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
