This educational video features Dr. Jared Gardner and hematopathology specialist Dr. Jeanette Ramos, who provides a comprehensive, step-by-step guide to evaluating peripheral blood smears (PBS). Dr. Ramos details the necessary steps before microscopic review, including checking specimen quality, reviewing the Complete Blood Count (CBC) and its parameters (MCV, MCHC, RDW), and contextualizing clinical questions. The lecture provides an in-depth morphological analysis of normal leukocytes and erythrocytes, followed by a review of numerous pathological conditions. Case examples illustrate various red cell abnormalities (microcytic, macrocytic, hemolytic anemias, hemoglobinopathies), white cell changes (toxic granulation, dyspoiesis), and critical findings related to infection (malaria, babesiosis, ehrlichiosis, histoplasmosis) and malignancy (CML, APL, AML, ALL, CLL, myeloma). A recurring theme emphasizes the importance of clinical correlation and recognizing common artifacts (EDTA effects, smudge cells, platelet aggregates) to avoid misdiagnosis.
The Pathologist’s Guide to Peripheral Blood Smears (PBS)
0:00 Pre-Evaluation Steps: Dr. Jeanette Ramos (heme path expert) introduces the PBS as a foundational skill. Necessary steps include checking patient/specimen identity, ensuring the smear is satisfactory, reviewing the Complete Blood Count (CBC), and understanding the clinical question (e.g., looking for acanthocytes).
2:20 Satisfactory Smear: A good PBS should have a film covering 2/3 to 3/4 of the slide, with smooth thickness, a slightly rounded (not bullet-sharp) edge, and lateral edges visible. Smears that are too thick can cause artifacts (e.g., Rouleaux).
5:08 Key CBC Parameters: Important metrics include: WBC, RBC, Hemoglobin, Hematocrit, MCV (mean cell volume), RDW (red cell distribution width, size variation), and Platelet count (MPV, PDW). MCHC is preferred over MCH for hemoglobin concentration. CBC is typically run from a lavender top (EDTA) tube.
8:15 Normal Morphology: A normal smear (shown from Dr. Ramos’s blood) features normal leukocyte density (at 200x) and normal RBCs (biconcave disks).
Neutrophils (11:00): Most common adult WBC, segmented (3–5 lobes), with fine, pink granules. Hypersegmentation (>5 segments or >5% of cells) is abnormal.
Lymphocytes (12:44): Size of an RBC nucleus, thin blue cytoplasm. Most common WBC in newborns.
Monocytes (13:12): Large, blue-gray cytoplasm, often contains vacuoles (helpful for differentiation). Nucleus is variably shaped (can look band-like).
Eosinophils (15:01): Easiest to spot; chunky, "Barbie pink" granules (often refractile in H&E).
Basophils (16:13): Least common; chunky purple granules (often degranulated).
18:27 RBC Abnormalities & Hemolytic Anemia: Normal central pallor is about 1/3 of the cell. Spherocytes (loss of central pallor) are shown in a case of severe anemia (Hb 7.7), suggesting autoimmune hemolysis (DAT/Coombs test needed). Hemolysis is correlated with decreased haptoglobin and increased bilirubin/LDH.
25:05 Echinocytes and Elliptocytes:Echinocytes (burr cells, spiky) can be real (uremia) or artifacts (blood sitting too long). Elliptocytes (oval cells) are seen in asymptomatic Hereditary Elliptocytosis.
32:59 Microcytic Anemia:Iron deficiency anemia shows small cells with enlarged central pallor. Distinguishing from Thalassemia (34:50): Thalassemia often adheres to the Rule of Threes (Hb x 3 = Hct), but Iron deficiency does not. Thalassemia also tends to feature more Target Cells (Codocytes).
38:10 Macrocytic Anemia: Characterized by high MCV (e.g., 112) and hypersegmented neutrophils (>5 lobes), suggesting folate deficiency (more common) or B12 deficiency.
40:54 Post-Splenectomy/Fibrosis Findings:Teardrop cells (Dacryocytes) suggest bone marrow infiltration/fibrosis. Sickle cell patients (with auto-splenectomy) often exhibit Howell-Jolly bodies (nuclear remnants) and Pappenheimer bodies (iron).
43:46 Hemoglobin SC Disease: Characterized by irregular SC crystals inside the red cells.
Cold Agglutinins: RBCs clumped together; often resolved by warming the slide.
Green Granules of Death (54:18): Ominous finding in neutrophils (often liver failure); urgent clinical notification required. Distinct from Döhle bodies.
Intracellular Fungus (1:00:37): Small intracellular yeast (e.g., Histoplasma).
Malaria (1:02:27): Key distinction between P. vivax (round gametocyte, ring form) and P. falciparum (banana-shaped gametocyte, multiple rings, critical diagnosis).
Babesiosis (1:05:32): Tick-borne, shows ring forms and Maltese Cross (tetrad) structure.
Ehrlichia/Anaplasma (1:06:33): Intracytoplasmic morulae (blue blob); Anaplasma classically in neutrophils, Ehrlichia in monocytes (but real-life presentation varies). This is an urgent diagnosis.
57:33 Lymphoid Differentiation:Reactive lymphocytes (Downy cells, infectious mononucleosis) show "Dutch skirting" (oozing around RBCs). Blasts (immature cells) are typically "bullies" that push RBCs aside.
APL (Acute Promyelocytic Leukemia): Features Auer rods (Faggot cells) in blasts, often with bilobed/cottage loaf nuclei. The microgranular variant is shown. APL is a critical diagnosis due to associated coagulopathy (DIC) and specific, highly effective ATRA treatment (if classic 15;17 translocation is present).
CML (1:27:48): Chronic Myeloid Leukemia shows a wide spectrum of myeloid maturation (blasts, myelocytes, metamyelocytes, segmented neutrophils) and often basophilia/eosinophilia ("marrow has hit the blood"). Diagnosis requires the BCR-ABL translocation test.
1:32:51 Plasma Cell Neoplasms: Circulating plasma cells (eccentric nucleus, clock-face chromatin, pale perinuclear hof). Associated with Rouleaux formation (RBCs stacking like pennies/Rolo candies, minimum four cells required), suggesting myeloma or autoimmune disease.
1:35:06 Platelet Artifacts: Platelet aggregates (false thrombocytopenia, often due to EDTA anticoagulant) and platelet satellitism (platelets sticking to neutrophils, leading to machine undercounting).
1:38:35 Cryoglobulins: Amorphous blue material in the background, distinct from cell pathology.