PATTERNS TO EASILY IDENTIFY AND TESTING TO EFFECTIVELY CONFIRM

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1 PATTERNS TO EASILY IDENTIFY AND TESTING TO EFFECTIVELY CONFIRM

2 WHERE DOES THIS DATA COME FROM? MY EXPERIENCE 3 YEARS REVIEWING CHARTS AT SMMH LITERATURE GUIDELINES

3 PROLOGUE >1000 SMMH BLOOD REVIEWS /YEAR = TO SJMH (KUDOS TO SMMH) COST (MEDICARE)=28$ COST AND VALUE OF TESTING ORDERED BEFORE AND AFTER IS THE FOCUS HERE

4 ANEMIA DEFINITION (WHO) MEN <13 G/DL WOMEN <12 G/DL MAY BE NORMAL FINDING IN CHILDREN, PREGNANCY (VOLUME EXPANSION),BLACK AGED?

5 DIURNAL HGB AND WBC CHANGES RBC, HGB,HCT-FALL DURING DAY, NADIR AT 12AM,.5 G/DL IN ATHLETES WBC AND NEUTROPHIL COUNT-RISE DURING DAY AND PEAK AT MIDNIGHT HCT INCREASES 11% ON STANDING FOR 30MIN AND DECREASES WITH RECUMBENCY

6 APPROACHES TO ANEMIA DIAGNOSIS AND CLASSIFICATION RBC SIZE-BEST 1)MICROCYTIC-MCV <89 2)NORMOCYTIC-MCV )MACROCYTIC-MCV >98

7 PATHOGENETIC CLASSIFICATION OF ANEMIA NOT AS VALUABLE TO ME BECAUSE OF SIZE OF DDX ES 1)IMPAIRED PRODUCTION 2)INCREASED DESTRUCTION 3)BLOOD LOSS

8 RETICULOCYTE COUNTS-WAYS TO ENUMERATE MOST ARE AUTOMATED WHICH IMPROVES PRECISION BUT NOT UTILITY AU STD-%AGE OF ALL RBCS, AN OVERESTIMATE BECAUSE #RBC S DECREASE IN ANEMIA ABSOLUTE RETIC CT (N<2.5%)=%AGE X RBC# RETICULOCYTE PRODUCTION INDEX=% X HCT/45 X1/X. X=1.5 IF HCT <30 AND 2 IF HCT IS<20% FUTURE (IRF, RTHBCT,..)

9 HOW TO EVALUATE ANEMIA 1) MCV 2)RETIC CT, IF MCV>90 (LEAST VALUABLE) 3)LOW PLATELET OR NEUTROPHILS WHEN #3 IS PRESENT, MDS AND MYELOPTHISIS ARE A POSSIBILITY. IF PLATELET IS HIGH BUT MCV AND HGB ARE LOW DO NOT CONSIDER ET OR PRV UNLESS TREATED

10 MICROCYTIC ANEMIA CAUSES (MCV <89) IRON DEFICIENCY (MEAN MCV=83) CHRONIC DISEASE (MEAN MCV=88) THALASSSEMIA TRAIT (RBC>5)-GET HGB ELECTROPHOSIS TO QUANT HBA2 HEMOGLOBINOPATHY (C OR E)- FAR EASTERN, TARGET CELLS, SIDEROBLASTIC ANEMIA (B6 DEF OR ETOH)

11 TYPICAL CBC IN FE DEF ANEMIA DEC MCV, USU LESS THAN 83 UNLESS TRNS DEC RBC#(COMPARE TO THAL TRAIT,>5) DEC MCHC RDW (MCV SD) INCR (ESP AFTER TRNS)-NL IN THAL AND CHRONIC DISEASE PLT # INCR (EVEN IF >1,000,000 DON T THINK MPN)

12 TESTS FOR FE DEF-WHICH? WHEN? SERUM FE BY ITSELF-INSENSITIVE, HEMOLYSIS INTERFERENCE,TRANSFUSION, DIURNAL VAR FREQUENTLY ORDERED AT SMMH ALONE FE/TIBC%-BETTER CUZ TIBC INCR, INCRSNG SENS TIBC-SERUM TRANSFERRIN X1.4-DECR IN MALNUTRITION AND CACHEXIA, MORE SENSITIVE THAN ALBUMIN BECAUSE T1/2 IS SHORTER 30% WNL, <15% SUGGEST FE DEF BUT CHR DIS CAN RESULT IN %AGE OF INCR FE AND DECR OR NL TIBC SUGGEST SIDEROBLASTIC OR HEMACHROMATOSIS (FE/TIBC RECOMMENDED SCREEN) NOT FERR OR DNA/PCR

13 FERRITIN BEST TEST FOR PRICE, TAT, AND QUALITY INCR IN INFL DIS ESP HEPATIC AND NECROSIS NORMAL RANGES ARE TOO LOW BECAUSE FE DEF IS ENDEMIC EVEN IF HGB IS WNL VALUES <100 WITH MICROCYTIC ANEMIA SUGGEST FE DEF

14 SOLUBLE TRANSFERRIN RECEPTOR NEW KID IN TOWN $$$ (380) BY REF LAB LONG TAT USE WHEN FERRITIN AND FE/TIBC AND CBC DATA ARE NOT CONCORDANT PROBABLY THE SINGLE BEST TEST USU EXPRESSED AS STFR/LOG FERRITIN

15 HGB ELECTROPHORESIS FOR HBA2 QUANT AND ID OF HBC AND HBE >4% HBA2 SUGGESTS BETA THAL <2% HBA2 SUGGESTS ALPHA THAL FE DEFICIENCY CAN DECR HBA2 AND CONFUSE. ORDER HGBE AND FERR COMBO. IF MICROCYTIC ANEMIA SHOWS TARGET CELLS DO THIS TEST TO IDENTIFY HBC AND HBE

16 PROBLEMS WITH IRON STUDIES AND CBC VALUES IN FE DEF ANEMIA FE PILLS-ABSORBED IN DUODENUM AND CAUSE SERUM FE TO RISE IN <1HR, BUT BACK DOWN IN 4 HRS INCR PLT# IS COMMON IN FE DEF AND NOT NECESSARILY ET OR PRV ANEMIA OF CHRONIC DIS DECREASES FE, TIBC, FE/TIBC%, BUT NOT FERRITIN.

17 A RECENT EXAMPLE OF MISLEADING FE STUDIES IRON STUDIES: FERRITIN 7 (>26) IRON 223 TIBC 346 ( ) %AGE SAT=64 CBC (67 MALE): RBC 3.8, HGB8.0,MCV 68, MCHC30.7, RDW 23.9

18 CBC AND FE IN MIC ANEMIAS DISEASE RBC MCV RDW MCHC DISEASE THAL SERUM INCR, FE >5 TIBC <79 NL FERRITIN DEC %FE SAT FE DEF TRT D I D MARKED D CHR DIS D D N D SIDEROBLAS TIC FE DEF DEC <83, VAR INCR, VAR CHR DIS DEC <88, MILD NL, OR SL I DEC DEC I NL TO D I I

19 NORMOCYTIC ANEMIA (MCV 89-98) WHILE IRON DEF AND CHRONIC DISEASE CAN SNEAK IN HERE, SYSTEMIC DISORDERS PREDOMINATE IF RETIC CT IS INCR (ABS AND RPI NOT JUST %AGE), GET INDIRECT BILI, LDH, SHISTOCYTE COUNT, HAPTOGLOBIN, COOMBS, ANA,U/A HISTORY OF CHRONIC LIVER AND KIDNEY DX

20 CBC CLUES IN NORMOCYTIC ANEMIA NRBC S IN THE ABSENCE OF STRESS OR TRAUMA OR HYPOXIA SUGGEST MYELOPTHISIS 50% OF NRBCS IN ADULTS ARE BENIGN (TRAUMA AND HYPOXIA AND CPR) ROULEAX WARRANTS PROTEIN ELECTRO FOR MYELOMA. SEVERE ANEMIA (HGB<6) ALWAYS HAS IT, REDUCING THE UTILITY. LOW PLATELETS AND INCR RETIC CT SUGG TTP AND WARRANT D DIMER TO EXCL DIC

21 HEMOLYSIS CLUES CHECK RBC MORPH-MORE IMPORTANT THAN BONE MARROW BURR CELLS AND SCHISTOCYTES INDICATE INTRAVASCULAR DUE TO DIC OR TTP OR HUS SPHEROCYTES SUGGEST EXTRAVASCULAR DUE TO DRUG OR AUTOIMMUNE OR COLLAGEN VASCULAR DX BURR CELLS WITHOUT LOW PLT# = UREMIA

22 MICROANGIOPATHIC HEMOLYSIS TTP-PLT # USU AROUND 50K, SCHISTOCYTES USU ARE MOD-MARKED, BUT THE PLT # NOT THE RBC S ARE THE BETTER GUIDE TO TREATMENT SUCCESS AND SEVERITY OF DISEASE ADAMTS-13 (VWF CLEAVING ENZYME) EXPENSIVE, LONG TAT, DOESN T HELP GI SYMPTOMS, OB PT, SUGGEST HUS NOT TTP SEPSIS SUGGESTS DIC-CONFIRM WITH D-DIMER>1000 ALL CBC S AT SMMH WITH DECR PLT# ARE SCANNED FOR SCHISTOCYTES TO EXCL TTP

23 MACROCYTIC ANEMIA (MCV>98) SUBDIVISIONS: MEGALOBLASTIC (MACROOVALOCYTES AND HEPERSEGMENTED (>5) NEUTROPHILS-ALWAYS COMMENTED ON IF PRESENT NON MEGALOBLASTIC (ABOVE ABSENT)

24 NON MEGALOBLASTIC MACROCYTIC ANEMIA ETIOLOGIES LIVER DISEASE ESP DUE TO ETOH- AST/ALT RATIO >2 SUGGESTS ETOH-GGT (FAST) AND CDT (SLOW) CONFIRM AST/PLT# RATIO SUGGESTS CIRRHOSIS BUT IS NOT STANDARDIZED ACROSS ALL INSTRUMENTS HYPOTHYROIDISM (IN BOOKS, RARE TO ME) MYELODYSPLASIA/PRELEUKEMIA HEMOLYSIS-ALL MACROCYTIC ANEMIAS NEED A RETIC CT

25 MEGALOBLASTIC ANEMIA CAUSES B12 FOLATE AZT 6-MP MDS ETOH MTX AZOTHIOPRINE

26 LAB TESTS FOR MACROCYTIC ANEMIA VITAMIN B12 CONGENITAL ASYMPTOMATIC DEF IS COMMON (SO CALLED R BINDER DEF) LOW B12 SHOULD BE CONFIRMED WITH HOMOCYSTEINE AND LDH (EASY AND CHEAP) MMA IS GOLD STD OF FUNCTIONAL DEF BUT TAKES AN EXTRA DAY BUT IS CHEAP LDH SHOULD BE MARKEDLY INCR IN PA

27 FOLATE DEFICIENCY IS VERY RARE OUTSIDE OF ETOH (FNCT), PREGNANCY (INCR NEED),CHRONIC HEMOLYSIS, MALABSORPTION RBC FOLATE IS NOW FELT TO BE OBSOLETE AND IS DECR IN B12 DEF LEADING TO POSS THER MISADVENTURE FIGLU IS OBSOLETE

28 CLUES TO MDS/PRELEUKEMIA ABNORMAL CELLS (BLASTS) AND NRBC S IN PB MACROCYTIC ANEMIA WITH MULTIPLE LINES LOW AND MACROCYTIC ANEMIA ALONE ELDERLY CHEMOTX IN REMOTE PAST (BAD PROGNOSIS),USU ALKYLATING AGENT, TOPOISOMERASE

29

30 PLATELET # BLEEDING RISK LOW PLATELET COUNT-DEFINITION BY BLEEDING RISK <50000 MILD-CHANGE FROM PAST (100) <20000 MODERATE-CHANGE FROM PAST (30) <10000 SEVERE

31 NEUTROPENIAS RISK LEVELS NEUTROPENIA-DEFINITION BY RISK OF INFECTION <1500 MILD <1000 MODERATE <500 SEVERE-HIGH PRECISION WITH CONTEMPORARY ANALYZERS-BETTER THAN PLT S CUZ PMN S ARE BIGGER AND HARDER TO MISTAKE AS SOMETHING ELSE

32 PSEUDOTHROMBOCYTOPENIA DEFINED AS LOW COUNT DUE TO CLUMPING IN VITRO BUT NOT IN VIVO LAB PROBLEM NOT A PATIENT PROBLEM EDTA DEPENDENT PH DEPENDENT AB SOMETIMES A BLUE TOP WILL BE ACCURATE LAB AUTOMATICALLY SENDS A TEAM OUT TO REDRAW INPTS,

33 SPECIAL FINDINGS IN LOW PLT# SHISTOCYTES SUGGEST DIC,TTP, HUS OR HELLP TEAR DROPS AND MACROOVALOCYTES AND NRBC S SUGGEST MDS PA OR MYELOFIBROSIS ATYPICAL LYMPHOCYTES AND AGE<50 WARRANT MONOSPOT ANTIBIOTICS, ESP VANCO, VALP AND HEPARIN LARGE PLTS, LOW PLT #(TYP <125,000) AND CHRONICITY SUGGEST B-S OR M-H CONG B9

34 NEUTROPENIA ARTEFACTUAL-SOMETIMES CLUMP LIKE PLTS ATYPICAL LYMPHS-DO MONO IF AGE<50 ATYPICAL MONO S OR BLASTS CONSIDER MDS >2000 LARGE GRANULAR LYMPHS SUGGEST T- GAMMA LYMPHOPROLIFERATIVE DISORDER T-LGL IS B9 REQUIRING LITTLE RX MEDICATIONS CONGENITAL OR CYCLIC NEUTROPENIAS

35 IMPORTANT HX IN NEUTROPENIA FAMILY AND PERSONAL HX OF LOW BLOOD CTS TO EXCLUDE CYCLIC AND CONGENITAL DRUGS ESP COCAINE-IMPURITIES LIKE LEVAMISOLE CAUSE AGRANULOCYTOSIS AUTOIMMUNE DISEASE ESP RA (FELTY S) AND SLE PANCREATIC DX (CALLED PEARSONS SYNDROME)

36 LYMPHOPENIA STRESS REACTION, ACUTE CORTICOSTEROIDS VIRAL DISEASE ESP HIV AND HBV NEOPLASMS ESP HODGKINS BUT ALSO NHL

37 PANCYTOPENIA WITH ABNORMAL CIRCULATING CELLS NEED BX OR BM TO CONFIRM MDS OR AML WITHOUT (MUCH MORE COMMON) R/0 B12 OR FOLATE (ESP IF ETOH HX) PNH MYELOPTHISIS MEDICATIONS LEUKEMIAS, ESP HCL APLASTIC COPPER DEFICIENCY ESP THAT DUE TO ZN EXCESS

38 LEUKOCTYTOSIS-GEN L COMMENTS NEUTROPHILIA IS NORMAL IN FIRST 3 DAYS NEVER USE %AGES ONLY ABS CTS TO IDENTIFY LYMPHOCYTES ARE > SEGS IN CHILDHOOD

39 LYMPHOCYTOSIS CLUES LYMPHOCYTOSIS>5000 OVER THE AGE OF 50 SUGGESTS B-CLL AND CAN BE CONFIRMED WITH FLOW CYTOMETRY OF BLOOD NOT BM IF AGE <50 AND/OR MORPHOLOGY ATYPICAL ORDER MONOSPOT TO CONFIRM EBV USE EBV SEROLOGY ON MONO NEG CASES-TYPICALY VERY YOUNG AND ADULTS IF SERONEG, CONSIDER EBV (IF VERY YOUNG OR ADULT), CMV (POST-CARDIOTOMY SYNDROME), TOXO, HSV, HIV

40 T GAMMA LYMPHOPROLIFERATIVE DISORDER AKA T-LGL, T-CLL, T-GAMMA ABSOLUTE LYM # FREQUENTLY WNL INCR LGL S IN SMEAR NEUTROPENIA SPLENOMEGALY (DDX FELTY S SYNDROME) LONG INDOLENT HX WITH SYMPTOMS DUE TO INFECTIONS AND RHEUMATOID DISEASE NOT TUMOR

41 NEUTROPHILIA INFECTIOUS TYPICALLY <50,000 CML CAN BE EXCLUDED BY BCR/ABL ON PB (FISH, LAP SCORING OBSOLETE) BASOPHILIA AND LEFT SHIFT SUGGEST CML MEDICATIONS SMOKERS

42 MONOCYTOSIS CHRONIC INFECTIONS MALIGNANCY ESP CARCINOMA LEUKEMIA (USU IMMATURE WITH BLASTS)

43 EOSINOPHILLIA NEARLY ALWAYS REACTIVE ALLERGY TO DRUG OR ENVIORMENT PARASITES RARELY MYELOPROLIFERATIVE IHES RESULTS IN TISSUE EOSINOPHILLIA ESP HEART LEADING TO ARRHYTMIAS

44 BASOPHILLIA BASOPHILLIA OF 600 OR MORE IS CML TPO NO MATTER WHAT THE WBC OR PLT# IS HYPOTHYROIDISM AND ULCERATIVE COLITIS ALLEGEDLY INCR BASO S BCR/ABL NOT LAP SCORE

45 THROMBOCYTOSIS MOST COMMON CAUSE IS OCCULT BLEEDING/IRON DEFICIENCY (85%) ALWAYS ORDER A FERRITIN WITH INCR PLT# CML AND ET ARE CHRONIC MPNS WITH SPLENECTOMY INFECTION W/U:FERRITIN, FOB,BCR/ABL,CRP, JAK 2

46 POLYCYTHEMIA DEHYDRATION-BUN/CR RATIO COPD-HX, PO2 PRV-JAK 2 (PRESENT IN >90%) ERYTHROPOETIN (LOW OR NORMAL) USU MILD NEUTROPHILIA AND THROMBOCYTOSIS PARANEOPLASTIC-ABDOMINAL CT ESP LIVER KIDNEY AND UTERUS HIGH AFFINITY HGB-P50

47 THE END!

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