Hematology and Blood Disorders Assessment

The complete blood count (CBC) is the most commonly ordered lab test. It measures: (1) White blood cells (WBC, K/uL): total count of infection-fighting immune cells. Low = immunosuppression, high = infection or leukemia. Normal ~4.5–11K. (2) Red blood cells (RBC, M/uL): oxygen-carrying cells. Low = anemia, high = polycythemia (too much blood). Normal ~4.5–5.5M men, ~4.0–5.0M women. (3) Hemoglobin (Hgb, g/dL): oxygen-carrying protein in RBCs. Low = anemia, high = dehydration or polycythemia. Normal ~13.5–17.5 men, ~12.0–15.5 women. (4) Hematocrit (Hct, %): percentage of blood volume occupied by RBCs. Low = anemia, high = polycythemia. Normal ~39–50% men, ~35–45% women. (5) Mean Corpuscular Volume (MCV, fL): average RBC size. Low = microcytic (small, iron deficiency), normal = normocytic, high = macrocytic (large, B12 deficiency). (6) Mean Corpuscular Hemoglobin (MCH, pg): average hemoglobin per RBC. Follows MCV. (7) Mean Corpuscular Hemoglobin Concentration (MCHC, g/dL): hemoglobin concentration. (8) Platelets (Plt, K/uL): clotting cells. Low = bleeding risk, high = thrombosis risk. Normal ~150–400K. (9) Reticulocyte count (%): immature RBCs. High = bone marrow response to anemia. (10) Differential: WBC breakdown into neutrophils (immune), lymphocytes (infection fighters), monocytes (scavengers), eosinophils, basophils. Together, CBC tells a comprehensive story of blood health.

A manual differential count is the microscopic examination of a blood smear (thin layer of blood on a glass slide, stained with Wright-Giemsa) to count white blood cell types and assess red and white cell morphology. The tech scans the smear under a microscope, identifies 100 WBCs, and calculates the percentage of each type: neutrophils (normal 50–70%), lymphocytes (20–40%), monocytes (2–10%), eosinophils (1–4%), basophils (0–2%). Abnormalities: high neutrophils = acute infection; high lymphocytes = viral infection or leukemia; high monocytes = chronic infection or malignancy; high eosinophils = allergy or parasitic infection. The differential also assesses RBC morphology for abnormalities: schistocytes (fragmented, hemolytic anemia), spherocytes (hereditary spherocytosis), target cells (liver disease, thalassemia), rouleaux (high protein), hypochromia (pale, iron deficiency), polychromasia (blue tint, immature RBCs). WBC morphology: blasts (immature, leukemia), bands (immature neutrophils, left shift = infection), toxic granulation (severe infection), Döhle bodies. Platelet morphology: giant platelets (Bernard-Soulier syndrome), clumping. A manual differential catches morphologic abnormalities that automated analyzers might miss, so it is essential for diagnosing leukemia, severe infections, and inherited disorders.

Hemolysis is the rupture of red blood cells (RBCs), releasing hemoglobin into the plasma. When hemoglobin is freed, it imparts a pink or red color to serum (visible hemolysis) and raises potassium, LDH, and bilirubin, falsifying results and requiring a redraw. Hemolysis can occur in vivo (in the body) or in vitro (during collection or processing). In vivo hemolysis causes: (1) Hemolytic anemia: RBCs are destroyed faster than bone marrow can replace them, leading to anemia, jaundice (high bilirubin), dark urine (hemoglobinuria), fatigue. Causes: antibodies (autoimmune hemolytic anemia, transfusion reaction), hereditary defects (sickle cell disease, hereditary spherocytosis, G6PD deficiency), infections (malaria), hypersplenism. Lab findings: low RBC, low hemoglobin, high reticulocyte count (bone marrow trying to compensate), high bilirubin, high LDH, low haptoglobin (consumed by free hemoglobin). In vitro hemolysis during blood draw causes: (1) Small-gauge needle (forcing blood through), (2) vigorous tube shaking, (3) prolonged tourniquet time, (4) drawing from a hematoma. Prevention: use appropriate needle gauge, gentle handling, release tourniquet within a minute, avoid drawing through a bruise. Clinical recognition: pink serum, elevated potassium/LDH despite normal values in prior tests, or unexplained anemia with high reticulocytes.

Anemia is a reduction in hemoglobin or RBC count below the reference range. Classification by RBC size (MCV): (1) Microcytic (MCV <80): small RBCs. Causes: iron deficiency (most common), thalassemia, lead poisoning. Labs: low ferritin (iron deficiency), normal ferritin + A2 band (thalassemia on hemoglobin electrophoresis). (2) Normocytic (MCV 80–100): normal-sized RBCs. Causes: acute blood loss, hemolysis, bone marrow disease, chronic kidney disease (low erythropoietin), hypersplenism. Labs: high reticulocyte count (hemolysis, blood loss — bone marrow responding), low reticulocyte count (bone marrow failing — leukemia, aplastic anemia). (3) Macrocytic (MCV >100): large RBCs. Causes: B12 deficiency, folate deficiency, alcohol, medications. Labs: low B12/folate levels, hypersegmented neutrophils on smear. Functional classification by reticulocyte response: (1) Low reticulocyte count (hypoproliferative): bone marrow is failing to make enough RBCs despite anemia — suggests bone marrow disease, kidney disease, or nutrient deficiency. (2) High reticulocyte count (hyperproliferative): bone marrow is responding to anemia by releasing immature RBCs — suggests RBC loss (bleeding) or destruction (hemolysis). Each anemia type has a different cause and treatment: iron deficiency = iron supplementation, B12 deficiency = B12 shots, hemolysis = immunosuppression, bleeding = source control.

A blast is an immature (undifferentiated) blood cell. In normal blood, blasts should be absent or very rare. Finding blasts in a blood smear is abnormal and raises concern for leukemia. Blasts are characterized by: large cell size, high nuclear-to-cytoplasmic ratio (nucleus dominates), fine chromatin (looks like lace), prominent nucleoli (one or more), and sparse cytoplasm. Types: myeloblasts (primitive myeloid cells, found in acute myeloid leukemia/AML), lymphoblasts (primitive lymphoid cells, found in acute lymphoblastic leukemia/ALL), and monoblasts (primitive monocytic cells). Finding blasts on a blood smear triggers: (1) Reflex to flow cytometry (immunophenotyping) to determine the exact lineage and stage of the leukemic cells. (2) Bone marrow biopsy for definitive diagnosis. (3) Cytochemical staining (MPO, PAS) to narrow the differential. (4) Urgent communication to the clinician. (5) Possible treatment initiation (some leukemias like acute promyelocytic leukemia are medical emergencies). Not all blasts are leukemia: severe infections (sepsis) can trigger a left shift with band forms that look immature, and immature RBCs (nucleated RBCs) can appear blast-like. Context and flow cytometry distinguish.

Hemostasis is the body's ability to stop bleeding through three mechanisms: (1) vascular integrity (blood vessel walls), (2) platelets (primary hemostasis), (3) coagulation cascade (secondary hemostasis, clot formation). Disorders: (1) Bleeding due to low platelets (thrombocytopenia): risk of spontaneous bleeding when platelets <20K. Causes: decreased production (bone marrow failure), increased destruction (ITP, TTP, DIC), or sequestration (splenomegaly). Lab: low platelet count on CBC. (2) Bleeding due to platelet dysfunction (normal count, abnormal function): causes include medications (aspirin), uremia, diabetes, von Willebrand disease. Lab: normal platelet count, prolonged bleeding time, abnormal platelet aggregation studies. (3) Bleeding due to coagulation factor deficiency: causes hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency), vitamin K deficiency (factors II, VII, IX, X), DIC (all factors consumed). Lab: prolonged prothrombin time (PT, factors I, II, V, VII, X), prolonged activated partial thromboplastin time (aPTT, factors VIII, IX, XI, XII), normal or low fibrinogen, low platelets (in DIC). (4) Thrombosis (clotting too much): causes factor V Leiden, prothrombin gene mutation, antiphospholipid syndrome. Lab: resistance to activated protein C, genetic testing. Assessment tools: CBC (platelet count), PT (extrinsic pathway), aPTT (intrinsic pathway), fibrinogen, D-dimer (marker of active clotting/fibrinolysis), bleeding time (outdated, now platelet function analysis), thrombin time (fibrinogen functional assay).

Iron deficiency anemia (IDA) and anemia of chronic disease (ACD) are the two most common anemias, both microcytic or normocytic, and both common in older patients with chronic diseases. Iron deficiency anemia: caused by iron loss (bleeding, including GI bleed), poor intake, or poor absorption. Symptoms: fatigue, weakness, cold hands/feet, pagophagia (eating ice). Labs: low iron, low ferritin, high TIBC (total iron-binding capacity), high transferrin saturation, microcytic RBCs, low reticulocyte count. Blood smear: hypochromic (pale) RBCs. Treatment: iron supplementation (oral ferrous sulfate or IV iron), find and stop the bleeding source. Anemia of chronic disease: caused by chronic infection (TB, endocarditis), inflammation (rheumatoid arthritis, lupus), cancer, kidney disease, or liver disease. Pathophysiology: elevated hepcidin (iron-regulating hormone) blocks iron absorption and reutilization. Symptoms: fatigue from underlying disease, not specific iron-deficiency symptoms. Labs: normal or high ferritin (ferritin is an acute-phase reactant, rises with inflammation), normal TIBC, low transferrin saturation, normocytic or mildly microcytic RBCs, low reticulocyte count. Blood smear: normochromic RBCs. Treatment: treat the underlying disease; iron supplementation doesn't help. Distinguishing them: Ask for bleeding history and inspect stool. Check ferritin (low = IDA, normal/high = ACD). Check TIBC (high = IDA, normal = ACD). Measure inflammatory markers (CRP, ESR): high in ACD, normal in IDA. If still unclear, check iron studies in more detail or do a bone marrow biopsy (Prussian blue stain for iron stores; absent in IDA, present in ACD).