1

Hematology
 2

IRON DEFICIENCY ANAEMIA

INVESTIGATIONS:
Specific

BASIC
o CBC
Low Hb/Hct High RDW
Low MCV/MCH/MCHC
o PERIPHERAL BLOOD FILM
Microcytic & Hypochromic anemia
o BONE MARROW EXAMINATION
IRON STUDIES
o Serum Iron/Ferritin/Transferrin saturation is decreased
o TIBC & Soluble transferrin receptor(TfR) is increased
OTHERS
o RFTS/LFTS o Stool examination for ova, cyst & occult
o Urine for hematuria blood

MANAGEMENT:
Supportive

Dietary advice Treatment of the underlying cause

Specific

IRON SUPPLEMENTATION
1. ORAL
Ferrous sulphate
(200 mg TDS)
OR
Ferrous gluconate
(300 mg BD)
OR
Ferrous fumarate
2. PARENTERAL
Iron sorbitol
1.5 mg/kg (i.m)
OR
Iron dextran
(infusion of LMW)
OR
Iron sucrose

Transfusion
o Severe anemia
o Angina, heart failure or evidence of cerebral hypoxia
 3

MEGALOBLASTIC ANAEMIA

INVESTIGATIONS:
Specific

BASIC
o CBC
Low Hb/Hct/count High MCV > 120 fL
o PERIPHERAL BLOOD FILM
Neutrophil hypersegmentation Oval macrocytosis
o BONE MARROW EXAMINATION
Increased cellularity increased iron in stores
OTHERS
o Serum Ferritin is ELEVATED *** o Heptoblobin is decreased
o LDH/Bilirubin is raised
SPECIFIC
o Folate levels o Schilling test
o Serum B12 /Methylmalonic acid o FIGLO test
o Anti-parietal /Anti-intrinsic factor ABs
MANAGEMENT:
Specific

BEFORE RESULTS OF THE TESTS

o Supplementation of both B12 & Folate
B12 DEFICIENCY
o Inj. Hydroxycobalamin 1000 g (intramuscular) 5 doses _ 2-3 days apart
o Maintenance therapy 1000 g every 3 months lifelong
o Follow up with Hct level & Retics counts every week
o Counselling: sensory neuropathy takes 6 12 months to correct
FOLATE DEFICIENCY
o Folic acid 5 mg OD 3 weeks (Acute deficiency)
o Folic acid 5 mg weekly (Maintenance dose)
o Prophylactic therapy in pregnancy/AHA/HB-pathies
o Supraphysiological supplementation to decrease risk of thromboembolism
TRANSFUSION
o Severe anemia o Angina, heart failure or evidence of cerebral hypoxia

SICKLE CELL DISEASE

HEMOLYSIS
Increased
o Retics
o Indirect bilirubin
o LDH
Decrease
o Heptoglobin
 4

INVESTIGATIONS:
Specific

BASIC
o CBC
Low Hb/Hct/count WBC/platelets are elevated
o PERIPHERAL BLOOD FILM
A reticulocytosis is present Sickle cells, target cells and features
of hyposplenism
OTHERS
o LDH/Bilirubin is raised o Heptoblobin is decreased
SPECIFIC
o Exposing red cells to a reducing agent (sodium dithionite)
o Hemoglobin electrophoresis

MANAGEMENT:
Supportive

AVOIDANCE OF PRECIPITATING FACTORS

o Hypoxia/Infections/Dehydration/Acidosis
ANALGESIA
o Opiates (morphine/Diamorphine)
PROPHYLAXIS
o ABXs (Penicillin V) from gram positive sepsis
o Supplementation of Folic acid 5 mg daily
o Vaccination against influenza, Hepatitis B, Pneumococcus & Meningococcus

Specific

VASO-OCCLUSIVE CRISES
o Aggressive rehydration o Adequate analgesia (which often requires
o Oxygen therapy opiates)
o Antibiotics
REGULAR TRANSFUSION PROGRAMME
o In severe aplastic crisis
o Cerebrovascular accidents in children or chest syndromes in adults
EXCHANGE TRANSFUSION
o In severe aplastic crisis/before surgery
HYDROXYUREA
o It increases Hb F level o To prevent recurrence
BMT (Allogenic)
 5

ITP

INVESTIGATIONS:
Specific

BASIC
o CBC
Isolated Thrombocytopenia
o PERIPHERAL BLOOD FILM
Normal
o BONE MARROW EXAMINATION
Increased megakaryocytes
SPECIFIC
o Bleeding time is prolonged *** o Platelets antibodies (IgG/IgM)
o PT/PTT normal
OTHERS
o Rule out infections (HIV) o Connective tissue disorders (ANA/ds-DNA)

DDs:

Leukemia/Lymphoma DIC
Aplastic anemia SLE

MANAGEMENT:
Supportive

AVOIDANCE OF PRECIPITATING FACTORS

o Trauma o Aspirin & other antiplatelet drugs

Specific

IF PLATELET COUNT > 30,000/cm3

o No treatment
IF PLATELET COUNT > 20,000/cm3 PLUS SYMPTOMS
o 1ST LINE
Prednisolone Reintroduce steroids if relapse
IVIG
o 2ND LINE
Splenectomy & vaccination (if 2 relapses)
o IF SPLENECTOMY FAILS
Low dose steroids Rituximab
IVIG/IV Anti-D Platelet transfusion
Danazol Thrombopoiesis proteins
Immunosuppressive:
Azathioprine/Cyclosporine
 6

Chronic Myeloid Leukaemia (CML)

CLINICAL:

Tiredness Weight loss

SOB Retinal hemorrhage
Splenomegaly (90%)/Hepatomegaly (50%) Lymphadenopathy is unusual***

INVESTIGATIONS:
BASIC
o CBC
Hb: Normal/Low (normochromic & normocytic) Platelets: Low/Raised/Normal
TLC: Raised (>100 109/L)
o PERIPHERAL BLOOD FILM
Neutrophilia Elevated basophils/monocytes
Occasional blasts
o BONE MARROW ASPIRATE
Increase cellularity Increased myeloid precursors
SPECIFIC
o CYTOGENETIC & MOLECULAR TECHNIQUES
FISH/RT-PCR
Philadelphia chromosome = t(9:22) translocation = BCR-ABL fusion

Also used to monitor treatment response
o LEUKOCYTE ALKALINE PHOSPHATASE (LAP) SCORE
LAP Score is low in CML
OTHERS
o LDH & Uric acid are elevated due to increase cell breakdown

MANAGEMENT:
Chronic phase

1st Line
o Initial therapy
Imatinib (tyrosine kinase inhibitor)
2nd line
o Dasatinib/Nilotinib o Alpha interferon alone or combination
o Hydroxyurea with Ara-c
o Allogeneic BMT cures CML

Accelerated phase and blast crisis

Imatinib is indicated if the patient has not Cytarabine

already received it Allogeneic BMT/Dasatinib/Nilotinib
Hydroxyurea
 7

Multiple Myeloma (MM)

DIAGNOSTIC CRITERIA:

PATIENT CRITERIA MGUS SMOLDERING SYMPTOMATIC

MYELOMA MYELOMA
M-protein < 3 g/dL 3g/dL In serum and/or in
spike spike urine
Monoclonal plasma cells < 10 10 10
in bone marrow (%)
End organ damage None None 1 CRAB
Features

CRAB
C=Calcium elevation (> 10.5 mg/dL)
R=Renal dysfunction (Cr > 2 mg/dL)
A=Anemia (Hb < 10g/dL)
B=Bone lesion (lytic lesion/osteoporosis)

INVESTIGATIONS:
BASIC
o CBC
Hb: Anemia Platelets: Normal/Low
TLC: Normal/Low ESR/CRP almost always raised ***
o PERIPHERAL BLOOD FILM
Rouleaux formation as a consequence of paraproteins
o BONE MARROW EXAMINATION
Plasma cell infiltration (> 10%) Amyloid may be present
SPECIFIC
o SERUM PROTEIN ELECTROPHORESIS & IMMUNOFIXATION
Monoclonal band M-spike
o 24 HRS. URINE ELECTROPHORESIS & IMMUNOFIXATION
Bence-Jones proteins
o SKELETAL SURVEY
X-ray Skull MRI Spine
o CYTOGENETIC/MOLECULAR TECHNIQUES
FISH
o PROGNOSIS
Beta2-microglobulin (2M) & s. albumin correlates with severity of disease
OTHERS
o RFTs (Urea & creatinine) o Hypercalcemia & Hyperuricemia
o Electrolytes o Total proteins/Albumin

DIFFERENTIALS:

Reactive marrow plasmacytosis Lymphoproliferative Disorders with monoclonal

Waldenstroms macroglobulinemia gammopathy
 8

Metastatic carcinoma

STAGING:

INTERNATIONAL STAGING SYSTEM

Stage Criteria
1 2-M (< 3.5 mg/L)
II Not stage I or III
III 2-M 5.5 mg/L)

POOR PROGNOSTIC FEATURES:

Cytogenetics/FISH High proliferation rate

Extramedullary disease Phenotype of tumor cell
ISS stage Age/Co-morbid conditions/Low socioeconomic
Renal failure due to MM/Plasma cell leukemia class
Anemia
MANAGEMENT:
Supportive

High fluid intake Bone problems

Analgesics for pain (radiotherapy/Chemotherapy/HD steroids &
Allopurinol for urate nephropathy Bisphosphonates)
Anemia (Transfusion/EPO may help) Pathological fractures
Infections (BS ABXs/Flu vaccination) (kyphoplasty/Vertebroplasty)
Plasmapheresis for hyperviscosity

Specific

Before 70 years
o VAD (Vincristine/Adriamycin/Dexamethasone)
o Autologous Stem cell transplantation
After 70 years
o If healthy (Thalidomide) o If fragile (Melphalan)

APLASTIC ANEMIA

CAUSES:
PRIMARY
o Idiopathic acquired (67%)/Fanconis anemia
SECONDARY
o Chemical (benzene/toluene/OPs)
 9

o Drugs (ABXs/DMARDs/Antithyroid/Anticonvulsant/Immunosuppressive)
o Insecticides/Ionizing radiations/infection (HIV, EBV, CMV, Hepatitis, Tuberculosis)
o PNH/Pregnancy

INVESTIGATIONS:
BASIC
o CBC
Pancytopenia Virtual absence of reticulocytes
o BONE MARROW EXAMINATION
Hypocellular/Aplastic bone Increase fat spaces
marrow
DDs:

Drugs
Bone marrow infiltration (Lymphoma/Ac. Leukemia/Myeloma/Myelofibrossis)
Megaloblastic anemia
Hypersplenism/Sepsis
SLE/PNH/DTB

MANAGEMENT:
Supportive

Hemopoetic Growth Factors

Transfusion/ABX/Analgesics
Treatment of cause

Specific

TRANSPLANTATION
o Allogenic BMT
IMMUNOSUPPRESSIVE TREATMENT (IF ABOVE 50 OR NO MATCHED DONOR)
o Antithymocyte globulin (ATG)/Antilymphocyte globulin (ALG)
o Cyclosporine/Tacrolimus
o Prednisolone