15.4 Hematopoietic System Pathology: Anemias, Coagulopathies, and Hematologic Neoplasms
Key Takeaways
- Microcytic anemia (MCV <80) is caused by iron deficiency, thalassemia, lead poisoning, or sideroblastic anemia; iron-deficiency anemia shows low serum iron and ferritin with high transferrin saturation, whereas thalassemia shows normal-to-high iron and target cells.
- Sickle cell disease (HbS, Glu6Val from a GAG→GTG point mutation) causes vaso-occlusive crisis, autosplenectomy with Howell-Jelly bodies, and a 500-fold increased risk of Salmonella osteomyelitis.
- Disseminated intravascular coagulation (DIC) shows the full coagulation profile deranged—prolonged PT/PTT, low fibrinogen, thrombocytopenia, and elevated D-dimer with schistocytes—because simultaneous microthrombi and consumption of platelets and factors coexist with fibrinolysis.
- Multiple myeloma (CD38/CD138 plasma cell neoplasm) produces a monoclonal M spike, CRAB criteria (hyperCalcemia, Renal failure, Anemia, Bone lesions), lytic punched-out lesions, and AL amyloidosis from light-chain overproduction.
- Hodgkin lymphoma is defined by Reed-Sternberg cells (CD15+/CD30+) arising from germinal-center B cells, while Burkitt lymphoma is driven by t(8;14) c-MYC translocation and classically presents as a jaw mass in the endemic (African) form linked to EBV.
15.4 Hematopoietic System Pathology
The NPLEX blueprint groups hematopoietic disease into five categories: production disorders, lysis disorders, clotting abnormalities, blood/lymph neoplasms, and infectious diseases of the blood. Because hematopoiesis, hemostasis, and hemoglobin biochemistry are taught in earlier chapters, this section focuses on clinicopathological recognition—the etiology, lab profile, and clinical consequences that distinguish each condition on a case-based vignette.
1. Diseases of Blood-Cell Production
Anemias are classified by MCV. Microcytic anemias (MCV <80) share the mechanism of impaired hemoglobin synthesis: iron deficiency (low serum iron, low ferritin, high TIBC), thalassemia (normal/high iron, target cells, basophilic stippling), lead poisoning (basophilic stippling, gum lead line, neuropathy), and sideroblastic anemia (ringed sideroblasts on Prussian blue, X-linked ALAS2 defect). Macrocytic anemia (MCV >100) reflects impaired DNA synthesis: megaloblastic anemia from B12 or folate deficiency (hypersegmented neutrophils, pancytopenia), with B12 deficiency additionally causing neurologic deficits (subacute combined degeneration) because B12 maintains myelin. Folate deficiency spares the nerves. Aplastic anemia is pancytopenia with a hypocellular marrow, from drugs, toxins, viruses (parvovirus B19, EBV, hepatitis), or idiopathic immune destruction of stem cells.
Polycythemia is an erythrocytosis. Polycythemia vera is a myeloproliferative neoplasm driven by a JAK2 mutation: autonomous RBC production with low erythropoietin, splenomegaly, itching after bathing, and thrombotic risk. Secondary polycythemia has high erythropoietin, driven by chronic hypoxia (high altitude, COPD), EPO-secreting tumors (renal cell), or rare high-affinity hemoglobin.
2. Diseases of Blood-Cell Lysis
Hemolytic anemias are divided into intravascular (schistocytes, hemoglobinemia, hemoglobinuria, high LDH, low haptoglobin) and extravascular (macrocytosis, splenomegaly, jaundice, pigment gallstones). Sickle cell disease (HbS, Glu6Val) polymerizes under deoxygenation, producing crescent cells, vaso-occlusive painful crises, splenic autoinfarction with Howell-Jolly bodies, and predisposition to Salmonella osteomyelitis and encapsulated-organism sepsis. Thalassemia is quantitative globin underproduction: α-thalassemia (chr 16, four genes; one-gene deletion is silent) and β-thalassemia (chr 11, two genes; major needs transfusions, with skull 'hair-on-end' radiographs). G6PD deficiency (X-linked) causes oxidative hemolysis after fava beans, primaquine, or sulfa drugs, with Heinz bodies and bite cells. Hereditary spherocytosis (autosomal dominant; spectrin/ankyrin defect) produces small dense cells that are destroyed in the spleen; osmotic fragility test confirms it and splenectomy is curative. Erythroblastosis fetalis is maternal anti-D (Rh) IgG crossing the placenta, prevented by Rho(D) immune globulin (RhoGAM) at 28 weeks and postpartum.
3. Clotting Abnormalities
| Disorder | Defect | Inheritance | Key labs | Bleeding type |
|---|---|---|---|---|
| Hemophilia A | Factor VIII | X-linked | ↑PTT, normal PT | Joint/muscle (deep) |
| Hemophilia B | Factor IX | X-linked | ↑PTT, normal PT | Deep |
| von Willebrand disease | vWF | AD (most common inherited) | ↑PTT (variable), abnormal ristocetin | Mucocutaneous |
| ITP | Anti-GPIIb/IIIa platelet destruction | Autoimmune | ↓platelets, ↑megakaryocytes | Mucocutaneous |
| DIC | Widespread coagulation activation | Acquired | ↑PT/PTT, ↓fibrinogen, ↓platelets, ↑D-dimer, schistocytes | Both + thrombosis |
| Vitamin K deficiency | Factors II,VII,IX,X, C,S | Acquired | ↑PT (early) | Mixed |
von Willebrand disease is the most common inherited bleeding disorder, with platelet-type mucocutaneous bleeding and abnormal ristocetin-induced platelet aggregation. ITP is peripheral platelet destruction with a compensatory megakaryocytic hyperplasia; acute ITP in children follows a viral illness and is self-limited, while chronic ITP in adults is treated with steroids, IVIG, or splenectomy. DIC is a consumptive coagulopathy triggered by sepsis, malignancy, obstetric catastrophe, or trauma: microvascular thrombosis and bleeding coexist, so the board-style vignette pairs a prolonged PT/PTT, low fibrinogen, thrombocytopenia, and elevated D-dimer with schistocytes on the smear. Vitamin K is a cofactor for the γ-carboxylation of factors II, VII, IX, X and proteins C/S; neonatal vitamin K deficiency is prevented by the routine IM vitamin K injection.
4. Blood & Lymph Neoplasms
Leukemias: ALL (children; CD10/CD19; favorable t(12;21), poor t(9;22)); AML (adults; Auer rods; t(15;17) acute promyelocytic leukemia is treated with ATRA); CML (myeloproliferative; t(9;22) Philadelphia chromosome forming BCR-ABL, treated with imatinib; high WBC, low LAP); CLL (older adults; smudge cells; CD5/CD23). Hodgkin lymphoma is defined by Reed-Sternberg cells (CD15+/CD30+) with B symptoms (fever, night sweats, weight loss); nodular sclerosis is the most common subtype. Non-Hodgkin lymphomas: follicular (t(14;18), BCL2, indolent); Burkitt (t(8;14), c-MYC, 'starry-sky' macrophages, jaw mass in endemic/EBV form, abdomen in sporadic); mantle cell (t(11;14), cyclin D1); diffuse large B-cell (aggressive, most common in West). Multiple myeloma is a plasma-cell neoplasm (CD38/CD138) producing a monoclonal M spike on serum protein electrophoresis; CRAB criteria—hyperCalcemia, Renal failure, Anemia, Bone lytic lesions—define the diagnosis; light-chain overproduction causes AL amyloidosis.
5. Infectious Diseases of the Blood
Malaria (Plasmodium; falciparum most severe, vivax/ovale have liver hypnozoites needing primaquine) produces cyclic fevers and intracellular trophozoites on smear. Babesiosis (Babesia microti via Ixodes tick) shows Maltese cross intraerythrocytic rings and hemolysis. Schistosomiasis drives a granulomatous response to deposited eggs, causing periportal fibrosis (Symmers pipestem) and hematuria (S. haematobium).
Key board signal: a child with painful crisis, pallor, and stroke-like symptoms → sickle cell; a neonate with pallor, jaundice, and hepatosplenomegaly in a Rh-incompatible pregnancy → erythroblastosis fetalis; an adult with epistaxis, heavy menses, and abnormal ristocetin → von Willebrand disease.
A 24-year-old African American man presents with severe chest pain and a hemoglobin of 7 g/dL. Peripheral smear shows sickled cells and Howell-Jolly bodies. He has a history of recurrent Salmonella osteomyelitis. Which molecular defect underlies this disease?
A 68-year-old man with sepsis and prolonged oozing from venipuncture sites has PT 40 s, PTT 55 s, fibrinogen 90 mg/dL, platelets 40,000, and D-dimer markedly elevated. Smear shows schistocytes. What is the most accurate description of the pathophysiology?