Case # 4: 2011, OSHU: Gyne cancer…. 47 yo JW admitted with vaginal bleeding and uterine pain; an abnormal pap in 2006 had been ignored/ treated homeopathically Hb 12.6 (4 mos pta)  3.7 gm/dl on admission; MCV 70.8; reticulocyte count rel/abs: 3.3 ( )/ 52.9 (10-90); INR 1.43; ferritin 19 (6-132); Cr 6.7 Found to have stage IV cervical cancer with ureteric obstruction  unable to stent  dialysis ~ 1 wk later  Initially treated for anemia and coagulopathy with: IV Fe++: Venofer 200 qd x 5 days Folic acid, B12, IV Vit K

 Hb continued to decrease  3.0 gm/dl: Persistent reticulocytopenia despite Fe++ and hematinics  High dose darbepoietin (200 mcgm q o d) begun  over next 2 weeks Hb 3.0  5.4 with increase in reticulocyte count : rel/abs: 3.3 ( ) / 52.9 (10-90)  12.3 / Opted for palliative care; survived for 3 mos; visited by many out of town relatives and friends

ESA use in adults with critical illness and with malignancy is associated with increased thrombogenicity (blood clots, heart failure, myocardial infarction, stroke).  consideration should be given to prophylactic doses of antithrombotics when using ESAs in such patients. In the case of cancer in adult populations, use of ESAs is also associated with increases in mortality independent of thrombogenicity and possibly mediated by tumor receptors for ESAs and promotion of angiogenesis.

The U.S. Food and Drug Administration (FDA) issued a block box warning for ESAs in 2007 (Mitka 2007) prompting a series of revised clinical guidelines (see Rizzo et al 2010) As of 2010, the FDA is requiring that all ESAs given to patients with malignancy be prescribed under a Risk Evaluation and Mitigation Strategy (REMS) which includes a medication guide to explain risks to patients and caregivers, and the ESA APPRISE (Assisting Providers and cancer Patients with Risk Information for the Safe use of ESAs) Oncology Program ( InformationforPatientsandProviders/ucm htm). Mitka M (2007) FDA sounds alert on anemia drugs. JAMA 297(17): Rizzo, JD, Brouwers M, Hurley Pet al. (2010) American Society of Hematology/ American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. Prepublished online as Blood First Edition paper, October 25, 2010 DOI /blood

Summary: Jehovah’s Witness Patients: Transfusion alternatives and “fractions” can be life-saving in Witness patients An integrated approach is best Work in partnership with the patient & JW community; act as patient’s advocate. Know & explore the acceptability of the full range of non-blood therapeutic options with the patient--and use them!! Act pre-emptively if possible Realize physiological tolerance of anemia is generally greater than you may think Don’t be afraid to get treatment advice elsewhere and ask for help

In pediatric patients use the same general guiding principles as in other JWs; try to involve a JW Hospital Liaison elder; communicate your legal obligation to transfuse to preserve life/ prevent serious harm to parents; try to avoid Court Orders or get them limited to blood products alone Don’t be afraid of intraoperative salvage in obstetrics Remember ESA’s work slowly, need Fe++ repletion, and work better pre-op and in the absence of inflammation; higher doses necessary post-op and in inflammation; risk of thrombogenicity and cancer progression and special consent (APPRISE) may be needed in cancer (esp being treated curatively)

Treatment of Witnesses poses many challenges BUT can provide unique opportunities both for learning and for the exercise of compassion