The Diagnosis and Treatment of Iron Deficiency in Primary Care: 34,741 CBCs Reconsidered

OR

What I learned from 55 Gallons of Baby’s Blood

OR

The Diagnosis and Treatment of Iron Deficiency in Primary Care: A Qualified Failure

Three Types of Prevention (Commission on Chronic Illness, 1957)   • Primary Prevention, which seeks to decrease the number of new cases of a disorder or illness; • Secondary Prevention, which seeks to lower the rate of established cases of a disorder or illness in the population (prevalence); • Tertiary Prevention, which seeks to decrease the amount of disability associated with an existing disorder.

The secondary prevention of IDA in toddlers is difficult. Findings:   The secondary prevention of IDA in toddlers is difficult. Success at CCRMC=30%, in line with four other studies. Most patients do not receive follow-up (38%) or remain anemic at follow-up (32%). Patients who remain anemic at follow-up have been affected for an mean of 147 days (range 15-836 days)

Background

Iron deficiency is the most common and widespread nutritional disorder in the world. The numbers are staggering: 2 billion people – over 30% of the world’s population – are anaemic, many due to iron deficiency.

Why do we care?

Iron is a cofactor in 200 enzymes and is important for various functions such as: Oxygen carriage in Hb Respiration Neurotransmitter synthesis Myelination

Performance Problems Temporal organization of sleep WISC-R intelligence test Average math scores Written expression, motor functioning, and some specific cognitive processes

Neurological Findings ( Young Humans) The hearing abilities, verbal and non-verbal sequential memory and localization Abnormal Visual Evoked Potential EEG and cognitive EPs (CEPs).

Behavioral Findings (Animals) Wisconsin General Testing Apparatus, Black/White Discrimination task was acquisition of Black/White Reversal (BWR) (Monkeys). Decreased activity and stereotypic behavior (Rats). Hippocampus-dependent learning (Rats)

What is the Gold Standard for the Diagnosis of ID?

Bone Marrow

What are the Clinical Diagnostic Criteria for Iron Deficiency?

Two Clinical Models

Ferritin Model (NHANES III) 2 or 3 of Following Abnormal: Low Ferritin Low Transferrin Saturation Hi Erythrocyte Protoporphyrin

Transferrin Receptor (Tfr) Body Iron Model (NHANES 2003-Onwards) A Function of Transferrin Receptor (Tfr) To 2) Ferritin

Body iron (mg/kg) = -[log10 (TfR*1000/ferritin) -2.8229]/0.1207

Anemia Is a Poor Predictor of Iron Deficiency Among Toddlers in the United States: For Heme the Bell Tolls Keith C. White, MD 2005;115:315–320;

In this study, ID was diagnosed if >=2 of the following pertained: ferritin <10 g/L transferrin saturation <10% EPP> 1.42 mol/L red blood cells.

Anemia was diagnosed if [Hb] was 110 g/L IDA was diagnosed if anemia accompanied ID

Sample Cohort: 893 Toddlers ↓Hb ↓MCV ↑RDW (PPV for ID=93%)

341 Lost to Follow-up (38%)

552 Followed Up

268 “Cured” (30%) i.e. 2nd Hb>11.0 g/dL

Demonstrated duration of disease= 284 Still Anemic (32%) Demonstrated duration of disease= 147 days (mean) range 15-836 days

Extraordinary Thanks to Maura Hoag

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REITZENSTEIN,JONATHAN,MD Ringo,Patrice M,MD SCHREIER,HERBERT M. D REITZENSTEIN,JONATHAN,MD Ringo,Patrice M,MD SCHREIER,HERBERT M.D. SPOONER-DEAN,KERRY,M.D. RHODES,GREGORY A,MD Risgalla,Edward,MD SCOTT,MALAIKA M,MD STALLINGS,RONALD,MD RIDDEL,JIM,NP Roberts,Jessica B,MD SEBAN,OLIVER,MD STEBER,BRIAN,MD RILEY,JENNY,MD Roberts,John Paul,MD SEED,CHRISTINA,DO STEELE WOODALL,VICKY,FNP RINGO,PATRICE,MD Robinson,Curtis,M.D. SEGALL,SERGE S,DDS STEELMAN,MARIA,MD RISGALLA,EDWARD,MD Rodarte,Christopher,M.D. SHAH,NISHANT H,MD STEFFENSON,SANDRA,MD ROBC Roe,Taiyun,MD SHAH,SAMIR,MD STEIN,MICHAEL R,MD ROBERTS,JESSICA,MD Romero-Duran,Adolfo,MD SHAIN,PHILIP,MD STEINER DOOHAN,NOEMI,MD ROE,TAIYUN,MD Roos,Joan A,FNP SHANAHAN,ROBIN,MD STEINHART,RACHEL,MD ROHWEDER,DANIEL A,MD Roos,Joan,FNP SHATZ,ARNOLD,MD STEIRN, FNP Schaffer,Sarah,MD ROMERO-DURAN,ADOLFO,MD Rosenfeld,Jack,DDS SHAW,MAYA S,MD STEIRN,FNP Schaplow,Reagan,MD ROMO,CECILIA Rosenthal,Macey H,MD SHEFA,MEHDI,MD STETTNER,MICHAEL,FNP Schechtman,Andrew,MD ROSENTHAL,PHILIP MD Rosenthal,Macey,MD SHEFA,Q,MD STEUBLE,B Scheffer,Jonathan L,MD ROSENTHAL,PHILIP,MD Ross,William,M.D. SHELDON,WILL C,MD STYCH,DEBORAH,FNP Scherzberg,Maureen,FNP ROSS,CHRISTINE,MD Rudlowski,Teresa,MD SHELTON-PRYOR,RUTH E,MD SWARZENSKI,BARBARA,MD Schnake,Ann L,FNP ROUX,JOAN W,MD Rush,Philip,MD SHOVLIN,PATRICIA M,MD Saffier,Kenneth A,MD Schnake,Ann,FNP RUDA,STEPHEN,DO SACHDEV, NEELAM,MD SIEGAL,JENNIFER Saffier,Kenneth,MD Schneider,Jeanette E, M.D. Rafal,Robert,MD SACHDEV,JANAK,MD SIEGEL,ALAN,MD Safianoff,David,MD Schreiber,John,MD Randles,Bradley,MD SACHDEVA,SURESH,MD SILVERSTEIN,STUART C,MD Saito,Hideto,MD Schwamberger,Shelle,MD Rapa,Katarzyna W,MD SAHEBKAR,FARHAD M,MD SIMMONS,JILL (HILTY) Salceda,Irene A,PA Schwartz,Jerrold,MD Raphael,David,MD SALSBURG,ELIZABETH L,MD SIMON-WEISBERG,DEBORAH,MD Sam,Michel,MD Schwedes,Judith,MD Raumer,Sheila,MD SAMPSON,OLIVIA,MD SINHA,NANDA,MD Sandler,Andrea E,MD Scott,Malaika M,MD Reedy,David B,MD SANDLER,ANDREA,MD SKOCHKO,GREG,MD Sandler,Maurice,MD Seawell,Elaine O,FNP Reese,Cote SAPIEN,ROBERT E,MD SMITH Sands,Michael,MD Seawell,Elaine O.,FNP Reif,Paul,MD SARASUA,JAMES,MD SMITH,CHRISTINE B,FNP Santiago,Daniel E,MD Severson,G. Kaye,FNP Reilly,Brenda,MD SAUERLAND,EBERHARDT,MD SMITH,THOMAS J,MD Sapien,Robert E,MD Shaffer,Ingeborg,MD Reisman,Jeanne,MD SAVAGE,CYNTHIA,MD SOLIS,ROBERTO A,MD Sarvasy,Paul,MD Shah,Nishant H,MD Render,Rebecca M,DO SCHAFFER,GERALD, MD* SOLOMON,DAVID J,MD Sarvi,Saunaz,DDS Shalen,William Reynolds,Nancy,MD SCHEFFER,LISA G,MD SONG,JACK,MD Saucedo,Jesus,M.D. Sharma,Aditya,MD Reynolds,Vera,FNP SCHESSER,JONATHAN,MD* SORIA,RAFAEL,MD Savage,Cynthia J,MD Shaw,Howard,FNP Riccio,Adrienne,RN SCHIFFMAN,LOLLY,MD SORRELL,ARTHUR,MD Savage,Walter T,MD Shaw,Maya S,MD Rice,Abraham C,MD SCHMIDT,D SCOTT,MD SPAIN,ALAN J,MD Sayani,Sam,MD Shaw,Michael Riedel,J Frederick,MD SCHNEIDER,LUREE,MD SPANGLER,LINDA,MD Siegel,Alan L,MD Sheldon,Will C,MD

Siegel,Jennifer,M.D. Stone,David,MD Treatment,Nurse WARNE,THOMAS,MD Weiner,Ira,MD Sigmond,Herbert,MD Stringer,Penney C,MD Tremain,Steven,MD WASHINGTON,SHARON D,MD Weingard,Herbert,MD Simon-Weisberg,Deborah,MD Strych,Deborah,FNP Truman,Kirsten C,MD WATERS,SHANNON,MD Weinreich,Don H,MD Singh,Deviner,MD Su,Cindy W,MD Tsai,Clark S,MD WATSON,JOHN,MD Weiss,Stephen,MD Skinner,Harry,MD Suchow,David,MD Tsai,Tsuong,MD WEBB,KINARI,MD Weng,Christiana Y,MD Slauson,Dana L,MD Sutherland,Sonia,MD Tsang,Jennifer,MD WEI,ALAN,MD Werner-Crohn,Mindy,MD Slauson,Dana,MD Swartz,Aubrey,MD Tysell,James R,MD WEIGOLD,SCOTT,MD Wernham,Aaron A,MD Smallhorne,Violet,MD TAI,DENICE K,MD Tysell,James,MD WEILAND,DAVID S,MD Westerman,Jennifer,FNP Smick,Kathryn,MD TANG,JOYCE,MD Tzvieli,Ori,MD WEINMAN,CHRISTIAN,MD Whalen,Jon,MD Smith,Daryl,MD TANTOD,BHAKTI,MD UDENYI,NKECHINYERE,MD WENG,CHRISTIANA,MD White,Keith C,MD Smith,James,MD TAVERNIER,LAURA,MD UNASSIGNED PCP WHINNERY,CATHERINE,MD White,Keith,MD Smith,Jeffrey V,MD TAYLOR,DENISE UNDERWOOD,VIRGINIA,MD WHITE,CHRISTINE,FNP White,Matthew P,MD Smith,Nora,MD TODD,MICHAEL,MD UNIS,CLAIRE,MD WHITE,NEAL,MD White,Ralph Devere,MD Smith,T,MD TODD,RODNEY,MD Urcuyo,Sergio,MD WHITE,VANEIDA,MD White,Thomas,MD Sobel,Daniel,MD TOMASULO,MICHELE,FNP VALVERDE WHITEHAIR,BREA,MD Wildfire,Gila,MD Solomon,David J,MD TORNABENE,FELICIA,MD VALVERDEE WHITEHALL,JUDI,MD Wille,Mark,MD Song,Jack J,MD TREATMENT,NURSE VAN HANDEL,MARK,MD WHITTEN,LAURA F,MD Williams,Kathryn,MD Sorensen,Gregg S,MD TREYGER,LEONID,MD VAN MEURS,DIRK,MD WIDDER,DONALD J,MD Williams,Tanya M,MD Spalding,Joanne,MD TZVIELI,ORI,MD VAN ORDEN,FRANK,MD WILDFIRE,GILA,MD Wong,Bryan M,MD Standefer,Charlotte B,MD Tai,Denice K,MD VAN SCHAVEN,EMILY,MD WILLIAMS,ROGER,MD Wong,DAN K,DDS Standefer,Charlotte,MD Tangco,Angelita,MD Van Duren,Michael,M.D. WIXOM,PHILIP A,MD Wong,Michelle,MD Stanger,Jennifer,MD Tantod,Bhakti D,MD Van Duren,Michael,MD Wadle,Dawn Marie,MD Wong,Sharman,OD Stanger,Jonathan R,MD Taylor,Denise,MD Van Konynenburg,Kristin,MD Wagner,Andrea,MD Wright,Lara M,MD Staniotes,Lizabeth N, M.D. Taylor,Opal I,MD Vastine,David R,MD Wagner,David,MD YANG-SHARMA,PATRICE,MD Steinberg,Jonathan D,DPM Tendero,Clarissa,MD Von Rydingsvard,Milton,M.D. Walker,Scott,DDS YASUL,JOSE,MD Steinberg,Susann,M.D. Tenduf-La,Tenki,MD Vonbuettner,Marion,MD Walker,Susan J,MD YATES,RACHEL L,MD Steinhart,Rachel,MD Thedinger,Blair,MD Vonrydingsvard,Milton,MD Walker,William,MD YOO,DAVID,MD Steirn,Cathy,FNP Thomas,Cecilia,DDS WAGNER,DAVID,MD Walsh,John R,MD Yang-Sharma,Patrice,MD Stephens,Claudell,MD Thomas,Michelle,MD WALKER,BRADLEY,MD Walsh,Judith M,MD Yasul,Jose I,MD Stephenson,Linda,FNP Timmerman,Laura A,MD WALKER,MIGNON,MD Walsh,Judith,MD ZAKS,CAMILO C,MD Stern,Richard S,MD Toma,Louay,MD WALSH,JOHN,MD Warne,Thomas R,MD ZELAN,SAUL,MD Stewart,Jerome,MD Tomasulo,Michele,FNP WANG,CATHERINE,MD Warner,Deborah,MD Zaks,Camilo C,MD Stinson,Mark,MD Trapnell,James,MD WANG,LINA,MD Wasko,Janet,FNP Zaks,Walter,MD Zimmerman,Daniel,MD Zerweck,Bradley W,MD Zamani,Christopher,MD

KASTEN,THOMAS,MD Keller,Lisa K,MD LEGGETT,MICHELLE Lee,Rebecca,MD KAUR,RAMANDEEP,MD Kelley,Juliette,MSS LEHMAN,TARA,MD Legg,Jill J,MD KEATING,LIAM,MD Kelly,Olga D,MD LEIGH,ERICA,MD Lehman,Tara A,MD KEBEBEW,POSITRON,MD Kemmet,Rebecca K,MD LEIGHTON,LYNETTE Leong,Craig,M.D. KELLY,KRISTEN Kershnar,Rebecca L,MD LERMAN,BENJAMIN S,MD Leong,Rudy,M.D. KELLY,OLGA,MD Keswani,Anita,MD LEWIS, NANCY E,MD Levin,Robert,M.D. KENT,ZACK,MD Kim,Hye-Kyung,MD LEWIS,BRAD,MD Levin,Sara K,MD KERLEY,SARA,MD Kleinerman,David I,MD LEWIS,ELISE,MD Lewis,Elise A,MD KERSHNAR,REBECCA,MD Kleinerman,David,MD LEWIS,STEPHEN B Lin,Alice,MD KEVAN, JONATHAN Kline,Todd M,MD LIN,ALICE,MD Lindsay,R. J.,M.D. MAYLAND,GABRIEL,MD KHAN,FARINA,RN Knight,Robert,MD LIN,JANET,MD Lindsey,David,M.D. MCADAMS,LANCE,MD KHOURY,RONALD,MD Koo,Ralph A,MD LIN,MARGARET,MD Lipson,John H,MD MCBRIDE,PAMELA,MD KIBELSTIS,THOMAS,MD Kramer,Theresa,MD LINDE,BRIAN,MD Lively,Daniel, M.D. MCCARTHY,CLAIR,MD KISSINGER,CATHY,FNP Kulinsky,Ilya,MD LINN-MAKUA,LIZABETH,FNP Lockhart,Ann B,MD MCCARTHY,EVE A,FNP KONKK Kullar,Ravjeet K,MD LIPSON,JOHN H,MD Loeliger,Scott F,MD MCCORMICK,JANE,MD KOO,RALPH A,MD Kumar,Pradeep,MD LOCKHART,ANN,MD Long,THOMAS MCCOY,THOMAS C,DO KRUTZ,REBECCA A,MD LAI,JAY LOEFFLER,ANN M,MD Longoria,Anthony M,FNP MCDANIEL,MARC KULLAR,RAVJEET,MD LAM,WENDY LOELIGER,SCOTT,MD Lopez,Carlos,M.D. MCDONALD,THOMAS,MD KULOVSKY,SUSAN M,DO LAMANUZZI,SARAH MD LONGORIA,ANTHONY M,FNP Lopez,Hector J.,MD MCENTEE,AMY,MD KURUVILLA,PRAMITA,MD LAXAMANA, DARLEEN DDS LOTRIDGE,JESSICA,MD Lucey,Bette B,FNP MESSINGER,JEFFREY,MD Kailikole,Theresa,MD LEACH,RANDY A,MD LUCEY,BETTE,FNP Lum,Karen, M.D. MEYER,JACOB M,MD Kaji,Troy T,MD LEAVITT,JONATHAN LUM,KAREN Luong,Lien,MD MEYER,JENNIFER,MD Kalkstein,Stephen W,MD LEE,BRIAN,P,MD LYONS,MICHAEL,MD MACCHOR,NADAL MEYER,LEIF Kalra,Sumita K,DO LEE,DANIEL A,MD Lackman, M. MD MACEDO,JOSEPH,MD MILLER,DAVID,MD Kamalnath,Prakash J,MD LEE,ERIN M MD Lantz,Donald J,MD MAHAR,DIANA,MD MILOJEVIC,DIANA MD Kang,Hanna,MD LEE,GEORGE,MD Lantz,Donald,MD MAHONEY,JOHN MINDY WERNER-CROHN, MD Karell,Manuel L.,M.D. LEE,JAMES, MD Lares,Beatriz,M.D. MALIK,RITU,MD MIRAMONTE, SHELLY Karpf,Esther,FNP LEE,KAI-MAN,MD Laxamana,Darleen G,DDS MANUNTAG,WILFRED MIRANDA,KRISTEN Kartun,Karen F,MD LEE,MICHAEL Lee,Daniel A,MD MANUNTAG,WILFREDO,MD MOELLER,KRISTIN,MD Katz,Samuel,MD LEE,SCOTT,MD Lee,Eun-Kyu,M.D. MARTINEZ,DAVID,MD MOHR,ARWEN,MD Katzman,Kenneth A,MD LEE,SU-MAY,MD Lee,John M,MD MARTINEZ,MICHAEL S,MD MONTANDON,MICHELE,MD Katzman,Kenneth,MD LEE,TABESSA I,MD Lee,John,M.D. MATSUNAGA,ALISON T,MD MOORE,JUDE J,MD Kaufman,Douglas,MD LEGG,JILL J,MD Lee,Michelle,MD Keating,Liam,MD MORAN,BRIDGET,FNP

MORGAN,JAMES,MD Martinez,Michael S,MD Morrison,Chantal L,DO PABERS,JOHN,MD Perez,Edith,MD MORRISON,CHANTAL L,DO Matsumura,Gary,MD Mueller,Robert A,MD PACKMAN,SEYMOUR,MD Perez,Greta,MD MOULTON-BARRETT,REX,MD Matsunaga,Alison T,MD Murai,Sarah E,MD PAIGE,THOMAS,MD Perez,Pauline,MD MOZA,JOSEPH,MD Mattka,F J,DDS NAIMA,IRAJ,MD PALMER,NANCY,MD Perez,Peter J,MD MUNNICH,JO MARIE,MD May,Daniel,MD NATION,ROMAN,MD PALOMINO,MICHAEL A,MD Perez-Baron,Gina,MD MURAI,SARAH,MD Mbanugo,Ogo S,MD NAVEL,DAVID,MD PALOMINO,MICHAEL A,MD Perez-Salinas,Dalia MacDannald,Harry,MD Mbanugo,Ogo,MD NAVEL,JAMIE,MD PAYNE,CHELSEA,MD Perlas,Maria K,MD MacDonald,David J,MD McAnich,Jana,MD NGUYEN,DAO M,MD PEHLING,JAMES R,MD Perry,Alison W,FNP MacDonald,David,MD McAninch,Jack W,MD NGUYEN,LOAN,DO* PEPPER,DAVID,MD Peterson,William J,MD Macedo,Joseph J,MD McCabe,Robert,MD NGUYEN,MYHOANG,MD PEREZ,JUAN,MD Pham,Julie,DO Madrigal,Teresa,MD McCoy,Thomas C,DO NIX,DEBBIE,FNP PEREZ-BARON,GINA,MD Picker,Robert,MD Magbitang,Fereyes,MD McDaniel,H Marc,MD Nagel,Charlotte,MD PERLAS,JANE,FNP Pierson-Brown,Leigh,FNP Mahan,Bernadette McDonald,Diana,FNP Navel,Jamie M,MD PESSL,ERICH,MD Pilcher,David W,MD Mahar,Dennis,MD McDonald,Michael Nelson-Munson,Karen,MD PETERSON,AARON,MD Pillai,Sangita S,MD Mahar,Diana H,MD McNabb,Thomas R,MD Nguyen,Myhoang P,MD PETERSON,WILLIAM J.,MD Pinto,Natasha J,MD Maher,Patrick,MD McNeil,Sarah,MD Nidorf,David,MD PETTIT,CHARLES R,MD Pitman,Dorothy,M.D. Maher,Terry,MD Melny,Richard,MD Nix,Debbie,FNP PHAM,AN T,MD Pizzo,Anthony,FNP Makhoul,Nicolas E,M.D. Mendoza,Julio,DDS Nordensjo,Anna K.,M.D. PHELPS,BRIAN,MD Polzin,David,MD Makhoul,Nicolas E,MD Mendoza,Zenaida M,MD O'LEARY,MAURA,MD PIERSON-BROWN,LEIGH,FNP Porter,William,MD Makow,Adele,MD Mendoza,Zenaida, M.M.D. O'MEANY,JUAN F,PA PIERSON-BROWN,LEIGH-ANNE,FNP Pramanik,Rajiv,MD Malik,Geeta,M.D. Meyer,Jacob M,MD OLDHAM,DEREK,RES PINTO,NATASHA,MD Public Health,Pittsburg Malik,Rajiv,MD Meyers,Leif E,MD ONISKO,NANCY,DO POLLICK,CHRISTOPHER,MD Public Health,Richmond Malik,Ritu,MD Miller,Barry,M.D. OWENS,MELISSA K,MD PONOMAREFF,GEORGE,MD Puell,Michael A,MD Mallen,Peter R,MD Miller,Daphne,M.D. OZAETA,LEE,MD POPULIS,AMELIA Puell,Michael,MD Mandiberg,Robert L,MD Miller,Fred,MD Olsen,Harvey,MD PRAMANIK,RAJIV,MD QADIR,MALIHA,MD Mansour,Karim M,MD Miller,Laura FNP Olsen,Richard,M.D. PRESCOTT,STACY MD QUIDES,KATHY,N.P. Manuntag,Wilfredo P,MD Miller,Michael,M.D. Olsen,SteveN PRIVATE DOCTOR QUINONES,LISA M,MD Maramonte,Shelly M,MD Milojevic,Diana,MD Olson,Donald,MD PRYSI,SCOTT,MD Quinones,Lisa M,MD Maramonte,Shelly,MD Moeller,Kristin A,MD Onisko,Nancy S,DO Paige,Thomas N,MD RANA,FARAH,MD Marchand,Erin,MD Mohr,Arwen E,MD Osborne,David F,MD Palmer,Nancy K,MD RAO,KALPANA,MD Maron,Steven,MD Montandon,Henri E,MD Osborne,Frederick M,MD Parkison,Gary,M.D. RAPA,KATARZYA,MD Marten,Timothy,MD Montandon,Michele M,MD Owen,Kenneth Dale,M.D. Pearson,Meg RASKIN,GORDON,MD Martin,Albert E,DDS Morrell,Rose E,MD Owens,Nancy,M.D. Pehling,James R,MD REEDY,DAVID B,MD Martin,Gail E.,M.D. Morrell,Rose,MD Owens,Nancy,MD Pepper,David R,MD REILLY,BRENDA,MD