The Yellow ManThe Yellow ManBetsy TrowbridgeBetsy TrowbridgeCase PresentationCase PresentationApril 12, 2006April 12, 2006

HistoryHistory A 90 yo male walked into clinic after his A 90 yo male walked into clinic after his

pharmacist told him to go see his doctor pharmacist told him to go see his doctor because he was yellow and it might be because he was yellow and it might be from his cholesterol medicine. His sister from his cholesterol medicine. His sister noticed he was yellow the day before.noticed he was yellow the day before.

He reports feeling fatigued for a few He reports feeling fatigued for a few months, worse in the last two weeks.months, worse in the last two weeks.

ROS positive for dark urine, otherwise ROS positive for dark urine, otherwise negneg

PMHPMH COPDCOPD HTNHTN ASHD with drug eluding stent placed 2 ASHD with drug eluding stent placed 2

months earlier.months earlier. Bronchioalveolar lung Ca with RUL Bronchioalveolar lung Ca with RUL

resection in 1993resection in 1993 TURP, cholecystectomy, R knee TURP, cholecystectomy, R knee

replacement, L hemicholectomyreplacement, L hemicholectomy Increased cholesterolIncreased cholesterol

HistoryHistory Allergies: NKDAAllergies: NKDA Meds:Meds:

ASA 81 mg po dailyASA 81 mg po dailyVerapamil 180 mg po dailyVerapamil 180 mg po dailyNTG patch .2 mg on AM off PMNTG patch .2 mg on AM off PMPlavix 75 mg po dailyPlavix 75 mg po dailySimvastatin 10 mg po dailySimvastatin 10 mg po daily

Physical ExamPhysical Exam General: jaundiced over whole General: jaundiced over whole

body with icteric scleraebody with icteric sclerae No adenopathyNo adenopathy Heart: II/VI SEMHeart: II/VI SEM Abd: no hepatosplenomegalyAbd: no hepatosplenomegaly Ext: +2 edemaExt: +2 edema Skin: 1 cm sub Q nodule L Skin: 1 cm sub Q nodule L

posterior shoulderposterior shoulder

DiagnosisDiagnosis Painless JaundicePainless Jaundice

Painless JaundicePainless JaundiceDifferentialDifferential

Cancer: pancreatic, cholangiocarcinomaCancer: pancreatic, cholangiocarcinoma Viral HepatitisViral Hepatitis DrugsDrugs Primary Biliary CirrhosisPrimary Biliary Cirrhosis Hemolytic AnemiaHemolytic Anemia Gilbert’s syndromeGilbert’s syndrome CHFCHF End-stage Liver diseaseEnd-stage Liver disease Primary Sclerosing CholangitisPrimary Sclerosing Cholangitis

Next Best TestNext Best Test

Bilirubin totalBilirubin total Bilirubin, direct and indirectBilirubin, direct and indirect LFT’sLFT’s CBCCBC LipaseLipase CT abd/pelvisCT abd/pelvis Abd ultrasoundAbd ultrasound

Bilirubin ResultsBilirubin 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 Bilirubin is a blood breakdown product

that is removed from the blood by the that is removed from the blood by the liver. When is is still in the blood it is liver. When is is still in the blood it is unconjugated. When it enters the liver unconjugated. When it enters the liver cells the bilirubin is conjugated and cells the bilirubin is conjugated and secreted into bile which is eliminated in secreted into bile which is eliminated in the feces.the feces.

Unconjugated Unconjugated HyperbilirubinemiaHyperbilirubinemia(In blood)(In blood) Increased Bilirubin productionIncreased Bilirubin production

– Hemolytic AnemiaHemolytic Anemia Impaired bilirubin uptakeImpaired bilirubin uptake

– CHFCHF– DrugsDrugs

Impaired bilirubin conjugationImpaired bilirubin conjugation– Gilbert’s syndromeGilbert’s syndrome

Cojugated Cojugated HyperbilirubinemiaHyperbilirubinemia (In liver cells) (In liver cells) Biliary ObstructionBiliary Obstruction

– Gall stonesGall stones– Cancer: pancreatic, cholangiocarcinomaCancer: pancreatic, cholangiocarcinoma– Primary sclerosing cholangitisPrimary sclerosing cholangitis

Intrahepatic cholestasisIntrahepatic cholestasis– Viral hepatitisViral hepatitis– DrugsDrugs– Primary Biliary CirrhosisPrimary Biliary Cirrhosis– End-stage liver diseaseEnd-stage liver disease

Further TestsFurther Tests Hct 21.5 Hgb 7.1, Plts 182, MCV Hct 21.5 Hgb 7.1, Plts 182, MCV

110.5110.5 Diff. 39% neut, 35% lymphs, 18% Diff. 39% neut, 35% lymphs, 18%

monos, 4% basos, 10% nuc. monos, 4% basos, 10% nuc. RBCs, 3% bands, 1% meta’s.RBCs, 3% bands, 1% meta’s.

LFT’s nl except ALT 22, AST 62LFT’s nl except ALT 22, AST 62 LDH 1236LDH 1236

DiagnosisDiagnosis Hemolytic anemiaHemolytic anemia

Shortened survival of RBCs. Usual Shortened survival of RBCs. Usual survival 120 days.survival 120 days.

Divided into intracorpuscular Divided into intracorpuscular (intrinsic) and extracorpuscular (intrinsic) and extracorpuscular (extrinsic) to the RBC. Intrinsic are (extrinsic) to the RBC. Intrinsic are hereditary like PNH. Extrinsic are hereditary like PNH. Extrinsic are acquired conditions that lead to acquired conditions that lead to RBC destruction.RBC destruction.

CaseCase Patient called at home and admitted to Patient called at home and admitted to

the hospital.the hospital. Ferritin 542, serum iron 123, folate 8.6Ferritin 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 positiveUrine hemosiderin positive Positive direct Coombs testPositive direct Coombs test Peripheral smear is negativePeripheral smear is negative Haptoglobin very lowHaptoglobin very low

Extracorpuscular Extracorpuscular CausesCauses Antibodies against the RBC Antibodies against the RBC

membrane, AIHAmembrane, AIHA HypersplenismHypersplenism Trauma: DIC, TTPTrauma: DIC, TTP Destruction of RBCs by pathogen: Destruction of RBCs by pathogen:

MalariaMalaria

DiagnosisDiagnosis

Warm Auto Immune Hemolytic Warm Auto Immune Hemolytic AnemiaAnemia

IgG and C3 positiveIgG and C3 positive

EtiologyEtiology LymphomaLymphoma CLLCLL SLESLE Drugs: PCNDrugs: PCN Idiopathic: Greater than 50%Idiopathic: Greater than 50%

CaseCase CT scan of neck, lungs, abd, and CT scan of neck, lungs, abd, and

pelvic revealed a 4 cm apical pelvic revealed a 4 cm apical mass suspicious for recurrent mass suspicious for recurrent bronchioalveolar carcinoma.bronchioalveolar carcinoma.

TreatmentTreatment High dose steroids early, 1mg/kg to High dose steroids early, 1mg/kg to

induce remission of antibody titersinduce remission of antibody titers Blood transfusions if symptomatic Blood transfusions if symptomatic

Dangerous with high risk of Dangerous with high risk of incompatibility. Must premedicate incompatibility. Must premedicate patient.patient.

SplenectomySplenectomy Other immunosuppressive drugsOther immunosuppressive drugs Follow daily hgb, retic count and indirect Follow daily hgb, retic count and indirect

bilirubin for response to treatmentbilirubin for response to treatment Treat underlying causeTreat underlying cause

CaseCase Likely idiopathic or secondary to Likely idiopathic or secondary to

presumed recurrent lung cancer.presumed recurrent lung cancer. Pt did receive two units of blood Pt did receive two units of blood

without complications only after OK without complications only after OK from Hematology.from Hematology.

Dilemma about lung lesion. Could Dilemma about lung lesion. Could not stop Plavix because of drug not stop Plavix because of drug eluding stent and DVI would not eluding stent and DVI would not biopsy.biopsy.

CaseCase Pt responded to treatmentPt responded to treatment Pt followed weekly in Hem Clinic Pt followed weekly in Hem Clinic

with prednisone tapered to 20 mg with prednisone tapered to 20 mg po BID with stable count at 8 po BID with stable count at 8 weeks.weeks.

SummarySummary Painless Jaundice: Get bilirubin Painless Jaundice: Get bilirubin

total, direct and indirect to guide total, direct and indirect to guide next steps in diagnosis.next steps in diagnosis.

Hemolytic anemia: YES if increased Hemolytic anemia: YES if increased LDH and decreased haptoglobin. If LDH and decreased haptoglobin. If direct coombs postive start with direct coombs postive start with aggressive steroid treatment early. aggressive steroid treatment early. Use blood transfusions carefully.Use blood transfusions carefully.