 month. HIT occurs in up to 3% of nonpregnant patients and should be suspected when platelet count decreases to <100,000/p.L or <50% of baseline value. Typical onset is between 5 and 10 days after starting heparin. In 25% to 30% of patients who develop HIT, onset occurs rapidly (within 24 hours) after starting heparin and is related to recent exposure to heparin. After obtaining a starting platelet level, ACOG recommends checking platelets again on day 5 and then periodically for the first 2 weeks of therapy. Others suggest platelets be monitored at 24 hours and then every 2 to 3 days for the first 2 weeks or weekly for the first 3 weeks. If HIT is acquired and ongoing anticoagulant therapy is required, danaparoid sodium (factor Xa inhibitor, not currcndy available in the United States) or argatroban (direct thrombin inhibitor) can be used.

Warfarin sodium crosses the placenta and, therefore, is a potential teratogen and may cause fetal bleeding. Warfarin is likely safe during the first 6 weeks’ gestation, but between 6 and 12 weeks’ gestation, a risk of skeletal embryopathy exists, con­sisting of stippled epiphyses and nasal and limb hypoplasia. One third of fetuses