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					Haematology

Shadi Abdel-Gadir
                                                                                                 • 7-10hrs  migrates to tissues
                                                                           Neutrophil            • Defence, phagocytosis, kills organisms


                                                                                                • In blood for less time than neutrophils
                                                      Granulocyte          Eosinophil
                                                                                                • Defence against parasites

                                                                            Basophil                 Allergies
Multipotent myeloid
     stem cell
                                                                          In blood for several days  migrates to tissues  macrophage
                                                      Monocyte            Scavenge + stores iron



                            Erythropoeisis                                                                               •120 days
                                                       Erythroid         (pro)erythroblast          Erythrocyte          •O2/CO2 transport
                         Req erythropoietin, in
                         kidney, in response to ↓O2                                                                      •Destroyed in spleen
  Pluripotent lymphoid
    myeloid stem cell

                                                                                                     • 10 Days
                                                         Megakaryocyte           Platelets           • Primary haemostasis, contributes
                                                                                                     phospholipid  ↑coagulation




                                                           T Cells

  Lymphoid stem cell                                                         Intravascular lifespan is very variable
                                                            B Cell           Recirculate to lymph nodes/ other tissues then back to blood

                                                           NK Cell
                                                                               RBC ABNORMALITIES

                                                        Round

                         Macrocytosis                    Oval
          Anisocytosis                                                          ↑Blue tinge to cytoplasm       Reticulocye stain using methylene blue
             (size)                                   Polychromatic             RBC is young                   Precipitates reticulum – more reliable,
                         Microcytosis                                                                           can count no. Of reticulocytes

                         ↑Area of central pallor
         Hypochromia     ↓Haeem content + conc., often with microcytosis


Colour                                               Spherical
                          Spherocytosis              Round/regular outline – lack of central pallor
                                                     ↓cell membrane + no change in cytoplasm  cell rounds up
          Hyperchromia
                                                     Irregular outline
                          Irregular                  Smaller
                          contracted cells           Result from oxidant damage to haemoglobin/ membrane

                                                    ↑Haemaglobin in central pallor area
                          Target Cells              Causes: jaundice, liver disease,
          Polkilocytes                              haemoglobinopathies, hyposplenism
            (shape)                                  Eliptical
                          Eliptocytes                Heriditary or Iron def.

                                                     Crescent shaped
                          Sickle Cells               Polymerisation of haemaglobin S when in high conc
                                                    .
                          Fragments                  Small pieces aka schistocytes.




                                           Irregular clumps
         Agglutinates
                                           Antibody on surface of cells
                                          .
         Rouleaux                          Stacks (coins)
                                           Alterations in plasma proteins
                                          .
         Howel-Jolly                       Nuclear remnant in RBC
         body                              Lack of splenic function
                                          .
              WBC ABNORMALITIES
Atypical lymphocyte – Abnormal cells in infectious mononucleosis
                          (glandular fever)


                                 Neutrophils


             Left Shift            Toxic               Hypersegmented
                                granulation

                                                  ↑Lobes/ segments
          ↑Non                       Heavy
          segmented              granulation of
          neutrophils              neutophils
                                                       ↓B12/ Folic Acid


                             Inflammation/Infection/
                              Necrosis but normal in
                                   pregnancy
                                                                     Iron def

                                                Haem
                                                                   Anaemia of
             Microcytic                                                                                       ↓prod of
                            Defects in                           Chronic disease
           (hypochromia)                                                                                    haemoglobin in
                                                                                                            bone marrow)
                                                                     α-thal
                                                Globin
                                                                     β-thal



                                    Peptic ulcer/ oespophageal varices/ trauma                     Blood Loss

            Normoocytic            Iron Def/ Aneamia of Chronic Disease/ Bone marrow               Failure of production of RBCs
          (normochromia)                     failure, suppression or infiltration


                                   Hypersplenism eg portal cirrhosis                               Pooling of RBCs in spleen
ANAEMIA

                                                                                                    Megaloblast = abnormal bone marrow erythroblast
                                  ↓B12/folic acid              Megaloblastic anaemia
                                                                                              Delay in maturation of nucleus while the cytoplasm continues to
                                                                                               mature  cell grows. Show nucleocytoplasmic dissociation.
                                                                                                             Cells become larger than normal
                                  Drugs interfering with DNA synthesis
             Macrocytic
           (normochromia)
                                   Liver disease, alcohol toxicity


                                    Recent major blood loss
                                   with adequate iron stores                     ↑reticulocyres are released into circulation.
                                                                                       They are 20% bigger  ↑MCV

                                   Haemolytic Anaemia
            Acute damage to RBC’s                                Intravascular             HAEMOLYTIC ANAEMIA                             Extravascular
                                                                                                                                                                                Defective RBCs by the spleen



                                        Inherited                                                                                                                           Acquired
                                                                                                                                                                                              Microorganism
                                                                                                                                                                                             malaria whole cell
                                                                                                                                     Whole cell                                                  microbial
   Cell membrane                                           Enzymes                                       Drugs -
                                Haemoglobin                                                                                           oxidant
                                                                                                         dapsone
                                                                                                                                                           Autoimmune                  Microangiopathic
                                                                                                                 Chemicals -
                                   Sickle cell                                                                                                             haeomolytic                    whole cell
                                                                                                                 napthalenne        Food eg
                                   anaemia                                                                                                                   anaemia                     mechanical
Hereditary spherocytosis                                                                                                          broad beans
or chronic compensatory
       haemolysis                                                                                                                                                      Corticosteroids/immunosuppressives
                                                    Pyruvate kinase def
                                                                                                           Causes haemolysis in                                        Splenectomy
                                                    (glycolytic pathway)
                                                                                   G6 phosphate
                                                                                 dehydrogenase def                                                         Autoantibodies                  Diagnosis
RBCs enter the circulation                                                        (pentose shunt)                                                           against RBC          Spherocytes, ↑reticulocytes
                                                                                                                                                              antigens           Ig on RBC surface
                                                                                                                                                                                 Antibodies to RBC antigens or
                                                                                                                                                                                other autoantibodies in plasma
   Lose membrane
      in spleen          Spherocytes – less flexible 
                          removed extravascularly                 Protects against       X linked                                                        Recognised by
                             BM ↑RBC output                       oxidant damage                                                                            splenic
                         polychromasia reticulocytosis                                                                                                    macrophages
  Become spherocytic                                                                               Causes intermittent
     and prone to                                              Exogenous     During
                                                                            infection            intravascular episodes
                                                                                                                                                           Removes
                                ↑Bilirubin –                                                                                                               membrane
     Haemolysis              Jaundice, gallstones                                                                   Haemoglobin
                                                                               Acute
                                                                             haemolysis                              denatured
                                                                                                Irregular
                                                                                             contracted cells                                             Spherocytosis
          Good diet – Folic Acid                                 Can require transfusion
                                                                                                                                                          – less flexible
          Splenectomy                                            Prevention important
                                                                                                                 Forms round inclusions
                                                                                                                     – Heinz bodies
                                                                                                                                                             Removal of
                                                                                                                                                            RBC by spleen


                                                                                        Removed in spleen                     Detected by
                                                                                         leaves defect in cell                 specific test
                                 Polycythaemia

                                                   Hyperviscosity
           True –       Pseudo
        ↑RBCs in        ↓plasma                                            Blood removed to
                                                         Vascular
        circulation     volume          Causes                               thin the blood
                                                        obstruction


↑Hb, RBC, PCV
compared with                   Erythropoeitin        Erythropoetin
healthy subjects of             dependent (too        independent
same age + gender                   much)

                      Hypoxia                                Polycthaemia vera – an
                                          Renal/             intrinsic bone marrow
                                         ectopic             disorder that is chronic
                       Administration    tumour                 myeloproliferative


                                                            Drugs that reduce bone
                                                            marrow production of
                                                            RBCs
                    FBC
• Red Cells: Hb, MCV
• WBC: cell type and presence of abnormal or
  immature forms
• Platelets
                            MCH & MCHC


    Mean Cell haemoglobin (MCH)                Mean cell haemoglobin concentration
                                                             (MCHC)
Amount of haemoglobin in given vol = Hb        Amount of haemoglobin in given vol          =    Hb
    No.of RBCs in given vol        RBC        Proportion of sample represented by RBC          PCV


   Absolute amount of haemoglobin in an           Concentration of haemoglobin in a red cell
              individual red cell
Parallels MCV in micro/macrocytic anaemmias            Related to the shape of red cells
                 Anaemia
• Hb
• MCV

    Microcytic      Normocytic            Macrocytic
 Iron def        Acute blood loss      B12
 Thalessaemia    Haemolytic            Folate
 ACD             Marrow infiltration   Alcohol
                 ACD                   Reticulocytosis
                                       Hypothyroid
               Haematinics
• Deficiencies can cause anaemia:

  Iron     Duodenum
  B12      Terminal ileum
  Folate   Duo and jejenum
Iron absorption
               Iron deficiency
• Blood loss
                  Intake vs Loss


        Diet                Desquamated cells of
                            the skin & gut
        Malabsorption not   Menstruation
        common

• Atrophic tongue!
                   IDA vs ACD

  Iron parameter      IDA       ACD
Serum iron
TIBC
Serum ferritin
Serum sTfR                       N
B12 absorption
                   B12 deficiency
                   Intake vs Utilisation


     Diet RARE
                                      Not common
     Small bowel disease
     Reduction in IF

•   Pernicious anaemia – autoantibodies
•   Neurological problems
•   Beefy tongue!
•   Schilling test – radioactive; im. With IF
               Folate defiency
                Intake vs Utilisation


    Diet COMMON                 Pregnancy
                                Lactation
    Coeliac disease             Adolescence
    Antifolate drugs
                                Excess turnover of cells:
• Neural tube defects           Haemolysis, malignancy
• NO neuropathy
             Haemolytic anaemia
 • Intravascular vs Extravascular : bilirubin, LDH
 • Polychromasia, reticulocytosis

                  Aquired vs Inherited

                               Hereditory spherocytosis
Damage to red cell membrane
                               Thalassaemia
Malaria
                               Sickle cell anaemia
Oxidant damage
                               G6PD deficiency
                               Pyruvate kinase deficiency
             G6PD deficiency
• X-linked
• Inability to detoxify oxidising agents
• Heinz bodies, spherocytosis
                Polycythaemia
           True                      Apparent

Primary:     Secondary                         Dehydration

               Hypoxia:            chronic smoking
PRV

             high altitude
                              lung disease

           Excess erythropoietin
Production by
                       RBC             Cell loss/
Bone marrow                            destruction


                             Shortened survival
Polycythemia                   bleeding
                               haemolysis
                                •Acquired (environment)
1. Haematinic deficiency            •Immune
2. BM infiltration/failure          •Microangiopathic
   • Haemopoietic cancer            •Malaria
   • Metastatic cancer              •**PNH
   • Aplasia                    • Inherited
                                    •Haemoglobin
                                    •Enzyme
                                    •Membrane
         Reduced cell counts

Three cell lines reduced/involved
• Think bone marrow failure/infiltration
(but don’t forget Vit B12/folate deficiency)

One cell line reduced
• Think increased destruction/loss (but
don’t forget iron deficiency in low RBC/Hb)
Production by
                   Platelets         Cell loss/
Bone marrow                          destruction



Primary: CML                 Immune mediated
Secondary: infection,        Hypersplenism
inflammation, pregnancy,     Disseminated
post-splenectomy             intravascular coagulation


1. Drug induced
2. BM infiltration/failure
   • Haemopoietic cancer
   • Metastatic cancer
   • Aplasia
                    Abnormal WBC
Cell Production              Cell Survival

Reactive
•   Infection
•   Inflammation
Malignant
•   Leukaemia
•   myeloproliferative




Impaired BM function
                             Immune breakdown
•B12 or Folate deficiency
•BM failure
    •Aplastic anaemia
    •Post chemotherapy
    •Metastatic cancer
    •Haematological cancer
                  White cells
• Neutrophilia: bacterial infections, inflammation,
  malignancy, necrosis, treatment with
  corticosteroids?
• Neutropenia: post-chemo, viral, adverse drug
  reactions eg. carbimazole
• Lymphocytosis: viral, lymphomas, chronic infections
  eg TB, chronic lymphocytic leukaemia
• Eosinophilia: parasite infection, atopic allergic,
  Hodgkin
• Acute vs Chronic
• Myeloid vs lymphoid

              IMMATURE CELLS    MATURE CELLS

     AML         Increased         Decreased

     CML                       Increase impaired

      ALL        Increased       No maturation

     CLL                       Increased abnormal
                                  mature B cells
Mature lymphocytes         Immature lymphoblasts
•CLL                       •Acute lymphoblastic leukaemia
•autoimmune/inflammatory
 disease
                 elevated WCC
                   All lineages or only one          Reactive/
                        neuts, eos, baso             infection

                   Lymphocytes
mature cells
                   Reactive(viral) or primary
                   (chronic lymphocytic leukaemia)



                            Neutrophils + myelocytes
   Mature+                  + basophils
   immature                 ?Chronic myeloid leukaemia



                                Blasts +
                                low Hb
Immature cells                  low platelets
                                ? Acute leukaemia
Bleeding disorders
      Coagulation screen
             What do you get?

Prothrombin time (± INR)
Activated partial thromboplastin time (APTT)
Thrombin time (TT)
   XII    XIIa                                   Blood coagulation

    XI            XIa                                                     Tissue factor
                                               VIIa                       (vessel damage)
                                               Ca2+
         IX                 IXa
                                                      VIIa                     EXTRINSIC
INTRINSIC               VIIIa                         Ca2+                     PATHWAY
PATHWAY                 Pl
                        Ca 2+

              X                      Xa                      X
                                          Va
                                          Pl
                                          Ca2+                               COMMON
                  Prothrombin                    thrombin (IIa)
                                                                             PATHWAY


                                  Fibrinogen                     Fibrin
                                                                          thrombin
                                                                     XIIIa      XIII
                                                        Crosslinkedfibrin
              Haemostasis screening
APTT                               INR (Prothrombin Time)
Measures                           Measures
intrinsic and common pathway       extrinsic & common pathway
Common abnormality                 Common abnormality
heparin                            warfarin
liver disease                      liver disease
DIC                                DIC
haemophilia

                               TT (thrombin time)
                               Measures
                               Fibrinogen&thrombin inhibition
                               Common abnormality
                               DIC
                               heparin
        What you need to know
• normal ranges for WBC, Hb, MCV, platelet count in
  adults
• If the WBC is abnormally high or abnormally low we
  expect you to be able to work out whether it is the
  count of neutrophils, lymphocytes or eosinophils
  that is causing the abnormality in the total WBC
• We expect you know that there are variations in
  haematological normal ranges related to gender, age
  and ethnic origin
Questions
                         EMQ
                          1. A patient with infectious
•   A Anaemia             mononucleosis.
•   B Lymphocytosis
                          2. A patient who has just started
•   C Lymphopenia         treatment with B12 and folate
•   D Neutropenia         for megaloblastic anaemia.
•   E Neutrophilia
                          3. A patient with chronic renal failure.
•   F Pancytopenia
•   G Polycythaemia       4. A patient with chronic obstructive
                          pulmonary disease.
•   H Reticulocytosis
•   I Thrombocytopenia    5. A patient with disseminated
•   J Thrombocytosis      intravascular coagulation.
                                  SBA
• A 61-year-old woman with pancytopenia, mild jaundice, and peripheral
  neuropathy is found to have decreased serum levels of vitamin B12.
  Which of the abnormal cell morphologies listed below is most likely to be
  present in a smear made from her peripheral blood?


• A. Hypersegmented PMNs

• B. Large granular lymphocytes

• C. Oval microcytes

• D. Pelger-Huet neutrophils

• E. Plasmacytoid lymphocytes
                             SQA
• A 16-year-old girl has a sore throat, enlarged tender cervical
  lymph nodes, and low-grade fever for 3 days. In addition to
  erythematous pharyngeal mucosa and cervical
  lymphadenopathy, physical examination reveals mild
  splenomegaly. A complete blood count (CBC) shows an
  increased number of white blood cells with a lymphocytosis
  and many reactive lymphocytes.


• What is the most likely diagnosis?

• What laboratory tests would be helpful in confirming the
  diagnosis?
                         SAQ
• 63 year old man presents with a left-sided TIA
• Similar episode 1 week earlier. Results of FBC:

•   Hb 21.2 (13.0-16.5)
•   Haematocrit 0.61
•   WCC 15.3 x 109 (4-11 x 109)
•   Increased neutrophils and eosinophils
•   Platelets 897 x 109 (150-400 x 109)
•   Bilirubin 8 (1-22)
•   AST 30 (19-48)
•   Cholesterol 3.6 (0.1-1.6)
                     SQA
• 58 year old woman with pallor, decreased
  sensation in both legs below the knee, absent
  ankle jerk
• Hb 8.2 (13.0-16.5)
• MCV 124 (80-100)
• WCC 2.4 x 109 (4-11 x 109)
• Platelets 102 x 109 (150-400 x 109)

				
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posted:4/11/2011
language:English
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