Pancytopenia: Difference between revisions

Latest revision as of 12:14, 28 August 2023

Background

Combination of anemia (<120-130), neutropenia (<1.8), and platelet (<150)

Clinical Manifestations

Increased infections, from leukopenia
Bleeding, from thrombocytopenia
Angina and other hypoxemic symptoms, from anemia

Differential Diagnosis

See also aplastic anemia
Congenital causes (chronic pancytopenia)
- Telomere diseases: dyskeratosis congenita (early hair graying, pulmonary fibrosis, cirrhosis)
- Fanconi anemia (short statue, café-au-lait spots, skeletal abnormalities, urogenital abnormalities)
- GATA2 deficiency (persistent or unusual infections)
- CTLA4 deficiency (intestinal disease, adenopathy, infections, autoimmune disorders)
- Schwachman-Diamond syndrome (skeletal abnormalities, exocrine pancreatic dysfunction)
- Wiskott-Aldrich syndrome (eczema, recurrent infections, low IgM, elevated IgA/E)
Medication-induced
- Immunosuppressants, chemotherapy, radiation
- Antiseizure: carbamazepine, levetiracetam, phenytoin, phenobarbital, valproate
- Gout: Allergic bronchopulmonary aspergillosis, colchicine
- Antibiotics: coadministration of TMP-SMX and methotrexate, albendazole, chloramphenicol, cidofovir, dapsone, foscarnet, ganciclovir, linezolid, quinine, sulfonamides, zidovudine
- NSAIDs: aspirin, diclofenac, ibuprofen, indomethacin, phenylbutazone, salicylates, sulindac
- Anti-thyroid: methimazole, propylthiouracil
- Cardiovascular: aspirin, amiodarone, captopril, lisinopril, nifedipine, quinidine, ticlopidine
- Diuretics: acetazolamide, furosemide, thiazides
- GI: cimetidine, nizatidine
- Psychiatric: bupropion, lithium, valproate
- Exposures: benzene, MDMA, glue, pesticides, radiation, organic solvents
Decreased production
- Infection
  - Viral
    - Epstein-Barr virus: chronic active EBV and primary infection that results in hemophagocytic lymphohistiocytosis
    - Parvovirus B19: usually transient, but can also cause pure red cell aplasia
    - Cytomegalovirus, if immunocompromised
    - Hepatitis A virus
    - Human immunodeficiency virus
    - Dengue virus
  - Bacterial
    - Mycobacterium tuberculosis, in the context of disseminated disease
    - Leptospira
    - Brucella
    - Bartonella henselae and Bartonella quintana, causing bacillary angiomatosis involving liver and spleen
    - Mycoplasma pneumoniae, associated with fulminant infection and the presence of cold agglutinin disease
    - Ehrlichia chaffeensis, causing hemophagocytic lymphohistiocytosis
  - Fungal
    - Pneumocystis jirovecii, from bone marrow necrosis
  - Parasitic
    - Visceral leishmaniasis
- Malignancy
  - Hematologic malignancy
  - Solid organ malignancy
    - Metastases
- Other
  - Sarcoidosis
  - Amyloidosis
- Nutritional
  - Vitamin B12 deficiency
  - May be from underlying severe caloric restriction, eating disorder, bariatric surgery, malabsorption, or alcohol use
Increased destruction with decreased production: autoimmune disorders, PNH, hematologic malignancies, HLH, sepsis
Increased destruction (hemolysis with increased reticulocytes): Evan syndrome, thrombotic microangiopathy, DIC
Sequestration (splenomegaly): portal hypertension, cirrhosis, infections, autoimmune disorders, myeloproliferative neoplasm, leukemia, lymphoma, storage diseases

Investigations

Initial investigations:
- Review prior CBCs to determine chronicity
- CBC with differential and reticulocyte count
- Peripheral blood film
  - Leukoerythroblastic reaction: BM infiltration and sepsis
  - Blasts: AML or ALL
  - Pelger-Huet anomaly or dysplasia: MDS
  - Megaloblastic: B12 or folate deficiency
  - Atypical lymphocytes: viral (such as EBV)
  - Schistocytes: DIC, sepsis, TMA
- Lytes/creatinine, uric acid, LDH
- Liver panel
- Coags
- Iron studies
- ESR/CRP
Consider the following, based on initial workup:
- Copper, zinc, B12/MMA, folate
- HLH workup
- Infectious workup
- Haptoglobin
- HIV, EBV, CMV, HBV, HCV, HHV6, parvovirus
- ANA, ENA
- DIC panel
Then consider the following, based on initial workup:
- Flow cytometry
- Tuberculosis or fungal workup
- US/CT/MRI/PET-CT
- Bone marrow aspirate and biopsy

@@ Line 1: / Line 1: @@
+== Background ==
-==Differential Diagnosis==
+* Combination of anemia (<120-130), neutropenia (<1.8), and platelet (<150)
-*Decreased production
+==Clinical Manifestations==
+*Increased infections, from [[leukopenia]]
+*Bleeding, from [[thrombocytopenia]]
+*Angina and other hypoxemic symptoms, from [[anemia]]
+== Differential Diagnosis ==
+*See also [[aplastic anemia]]
+*'''Congenital causes''' (chronic pancytopenia)
+**Telomere diseases: [[dyskeratosis congenita]] (early hair graying, [[pulmonary fibrosis]], [[cirrhosis]])
+**[[Fanconi anemia]] (short statue, [[Café-au-lait spot|café-au-lait spots]], skeletal abnormalities, urogenital abnormalities)
+**[[GATA2 deficiency]] (persistent or unusual infections)
+**[[CTLA4 deficiency]] (intestinal disease, adenopathy, infections, autoimmune disorders)
+**[[Schwachman-Diamond syndrome]] (skeletal abnormalities, exocrine pancreatic dysfunction)
+**[[Wiskott-Aldrich syndrome]] (eczema, recurrent infections, low IgM, elevated IgA/E)
+*'''Medication-induced'''
+**[[Immunosuppressive therapy|Immunosuppressants]], [[chemotherapy]], [[Radiation therapy|radiation]]
+**Antiseizure: [[carbamazepine]], [[levetiracetam]], [[phenytoin]], [[phenobarbital]], [[valproate]]
+**Gout: [[Allopurinol|Allergic bronchopulmonary aspergillosis]], [[colchicine]]
+**Antibiotics: coadministration of [[TMP-SMX]] and [[methotrexate]], [[albendazole]], [[chloramphenicol]], [[cidofovir]], [[dapsone]], [[foscarnet]], [[ganciclovir]], [[linezolid]], [[quinine]], [[Sulfonamide|sulfonamides]], [[zidovudine]]
+**NSAIDs: [[aspirin]], [[diclofenac]], [[ibuprofen]], [[indomethacin]], [[phenylbutazone]], [[Salicylate|salicylates]], [[sulindac]]
+**Anti-thyroid: [[methimazole]], [[propylthiouracil]]
+**Cardiovascular: [[aspirin]], [[amiodarone]], [[captopril]], [[lisinopril]], [[nifedipine]], [[quinidine]], [[ticlopidine]]
+**Diuretics: [[acetazolamide]], [[furosemide]], [[Thiazide|thiazides]]
+**GI: [[cimetidine]], [[nizatidine]]
+**Psychiatric: [[bupropion]], [[lithium]], [[valproate]]
+**Exposures: [[benzene]], [[MDMA]], glue, [[Pesticide|pesticides]], [[Radiation toxicity|radiation]], organic solvents
+*'''Decreased production'''
 **Infection
-***Viral infection
+***Viral
-****[[Epstein-Barr virus]]
+****[[Epstein-Barr virus]]: chronic active EBV and primary infection that results in [[hemophagocytic lymphohistiocytosis]]
-****[[Parvovirus B19]]
+****[[Parvovirus B19]]: usually transient, but can also cause pure red cell aplasia
 ****[[Cytomegalovirus]], if immunocompromised
+****[[Hepatitis A virus]]
 ****[[Human immunodeficiency virus]]
 ****[[Dengue virus]]
+***Bacterial
-****[[Viral hepatitis]]
+****[[Mycobacterium tuberculosis]], in the context of disseminated disease
-***Other
-****[[Leptospirosis]]
+****[[Leptospira]]
+****[[Brucella]]
+****[[Bartonella henselae]] and [[Bartonella quintana]], causing [[bacillary angiomatosis]] involving liver and spleen
+****[[Mycoplasma pneumoniae]], associated with fulminant infection and the presence of cold agglutinin disease
+****[[Ehrlichia chaffeensis]], causing [[hemophagocytic lymphohistiocytosis]]
+***Fungal
+****[[Pneumocystis jirovecii]], from bone marrow necrosis
+***Parasitic
+****[[Visceral leishmaniasis]]
 **Malignancy
 ***[[Hematologic malignancy]]
-***[[Solid-organ malignancy]]
+***[[Solid organ malignancy]]
 ****[[Metastases]]
 **Other
 ***[[Sarcoidosis]]
 ***[[Amyloidosis]]
+**Nutritional
-**Systemic
 ***[[Vitamin B12 deficiency]]
+***May be from underlying severe caloric restriction, [[eating disorder]], bariatric surgery, [[malabsorption]], or alcohol use
-*Increased destruction
+*'''Increased destruction with decreased production''': autoimmune disorders, [[PNH]], [[Hematologic malignancy|hematologic malignancies]], [[HLH]], [[sepsis]]
-*Sequestration
+*'''Increased destruction''' ([[hemolysis]] with increased reticulocytes): [[Evan syndrome]], [[thrombotic microangiopathy]], [[DIC]]
+*'''Sequestration''' (splenomegaly): [[portal hypertension]], [[cirrhosis]], infections, autoimmune disorders, [[myeloproliferative neoplasm]], [[leukemia]], [[lymphoma]], storage diseases
+== Investigations ==
-==Clinical Manifestations==
+* Initial investigations:
-*Increased infections
+** Review prior CBCs to determine chronicity
-*Bleeding
+** CBC with differential and reticulocyte count
-*Angina and other hypoxemic symptoms
+**Peripheral blood film
+***[[Leukoerythroblastic reaction]]: BM infiltration and sepsis
+***Blasts: [[AML]] or [[ALL]]
+***[[Pelger-Huet anomaly]] or dysplasia: [[MDS]]
+***Megaloblastic: [[Vitamin B12 deficiency|B12]] or [[Folate deficiency|folate]] deficiency
+***Atypical lymphocytes: viral (such as [[EBV]])
+***Schistocytes: [[DIC]], [[sepsis]], [[TMA]]
+** Lytes/creatinine, uric acid, LDH
+** Liver panel
+** Coags
+** Iron studies
+** ESR/[[CRP]]
+* Consider the following, based on initial workup:
+** Copper, zinc, B12/MMA, folate
+** [[HLH]] workup
+** Infectious workup
+** Haptoglobin
+** [[HIV]], [[EBV]], [[CMV]], [[HBV]], [[HCV]], [[HHV6]], [[parvovirus]]
+** ANA, ENA
+** DIC panel
+* Then consider the following, based on initial workup:
+** Flow cytometry
+** Tuberculosis or fungal workup
+** US/CT/MRI/PET-CT
+** Bone marrow aspirate and biopsy
 [[Category:Hematology]]