Hematopoietic System

Acute Blood Loss

  • Identify and manage the specific site of bleeding.

  • CBC during active bleeding: initial hemoglobin (Hb) and hematocrit (Hct) may be normal if checked immediately; it may take several hours for blood loss to appear in CBC and platelet count.

  • Reticulocyte count (0.5%–2%) will increase within a few days; reticulocytosis is a normal response in acute blood loss.

  • Hemodynamic changes by blood loss percentage:

    • Up to 15\% of blood volume (class I hemorrhage): minimal increase in heart rate; no changes in BP and respiratory rate.

    • 15\%!\text{ to }! 30\% (class II hemorrhage): tachycardia (100\text{--}120\ \text{bpm}), tachypnea (20\text{--}24\ /\text{min}), decrease in pulse pressure.

    • Significant BP drop usually does not manifest until about 30\%\text{ to }40\% blood loss (severe hemorrhage).

    • Tachycardia (pulse > 120\,\text{bpm}), weaker pulse, elevated respiratory rate, diminished urine output, and mental status changes; look for signs and symptoms of shock.

  • Note on hemovigilance and early management: monitor trends, anticipate delayed CBC changes, and treat hypovolemia and ongoing bleeding promptly.

Hemophilia A

  • Most common type of hemophilia in the United States.

  • X-linked recessive disease; predominantly affects males with only one X chromosome.

  • Caused by factor VIII (FVIII) deficiency.

  • Signs/symptoms: easy/unusual bruising, bleeding into joints (hemarthrosis), delayed bleeding or bleeding for several hours to days (circumcision, dental extractions), severe bleeding with minor trauma, heavy menses, and hematuria.

  • Medications that increase bleeding (to be avoided): anticoagulants, aspirin, and NSAIDs.

  • Laboratory pattern: activated partial thromboplastin time (aPTT) often prolonged; prothrombin time (PT), fibrinogen, and platelets typically normal.

Hodgkin’s Lymphoma

  • Cancer of the beta lymphocytes (B cells).

  • Classic B symptoms: night sweats, fevers, pain with ingestion of alcoholic drinks (occasionally), generalized pruritus with painless enlarged lymph nodes (neck).

  • Other symptoms: anorexia and weight loss.

  • Epidemiology: higher incidence among young adults (20–40 years) or older adults (>60 years); more common in males and White/Black Americans; median age at diagnosis ~39\text{ years} in the United States.

  • Identified by the presence of Reed–Sternberg cells.

Multiple Myeloma

  • Cancer of the plasma cells.

  • Symptoms: fatigue, weakness, bone pain (often in the back or chest).

  • Associated findings: proteinuria with Bence–Jones proteins, hypercalcemia, normocytic anemia.

  • Epidemiology: more common in older adults; median age at diagnosis 65\text{ to }74\,\text{years}.

Neutropenia

  • Definition: absolute neutrophil count (ANC) often < 1{,}500\,/\mu L in adults.

  • Most common causes: inherited disorders and drug-induced neutropenia.

  • Medication etiologies: psychotropics, antivirals, antibiotics, NSAIDs, antithyroids, ACE inhibitors (e.g., enalapril, captopril), propranolol.

  • Initial evaluation:

    • CBC with differential, blood smear, health history, medications (including OTC meds), and physical examination.

  • Febrile patients with suspected bacterial infection require urgent evaluation due to high risk for bacteremia/sepsis.

  • Ethnicity note: African Americans may have slightly lower ANC (benign ethnic neutropenia).

Non-Hodgkin’s Lymphoma

  • Group of malignant lymphoproliferative disorders derived from B cell progenitors, T cell progenitors, mature B cells, mature T cells, or natural killer cells.

  • Usually occurs in older adults (>65 years).

  • Presentation: night sweats, fever, weight loss, painless generalized lymphadenopathy.

  • Prognosis: generally poorer compared with some other lymphomas; varies by subtype.

Thrombocytopenia

  • Definition: platelet count < 150{,}000\,/\mu L.

  • Normal platelet range: 150{,}000\,/\mu L\text{ to }450{,}000\,/\mu L.

  • Symptoms usually do not appear until platelets < 100{,}000\,/\mu L.

  • Clinical signs: easy bruising (ecchymosis, petechiae), gum bleeding, spontaneous epistaxis, hematuria.

Vitamin B12 Deficiency

  • Presentation: gradual onset of symmetric peripheral neuropathy starting in the feet and/or arms; numbness, ataxia (positive Romberg), loss of vibration and position sense, impaired memory, dementia in severe cases.

  • Peripheral smear: macro-ovalocytes, some megaloblasts, multi-segmented neutrophils (> five or six lobes).

  • MCV: > 100\ \text{fL} (macrocytosis).

Laboratory Testing and Norms

  • Hemoglobin (Hb): concentration of Hb in whole blood.

    • Males: 13.6\text{ to }16.9\ \text{g/dL}

    • Females: 11.9\text{ to }14.8\ \text{g/dL}

    • Factors lowering Hb/Hct: vigorous activity, pregnancy, older age.

    • Factors increasing Hb/Hct: smoking, certain medications, dehydration or hypovolemia, high altitude.

  • Hematocrit (Hct): proportion of RBCs in 1 mL of blood.

    • Males: 40\%\text{ to }50\%

    • Females: 36\%\text{ to }44\%

  • Mean Corpuscular Volume (MCV): average size of RBCs.

    • Normal: 82.5\text{ to }98\ \text{fL}

    • Interpretation:

    • \text{MCV} < 80\ \text{fL}: microcytic anemia

    • 80\ \leq \text{MCV} \leq 100\ \text{fL}: normocytic anemia

    • \text{MCV} > 100\ \text{fL}: macrocytic anemia

  • Mean Corpuscular Hemoglobin Concentration (MCHC): Hb concentration per RBC.

    • Normal: 32.5\text{ to }35.2\ \text{g/dL}

    • Decreased in iron-deficiency anemia (IDA) and thalassemia (hypochromic).

    • Normal in macrocytic and normocytic anemias; very high suggests spherocytosis or RBC agglutination.

  • Mean Corpuscular Hemoglobin (MCH): average Hb per RBC.

    • Normal: 25.0\text{ to }35.0\ \text{pg/cell}

    • Decreased in IDA and thalassemia; normal in macrocytic anemia.

  • Total Iron-Binding Capacity (TIBC): measure of transferrin availability to bind iron.

    • Calculation: transferrin concentration × 1.389 ⇒ TIBC.

    • Elevated in iron deficiency anemia (IDA); normal in thalassemia, vitamin B12 deficiency, folate-deficiency anemia.

    • Normal value: 300\text{ to }360\ \mu\text{g/dL}

  • Serum Ferritin: stored form of iron; correlates with iron stores; most sensitive test for IDA.

    • Also an acute phase reactant (can be elevated with inflammation/infection regardless of iron status).

    • Serum ferritin decreased in IDA.

    • With thalassemia trait, ferritin levels are normal to high; may be high if iron supplementation was given due to misdiagnosis.

    • Normal value: 40\text{ to }200\ \text{ng/mL}

  • Serum Iron: decreased in IDA; normal to high in thalassemia and macrocytic anemias; value alone is not diagnostic.

    • Affected by recent transfusions and dietary/pharmacologic iron.

    • Normal value: 60\text{ to }150\ \mu\text{g/dL}

  • Red Cell Distribution Width (RDW): variability in RBC size; elevated in IDA, vitamin B12/folate deficiency, and myelodysplastic syndromes.

  • Reticulocytes: immature RBCs that reflect RBC production; normally released in small amounts.

    • Reticulocyte count sources: 16\text{ to }130\times 10^3/\mu L (males); 16\text{ to }98\times 10^3/\mu L (females).

    • Reticulocytosis defined as >2.5\% of total RBC count.

    • Elevates within a few days with iron/folate/B12 supplementation, during acute bleeding, hemolysis, leukemia, and with erythropoietin (EPO) treatment.

    • Chronic bleeding does not typically cause reticulocytosis due to compensation.

  • White Blood Cells (WBC) with differential: percentage of each leukocyte type; sum of differential equals 100%.

    • Normal WBC: 3.8\text{ to }10.4\times 10^3/\mu L

    • Neutrophils (segmented): 55\%\text{ to }70\%

    • Band forms: 0\%\text{ to }5\%

    • Lymphocytes: 20\%\text{ to }40\%

    • Monocytes: 2\%\text{ to }8\%

    • Eosinophils: 1\%\text{ to }4\%

    • Basophils: 0.5\%\text{ to }1\%

  • Platelets:

    • Normal range: 152\text{ to }324\times 10^3/\mu L (males); 153\text{ to }361\times 10^3/\mu L (females).

    • Platelets form clots to stop/prevent bleeding; thrombocytosis can be reactive or neoplastic; thrombocytopenia can reflect destruction, sequestration, or ineffective thrombopoiesis.

  • Hemoglobin Electrophoresis: gold-standard to diagnose hemoglobinopathies (sickle cell disease, thalassemias, etc.).

    • Normal adult Hb: HbA \approx 97\%, HbA2 \approx 2.5\%, HbF < 1\% (fetal Hb).

Tips: RBC Size Descriptions

  • Common RBC-size descriptors:

    • \text{MCV} < 80\text{ fL}: microcytic and hypochromic RBCs (small and pale).

    • \text{MCV} > 100\text{ fL}: macrocytes or macro-ovalocytes (larger RBCs).

  • When evaluating MCV > 100 fL, order both vitamin B12 and folate levels.

  • Learn food groups for both folate and vitamin B12.

Anemias (Overview and Lab Comparisons)

  • Anemia definition: decrease in Hb/Hct or RBC mass below the norm for age/sex due to various causes (blood loss, bone marrow failure, impaired production, or hemolysis).

  • Table compare common anemias (highlights):

    • Iron Deficiency Anemia (IDA): ferritin/serum iron decreased; TIBC ↑; RDW ↑; RBCs microcytic (MCV < 80 fL); MCHC ↓; poikilocytosis and anisocytosis.

    • Thalassemia: Hb analysis/genetic testing; microcytic RBCs; hypochromia; ferritin/iron normal.

    • Vitamin B12 deficiency (pernicious anemia): B12 ↓; hypersegmented neutrophils (>5–6 lobes); macrocytic RBCs; normal color; MCV > 100 fL.

    • Folate deficiency: folate ↓; homocysteine ↑; macrocytic/megaloblastic RBCs; normal color.

    • Anemia of Chronic Disease: MCV 80–100 fL; history of chronic/inflammatory disease; normocytic RBCs.

    • Sickle Cell Anemia: Hb electrophoresis with HbS/HbF ↑; reticulocytosis; hemolytic features; RBCs normocytic/normochromic; sickle-shaped RBCs with shortened lifespan (10–20 days; norm is 120 days).

Iron Deficiency Anemia (IDA)

  • Etiology: most common worldwide; major cause is blood loss (overt or occult).

    • Adults: GI blood loss (peptic ulcer disease, NSAID use, cancer) most likely.

    • Reproductive-aged females: heavy periods, pregnancy.

    • Other risk: poor diet, post-gastrectomy, increased physiologic need.

  • Pediatric considerations: children—low dietary intake; infants—rule out chronic cow’s milk intake causing GI bleeding before 12 months.

  • Classic case features: many are asymptomatic when mild; moderate/severe may have pallor, fatigue, exertional dyspnea; glossitis; angular cheilitis; pica (cravings for nonfood items).

  • Severe anemia: possible tachycardia, murmur, or heart failure.

  • Early labs: Hb/Hct decreased; MCV may still be normal in early IDA or acute blood loss; RBCs may appear normocytic/normochromic in early stages and even CBC normal in high-resource settings.

  • Peripheral smear: anisocytosis, poikilocytosis.

  • Treatment:

    • Identify and correct cause; GI malignancy consideration in older patients.

    • Ferrous sulfate: 325\ \text{mg} \text{ PO } \text{TID}; take with vitamin C for absorption; can be taken with meals due to GI distress.

    • Hb/Hct normalization typically in 6\ to\ 8\ \text{weeks}; ferritin normalization may take 3\ to\ 6\ months to replace iron stores.

    • Severe/symptomatic anemia: RBC transfusion.

    • Diet/absorption tips: cast-iron cookware can help vegans/vegetarians; increase fiber and fluids; consider fiber supplements for constipation.

    • Iron-rich foods: red meat, some beans (e.g., black beans), and leafy greens.

  • Common side effects of iron: constipation, black stools; stomach upset; stool softener (Colace) may be used; avoid taking iron with antacids, dairy, quinolones, or tetracyclines (iron binding reduces effectiveness).

  • Reticulocytosis after iron supplementation: modest rise in 7\text{ to }10\,\text{days} in moderate/severe anemia; mild anemia may show little to no reticulocytosis.

  • Lab differentiation tips: IDA vs thalassemia trait/minor

    • If serum iron and ferritin are low with high TIBC: IDA.

    • If TIBC and ferritin are normal: thalassemia trait.

Thalassemia

  • Inherited hemoglobinopathies common in certain regions (sub-Saharan Africa, Asian-Indian subcontinent, Southeast Asia, Mediterranean).

  • Types: decreased production of alpha or beta chains of hemoglobin (alpha and beta thalassemias) leading to microcytic/hypochromic anemia.

  • Alpha thalassemia:

    • More common in southern China, Malaysia, Thailand; mild forms seen in African ancestry.

  • Beta thalassemia: prevalent in Africa.

  • Classic case: majority asymptomatic; discovered incidentally via abnormal CBC showing microcytosis/hypochromia; total RBC count may be mildly elevated.

  • Labs: Hb analysis/genetic testing; alpha-thalassemia shows Hb Bart’s (gamma tetramers) or Hb H (beta tetramers); DNA testing required for alpha-thalassemia minor/minima; beta-thalassemia shows elevated HbA2 and HbF.

  • RBC changes: microcytosis, increased RBC count, nonimmune hemolysis; blood smear shows poikilocytosis, target cells, teardrop cells, and cell fragments.

  • Ferritin/iron typically normal (helps distinguish from IDA).

  • Treatment: individualized; some may need transfusions during stress; thalassemia minor often does not require treatment if anemia is mild.

  • Genetic counseling and reproductive planning: educate about risk to offspring; consider routine testing for individuals with thalassemia.

  • Confirmation: Hb analysis and/or genetic testing required for diagnosis.

  • Ethnic background considerations: thalassemia prevalence varies by ethnicity; questions may not reveal ethnicity.

Anemia of Chronic Disease / Inflammation

  • Also called anemia of inflammation or hypoferremia of inflammation; second most common worldwide.

  • Mechanism: autoimmune/inflammatory diseases increase cytokine production and hepcidin, which sequesters iron and reduces RBC production.

  • Presentation: mild to moderate anemia; normochromic, normocytic RBCs (MCV 80–100 fL).

  • Inflammatory markers: ESR (sed rate) or CRP often elevated.

  • Treatment: treat underlying autoimmune/inflammatory disease to reduce inflammation and allow bone marrow recovery.

Anemia of Chronic Kidney Disease (CKD)

  • Prevalence increases as glomerular filtration rate (GFR) declines.

  • Definition by Hb: < 13\,\text{g/dL} in adult males and postmenopausal women; < 12\,\text{g/dL} in premenopausal women.

  • Morphology: hypoproliferative, normocytic, normochromic anemia.

  • Pathophysiology: decreased renal EPO production reduces reticulocyte/RBC production; possible functional iron deficiency and/or inflammatory conditions.

  • Initial testing: CBC, ferritin, transferrin saturation, vitamin B12, folate, reticulocyte count.

  • Treatment plan:

    • Conventional therapy for anemia.

    • Erythropoiesis-stimulating agents (ESAs) if Hb < 10\,\text{g/dL} or not improving with standard therapy.

    • Iron therapy (oral or IV): PO iron for patients not on dialysis; IV iron for hemodialysis patients with severe iron deficiency, severe anemia, ongoing blood loss risk, or intolerance to oral iron.

  • Pearls on iron therapy:

    • Best absorbed and cheapest iron form: ferrous sulfate.

    • Antacid wait time: wait ~4\ \text{hours} before taking iron to reduce binding.

    • Iron interactions: iron binds with tetracyclines, levothyroxine, and bisphosphonates; take iron 2 hours before/after antibiotic.

    • Nonresponse to iron therapy despite adherence may indicate ongoing blood loss, misdiagnosis, or malabsorption (e.g., celiac disease).

  • Safety note: Iron poisoning in children (esp. < 6\ years) can be fatal; store supplements out of reach of children.

  • Medications that may lower Hb and worsen anemia in chronic diseases: ARBs and ACE inhibitors.

Macrocytic/Megaloblastic Anemias

Vitamin B12–Deficiency Anemia

  • Cause: deficiency in vitamin B12, essential for neuronal health and DNA production in RBCs; total body supply lasts 3\ to\ 4\ \text{years}.

  • Common causes: malabsorption (pernicious anemia, gastric disease/infections, medications such as PPIs, H2 blockers, metformin).

  • Chronic deficiency can cause irreversible neuropathy/brain damage; highest incidence in older women; pernicious anemia is a common cause.

  • Pernicious anemia (a type of B12 anemia): autoimmune destruction of parietal cells → cessation of intrinsic factor production (intrinsic factor needed for B12 absorption).

  • Other causes: dietary insufficiency; gastric/bowel/pancreatic disorders; strict vegetarianism; gradual dietary deficiency may take >5 years.

  • B12 sources: all foods of animal origin (meat, poultry, eggs, milk, cheese).

  • Classic case: older adult with jaundiced/yellow skin; glossitis; neuropathic symptoms (paresthesias, difficulty walking, fine motor difficulties); possible cognitive effects.

  • Objective findings: decreased reflexes; possible reduced ankle reflex if legs involved; inflamed tongue glossitis.

  • Warning: always check both serum B12 and serum folate in macrocytic anemias; dual deficiency possible; folate-enriched diets may mask B12 deficiency.

  • Labs:

    • B12 level: normal > 300\,\text{pg/mL}; borderline 200\text{ to }300\,\text{pg/mL}; deficient < 200\,\text{pg/mL}.

    • CBC: decreased Hb/Hct; macrocytosis (MCV > 100\,\text{fL}); mild leukopenia; thrombocytopenia; low reticulocyte count.

    • Antibodies: antiparietal antibodies; autoantibodies to intrinsic factor.

    • Metabolite testing: MMA elevated (not definitive for B12 deficiency); homocysteine elevated.

    • Schilling test (historic): positive if B12 excretion normal after intrinsic factor; has limited current use.

    • Peripheral smear: macrocytosis, hypersegmented neutrophils (>5–6 lobes).

    • Treatment:

    • Parenteral B12: 1000 mcg (1 mg) IM/SC weekly for 1 month, then monthly.

    • Oral B12: 1000–2000 mcg daily if adherence is reliable and absorption is adequate.

  • Tips:

    • Pernicious anemia is macrocytic, normochromic with risk of neurologic symptoms due to intrinsic factor loss.

    • B12 level < 200\,\text{pg/mL} is consistent with deficiency.

    • CBC is a common screening test for anemia; chronic illness/autoimmune disease increases risk for normocytic anemia.

    • Test reticulocyte count after starting therapy to gauge response (approx. 2 weeks).

Folic Acid (Folate) Deficiency Anemia

  • Deficiency in folate (vitamin B9) causes DNA damage in RBCs and macrocytosis (MCV > 100\,\text{fL}).

  • Body’s folate stores last 2\ to\ 3\ months; most common causes: inadequate dietary intake (elderly, infants, alcoholics, overcooking vegetables, low citrus intake).

  • Other causes: increased physiologic need (pregnancy); malabsorption (e.g., gluten enteropathy, gastric bypass);

  • Drugs that interfere with folate absorption: Phenytoin, TMP-SMX, metformin, methotrexate, sulfasalazine, zidovudine, and others.

  • Classic case: older patient or patient with alcoholism; fatigue, pallor or jaundice; glossitis; progressive weakness, ataxia, paresthesias (less common than B12).

  • Labs: CBC shows macrocytic RBCs; macro-ovalocytes; hypersegmented neutrophils; folate level normal or low depending on intake;

    • Folate level interpretation: > 4\ ng/mL normal; 2–4 ng/mL borderline; < 2\ ng/mL consistent with deficiency.

    • MMA typically normal; homocysteine elevated with folate deficiency.

  • Treatment: folic acid supplementation 1–5 mg/day PO; treat for 1–4 months or until CBC/RBC indices normalize; chronic deficiency may require ongoing therapy.

  • Women of childbearing age: 400 mcg daily folic acid to prevent neural tube defects; higher doses (4 mg daily) for those with previous neural tube defects.

Aplastic Anemia

  • Caused by destruction of pluripotent stem cells in the bone marrow; multiple causes (radiation, drug toxicity, viral infections).

  • Bone marrow production slows/stops; all cell lines affected → pancytopenia (leukopenia, anemia, thrombocytopenia).

  • Classic case: fatigue, pallor; tachycardia; mucosal bleeding; neutropenia → infections; thrombocytopenia → bruising.

  • Labs: CBC with differential often shows normocytic/macrocytic RBCs; few mature neutrophils; platelets decreased; low reticulocyte count; bone marrow biopsy required for diagnosis.

  • Management: refer to hematologist; if septic, ED referral.

Erythrocytosis (Polycythemia)

  • Definition: abnormal elevation of Hb and/or Hct.

  • Classification: absolute polycythemia (primary or secondary) vs relative polycythemia (hemoconcentration due to decreased plasma volume).

  • Absolute polycythemia: mutation-driven (acquired/inherited) increase in RBC mass.

  • Criteria for polycythemia in adults:

    • Hct > 48\% in women, > 49\% in men

    • Hb > 16.0\ \text{g/dL} in women, > 16.5\ \text{g/dL} in men

Hemochromatosis

  • Hereditary hemochromatosis: genetic iron overload due to increased intestinal iron absorption.

  • Pathophysiology: gradual iron deposition over decades; iron overload damages liver, heart, joints, and other organs.

  • Symptoms: fatigue, skin hyperpigmentation (bronze), joint stiffness, swelling (2nd/3rd metacarpophalangeal joints).

  • Lab findings: elevated AST/ALT, high ferritin (often > 500\ ng/dL), elevated transferrin saturation.

  • Treatment: therapeutic phlebotomy for symptomatic iron overload.

Hemolytic Anemias

  • Group of inherited or acquired conditions with shortened RBC lifespan and increased RBC destruction.

  • Exam focus on two: sickle cell trait and G6PD deficiency.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

  • X-linked recessive; more common in males; often asymptomatic unless hemolysis occurs.

  • G6PD protects RBCs against oxidative damage; five known variants.

  • Populations: common in tropical/subtropical regions; Kurdish Jews have higher prevalence.

  • Triggers of hemolysis: certain drugs (e.g., primaquine, hydroxychloroquine, sulfa drugs, acetazolamide, dapsone), fava beans, infections, stress, fever, etc.

  • Hemolytic episode timing: typically 2–4 days after triggering exposure; symptoms:

    • Jaundice, yellow sclerae, pallor, fatigue, tachycardia, dark urine; abrupt Hgb drop by ~3!-\,4\,\text{g/dL}.

  • Evaluation: CBC and peripheral smear.

  • Genetics: Pedigree patterns show X-linked inheritance; carrier status in females; affected sons and carrier daughters in typical patterns.

Sickle Cell Disease / Trait

  • US prevalence: ~100,000 Americans with sickle cell disease; HbSS median survival ~58\ years.

  • Ethnic risk: higher in African, Mediterranean, Middle Eastern, some Indian populations.

  • Complications: acute chest syndrome, anemia, AVN, thrombosis, dactylitis, fever/infections, renal/hepatic issues, leg ulcers, pain crises, priapism, pulmonary hypertension, sleep-disordered breathing, splenic sequestration, stroke, vision loss.

  • Classic case: sickle cell trait usually asymptomatic; disease may present with aplastic crises or frequent vaso-occlusive episodes; sudden severe pain episodes in extremities, back, chest, or abdomen; may have dyspnea, weakness.

  • Triggers of sickling: hypoxia, infections, high altitude, dehydration, stress, surgery, blood loss, acidosis.

  • Lab features: CBC shows anemia; peripheral smear shows sickle-shaped RBCs.

  • Diagnosis: screen with HPLC, isoelectric focusing (IEF), or gel electrophoresis; combined HPLC + IEF provides definitive diagnosis in older children/adults.

  • Management/Genetics:

    • Sickle cell is autosomal recessive; genetic counseling recommended if both partners at risk.

    • Prenatal screening available as early as 8–10 weeks (CVS or amniocentesis).

    • Individuals with family history or clinical signs should be screened with peripheral smear, Hb solubility test, and hemoglobin electrophoresis.

    • Management typically involves hematology specialty for acute and chronic complications.

  • High-altitude stress: lower barometric pressure reduces arterial PO2; CAD/CHF/sickle cell patients at higher risk; advise avoiding elevations > 7,000 ft.

  • Newborn screening: all US states require newborn screening for sickle cell disease at birth.

Microcytic Anemias Summary

  • Iron-Deficiency Anemia vs Thalassemia Trait:

    • Ferritin: low in IDA; normal in thalassemia trait.

    • Serum Iron: decreased in IDA; normal in thalassemia trait.

    • TIBC: elevated in IDA; normal in thalassemia trait.

    • MCHC: decreased in both IDA and thalassemia trait (hypochromia).

    • Hb electrophoresis: normal in IDA; abnormal (beta-thalassemia) with specific HbA2/HbF patterns in thalassemia.

  • Ethnic background: IDA most common overall; alpha-thalassemia common in southern China/Malaysia/Thailand and mild forms in African ancestry; beta-thalassemia common in Africa.

Practical/Clinical Pearls & Messages

  • Serum ferritin is the most sensitive test for IDA but may be affected by inflammation; interpret with context.

  • Always consider coexisting B12 and folate deficiencies; check both in macrocytic anemia.

  • Reticulocytosis (> 2.5\%) indicates marrow response; lack of reticulocytosis after acute bleed or supplementation prompts marrow failure workup (aplastic anemia) with bone marrow biopsy.

  • For IDA, iron therapy is generally effective; monitor response by Hb/Hct and ferritin; if not responding, reassess for ongoing blood loss or malabsorption.

  • In CKD/CKD-related anemia, ESAs and iron therapy must be balanced; IV iron is preferred in dialysis patients.

  • In conditions like hemochromatosis, phlebotomy is a mainstay treatment for iron overload.

  • Genetic conditions require counseling and family planning discussions; testing should be offered to at-risk individuals.

  • Many medications can affect hematologic parameters; monitor drug side effects on Hb, iron status, and marrow health.

  • Safety note: certain deficiencies (e.g., B12) can cause irreversible neurologic damage if untreated; early diagnosis and treatment are critical.

Formulas and Key Numbers (summary)

  • Reticulocyte percentage thresholds:

    • Normal: 0.5\%\leq \text{retic} \leq 2\%

    • Reticulocytosis: \text{retic} > 2.5\%

  • Blood loss classifications (percent of blood volume):

    • Class I: \%\text{ blood loss} \leq 15\%

    • Class II: 15\% \leq \% \leq 30\%

    • Severe: 30\% \leq \% \leq 40\%

  • Common normal laboratory ranges (selected):

    • Hb (males): 13.6\text{ to }16.9\ \text{g/dL}

    • Hb (females): 11.9\text{ to }14.8\ \text{g/dL}

    • Hct (males): 40\%\text{ to }50\%

    • Hct (females): 36\%\text{ to }44\%

    • MCV: 82.5\text{ to }98\ \text{fL}

    • MCHC: 32.5\text{ to }35.2\ \text{g/dL}

    • MCH: 25.0\text{ to }35.0\ \text{pg/cell}

    • TIBC: 300\text{ to }360\ \mu\text{g/dL}

    • Serum ferritin: 40\text{ to }200\ \text{ng/mL}

    • Serum iron: 60\text{ to }150\ \mu\text{g/dL}

    • WBC count: 3.8\text{ to }10.4\times 10^3/\mu L

    • Platelet count: 152\text{ to }324\times 10^3/\mu L (males); 153\text{ to }361\times 10^3/\mu L (females)

  • Hemoglobin Electrophoresis (typical adult proportions): HbA \approx 97\%, HbA2 \approx 2.5\%, HbF < 1\%

  • Vitamin B12 levels: normal > 300\ \text{pg/mL}; borderline 200\text{ to }300\ \text{pg/mL}; deficient < 200\ \text{pg/mL}

  • Folate levels: normal > 4\ ng/mL; borderline 2\text{ to }4\ ng/mL; deficient < 2\ ng/mL

Notes on Diagnostic Pathways and Counseling

  • When evaluating anemia, CBC is a screening test; interpret Hb/Hct along with MCV, MCHC, MCH, RDW, ferritin, serum iron, TIBC, and reticulocyte count.

  • Use Hb electrophoresis and/or genetic testing to confirm thalassemia vs IDA in microcytic anemias when labs are equivocal.

  • Consider age, sex, ethnicity, and exposure history (diet, alcohol use, medications, infections) to guide testing for B12/folate deficiencies and CKD-related anemia.

  • Risk communication: discuss genetic risks and family planning with patients when hereditary conditions (thalassemia, sickle cell) are identified.