STEPTRACKERHEMATOLOGY | PATHOLOGY | HIGH-YIELD REVIEW

Marrow Failure & Polycythemia

Too few cells because the factory failed or was crowded out — and too many red cells, appropriately or not.

FOCUS ON
Aplastic anemia = pancytopenia + empty, fatty marrow (drugs, viruses, Fanconi). Myelophthisis = marrow crowded out → teardrop cells and a leukoerythroblastic smear. For polycythemia, measure EPO and SaO₂: PV has low EPO, hypoxia raises EPO, and tumors raise EPO with normal SaO₂.
DISORDER
MECHANISM
CAUSES · FEATURES
LABS · TREATMENT
Aplastic anemia
stem-cell failure
Hematopoietic stem cells destroyed (often by autoreactive T cells) → pancytopenia.
Idiopathic (most); drugs (chloramphenicol, benzene, alkylators, carbamazepine); radiation; viruses (non-A–E hepatitis, EBV, HIV, parvovirus in some)
Hypocellular fatty marrow, low retic, no splenomegaly · ATG + cyclosporine, stem cell transplant
Fanconi anemia
inherited
DNA crosslink repair defect (autosomal recessive mostly).
Short stature, absent/abnormal thumbs and radii, café-au-lait spots, pancytopenia in childhood
↑ AML and SCC risk; chromosome breakage test
Pure red cell aplasia
Only erythroid precursors lost.
Thymoma, parvovirus B19 (in hemolytic patients), Diamond-Blackfan (congenital)
Anemia with retic ≈ 0; WBC and platelets normal
Myelophthisic anemia
crowded marrow
Marrow replaced by tumor, fibrosis or granulomas.
Metastatic breast/prostate cancer, myelofibrosis, TB, Gaucher disease
Leukoerythroblastic smear: teardrop cells, nucleated RBCs, immature WBCs
Relative polycythemia
Plasma volume falls; RBC mass is normal.
Dehydration, burns, diuretics
Corrects with fluids
Polycythemia vera
primary
JAK2 V617F → RBC production without EPO.
Itching after a hot shower, plethora, erythromelalgia, splenomegaly, gout, thrombosis (Budd-Chiari)
↓ EPO; often ↑ WBC and platelets · phlebotomy, aspirin, hydroxyurea
Secondary — appropriate
hypoxia-driven
Low tissue O₂ → kidney ↑ EPO.
High altitude, COPD, sleep apnea, cyanotic heart disease, smoking (CO)
↑ EPO, ↓ SaO₂
Secondary — inappropriate
EPO made without hypoxia, or other stimulants.
RCC, HCC, hemangioblastoma, leiomyoma, pheochromocytoma; after kidney transplant; testosterone; EPO doping
↑ EPO, normal SaO₂

Mechanism — where production stops

Stem cellAplastic anemia, Fanconi
→
Erythroid progenitorPure red cell aplasia
→
Mature RBCReleased to blood
Kidney senses O₂Hypoxia → EPO ↑
→
EPO drives marrowSecondary polycythemia
→
JAK2 always onPV — no EPO needed

Sorting a high hematocrit

TYPE
RBC MASS
SaO₂
EPO
Relative
Normal
Normal
Normal
Polycythemia vera
↑
Normal
↓
Hypoxic secondary
↑
↓
↑
Tumor / inappropriate
↑
Normal
↑

How it's tested

COMMON CONFUSIONAplastic anemia has no splenomegaly and a fatty marrow. A big spleen or teardrop cells point to infiltration or myelofibrosis instead.
THE TRAPA high hematocrit with a low EPO level is PV until proven otherwise. A high EPO with normal oxygen saturation means look for a tumor (kidney first).
YOUR APPROACHLow counts: marrow cellularity and smear (empty vs infiltrated). High Hct: plasma volume → SaO₂ → EPO → JAK2.

If you see… think…

Pancytopenia, fatty empty marrow, no splenomegaly → aplastic anemia
Pancytopenia weeks after chloramphenicol → drug-induced aplastic anemia
Short child, absent thumbs, pancytopenia → Fanconi anemia
Isolated anemia with zero reticulocytes + mediastinal mass → thymoma with red cell aplasia
Teardrop cells and nucleated RBCs in a breast cancer survivor → myelophthisic marrow
Itching after hot showers, Hct 60%, low EPO → polycythemia vera (JAK2)
COPD patient with high Hct and high EPO → appropriate secondary polycythemia
Flank mass, high Hct, high EPO, normal SaO₂ → RCC
Dehydrated patient, high Hct, normal RBC mass → relative polycythemia