4.5 Hematology, Anemia Evaluation, Transfusion Medicine, & Common Cancers
Key Takeaways
- Microcytic anemia evaluation relies on serum ferritin (ferritin < 30 µg/L is diagnostic of Iron Deficiency Anemia); newly diagnosed IDA in men or postmenopausal women requires endoscopic evaluation to rule out GI malignancy.
- Macrocytic anemia with hypersegmented neutrophils indicates megaloblastic etiology; Vitamin B12 deficiency causes subacute combined degeneration with elevated MMA and homocysteine, whereas folate deficiency elevates homocysteine alone.
- Canadian Blood Services (CBS) transfusion guidelines recommend a restrictive RBC transfusion threshold of Hb < 70 g/L for stable patients (target Hb 70–80 g/L; target Hb ≥ 80–90 g/L in active acute coronary syndrome).
- Transfusion-Related Acute Lung Injury (TRALI) is distinguished from Transfusion-Associated Circulatory Overload (TACO) by normal/low BP, normal JVP, normal BNP, and lack of response to diuretics.
- Febrile neutropenia (ANC < 0.5 x 10^9/L with fever ≥ 38.3°C) is a medical emergency requiring immediate empiric broad-spectrum IV antipseudomonal monotherapy (piperacillin-tazobactam) within 1 hour.
4.5 Hematology, Anemia Evaluation, Transfusion Medicine, & Common Cancers
Algorithmic Evaluation of Anemia by MCV
Anemia is defined as hemoglobin < 130 g/L in adult males and < 120 g/L in non-pregnant adult females. Initial evaluation categorizes anemia by Mean Corpuscular Volume (MCV).
1. Microcytic Anemia (MCV < 80 fL) - Differential Mnemonic: TAILS
- Iron Deficiency Anemia (IDA): Most common cause worldwide. Serum ferritin < 30 µg/L is the single most sensitive and specific diagnostic marker. Further labs: Low serum iron, high TIBC, low transferrin saturation (< 20%). Peripheral film shows microcytic hypochromic RBCs and pencil cells.
- Mandatory Clinical Rule: Any adult male or postmenopausal female with newly diagnosed IDA requires endoscopic evaluation (Colonoscopy + Gastroscopy) to rule out occult gastrointestinal malignancy (e.g., cecal adenocarcinoma).
- Anemia of Chronic Disease / Inflammation (ACD): Driven by elevated hepcidin, which sequesters iron in macrophages. Serum ferritin is normal or elevated (acute phase reactant), low TIBC, low serum iron.
- Thalassemia Trait (Alpha or Beta): Microcytosis out of proportion to mild anemia. Mentzer Index (MCV / RBC count) < 13 strongly points to Thalassemia trait (Index > 13 points to IDA). Confirmed via hemoglobin electrophoresis (elevated HbA2 > 3.5% in Beta-thalassemia trait).
- Lead Poisoning: Basophilic stippling on peripheral film, ringed sideroblasts in marrow.
2. Normocytic Anemia (MCV 80 – 100 fL)
Evaluate the Reticulocyte Production Index (RPI):
- Hyperproliferative (RPI > 2%): Indicates intact marrow response to Hemolysis or acute blood loss. Hemolytic markers: Elevated LDH, decreased haptoglobin, elevated indirect bilirubin, spherocytes or schistocytes.
- Direct Antiglobulin Test (DAT / Coombs Test): Positive = Autoimmune Hemolytic Anemia (AIHA) (Warm IgG vs Cold IgM); Negative = Non-immune hemolysis (G6PD deficiency, Hereditary Spherocytosis, PNH).
- Hypoproliferative (RPI < 2%): Bone marrow failure/suppression, early iron deficiency, Chronic Kidney Disease (erythropoietin deficiency), hypothyroidism.
3. Macrocytic Anemia (MCV > 100 fL)
Inspect peripheral blood film for hypersegmented neutrophils (≥ 5% of neutrophils with ≥ 5 lobes or 1 neutrophil with ≥ 6 lobes):
- Megaloblastic Anemia (Hypersegmented neutrophils present -> Impaired DNA synthesis):
- Vitamin B12 (Cobalamin) Deficiency: Pernicious anemia (anti-intrinsic factor antibodies), ileal resection, strict vegan diet. Clinical features: Macrocytic anemia PLUS neurological deficits (Subacute Combined Degeneration of spinal cord: loss of vibration/proprioception, spastic paraparesis). Labs: Elevated Methylmalonic Acid (MMA) AND elevated Homocysteine.
- Folate Deficiency: Alcohol use disorder, malnutrition, methotrexate. Clinical features: Macrocytic anemia WITHOUT neurological deficits. Labs: Elevated Homocysteine ONLY; Normal MMA.
- Non-Megaloblastic Macrocytosis (No hypersegmented neutrophils): Alcohol use disorder, chronic liver disease, hypothyroidism, reticulocytosis, Myelodysplastic Syndrome (MDS).
Bleeding Disorders & Coagulation Cascade Interpretation
Primary vs Secondary Hemostasis
| Parameter | Primary Hemostasis Disorders | Secondary Hemostasis Disorders |
|---|---|---|
| Primary Defect | Platelets or vessel wall defect | Coagulation factor deficiency or inhibitor |
| Bleeding Pattern | Mucosal bleeding (epistaxis, menorrhagia, gingival), petechiae, purpura | Deep tissue hematomas, hemarthrosis (joint bleeding), delayed surgical bleeding |
| Screening Tests | Platelet count, Bleeding Time / PFA-100 | Prothrombin Time (PT/INR), Activated Partial Thromboplastin Time (aPTT) |
| Prototype Conditions | vWD, ITP, TTP, DIC, Aspirin/Clopidogrel | Hemophilia A (Factor VIII), Hemophilia B (Factor IX), Warfarin, Vitamin K deficiency |
Key Hemostatic Pathologies
- von Willebrand Disease (vWD): Most common inherited bleeding disorder (Autosomal Dominant). vWF mediates platelet adhesion and carries Factor VIII. Screening: Normal platelet count, prolonged bleeding time, prolonged or normal aPTT, normal PT. Treatment: Desmopressin (DDAVP) (releases stored vWF from Weibel-Palade bodies) for mild type 1 vWD; vWF/Factor VIII concentrate for severe cases.
- Hemophilia A & B: X-linked recessive factor deficiencies (Factor VIII = Hemophilia A; Factor IX = Hemophilia B). Features: Isolated prolonged aPTT, normal PT, normal platelets. 1:1 Mixing Study corrects aPTT. Treatment: Recombinant Factor VIII or IX replacement.
- Disseminated Intravascular Coagulation (DIC): Widespread microvascular thrombosis with consumptive coagulopathy. Causes: Sepsis, trauma, obstetric catastrophes, APL. Labs: Thrombocytopenia, prolonged PT/INR and aPTT, low fibrinogen (<1.5 g/L), elevated D-dimer, and schistocytes.
Transfusion Medicine & Canadian Blood Services (CBS) Guidelines
Restrictive RBC Transfusion Strategy
Canadian Blood Services and Choosing Wisely Canada recommend a restrictive transfusion threshold of Hb < 70 g/L for hemodynamically stable adult inpatient populations, transfusing 1 unit of RBCs at a time to maintain a target Hb of 70–80 g/L. Exception: In patients with active Acute Coronary Syndrome (ACS) or symptomatic myocardial ischemia, maintain a target Hb threshold of ≥ 80–90 g/L.
Acute Transfusion Reactions Comparison
| Reaction Type | Pathophysiology | Key Clinical Features | Management |
|---|---|---|---|
| Acute Hemolytic (AHTR) | ABO incompatibility | Fever, flank pain, hypotension, hemoglobinuria, DIC | STOP transfusion, IV normal saline, maintain urine output |
| TRALI | Donor anti-HLA antibodies -> neutrophil activation in lungs | Non-cardiogenic edema, hypoxia, Normal/Low BP, bilateral infiltrates within 6h | STOP transfusion, oxygen, mechanical ventilation (Do NOT give diuretics) |
| TACO | Volume overload from rapid transfusion | Cardiogenic edema, hypoxia, Elevated BP, elevated JVP, elevated BNP | STOP transfusion, oxygen, IV Furosemide (diuresis) |
| Febrile Non-Hemolytic | Cytokines accumulated in stored blood | Mild fever (>1°C rise), chills, no hemolysis or hypoxia | STOP transfusion to rule out hemolysis; Antipyretics; Leukoreduction |
| Anaphylaxis | Recipient anti-IgA antibodies reacting against donor IgA | Sudden bronchospasm, stridor, hypotension, urticaria | STOP transfusion, IM Epinephrine, IV fluids, washed RBCs in future |
Oncologic Emergencies & Common Malignancies
Febrile Neutropenia
Defined as a single oral temperature ≥ 38.3°C (or ≥ 38.0°C sustained over 1 hour) PLUS an Absolute Neutrophil Count (ANC) < 0.5 x 10^9/L (or ANC < 1.0 x 10^9/L with expected drop to < 0.5 x 10^9/L).
- Emergency Management: Medical emergency! Obtain 2 sets of blood cultures (peripheral + central line). Initiate empiric broad-spectrum IV antipseudomonal monotherapy within 1 hour of presentation. First-line agent: Piperacillin-tazobactam (Tazocin) 4.5 g IV q6h (or Cefepime 2 g IV q8h, or Meropenem 1 g IV q8h). Do NOT delay antibiotic administration for diagnostic imaging or laboratory results!
Tumor Lysis Syndrome (TLS)
Massive destruction of rapidly proliferating malignant cells (e.g., Burkitt lymphoma, ALL) post-chemotherapy.
- Laboratory Triad: Hyperuricemia, Hyperkalemia, Hyperphosphatemia, with Secondary Hypocalcemia.
- Prevention & Treatment: Aggressive IV hydration (2–3 L/m²/day). Rasburicase (recombinant urate oxidase) for high risk; Allopurinol for low-to-moderate risk.
Multiple Myeloma
Plasma cell dyscrasia secreting monoclonal immunoglobulin (M-spike on SPEP).
- CRAB Criteria:
- C: Calcium elevated (> 2.75 mmol/L).
- R: Renal insufficiency (creatinine > 177 µmol/L due to light chain cast nephropathy).
- A: Anemia (normocytic normochromic, Hb < 100 g/L).
- B: Bone lesions (lytic punched-out lesions on skeletal survey, pathologic fractures).
- Diagnostic Markers: Rouleaux formation on blood film, elevated ESR (>100 mm/h), Bence Jones proteinuria (UPEP), >10% clonal plasma cells on bone marrow biopsy.
[!WARNING] MCCQE1 High-Yield Distinction: TRALI vs TACO Acute respiratory distress occurring within 6 hours of blood transfusion: • TRALI: Non-cardiogenic, Normal or Low BP, Normal JVP, Normal BNP. Treatment: Oxygen & Mechanical Ventilation (Do NOT give diuretics!). • TACO: Cardiogenic volume overload, Elevated/High BP, Elevated JVP, Elevated BNP. Treatment: Oxygen & IV Furosemide.
A 72-year-old male presents with fatigue and numbness in his feet. On examination, he has pale conjunctivae, loss of vibration and proprioception in both lower extremities, and an ataxic gait. Hemoglobin is 84 g/L, MCV is 114 fL, and blood film shows neutrophils with 6 lobes. Serum Folate is normal. Which of the following laboratory findings confirms the underlying diagnosis?
A 65-year-old female receiving a 2nd unit of packed red blood cells following hip surgery develops severe shortness of breath and a non-productive cough 3 hours into the transfusion. Vitals: BP 165/98 mmHg, HR 112/min, RR 28/min, SpO2 84% on room air. Exam shows bilateral basalar crackles, a prominent S3 gallop, and jugular venous distension 5 cm above the sternal angle. Chest X-ray reveals bilateral pulmonary infiltrates. What is the diagnosis and most appropriate management?
A 54-year-old female with non-Hodgkin lymphoma receiving chemotherapy presents to the emergency department with a single oral temperature of 38.6°C. She feels chilled but has no specific localizing symptoms of infection. Labs: WBC 0.8 x 10^9/L, Absolute Neutrophil Count (ANC) 0.3 x 10^9/L, Hb 95 g/L, and Platelets 85 x 10^9/L. Blood cultures are drawn. What is the single most critical immediate management action?