APPROACH TO

PANCYTOPENIA

MODERATOR – DR VISHAl GUPTA

MD MEDICINE

PRESENTED BY- DR NARENDRA SINGH

RESIDENT DOCTOR 2
 THE TERM
Cytopenia reduction in either of the cellular component
of blood

• Pancytopenia: Reduction in all the cell lines of blood

The values of the 3 components being:

• Hb <13.5(M)/ 11.5(F) g/dl

• TLC< 4000/cu mm

• Platelets <1,50,000/ cu mm

• Absolute neutrophil count <1500/cu mm

It can occur due to
• Bone marrow failure

A. Marrow space occupying lesions

B .Ineffective marrow production

• Peripheral destruction of hematopoietic cells

 CAUSES OF
PANCYTOPENIA

INHERITED ACQUIRED
 INHERITED CAUSES
1. FANCONI ANEMIA

2. DYSKERATOSIS CONGENITA

3. SHWCHMAN-DIAMOND SYNDROME

4. CONGENITAL AMEGAKARYOCYTIC
THROMBOCYTOPENIA

5.HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
IMMUNE DISORDERS •SLE •HYPERCELLULR
•EVANS SYNDROME •HYPERCELLULAR
•THYMOMA •HYPOCELLULAR

ACQUIRED CLONAL BONE PNH VARIABLE

MARROW FAILURE
DISORDER

METABOLIC •HYPOTHERMIA •VARIABLE

•ANOREXIA NERVOSA •HYPOCELLULAR WITH
FAT NECROSIS

OTHERS HYPERSPLENISM HYPERCELLULAR

NON MALIGNANT •STORAGE DISORDERS •INFILTRATED

INFILTRATION •OSTEOPETROSIS •INCREASED BONY
TRABECULAE

INFECTION CME,EBV,PARVOVIRUS,HHV HYPOCELLULAR(PROERYT

-6,HEPATITIS,HIV HROBLASTS IN
PARVOVIRUS)
 PANCYTOPENIA

HYPOCELLU HYPERCELLUL
LAR AR
•Metabolic •Immune disorder
Hypothermia
Anorexia nervosa SLE,Evan’sSyndrom
•Infection e
CMV,EBV,HEP •Others
Virus, Parvo virus. Hypersplenism
 HOW TO APPROACH ?
PHYSICAL EXAMINATION
HISTORY
INVESTIGATION
 Points to consider in history

• Age- inherited cause of bone marrow failure

• Duration of symptoms-tells about the severity

• Bone pains(acute leukemias) fever(infections), night

sweats(Hodgkins disease), malaise,
weightloss(tuberculosis,malignancy)

• Bleeding from any site(magnitude of thrombocytopenia)

• Jaundice(hepatitis viruses)

• Joint pain, rash, photosensitivity(lupus)

• Any radiation exposure

• Exposure to potentially toxic chemicals

• Treatment history including herbals and drug intake, blood

Transfusions

• Dietary history

• Occupational exposure history

 Clinical Examination
• Anthropometry including short stature in fanconi anemia

• Dysmorphic features (Fanconi anemia)

• Pallor(severity of anemia ), (hepatitisvirus) ,

Lymphadenopathy (leukemia), Edema sign of CHF

• Stomatitis, cheilitis (neutropenia nutrtional deficiency)

• Nail dystrophy, leukoplakia, skin

pigmentation(DYSKERATOSIS CONGENITA)
• Oral candidiasis, pharyngeal exudates (neutropenia)

• Petechiae, purpura, hyperpigmentation (thrombocytopenia)

• Sternal tenderness (acute leukemia)

• Gum hypertrophy (acute myeloid leukemia)

• Hepatosplenomegaly (SLE)

• Joint swelling, sinusitis (SLE)

 LAB EVALUATION

1. CBC WITH PERIPHERAL BLOOD SMEAR

2. BONE MARROW ASPIRATION AND BIOPSY

3. SPECIFIC INVESTIGATIONS
 CBC

Hb<11-13

MCV75-91

MCV<75 MCV75-91 MCV>91

MICROCYTIC NORMOCYTIC MACROCYTIC
ANEMIA ANEMIA ANEMIA

RDW11.6-14.6
RDW11.6-14.6
RDW11.6-14.6

11.6-14.6
11.6-14.6
>14.6 ANEMIA OF >14.6 >14.6
ACUTE BLOOD 11.6-14.6
IDA/SCD CHRONIC DIMORPHIC LOSS FOLATE AND VIT
ANEMIA APLASTIC ANEMIA
DISEASE HEMOLYSIS B12 DEFICIENCY
 MCH
26-33 Pg OF Hb/RBC
MCH>33-MACROCYTIC ANEMIA
MCH<26-MICROCYTIC ANEMIA

MCHC
33-36Pg/dl
MCHC<33-HYPOCHROMIC ANEMIA
MCHC>36-HEREDITARY SPHEROCYTOSIS

PCV
36-46%
PCV<36BLOOD LOSS
PCV>46 DEHYDRATION
 PERIPHERAL BLOOD SMEAR
•Anisocytosis and poikilocytosis

•WBC and RBC precursors

•Platelets

•Granulation in neutrophils (Abnormally increased/decreased)

•Neutrophils(Hypo/Hypersegmentation)

•ESR
ANISOCYTOSIS & POIKILOCYTOS

MODERATE
DEGREE
COMMON

VERY MARKED LESS DEGREE ABSENT

MYELOFIBROSIS APLASTIC ANEMIA ACUTE LEUKEMIA

LYMPHOMA/
MULTIPLE MYELOMA
 WBC AND RBC
PRECURSORS

PLASMACYTIC IMMATURE
BLAST CELLS
CELLS LYMPHOCYTES

Marrow involvement
Myelofibrosis Multiple myeloma by lymphoma
Acute leukemias
Subleukemic leukemias
 RBC INCLUSIONS

HOWEL JOLLY BODIES

• Basophilic nuclear remnants (clusters of DNA) in R
• Megaloblastic anemia
• MDS
 PLATELETS

NORMAL GIANT
PLATELETS PLATELETS
MDS
Aplastic Anemia Hypersplenism
 NEUTROPHIL

SHAPE GRANULE

HYPOGRANULAR
HYPERSEGMENTAL HYPOSEGMENTAL
TOXIC GRANULE MDS
MEGALOBLASTIC CHRONIC LEUKEMIA
INFECTION PELGER HUET LIKE CELLS
ANEMIA FOLATE B12 DEFICIENCY
HYPERSEGMENTATION
 CELULARITY OF BONE
MARROW

The differential diagnosis of pancytopenia are based on

cellularity of bone marrow :

Hypocellular: excessive amount of fat cells

Normocellular: 50-70% hematopoietic cells & 30-50% fat

Hypercellular: 80-100% cells with little fat

 BONE MARROW
EXAMINATION
Almost always indicated in cases of pancytopenia unless
cause is apparent
Both aspiration and biopsy are indicated
Specifically, bone marrow aspirate permits examination of:

• Cytology (megaloblastic change, dysplastic changes,

abnormal cell infiltrates)

• Immunophenotyping : antigen or marker on cells

surfaces e.g ( leukemias, lymphoproliferative disorders)

• Cytogenetics : structure of chromosome

(myelodysplasia, leukemias, lymphoproliferative
disorders)
HYPERCELLULAR
Features Seen in
CELLULARITY HYPERCELLULAR: Megaloblastic anemia,
Hyperslenism
DRY TAP: Myelofibrosis
HYPOPLASTIC: Myelodysplastic syndromes

ERYTHROPOIESIS DYSPLASTIC: MDS, some AML

INCREASED: Hemolysis

MYELOPOIESIS DYSPLASTIC: Myelodysplastic syndrome

Mophologically normal: Myeloproliferating
disorders

BLASTS Myelodysplastic disorders, Acute Leukemias

MEGAKARYOPOIESIS DYSPLASTIC: Myelodysplastic disorder

OTHER CELLS Reedsternberg cell: Hodgkin cell

Bacteria, Fungus, Parasite, Viruses, LD
bodies
SPECIFIC INVESTIGATIONS
 RATIONALE
TEST
BONE X-RAYS Multiple myeloma, metastasis

ANA test Systemic Lupus Erythematous

BLOOD CULTURE Infectious agent- Tuberculosis or virus

VITAMIN B12 AND FOLATE ASSAYS Megaloblastic anemia

LFT Evaluate hepatitis

KFT Assess for Chronic Renal Failure

SEROLOGY HIV, EBV, Hepatitis

HAM’S TEST Paroxysmal Nocturnal Haemoglobunuria

CHROMOSOMAL BREAKAGE Fanconi anemia

STUDIES
INITIAL MANAGEMENT OF
PANCYTOPENIA
•Discontinue any potential affending drug and use an alternative
class of agent if essential

•Anemia transfusion of leukocyte depleted irradiated red cells as

required for severe anemia.

•Very severe thrombocytopenia or bleeding consider gamma

aminocaproic acid transfusion of platelets as required.

•Severe neutropenia use infections precautions.

•Fever(suspected infection, microbial cultures broad
spectrum antibiotics if specific organism not identified.

•If infection is profound and not covered by antibiotic then

consider neutrophil transfusion from a G-CSF.

•Immediate assesment from allogenic stem cell

transplantation. Histocompatibility testing of patient,
parents and siblings. Search databases for unrelated donor,
if appropriate .
 TREATMENT

1Supportive treatment

2Specific treatment
•Syngenic or allogenic hematopoeitic cell transplantation

•Combination immunosuppressive therapy with

ATG and cyclosporine
 SUPPORTIVE CARE

Red Cell Transfusion

Packed red cells to alleviate symptoms of anemia usually

are indicated at hemoglobin values below (8g/dl).

•Should be leukocyte-depleted to lessen leukocyte and platelet

sensitization and to reduce subsequent transfusion reactions and
radiated to reduce the potential for a transfusion-related graft-
versus-host reaction.

•It is important to transfuse patients with red cells (or platelets)

from family members if transplantation within the family is
remotely possible.
 PLATELET TRANSFUSION
Most patients tolerate counts of 10,000/microlitre
(10-109/L)without undue bruising or bleeding, unless a
systematic infection is present or vascular integrity is impaired.

A traumatic injury or surgery requires transfusion to greater than

50,000/microlitre or greater than 100,000/microlitre respectively.

Administration of gamma aminocaproic acid ,50 mg/kg per dose

every 4hours orally or intravenously, may reduce the bleeding
tendency.

Patients should also get ABO-identical platelets because this

enhances platelet survival and further decreases refractoriness to
platelet transfusion
MANAGEMENT OF NEUTROPENIA
•Level of neutrophils requiring precautions is fewer than 500/microL

•Neutrophils can be increased by adminstering granulocyte

Colony –stimulating factor