Etiology: Pancytopenia with Hypocellular Bone Marrow

Aplastic Anemia (see Aplastic Anemia)

Hereditary

• Amegakaryocytic Thrombocytopenia
• Down Syndrome
• Dubowitz Syndrome
• Dyskeratosis Congenita
• Familial Aplastic Anemia
• Fanconi Anemia
• Preleukemia: monosomy 7, etc
• Reticular Dysgenesis
• Seckel Syndrome
• Shwachman-Diamond Syndrome

Acquired

• Drug
  • Acetazolamide (see Acetazolamide, Acetazolamide): moderate risk of aplastic anemia
  • Acetylsalicylic Acid (Aspirin) (see Acetylsalicylic Acid, Acetylsalicylic Acid)
  • Allopurinol (see Allopurinol, Allopurinol): unclear association with aplastic anemia
  • Bismuth (see Bismuth, Bismuth)
  • Captopril (see Captopril, Captopril): low risk of aplastic anemia
  • Carbamazepine (see Carbamazepine, Carbamazepine)
  • Carbimazole: unclear association with aplastic anemia
  • Chloramphenicol
  • Chlordiazepoxide: unclear association with aplastic anemia
  • Chloroquine (see Chloroquine, Chloroquine)
  • Chlorothiazide (see Chlorothiazide, Chlorothiazide): low risk of aplastic anemia
  • Chlorpheniramine
  • Chlorpromazine: unclear association with aplastic anemia
  • Chemotherapeutic Cytotoxic Drugs: cause bone marrow depression at commonly employed doses
    • Alkylating Agents: busulfan, cyclophosphamide, melphalan, nitrogen mustard
    • Antimetabolites: 5-fluorouracil, mercaptopurine, methotrexate
    • Antimitotics
    • Cytotoxic Antibiotics: daunorubicin, doxorubicin, mitoxantrone
  • Cimetidine (see Cimetidine, Cimetidine)
  • Colchicine (see Colchicine, Colchicine)
  • Dapsone (see Dapsone, Dapsone): low risk of aplastic anemia
  • Estrogens: in pregnancy and in high doses in animal studies
  • Felbamate
  • Flucytosine: unclear association with aplastic anemia
  • Furosemide (see Furosemide, Furosemide): low risk of aplastic anemia
  • Gaunidine: unclear association with aplastic anemia
  • Gold (see Gold, Gold)
  • Ibuprofen (see Ibuprofen, Ibuprofen)
  • Indomethacin (see Indomethacin, Indomethacin)
  • Lithium (see Lithium, Lithium): unclear association with aplastic anemia
  • Mepacrine
  • Mebendazole: unclear association with aplastic anemia
  • Meprobamate: unclear association with aplastic anemia
  • Methicillin: unclear association with aplastic anemia
  • Methimazole (see Methimazole, Methimazole): low risk of aplastic anemia
  • Methlydopa: unclear association with aplastic anemia
  • Methylprylon: unclear association with aplastic anemia
  • Penicillamine (see Penicillamine, Penicillamine)
  • Phenacemide
  • Phenylbutazone (see Phenylbutazone, Phenylbutazone)
  • Phenytoin (Dilantin) (see Phenytoin, Phenytoin)
  • Piperacetazine: unclear association with aplastic anemia
  • Potassium Perchlorate: unclear association with aplastic anemia
  • Prochlorperazine: unclear association with aplastic anemia
  • Propylthiouracil (see Propylthiouracil, Propylthiouracil): low risk of aplastic anemia
  • Quinacrine
  • Quinidine: unclear association with aplastic anemia
  • Streptomycin: unclear association with aplastic anemia
  • Sulfamethoxazole-Trimethoprim (see Sulfamethoxazole-Trimethoprim, Sulfamethoxazole-Trimethoprim): unclear association with aplastic anemia
  • Sulfonamides: sulfa antibiotics, methimazole, methylthiouracil, propylthiouracil, tolbutamide, chlorpropamide, acetazolamide, methazolamide
  • Sulindac
  • Tetracycline (see Tetracycline, Tetracycline): unclear association with aplastic anemia
  • Thiocyanate: unclear association with aplastic anemia
  • Ticlopidine (see Ticlopidine, Ticlopidine): low risk of aplastic anemia
• Infection
  • Epstein-Barr Virus (see Epstein-Barr Virus, Epstein-Barr Virus)
  • Hepatitis (non-A, non-B, non-C)
  • Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus, Human Immunodeficiency Virus)
  • Parvovirus B19 (see Parvovirus B19, Parvovirus B19)
• Toxin
  • Arsenic (see Arsenic, Arsenic)
  • Benzene (see Benzene, Benzene): frequently produces bone marrow depression
  • Hydrocarbons (see Hydrocarbons, Hydrocarbons): chlorinated hydrocarbons
  • Mercury (see Mercury, Mercury)
  • Organophosphates (see Organophosphates, Organophosphates)
• Other
  • Eosinophilic Fasciitis
  • Graft vs Host Disease (see Graft vs Host Disease, Graft vs Host Disease)
  • Grave’s Disease (see Grave’s Disease, Graves Disease)
  • Hashimoto’s Thyroiditis (see Hashimoto’s Thyroiditis, Hashimotos Thyroiditis)
  • Hyperimmunoglobulinemia
  • Idiopathic Aplastic Anemia
  • Paroxysmal Nocturnal Hemoglobinuria (PNH) (see Paroxysmal Nocturnal Hemoglobinuria, Paroxysmal Nocturnal Hemoglobinuria)
  • Pregnancy (see Pregnancy, Pregnancy)
  • Radiation
  • Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis, Rheumatoid Arthritis)
  • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus, Systemic Lupus Erythematosus)
  • Thymoma/Thymic Carcinoma

Other

• Acute Lymphocytic Leukemia (ALL) (see Acute Lymphocytic Leukemia, Acute Lymphocytic Leukemia): some cases
• Aleukemic Leukemia
• Lymphoma (see Lymphoma, Lymphoma): involving bone marrow
• Myelodysplastic Syndrome (see Myelodysplastic Syndrome, Myelodysplastic Syndrome)

Etiology: Pancytopenia with Cellular Bone Marrow

Bone Marrow Infiltration

• Malignancy
  • Acute Lymphocytic Leukemia (ALL) (see Acute Lymphocytic Leukemia, Acute Lymphocytic Leukemia)
  • Acute Megakaryocytic Leukemia
  • Acute Myeloid Leukemia (AML) (see Acute Myeloid Leukemia, Acute Myeloid Leukemia)
  • Chronic Lymphocytic Leukemia (CLL) (see Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia)
  • Chronic Myeloid Leukemia (CML) (see Chronic Myeloid Leukemia, Chronic Myeloid Leukemia)
  • Hairy Cell Leukemia (see Hairy Cell Leukemia, Hairy Cell Leukemia)
  • Hodgkin’s Disease (see Hodgkin’s Disease, Hodgkins Disease)
  • Lymphoma (see Lymphoma, Lymphoma)
  • Metastases to Bone Marrow
    • Breast Cancer (see Breast Cancer, Breast Cancer)
    • Lung Cancer (see Lung Cancer, Lung Cancer)
    • Neuroblastoma
    • Prostate Cancer (see Prostate Cancer, Prostate Cancer)
    • Renal Cell Carcinoma (see Renal Cancer, Renal Cancer)
    • Sarcoma
    • Thyroid Cancer (see Thyroid Cancer, Thyroid Cancer)
  • Multiple Myeloma (see Multiple Myeloma, Multiple Myeloma)
  • Myelodysplastic Syndrome (see Myelodysplastic Syndrome, Myelodysplastic Syndrome)
  • Polycythemia Vera (see Polycythemia Vera, Polycythemia Vera)
  • Primary Myelofibrosis (see Primary Myelofibrosis, Primary Myelofibrosis): aka Idiopathic Myelofibrosis, Myelofibrosis with Myeloid Metaplasia, Agnogenic Myeloid Metaplasia
  • Systemic Mastocytosis (see Systemic Mastocytosis, Systemic Mastocytosis)
• Infection
  • Brucellosis (see Brucellosis, Brucellosis)
  • Histoplasmosis (see Histoplasmosis, Histoplasmosis)
  • Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus, Human Immunodeficiency Virus)
  • Leishmaniasis (see Leishmaniasis, Leishmaniasis)
  • Mucormycosis (see Mucormycosis, Mucormycosis)
  • Mycobacterium Avium Complex (MAC) (see Mycobacterium Avium Complex, Mycobacterium Avium Complex)
  • Toxoplasmosis (see Toxoplasmosis, Toxoplasmosis)
  • Tuberculosis (see Tuberculosis, Tuberculosis)
• Macrophages
  • Gaucher’s Disease (see Gaucher’s Disease, Gauchers Disease): marrow infiltration by macrophages containing indigestible material
  • Niemann-Pick Disease (see Niemann-Pick Disease, Niemann-Pick Disease): marrow infiltration by macrophages containing indigestible material
• Bone Marrow Necrosis
  • Arsenic (see Arsenic, Arsenic): associated with use for promyelocytic leukemia
  • Sepsis (see Sepsis, Sepsis): rare cases of bone marrow necrosis have been reported
  • Sickle Cell Disease (see Sickle Cell Disease, Sickle Cell Disease): bone marrow necrosis may occur
  • Tumors
• Other
  • Osteopetrosis
  • Oxalosis: marrow infiltration by calcium oxalate crystals
  • Sarcoidosis (see Sarcoidosis, Sarcoidosis): marrow infiltration by granulomas

Myelofibrosis/Myelophthisis

(myelofibrosis is marrow fibrosis due to a primary hematologic process, while myelophthisis is marrow fibrosis due to a non-hematologic process)

• Malignancy
  • Acute Lymphocytic Leukemia (ALL) (see Acute Lymphocytic Leukemia, Acute Lymphocytic Leukemia)
  • Acute Megakaryocytic Leukemia
  • Acute Myeloid Leukemia (AML) (see Acute Myeloid Leukemia, Acute Myeloid Leukemia)
  • Chronic Lymphocytic Leukemia (CLL) (see Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia)
  • Chronic Myeloid Leukemia (CML) (see Chronic Myeloid Leukemia, Chronic Myeloid Leukemia)
  • Hairy Cell Leukemia (see Hairy Cell Leukemia, Hairy Cell Leukemia)
  • Hodgkin’s Disease (see Hodgkin’s Disease, Hodgkins Disease)
  • Lymphoma (see Lymphoma, Lymphoma)
  • Metastases
    • Breast Cancer (see Breast Cancer, Breast Cancer)
    • Lung Cancer (see Lung Cancer, Lung Cancer)
    • Neuroblastoma
    • Prostate Cancer (see Prostate Cancer, Prostate Cancer)
    • Renal Cell Carcinoma (see Renal Cancer, Renal Cancer)
    • Sarcoma (see Sarcoma, Sarcoma)
    • Thyroid Cancer (see Thyroid Cancer, Thyroid Cancer)
  • Multiple Myeloma (see Multiple Myeloma, Multiple Myeloma)
  • Myelodysplastic Syndrome (see Myelodysplastic Syndrome, Myelodysplastic Syndrome)
  • Polycythemia Vera (see Polycythemia Vera, Polycythemia Vera)
  • Primary Myelofibrosis (see Primary Myelofibrosis, Primary Myelofibrosis): aka Idiopathic Myelofibrosis, Myelofibrosis with Myeloid Metaplasia, Agnogenic Myeloid Metaplasia
  • Systemic Mastocytosis (see Systemic Mastocytosis, Systemic Mastocytosis)
• Infection
  • Histoplasmosis (see Histoplasmosis, Histoplasmosis)
  • Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus, Human Immunodeficiency Virus)
  • Leishmaniasis (see Leishmaniasis, Leishmaniasis)
  • Mucormycosis (see Mucormycosis, Mucormycosis)
  • Mycobacterium Avium Complex (MAC) (see Mycobacterium Avium Complex, Mycobacterium Avium Complex)
  • Toxoplasmosis (see Toxoplasmosis, Toxoplasmosis)
  • Tuberculosis (see Tuberculosis, Tuberculosis)
• Macrophages
  • Gaucher’s Disease (see Gaucher’s Disease, Gauchers Disease): marrow infiltration by macrophages containing indigestible material
  • Niemann-Pick Disease (see Niemann-Pick Disease, Niemann-Pick Disease)
• Bone Marrow Necrosis
  • Sickle Cell Disease (see Sickle Cell Disease, Sickle Cell Disease): bone marrow necrosis may occur
• Other
  • Gray Platelet Syndrome
  • Hyperparathyroidism (see Hyperparathyroidism, Hyperparathyroidism)
  • Renal Osteodystrophy
  • Sarcoidosis (see Sarcoidosis, Sarcoidosis)
  • Systemic Lupus Erythematosus (see Systemic Lupus Erythematosus, Systemic Lupus Erythematosus)
  • Vitamin D Deficiency (see Vitamin D, Vitamin D)
  • Thorium Dioxide (see Thorium Dioxide, Thorium Dioxide)

Other

• Ethanol (see Ethanol, Ethanol)
• Folate Deficiency (see Folate, Folate)
• Hypersplenism (see Splenomegaly, Splenomegaly)
• Paroxysmal Nocturnal Hemoglobinuria (PNH) (see Paroxysmal Nocturnal Hemoglobinuria, Paroxysmal Nocturnal Hemoglobinuria)
• Vitamin B12 Deficiency (see Vitamin B12, Vitamin B12)

Etiology: Hypocellular Bone Marrow with/without Pancytopenia

• Anorexia Nervosa
• Legionellosis (see Legionellosis, Legionellosis)
• Mycobacterium Avium Complex (MAC) (see Mycobacterium Avium Complex, Mycobacterium Avium Complex)
• Q Fever (see Q Fever, Q Fever)
• Starvation
• Tuberculosis (see Tuberculosis, Tuberculosis)

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Diagnosis

• Peripheral Smear
  • Leukoerythroblastic Smear: smear with precursor cells of the myeloid and erythroid lineage, which usually indicates the presence of extramedullary hematopoiesis (predominantly in the spleen)
    • Etiology
      • Bone Marrow Infiltration
      • Myelofibrosis/Myelophthisis
      • Severe Stress: due to blood loss, infection, hemolysis, etc
    • Features
      • Immature Myeloid Cells
      • Megakaryocytic Fragments
      • Teardrop-Shaped RBC (Dacrocytes)
      • Immature Nucleated RBC
      • Anisocytosis
      • Poikilocytosis
      • Polychromasia
• Bone Scan: sensitive for detecting bone mets
• MRI: sensitive for marrow infiltration
• Bone Marrow Biopsy
  • Myelofibrosis/Myelophthisis: “dry tap” on aspirate (as fibrosis makes aspiration difficult), biopsy usually diagnostic
  • Tuberculosis: caseating granulomas with positive acid-fast organisms (granulomas also may have typical Langhans-type giant cells with multiple nuclei)

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Clinical

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References

• Bone marrow infiltration patterns and their prognostic significance in chronic lymphocytic leukemia: correlations with clinical, immunologic, phenotypic, and cytogenetic data. JCO June 1984 vol. 2 no. 6 562-570
• Intrasinusoidal bone marrow infiltration: a common growth pattern for different lymphoma subtypes. Br J Haematol. 2002 Dec;119(4):916-22
• Detection of bone marrow infiltration of lymphoma cells by fluorescence in situ hybridization. Clinica Chimica Acta Volume 344, Issues 1–2, June 2004, Pages 79–82