Pancytopenia DRUGS –see aplastic anaemia

It is a condition in which there is decrease in all three  Idiopathic cytopenia of undetermined significance
blood cell lines: RBCs, WBCs, and platelets. (Cytopenia which remains undiagnosed for more
than 6 months despite of adequate evaluation)
Causes:
History
1.HYPOCELLULAR BONE MARROW
 Symptoms of anemia (easy fatigability ,dyspnea
 Malignancies: Hypoplastic MDS/AML/ALL
on exertion,swelling of limbs )leucopenia (fever
,Lymphoma- HD/NHL
 Aplastic anaemia – acquired/inherited (see causes ,repeated infections-pneumonia ,skin
for aplastic anaemia ) ),thrombocytopenia(skin and mucus membrane
 DRUGS –see aplastic anaemia bleeding )

2.CELLULAR BONE MARROW  h/o infections/medications,exposure to toxins

 Family history of blood disorders, early graying
PRIMARY BONE MARROW of hair
 History of Diet/Habits
 Malignant: AML, ALL, Lymphoma,  Hairy cell
leukemia, myeloma, LGL Leukemia Examination
 Myelodysplastic syndrome
 Myelofibrosis: Primary and secondary  Pallor,bruises ,petichial rash ,fever, signs of sepsis
 Paroxysmal nocturnal hemoglobinuria  Specific features such as seen in Fanconi syndrome
 Hemophagocytic lymphohistiocytosis (Short stature ,Dysmorphic facial features ,Thumb
 Metastatic solid tumors abnormalities ,)Café au lait spots
 Bone marrow necrosis   
 Leukoplakia in HIV,malignancies
SYSTEMIC DISEASE-  Jaundice and stigmata of chronic liver disease
Immune related - Systemic lupus erythematosus)  Lymphadenopathy in lymphoma ,tb
, Sjogren syndrome ,Rheumatoid arthritis/ Feltry  Splenomegaly in leukemia,lymphomas
syndrome,Sarcoidosis,Autoimmune lymphoproliferative
Investigations:
syndrome , Common variable
immunodeficiency ,Thymoma .  CBC - decrease in all three blood cell lines

Nutritional/toxic -Vitamin B12 deficiency , Folate  Peripheral smear: Look for

deficiency ,Copper deficiency
,Alcoholism ,Hyperparathyroidism o Macrocytic RBCs, macro-ovalocytes and
hypersegmented neutrophils in megaloblastic
Infections anemia.
Overwhelming infection/sepsis o Virocytes in EBV, dengue or other viral infection
Virus: Covid-19, HIV, Parvovirus, Hepatitis associated pancytopenia.
A/B/C,CMV,EBV,HHV6 o Schistocytes in case of sepsis related DIC.
Brucellosis ,Ehrlichiosis ,Mycobacteria ,Leishmaniasis ,Di o Blasts/ abnormal promyelocytes.
sseminated fungal infection o Hairy cells or atypical lymphoid cells of NHL spill
over.
Storage disease -Goucher disease,Niemann-Pick disease o Pseudo Pelger Huet anomaly and cytoplasmic
hypogranularity in MDS.
others o Leukoerythroblastic reaction with tear drop
cells in myelofibrosis.
Sarcoidosis
Anatomic- Hypersplenism  Vitamin B12 levels and LDH
Osteopetrosis  LFT- deranged in CLD
  Ferritin, S. Triglycerrides and fibrinogen levels
 USG abdomen: To note splenomegaly,
metastasis in liver etc Diagnostic algorithm- See fig below
 Absolute reticulocyte count
<25*10*9 /l aplastic anaemia  Myelofibrosis
25-50 *10*9 /l –check serum vit b12 ,folate if
low nutritional,if normal do bmx Primary autoimmune myelofibrosis
>100*10*9 /l rule out sepsis/malaria if negative Disseminated TB or histoplasmosis
do BMx Metastatic carcinoma (Esp breast, prostate etc)
 Bone marrow aspiration and biopsy- with Other MPN in fibrotic phase
Hairy cell leukemia
 Flow cytometry Renal osteodystrophy
Vitamin D deficiency
 Cytogenetics SLE/ Scleroderma
Radiation exposure
SPECIFIC WORK UP Osteopetrosis
Paget’s disease
 PNH work up Benzene exposure
 NGS (next generation sequence )for MDS Mastocytosis
related mutations EX: SF3B1, TET2, SRSF2, HL/ NHL
DNMT3A, ASXL1 If all above are ruled out- Primary myelofibrosis
 S. Ferritin, Triglyceride- for HLH
 Skull X ray lateral view and protein
electrophoresis- For myeloma  Myelodysplastic changes
 HIV, HBsAg, HCV, Parvo, EBV, CMV, HSV, VZV
 SBDS gene study –schwachman diamond Megaloblastic anemia
syndrome Heavy metal toxicity
 ANA profile Alcohol abuse
 S. Calcium and PTH levels HIV, Parvovirus
 Blood culture Antitubercular therapy
 Fanconi testing Drugs- MMF, chemotherapy, valproate
 Telomere length analysis PNH
Note: Copper deficiency
Chronic liver disease
 Nearly 50% of pancytopenia in India are If all of the above are ruled out- Myelodysplastic
secondary to megaloblastic anemia. Hence if syndrome
there is macrocytosis, increased LDH/
decreased vitamin B12 levels, avoid further
 BM Necrosis
evaluation such as bone marrow aspiration and
biopsy. Tumors- ALL, MPN, HL, solid tumors
Infections- Sepsis, TB
 In some selected cases consider therapeutic Drugs- Chemotherapy, interferons
trial of Vitamin B12 Sickle cell disease
DIC
 Some of the pancytopenia are multifactorial. HUS
Examples include: APLA
Hyperparathyroidism
 Alcohol, megaloblastic anemia, SLE
hypersplenism Anorexia nervosa
Radiation exposure
 HIV infection, HAART therapy and AIDS
associated lymphoma
reference :howitreat.in

 Normal BM or Hypercellular marrow without

specific pathology

Autoimmune cytopenia
PNH
Alcohol induced BM suppression
Sepsis related cytopenia
Drug/ radiation induced cytopenia
Viral infection related cytopenia
Hypersplenism related pancytopenia