ABSTRACT
A patient with rheumatoid arthritis presented with increasing fatigue, fever, gingival bleeding, and petechial rash. Her symptoms started 1 week after the first injection of etanercept (Enbrel). Her only other medications (methotrexate and hydroxychloroquine) had been unchanged for years. Tests revealed severe pancytopenia and bone marrow aplasia. She recovered with supportive treatment within 12 days. The literature on serious blood dyscrasias associated with anti-tumor necrosis factor-α therapy is reviewed, an intriguing postulated mechanism is discussed, and selective patient monitoring is recommended.
Subject(s)
Anemia, Aplastic/therapy , Bone Marrow/pathology , Immunoglobulin G/adverse effects , Pancytopenia/therapy , Anemia, Aplastic/diagnosis , Anti-Bacterial Agents/therapeutic use , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/therapy , Etanercept , Female , Filgrastim , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulin G/administration & dosage , Methotrexate/therapeutic use , Middle Aged , Pancytopenia/diagnosis , Receptors, Tumor Necrosis Factor/administration & dosage , Recombinant Proteins/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
OBJECTIVES: We hypothesized that the guideline-recommended peak anti-Xa levels for pregnant women with mechanical prosthetic heart valves (MPHVs) receiving adjusted dose low-molecular-weight heparin (LMWH) are associated with subtherapeutic trough levels and consequently with an inadequate level of anticoagulation. BACKGROUND: Low-molecular-weight heparin is often used for anticoagulation in pregnant women including those with MPHV. American College of Cardiology/American Heart Association guidelines recommend monitoring of plasma anti-Xa factor peak levels and adjustment of the dose to achieve peak levels of 0.7 to 1.2 U/mL. In spite of these recommendations, cases of valve thrombosis during pregnancy continue to occur. METHODS AND RESULTS: We studied 30 pregnant patients receiving anticoagulation for various indications with adjusted dose LMWH given subcutaneously twice a day which had both trough and peak anti-Xa levels throughout pregnancy for a total of 187 paired determinations. The recommended peak anti-Xa levels (0.7-1.2 U/mL) were obtained in 123 (66%) of the measurements but in 80% of them, the trough levels were found to be subtherapeutic (<0.6 U/mL). Subtherapeutic trough levels were found in 8 (73%) of the 11 measurements with peak levels of 0.7 to 0.79 U/mL, 17 (74%) of the 23 of 0.8 to 0.89 U/mL, 21 (72%) of the 29 of 0.9 to 0.99 U/mL, and 28 (44%) of the 63 of 1.0 to 1.2 U/mL. There were 42 measurements with peak anti-Xa levels >1.2 U/mL and even in these cases, 13 (31%) of the trough levels were found to be subtherapeutic. CONCLUSIONS: Anticoagulation with adjusted dose LMWH aimed to achieve guideline-recommended peak levels of anti-Xa for patients with MPHVs is commonly associated with subtherapeutic trough levels. Routine measurement of trough anti-Xa levels is therefore advisable in women with MPHV treated with LMWH during pregnancy to assure adequate level of anticoagulation.
