Case Studies Hemoglobinopathies

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					CASES STUDY/ DATA
 INTERPRETATION
  HAEMATOLOGY
   DR. :HASHIM AHMED
   FULL BLOOD COUNT

• THE ELEMENTS :
 1- RBCS
 2 - WBCS
 3- PLATELETS
          RBCS
• ELEMENTS :
  HB.
  ERYTHROCYTE COUNT
  HCT
  MCV
  MCH / MCHC
  RDW
  RETICULOCYTE
  ESR
         WBCS

• ELEMENTS :
 NEUTROPHILS
 LYMPHOCYTES
 MONOCYTES
 EOSINOPHILS
 BASOPHILS
 BLAST
       PLATELETS
• ELEMENTS :
  INCREASE
  DECREASE
    GENERAL TOPICS
• THE IMPACT OF
  HAEMOGLOBINPATHIES
• PERIMARIATAL SCREENING
            ANAEMIA
• DEFINITION:
  IT IS A DECREASE IN THE NUMBER OF
  CIRCULATING RBCS.
• ETIOLOGY:
  1-BLOOD LOSS
  2- DECREASE PRODUCTION
  [ MARROW FAILURE]
  3- INCREASE DESTRUCTION
  [ HAEMOLYSIS]
                                 Low Hb=Anemia
                                        MCV

   Low=microcytic               Normal=normocytic                 High=macrocytic


        Ferritin                                              Measure B12 + folate

Fe deficient       Fe normal
                                                     Normal                Low -
                                                                           Establish cause
Establish          Anemia of
                                              Obvious    Cause not obvious
cause              chronic disease
                                              cause      Consider bone marrow
                   or
                   hemoglobinopathy


                                 Reticulocyte count



               Hemolysis         high          low            Anemia of chronic disease
               or blood                                       Renal failure
               loss                                           Marrow failure
     CASE / DISCUSSION
• 19-YEAR OLD FEMALE STUDENT
  PRESENT TO THE STUDENTS HEALTH
  SERVICE WITH INCREASE FATIGUE&
  MALAISE.
  NO BLEEDING
  MENSTRUAL CYCLE NORMAL.
• P/E NAD
• WHAT IS THE NEXT STEP/S?
                  CBC
•   HB      7
•   HCT 22.8
•   MCV 72
•   RETIC.COUNT 1.1%
•   VIT. B 12 & FOLATE NORMAL
•   WBCS 5000
•   PLATELETS 285000
•   WHAT IS NEXT?
              CONT,
• FERRITIN < 4 [ N 12- 200]
• DIAGNOSIS : [ I D A]
• TREATMENT :
  A- NON- PHARM.
  B- PHARM.
   CONT,

IDA CRITERIA
     LOW HB
     LOW HCT
    LOW MCV
    LOW MCH
    MCHC LOW / N
    LOW FERRITIN
    LOW FE
    HIGH TIBC
    HIGH RDW
      CASE / DISCUSSION
• AN 18-YEAR OLD MALE DIABETIC
  COLLEGE STUDENT, WHO REQUIRES
  INSULIN, PRESENT TO THE STUDENTS
  HEALTH SERVICE WITH A LOW GRADE
  FEVER & COUGH FOR 10 DAYS DURATION.
• P/E: CRACKLES ARE HEARED ON
  AUSCULTATION OF BOTH LUNGS AT THE
  RIGHT BASE, BUT THERE ARE NO SIGNS
  OF CONSOLIDATION.
        LAB. RESULTS
• CBC:
• LEUKOCYTES COUNT : 11500
  NEUTROPHILS COUNT: 68%
  LYMPHOCYTES COUNT: 24%
  MONOCYTES COUNT :7%
  EOSINOPHILS COUNT:1%
  BASOPHILS COUNT: 0%
• PLATELETS COUNT: NORMAL
             CONT,
• HEMOGLOBIN :10.5
  ERYTHROCYTE: 3.13 MILLION
  HCT          :32
  MCV         :131
  MCH         :30.6
  MCHC        :42.5
• WHAT ARE/ IS THE OTHER TESTS
  YOU WILL REQUEST?
                CONT,
•   VIT. B12 & FOLATE [ B 12 WAS LOW]
•   SCHILLINGS TEST [ +VE]
•   LFT [ GAMMA G –T]
•   H/O : COELIAC DISEASE OR
    ALCOHOL INTAKE /??
              CONT,
• THE FINAL DIAGNOSIS [ B12 DEF.]
• TREATMENT:
  VIT B12 1000 U IM DAILY X 7 DAYS
  THEN WEEKLY X 4 WEEKS
  THEN MONTHLY X 4 MONTHS
        Haemoglobinopathy Investigation
    Usually prompted by clinical findings and/or CBC.
    Includes:


•   Hb Electrophoresis
•   Quantitation of Hb A2 and Hb F
•   Detection of Hb H Inclusions
•   Sickle Solubility Test if relevant

    Other information required : patient age, ethnicity
    Additional tests : serum ferritin if microcytic, occasionally molecular studies
    and/or family studies
                 Haemoglobin Electrophoresis
                                         (alkaline pH )


         Carbonic     Hb A2
         Anhydrase
                                                                       Normal
                                                               Hb A
                                                                       Control


Haemolysate applied                                                   Patient


                                                                      Abnormal
                                                                      Control

                                Hb C          Hb S   HbA
            Moves in same position as Hb A2
                                  Hemoglobin Electrophoresis          Anode
                Cathode                at alkaline pH                         Anode
                 Case 1

 18 year old young man seen for medical
  examination prior to immigration
 Past medical history unremarkable.
 Family of Sicilian descent.
 Physical examination normal
            Case 1


Hb      132 g/L (140-180)
MCV     66.1 fL (80-100)


Blood Film: hypochromia,
             microcytosis
CASE 1: Blood Film




               Lymphocyte
Hb A2           Hb A
                                     Normal
                                     Control

                                     Patient
                                     Case 1

                                     Abnormal
                                     Control



        Hemoglobin Electrophoresis      Anode
             at alkaline pH

                Case 1
                 Case 1

Haemoglobin Electrophoresis:
                     Hb A 93.8 %
                     Hb F    1.0 %
                     Hb A2 5.2 %
             Diagnosis: β Thalassemia trait
                  Genotype αααα ββ or β- δδ γγ


                  Haemoglobins Produced


         α                    α    δ              α
              β                                        γ
        β                    δ                   γ



        Hb A                 Hb A2               Hb F

Laboratory diagnosis of β Thalassemia trait made by CBC, and Hb A2 >3.5%.
                  Serum ferritin is normal or increased.
                 Case Two
• A -12-Year old African boy is tested for Sickle
  Cell Disease pre-operatively
• His father is known to have Sickle Cell Triat
• Results:
• HB          10.1g\dl
• RBCS         6.1X10X12\l
• MCV          65fl
• MCH         21.1pg
• MCHC         30g\dl
Cont,
• What is the next step in your investigtions ?
            CONT,
• SICKLING TEST
• HB. ELECTROPHORESIS
             CONT,
• SICKLING TEST WAS +VE
• IS THAT ENOUGH?
             CONT,
• HB. ELECTROPHORESIS RESULT :
  HBS         45%
  HBA         53%
  HBA2         5.2%
  HBF          0%
  FERRITIN LEVEL NORMAL
Questions
• What Haemoglobinopathy does the boy
  have?
• What Haemoglobinopathy would you
  expect on testing the mother?
Answer
•   [ Sickle- Thal]
•   The mother is expected to have Thalassaemia Trait
•   NB:
•   Presence of Hb A exclude SCD and THAL
    .MAJOR
•   Presence of HbF ONLY = THAL. MAJOR
•   Presence of HbS ONLY = SICKLE CELL DIS.
•   Presence of HbS +HbA= Sickle trait
•   Presence of HbA+ HbA2 of more than
    3.5=THAL.TRAIT
•   Presence of HbA + HbA2 + Hbs = Sickle- Thal
                     Case 3
6 year old girl from Geizan
Admitted to hospital with abdominal pain and fever.
Past history : swelling of hands and feet at age 1
              : previous episodes of abdominal pain
Physical examination:
                pallor of mucous membranes
                mild jaundice
                hepatomegaly
                no splenomegaly
                no evidence of infection
Parents healthy : OK
                      Case 3

Hb         84 g/L (115-155)
MCV        86.5 fL (77-95)


Blood Film - sickle cells
             erythroblasts
             Howell-Jolly bodies
             polychromasia
             target cells
       Case 3




                Howell Jolly
                Body

Erythroblast
Hb C   Hb S Hb F Hb A
                          Abnormal
                           Control




                           Patient
                           Case 2

                           Normal
                           Control


                 Case 2
            Hb S Solubility Test
+ Control       - Control          Case 2
                                   Case
                Case 3
              Case 3

Haemoglobin Electrophoresis:

              Hb A     0 %
              Hb S    87.0 %
              Hb F     9.7 %
              Hb A2    3.3 %
                       Diagnosis: Hb SS Disease
                       Genotype αααα βsβs δδ γγ

          Haemoglobins Produced :


             α                         α     δ                 α
                  s                                                 γ
            s                        δ                        γ



             Hb S                     Hb A2                    Hb F

Laboratory diagnosis of sickle cell anaemia made by presence of only Hb S, Hb A2, and Hb
F on Hb electrophoresis with no Hb A, a positive sickling test and presence of sickle cells in
                                        blood film
                    Case 4
 6 month old baby girl from the Eastern
Province. The chief complaints:
 Failure to thrive, and pallor.
 Family History:
    No definite history of a blood problem
    Mother "anaemic" during pregnancy, and
       prescribed iron
    One sibling with history of mild anaemia,
       previously treated with iron
 Physical Examination:
      pallor
      hepatosplenomegaly
                   Case 4

Hb          72 g/L (105-135)
MCV         68.5 fL (70-86)

Blood Film: hypochromia
            microcytosis
            tear drop cells
            poikilocytosis
            polychromasia
            erythroblasts
            target cells
             Case 4




                      Erythroblast
Microcytes
Case 4

                      Mother


                      Case 4


                      Father

                      Normal
                      Control
         HbA2   HbA
               Case 4

Haemoglobin Electrophoresis:

                        Hb A 0 %
                        Hb A2 3.5 %
                        Hb F 96.5 %
             Diagnosis: β Thalassemia major
                   Genotype            αααα - - δδ γγ

                         Haemoglobins Produced


                                  α    δ                α     γ
                                 δ                      γ



                                Hb A2                   Hb F

 Laboratory diagnosis of β thalassemia major made by CBC, absence of Hb A, with
increased Hb F. Some patients have small amounts of Hb A if some β globin chain is
                                    produced.
                    Case 5

28 year old Thai woman
Life long history anaemia and mild jaundice.
Past history : splenectomy.
Family History :
  • Mother: life long history microcytic
    hypochromic anaemia, unresponsive to iron
  • Father and sister: no known history of a blood
    problem.
                 Case 5

Hb            97 g/L (140-180)
MCV           72.1 fL (80-100)

Blood Film: Microcytosis
            Hypochromia
            Target cells
            Fragmented cells
            Howell-Jolly bodies
Case 5
HbA2   HbA    Case 5
             Normal
             Control


             Abnormal
              Control


             Abnormal
              Control


             Patient
             Case 5
              Case 5

Haemoglobin Electrophoresis:
             Hb A 91.5 %
             Fast moving band 8.5%
             Hb A2 and Hb F decreased
         Hb H Preparation




                      Hb H inclusions
                      in RBCs
Case 5
               Hb H Disease
          Diagnosis: Hb H Disease
            Genotype ---α ββ δδ γγ

                                                          β     β
Haemoglobins Produced :


 α                      α    δ               α
      β                                           γ
                                                              Hb H
 β                     δ                    γ



 Hb A                 Hb A2                  Hb F

 Laboratory diagnosis made by CBC, and presence of Hb H on Hb
          electrophoresis and in the Hb H preparation.
      Case 5: Family Studies
Father: Hb            139 g/L (140-180)
           MCV          79 fl (80-100)
 Hb Electrophoresis normal.
 Hb H preparation negative
Mother: Hb            100 g/L
            MCV          66 fl
 Hb Electrophoresis normal.
 Hb H preparation : very occasional cell
 positive for Hb H inclusions
       CASE SCENARIO
• A 65- YEAR OLD MAN PRESENTED
  WITH H/O :
• WT. LOSS, NIGHT SWEATS & FEVER
• P/E : LYMPHADENOPATHY
  HEPATOSPLENOMEGALY
• HOW CAN YOU APPROACH SUCH A
  PATIENT? & WHAT INVESTIGAION/S
  ARE YOU GOING TO CARRY OUT?
                      Blood Count
W x 1 9/L
 BC 0                   150.0        1
                                 [4-1 ]
Hb g/L                  98       [1     6
                                   20-1 0]
MCVfl                   87       [79-98]
Plat elet s x 1 9/L
               0        48       [150-450]

Neut s x 1 9/L
          0             1 .5     [2-7.5]
Lymphs x 1 9/L
           0            1 30.0   [1.5-4]
Monos x 1 9/L
          0             0 .5     [0.2-0.8]
Eos x 1 9/L
       0                -        [0-0.7]
Basos x 1 9/L
          0             -        [0-0.1]

Smudge cells x 1 9/L
                0       28.0     [0]

Film Comment : appearances suggest CLL
 CLL – presenting clinical features
• Chance finding
• Marrow failure
• Symptoms
  – weight loss
  – night sweats
  – fevers
• Lymphadenopathy
• Splenomegaly, hepatomegaly
lymphocytes
           lymphocytes

‘smudge’ cells
       CASE SCENARIO
• A 40-YEAR OLD FEMALE PRESENTED
  WITH H/O :
• WT. LOSS, NIGHT SWEATS &
  MULTIPLE JOINTS PAIN.
• P/E : PALE LOOKING & BIG SPLEEN
• WHAT SORT OF INVESTIGATION/ S
  ARE YOU GOING TO PERFORM ?
                        Blood Count
W BC x 1 9 / L
         0                    122.0        1
                                       [4-1 ]
     /
Hb g L                        9 8 .5   [1     6
                                         20 -1 0 ]
   V
MC fl                         87       [79-9 8 ]
Plat elet s x 1 9 / L
               0              8 43     [150 -450 ]

Neu s x 1 9 / L
   t      0                   8 0 .0   [2-7.5]
L m h x 1 9/ L
 y p s      0                 2.0      [1.5-4]
Mo o x 1 9 / L
  n s      0                  2.0      [0 .2-0 .8 ]
         9
  s    0
Eo x 1 / L                    1.0      [0 -0 .7]
Baso x 1 9 / L
     s     0                  5.0      [0 -0 .1]

Blast s x 1 9 / L
           0                  2.0      [0 ]
Pro yelo
   m      cyt es x 1 9 / L
                      0       4.0      [0 ]
                    9
    lo  t
Mye cy es x 1 / L 0           20 .0    [0 ]
Met am elo
       y    cy es x 1 9 / L
                t       0     4.0      [0 ]

Nucleat ed R C x 1 9 / L
            B     0           2.0      [0 ]

      o m  t    p
Film C m en : ap earan      g est C
                      ces su g     ML
    CML - clinical features of chronic
                 phase
•   Peak age 20 to 40 years
•   Weight loss, night sweats
•   Big spleen
•   Gout
•   Often found by chance
        basophil
                   blast

neutrophils
and                        promyelocyte
precursors
CASE 1
A 73 year old man is to undergo surgery to repair a left inguinal hernia. He is seen for a pre-
operative medical assessment and had the following blood work done the day prior. He has
otherwise been well and is on no medications   .
test                result                          normal range           units
leukocytes          5.2                             4.0-11.0               x109/L
hemoglobin          14.2                            14-18                  g/L
MCV                 84.5                            80-100                 fL
platelets           98                              140-400                x109/L
neutrophils         3.0                             2.0-7.5                x109/L
neutrophils         1.5                             1.5-4.0                x109/L
monocytes           0.6                             0.2-0.8                x109/L
eosinophils         0.1                             0.0-0.7                x109/L
basophils           0.0                             0.0-0.1                x109/L
CASE 2
A 23 years old male is seen in the clinic because of a 2 month history of recurrent epistaxis
and increased bruising. The following result were obtained on a CBC

test                result                          normal range          units
leukocytes          4 .2                           4.0-11.0               x109/L
hemoglobin          14.2                           140-180                g/L
MCV                 84.5                           80-100                 fL
RDW                 13.1                           11.5-14.5
platelets           28                             140-400                x109/L
neutrophils         2.2                            2.0-7.5                x109/L
neutrophils         1.6                            1.5-4.0                x109/L
monocytes           0.4                            0.2-0.8                x109L
eosinophils         0.1                            0.0-0.7                x109/L
basophils           0.0                            0.0-0.1                x109/L

				
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