1. The Yellow Man Betsy Trowbridge Case Presentation April 12, 2006

2. History A 90 yo male walked into clinic after his pharmacist told him to go see his doctor because he was yellow and it might be from his cholesterol medicine. His sister noticed he was yellow the day before. A 90 yo male walked into clinic after his pharmacist told him to go see his doctor because he was yellow and it might be from his cholesterol medicine. His sister noticed he was yellow the day before. He reports feeling fatigued for a few months, worse in the last two weeks. He reports feeling fatigued for a few months, worse in the last two weeks. ROS positive for dark urine, otherwise neg ROS positive for dark urine, otherwise neg

3. PMH COPD COPD HTN HTN ASHD with drug eluding stent placed 2 months earlier. ASHD with drug eluding stent placed 2 months earlier. Bronchioalveolar lung Ca with RUL resection in 1993 Bronchioalveolar lung Ca with RUL resection in 1993 TURP, cholecystectomy, R knee replacement, L hemicholectomy TURP, cholecystectomy, R knee replacement, L hemicholectomy Increased cholesterol Increased cholesterol

4. History Allergies: NKDA Allergies: NKDA Meds: Meds: ASA 81 mg po daily Verapamil 180 mg po daily NTG patch.2 mg on AM off PM Plavix 75 mg po daily Simvastatin 10 mg po daily

5. Physical Exam General: jaundiced over whole body with icteric sclerae General: jaundiced over whole body with icteric sclerae No adenopathy No adenopathy Heart: II/VI SEM Heart: II/VI SEM Abd: no hepatosplenomegaly Abd: no hepatosplenomegaly Ext: +2 edema Ext: +2 edema Skin: 1 cm sub Q nodule L posterior shoulder Skin: 1 cm sub Q nodule L posterior shoulder

6. Diagnosis Painless Jaundice Painless Jaundice

7. Painless Jaundice Differential Painless Jaundice Differential Cancer: pancreatic, cholangiocarcinoma Cancer: pancreatic, cholangiocarcinoma Viral Hepatitis Viral Hepatitis Drugs Drugs Primary Biliary Cirrhosis Primary Biliary Cirrhosis Hemolytic Anemia Hemolytic Anemia Gilbert’s syndrome Gilbert’s syndrome CHF CHF End-stage Liver disease End-stage Liver disease Primary Sclerosing Cholangitis Primary Sclerosing Cholangitis

8. Next Best Test Bilirubin total Bilirubin total Bilirubin, direct and indirect Bilirubin, direct and indirect LFT’s LFT’s CBC CBC Lipase Lipase CT abd/pelvis CT abd/pelvis Abd ultrasound Abd ultrasound

9. Bilirubin Results Total Bilirubin 7.6 (increased) Total Bilirubin 7.6 (increased) Unconjugated Bilirubin 6.7 (increased) Unconjugated Bilirubin 6.7 (increased) Conjugated Bilirubin.9 (mildly increased) Conjugated Bilirubin.9 (mildly increased) Bilirubin is a blood breakdown product that is removed from the blood by the liver. When is is still in the blood it is unconjugated. When it enters the liver cells the bilirubin is conjugated and secreted into bile which is eliminated in the feces. Bilirubin is a blood breakdown product that is removed from the blood by the liver. When is is still in the blood it is unconjugated. When it enters the liver cells the bilirubin is conjugated and secreted into bile which is eliminated in the feces.

10. Unconjugated Hyperbilirubinemia (In blood) Increased Bilirubin production Increased Bilirubin production –Hemolytic Anemia Impaired bilirubin uptake Impaired bilirubin uptake –CHF –Drugs Impaired bilirubin conjugation Impaired bilirubin conjugation –Gilbert’s syndrome

11. Cojugated Hyperbilirubinemia (In liver cells) Biliary Obstruction Biliary Obstruction –Gall stones –Cancer: pancreatic, cholangiocarcinoma –Primary sclerosing cholangitis Intrahepatic cholestasis Intrahepatic cholestasis –Viral hepatitis –Drugs –Primary Biliary Cirrhosis –End-stage liver disease

12. Further Tests Hct 21.5 Hgb 7.1, Plts 182, MCV 110.5 Hct 21.5 Hgb 7.1, Plts 182, MCV 110.5 Diff. 39% neut, 35% lymphs, 18% monos, 4% basos, 10% nuc. RBCs, 3% bands, 1% meta’s. Diff. 39% neut, 35% lymphs, 18% monos, 4% basos, 10% nuc. RBCs, 3% bands, 1% meta’s. LFT’s nl except ALT 22, AST 62 LFT’s nl except ALT 22, AST 62 LDH 1236 LDH 1236

13. Diagnosis Hemolytic anemia Hemolytic anemia Shortened survival of RBCs. Usual survival 120 days. Shortened survival of RBCs. Usual survival 120 days. Divided into intracorpuscular (intrinsic) and extracorpuscular (extrinsic) to the RBC. Intrinsic are hereditary like PNH. Extrinsic are acquired conditions that lead to RBC destruction. Divided into intracorpuscular (intrinsic) and extracorpuscular (extrinsic) to the RBC. Intrinsic are hereditary like PNH. Extrinsic are acquired conditions that lead to RBC destruction.

14. Case Patient called at home and admitted to the hospital. Patient called at home and admitted to the hospital. Ferritin 542, serum iron 123, folate 8.6 Ferritin 542, serum iron 123, folate 8.6 Retic count 12.4 with absolute count 238. Retic count 12.4 with absolute count 238. Urine hemosiderin positive Urine hemosiderin positive Positive direct Coombs test Positive direct Coombs test Peripheral smear is negative Peripheral smear is negative Haptoglobin very low Haptoglobin very low

15. Extracorpuscular Causes Antibodies against the RBC membrane, AIHA Antibodies against the RBC membrane, AIHA Hypersplenism Hypersplenism Trauma: DIC, TTP Trauma: DIC, TTP Destruction of RBCs by pathogen: Malaria Destruction of RBCs by pathogen: Malaria

16. Diagnosis Warm Auto Immune Hemolytic Anemia IgG and C3 positive

17. Etiology Lymphoma Lymphoma CLL CLL SLE SLE Drugs: PCN Drugs: PCN Idiopathic: Greater than 50% Idiopathic: Greater than 50%

18. Case CT scan of neck, lungs, abd, and pelvic revealed a 4 cm apical mass suspicious for recurrent bronchioalveolar carcinoma. CT scan of neck, lungs, abd, and pelvic revealed a 4 cm apical mass suspicious for recurrent bronchioalveolar carcinoma.

19. Treatment High dose steroids early, 1mg/kg to induce remission of antibody titers High dose steroids early, 1mg/kg to induce remission of antibody titers Blood transfusions if symptomatic Dangerous with high risk of incompatibility. Must premedicate patient. Blood transfusions if symptomatic Dangerous with high risk of incompatibility. Must premedicate patient. Splenectomy Splenectomy Other immunosuppressive drugs Other immunosuppressive drugs Follow daily hgb, retic count and indirect bilirubin for response to treatment Follow daily hgb, retic count and indirect bilirubin for response to treatment Treat underlying cause Treat underlying cause

20. Case Likely idiopathic or secondary to presumed recurrent lung cancer. Likely idiopathic or secondary to presumed recurrent lung cancer. Pt did receive two units of blood without complications only after OK from Hematology. Pt did receive two units of blood without complications only after OK from Hematology. Dilemma about lung lesion. Could not stop Plavix because of drug eluding stent and DVI would not biopsy. Dilemma about lung lesion. Could not stop Plavix because of drug eluding stent and DVI would not biopsy.

21. Case Pt responded to treatment Pt responded to treatment Pt followed weekly in Hem Clinic with prednisone tapered to 20 mg po BID with stable count at 8 weeks. Pt followed weekly in Hem Clinic with prednisone tapered to 20 mg po BID with stable count at 8 weeks.

22. Summary Painless Jaundice: Get bilirubin total, direct and indirect to guide next steps in diagnosis. Painless Jaundice: Get bilirubin total, direct and indirect to guide next steps in diagnosis. Hemolytic anemia: YES if increased LDH and decreased haptoglobin. If direct coombs postive start with aggressive steroid treatment early. Use blood transfusions carefully. Hemolytic anemia: YES if increased LDH and decreased haptoglobin. If direct coombs postive start with aggressive steroid treatment early. Use blood transfusions carefully.