Pancytopenia resident survival guide

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sanjana Nethagani, M.B.B.S.[2]

Synonyms and keywords: Approach to pancytopenia, Pancytopenia management, Pancytopenia work-up

Pancytopenia Resident Survival Guide Microchapters


Pancytopenia is described as a decrease in the 3 cell lines which are red blood cells, white blood cells, and platelets. Clinically, pancytopenia is defined as hemoglobin< 9gm, white blood cell count< 4,000/cm and platelets < 100,000/cmm. It can be due to decreased production in the bone marrow or increased destruction of cells in the periphery. Pancytopenia can also be caused due to drugs such as chemotherapy agents. Treatment involves identifying the underlying cause and appropriate therapy.


Decreased production of cells

Increased peripheral destruction

Other causes

For a full list of pancytopenia causes, click here.


Diagnosis of pancytopenia is outlined in the algorithm below in accordance with the approach to pancytopenia: Diagnostic algorithm for clinical hematologists published in Blood Reviews,2018 and Pancytopenia: A Clinico Hematological study published in the Journal of Laboratory Physicians in 2011. [4][5]

Abbreviations: RBC- Red blood cell, WBC-White blood cell, HIV- Human Immunodeficiency Virus, LD body- Leishman-Donovan body, PCR- Polymerase chain reaction

Thorough history must be taken including
Symptoms of autoimmune disease such as
* Joint pain and swelling
* Lymphadenopathy etc
❑ History of malignancy
❑ History of recent infections
❑ History of usage of drugs which cause marrow suppression such as
* Azathioprine and other chemotherapy drugs
* Corticosteroids
* Linezolid
* Chloramphenicol etc
❑ History of chemo or radiotherapy
Nutritional status
❑ Family history of anemia or pancytopenia
Manifestations of decrease in each cell line
Decrease in RBCs
Chest pain
Decrease in WBCs
❑ Increased susceptibility to infections
Decrease in platelets
Easy bruising
Other signs to look for are
Signs of liver disease
Signs of eating disorders
Signs of alcoholism
Signs of Vitamin B12 or folate deficiency
First line investigations
Peripheral smear
Look for dysplastic cells such as Macrocytes and blasts
Complete blood count with reticulocyte count
Iron studies
Erythrocyte sedimentation rate
C reactive protein
Liver function tests
Lactate dehydrogenase level
Additional investigations
HIV serology
Hepatitis serology
❑ Screening for tuberculosis
Antinuclear antibody level
Coomb's test
Thyroid profile
Bone marrow aspiration
Hypocellular marrow
Cellular marrow
Investigate for following conditions
Aplastic anemia
❑ Congenital aplastic anemia such as Diamond-Blackfan syndrome
❑ Blast cell morphology and CD cell markers
Paroxysmal nocturnal hemoglobinuria
Normal morphology
Dysplastic cells, marrow fibrosis or infiltration
Systemic causes
Additional tests to confirm
Myelodysplastic syndrome
Infections such as
HIV serology
Hepatitis serology
❑ PCR for tuberculosis
❑ Smear for malarial parasite
❑ LD body for leishmaniasis
Megaloblastic anemia
❑ Vitamin assays
Antiparietal cell antibodies
❑ Evaluation for malabsorption syndromes


Treatment of pancytopenia is outlined in the algorithm below.[6]

Abbreviations: LDH- Lactate dehydrogenase, RBC- Red blood cell, G-CSF - Granulocyte colony stimulating factor, CNS- Central nervous system, ATG- Anti-thymocyte globulin, HIV- Human Immunodeficiency Virus, ART- Anti Retroviral Therapy

Pancytopenia diagnosis established
Hemoglobin < 10gm/dl
Leucocyte count < 4000/mcL
Platelet count < 150,000/mcL
Initial investigations
Peripheral blood smear
❑ Coagulation profile
❑ Serum LDH level
Complete blood count with reticulocyte level
Bilirubin level
Coomb's test
Acute bleeding
Prompt treatment with
❑ Insert two large bore IVs
❑ Type and match blood
❑ IV fluids to correct hypovolemia
❑ Packed RBCs
Fresh frozen plasma
Platelet transfusion for platelet count < 10,000/mcL to prevent intracranial bleeding
❑ Monitor vital signs and laboratory parameters at frequent intervals
Neutropenic fever
❑ Send two sets of blood cultures
❑ Empirical intravenous antibiotic therapy should be started with an antipseudomonal beta lactam such as cefepime/ a carbepenem or piperacillin-tazobactam
❑ Modify antibiotics once culture and sensitivity results come back
❑ If MRSA is suspected, vancomycin/daptomycin or linezolid may be started
❑ Empirical treatment with antifungals is not recommended
❑ Periodic assessment of response to therapy
❑ Monitor vitals regularly
G-CSF therapy is recommended in patients undergoing chemotherapy
Hypocellular marrow
Investigate for and treat probable causes such as
Aplastic anemia
* Drugs such as cyclophosphamide
* Blood transfusions
* Bone marrow transplant is curative
Paroxysmal nocturnal hemoglobinuria
* Warfarin to decrease risk of thrombosis
* Blood transfusions when needed
* Eculizumab therapy
* Meningococcal vaccination
Congenital aplastic anemia
* Hematopoietic stem cell transplant
Dysplastic cells in bone marrow or infiltration
* Induction and consolidation chemotherapy
* CNS prophylaxis
* Bone marrow transplant
* Chemotherapy
* rituximab
* stem cell transplantation
* Supportive care with blood products and erythropoietin
* Eligible candidates may receive a bone marrow transplant
* Chemotherapy
Nutritional causes
Vitamin B12 deficiency
* Initially, a single intramuscular dose of cobalamin is sufficient to reverse Vitamin B12 deficiency anemia
* Injections of cobalamin are associated with allergic reactions which can be circumvented with antihistamine therapy prior to treatment
* Maintenance therapy with a dose of 1,000 mcg every week or 6-8 times per month is required
Folate deficiency
* Folate deficiency often co-exists with Vitamin B12 deficiency
* Oral doses of 1-5 mg daily treats anemia
* In patients taking methotrexate, folonic acid is used to prevent folic acid deficiency
* Patients must be encouraged to take a diet rich in fresh fruit and vegetables
Other causes
* Partial splenic embolisation[7]
* Splenectomy
Systemic Lupus Erythematous[8]
* Erythropoietin stimulates erythropoiesis in anemia
* Autoimmune hemolytic anemia and thrombocytopenia in SLE responds to steroid therapy
* Refractory pancytopenia may be treated with cyclophosphamide
* Mycofenolate mofetil is used as an immunosuppressive agent in some refractory cases
* Other agents used are rituximab and eltrombopag
* Hypersplenism in sarcoidosis is treated with splenectomy
* Steroids and methotrexate are also used in treatment
Infectious causes
HIV infection[9]
* ART is effective in preventing and correcting pancytopenia in HIV infected individuals
* Opportunistic infections in HIV infection lead to pancytopenia through bone marrow suppression, thus prompt prophylaxis with relevant drugs may prevent this complication
* Hepatitis associated aplastic anemia is treated with bone marrow transplant
* ATG and cyclosporine are also used
* Other agents such as erythropoietin, G-CSF, androgens etc are used to improve cell counts
* Antitubercular medication such as rifampicin and pyrazinamide cause immune mediated hemolytic anemia, sideroblastic anemia and even agranulocytosis in some cases
* Prompt treatment with antituberular therapy regimen induces a reversal
Parvovirus B19 infection [12]
* Supportive therapy with blood and packed cell transfusions
* Bone marrow transplant with immunosuppressive therapy in severe cases
* Chloroquine therapy started immediately after detection of malarial infection reduces the risk of development of pancytopenia
* Frequent blood smears must be done to detect response to therapy



  • Don't prescribe aspirin or NSAIDs, or any other drugs that may precipitate bleeding in patients with pancytopenia.[16]
  • Don't wait for culture and sensitivity reports in case of neutropenic fever or sepsis in pancytopenic patients. Prompt treatment with broad-spectrum antibiotics is key.
  • Don't progress to treatment without correcting underlying nutritional deficiencies such as Vitamin B12 or folate deficiency.


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  2. Green AM, Kupfer GM (2009). "Fanconi anemia". Hematol Oncol Clin North Am. 23 (2): 193–214. doi:10.1016/j.hoc.2009.01.008. PMC 5912671. PMID 19327579.
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  7. Hanafiah M, Shahizon AM, Low SF, Shahrina MH (2013). "Severe thrombocytopenia due to hypersplenism treated with partial splenic embolisation". BMJ Case Rep. 2013. doi:10.1136/bcr-2013-010163. PMC 3736271. PMID 23833091.
  8. Bashal F (2013). "Hematological disorders in patients with systemic lupus erythematosus". Open Rheumatol J. 7: 87–95. doi:10.2174/1874312901307010087. PMC 3816272. PMID 24198852.
  9. Santiago-Rodríguez EJ, Mayor AM, Fernández-Santos DM, Hunter-Mellado RF (2015). "Profile of HIV-Infected Hispanics with Pancytopenia". Int J Environ Res Public Health. 13 (1): ijerph13010038. doi:10.3390/ijerph13010038. PMC 4730429. PMID 26703689.
  10. Rauff B, Idrees M, Shah SA, Butt S, Butt AM, Ali L; et al. (2011). "Hepatitis associated aplastic anemia: a review". Virol J. 8: 87. doi:10.1186/1743-422X-8-87. PMC 3052191. PMID 21352606.
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  12. Rajput R, Sehgal A, Jain D, Sen R, Gupta A (2012). "Acute parvovirus b19 infection leading to severe aplastic anemia in a previously healthy adult female". Indian J Hematol Blood Transfus. 28 (2): 123–6. doi:10.1007/s12288-011-0112-0. PMC 3332267. PMID 23730023.
  13. Albaker W (2009). "Acute Plasmodium vivax malaria presenting with pancytopenia secondary to hemophagocytic syndrome: case report and literature review". J Family Community Med. 16 (2): 71–3. PMC 3377033. PMID 23012194.
  14. Kerr JR (2015). "A review of blood diseases and cytopenias associated with human [[parvovirus B19]] [[infection]]". Rev Med Virol. 25 (4): 224–40. doi:10.1002/rmv.1839. PMID 25962796. URL–wikilink conflict (help)
  15. Kimura H, Cohen JI (2017). "Chronic Active Epstein-Barr Virus Disease". Front Immunol. 8: 1867. doi:10.3389/fimmu.2017.01867. PMC 5770746. PMID 29375552.
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