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The Numbers Game

The Numbers Game. Dr Minh Nguyen. Why is it important to understand blood tests?. We do them almost every day! We need to fix the abnormality, not ignore it. Lots of “stars-next-to-numbers fatigue” or “ red number fatigue” *** Sometimes we need to investigate the investigation!

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The Numbers Game

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  1. The Numbers Game Dr Minh Nguyen

  2. Why is it important to understand blood tests? We do them almost every day! We need to fix the abnormality, not ignore it. Lots of “stars-next-to-numbers fatigue” or “red number fatigue” *** Sometimes we need to investigate the investigation! We need to be able to explain why we did those blood tests (Cost vs benefit scenario)

  3. Not enough RBC - Anaemia What type of anaemia? • Microcytic (MCV < 80) • Normocytic (MCV 80-99) • Macrocytic (MCV >/= 100)

  4. Anaemia Microcytic anaemia Differentials • Iron deficiency • Anaemia of chronic disease • Thalassaemia • Sideroblastic anaemia • Lead poisoning Investigations • Iron studies +/- Soluble transferrin receptor levels • Hb Electrophoresis • Lead levels

  5. Anaemia Normocytic Anaemia With low reticulocyte count • Pancytopenia (Aplastic anaemia, myelodysplastic disorders, myelofibrosis, leukaemia, chemo) • Non pancytopenia (Anaemia of chronic disease, renal/liver disease) With high reticulocyte count • Blood loss • Haemolysis Investigations • Haemolytic screen: LDH, blood film, reticulocytes, unconjugated bilirubin, DAT • CRP/ESR • Bone marrow

  6. Anaemia Macrocytic anaemia Megaloblastic • B12 deficiency • Folate deficiency Non-megaloblastic • Hypothyroidism • Chronic liver disease • Alcoholism Investigations • B12 /folate level • TSH • Ask about ETOH history • LFTS

  7. Too many RBC - Erythrocytosis Primary • Polycythaemia Rubra Vera (Genetic issue – JAK2/Calreticulin mutation). High RBC/WCC/Plts • Men Hb> 185, women Hb > 165 Secondary • Physiological: smoking, high altitude, CO poisoning • Pulmonary disease: COPD/sleep apnoea/Pulmonary HTN • Cardio disease: R->L shunt Too much EPO! - Tumours eg. Renal cell Ca, HCC, phaeochromocytoma

  8. White cell abnormalities Neutropenia Mild 1 – 1.5 x 10^9/L Mod 0.5 – 1.0 x 10^9/L Severe <0.5 x 10^9/L Profound <0.1 x 10^9

  9. White cell abnormalities Why is neutropenia important? INFECTIONS ++++ ! NEED TO ASK FOR NEUTROPENIC PRECAUTIONS STAT! Oh…but what are neutropenic precautions?

  10. White cell abnormalities Neutropenic precautions: • Hand hygiene should be used; this is the most effective measure for preventing the transmission of infection. • Standard barrier precautions should be used for all patients (ie, when contact with body fluids is anticipated), and infection-specific isolation precautions should be used for patients with signs and symptoms of certain infections. • (HEPA) filtration rooms for HCT patients • No plants or fresh flowers • Visitors/hospital staff to report their illnesses or exposures. • No rectal thermometers, enemas, suppositories, or digital rectal examinations • Neutropenic diet — A "neutropenic diet" consisting of well-cooked foods is usually given to neutropenic patients. Prepared luncheon meats should be avoided given the risk of listeriosis. Well-cleaned, uncooked raw fruits and vegetables can be given as can cooked foods brought from home or restaurants, provided that the freshness of ingredients and a safe means of preparation can be confirmed.

  11. White cell abnormalities Neutropenia Causes • Decreased production - Infections, haematological diseases, drug induced, nutritional, idiopathic • Peripheral destruction/ sequestration - Anti-neutrophil Ab, spleen/lung trappingExcessive margination  Transient neutropenia - Idiopathic , overwhelming bacterial infection

  12. White cell abnormalities

  13. White cell abnormalities Neutrophilia (> 7.7 x10^9) Causes • Primary: CML, PRV, ET, MF, leukocyte adhesion deficiency • Secondary: stress, exercise, obesity, inflammation, malignancy, medications (steroids, lithium, G-CSF)

  14. White cell abnormalities Lymphopenia ! (<1.5 x10^9) “It’s probably viral” Causes • Idiopathic • Malnutrition • Alcoholism • Radiation • HIV/AIDS • Hep B/C

  15. White cell abnormalities Lymphocytosis (> 4 x 10^9) Causes • Infection: viral, TB, pertussis, toxoplasmosis • Smoking • Stress response • Neoplasm eg. ALL, CLL, Lymphoma Investigations • Peripheral Blood film • Peripheral flow cytometry

  16. imagebank.hematology.org

  17. merckmanuals.com

  18. White cell abnormalities Eosinophilia (> 0.5 X 10^9) • Primary - Hypereosinophilic syndrome - Clonal bone marrow disorder 2. Secondary • Parasitic • Allergic reactions • Respiratory causes eg. Asthma, eosinophilic pneumonia, Churg-strauss • Polyarteritisnodosa

  19. Platelet abnormalities Thrombocytosis (plt > 400 x 10^9) • Primary - Myeloproliferative disorders (CML, PRV, MF) 2. Secondary - Reactive (it is an acute phase reactant) eg secondary to infection, trauma, inflammation

  20. pcds.org.uk

  21. Platelet abnormalities Thrombocytosis investigations • CRP • ESR • Blood film • Iron studies • Bone marrow biopsy if reactive process ruled out

  22. Platelet abnormalities Thrombocytopenia (<150 x 10^9) 1. Decreased production eg.Vit B12/folate deficiency, congenital (alport’s, fanconi), Marrow damage (from MDS, chemo, drugs, chemo, radiation, aplastic anaemia) 2. Increased destruction eg. ITP, TTP, DIC, HITS 3. Sequestration by spleen 4. Haemodilutioneg massive transfusion

  23. Platelet abnormalities Thrombocytopenia investigations • FBE • Blood film: other cell line abnormalities, large platelets, schistocytes, platelet clumping • B12 and folate • Coagulation studies if DIC suspected • LFTs

  24. Renal Impairment Acute renal impairment • FBE, UEC, CMP • Urine MCS looking for • Bland sediment or • Active sediment: Haematuria, proteinuria (protein-Creatinine ratio), urinary casts, crystals • WCC ? Infection and growth • Monitor urine output Pre-renal: Medication check (NSAIDs, ACEi,ARBs, cyclosporin, tacolimus), Blood pressure, other fluid losses Renal: ATN/AIN/GN/vascular causes/Myeloma • ANA, ENA, dsDNA, C3 and 4, ANCA, SPEP, FLC • Urinary bence jones • ASOT, Anti Dnase B Post-renal: Renal tract US/ CT KUB

  25. Hyponatremia • Na+ < 135 I find this hard to get my head around sometimes! Basic Investigations • Serum Na+ • Serum osmolality (normal is usually around 280mOsm/kg) (2 x Na) +gluc+urea • Urine Na+ (Normal is between 25-40 mEq/L on random sample) • Urine Osmolality (500-800mOsm/kg) Exam: Fluid assessment

  26. Hyponatremia 3 types of hyponatremia • Hyperosmolar hyponatremia - IvIg, mannitol, glycine • IsoosmolarHyp onatremia- pseuohyponatremia • Hypoosmolar hyponatremia • - Hypovolemia - GI losses, renal losses ( diuretics, adrenal insufficiency) • - euvolemia - psychogenic polydipsia, beer potomania, tea and toast diet  • - Hypervolemia - CCF, ascites, nephrotic syndrome • SIADH dx of exclusion

  27. Uptodate Corrected Sodium (Hillier, 1999) = Measured sodium + 0.024 * (Serum glucose - 100)

  28. Hypernatremia Na+ > 145 • Always hyperosmolar • Usually due to net water loss • Always examine the patient for the following causes: Causes • Reduced intake • Elderly with dementia, swallowing difficulty • Infant • Coma • Surgical patient • Increased losses • Renal losses: central diabetes insipidus (too little ADH), nephrogenic diabetes insipidus (resistance to ADH), osmotic diuresis eg. Diabetes • Extra-renal losses: GI loss, insensible losses Treatment: Oral free water if able to tolerate or 5% dextrose. Aim no more than 8 mmol/24 hour decrease in Na+ to avoid central pontine demyelination

  29. Calcium • The total serum calcium concentration consists of three fractions • 15 percent is bound to organic and inorganic anions • 40 percent is bound to albumin • 45 percent is physiologically active ionized (or free) calcium • Hyperca2+ = Corrected Ca2+ > 2.6 mmol/L

  30. Hypercalcemia • Corrected Ca2+ > 2.6 mmol/L Approach • Is patient hypercalcemic? • Correct for albumin: calcium + 0.02 (40-alb) • Measure PTH, PO4 levels and and 1,25 hydroxyvitamin D levels • Renal function • PTHrP level

  31. Also: Hypercalcemia of Immobilisation Drugs: theophylline, thiazide diuretics

  32. Hypoalbuminaemia • Levels < 35g/L • Important prognostic factor: every 10 g/L decrease in serum albumin, mortality is increased by 137% and morbidity increased by 89% • Made and secreted by liver • Albumin is a transport protein and provides ~80% plasma oncotic pressure and 50% of plasma protein content • At the time of hospital admission, 20% of patients have hypoalbuminemia.

  33. Hypoalbuminaemia Causes • Protein malnutrition  loss of RNA and disaggregation of endoplasmic reticulum leading to decreased albumin synthesis - Refer to dietician for protein intake assessment • Defective synthesis – eg. In cirrhosis hepatic cell mass is decreased - Check coagulation studies • Nephrotic syndrome • -24 hour urine collection, albumin > 3.5g/day and renal referral if fits criteria • Protein losing enteropathy (normally only 10% albumin lost through gut) - Alpha 1 antitrypsin level & gastro referral • Extensive burns • Hemodilutioneg from ascites, CCF • Acute and chronic inflammation (negative phase reactant) - Check CRP and ESR

  34. Liver function tests • Raised AST and ALT (with ALT> AST most common pattern)– any hepatocellular damage. ALT is more specific than AST. GGT is most useful when looking for hepatocellular damage (but less specific) eg. • AST and ALT > 1000 = hepatic ischaemia, autoimmune hepatitis, drugs, viral • Raised GGT, ALP and bilirubin - suggest biliary obstruction with hepatocellular damage • Raised ALP alone = pregnancy, bone pathology (egpagets, bony mets), hyperparathyroidism, CCF, diabetes, hodgkins • Raised GGT alone = ETOH ingestion, drugs eg anticonvulsants, benzodiazepines, tricyclics, warfarin • Raised bilirubin alone = Gilbert’s, haemolysis, drugs eg. rifampicin • ALT > AST, GGT = NAFLD, viral hepatitis, autoimmune hepatitis, Ischaemic hepatitis,ETOH hepatitis, toxic hepatitis • Raised ALT, AST, GGT, ALP = Mixed hepatic/ cholestatic picture. Viral, medication induced or toxic hepatitis, autoimmune hepatitis, chronic active hepatitis (increased IgG levels), hepatic space occupying mass, biliary disease, cirrhosis and ethanol

  35. Liver function tests History • Medication review • ETOH history • Calculating BMI • Travel/ IVDU/ Sexual history • Previous tranfusions history Investigations • Tests of liver function: coagulation studies, albumin • Hepatitis A/B/C serology depending on history • Autoimmune Ab eg. AMA, Anti-smooth muscle, Anti-LKM • Iron studies looking for haemochromatosis • Serum caeruloplasm for wilson’s disease • Abdominal US looking for biliary obstruction, liver pathology

  36. Any questions?

  37. https://www.uptodate.com/contents/diagnostic-approach-to-hypercalcemia?search=hypercalcemia&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1https://www.uptodate.com/contents/diagnostic-approach-to-hypercalcemia?search=hypercalcemia&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 • https://www.uptodate.com/contents/relation-between-total-and-ionized-serum-calcium-concentrations#! • https://emedicine.medscape.com/article/166724-overview#a2

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