Introduction to hematology

Summary

Hematology is the study of blood and the organs that make it (bone marrow, spleen, lymph nodes, thymus). Blood has two parts:

• Plasma (55%) – water, proteins (albumin, clotting factors, immunoglobulins), electrolytes.
• Cells (45%) – red blood cells (RBCs), white blood cells (WBCs), and platelets.

All blood cells come from a single hematopoietic stem cell (HSC) in the bone marrow. They split into two main lines:

• Myeloid line → RBCs, platelets, granulocytes (neutrophil, eosinophil, basophil), monocytes.
• Lymphoid line → B cells, T cells, NK cells.

This first lesson gives you the framework you need before studying anemias, leukemias, bleeding disorders, and transfusion medicine. Focus on three big ideas:

1. How blood cells are made (hematopoiesis).
2. How blood stops bleeding (hemostasis).
3. How to read a basic CBC and peripheral smear.

Blood composition

When you spin a tube of blood in a centrifuge, it separates into three layers:

• Plasma (top, ~55%): yellow fluid; contains albumin, globulins, fibrinogen, clotting factors, hormones, electrolytes.
• Buffy coat (thin middle layer, <1%): WBCs and platelets.
• RBCs (bottom, ~45%): this volume = the hematocrit (Hct).

Serum = plasma after clotting (no fibrinogen, no clotting factors). This is what most chemistry tests use.

Key cell counts (adult)

• RBCs: 4.5–5.5 million/μL
• Hemoglobin (Hgb): M 13.5–17.5 g/dL · F 12–16 g/dL
• Hematocrit: M ~41–53% · F ~36–46%
• WBCs: 4,000–11,000/μL
• Platelets: 150,000–400,000/μL

Lifespan: RBC ~120 days · platelet ~7–10 days · neutrophil hours to days · lymphocyte days to years.

Hematopoiesis

Hematopoiesis = the process of making blood cells. It happens in different sites depending on age:

• 0–2 months fetal life: yolk sac
• 2–7 months: liver and spleen
• From 7 months onward: bone marrow
• Adult: bone marrow of axial skeleton (vertebrae, sternum, ribs, pelvis, proximal femur/humerus)

All cells start from one pluripotent hematopoietic stem cell (HSC), which divides into:

• Common myeloid progenitor → RBCs, platelets, granulocytes (neutrophil, eosinophil, basophil), monocytes/macrophages.
• Common lymphoid progenitor → B cells, T cells, NK cells.

Key cytokines (who tells the cells to grow?)

• EPO (erythropoietin, from kidney) → RBCs
• TPO (thrombopoietin, from liver) → platelets
• G-CSF → neutrophils · M-CSF → monocytes · GM-CSF → both
• IL-3 → "the bone marrow IL"; supports all lines
• IL-5 → eosinophils · SCF → stem cell survival

Red blood cells and hemoglobin

RBCs are biconcave discs, no nucleus, no mitochondria. They carry oxygen using hemoglobin (Hb).

Hemoglobin structure

• 4 globin chains + 4 heme groups (each holds 1 Fe²⁺ → binds 1 O₂)
• HbA (adult, >95%) = 2α + 2β
• HbA2 (~2%) = 2α + 2δ — ↑ in β-thalassemia
• HbF (fetal, <1% in adult) = 2α + 2γ — higher O₂ affinity

Oxygen-dissociation curve

The Hb curve is sigmoid (cooperative binding); myoglobin is hyperbolic. P50 of Hb ≈ 26 mm Hg.

• Right shift (Hb releases O₂ to tissues) → ↑ CO₂, ↑ H⁺ (low pH), ↑ temperature, ↑ 2,3-BPG. Think "exercising muscle."
• Left shift (Hb holds O₂) → opposite, plus HbF, CO poisoning, methemoglobin.

Erythropoiesis in 1 line

Low O₂ → kidney makes EPO → bone marrow makes RBCs (proerythroblast → erythroblast → normoblast → reticulocyte → mature RBC).

Reticulocyte count tells you if the marrow is responding: high = marrow working (e.g., hemolysis, bleeding); low = marrow failure or deficiency (Fe, B12, folate).

White blood cells

WBCs are the immune cells. Normal total = 4,000–11,000/μL.

Differential (typical adult)

• Neutrophils 40–70% – first responders to bacterial infection. Multi-lobed nucleus.
• Lymphocytes 20–40% – B, T, NK cells; viral infections, chronic inflammation.
• Monocytes 2–10% – mature into tissue macrophages.
• Eosinophils 1–6% – parasites, allergy.
• Basophils <1% – allergy, releases histamine.

Patterns to recognize

• Neutrophilia + left shift (more bands/immature forms) → acute bacterial infection.
• Lymphocytosis + atypical lymphocytes → viral (think EBV, CMV).
• Eosinophilia (NAACP): Neoplasia, Allergy/Asthma, Adrenal insufficiency, Collagen vascular disease, Parasites.
• Neutropenia (<1,500/μL) → infection risk; <500 = severe → febrile neutropenia is an emergency.

Memorize the differential percentages with the mnemonic "Never Let Monkeys Eat Bananas" in order of frequency: Neutrophil > Lymphocyte > Monocyte > Eosinophil > Basophil.

Hemostasis – primary and secondary

When a vessel is injured, the body stops the bleeding in two coordinated steps.

1. Primary hemostasis (platelet plug)

Happens in seconds. Involves platelets + von Willebrand factor (vWF).

1. Vasoconstriction – endothelial injury → reflex constriction.
2. Adhesion – platelets bind exposed collagen via vWF using GPIb receptor.
3. Activation – platelets release ADP, TXA2 → recruit more platelets.
4. Aggregation – platelets stick to each other via GPIIb/IIIa and fibrinogen.

Defects → mucocutaneous bleeding (gums, nose, petechiae, easy bruising). Examples: ITP, vWD, Bernard-Soulier (no GPIb), Glanzmann (no GPIIb/IIIa).

2. Secondary hemostasis (coagulation cascade)

Happens over minutes. Activates clotting factors → ends with fibrin stabilizing the platelet plug.

• Extrinsic pathway = tissue factor + VII. Measured by PT/INR. (Warfarin works here.)
• Intrinsic pathway = XII → XI → IX → VIII. Measured by aPTT. (Heparin works here.)
• Common pathway = X → V → II (prothrombin → thrombin) → I (fibrinogen → fibrin) → XIII (cross-links fibrin).

Defects → deep bleeding (hemarthrosis, intramuscular hematoma, delayed bleeding after surgery). Examples: hemophilia A (factor VIII), hemophilia B (IX), vitamin K deficiency (II, VII, IX, X, C, S).

Approach to anemia (MCV-based)

Anemia = ↓ hemoglobin (M <13.5 g/dL, F <12 g/dL) or ↓ hematocrit. Symptoms: fatigue, pallor, dyspnea, tachycardia.

The first step in classification is the MCV (mean corpuscular volume):

Normocytic is further split by reticulocyte count:

• High retic (>2%) → marrow is responding → hemolysis or acute bleed.
• Low retic → marrow not responding → aplastic anemia, CKD (low EPO), early IDA.

Key labs in anemia

• Iron studies: serum iron, ferritin, TIBC, transferrin saturation.
• Peripheral smear: shape (sickle, spherocyte, schistocyte), size, inclusions.
• Reticulocyte count + LDH + haptoglobin + bilirubin → look for hemolysis.

Click for the iron-studies reference table comparing IDA vs. thalassemia vs. ACD, and the macrocytic differential (MCV >100).

Approach to bleeding disorders

When a patient bleeds abnormally, ask three questions:

1. Where is the bleeding? Mucocutaneous (platelet/vWF problem) vs. deep tissue (coagulation factor problem).
2. What does the platelet count show? Low → thrombocytopenia; normal → think function defect or coagulation.
3. What do PT and aPTT show?

Click for the bleeding-disorder reference table comparing vWD, ITP, TTP/HUS, and DIC.

Essential lab tests in hematology

Complete Blood Count (CBC)

The starting point for almost every hematology problem. Look at:

• Hgb / Hct – anemia or polycythemia.
• MCV – classifies anemia by size.
• RDW – red cell size variation. ↑ in IDA, mixed deficiency.
• WBC + differential – infection, leukemia screening.
• Platelet count – thrombocytopenia or thrombocytosis.

Peripheral blood smear

Cheap but powerful. Look for abnormal shapes:

• Schistocytes (fragmented) → MAHA: TTP, HUS, DIC.
• Spherocytes → hereditary spherocytosis, warm AIHA.
• Target cells → thalassemia, liver disease, post-splenectomy.
• Sickle cells → sickle cell disease.
• Hypersegmented neutrophils → B12/folate deficiency.
• Howell-Jolly bodies → asplenia/hyposplenism.
• Basophilic stippling → lead poisoning, sideroblastic anemia.

Other key tests

• Reticulocyte count – marrow response.
• Iron studies – Fe, ferritin, TIBC, % saturation.
• LDH, haptoglobin, indirect bilirubin – hemolysis.
• Coombs test (DAT) – autoimmune hemolysis.
• PT, aPTT, INR, fibrinogen, D-dimer – coagulation.
• Bone marrow biopsy – when peripheral tests don't give the answer (leukemia, MDS, aplastic anemia, myeloma).

Mnemonics

Key Points for Exams – نقاط مهمة للامتحانات

• All blood cells come from a pluripotent HSC in the bone marrow → myeloid (RBCs, platelets, granulocytes, monocytes) and lymphoid (B, T, NK) lines.
• EPO from kidney drives RBC production; TPO from liver drives platelets.
• HbA = 2α2β · HbA2 = 2α2δ (↑ in β-thal) · HbF = 2α2γ (higher O₂ affinity).
• Right shift of O₂ curve = release O₂ to tissues (high CO₂, H⁺, 2,3-BPG, temperature).
• Primary hemostasis = platelet + vWF → mucocutaneous bleeding when broken.
• Secondary hemostasis = coagulation factors → deep bleeding (hemarthrosis) when broken.
• PT measures extrinsic (factor VII, warfarin); aPTT measures intrinsic (heparin, hemophilia).
• Vitamin K-dependent factors: II, VII, IX, X, C, S (mnemonic "1972 + CS").
• Anemia classification: start with MCV. <80 microcytic · 80–100 normocytic · >100 macrocytic. Then use reticulocyte count.
• Hemolysis labs: ↑ LDH, ↑ indirect bilirubin, ↓ haptoglobin, ↑ reticulocytes.
• Smear pearls: schistocytes = MAHA · spherocytes = HS/AIHA · target cells = thal/liver · sickle cells = SCD · hypersegmented neutrophils = B12/folate · Howell-Jolly = asplenia.
• Adult hematopoiesis happens in axial skeleton; extramedullary hematopoiesis (liver/spleen) appears in chronic hemolysis (β-thal major) or marrow failure.
• Febrile neutropenia (ANC <500 + fever) is a medical emergency – start broad-spectrum antibiotics immediately.