Anesth Analg 2005;101:1821-1823
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000184135.00502.3E
OBSTETRIC ANESTHESIA
The Use of Central Neuraxial Techniques in Parturients with Factor V Leiden Mutation
Miriam J. Harnett, MB, FFARCSI,
Mary E. Walsh, MB, FFARCSI,
Thomas F. McElrath, MD, PhD, and
Lawrence C. Tsen, MD
Departments of Anesthesia, Perioperative and Pain Medicine, and Obstetrics and Gynecology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
Address correspondence and reprint requests to Lawrence C. Tsen, MD, Department of Anesthesia, Perioperative and Pain Med, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115. Address e-mail to ltsen{at}zeus.bwh.harvard.edu.
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Abstract
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The factor V Leiden (FVL) mutation is a leading cause of thrombosis, particularly during pregnancy. During pregnancy, women with thrombotic disorders including FVL are often considered candidates for antepartum anticoagulation with low molecular weight heparin. Pregnancy complications related to thrombosis and the unpredictable timing of labor cause unique challenges with regard to the provision of regional anesthesia. A patient with heterozygotic FVL presenting with thrombotic disease and a complicated anticoagulation status lead us to review 16 additional parturients with FVL. This report focuses on the anesthetic implications that arise in parturients with FVL. We recommend that anesthesiologists be made aware of FVL patients before their due date, anticoagulation with low molecular weight heparin should be transitioned to unfractionated heparin before the 38th gestational week, and multidisciplinary collaborative investigation and care should continue for this disorder.
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Introduction
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Venous thromboembolism is the leading cause of maternal morbidity and mortality in the developed world (1). Factor V Leiden (FVL), a single point mutation that confers factor V resistance to protein C degradation, is the most common genetic cause of thrombophilia and is present in 4%–7% of the United States population (2). Parturients with the FVL mutation have been reported to be at increased risk for deep vein thrombosis (DVT), preeclampsia, placental abruption and pregnancy loss (3). Patients with heterozygous FVL and other thrombotic risk factors or the less common homozygous FVL are commonly treated with low molecular weight heparin (LMWH). LMWH is preferable to unfractionated heparin (UH) and warfarin given its limited need for testing, reduced thrombocytopenia and bone demineralization risk, inability to cross the placenta, and improvement in live birth rates (4–7). We highlight a case and series of parturients with FVL, focusing on the anesthetic implications that arise as a consequence of the disease and anticoagulation management.
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Case Report
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A 35-yr-old G4P2 woman presented in labor at 38 wk gestation. Two pregnancy losses followed by a DVT resulted in the diagnosis of heterozygous FVL, antiphospholipid syndrome and protein S deficiency. During her third pregnancy, thromboembolic prophylaxis with UH resulted in the delivery of a healthy infant. LMWH was started during the current pregnancy and transitioned to UH at 35 wk gestation.
Despite the last UH dose being 9 h before admission, the patient’s activated partial thromboplastin time (aPTT) was 48.2 s (normal: 20–30 s; therapeutic: 1.5–2.5x normal aPTT) (8). Four hours later, with a request for epidural labor analgesia, a cervical dilation of 4.5 cm, and an aPTT of 40.5 s, the patient was provided IV fentanyl patient-controlled analgesia (PCA). Five hours later, despite multiple alterations in her PCA regimen, the patient again requested epidural analgesia; a repeat aPTT was 38.4. Because of an unclear etiology of this prolonged level, 2 units of fresh-frozen plasma (FFP) were administered, an epidural catheter was placed, and 4 h later a healthy baby was delivered.
A six-week course of LMWH (Enoxaparin) and aspirin was initiated and the patient was discharged on postpartum day 2. Three days later, the patient was admitted with right lower quadrant and flank pain. A computed tomography pelvis scan revealed a possible ovarian vein thrombosis, however, the appendix was not visualized. An exploratory laparotomy was performed that identified a right ilial vein thrombosis. The thrombosis was managed medically with IV heparin and warfarin and the patient was discharged the following day with an INR of 2–3, (normal: 10–14 s; therapeutic international normalized ratio, 2–3) (8).
All available cases of parturients with FVL during a 2-yr period (2000–2002) were reviewed after approval by the IRB. Records were analyzed for basic demographic information and the hematologic, obstetric, and anesthetic management of FVL during pregnancy and the peripartum period (Table 1). Fifteen of the 17 patients were initiated and maintained on LMWH from the first trimester until approximately 2 wk before a scheduled induction or delivery, when converted to UH; LMWH was reinstituted 6 h postpartum for 6 wk. Similar approaches have been used at other institutions (9–11).
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Discussion
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Although responses to pregnancy, FVL, and anticoagulants vary with each patient, our case series emphasizes two anesthetic concerns. First, anesthetic consultations with FVL parturients and their providers should optimally occur early in the third trimester to discuss their underlying disease process, anticoagulant dosing alterations, and analgesic and anesthetic options. Hematologic and obstetric colleagues should be encouraged to transition patients from LMWH to UH before the 38th gestational week, as thrombophilias have been increasingly associated with preterm delivery (12). Of the 8 parturients in our series who underwent spontaneous labor, 6 labors occurred on or before the 38th week; although only the index case required active reversal of anticoagulation, delayed transitions can increase the risk of bleeding, prompt the need for reversal, or delay obstetric and anesthetic interventions. The current practice bulletin of the American College of Obstetricians and Gynecology on Thromboembolism in Pregnancy offers no guidance on when the transition from LMWH to UH should occur (13); this will become more important as current LMWH dosing regimens appear to provide inadequate thromboprophylaxis during pregnancy (14,15). Careful consideration of the parturient, hematologic, obstetric, and anesthetic issues should also address the resumption of anticoagulant drugs in the postpartum period.
Second, the use and reversal of anticoagulation therapies can be difficult to manage and assess. Although anti-Xa levels can be used for monitoring LMWH, "normal" levels and those predictive of the risk for bleeding remain controversial (16). After the last administration of LMWH at thromboprophylaxis and treatment doses, at least 10–12 hours and 24 hours should elapse, respectively, before needle placement (16); after the last dose of UH, 4–6 hours should elapse, and a confirmation of coagulation status (aPTT) should be made before neuraxial blockade (17). The 7 anti-Xa assays performed in our series between 12.5 and 168 hours from the last LMWH administration produced levels of <0.14 U/mL (therapeutic range 0.4–1.0 U/mL (18)). Of interest, patient #8 had an abnormal anti-Xa level for more than 4 days; most likely this was related to UH use, which can alter anti-Xa levels (19). The aPTT and prothrombin time studies were performed in 12 cases and were normal with the exception of the index case; in this case, more than 18 hours and 3 weeks that had elapsed since the last UH dose and LMWH, respectively. LMWH does not usually affect aPTT (18); however, the onset of anticoagulant effects has been noted to be relatively faster than their resolution (16,20). Although no agent, including FFP, vitamin K or protamine, is effective for complete reversal of LMWH anticoagulation, protamine—which will neutralize approximately 60% of the anticoagulant effect of LMWH—should be considered in patients with severe life-threatening bleeding (21). Protamine should be administered as a mg per mg of LMWH given over the previous 4 hours; if more than 6 hours has elapsed since the last dose of LMWH, the dose of protamine should be halved. In the absence of UH or LMWH molecules, however, protamine can result in anticoagulation and should be avoided; this was the reason FFP was administered in our index case.
In conclusion, we present a case series of parturients with FVL. We conclude that early consultation and discussion of analgesic and anesthetic options should occur with parturients, transition from LMWH to UH should occur before the 38th gestational week, and that multidisciplinary collaborative work should be initiated for the care of parturients with this disorder.
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Footnotes
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Accepted for publication June 22, 2005.
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Abstract
Introduction
