Alice J. Cohen

Aging in Sickle Cell Disease: Co-morbidities and New Issues in Management

Abstract Availability of hydroxyurea (HU) coupled with early therapeutic interventions has increased the life expectancy of patients with sickle cell disease. Hence, the sickle cell community needs to be aware of common diseases of aging that survivors are predisposed to. We chose to investigate the sickle cell disease-related complications as well as non sickle cell disease-related medical problems of aging in 45 sickle cell patients over the age of 40 years. The most frequent chronic complications of sickle cell disease were elevated tricuspid regurgitant jet velocity on echocardiogram, chronic renal disease, iron overload and leg ulcers. Medical co-morbidities in this patient group included hypertension, diabetes mellitus (DM), hypercholesterolemia and symptomatic coronary artery disease (CAD). In our cohort, only 38.0% had a primary care doctor. Only 11.0% over age 50 had a screening colonoscopy, and of the women, 42.0% had a screening mammography. Medical co-morbidities and lack of health maintenance in older sickle cell patients are likely to impact overall health and mortality. Aging patients with sickle cell disease may benefit from a primary medical home for age appropriate comprehensive health care.

A Case of Imported Severe Plasmodium falciparum Malaria in the Emergency Department and the Current Role of Exchange Transfusion Treatment

BACKGROUND The role of exchange transfusion in the management of severe malaria is not well documented in Emergency Medicine literature. OBJECTIVES The goal of this article is to review the importance of considering malaria in the differential diagnosis of the febrile returned traveler and to discuss the role of exchange transfusion in the management of severe Plasmodium falciparum malaria. CASE REPORT A 59-year-old woman presented to the Emergency Department (ED) with severe P. falciparum malaria. Her physical examination was remarkable for scleral icterus, dry mucous membranes, and tachycardia. Her complete blood count revealed a white blood cell count of 6.9 k/uL, with 71% segmented neutrophils, 19% bands, a hemoglobin level of 11.9 g/dL, hematocrit of 37.2%, and a platelet count of 9 k/uL. Hepatorenal impairment was present and malaria parasites with ring form were seen on malaria prep in 18% of red blood cells. The patient was treated with fluids, platelets, quinidine gluconate, doxycycline, and exchange transfusion with significant improvement in the patients clinical condition. CONCLUSIONS The high level of parasitemia presenting with acute kidney injury, hyperbilirubinemia, and thrombocytopenia supported the use of exchange transfusion as adjunct therapy. Exchange transfusion was a reasonable consideration in this case and was well tolerated by our patient. Institutions that are equipped with apheresis units should evaluate each case individually in concert with Centers for Disease Control experts and local consultants and weigh the risks and benefits of the use of exchange transfusion as an adjunct in the treatment of severe P. falciparum malaria.

Management of pregnancy in a patient with severe hemophilia type a.

Hemophilia type A is a rare inherited bleeding disorder with a diversity of clinical manifestations ranging from persistent bleeding after minor trauma, spontaneous deep muscle or joint hemorrhage, to intracranial hemorrhage. As an X-linked disorder, hemophilia is rare in females and therefore there is little experience with pregnancy and no standardized guidelines to prevent bleeding antepartum, at delivery, and postpartum. We report the clinical course and management of a woman with severe hemophilia A who on two occasions had uncomplicated pregnancies and vaginal deliveries at term utilizing bolus recombinant factor VIII concentrate.

Comparison of the effects of ketoprofen on platelet function in the presence and absence of aspirin

PURPOSE Although aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) exert inhibitory effects on platelets in vitro and in vivo, there are insufficient data to substantiate the use of NSAIDs alone as antiplatelet drugs in patients already taking aspirin. We therefore sought to determine whether aspirin, added to NSAID therapy, further suppresses platelet function. SUBJECTS AND METHODS We enrolled 25 healthy adult volunteers who were administered ketoprofen (extended-release capsules, 200 mg daily) for 1 week, followed by ketoprofen (200 mg daily) and aspirin (325 mg daily) or ketoprofen (200 mg daily) alone during the second week. Platelet aggregation, stimulated by epinephrine and arachidonic acid, and cyclooxygenase activity, measured by thromboxane B(2), were measured at baseline, on day 8, and on day 15. RESULTS On day 8, all subjects demonstrated abnormal platelet aggregation (>50% inhibition), which persisted at day 15 in both the aspirin and no aspirin groups. One week of ketoprofen treatment reduced thromboxane B(2) levels by 84% in the aspirin group and by 85% in the no aspirin group (P = 0.8), without any further inhibition measured on day 15. CONCLUSION Extended-release ketoprofen significantly inhibited platelet aggregation and thromboxane B(2) production in healthy volunteers. Addition of aspirin had no additional effect. Trials are warranted to determine whether these in vitro effects result in clinical antiplatelet activity in patients who require chronic treatment with NSAIDs, thereby avoiding the toxicity of NSAID/aspirin combination therapy.

Renal Lymphoma: Unusual Lymphoproliferative Manifestation of Sjögren’s Syndrome

To the Editor: Sjogren’s syndrome (SS) is a chronic autoimmune disease characterized early in its course by lymphocytic infiltration in the salivary and lacrimal glands, resulting in the major manifestations of keratoconjunctivitis sicca and xerostomia. Presumably through a multistep lymphoproliferative process, SS has been associated with the development of non-Hodgkin’s lymphoma (NHL) in 5%–10% of patients1. Mucosa-associated lymphoid tissue (MALT) lymphomas constitute the majority of NHL subtypes seen in SS, followed by nodal marginal zone lymphomas and diffuse large B-cell lymphomas (DLBCL)2. We describe what could be the first case of primary DLBCL of the kidney, a rare extranodal lymphoma, as a lymphoproliferative complication of SS. A 64-year-old woman presented at age 39 with polyarthralgias and morning stiffness attributed to rheumatoid arthritis (RA). She was treated with hydroxychloroquine and nonsteroidal agents. She subsequently developed dry eyes, dry mouth, difficulty swallowing without drinking fluids, and vaginal and nasal dryness, which she treated with topical moisturizing agents. At age 58, she was noted to have mild pancytopenia with leukocytes 3600/mm3, hemoglobin 11.3 g/dl, and platelets 95,000/mm3. Bone marrow examination revealed erythroid hyperplasia, megakaryocytic hyperplasia, and atypical lymphocytosis. Urinalysis showed 20–30 white blood cells/high-powered field (HPF), without red cells, bacteria, nitrite, or proteinuria. Serological testing revealed antinuclear antibody (ANA) 1:640 speckled pattern; absence of antibodies to dsDNA and Sm/RNP; anti-SSA antibody 413 U (strongly positive); anti-SSB 129 U (weakly positive); rheumatoid factor (RF) 32 IU (normal … Address correspondence to Dr. E.D. Rosenstein, Institute for Rheumatic and Autoimmune Diseases, Overlook Medical Center, 33 Overlook Road, Summit, New Jersey 07901, USA., E-mail: elliot.rosenstein{at}atlantichealth.org

Adult-Onset Ligneous Conjunctivitis with Detection of a Novel Plasminogen Gene Mutation and Anti-Plasminogen IgA Antibody: A Clinicopathologic Study and Review of Literature

Abstract Purpose: To report a novel plasminogen gene mutation and detection of anti-plasminogen antibodies in a patient with ligneous conjunctivitis successfully treated with 60% fresh frozen plasma (FFP). Methods: Retrospective data collected on a 45-year-old Caucasian female presenting with unilateral chronic membranous lesions. Results: Laboratory investigation demonstrated decreased plasminogen antigen level, plasminogen activity, and rate of plasminogen activation by u-PA or t-PA, and elevated plasminogen activator inhibitor-1. Anti-plasminogen IgG and IgA antibodies were detected. DNA analysis revealed a novel Asp432Asn heterozygous missense mutation in the plasminogen gene (exon 11). The patient was treated with topical 60% FFP, achieved complete remission after four months, and remained membrane-free for over five years of follow-up. Conclusions: A novel plasminogen gene mutation, deficiency of plasminogen antigen and activity, and anti-plasminogen IgG and IgA antibodies were identified in a patient with adult-onset ligneous conjunctivitis. Sixty percent FFP maintained this patient disease-free for over five years.

T-Cell Lymphoblastic Leukemia/Lymphoma: Relapse 16 Years after First Remission

Little information is available regarding late relapse in patients with T-lymphoblastic leukemia/lymphoma (T-LBL). Because of the aggressive nature of this disease, relapse is common and often happens early. Late relapses are rare and generally occur within a few years after initial remission. The relapse rate after 3 years has been reported to steadily decrease over time yet does not parallel with cure. We report a case of a 26-year-old female with T-LBL and relapse 16 years after her first remission with successful treatment with HyperCVAD and L-asparaginase.

Abstract P4-12-15: Are we appropriately referring and testing breast cancer women for genetic mutations?

Background – Annually it is estimated that Hereditary Breast and Ovarian Syndrome (HBOC) accounts for 5 - 6% of breast cancer in the US. The majority of HBOC are associated with gene mutations in BRCA 1 & 2; other mutations include p53, PTEN, CH1, STK11. These genes are tumor suppressor genes and play a role in the maintainence of genomic integrity. Women with BRCA mutations have a life time risk of developing breast cancer (50 -85%) and ovarian cancer (15-40%). Other cancers have been associated with these mutations as well. The estimated frequency of a mutation in the BRCA gene is 1/800-1/1000. As a primary oncologist it is our responsibility to screen breast cancer patients who may harbour such deleterious mutation and offer appropriate screening, counselling, testing and management. As tests are now available without trained genetic counsellors, the question remains are all appropriate patients being offered genetic testing to assist in treatment and does onsite genetic counselling improve testing rates. Purpose of study – To evaluate the difference in identification of high risk breast cancer patients and the number of women who undergo genetic testing with or without an onsite genetic counsellor. Methods – A retrospective chart review was performed of all newly diagnosed breast cancer patients from March 2012 – February 2014. Year 1 was without a genetic counsellor, March 2012 - February 2013 (Gr.1) and year 2 with an onsite genetic counsellor, March 2013 – February 2014 (Gr.2). Information collected included age, stage of breast cancer, receptor type, reason for referral or genetic testing based on NCCN criteria for HBOC testing and results of tests. Results – 135 new breast cancer patients were identified and 125 were evaluable. In Gr 1, 27/72 (37.5%) met criteria for genetic testing. 15 were offered testing (55.5%). 5/15 (33.3%) completed testing with no patient positive for BRCA mutation; 10 patients were non compliant with recommended testing; 3 patients were tested outside of guidelines with negative results. In Gr 2, 22/53 (41.5%) met criteria for genetic testing. 16 were offered testing (72.3%); 8/16 (50%) completed testing with 4 positive for a BRCA mutation; 8 patients were not tested (6 patients non compliant with recommended testing, 1 due to insurance issuses and 1 refused). See Table 1. The most common reason for genetic testing was patients with primary breast cancer age Conclusion – A greater number of women with newly diagnosed breast cancer were identified and offered genetic testing with an onsite genetic counsellor. The precentage of individuals tested increased with an onsite counsellor. Citation Format: Pankhoori Saraf, Dipen Patel, Alice J Cohen. Are we appropriately referring and testing breast cancer women for genetic mutations? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-12-15.

Body mass index: A potential risk factor for breast cancer in minority patients.

1599 Background: Breast cancer (BC), the most common cancer among women in the United States, has many established risk factors including reproductive factors, hormone use, and obesity. Obesity has also been associated with a poorer prognosis. Serum estrogen levels are higher in obesity, and may influence the characteristics and development of BC. African-Americans (AA) have been found to have a poorer prognosis for undefined reasons. In previous studies linking obesity to BC prognosis, AA women have been under-represented. This study was undertaken to look at the association of body mass index (BMI), estrogen receptor (ER) status, and stage at diagnosis (dx) in minority patients (pts). METHODS A retrospective review of the tumor registry at an urban, tertiary care medical center identified 474 women with pathologically confirmed BC from 2005 to 2010. Clinical information at dx including race, age, family history, stage, height and weight, and menopausal status was obtained. The BMI (lb/in²) at dx was calculated and pts were categorized into four groups: obese (OB) (>30), over-weight (OW) (25-29.9), normal weight (NW) (18.5-24.9), and underweight (UW) (<18.5). Pathology was reviewed to confirm ER status. 60% (284/474) of pts had complete information and were evaluable. RESULTS Of the 284 pts, 71% were AA, 3% Asian, 5% Hispanic, 14% White Non-Hispanic, and 7% other. The age range was 28 to 96 years (mean 60 years). 80% of pts were post-menopausal. 41% had a family history of malignancy. Staging was as follows: 16%, DCIS, 22% stage I, 37% stage II, 18% stage III, and 7% stage IV. 70% were ER (+). 2% were UW. 20% were NW. 30% were OW. 48% were OB. Higher BMI pts were more likely to have ER (+) BC (p==0.044) (see table). There was statistically significant correlation between higher BMI and advanced stage in this cohort (p==0.050). CONCLUSIONS The majority of BC pts in this cohort were AA and OW or OB. A higher BMI correlated with ER (+) status and advanced stage. The impact that obesity has on BC characteristics and prognosis is complicated as it is influenced by path-physiology, as well as psycho-social factors. Further studies including evaluation of weight control on BC in AA women is warranted. [Table: see text].