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Hematocrit - A Detailed Overview

1. Definition

• Example: a hematocrit of 40 means 40% of the blood volume is red blood cells; the remainder is mainly plasma, with white blood cells and platelets making up only ~1%.
• It is one of the most commonly used tests to assess the red cell mass, alongside hemoglobin concentration and RBC count.

"Hematocrit is the percentage of packed blood containing intact RBCs after it has been spun in a centrifuge."

• Frameworks for Internal Medicine

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2. Methods of Measurement

A. Macromethod (Wintrobe)

• Blood is placed in a graduated tube (Wintrobe tube) and centrifuged.
• The packed red cell volume is read directly from the graduation.

B. Micromethod (Standard Clinical Practice)

• A capillary tube ~7 cm long with ~1 mm bore is filled by capillary action from a skin puncture or well-mixed venous sample to at least 5 cm.
• The end is sealed with modeling clay and placed radially in a microhematocrit centrifuge head, sealed end outward.
• Centrifuged at 10,000-12,000 g for 5 minutes (if Hct >50%, extend to 10 minutes to ensure complete packing).
• The red cell column length divided by total blood column length (measured with a millimeter rule and magnifying lens) gives the Hct value.

C. Automated/Calculated Method

Hct (%) = RBC count × MCV / 10

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3. Reference Ranges

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4. The "Rule of Three"

• RBC × 3 = Hemoglobin (g/dL)
• Hemoglobin × 3 = Hematocrit (%)

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5. Hematocrit Values in Health and Disease

Decreased Hematocrit (Low Hct = Anemia)

• Iron deficiency anemia (most common cause globally)
• Vitamin B12 / Folate deficiency (megaloblastic anemia)
• Anemia of chronic disease/inflammation
• Hemolytic anemias (hereditary spherocytosis, autoimmune hemolytic anemia, sickle cell disease)
• Aplastic anemia (bone marrow failure)
• Thalassemia
• Hydremia of pregnancy (dilutional - plasma volume expands more than RBC mass; Hct falls but total RBC mass is not reduced)
• Shock with acute blood loss - Hct may be normal or even high immediately after hemorrhage (hemoconcentration); it is unreliable as an estimate of anemia immediately after blood loss or transfusion

Elevated Hematocrit (High Hct = Polycythemia/Erythrocytosis)

• Polycythemia vera (primary myeloproliferative disorder)
• Secondary polycythemia: high altitude, chronic hypoxia, COPD, sleep apnea, EPO-secreting tumors
• Dehydration / hemoconcentration (e.g., severe burns, vomiting, severe acute pancreatitis - where Hct rise is a marker of disease severity due to capillary leakage)
• Relative polycythemia (reduced plasma volume)

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6. Relationship to Blood Viscosity (Physiological Importance)

• Normal hematocrit: whole blood viscosity is 3-4 times that of water.
• Polycythemia (Hct 60-70): viscosity can be up to 10 times that of water.
• This exponentially increases vascular resistance per Poiseuille's law (resistance ∝ viscosity), severely impairing blood flow and oxygen delivery to tissues.
• Paradoxically, lowering hematocrit (hemodilution) decreases viscosity and can improve cerebral blood flow - but reduces oxygen-carrying capacity.
• Plasma viscosity itself is only ~1.5x that of water, making its contribution minor compared to RBC mass.

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7. Hematocrit vs. Hemoglobin vs. RBC Count

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8. Hematocrit in Automated Analyzers - The Hematocrit Effect (POCT)

• POCT systems (e.g., glucometers, bedside analyzers) use whole blood on dipstick-style reagent strips.
• High hematocrit → fewer RBCs allow less plasma to pass to the reagent → falsely low results for the analyte measured.
• Low hematocrit (more common in hospitalized patients) → more plasma passes → falsely elevated results.
• Only systems with a plasma-separation step before reagent contact can avoid this error.
• Patients should calibrate their POCT meter results with simultaneous standard laboratory plasma/serum measurements to account for this effect. - Henry's Clinical Diagnosis and Management by Laboratory Methods

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9. Sources of Error in Hematocrit Measurement

1. Inadequate mixing - Blood tubes need at least 60 inversions before sampling; less causes unacceptable imprecision.
2. Trapped plasma - During centrifugation, ~1-3% of the red cell column contains trapped plasma (more at high Hct values), causing a slight overestimation of true Hct.
3. Inadequate centrifugation speed or time - Leads to incomplete packing and falsely high values.
4. Plasma abnormalities visible after spinning:
   • Orange/green plasma → elevated bilirubin
   • Pink/red plasma → hemoglobinemia
   • Cloudy plasma → lipemia (nephrosis, cryoglobulinemia)
5. Buffy coat - The grayish-red layer above the red cell column contains leukocytes and platelets; in leukocytosis or thrombocytosis, this can contribute to apparent Hct elevation.

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10. Derived Red Cell Indices from Hematocrit

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11. Special Situations

Pregnancy

• Plasma volume expands by ~40-50% while RBC mass expands by only ~20-30% → physiological dilutional anemia (Hct ~32-34%).
• Total RBC mass is NOT reduced, so this is not true anemia.

Shock and Hemorrhage

• Hct is unreliable immediately after acute blood loss because both red cells and plasma are lost proportionally.
• Hemodilution by fluid shifts or IV fluids takes hours to fully manifest, after which Hct falls to reflect true losses.
• Conversely, with dehydration/hemoconcentration (e.g., severe burns, acute pancreatitis), rising Hct indicates severity of volume depletion.

Anesthesia / Cardiac Surgery

• Hemodilution on cardiopulmonary bypass deliberately lowers Hct by adding crystalloid prime to the circuit.
• Mixed Hct post-bypass = (patient blood volume × patient Hct + total prime volume × 0) / (patient BV + total prime volume).
• Target Hct during CPB is typically 21-28%; lower values are associated with neurodevelopmental consequences in infants.

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Summary Table

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• Guyton & Hall Textbook of Medical Physiology, Chapters 14 & 33
• Henry's Clinical Diagnosis and Management by Laboratory Methods, Chapters 31 & 10
• Tietz Textbook of Laboratory Medicine, 7th Ed., Chapter 74
• Frameworks for Internal Medicine
• Fishman's Pulmonary Diseases and Disorders

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Alcohol Withdrawal Syndrome - Symptoms and Treatment

1. Pathophysiology

• GABA receptors are downregulated (less inhibition)
• NMDA/glutamate receptors are upregulated (more excitation)
• The dopaminergic reward pathway is disinhibited

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2. DSM-5 Diagnostic Criteria

1. Cessation or reduction of heavy, prolonged alcohol use
2. At least 2 of the following symptoms within hours to days:
   • Autonomic hyperactivity (sweating, tachycardia >100 bpm)
   • Hand tremor
   • Insomnia
   • Nausea or vomiting
   • Transient hallucinations or illusions
   • Psychomotor agitation
   • Anxiety
   • Generalized tonic-clonic seizures
3. The symptoms cause clinically significant distress or impairment
4. Not attributable to another medical condition or substance

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3. Clinical Stages and Timeline

• Mild symptoms may persist for 4-6 months as a protracted abstinence syndrome
• ~2% of patients with alcohol use disorder experience withdrawal seizures
• ~1% develop DTs
• DTs carry an estimated mortality of 5-15% if untreated

"AWS is a continuum of syndromes that begins after a decrease in the amount of intake of ethanol. Therefore, only a reduction, not the abrupt cessation, of ethanol intake may result in withdrawal."

• Rosen's Emergency Medicine

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4. Risk Factors for Severe Withdrawal

• Previous history of DTs or withdrawal seizures (most important risk factor)
• Older age
• Concurrent medical illness (infection, liver failure, GI bleeding)
• Polydrug use
• Higher quantity and duration of alcohol use
• Prior alcohol withdrawal episodes (kindling phenomenon - each episode lowers the seizure threshold)
• Electrolyte or metabolic imbalances

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5. Severity Assessment - The CIWA-Ar Scale

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6. Treatment

A. General Supportive Measures (All Patients)

1. Thiamine (Vitamin B1): 250-500 mg IM/IV for 3-5 days, then 100-250 mg PO daily
   • Give BEFORE glucose - if glucose is given first to a thiamine-deficient patient, it can precipitate Wernicke encephalopathy
2. Multivitamins containing folic acid
3. Hydration: Most alcohol withdrawal patients are normally or mildly overhydrated - avoid routine IV fluids unless there is significant bleeding, vomiting, diarrhea, or fever/diaphoresis
4. Electrolyte correction: Alcoholics are particularly prone to:
   • Hypomagnesemia
   • Hypokalemia
   • Hypoglycemia
5. Balanced diet as tolerated
6. Reassurance and a quiet, calm environment
7. Screen for co-existing conditions: Hepatic failure, GI bleeding, cardiac arrhythmias, infections, traumatic injuries, pancreatitis

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B. Pharmacologic Treatment

First-Line: Benzodiazepines (BZDs)

• Symptom-triggered (preferred): Dose only when CIWA-Ar exceeds threshold; reduces total BZD dose and duration
• Fixed/scheduled taper: Less preferred; risk of under- or over-treatment
• Front-loading: Large initial doses titrated to sedation; useful in severe withdrawal

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Second-Line / Alternative: Phenobarbital

• Long half-life (~4-5 days) providing a self-tapering effect
• Direct GABA-A receptor activation at a different site than BZDs
• Anticonvulsant properties
• Two recent 2024 systematic reviews (Lee CM et al., Acad Emerg Med 2024) and (Punia K et al., SAEM GRACE 2024) found phenobarbital effective and safe for AWS management in the ED, with comparable or lower rates of ICU admission vs. BZDs alone
• A 2024 network meta-analysis (Qu L et al., Int Clin Psychopharmacol) compared multiple pharmacologic treatments for AWS

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Adjunctive Agents

"Phenytoin does not prevent alcohol withdrawal-related seizures when used on its own or in combination with benzodiazepines. There is no need to continue anticonvulsants long term when used to prevent seizures in alcohol withdrawal."

• Maudsley Prescribing Guidelines in Psychiatry, 15th Ed.

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C. Treatment by Severity Level

Mild Withdrawal (CIWA-Ar < 8)

• Supportive care: hydration, nutrition, reassurance
• Thiamine + multivitamins
• Monitor vitals serially
• Oral BZD only if symptoms worsen
• Outpatient management possible with 1-2 day medication supply, daily follow-up

Moderate Withdrawal (CIWA-Ar 8-15)

• Oral BZD taper (chlordiazepoxide 25-50 mg q6-8h or lorazepam 1-2 mg TID)
• Thiamine, electrolyte replacement
• Consider inpatient if co-morbidities, no social support, or prior severe withdrawal

Severe Withdrawal / DTs (CIWA-Ar > 15)

• ICU admission for DTs
• IV benzodiazepines (diazepam 10 mg IV q5-10 min OR lorazepam 2-4 mg IV q15 min) titrated to symptom control
• Phenobarbital for BZD-refractory cases
• Propofol infusion or intubation for extreme cases
• Continuous cardiac and hemodynamic monitoring
• Aggressive electrolyte/fluid management

Alcohol Withdrawal Seizures

• Treat actively with IV diazepam or lorazepam
• Antiepileptic drugs (AEDs) are not indicated for routine alcohol withdrawal seizures (seizures are self-limited)
• Head CT to rule out structural cause (hemorrhage, trauma)
• Thiamine must be given before glucose
• Long-acting BZD prophylaxis in patients with prior seizure history
• Observe for at least 6 hours after last seizure before discharge consideration; admit if ≥ 2 seizures in 6 hours

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7. Disposition Criteria

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8. Prevention of Relapse (Post-Withdrawal)

• Naltrexone (50 mg/day PO or monthly IM injection "Vivitrol") - blocks opioid-mediated reward from alcohol; reduces craving and heavy drinking days
• Acamprosate - reduces glutamate-driven craving and protracted withdrawal symptoms
• Disulfiram - aversion therapy (causes severe flushing/nausea with alcohol via acetaldehyde accumulation)

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Summary

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• Harrison's Principles of Internal Medicine, 22e - Chapter on Alcohol and Alcoholism
• Rosen's Emergency Medicine, 9th Ed. - Chapter 137
• The Washington Manual of Medical Therapeutics
• Goldman-Cecil Medicine, International Ed. - Chapter 364
• Maudsley Prescribing Guidelines in Psychiatry, 15th Ed.
• Kaplan & Sadock's Synopsis of Psychiatry
• Recent evidence: Phenobarbital for AWS - SR/MA, Acad Emerg Med 2024 | Network meta-analysis of AWS pharmacotherapy, 2024 | GRACE-4 ED Guidelines 2024

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Complete Blood Count (CBC) - Full Explanation and Analysis Guide

1. What Is a CBC?

1. Red blood cells (RBCs / erythrocytes) - oxygen transport
2. White blood cells (WBCs / leukocytes) - immune defense
3. Platelets (thrombocytes) - hemostasis

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2. CBC Components - The Complete Parameter List

A. RED BLOOD CELL PARAMETERS

1. RBC Count

• What it measures: Number of red blood cells per microliter (µL) of blood
• Normal ranges:
  • Adult males: 4.5-5.9 × 10⁶/µL (4.5-5.9 × 10¹²/L)
  • Adult females: 4.0-5.2 × 10⁶/µL
  • Newborns: Higher (relative hypoxia in utero stimulates more RBC production)
• ↑ Erythrocytosis: Polycythemia vera, high altitude, chronic hypoxia (COPD, sleep apnea), smoking, EPO-producing tumors
• ↓ Low count: Anemia (various causes)

2. Hemoglobin (Hgb / Hb)

• What it measures: Concentration of hemoglobin in whole blood (g/dL)
• Normal ranges:
  • Adult males: 13.5-17.5 g/dL
  • Adult females: 12.0-15.5 g/dL
  • Anemia defined as: Hb < 13.0 g/dL (male), < 12.0 g/dL (female)
• The single most important indicator of oxygen-carrying capacity
• Caution: Unreliable immediately after acute hemorrhage (plasma and RBCs lost together; dilution effect takes hours)

3. Hematocrit (Hct / PCV)

• What it measures: Percentage of blood volume occupied by RBCs
• Normal: Males 41-51%, Females 36-45%
• Rule of Three: Hct ≈ 3 × Hb ≈ 9 × RBC count (valid only for normocytic cells)
• Calculated: Hct = RBC × MCV / 10

4. Mean Corpuscular Volume (MCV) ← Most Important Red Cell Index

• What it measures: Average volume (size) of a single RBC, in femtoliters (fL)
• Normal: 80-100 fL
• Classification of anemia by MCV:

• Concurrent megaloblastic anemia + thalassemia can normalize MCV - check RDW and smear
• MCV rises spuriously if EDTA sample is analyzed >2-3 days old (RBCs swell)
• In infancy and early childhood, normal MCV is lower than adults - do not over-investigate

5. Mean Corpuscular Hemoglobin (MCH)

• What it measures: Average Hb content per single RBC (picograms, pg)
• Calculated: MCH = Hb (g/dL) × 10 / RBC (millions/µL)
• Normal: 27-33 pg
• Parallels MCV (larger cells generally contain more Hb)
• ↓ Low MCH: Hypochromia (iron deficiency, thalassemia)
• ↑ High MCH: Hyperchromia (spherocytes, sickle cell, Hb C disease)
• More stable than MCV with sample storage - preferred for thalassemia screening in some countries (UK)

6. Mean Corpuscular Hemoglobin Concentration (MCHC)

• What it measures: Average Hb concentration per unit volume of RBCs (g/dL or %)
• Calculated: MCHC = Hb (g/dL) × 100 / Hct (%)
• Normal: 32-36 g/dL
• ↓ Low MCHC: Hypochromia - most sensitive indicator for iron deficiency
• ↑ Elevated MCHC: Strongly suggests hereditary spherocytosis or autoimmune hemolytic anemia (spherocytes have less surface area relative to volume → more concentrated Hb); also elevated in homozygous sickle cell or Hb C disease
• MCHC is unaffected by MCV, making it useful to independently assess chromicity

7. Red Cell Distribution Width (RDW)

• What it measures: Coefficient of variation (CV%) of RBC volume - reflects size variability (anisocytosis)
• Normal: 11.5-14.5% (CV method)
• ↑ Elevated RDW (high anisocytosis): Indicates two or more cell populations of different sizes
  • Iron deficiency anemia (characteristic - high RDW with low MCV)
  • Mixed deficiency (B12/folate + iron)
  • Post-transfusion
  • Early nutritional deficiency
  • Reticulocytosis (reticulocytes are larger)
• Normal RDW with low MCV: Suggests thalassemia trait (all cells uniformly small; RDW low or normal) - helps distinguish from iron deficiency

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B. RETICULOCYTE PARAMETERS

8. Reticulocyte Count

• What it measures: Percentage of immature RBCs (reticulocytes) in blood
• Normal: 0.4-2.9% (or 25,000-75,000/µL absolute count)
• Reticulocytes are newly formed RBCs that retain cytosolic mRNA for 1 day after losing their nucleus; stain blue with methylene blue (polychromasia on Wright stain)
• Reflects bone marrow erythropoietic activity

RI = (Reticulocyte % / maturation correction factor) × (Patient Hct / Normal Hct [45])

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C. WHITE BLOOD CELL PARAMETERS

9. Total WBC Count (Leukocyte Count)

• Normal: 4,000-11,000/µL (4-11 × 10⁹/L)
• Automated analyzers count all nucleated WBCs; abnormal cells (blasts, atypical lymphocytes) are flagged
• Leukocytosis (>11,000/µL): Infection, inflammation, stress, steroids, leukemia
• Leukopenia (<4,000/µL): Viral infections, sepsis (paradoxically), bone marrow suppression, autoimmune destruction
• Critical: Always interpret using absolute counts, not just percentages

10. WBC Differential Count (Five-Part Differential)

Differential Interpretation Guide

• Bacterial infection (most common)
• Inflammation, surgery, trauma, burns
• Corticosteroids (demarginate neutrophils)
• Myeloproliferative disorders
• Physiologic (exercise, stress, pregnancy)
• "Left shift": Increased band forms (immature neutrophils) - indicates acute bacterial infection or bone marrow stress; if metamyelocytes/myelocytes appear = "severe left shift"

• Viral infections (common), sepsis
• Drug-induced (chemotherapy, clozapine, methimazole, carbimazole)
• Autoimmune (SLE, Felty syndrome)
• Bone marrow failure
• Absolute Neutrophil Count (ANC) < 500/µL = severe neutropenia → risk of life-threatening infections

• Viral infections: Infectious mononucleosis (EBV), CMV, hepatitis, HIV, pertussis
• Chronic infections: TB, brucellosis
• Chronic lymphocytic leukemia (CLL) - sustained high lymphocytes in older adults
• Atypical lymphocytes on smear = EBV/CMV/viral hepatitis

• HIV/AIDS (specifically CD4 T-cell depletion)
• Corticosteroids
• Autoimmune diseases (SLE)
• Malignancy, chemotherapy, radiation

• NAACP mnemonic: Neoplastic, Addison's disease, Allergic/Asthma/Atopy, Collagen vascular disease, Parasitic infection
• Also: Drugs, Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis)
• Hypereosinophilic syndrome: Eosinophils > 1,500/µL with organ damage

• Chronic myelogenous leukemia (CML) - classic finding (basophilia + leukocytosis + splenomegaly)
• Myeloproliferative disorders, inflammatory conditions, allergic reactions

• Bacterial infections: TB, subacute bacterial endocarditis, brucellosis, Listeria
• Chronic inflammatory diseases
• Monocytic leukemias (AML-M5, CMML)
• Recovery phase after chemotherapy

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D. PLATELET PARAMETERS

11. Platelet Count (PLT)

• Normal: 150,000-400,000/µL (150-400 × 10⁹/L)
• Thrombocytopenia (< 150,000/µL):

• Thrombocytosis (> 400,000/µL):
  • Reactive (most common): Iron deficiency, infection, inflammation, post-splenectomy
  • Primary (essential thrombocythemia): Myeloproliferative disorder; thrombosis risk when PLT > 1,000,000/µL

12. Mean Platelet Volume (MPV)

• What it measures: Average platelet size (fL)
• Normal: 7.5-12.5 fL
• Larger platelets are younger and more metabolically active
• ↑ High MPV with low PLT count: Increased peripheral platelet destruction (ITP - immune-mediated; platelets consumed, marrow releases larger, younger platelets)
• ↓ Low MPV with low PLT count: Decreased platelet production (bone marrow failure, chemotherapy)
• Technical caution: MPV increases in EDTA-anticoagulated samples over time; standardize to 2-hour measurement

13. Immature Platelet Fraction (IPF)

• Quantifies reticulated (youngest) platelets with high RNA content
• ↑ High IPF: Peripheral destruction (ITP) - marrow compensating
• Useful for: monitoring thrombopoiesis recovery post-transplant/chemotherapy, differentiating destructive vs. hypoproliferative thrombocytopenia

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3. How to Systematically Analyze a CBC

Step-by-Step Approach

STEP 1 - Screen for Critical Values First

STEP 2 - Analyze the Red Cell Line

• If YES → classify by MCV (microcytic/normocytic/macrocytic)
• Check RDW (elevated = mixed population or nutritional deficiency; normal = uniform cell population like thalassemia)
• Check reticulocyte count/RI (< 2 = hypoproliferative; > 2 = hyperproliferative/hemolytic)
• Check MCHC (low = hypochromia → iron deficiency; high → spherocytes)
• Request peripheral blood smear for morphology

• Primary (polycythemia vera) vs. secondary (hypoxia, EPO-producing tumor)

STEP 3 - Analyze the White Cell Line

1. Is the total WBC count normal, elevated, or low?
2. Look at the differential - which cell type is abnormal?
3. Use absolute counts, not percentages
4. Check for a "left shift" (band neutrophils >10% or presence of metamyelocytes/myelocytes = acute bacterial infection or bone marrow stress)
5. Look for blasts (circulating immature cells = leukemia until proven otherwise)
6. Correlate with clinical context (fever, infection, drug history, lymphadenopathy)

• Leukemoid: WBC 50,000-100,000 with left shift but no blasts; LAP (leukocyte alkaline phosphatase) stain is HIGH; reactive condition
• CML: WBC very high, basophilia, all stages of maturation; LAP is LOW; BCR-ABL positive

STEP 4 - Analyze Platelets

1. Is PLT count normal, low, or high?
2. If low: check MPV and IPF (peripheral destruction vs. reduced production)
3. Check for platelet clumping on smear (can cause falsely low automated count = pseudothrombocytopenia - use citrate tube or smear to verify)
4. Rule out HIT if on heparin
5. If very high: reactive vs. myeloproliferative

STEP 5 - Integrate ALL Three Cell Lines

STEP 6 - Peripheral Blood Smear Review (Always for Abnormal CBC)

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4. Four Basic Anemia Patterns to Recognize

"There are basically four types of anemia: iron deficiency, anemia of chronic disease, hemolytic anemia, and macrocytic/nutritionally deficient anemia. These can be readily distinguished from one another both by the hematologic profile and simple laboratory testing."

• Henry's Clinical Diagnosis and Management by Laboratory Methods

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5. Reference Ranges Summary Table

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6. Pre-Analytical Considerations (Sources of Error)

• Anticoagulant: EDTA (K2 or K3) is standard - causes platelet swelling (MPV rises over time), but is best for morphology preservation
• Sample timing: Analyze within 4-6 hours for most reliable results; MCV rises with prolonged EDTA storage (>24 h)
• Mixing: At least 8-10 gentle inversions before analysis; inadequate mixing causes microclots and erroneous counts
• Pseudothrombocytopenia: EDTA-induced platelet clumping (platelet satellitism) causes falsely low automated PLT count; verify with peripheral smear or citrated sample
• Lipemia: High triglycerides scatter light, may falsely elevate Hgb (optical method)
• Hemolysis: Free Hgb in plasma falsely elevates Hgb; also lyses RBCs, affecting count

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• Tietz Textbook of Laboratory Medicine, 7th Ed. - Chapters 74, 77
• Henry's Clinical Diagnosis and Management by Laboratory Methods - Chapters 2, 31
• The Washington Manual of Medical Therapeutics - Hematology Chapter
• Goldman-Cecil Medicine, International Ed.
• Frameworks for Internal Medicine