4.2 Hematologic

Key Takeaways

  • The Hematologic System is 4% of the PANRE blueprint; the highest-yield skill is classifying anemia by mean corpuscular volume into microcytic, normocytic, and macrocytic categories
  • Iron deficiency is the most common cause of microcytic anemia and typically shows low ferritin, low serum iron, and high total iron-binding capacity
  • Vitamin B12 and folate deficiency cause macrocytic megaloblastic anemia; B12 deficiency can also cause neurologic deficits that folate does not
  • Warfarin is monitored with the INR, while heparin-class and direct oral anticoagulants have distinct monitoring and reversal considerations
  • Acute leukemia presents with rapid marrow failure (anemia, infection, bleeding), whereas Hodgkin lymphoma is classically associated with Reed-Sternberg cells
Last updated: May 2026

The Hematologic System is 4% of the NCCPA PANRE blueprint. Although it is a lower-weight section, the topics overlap heavily with cardiovascular, infectious disease, and oncology questions, so the return on review is high. The recurring testable skill is interpreting a complete blood count (CBC) and coagulation studies, then choosing the next diagnostic or management step.

Classifying Anemia

The mean corpuscular volume (MCV) is the anchor. Classify first, then work up.

MCV CategoryCommon CausesKey Labs
Microcytic (low MCV)Iron deficiency, thalassemia, anemia of chronic disease (can be normocytic)Ferritin, iron studies
Normocytic (normal MCV)Acute blood loss, anemia of chronic disease, hemolysis, renal diseaseReticulocyte count, hemolysis labs
Macrocytic (high MCV)Vitamin B12 deficiency, folate deficiency, alcohol use, hypothyroidismB12, folate, peripheral smear

Iron Deficiency vs Anemia of Chronic Disease

Iron deficiency anemia is the most common anemia worldwide. It shows low ferritin, low serum iron, and high total iron-binding capacity (TIBC). In adults, new iron deficiency without an obvious source raises concern for occult gastrointestinal blood loss. Anemia of chronic disease typically shows normal or high ferritin (an acute-phase reactant) with low TIBC.

Macrocytic Anemia

Vitamin B12 and folate deficiency cause megaloblastic macrocytic anemia, often with hypersegmented neutrophils on smear. A critical distinction: B12 deficiency can cause neurologic findings (peripheral neuropathy, subacute combined degeneration); folate deficiency does not. Replacing folate alone in true B12 deficiency can mask the anemia while neurologic damage progresses.

Bleeding and Clotting Disorders

Use the coagulation panel to localize the defect.

FindingSuggests
Isolated prolonged PT/INROften warfarin effect or vitamin K-dependent factor issue
Isolated prolonged aPTTHeparin effect, hemophilia, or factor deficiency in that pathway
Low plateletsThrombocytopenia (ITP, drug-induced, marrow disease, consumption)
Prolonged PT and aPTT with low platelets and low fibrinogenDisseminated intravascular coagulation (DIC)
  • Immune thrombocytopenia (ITP) is isolated low platelets without another explanation.
  • Von Willebrand disease is the most common inherited bleeding disorder.
  • Hemophilia A and B are X-linked factor deficiencies causing deep tissue and joint bleeding.
  • Venous thromboembolism (VTE): deep vein thrombosis and pulmonary embolism are the clotting-side counterpart and are managed with anticoagulation.

Anticoagulation

Agent ClassExampleMonitoringReversal Concept
Vitamin K antagonistWarfarinINRVitamin K; clotting factors for serious bleeding
Unfractionated heparinHeparinaPTTProtamine
Low-molecular-weight heparinEnoxaparinUsually none routinelyPartial protamine effect
Direct oral anticoagulant (DOAC)Apixaban, rivaroxaban, dabigatranNot routinely monitoredSpecific reversal agents exist for some

Exam items often test that warfarin is monitored with the INR and interacts with diet and many drugs, while heparin-class agents are parenteral with faster onset.

Leukemias and Lymphomas Overview

  • Acute leukemia (acute lymphoblastic or acute myeloid) causes rapid bone marrow failure: anemia, infection from neutropenia, and bleeding from thrombocytopenia.
  • Chronic leukemia (chronic lymphocytic or chronic myeloid) is often more indolent and may be found incidentally.
  • Hodgkin lymphoma is classically associated with Reed-Sternberg cells and can present with painless lymphadenopathy and B symptoms (fever, night sweats, weight loss).
  • Non-Hodgkin lymphoma is a broad, heterogeneous group of lymphoid malignancies.

Transfusion Concepts

Packed red blood cells raise oxygen-carrying capacity in symptomatic anemia. Type and crossmatch reduces incompatibility risk. Acute hemolytic transfusion reaction (often ABO mismatch) is a medical emergency requiring immediate transfusion cessation and supportive care. Febrile nonhemolytic and allergic reactions are more common but generally less catastrophic. Know the difference between stopping the transfusion versus slowing it based on reaction severity.

Exam Strategy

Classify by MCV before ordering studies, localize bleeding with PT/aPTT/platelets, and match anticoagulants to their monitoring test and reversal agent.

Relative Frequency of Anemia Categories Seen in Primary Care
Test Your Knowledge

A 47-year-old man has fatigue and a hemoglobin of 9.8 g/dL with a low MCV. Ferritin is low, serum iron is low, and total iron-binding capacity is high. What is the most appropriate next consideration?

A
B
C
D
Test Your Knowledge

A patient on chronic warfarin therapy presents with minor bleeding and a markedly elevated INR. Which test is used to monitor warfarin, and which agent is most appropriate to address the elevated INR in this setting?

A
B
C
D
Test Your Knowledge

Which laboratory pattern is most consistent with disseminated intravascular coagulation (DIC)?

A
B
C
D