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)
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
- Etiology
- Leukoerythroblastic Smear: smear with precursor cells of the myeloid and erythroid lineage, which usually indicates the presence of extramedullary hematopoiesis (predominantly in the spleen)
- 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)
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