APPROCH TO A PATIENT WITH MACROCYTIC ANEMIA by 1jNFv9

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									APPROCH TO A PATIENT

       WITH

 MACROCYTIC ANEMIA

                   Presented By
              Dr Farah Nazneen
                     (HO MUII)
                            1
      MACROCYTIC ANEMIA
Definition:

  Is defined as anemia with a raised mean
cell volume (MCV) and macrocytes on the
blood film.

   Mean cell volume is more than 96fl
                                             2
           TYPES OF
      MACROCYTIC ANEMIA
   (apperance of bone marrow)


Megaloblastic        Normoblastic
Anemia               Anemia



                                3
         Megaloblastic Anemia
   MCV >110 FL

   CAUSE
       Vitamin B-12 deficiency

       Folate deficiency



                                  4
         Normoblastic Anemia

CAUSE
 Physiological

           Pregnancy
           Newborn

   Pathological
          Alcohol excess
          Hypothyroidism
          Reticulocytosis
                               5
   Increase RBC membrane surface area
       obstructive jaundice
        hepatic disease
       post spleentomy



   Some haematological disorders
     aplastic anemia
      sideroblastic anemia
     pure red cell aplasia
     Myelophthisic anemia
     myelodysplasia
                                         6
 Drugs

      Azathioprine
        zidovudine

    Spurious

      agglutinated red   cells measured on red cell
         counters


    Cold agglutinins due to auto agglutination of
    red cells

      the  MCV decreases to normal with warming of the
         sample to 37 C
                                                          7
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          HOW TO APPROACH
   History

   Examination

   Investigation

   Treatment

                            9
                      HISTORY
   Fatigue                  hallucinations
   Anorexia                 Paraesthesiae
   dyspnoea                 visual disturbance
   poor memory              Sore mouth
   depression               Weight loss
   Headache                 Altered skin pigmentation
   personality changes      Gray hair
   impotence                features of underlying
   bowel disturbance         disease


                                                      10
   Past surgical history (total gastrectomy,
    partial gastrectomy, resection of terminal
    ileum)

   Dietary habits

   Family history



                                                 11
                EXAMINATION
   GENERAL PHYSICAL EXAMINATION
     Pallor  (lemon yellow color)
     Pyrexia
     Glossitis
     Angular stomatitis
     Vertiligo
     Skin pigmentation



                                     12
    SYSTEMIC EXAMINATION
   CNS EXAMINATION
         Higher mental function
         Decrease vibration and position sense
         Symmetrical loss of light touch
         Paraplegia
         Altered color vision
         Optic atrophy
         Ataxia



                                                  13
 CVS   EXAMINATION

   Tachycardia
   murmurs
   cardiacenlargement
   heart failure (if severe anemia)


 GIT   EXAMINATION

   Hepatomegaly



                                       14
              INVESTIGATION
1.  FBC and Peripheral film
2.  Serum vitamin B 12 assay
3.  Serum folate level
4.  Red cell folate
5.  Schilling test
6.  Autoantibody screen
7.  Bone marrow aspiration
8.  LFT
9.  Thyroid function test
10. Endoscopy and biopsy
11. LDH
                               15
1.   FBC and Peripheral film
     •   Megaloblastic anemia

             Full blood count:

                  Low haemoglobin (Hb) and increased mean cell volume (MCV) — although
                   macrocytosis can precede the development of anaemia.

                  Pancytopenia in severe cases.

                  Reticulocyte count low for the degree of anaemia (1–3% only).

                  MCV may be normal if there is associated iron deficiency. There is the possibility
                   that coexistent pathology could be missed. There will be a dimorphic blood film.
                   The ferritin level should be checked.

             Blood film:

                  macrocytic red cells, neutrophils with hypersegmented nuclei, and Howell-Jolly
                   bodies

        Reticulocytosis:

             Polychromasia seen on a blood film due to increased erythropoietin
              following haemorrhage or haemolysis                                                       16
 Liver    Disease:

   Round macrocytes and target cells
   May get a normochromic microcytic anaemia


 Alcohol:


   Inc. RBC production may cover the causes of this
    anaemia such as hamolysis, impaired BM response
    (due to a direct toxic/suppressing effect), folate
    deficiency and blood loss



                                                     17
Megaloblastic Anemia, Peripheral Blood Smear:
                                                                                                 18
Note macroovalocytosis, hypersegmentation (3-lobed eosinophil, for example), thrombocytopenia.
Megaloblastic Anemia, Peripheral Blood Smear:
                                                19
Macroovalocytes.
Anemia Secondary to Liver Disease:
Note moderate macrocytosis, target cells, lack of hypersegmentation and macroovalocytosis
                                                                                            20
Spur Cells:
Spur cells from a patient with severe liver disease
                                                      21
2.   Serum vitamin B12 and serum or red-cell folate
     levels:
        Folate deficiency will result in reduced levels of serum and red-
         cell folate. Red-cell folate is a better guide to body folate stores
         than is serum folate.

        Vitamin B12 deficiency will result in reduced serum vitamin B12
         levels. It may also result in increased serum folate and reduced
         red-cell folate levels, because of the effect on intracellular folate
         metabolism. Combined deficiency usually results in both
         reduced serum vitamin B12 and serum folate levels.

        False-positive vitamin B12 levels (low levels in the absence of
         deficiency) may occur in folate deficiency, pregnancy, multiple
         myeloma, and excessive vitamin C intake.

        False-negative vitamin B12 levels (normal levels in the presence
         of deficiency) may occur in true deficiency, liver disease,
         lymphoma, autoimmune disease, and myeloproliferative
         disorders

                                                                            22
3.   Autoantibody screen:
        Intrinsic factor (IF) antibodies are virtually
         diagnostic of pernicious anaemia (PA).
         However, absence of IF antibodies does not
         exclude the diagnosis, as they are present in
         only 50% of people with PA (i.e. it has high
         specificity but low sensitivity).

        Gastric parietal-cell antibodies are present in
         85% of people with PA, but are also found
         in 3–10% of people who do not have PA
         (i.e. it has high sensitivity but low
         specificity).

                                                       23
4.   Schilling test (radioactive vitamin B12
     absorption study):

          to determine if malabsorption of vitamin B12 is
         occurring and whether it is due to PA or due to an
         intestinal lesion. People with PA show impaired
         absorption of vitamin B12, which can be corrected
         by giving IF. People with malabsorption because of
         an intestinal lesion do not respond to IF.

        The Schilling test has many limitations, and the
         result often does not alter clinical management.


                                                              24
5.    Bone marrow aspiration
      Megaloblastic Anemia


          The bone marrow is hypercellular with a
           decreased myeloid/erythroid ratio and
           abundant stainable iron.

          RBC precursors are abnormally large and
           have nuclei that appear much less mature
           than would be expected from the
           development of the cytoplasm(nuclear-
           cytoplasmic asynchrony)

                                                     25
   The  nuclear chromatin is dispersed and condenses
    in a peculiar fenestrated pattern that is very
    characteristic of megaloblastic erythropoiesis
   Granulocyte precursors show giant bands and
    metamyelocytes
   Megakaryocytes are decreased and show abnormal
    morphology


 Normoblastic     Anemia
   Normoblast  are seen in bone marrow
   aspiration instead of megaloblastic



                                                    26
Megaloblastic Anemia, Bone Marrow Aspirate:
Typical megaloblastic changes are seen in the RBC and WBC precursors. The cells are large and
exhibit nuclear-cytoplasmic asynchrony. The chromatin is dispersed, yet the cytoplasm is relatively
                                                                                                      27
mature.
Megaloblastic Anemia, Bone Marrow Aspirate:
Giant megaloblastic red cell precursors.
                                              28
6.   LFT

7.   Thyroid function test

8.   Endoscopy and biopsy

9.   LDH



                             29
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                       TREATMENT
   Treatment of vitamin B-12 deficiency
     Specific    therapy
           antibiotics for intestinal over growth with
        e.g
        bacteria
     Replacement         therapy
        Parental treatment
              Initially 1mg 3 times a week for 2 weeks then 1 mg
               every 3 months
              In neurological involvement initially 1mg on alternate
               days until no further improvement then 1mg every 2
               months
        Oral treatment
                                                                        31
              2mg crystalline B-12 per day
   Response to the treatment

     Marrow    morphology begin to revert towards
      within a few hour after treatment is initiated
     Reticulocytosis begins 4-5 days after therapy
      is started and peaks at about day 7
     If reticulocytosis does not occur or if it is less
      brisk than expected from the level of the
      hematocrit, a search should be made for
      other factors contributing to the anemia
     Hypokalaemia, iron deficiency, hyperuricaemia


                                                       32
   Treatment of folate deficiency

     Replacement      therapy
        Oral treatment
           Dose of folic acid is 1mg per day but higher dose upto
            5mg per day may be required for folate deficiency due to
            malabsorption



   Response to the treatment

     Reticulocytosis after about 4 days followed by
      correction of anemia over next 1-2 month
                                                                   33
     PROPHYLACTIC TREATMENT
   B-12 prophylaxis
     0.1mg   oral crystalline cobalamine prophylaxis
      daily in people over age 65 years
   Folic acid prophylaxis
     400 micro gram daily recommended by for all
      women planning a pregnancy
     Women who have had a child with a neural
      tube defect should have 5mg folic acid before
      and during a subsequent prenancy
     Also given in chronic hematological disorders
      where there is rapid cell turn over in a dose of
      5mg each week                                     34
ISSUE RELATED TO TREATMENT
   Role of blood transfusion




                                35
                 MCQ’s
Q- Macrocytosis is defined as MCV value
  more than



 A. 94 fl
 B. 96 fl
 C. 98 fl



                                          36
ANSWER




B) 96 fl



           37
Q- Neurological involvement in B-12 deficiency does not
    cause

A.   Dementia

B.   Loss of position sense

C.   Loss of temperature sense

D.   Decrease vibration sense




                                                          38
        ANSWER




C) Loss of temperature sense




                               39

								
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