Postscript

Introduction

Pancytopenia is defined as a decrease in all three blood cell lines.
Pancytopenia can be associated with a multitude of disease states, some of which are life-threatening.
Patients may be asymptomatic or they may present with symptoms related to the cytopenias or the underlying disease causing the cytopenias.
Pancytopenia is one of the most common reasons for consultation from hematologists.
Pancytopenia is not a disease in itself but rather a finding due to an underlying disease process affecting the bone marrow or the peripheral cell lines.
Note: Many disorders that cause pancytopenia can also cause bicytopenia.

Definitions

Pancytopenia is defined as a decrease in all three blood cell lines:
- Anemia is defined as Hb < 12 g/dL in women, < 13 g/dL in men
- Leukopenia is defined as white blood cell count < 3.6 x 10⁹/L
  - Neutropenia is defined as absolute neutrophil count < 1.8 x 10⁹/L
- Thrombocytopenia is defined as platelet count < 150 x 10⁹/L

Classification

Pancytopenia may be:
- Inherited vs acquired
- Transient or acquired
- Mild, moderate or severe
- Pancytopenia may be malignant or benign
Mechanistic classification:
- Bone marrow underproduction
- Bone marrow infiltration
- Destruction
- Sequestration

Causes of pancytopenia (according to predominant mechanism)

Impaired production – reduced to absent hematopoiesis
- Congenital aplastic anemia:
  - Fanconi anemia
  - Shwachman-Diamond syndrome
  - Dyskeratosis congenita
  - Congenital amegakaryocytic thrombocytopenia
  - HLH
- Acquired aplastic anemia
  - Idiopathic (immune-mediated) – the majority of cases (70%-80%)
  - PNH
  - Hypoplastic MDS
  - Drugs:
    - Chloramphenicol
    - NSAIDs
    - Antithyroid drugs:
      - Methimazole
      - Propylthiouracil
      - Methylthiouracil
    - Corticosteroids
    - Penicillamine
    - Allopurinol
    - Gold
    - Ticlopidine
    - Antihistamines:
      - Cimetidine
      - Ranitidine
      - Chlorpheniramine
    - Lithium
  - Chemicals
    - Benzene
    - Insecticides
    - Potassium perchlorate
    - Hydrocarbon-based glue vapors
  - Radiation – bone marrow hypoplasia develops at cumulative doses > 5 Gy
  - Alcohol
  - Infections:
    - Parvovirus B19
    - HIV
    - Hepatitis – typically non-A, non-B, non-C, non-G hepatitis
    - Epstein Barr virus
    - Cytomegalovirus
    - Herpes simplex virus
    - Herpes zoster
    - Adenovirus
  - Pregnancy
  - Copper deficiency
  - HLH
  - Medical disorders:
    - Graves disease
    - Eosinophilic fasciitis
    - Thymoma and thymic carcinoma
Bone marrow infiltrative (replacement) disorders
- Cells:
  - Benign:
    - B12 deficiency
    - Folate deficiency
  - Malignant:
    - Metastatic cancer
    - Hematological
      - Leukemias:
        
        Acute leukemias
        
        Chronic leukemias/myeloproliferative neoplasms (MPN)
      - Myelodysplastic syndromes (MDS)
      - Multiple myeloma
- Extracellular substances
  - Collagen (fibrotic diseases):
    - Primary myelofibrosis
    - Malignant lymphomas
    - Autoimmune fibrosis
  - Granulomas:
    - Sarcoidosis
    - Disseminated miliary tuberculosis
  - Storage diseases:
    - Gaucher disease
  - Anorexia nervosa with gelatinous degeneration
Peripheral destruction
- Autoimmune hemolytic pancytopenia, especially SLE
Sequestration – hypersplenism:
- Portal hypertension/cirrhosis
- Infections (eg, EBV)
- Autoimmune disorders (eg, SLE, RA/Felty syndrome)
- Malignancies (eg, lymphomas, MPN)
- Myelofibrosis with myeloid metaplasia
- Storage diseases (eg, Gaucher)

Note: many of the underlying causes involve multiple mechanisms that result in pancytopenia

Clinical presentation

Patients may be diagnosed incidentally with a complete blood count.
Patients may present with symptoms related to:
- Cytopenias:
  - Anemia:
    - Fatigue
    - Shortness of breath
    - Exercise intolerance
    - Chest pain
    - Headache
  - Leukopenia:
    - Fevers
    - Chills
    - Symptoms of focal infection
  - Thrombocytopenia:
    - Petechiae
    - Purpura
    - Bleeding
- Underlying cause of the pancytopenia
History should address:
- Chronicity of pancytopenia
- Constitutional symptoms, including fevers, night sweats, and/or weight loss
- Nausea, vomiting, and jaundice that may be associated with liver disease
- Alcohol intake
- Medications
- Personal and occupational exposures

Diagnosis

Diagnosis confirmed by complete blood count showing reduction in all three blood cell types.
Other tests include:
- Reticulocyte count:
  - Low in most cases
  - May be elevated in patients with:
    - Hypersplenism
    - Autoimmune pancytopenia

- Peripheral smear

Other labs as shown in graphic:

Treatment

Regardless of the underlying cause of pancytopenia, patients who are clinically unstable from their low counts require urgent stabilization and may need hospitalization with supportive therapy including:
- Blood transfusions
- Antibiotics
- Cytokines:
  - G-CSF
  - t-PO receptor agonists
Treatment is geared towards the underlying disease.

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