Hematologic and Vascular Foundations

Blood and the vascular system work together to deliver oxygen and nutrients, defend against infection, and stop bleeding without allowing clots to form where they are not needed. Hematologic and vascular disease develops when red cells cannot carry enough oxygen, white cells cannot defend the host, hemostasis tips toward bleeding or thrombosis, or the vessels and heart cannot maintain adequate perfusion (Davoren & Hsu, 2019; Mitrovic, 2019; Norris, 2020).

Study strategy: For each disorder, identify the normal function being lost, the primary defect, the compensatory response, the findings produced by that sequence, and the point at which compensation becomes harmful (Braun, 2026).

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Formed Elements and Hematopoiesis

• All formed elements arise from pluripotent hematopoietic stem cells in the bone marrow. In adults, active marrow is concentrated in the vertebrae, sternum, ribs, and pelvis (Davoren & Hsu, 2019; Norris, 2020).
• Erythropoietin, produced mainly by the kidneys in response to reduced oxygen delivery, drives red cell production. Chronic kidney disease removes this signal (Davoren & Hsu, 2019; Norris, 2020).
• Granulocyte colony-stimulating factor (G-CSF) and related cytokines drive neutrophil production, and thrombopoietin drives platelet production (Davoren & Hsu, 2019).
• Life spans differ widely: red cells survive about 120 days, platelets about 10 days, and neutrophils only hours in the circulation. When the marrow fails, neutrophil counts fall first and red cell counts last (Davoren & Hsu, 2019; Norris, 2020).
• Mature red cells lack nuclei and mitochondria, rely on glycolysis, and are removed by macrophages in the spleen. Heme is converted to bilirubin, which the liver conjugates for excretion (Norris, 2020).

Oxygen Delivery

Oxygen delivery depends on hemoglobin concentration, oxygen saturation, and cardiac output. Almost all oxygen is carried bound to hemoglobin, so a falling hemoglobin reduces arterial oxygen content even when PaO₂ and oxygen saturation are normal (Norris, 2020). The body compensates for anemia by increasing cardiac output, redistributing blood flow away from the skin and kidneys, and increasing red cell 2,3-bisphosphoglycerate, which shifts the oxyhemoglobin curve to the right and promotes oxygen unloading in tissues. Slowly developing anemia allows these adaptations to take effect, so a patient with chronic anemia may tolerate a hemoglobin level that would cause symptoms after acute blood loss (Davoren & Hsu, 2019; Norris, 2020).

Arterial oxygen content (approximate): CaO₂ ≈ 1.34 × Hb × SaO₂ (Braun, 2026)

Systemic oxygen delivery: DO₂ = CO × CaO₂ (Braun, 2026)

The Complete Blood Count

The complete blood count (CBC) reports the number of red cells, white cells, and platelets, along with red cell indices that describe cell size and hemoglobin content (Norris, 2020). Automated counts flag abnormal values, and a peripheral smear adds morphology, including target cells, hypersegmented neutrophils, fragmented red cells, large platelets, and immature white cells, and should be reviewed whenever a blood disorder is suspected (Davoren & Hsu, 2019).

Adult reference ranges vary by laboratory. Representative values include (Norris, 2020; Pereiras & Arnall, 2026):

• Hemoglobin: Men 14–16.5 g/dL; women 12–15 g/dL. Establishes whether anemia is present and how severe it is.
• Hematocrit: Men 40%–50%; women 37%–47%. Reflects plasma volume as well as red cell mass, so it rises with dehydration and falls with volume expansion.
• Red cell count: Men 4.2–5.4 × 10⁶/μL; women 3.6–5.0 × 10⁶/μL.
• Reticulocytes: 1.0%–1.5% of red cells. Indicates the rate of marrow red cell production.
• Mean corpuscular volume (MCV): 85–100 fL. Average cell size; the starting point for classifying anemia.
• Mean corpuscular hemoglobin concentration (MCHC): 31–35 g/dL. Hemoglobin concentration per cell; low values indicate hypochromia.
• Mean corpuscular hemoglobin (MCH): 27–34 pg/cell. Hemoglobin mass per cell; less useful for classification.
• Red cell distribution width (RDW): 11.5%–14.5%. Variation in cell size; a high RDW makes the MCV less reliable.

The hemoglobin and hematocrit can mislead in acute hemorrhage. Red cells and plasma are lost together, so both may appear normal until fluid shifts into the vascular space and dilutes the remaining red cells (Norris, 2020).

Classifying Anemia

Anemia results from blood loss, red cell destruction, defective production, or marrow failure (Norris, 2020). The MCV narrows the mechanism (Davoren & Hsu, 2019):

• Microcytic (low MCV): Impaired hemoglobin synthesis, as in iron deficiency and the thalassemias.
• Normocytic (normal MCV): Acute blood loss, hemolysis, marrow failure or infiltration, low erythropoietin in chronic kidney disease, and anemia of chronic inflammation.
• Macrocytic (high MCV): Impaired DNA synthesis from vitamin B12 or folate deficiency, drugs that interfere with DNA synthesis, myelodysplasia, or a high proportion of large young reticulocytes.

The reticulocyte count adds information the MCV cannot provide. About 1% of the red cell mass is replaced each day, so the count reflects real-time marrow activity (Norris, 2020). A high count in an anemic patient suggests blood loss or hemolysis with an appropriate marrow response. A low count suggests a production problem, such as missing iron, B12, or folate, low erythropoietin, or marrow suppression. Because the count is reported as a percentage of a reduced red cell mass, it should be interpreted in light of the degree of anemia (Norris, 2020).

Iron Studies

Iron studies help separate iron deficiency from anemia of chronic disease (Davoren & Hsu, 2019; Pereiras & Arnall, 2026):

• Serum ferritin: Low in iron deficiency; normal or high in anemia of chronic disease. Ferritin is the best indirect measure of body iron stores but is also an acute-phase reactant, so inflammation can raise it into the normal range despite true iron deficiency.
• Total iron-binding capacity (TIBC): High in iron deficiency; low in anemia of chronic disease.
• Serum iron and transferrin saturation: Low in both conditions, so neither separates them.
• Soluble transferrin receptor: High in iron deficiency and normal in anemia of chronic disease; a high soluble transferrin receptor-to-ferritin ratio supports iron deficiency when ferritin is not diagnostic.

The White Cell Differential

The differential reports the proportion of each white cell type and helps identify the process behind an abnormal count (Davoren & Hsu, 2019; Norris, 2020):

• Neutrophils (55%–65%): Increase with bacterial infection, inflammation, physiologic stress, and corticosteroids; decrease with chemotherapy, drug reactions, viral infection, marrow infiltration, and overwhelming sepsis.
• Lymphocytes (20%–30%): Increase with viral infections such as mononucleosis and with chronic lymphocytic leukemia; decrease with corticosteroids and HIV infection.
• Monocytes (3%–8%): Increase with chronic inflammation.
• Eosinophils (1%–3%): Increase with allergic reactions, asthma, and parasitic infection.
• Basophils (0.3%–0.5%): Increase with hypersensitivity reactions and chronic myelogenous leukemia.

A left shift is an increase in band neutrophils, immature cells released from the marrow storage pool during active infection; a rising band count suggests significant, usually systemic, infection (Davoren & Hsu, 2019; Norris, 2020). Stress neutrophilia occurs because corticosteroids and endogenous stress hormones release neutrophils normally adherent to vessel walls, so a mildly elevated count in a patient taking prednisone does not by itself indicate infection (Davoren & Hsu, 2019).

The absolute neutrophil count (ANC) predicts infection risk better than the neutrophil percentage and is calculated from the total white blood cell (WBC) count (Chan & Nguyen, 2026):

ANC = total WBC × (% segmented neutrophils + % bands)

Hemostasis

Hemostasis stops bleeding at a site of injury while keeping blood fluid elsewhere. It proceeds through three overlapping processes (Davoren & Hsu, 2019):

• Primary hemostasis: Vasoconstriction, then platelet adhesion to exposed subendothelium through von Willebrand factor, platelet activation, and aggregation into a platelet plug.
• Secondary hemostasis: Tissue factor exposed by injury activates factor VII and initiates thrombin generation. Thrombin activates platelets and factors V, VIII, and XI, and a burst of thrombin on the platelet surface converts fibrinogen to fibrin, which stabilizes the plug.
• Fibrinolysis: Plasmin breaks fibrin into degradation products, limiting clot size and removing the clot as the vessel heals.

Natural anticoagulants confine clotting to the injury. Activated protein C, with protein S as its cofactor, inactivates factors Va and VIIIa. Antithrombin inhibits thrombin and factors IXa, Xa, and XIa, an action accelerated up to 2000-fold by heparin. Tissue factor pathway inhibitor limits the initiation phase. Factors II, VII, IX, and X and proteins C and S depend on vitamin K, which is why warfarin affects both clotting factors and natural anticoagulants (Davoren & Hsu, 2019).

Platelet and Coagulation Testing

• Platelet count: Thrombocytopenia is usually defined as a count below 150,000/μL (Norris, 2020). The smear confirms a true low count, shows large platelets when production is increased, and identifies fragmented red cells in microangiopathic processes (Davoren & Hsu, 2019).
• Prothrombin time (PT) and international normalized ratio (INR): Assess the tissue factor (extrinsic) and common pathways and monitor warfarin. Factor VII has the shortest half-life of the vitamin K-dependent factors, so the PT prolongs first when these factors fall (Davoren & Hsu, 2019).
• Activated partial thromboplastin time (aPTT): Assesses the intrinsic and common pathways, prolongs with deficiency or inhibition of factors VIII and IX, and monitors unfractionated heparin (Davoren & Hsu, 2019).
• D-dimer: A marker of fibrin breakdown that is sensitive but nonspecific for thrombosis (Huynh et al., 2026).

The bleeding pattern often localizes the defect. Platelet disorders and von Willebrand disease produce mucocutaneous bleeding, including petechiae, purpura, epistaxis, gum bleeding, and heavy menses. Coagulation factor deficiencies produce deep bleeding into joints and muscles, large hematomas, and delayed bleeding after trauma or surgery (Norris, 2020). Von Willebrand disease impairs platelet adhesion and reduces factor VIII stability, while hemophilia A and B are factor VIII and IX deficiencies, respectively (Davoren & Hsu, 2019).

Blood Flow and Blood Pressure

Blood flow depends on the pressure difference across a vessel and the resistance to flow: Flow = ΔP / resistance. Mean arterial pressure is the product of cardiac output and systemic vascular resistance (Mitrovic, 2019):

Mean arterial pressure ≈ cardiac output × systemic vascular resistance

Resistance varies inversely with the fourth power of the vessel radius, so small changes in arteriolar diameter produce large changes in pressure and flow. Doubling a vessel’s radius reduces its resistance to about 6% of the original value (Mitrovic, 2019).

Each part of the vascular tree has a distinct role (Mitrovic, 2019; Norris, 2020):

• Arteries: Distribute pressure and flow; atherosclerosis narrows them and can weaken the wall to form aneurysms.
• Arterioles: The main resistance vessels; they set peripheral vascular resistance.
• Capillaries: The exchange surface, where hydrostatic pressure pushes fluid out at the arteriolar end and plasma oncotic pressure draws fluid back at the venular end. Excess filtered fluid returns through the lymphatics.
• Veins: High-capacity vessels that hold most of the blood volume and return it to the heart; venous pooling reduces preload.

Short-term pressure regulation depends on the baroreceptor reflex and the sympathetic nervous system, while long-term regulation depends on the kidney’s control of sodium and water balance, the renin-angiotensin-aldosterone system, and endothelial mediators such as nitric oxide (Mitrovic, 2019; Norris, 2020). Normal blood pressure falls during sleep, and loss of this nocturnal dipping is common in hypertension (Mitrovic, 2019).

Red Cells Across the Lifespan

The Neonate

Hemoglobin is high at birth, reflecting the red cell production needed for oxygen delivery in utero. Levels begin to decline at the end of the first week and reach a nadir at about 2 months, a physiologic anemia caused by reduced red cell production and dilution as blood volume grows. It seldom causes symptoms and does not respond to nutritional supplements. Neonatal red cells survive only 50 to 70 days, and fetal hemoglobin, which binds oxygen more tightly, is gradually replaced by adult hemoglobin, improving oxygen unloading. Anemia of prematurity is an exaggerated form driven by a poor erythropoietin response and compounded by frequent blood sampling (Norris, 2020).

Neonatal Hyperbilirubinemia

Physiologic jaundice appears on the second or third day of life in term infants. It reflects increased red cell breakdown combined with an immature liver that cannot yet conjugate bilirubin efficiently, and most cases resolve within a week (Norris, 2020).

Unconjugated bilirubin is lipid soluble, crosses the more permeable neonatal blood-brain barrier, and can deposit in the basal ganglia, causing kernicterus. Early signs include lethargy and poor feeding; severe injury produces rigidity, tremor, hearing loss, and seizures. Phototherapy converts bilirubin in the skin to a more water-soluble isomer that can be excreted, and exchange transfusion is reserved for signs of kernicterus or levels that continue to rise despite phototherapy (Norris, 2020). Bilirubin thresholds for treatment come from current pediatric guidelines, which the course texts do not cover.

Hemolytic Disease of the Newborn

An Rh-negative mother exposed to Rh-positive fetal red cells, usually at delivery, forms anti-Rh antibodies. The first Rh-positive infant is usually spared, but in later pregnancies maternal IgG crosses the placenta and hemolyzes fetal red cells, causing anemia, jaundice, and in severe cases hydrops fetalis, with a risk of kernicterus after birth. Rh immune globulin given at 28 weeks and within 72 hours of delivery, abortion, amniocentesis, or fetal-maternal bleeding prevents sensitization but is of no value once sensitization has occurred (Norris, 2020).

The Older Adult

Anemia becomes more common with age and is associated with increased mortality. Many older adults maintain normal hemoglobin at rest, but marrow reserve declines: active marrow shifts to the axial skeleton, progenitor numbers fall, and age-related inflammatory cytokines blunt the response to erythropoietin, so red cells are replaced more slowly after bleeding or other stress. Most anemia in asymptomatic older adults results from iron deficiency or anemia of chronic disease from inflammation, malignancy, or chronic kidney disease. Evaluation includes a smear, reticulocyte count and index, and assessment for gastrointestinal bleeding, malignancy, and pernicious anemia (Norris, 2020).

Evaluating Fatigue

Fatigue is one of the most common complaints in primary care and is a common symptom of anemia, but it is nonspecific. It is reported by 24% to 32% of adult primary care patients, and psychiatric causes such as depression and anxiety are more common than medical ones. Among medical causes, anemia, hypothyroidism, heart failure, chronic lung disease, sleep apnea, infection, malignancy, and medications are important considerations (Simons & Swallow, 2012).

High-yield questions include:

• Is the complaint fatigue, sleepiness, exertional dyspnea, or true muscle weakness?
• When did it begin, and has it progressed?
• Does it limit specific activities, or is the patient tired all the time?
• Are there weight loss, fever, or night sweats?
• Are there symptoms of bleeding, such as melena, hematochezia, or heavy menses?
• Are there neurologic symptoms, such as numbness, tingling, or balance problems?
• Which prescription and over-the-counter medications are being taken?
• Are depression, anxiety, substance use, or major life stressors present?

Fatigue linked to specific activities and accompanied by organ-specific symptoms is more likely to have a medical cause. Laboratory testing has little diagnostic value without suggestive history or examination findings, although anemia and thyroid disease are commonly identified through basic testing (Simons & Swallow, 2012).

Red Flags

Urgent evaluation is required for:

• Hemodynamic instability, syncope, or orthostatic changes with suspected blood loss
• Melena, hematochezia, or hematemesis
• Fever in a patient with known or suspected neutropenia
• Platelet count falling during heparin therapy
• Petechiae with a very low platelet count, or bleeding with neurologic change
• Simultaneous bleeding and thrombosis
• Microangiopathic hemolysis with thrombocytopenia
• Blood pressure above 180/120 mm Hg with signs of target-organ damage
• Altered mentation, oliguria, cool or mottled skin, or rising lactate
• New neurologic deficits with macrocytic anemia or known B12 deficiency

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References

Braun, C. (2026). Week 3: Overview of hematologic and vascular diseases [PowerPoint slides]. NRSG 435/535, College of Saint Benedict and Saint John’s University.

Chan, A., & Nguyen, L. (2026). Supportive care in oncology. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw Hill.

Davoren, J. B., & Hsu, G. (2019). Blood disorders. In G. D. Hammer & S. J. McPhee (Eds.), Pathophysiology of disease: An introduction to clinical medicine (8th ed.). McGraw-Hill Education.

Huynh, N. S., Cantrell, M., & Lee, J. C. (2026). Venous thromboembolism. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw Hill.

Mitrovic, I. (2019). Cardiovascular disorders: Vascular disease. In G. D. Hammer & S. J. McPhee (Eds.), Pathophysiology of disease: An introduction to clinical medicine (8th ed.). McGraw-Hill Education.

Norris, T. L. (2020). Porth’s essentials of pathophysiology (5th ed.). Wolters Kluwer.

Pereiras, M. A., & Arnall, J. R. (2026). Anemia. In M. A. Chisholm-Burns, P. M. Malone, J. M. Kolesar, K. C. Lee, P. B. Bookstaver, & K. R. Matthias (Eds.), Pharmacotherapy principles & practice (7th ed.). McGraw Hill.

Simons, R. J., & Swallow, N. A. (2012). Fatigue. In M. C. Henderson, L. M. Tierney, Jr., & G. W. Smetana (Eds.), The patient history: An evidence-based approach to differential diagnosis (2nd ed., pp. 58–69). McGraw-Hill Medical.