Using Blood Tests in Gastroenterology

1. Using Blood Tests in Gastroenterology Philip Koszyk, MD, FACG Digestive Disease Consultants, LTD Normal, IL

2. Objectives Use of standard blood tests to aid in care of pts w/ digestive disease Application of GI-specific blood tests (IBD, CD, liver) Case presentations

3. CBC Hgb/RBC WBC Platelets MCV- mean corpuscular volume RDW- RBC distribution width (degree of variation in RBC size)

4. Hemoglobin Fe-containing metalloprotein that binds and transports O2

5. Oxygen Delivery to Tissue Hypoxia- insufficient O2 supply to tissue Hypoxemia- decreased partial press. O2 Anemia-decreased Hgb

6. Types of Anemia Microcytic- Fe deficiency, thallasemia Macrocytic- B12/folate deficiency, EtOH, hypothyroid Normocytic- anemia of chronic disease can be (early)Fe deficiency

7. Fe deficiency Low MCV Low Fe, high TIBC, low %sat (vs. low Fe, low TIBC in chronic disease) High RDW (often) Low ferritin- diagnostic

8. WBC Elevated- infection inflammation leukemia Low- hypersplenism medication infection (viral, sepsis)

9. Platelets Low- hypersplenism EtOH autoimmune Elevated- inflammation(�poor man�s ESR�)

10. Liver Tests Hepatocellular- ALT AST Cholestatic- AP GGTP Bilirubin PT/INR

11. Hepatitis Viral- HB surface Ag, HCV Ab Fatty liver (NAFL) EtOH Autoimmune- ANA, ASMA Fe, Cu- Ferritin, ceruloplasmin Meds

12. Cholestasis PBC (small ducts)- AMA (antimitochondrial Ab) PSC (bigger ducts) Meds Biliary obstruction Tumors (space occupying)

13. Celiac Sprue Immune response to gluten and related proteins in wheat, rye and barley Estimated in 1% of US population (underdiagnosed) Dx: clinical suspicion duodenal bx serology (TTG, EMA, AGA) SB capsule

14. Tissue Transglutaminase TTG- enzyme in endomysium(connective tissue surrounding smooth muscle) TTG alters gliadin ? target for T-cell induced damage in susceptible individuals TTG-IgA: 95% sensitive, 97% specific 90% PPV, 95% NPV (check total serum IgA also; IgA deficiency in 6% of population)

15. Other celiac markers EMA: anti-endomysial Ab 100% specific (no false positives) AGA: anti-gliadin Abs (IgG, IgA)- less sens/spec Anti-DGP (deamidated gliadin peptides) IgG: may be as good as TTG IgA (needs validation) HLA DQ2/8: if (-), cannot have celiac

16. Inflammatory Bowel Disease Dx made by endoscopic, histologic and radiographic findings UC: colonic mucosal inflammation CD: transmural inflammation of SB and/or colon Indeterminate colitis: 10% What is the role for blood tests in dx IBD?

17. IBD Serology Pts have abnormal immune response to gut microbes ASCA (anti-saccharomyces cervisiae Ab) - baker�s/brewer�s yeast - usually seen in small bowel Crohn�s - specific (90%) but not sensitive (50%) - maybe associated w /more aggressive dz

18. IBD Serology(cont) OmpC (outer membrane porinC of EColi) CBir1 (anti-flagellin) May be associated w/ more aggressive (faster) course and/or more complicated (stricture, fistula) disease

19. More IBD Serology pANCA (anti-neutrophil cytoplasmic Ab) - directed against host neutrophils - UC >> Crohn�s colitis - 50-70% sensitive for dx UC - 92% specific if ANCA+, ASCA-

20. What is role for serology in IBD? Adjunct to dx Indeterminate colitis (surg considerations) May be useful in predicting aggressive dz Not useful as 1st line test or if no signs IBD Austin G et al. Positive and negative predictive values: Use of IBD serologic markers. AmJGastro 2006;101:413-6. Dubinsky M et al. Serum immune responses predict rapid disease progression among children w/ Crohn�s. AmJGastro 2006;101:360-7.

21. Case 1: 48yo F w/ 6mo diarrhea & 15# wt loss PHx- chole Meds- none PEx- Thin Mild diffuse abd T Heme+ WBC 11.5 Hgb 8.6 plt 455 MCV 72 Question 1: What type of anemia? Question 2: DDx?

22. Case 1 (cont) Fe 20 TIBC 440 ferritin 9 TTG nl (serum IgA nl) CRP 30.8 C-scope: mod pancolitis w/ relative rectal sparing; unable to intubate TI Question 3: UC vs Crohns?

23. Case 1 (cont) pANCA- nl ASCA IgA- 20.2 (nl<20) ASCA IgG- nl OmpC- 24.4 (nl<16.5) CBir1- 37.7 (nl< 21.0) CT enterography- ileitis

24. Case 2: 51 yo alcoholic w/ melena Meds- ranitidine PEx- jaundiced (+) ascites 2+ edema (+) spiders WBC 2.3 Hgb 9.7 plt 69 MCV 107 Question 1: What type of anemia?

25. Case 2 (cont) B12 1408 Folate-borderline TSH 4.0 Fe 124 TIBC 245 Ferritin 457 Macrocytosis of alcoholism Question 2: Why leukopenic?

26. Case 2 (cont) AST 135 ALT 57 AP 166 TBili 3.3 alb 2.6 INR 1.9 Question 3: What�s going on w/ liver?

27. Case 2 (cont) Cholestasis vs hepatocellular US abd- hepatomegaly mild splenomegaly CBD 5 mm ALD- R/O coexistent HCV Hemochromatosis

28. Case 3: 47yo w/ RUQ pain, fever, 10# wt loss PHx- colitis X 10 yrs Meds- mesalamine, omeprazole PEx- Mild icterus Tender liver edge 2cm below RCM +/- spleen tip WBC 9.9 Hgb 10.6 plt 395 MCV 79 Question 1: What type of anemia?

29. Case 3 (cont) Fe low nl TIBC nl ferritin low nl AP 343 AST 79 ALT 95 TBili 2.8 Question 2: What�s going on with liver? Cholestatic vs hepatocellular GGTP

30. Case 3 (cont) CT abd- no mass or ductal dilation (+) pANCA High suspicion for PSC- MRCP/ERCP LBx

31. Take Home Points Type of anemia leads to possible diagnoses and further w/u Distinguish between hepatocellular vs cholestatic picture Celiac serologies are excellent! IBD serologies play an important role