12.1 Hematopoietic Pathology: Anemias, Polycythemia, Bleeding Disorders, DIC & Lymphoid and Myeloid Neoplasms
Key Takeaways
Iron deficiency causes microcytic, hypochromic anemia with low ferritin and high TIBC; anemia of chronic disease has low iron but normal or high ferritin, because hepcidin traps iron.
Hemolytic anemias show reticulocytosis, high unconjugated bilirubin and LDH, and low haptoglobin; spherocytes suggest hereditary spherocytosis or warm autoimmune hemolysis (Coombs test separates them).
G6PD deficiency (X-linked) causes episodic hemolysis with Heinz bodies and bite cells after oxidant drugs, infections or fava beans; thalassemias cause microcytosis with target cells and a normal or high RBC count.
Acute leukemias have more than 20% blasts in the marrow; Auer rods mark AML, and t(15;17) acute promyelocytic leukemia causes DIC and responds to all-trans retinoic acid.
Reed-Sternberg cells (CD15 and CD30 positive) define Hodgkin lymphoma; CML carries t(9;22) BCR-ABL; multiple myeloma causes lytic lesions, an M spike, Bence Jones proteinuria and hypercalcemia.
Why this area matters
The TOS lists:
- anemia of blood loss, hemolytic anemia and anemia of diminished erythropoiesis;
- polycythemia;
- bleeding disorders, hemorrhagic diathesis and DIC;
- lymphoid and myeloid neoplasms.
Anemia is very common in Filipino women and children, thalassemia and G6PD deficiency are prevalent, and dengue and leptospirosis produce bleeding and cytopenias. The same material is tested in Medicine and Pediatrics.
Anemia: approach by red cell size
| MCV | Main causes | Key findings |
|---|---|---|
| Microcytic (below 80 fL) | Iron deficiency, thalassemia, anemia of chronic disease (late), sideroblastic anemia (lead) | Iron deficiency: low ferritin, high TIBC, pencil cells, high RDW. Thalassemia: target cells, normal or high RBC count, low Mentzer index, abnormal hemoglobin electrophoresis |
| Normocytic (80 to 100 fL) | Acute blood loss, hemolysis, anemia of chronic disease, chronic kidney disease (low erythropoietin), marrow failure | Reticulocyte count separates high-output from low-output causes |
| Macrocytic (above 100 fL) | Megaloblastic: B12 or folate deficiency (hypersegmented neutrophils, oval macrocytes). Non-megaloblastic: liver disease, alcohol, hypothyroidism, reticulocytosis | B12 deficiency also causes neurologic disease (subacute combined degeneration) and raised methylmalonic acid |
Anemia of blood loss:
- In acute loss, the hemoglobin is initially normal because whole blood is lost. It falls as fluid shifts in over hours, and a reticulocyte response follows in days.
- Chronic loss (menstruation, hookworm, peptic ulcer, colon cancer) causes iron deficiency. In an adult man or postmenopausal woman, look for a GI source.
Anemia of chronic disease: IL-6 increases hepcidin, which blocks iron release from macrophages and iron absorption. Serum iron is low, TIBC is low, and ferritin is normal or high. It occurs in TB, rheumatoid arthritis and cancer.
Aplastic anemia: pancytopenia with a hypocellular, fatty marrow. Causes are idiopathic autoimmune, drugs (chloramphenicol), benzene, viruses (hepatitis, parvovirus B19 in hemolytic states) and Fanconi anemia.
Hemolytic anemias
Common laboratory signs are reticulocytosis, high unconjugated bilirubin (jaundice, pigment gallstones), high LDH and low haptoglobin. Intravascular hemolysis adds hemoglobinuria and hemosiderinuria.
| Disorder | Defect | Hallmarks |
|---|---|---|
| Hereditary spherocytosis | Membrane proteins (ankyrin, spectrin) | Spherocytes, high MCHC, osmotic fragility, splenomegaly; Coombs-negative; splenectomy curative |
| G6PD deficiency | X-linked enzyme defect, so less NADPH and glutathione | Episodic hemolysis after oxidants (primaquine, sulfonamides, nitrofurantoin), infection or fava beans; Heinz bodies and bite cells. Detected on Philippine newborn screening |
| Sickle cell disease | HbS (Glu to Val at beta-6) polymerizes when deoxygenated | Sickled cells, vaso-occlusive crises, autosplenectomy, Salmonella osteomyelitis; less common in Filipinos |
| Thalassemias | Reduced alpha- or beta-globin synthesis | Beta-thalassemia major (Cooley): severe anemia from about 6 months, "hair-on-end" skull, chipmunk face, hepatosplenomegaly, iron overload from transfusions. Alpha-thalassemia: HbH (beta-4), and hydrops fetalis with Hb Bart's (gamma-4). Alpha-thalassemia is common in Southeast Asia |
| Autoimmune hemolytic anemia | Warm (IgG, extravascular; SLE, CLL, drugs) or cold (IgM, complement; Mycoplasma, EBV) | Coombs-positive; spherocytes in the warm type |
| Microangiopathic | Red cells sheared in damaged small vessels | Schistocytes: DIC, TTP (ADAMTS13 deficiency), HUS (E. coli O157:H7), malignant hypertension, mechanical valves |
| Malaria | Parasite destroys red cells | Splenomegaly, hemoglobinuria (blackwater fever) |
Polycythemia
- Relative polycythemia comes from dehydration (low plasma volume).
- Secondary polycythemia comes from high erythropoietin: high altitude, COPD, cyanotic heart disease, or EPO-secreting renal cell carcinoma or hepatoma.
- Polycythemia vera is a myeloproliferative neoplasm with the JAK2 V617F mutation. Erythropoietin is low, with itching after bathing, plethora, thrombosis and splenomegaly.
Bleeding disorders
| Category | Examples | Typical test pattern |
|---|---|---|
| Vascular | Scurvy, Ehlers-Danlos syndrome, IgA vasculitis, dengue | Normal platelet count and coagulation tests; petechiae and purpura |
| Platelet number | ITP (antiplatelet IgG; acute in children after viral infection, chronic in adult women), drugs, marrow failure, dengue, hypersplenism, TTP | Low platelets; mucocutaneous bleeding |
| Platelet function | Von Willebrand disease (most common inherited bleeding disorder), Bernard-Soulier, Glanzmann, aspirin, uremia | Abnormal platelet function; vWD may prolong the aPTT |
| Coagulation factors | Hemophilia A (factor VIII) and B (factor IX), X-linked; vitamin K deficiency; liver disease | Prolonged aPTT and/or PT; deep tissue and joint bleeding |
| DIC | Sepsis, obstetric complications, trauma, cancer, envenomation | Low platelets, prolonged PT and aPTT, low fibrinogen, high D-dimer, schistocytes |
Myeloid neoplasms
- Acute myeloid leukemia (AML): more than 20% myeloblasts with Auer rods (myeloperoxidase positive), mostly in adults.
- Acute promyelocytic leukemia, t(15;17) PML-RARA, causes DIC and responds to all-trans retinoic acid and arsenic.
- Down syndrome raises the risk of acute megakaryoblastic leukemia (AML-M7).
- Chronic myeloid leukemia: t(9;22) Philadelphia chromosome, BCR-ABL. Marked leukocytosis with the full range of myeloid cells, basophilia, low leukocyte alkaline phosphatase and splenomegaly. Treated with imatinib. It may progress to blast crisis.
- Other myeloproliferative neoplasms: polycythemia vera, essential thrombocythemia and primary myelofibrosis (teardrop cells, dry tap) are associated with JAK2 mutations.
- Myelodysplastic syndromes: ineffective hematopoiesis with dysplasia (ring sideroblasts, pseudo-Pelger cells) in older adults. They can transform to AML.
Lymphoid neoplasms
- Acute lymphoblastic leukemia (ALL): the most common childhood cancer, with a peak at 2 to 5 years. Blasts are TdT positive. Most are pre-B (CD10, CD19); T-ALL presents with a mediastinal mass in adolescent boys. The t(12;21) translocation carries a good prognosis, and t(9;22) a poor one.
- Chronic lymphocytic leukemia / small lymphocytic lymphoma: the most common leukemia in older adults in Western countries. Smudge cells, CD5+ B cells, hypogammaglobulinemia and warm autoimmune hemolytic anemia.
- Hodgkin lymphoma:
- Reed-Sternberg cells (large, binucleate "owl-eye" cells, CD15 and CD30 positive) in a reactive background.
- Spreads contiguously, often from the cervical and mediastinal nodes.
- B symptoms are fever, night sweats and weight loss.
- Nodular sclerosis is the most common subtype, in young women. Mixed cellularity is linked to EBV.
- Non-Hodgkin lymphomas:
- Diffuse large B-cell lymphoma is the most common type.
- Follicular lymphoma carries t(14;18) BCL2.
- Burkitt lymphoma carries t(8;14) MYC, has a "starry-sky" pattern and is associated with EBV.
- Mantle cell lymphoma carries t(11;14) cyclin D1.
- MALT lymphoma is associated with H. pylori.
- Adult T-cell leukemia/lymphoma is caused by HTLV-1.
- Plasma cell neoplasms:
- Multiple myeloma shows marrow plasma cells, an M spike, Bence Jones proteinuria, lytic "punched-out" bone lesions, hypercalcemia, renal failure, anemia with rouleaux, and AL amyloidosis.
- Waldenström macroglobulinemia (IgM) causes hyperviscosity.
A 6-year-old boy develops dark urine, pallor and jaundice 2 days after taking primaquine for malaria. The smear shows bite cells and supravital staining reveals Heinz bodies. Which mechanism explains the hemolysis?
Deficient G6PD lowers NADPH, so red cells cannot keep glutathione reduced against oxidants
Mutant hemoglobin polymerizes when deoxygenated, distorting the cells
IgG antibodies coat red cells and are removed by splenic macrophages
Membrane spectrin deficiency produces spherocytes that are destroyed in the spleen during oxidant stress
A 35-year-old man has bleeding gums, extensive ecchymoses and fever. Labs show pancytopenia, prolonged PT and aPTT, low fibrinogen and high D-dimer. The marrow is packed with abnormal promyelocytes containing many Auer rods. Which genetic lesion and treatment apply?
t(15;17) PML-RARA; all-trans retinoic acid
t(9;22) BCR-ABL; imatinib
JAK2 V617F; phlebotomy
t(8;14) MYC; rituximab-based chemotherapy
A 68-year-old woman has back pain, anemia, hypercalcemia and rising creatinine. Skull X-ray shows multiple punched-out lytic lesions, and serum protein electrophoresis shows a monoclonal spike. What is the diagnosis?
Chronic lymphocytic leukemia
Multiple myeloma
Metastatic prostate carcinoma
Primary hyperparathyroidism
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