Hematological System

Blood Cell Formation

• Red blood cells (RBCs), white blood cells (WBCs), and platelets originate from stem cells.

Response to Infection:

• Bacterial or Allergic Reactions:
  • Neutrophils – Respond to bacterial infections
  • Eosinophils – Involved in allergic reactions
  • Basophils – Play a role in anaphylaxis
• Viral Infections:
  • Lymphocytes – Key defenders against viral infections
• Tissue Damage:
  • Monocytes – Assist in tissue repair and immune response

Interpreting Lab Results:

• Poly/Lymphocyte ratio:
  • Similar levels → Suggests viral infection
  • Wide difference → More indicative of bacterial infection
• Clinical correlation: The patient’s symptoms should align with lab findings.

Anemia Overview

• Cluster of symptoms and clinical findings
  • Decreased red blood cell (RBC) count, hemoglobin (Hgb), and hematocrit (Hct)

Types and Causes of Anemia:

Blood Loss:

• Acute blood loss – Rare in primary care settings
• Chronic blood loss – Frequently encountered in primary care
  • Causes: Erosive gastritis, heavy menstrual bleeding (menorrhagia), gastrointestinal malignancy
  • Results in: Iron deficiency anemia (IDA)

Impaired RBC Production (“Bone Marrow Dysfunction”)

• Contributing factors:
  • Nutrient deficiencies: Vitamin B12, folic acid, iron
  • Chronic conditions: Anemia of chronic disease, bone marrow suppression, chronic kidney disease (low erythropoietin)
  • Medication effects: Proton pump inhibitors (PPIs), metformin

Increased RBC Destruction (Less Common)

• Shortened RBC lifespan (normal lifespan: 90–120 days)
• Examples:
  • Sickle cell disease
  • Thalassemia
  • Hemolytic anemia (e.g., glucose-6-phosphate dehydrogenase [G6PD] deficiency)

Response to Treatment:

• If bone marrow function is normal, supplementing the deficient nutrient (iron, B12, folate) leads to an increase in hemoglobin/hematocrit (H/H) within 1–2 weeks, with full normalization in 4–8 weeks.

Hemogram Interpretation in Anemia

1. Hematocrit (Hct), Hemoglobin (Hgb), and RBC Count

• Normal Hgb-to-Hct ratio: 1:3
  • Hgb 10 → Hct 30%
  • Hgb 12 → Hct 36%
  • Hgb 15 → Hct 45%
• Influencing factors:
  • Severe dehydration → artificially elevated hematocrit
  • Testosterone increases RBC production → males have naturally higher hematocrit

2. RBC Size (Mean Corpuscular Volume – MCV)

• MCV remains consistent throughout RBC lifespan
• MCV classifications:
  • Microcytic (<80 fL)
  • Normocytic (80–96 fL)
  • Macrocytic (>96 fL)
• Trends in evolving anemia:
  • Microcytic anemia: As MCV decreases, RDW increases
  • Macrocytic anemia: As MCV increases, RDW increases

3. Hemoglobin Content (MCH/MCHC – “Chromic” Classification)

• MCH/MCHC measures RBC color (hemoglobin concentration):
  • Normochromic: 31–37
  • Hypochromic: <31

4. RBC Distribution Width (RDW)

• Measures variation in RBC size
• Abnormal RDW: >15% (>0.15 proportion)
  • Indicates presence of new RBCs that differ in size
  • Early marker of evolving microcytic or macrocytic anemia

5. Reticulocyte Count (Percentage of Immature RBCs)

• Measures bone marrow response to anemia
• Normal: 1–2%
• Increased (>2%) → Active response to anemia
• Decreased (“Reticulocytopenia”) → Bone marrow unable to compensate for anemia

Types of Anemia by MCV

Microcytic Anemias (Low MCV, Low MCHC)

• Thalassemia
• Iron Deficiency Anemia
  • May be caused by lead poisoning
• Anemia of Chronic Disease

Macrocytic Anemias (Low H/H, High MCV)

• Vitamin B12 Deficiency
• Folic Acid Deficiency
  • Contributing factors:
    • Liver dysfunction
    • Hypothyroidism
    • Reticulocytosis

Drug-Induced Macrocytosis (Without Anemia)

• Caused by substances such as:
  • Excessive alcohol consumption (>5 drinks/day in men, >3 in women)
  • Medications:
    • Carbamazepine
    • Valproic acid
    • Phenytoin
    • Zidovudine (reversible)
  • Malabsorption issues
• Key lab findings:
  • Normal Hgb, Hct, RBC, MCHC, and RDW
  • Increased MCV
  • Heavy alcohol use leads to enlarged RBCs (swollen cells)
  • Solution: Discontinue alcohol intake if contributing to the condition

Laboratory Tests for Iron and RBC Assessment

• Serum Iron: Measures circulating iron levels.
• Serum Ferritin: Reflects stored iron levels; values <15 indicate deficiency.
  • Elevated in chronic smokers, COPD, or high-altitude dwellers.
  • Hematocrit (Hct) thresholds:
    • >48% in women
    • >52% in men
  • Hemoglobin (Hgb) thresholds:
    • >16.5 in women
    • >18.5 in men
• Reticulocyte Count: Assesses bone marrow function and RBC production capability.
• Total Iron Binding Capacity (TIBC): Evaluates iron transport in the blood.
  • TIBC increases when iron is low.
  • TIBC decreases when iron is high.
• Effects of High-Altitude Stress:
  • Reduced barometric pressure leads to lower arterial PO₂, triggering physiological adaptations.

Herbal Supplements That Elevate Bleeding Risk

• Panax Ginseng
• Ginkgo Biloba
• Omega-3 Fatty Acids (Fish Oil)

Impact on Hemoglobin and Hematocrit (H/H)

Condition/Factor	Effect
Chronic Obstructive Pulmonary Disease (COPD)	Increased risk
Chronic Kidney Disease (CKD)	Decreased function
Hypertension	No significant change
Diabetes (A1c 13.8%)	Decreased control
Aspirin Use	No significant impact
Testosterone Therapy	Increased levels
Living in Denver, CO (High Altitude)	Increased risk
Age (84 years old)	Decreased function

Medications That Aggravate Anemia

• ARB & ACEI – Can exacerbate anemia in individuals with chronic kidney disease (CKD), diabetes, congestive heart failure (CHF), and hypertension (HTN).

Feature	Thalassemia	Iron Deficiency Anemia (IDA)
Hemoglobin Electrophoresis	Abnormal	Normal
MCV (Mean Corpuscular Volume), MCH (Mean Corpuscular Hemoglobin)	Decreased	Decreased
RDW (Red Cell Distribution Width)	Normal	Increased
Serum Iron Levels	Normal or Elevated	Decreased
Total Iron Binding Capacity (TIBC)	Normal	Increased
Serum Ferritin	Normal	Decreased
Ethnic Predisposition	Common in Asians, Mediterraneans, North Africans, Middle Eastern populations	Affects individuals of any ethnicity
Subtype Note	Alpha Thalassemia is more common in Asian populations	N/A

Diagnostic Sequence for Anemia Evaluation

1. Complete Blood Count (CBC) – Initial assessment
2. Iron Studies – Determine iron status
3. Hemoglobin Electrophoresis – Identify hemoglobinopathies

HEMORRHAGE

• Occurs with a blood loss exceeding 15%
  • May cause orthostatic hypotension
  • Can lead to shock-related symptoms

RBC TESTING

• Hemoglobin Levels:
  • Males: 14-18 g/dL
  • Females: 12-16 g/dL
• Hematocrit (% of blood volume occupied by RBCs):
  • Males: 40-50%
  • Females: 36-45%
• Mean Corpuscular Volume (MCV) – RBC Size:
  • Microcytic (<80 fL)
  • Normocytic (80-100 fL)
  • Macrocytic (>100 fL)
• Mean Corpuscular Hemoglobin Concentration (MCHC) – RBC Color:
  • Normochromic (31-37 g/dL)
  • Decreased in IDA and Thalassemia
• Mean Corpuscular Hemoglobin (MCH) – Indirect Color Measurement:
  • Range: 25-35 pg
  • Decreased in IDA and Thalassemia
• Total Iron Binding Capacity (TIBC) – Iron Carrying Capacity:
  • Range: 250-410 mcg/dL
  • ↑ in IDA
  • Normal in Thalassemia, B12, and Folate Deficiency
• Serum Ferritin – Stored Iron Indicator (Sensitive for IDA):
  • Range: 20-400 ng/mL
  • ↓ in IDA
  • Normal to elevated in Thalassemia
• Serum Iron – Circulating Iron Measurement:
  • Range: 50-175 mcg/dL
  • ↓ in IDA
• Red Cell Distribution Width (RDW) – RBC Size Variability:
  • >15% indicates variation in RBC size
  • ↑ in IDA and Thalassemia
• Reticulocytes – Immature RBCs (Lifespan of RBC = 120 days):
  • Normal: 0.5-2.5%
  • ↑ in response to iron, folate, B12 supplementation, acute bleeding, hemolysis, leukemia, or erythropoietin (EPO) therapy
• Peripheral Smear Findings:
  • Poikilocytosis – Abnormal RBC shape (seen in IDA)
  • Anisocytosis – Variability in RBC size
• Serum Folate – Important for RBC Formation:
  • Range: 3.1-17.5 ng/mL
  • ↓ in Macrocytic Anemia
• Vitamin B12 – Essential for RBC Production:
  • Normal: >250 pg/mL
  • ↓ in Macrocytic Anemia

Hemoglobin Analysis

• Electrophoresis – Gold Standard Test:
  • Used for diagnosing Sickle Cell Anemia and Thalassemia
• Secondary Polycythemia – Causes & Indicators:
  • Common in chronic smokers, COPD patients, and individuals at high altitudes
  • Elevated Hematocrit (Hct):
    • Women: >48%
    • Men: >52%
  • Increased Hemoglobin (Hgb):
    • Women: >16.5 g/dL
    • Men: >18.5 g/dL
• Effects of High Altitude Stress:
  • Lower barometric pressure reduces arterial PO2
  • Increased risk of complications in individuals with CAD, CHF, or Sickle Cell Disease

White Blood Cell (WBC) Testing

• Normal Range: 5.0–10.0 × 10⁹/L
• WBC Differential Breakdown:
  • Neutrophils (55–70%) – Also called polys or segs
    • Bands (>6%) indicate an increase in immature neutrophils (left shift)
  • Lymphocytes (20–40%) – Typically elevated in viral infections
  • Monocytes (2–8%) – Responsible for clearing cellular debris
  • Eosinophils (1–4%) – Associated with allergies, parasitic infections, and autoimmune disorders (“worms, wheezes, and weird diseases”)
  • Basophils (0.5–1%) – Involved in anaphylaxis; function not fully understood
• Common White Blood Cell Abnormalities:
  • Leukocytosis (WBC >10.0 × 10⁹/L) – Typical response to bacterial infections
  • Neutrophilia – Elevated neutrophil count
  • Lymphocytosis – Increased lymphocytes
  • Monocytosis – Higher monocyte levels
  • Eosinophilia – Increased eosinophils
  • Basophilia – Higher basophil count

Condition	Cause	Signs & Symptoms	Diagnostics	Treatment	Concerns
Neutropenia	Low absolute neutrophil count (ANC)	Fever, sore throat, oral thrush	ANC < 1500	Depends on underlying cause	African Americans tend to have a lower baseline ANC
Vitamin B12 Deficiency	Insufficient B12 intake or absorption	Gradual onset of symmetrical neuropathy, numbness, ataxia, impaired vibration and position sense, cognitive decline, pale conjunctiva, systolic murmur, red swollen tongue (glossitis)	MCV > 100, macroovalocytes and megaloblasts on peripheral smear, hypersegmented neutrophils	Treat underlying cause, B12 supplementation	Nerve damage may be reversible if treated within 6 months; vegans need supplementation
Hodgkin’s Lymphoma	Cancer of beta lymphocytes	Night sweats, fever, pain after alcohol consumption, pruritus, painless lymph node enlargement (usually in the neck), anorexia, weight loss	Biopsy, imaging, blood tests	Chemotherapy, radiation, immunotherapy	Peaks at ages 20-40 and >60; more common in white males
Non-Hodgkin’s Lymphoma	Cancer of lymphocytes & killer cells	Night sweats, fever, weight loss, painless generalized lymphadenopathy	Biopsy, imaging, blood tests	Chemotherapy, targeted therapy, radiation	Poor prognosis; more common in individuals over 65
Multiple Myeloma	Plasma cell malignancy	Fatigue, weakness, bone pain (commonly in back or chest), proteinuria (Bence-Jones proteins), hypercalcemia, normocytic anemia	Serum protein electrophoresis, bone marrow biopsy	Chemotherapy, targeted therapy, bone marrow transplant	Poor prognosis; most often affects the elderly
Thrombocytopenia	Low platelet count (<150,000)	Often asymptomatic unless count drops below 100,000; easy bruising, gum bleeding, spontaneous nosebleeds, hematuria, petechiae, purpura, hematomas	CBC, PT/PTT, rule out coagulation disorders	Address underlying cause, discontinue causative medications	If active bleeding, check for aspirin, NSAID, warfarin, SSRI, steroid use
Iron Deficiency Anemia (IDA)	Chronic low-volume blood loss or inadequate dietary intake	Often asymptomatic; fatigue, weakness, pale skin, headache, irritability, glossitis, angular cheilitis, brittle nails, tachycardia, systolic murmurs, cravings for pica	↓ Hgb, ↓ Hct, ↓ Serum Fe, ↓ Ferritin, ↓ MCV (microcytic), ↓ MCH (hypochromic), ↑ TIBC, ↑ RDW > 15%	Iron-rich diet (red meat, beans, greens), iron supplementation (150-200 mg elemental iron daily), Ferrous sulfate 325 mg PO TID with vitamin C, recheck in 4-6 weeks	Avoid taking iron with antacids, dairy, levothyroxine, quinolones, tetracyclines; side effects include constipation and dark stools; iron toxicity risk in children
Anemia of Chronic Disease (ACD)	Decreased erythropoietin (EPO) production due to chronic illness	Most common anemia in elderly (after IDA and pernicious anemia); fatigue, pallor	↓ Hgb (<12 in women, <13 in men), normocytic, normochromic anemia, reticulocytopenia, check ferritin, TIBC, B12, and folate	Manage underlying condition	Common in chronic kidney disease, inflammatory disorders, and malignancy

Condition	Cause	Signs & Symptoms	Diagnostics	Treatment	Concerns
Thalassemia Minor	Inherited disorder causing abnormal hemoglobin production	Usually asymptomatic; often detected through routine CBC showing microcytic/hypochromic RBCs. Beta Thalassemia Major (Cooley’s anemia): Severe transfusion-dependent anemia, identified in infancy	↓ Hgb, ↓ Hct, ↑ RBC, ↓ MCV, ↓ MCHC, Normal RDW, Normal to ↑ ferritin & iron, Normal TIBC	Diagnostic test: Hemoglobin electrophoresis Beta-thalassemia: Abnormal Iron Deficiency Anemia (IDA): Normal Blood smear: Microcytosis, anisocytosis, poikilocytosis	No treatment required for thalassemia; genetic counseling recommended before pregnancy
Aplastic Anemia	Bone marrow failure due to stem cell destruction (radiation, drugs, viral infections)	Severe reduction in bone marrow production; fatigue, weakness, pallor, tachycardia, systolic murmur, neutropenia, thrombocytopenia	CBC w/ differential, platelet count, Bone marrow biopsy (gold standard)	Refer to hematologist	Pancytopenia (low WBCs, RBCs, and platelets)
Pernicious Anemia	Autoimmune destruction of parietal cells leading to vitamin B12 deficiency; gastrectomy, vegan diet, alcoholism, bowel disease	Gradual onset of neuropathy, tingling in hands/feet, pallor, glossitis, difficulty with fine motor skills	B12/folate levels (B12 can be falsely normal in 5% of deficient patients), Antiparietal & anti-intrinsic factor antibody test, 24h urine for methylmalonic acid, Homocysteine level elevated, Peripheral smear (macrocytosis)	B12 deficiency may take >5 years to develop. Sources: Animal-based foods (meat, poultry, eggs, dairy). Treatment: B12 injections or nasal spray (1000 mcg weekly x4 weeks, then monthly for life), Oral: 1000-2000 mcg daily; multivitamin with iron (often coexists with IDA)	Risk factors: Older women, gastric disease, chronic infections, long-term antacid or metformin use. Concerns: Irreversible nerve damage if untreated, 2-3x increased risk of gastric cancer. Screen all dementia or neuropathy patients for B12 deficiency
Folic Acid Deficiency	Poor dietary intake leading to impaired DNA & RBC production	Fatigue, pallor, sore/red tongue, glossitis, weakness, tachycardia, palpitations, potential heart failure	Macrocytic normochromic anemia, Peripheral smear: Macroovalocytes, Folate levels <4	Body stores last 2-3 months. Treatment: Increase dietary folate (leafy greens, grains, liver, beef), PO folic acid 1-5 mg/day, Pregnancy: 400 mcg/day	High-risk groups: Elderly, infants, alcoholics, those with poor vegetable/citrus intake, malabsorption (gluten intolerance). Drugs that interfere: Phenytoin, sulfa, metformin, methotrexate, zidovudine
Sickle Cell Anemia	Genetic disorder causing abnormal RBC shape and reduced oxygen-carrying capacity	Most asymptomatic, but can have severe anemia, pain crises, ischemic necrosis (bones, skin), organ dysfunction (renal/liver), priapism, hemolytic episodes, recurrent infections. Fever in children = immediate concern	CBC, Sickledex (screening test), Hemoglobin electrophoresis (gold standard), Mean Hgb: ~8.0, RBC lifespan: 17 days vs. normal 120 days	Refer to hematologist. Screening: Part of newborn tests; Genetics: Autosomal recessive (if both parents carry the trait, 25% chance of child having disease). Prenatal testing: Chorionic villus sampling/amniocentesis (8-10 weeks)	Prevalence: 1 in 500 African Americans in the U.S. Increased risk of infections: Strep pneumoniae, H. influenzae due to functional hyposplenism