Pancytopenia resident survival guide

Jump to navigation Jump to search

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
Overview
Causes
Diagnosis
Treatment
Dos
Don'ts

Overview

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.

Causes

Decreased production of cells

Increased peripheral destruction

Other causes

For a full list of pancytopenia causes, click here.

Diagnosis

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
*Rash
* 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
Dyspnea
Fatigue
Pallor
Chest pain
Decrease in WBCs
❑ Increased susceptibility to infections
Fever
Decrease in platelets
Petechiae
Easy bruising
Bleeding
Other signs to look for are
Signs of liver disease
Splenomegaly
Lymphadenopathy
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
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Morphology
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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
Leukemia
Lymphoma
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

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
* ATG
* 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
Leukemia
* Induction and consolidation chemotherapy
* CNS prophylaxis
* Bone marrow transplant
Lymphoma
* Chemotherapy
* rituximab
* stem cell transplantation
Myelodysplasia
* 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
Hypersplenism
* 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
Sarcoidosis
* 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[10]
* 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
Tuberculosis[11]
* 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
Malaria[13]
* 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

Dos

Dont's

  • 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.

References

  1. Da Costa L, Narla A, Mohandas N (2018). "An update on the pathogenesis and diagnosis of Diamond-Blackfan anemia". F1000Res. 7. doi:10.12688/f1000research.15542.1. PMC 6117846. PMID 30228860.
  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.
  3. Marks PW (2013). "Hematologic manifestations of liver disease". Semin Hematol. 50 (3): 216–21. doi:10.1053/j.seminhematol.2013.06.003. PMID 23953338.
  4. Gnanaraj J, Parnes A, Francis CW, Go RS, Takemoto CM, Hashmi SK (2018). "Approach to pancytopenia: Diagnostic algorithm for clinical hematologists". Blood Rev. 32 (5): 361–367. doi:10.1016/j.blre.2018.03.001. PMID 29555368\ Check |pmid= value (help).
  5. Gayathri BN, Rao KS (2011). "Pancytopenia: a clinico hematological study". J Lab Physicians. 3 (1): 15–20. doi:10.4103/0974-2727.78555. PMC 3118050. PMID 21701657.
  6. Sharma R, Nalepa G (2016). "Evaluation and Management of Chronic Pancytopenia". Pediatr Rev. 37 (3): 101–111, quiz 112-3. doi:10.1542/pir.2014-0087. PMC 4764024. PMID 26933225.
  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.
  11. Hunt BJ, Andrews V, Pettingale KW (1987). "The significance of pancytopenia in miliary tuberculosis". Postgrad Med J. 63 (743): 801–4. doi:10.1136/pgmj.63.743.801. PMC 2428536. PMID 3444806.
  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.
  16. García Rodríguez LA, Martín-Pérez M, Hennekens CH, Rothwell PM, Lanas A (2016). "Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies". PLoS One. 11 (8): e0160046. doi:10.1371/journal.pone.0160046. PMC 4973997. PMID 27490468.