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dependent prozone-like effect was limited.3 Furthermore, no inhibition by nonspecific IgM was noted when the regular IgG-SAB assay was performed. Although we recognize the potential limitations of the IgG-SAB assay through the prozone-like effect, the results presented in our study were unlikely to have been affected by this phenomenon. Finally, Lawrence et al. stress the importance of the class of donor-specific anti-HLA antibodies among patients with C1q-binding antibodies. We would like to clarify this particular point by providing a supplementary analysis. Among the 77 patients with C1q-binding donor-specific anti-HLA antibodies, 23 (30%) had class I antibodies, 48 (62%) had class II antibodies, and 6 (8%) had both class I and class II antibodies. Even though more patients had class II antibodies than class I antibodies, the presence of C1qbinding antibodies was equally distributed across classes. In addition, the distribution of graft-injury phenotypes and rates of allograft survival were similar across all classes. Therefore, the clear message is that both class I and


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class II of donor-specific anti-HLA antibodies after transplantation are harmful, which supports the concept that the complement-binding property is not dependent on the HLA-antibody class. Carmen Lefaucheur, M.D., Ph.D. Alexandre Loupy, M.D., Ph.D. Paris Translational Research Center for Organ Transplantation Paris, France [email protected]

Adriana Zeevi, Ph.D. University of Pittsburgh Medical Center Pittsburgh, PA Since publication of their article, the authors report no further potential conflict of interest. 1. Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS.

Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008;27:157-72. 2. Lefaucheur C, Loupy A, Hill GS, et al. Preexisting donorspecific HLA antibodies predict outcome in kidney transplantation. J Am Soc Nephrol 2010;21:1398-406. 3. Zeevi A, Lunz J, Feingold B, et al. Persistent strong anti-HLA antibody at high titer is complement binding and associated with increased risk of antibody-mediated rejection in heart transplant recipients. J Heart Lung Transplant 2013;32:98-105. DOI: 10.1056/NEJMc1313506

Diagnostic Criteria for Nonviable Pregnancy To the Editor: In their article on diagnostic criteria for nonviable pregnancy early in the first trimester, Doubilet et al. (Oct. 10 issue)1 provide important data for clinicians caring for women with desired pregnancies. However, given that almost half of all U.S. pregnancies are unintended and that half of these end in abortion, it is unreasonable to assume that all pregnancies are desired.2 The first key question when encountering a patient with symptomatic early pregnancy should be, “Is this a desired pregnancy?” If the pregnancy is desired, only then should attention turn to answering the question, “Is there a chance of a viable pregnancy?” If the pregnancy is undesired, we recommend prompt uterine evacuation both to resolve the undesired pregnancy and to facilitate diagnosis of an ectopic pregnancy.3 The patient’s plans for the pregnancy must be considered when maximizing the specificity of diagnostic criteria at the expense of sensitivity. Shared decision making plays a key role in the management of symptomatic early


pregnancy. Otherwise, we unnecessarily risk the lives and welfare of our patients. Meredith Warden, M.D., M.P.H. University of California, San Francisco San Francisco, CA [email protected]

Courtney A. Schreiber, M.D., M.P.H. University of Pennsylvania Philadelphia, PA

Jody Steinauer, M.D. University of California, San Francisco San Francisco, CA No potential conflict of interest relevant to this letter was reported. 1. Doubilet PM, Benson CB, Bourne T, et al. Diagnostic criteria

for nonviable pregnancy early in the first trimester. N Engl J Med 2013;369:1443-51. 2. Finer LB, Zolna MR. Unintended pregnancy in the United States: incidence and disparities, 2006. Contraception 2011;84: 478-85. 3. Ailawadi M, Lorch SA, Barnhart KT. Cost-effectiveness of presumptively medically treating women at risk of ectopic pregnancy compared with first performing a dilatation and curettage. Fertil Steril 2005;83:376-82. DOI: 10.1056/NEJMc1313769

n engl j med 370;1 january 2, 2014

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