Laboratory interpretation Lalita Norasetthada, MD Hematology Division, Department of internal medicine, CMU

Laboratory interpretation Hematology lab CBC Coagulogram Blood chemistry Liver function Kidney function FPG and lipid profile Serologic test

Normal Laboratory Values Abnormal 2 SD mild elevation in 2.5% of normal population normal range included a small subset of patients with subclinical liver disease normal values = mean ± 2SD of normal population

CBC : Complete Blood Count

CBC

White blood cell count ปริมาณลดลง ปริมาณเพิ่มขึ้น การติดเชื้อไวรัส Normal range 4,500-10,000 cell/mm3 4.5-10 x 103/uL ปริมาณลดลง การติดเชื้อไวรัส ยาบางชนิด โรคของไขกระดูกทำให้สร้างเม็ดเลือดขาวลดลง ปริมาณเพิ่มขึ้น การตอบสนองของร่างกายปกติที่เกิดในภาวะติดเชื้อหรือการ อักเสบ (< 30,000/uL) มะเร็งเม็ดเลือดขาว

WBC morphology

Increased risk of infection when Absolute neutrophil count (ANC) < 1,000/mm3 or 1.0 x 103/uL

CBC

Hemoglobin Hematocrit การตรวจ ค่าผลการตรวจ ภาวะเสียเลือด ต่ำ สูง Hemoglobin Hematocrit ภาวะเสียเลือด ขาดสารอาหาร เช่น ธาตุเหล็ก, ขาดวิตามิน ภาวะเม็ดเลือดแดงแตก จากการติดเชื้อ, สารพิษ, ยา หรือดแตกเองในร่างกาย ไขกระดูกผ่อหรือไม่ทำงาน มะเร็งของเม็ดเลือด ขาดสารน้ำ ภาวะที่มี OXYGEN ในเลือดต่ำเรื้อรัง เช่น สูบบุหรี่ ไขกระดูกสร้างเม็ดเลือดสูงผิดปกติ

RBC morphology

Concerning values For general dental procedure Procedure under GA Hb > 7 gm/dl Procedure under GA Hb > 9.5-10 gm/dl

CBC

การนับจำนวนเกร็ดเลือด (platelet count) 100,000-450,000/mm3 100-450 x 103/uL

เกร็ดเลือด การตรวจ ค่าผลการตรวจ ม้ามโต ต่ำ สูง เกร็ดเลือด ม้ามโต เกร็ดเลือดถูกทำลายมากขึ้น จากยา, ภูมิต้านทาน เกร็ดเลือดสร้างได้น้อยจากความผิดปกติของไขกระดูก ไขกระดูกฝ่อ หรือทำงานผิดปกติ ไขกระดูกถูกแทรกซึมจากการติดเชื้อหรือมะเร็ง โรคมะเร็งเม็ดเลือด การอักเสบหรือการติดเชื้อเรื้อรัง มะเร็งของอวัยวะอื่น โรคไขกระดูกสร้างเม็ดเลือดเพิ่มมากผิดปกติ มะเร็งเม็ดเลือดขาวเรื้อรัง

Platelet morphology

Increased risk of bleeding when Platelet count <50,000/mm3 or < 50 x 103/uL > 1,000,000/mm3 or > 1,000 x 103/uL In mild thrombocytopenia, all dental procedure can be done safely (50,000- 100,000/mm3)

Coagulation test

Primary hemostasis

Secondary Hemostasis In vivo In vitro

Coagulation test PT : prothrombin time Range 8-11 seccods aPTT : activated partial thromblastin time Range 28-32 seconds

Isolated PT Prolongation Inherited FVII deficiency Acquired Vitamin K deficiency Liver disease Warfarin administration Inhibitor of FVII

Isolated PTT prolongation Inherited Deficiency of F VIII, IX, XI Deficiency of FXII, prekallikrein, HMW kininogen VWD Acquired Lupus anticoagulant Inhibitor to FVIII, IX, XI, XII Heparin administration

Combined PT and PTT prolongation Inherited Deficiency of FV, X, fibrinogen, prothrombin Acquired Liver disease DIC Supratherapeutic dose of warfarin and heparin Inhibitor of FV, X, fibrinogen, prothrombin Primary amyloidosis associated FX deficiency

Bleeding risk Increased risk of bleeding after invasive procedure when Either PT or aPTT increases > 1.5 folds above mid normal range Ex. PT 24 secs (8-12), INR 2.5 PTT 40 secs (28-32)

Bleeding disorder in the setting of normal screening test Platelet dysfunction Drug : aspirin, NSAID, clopidrogrel Chronic disease : liver/kidney failure Hereditary disorder Impaired fibrin crosslink and fibrinolytic disorder

Blood Chemistry BUN Cr Kidney function Albumin / Globulin GOT / GPT Alk. Phosphatase Cholesterol Bilirubin Triglyceride HDL LDL Plasma glucose Kidney function Liver function test Lipid Profile

Kidney function test

Laboratory test to evaluate kidney function Glomerular filtration rate (GFR) Plasma creatinine Plasma urea Urine volume Urine electrolytes, protein, urea, osmolality

Glomerular filtration rate Value always adapted to the BSA!! Ideal BSA in adults is 1.73m2 Schwartz equation : GFR= v x 0.808 Pcr (umol/L) How to assess easy if plasma creatinine is OK

Creatinine and Urea Plasma Concentration- hyperbolic correlation pCr, pUrea Lower limit 90 ml/Min./1.73 m2 Normal range-> 140 mL/min (100%) 0 mL/min (0%) GFR 50%

Plasma urea (BUN) BUN (blood urea nitrogen) 10-20 mg/dl Urea: product of protein catabolism Synthesized by liver, excreted by kidney, partially reabsorbed in tubuli Plasma concentration increases with decreased GFR

BUN in patients with kidney diseases Useful test but must be interpreted with great care urea plasma level is more than creatinine dependent on protein intake Most useful when considered along with creatinine High in high protein intake, UGI bleeding Low in severe liver dysfunction

Plasma creatinine and renal function Creatine : main storage compound of high energy phosphate needed for muscle metabolism Creatinine: anhydride of creatine Creatinine is freely filtered by the glomerulii and is not reabsorbed In most circumstances the measurement of plasma creatinine can provide a specific test of glomerular function. The reference range is wide. A body builder may have a plasma creatinine at the top end and an old lady a value at the low end and this reflects muscle mass. Plasma creatinine should not be measured until 8 hours after a meal as there is some evidence that the concentration increases after meat ingestion. Plasma creatinine concentration increases when GFR falls. The problem is that GFR has to fall quite a bit before plasma creatinine concentration reliably increases. There are some important analytical interferences which you should check with the laboratory. A patient with ketoacidosis, jaundice or infection might have agents in the plasma which could invalidate the measurement of creatinine. Overhead 1 follows Creatine Creatinine (Waste product) H2O

Analytic method Plasma creatinine Male 0.6-1.2 mg/dL, Female 0.5-1.0 mg/dL Pre-renal disorder BUN:Cr ratio >20 Renal and postrenal disorders BUN: Cr 10-20 both elevated

Liver function test

Liver Function Test Liver chemistry test Clinical implication of abnormality ALT Hepatocellular damage AST Bilirubin Cholestasis, impair conjugation, or biliary obstruction ALP Cholestasis, infiltrative disease, or biliary obstruction PT Synthetic function Albumin GGT Cholestasis or biliary obstruction Bile acids 5`-nucleotidase LDH Hepatocellular damage, not specific no single test provide accurate global assessment of hepatic function

Normal values

Liver Function Test Advantages Sensitive, noninvasive method of screening liver dysfunction Pattern of laboratory test abnormalities to recognize type of liver disorder Assess severity of liver dysfunction Follow cause of liver disease Disadvantages Not specific for liver dysfunction Seldom lead to specific diagnosis

Liver function test

Liver Function Test Classified in 3 groups Synthetic function : albumin, prothrombin time (PT) Hepatocyte injury : AST, ALT Cholestasis : bilirubin, ALP, GGT PT, albumin, bilirubin : most common tests used as prognostic factors

Liver function test

Albumin Depending on nutrition, volume status, vascular integrity, catabolism, hormone, loss in stool and urine Not specific for liver disease T1/2 19-21 D decrease : poor nutrition status, severe illness with protein catabolism, nephrosis, malabsorption, PLE, burns, heavy alcohol intake

Globulin Produced by stimulated B-lymphocyte Elevation in chronic liver disease chronic inflammation and malignant disease

Hypoalbuminemia globulin chol/TG Hb 1.decrease synthesis -protein malnutrition -chronic liver disease -chronic inflammation 2.increase loss -Protein loosing enteropathy -NS 3.increase Vd (ascites, overhydration)

Metabolic Syndrome

Cardiometabolic Risk - Graphic Overweight / Obesity Glucose BP  Lipids Age Genetics Insulin Resistance Abnormal Lipid Metabolism LDL  ApoB  HDL  Trigly.  Insulin Resistance Syndrome Cardiometabolic Risk Global Diabetes / CVD Risk Age, Race, Gender, Family History Start off with a rundown of cardiometabolic risk factors Smoking Physical Inactivity Unhealthy Eating Inflammation Hypercoagulation Hypertension

Interpreting Blood Glucose Levels Fasting glucose : No caloric intake > 8 hours Healthy BG FPG < 100 mg/dL Pre-diabetes FPG 100–125 mg/dL (Impaired fasting glucose) Diabetes FPG ≥126 mg/dL Random plasma glucose PG > 200 mg/dl

Total Cholesterol Goals34 Desirable — Less than 200 mg/dL Borderline high risk — 200–239 mg/dL High risk — 240 mg/dL and over American Diabetes Association. Understanding Cardiometabolic Risk: Broadening Risk Assessment and Management, Dyslipidemia Richard M Bergenstal, MD International Diabetes Center

Lipid profile No caloric intake > 12 H Lipid profle Total choleterol LDL HDL TG

Cholesterol Management LDL-C-lowering Category of risk LDL-C Goal 0-1 risk factor* < 160 mg/dL or lower Multiple (2+) risk factors* < 130 mg/dL or lower People with coronary heart disease or risk equivalent (e.g., diabetes) < 100 mg/dL or lower Known CAD and DM < 70 mg/dL or lower may be ideal

Serologic tests

Test and window period Virus marker window period mean range HBV HBsAg 59 37-87 HCV anti-HCV 82 54-192 HIV anti-HIV-1/2 22 6-38 HTLV anti-HTLV-I 51 36-72 NAT yield in Thailand : The National Blood Centre Thai Red Cross Society HIV 1:97,000 HCV 1:490,000, HBV 1:2,800

Viral hepatits Acute AntiHAV HBsAg Chronic AntiHCV

Main Ways to Get Hepatitis A 1 Fecal-oral route

Viral hepatitis A

Main Ways to Get Hepatitis B 1 Having sex without condoms with someone who has hepatitis B 2 Being born to a mother who has hepatitis B 3 Sharing needles and syringes Receiving blood component from HBV infected donor 4

Natural history of HBV - related infection Acute hepatitis Asymptomatic 30% Fulminant hepatitis 1% Contamination 95% 5% Resolution Chronic infection 66% 33% Chronic hepatitis 10-20% Inactive carriage HCC Cirrhosis 3-5% yearly

Viral hepatitis B

Hepatitis B can be prevented! If you have never had hepatitis B, you can get 3 shots . . . 3 2 1 . . . and get long lasting protection.

Main Ways to Get Hepatitis C 1 Sharing needles and syringes 2 Receiving blood component from HCV infected donor

Hepatitis C Virus (HCV) HCV Infection Acute infection Mild symptoms 50-70% of affected patients develop chronic hepatitis 20% of affected patients develop cirrhosis or hepatocellular carcinoma

Viral hepatitis C

HIV infection AIDs situation in Thailand, March 2011 Prevalence 0.6% Total HIV infected cases 372,874 persons  Already died 98,153 persons

Main Ways to HIV 1 2 3 4 Being born to a mother who has HIV Having sex without condoms with HIV infected persons 2 Being born to a mother who has HIV 3 Sharing needles and syringes Receiving blood component from HBV infected donor 4

HIV Strauss JM & Strauss EG,2002

Who to Test for HIV High risk groups include MSM Injection drug users or history injection drugs Heterosexual partners of those listed above Those interested in HIV testing People presenting with an opportunistic infection or recurrent/severe infections that can not otherwise be explained Adults with thrush, recurrent pneumonia

HIV Testing EIA- standard serologic screening test Needs to be repeatedly positive Should not give the patient this test result until confirmed Western Blot-confirmatory test. 2 bands of the following: p24, gp41 or gp120/160 Antibodies to p24 and p55 appear earliest but decrease or become undetectable. Antibodies to gp31, gp41, gp120, and gp160 appear later but are present throughout all stages of the disease EIA and Western Blot >99.9% sensitive and specific

Window period in HIV infection

HIV Testing 4-20% of test results are indeterminate with WB assays with positive bands for HIV-1 proteins Causes of indeterminate tests include Patients in the process of seroconversion HIV-2 infection Cross-reacting nonspecific antibodies Testing should be repeated at 6-8 weeks, 3, and 6 months The reason for cross reacting with nonspecific antibodies include idu, cvd, autoimmune disease, lymphoma liver disease, ms and pregnancy May lose the core ab in late stage disease New tests now available SUDS, orasure and to be available soon

HIV Testing Rapid testing Two tests FDA approved, SUDS and Oraquick Oraquick much easier and very accurate Sensitivity and Specificity is 99.5% Positives still need confirmation Similar to performing a pregnancy test

The End