Haematology Team431
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  White Blood Cells
       Abdulrahman Alkadhaib & Alaa Alanazi
              Mohammed
               Page 1  Al-Dhaheri
                                                                          Haematology Team431
    Red color = Important information
    Blue color = Additional notes
Objectives:
   •   Identify the types of white blood cells in a normal differential count.
   •   Know the various leukocyte functions.
   •   Recognize the abnormalities of the white blood cells and what they imply.
   •   Interpret the results and correlate the changes with the patient’s clinical state
       (presentation, symptoms and signs, etc….).
Pluripotent stem cells can differentiate into:
    Mixed Myeloid Progenitor: produces red cells, platelets, monocytes, neutrophils, basophils
     and eosinophils.
    Lymphoid Progenitor: produces T and B lymphocytes.
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This picture shows the different factors that controls Haematopoiesis (formation of blood cells)
                      such as colony stimulating factors and interleukins.
           Granulopoiesis
       Stages of Granulopoiesis (the formation of granulocytes within the bone marrow).
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            Haematology Team431
         This normal peripheral
         smear demonstrates:
         Segmented neutrophil
         and
         Band neutrophil
          This normal peripheral
          smear demonstrates:
          Segmented neutrophil
          and
          Lymphocyte
          Lymphocytes are
          characterized by a large
          nucleus
           This normal peripheral
           smear demonstrates:
           Monocyte
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                                                  Haematology Team431
                                               This normal peripheral smear
                                               demonstrates:
                                               Eosinophil
                                               and
                                               Lymphocyte.
             Normal white blood cells (WBCs)
  Band
Neutrophil                                                        Eosinophil
Lymphocyte
                                                                  Segmented
                                                                  Neutrophil
Monocyte
                                                                   Basophil
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Functions of White Blood Cells:
  1- Phagocytosis
   The neutrophils and the monocytes engulf foreign particles and bacteria
   through their phagocytic action, thereby destroying their action.
  2- Body defense
   WBC manufactures anti-bodies and immune bodies to increase the power
   of resistance against any infection.
  3- Formation of fibroblast
     Lymphocytes may be converted to fibroblasts in the area of inflammation
     and help the process of tissue repair and regeneration.
  4- Secretion of heparin
   The basophile leucocytes are supposed to secrete heparin (a substance of
   liver), which prevent, intravascular clotting.
  5- Anti histamine functions
     The eosinophils are believed to defend the body against allergic
     conditions in which histamine like bodies are produced in excess.
  6- Production of thromboplastic substances
   Due to the production of such substances, the process of coagulation and
   the deposit of clot are facilitated.
  7- Destroy Cancer Cells
   In addition to recognizing and killing virally infected cells, T lymphocytes
   can also target and kill tumor cells or abnormal cells that may represent
   the early beginnings of a tumor.
  8- Manufacture of trephones:
    Leucocytes manufacture certain substances called trephones from plasma
    protein, which exert great influence on the nutrition, growth and repair of
    tissues.
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White Blood Cells Abnormalities:
   Benign
    1- Quantitative abnormalities (abnormality in the number of blood cells)
  - Leukocytosis (an increase in the number of white blood cells in the blood)
  - Leukopenia (a decrease in the number of white blood cells blood)
     2- Qualitative Abnormalities (abnormality in the function of blood cells)
     3- Leukemia
Laboratory Evaluation of Leukemia:
Morphology
Cytochemistry
Genetic analyses
Chromosomal molecular Immunology
   Acute
  - Myeloid Leukemia
  - Lymphoid Leukemia
   Chronic
  - Myeloproliferative Disorders
  - Lymphoid Leukemia
   Myelodysplastic Syndromes
   Lymphoma
   Immunosecretory Disorders (a group of disorders characterized by monoclonal
     proliferation of immunoglobulin-producing cells that resemble lymphocytes or plasma cells)
   Myeloma (a cancer of plasma cells)
   Other Plasma Cell Disorders
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                              Neutrophilia
                (An increase in number of neutrophils in the blood)
Causes:
    Acute infections          Bacterial, viral, fungal, mycobacterial and
                                                   rickettsial.
    Physical stimuli          Pregnancy (the main cause of Neutrophilia) ,
                                      trauma, electric shock, Anoxia.
                                             Corticosteroids
  Drugs and chemicals                       adrenaline, lead
                                       mercury poisoning, lithium
                                    Acute haemorrhage, acute haemolysis,
 Hematological causes           transfusion reactions, post-splenectomy,
                                 Leukemia and myeloproliferative disorders.
   Malignant disease       Carcinoma, especially of gastro-intestinal tract, liver
                                              or bone marrow
Miscellaneous conditions      Certain dermatoses, hepatic necrosis, chronic
                                         idiopathic leucocytosis
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                                   Lymphocytosis
             (An increase in the number of lymphocytes in the blood)
Non-Malignant causes:
                       Infectious mononucleosis
Virus infections
                       Infectious lymphocytosis
(main cause)
                       Cytomegalovirus infection
                       Occasionally mumps, varicella, hepatitis, rubella, influenza
                       Pertussis
Bacterial Infections
                       Occasionally cat-scratch fever, tuberculosis, syphilis, brucellosis
Protozoal infections Toxoplasmosis
                     Occasionally malaria
Other rare causes      Hyperthyroidism, congenital adrenal hyperplasia
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                               Monocytosis
            (An increase in the number of monocytes in the blood)
Causes:
Chronic bacterial infections     Tuberculosis, subacute bacterial
                                 endocarditis, brucellosis
Other Specific Infections        Malaria, Kala-azar, trypanosomiasis,
                                 typhus, Rocky Mountain spotted fever
Malignant diseases               Hodgkin’s disease, carcinoma
                                 Acute myeloid leukemia
Leukemia                         Chronic monocytic leukemia
                                 Familial benign and severe neutropenia
Neutropenias                     Cyclical neutropenia
                                 Drug-induced Agranulocytosis
                                 Cirrhosis, systemic lupus erythematosus,
Miscellaneous                    rheumatoid arthritis
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                                   Eosinophilia
                          (Increase in number of eosinophil)
Causes:
Allergic reactions   Asthma, hay fever, urticaria, angioneurotic edema
Parasitic            Tissue parasites – trichinosis, filariasis,
Infestation          Visceral larva migrans, etc...
                     Intestinal parasites – Ascaris, Taenia, etc. (less regularly)
Skin disorders       Pemphigus, pemphigoid, eczema, psoriasis, (dermatitis herpetiformis)
Drug                 Especially iodides, penicillin, allopurinol, gold salts, tartrazine
hypersensitivity     Loffler’s pulmonary syndrome and Loffler’s endomyocarditis
reactions
                     Tropical eosinophilia (probably filarial)
                     Especially Hodgkin’s disease,
Malignant diseases carcinoma of ovary, lung stomach,
                     angioimmunoblastic lymphadenopathy.
Following            Hypereosinophilic syndromes
irradiation or       Eosinophilic leukemia
splenectomy
                     Polyarteritis nodosa, ulcerative colitis, sarcoidosis, scarlet fever,
Miscellaneous        pernicious anaemia, chronic active hepatitis, eosinophilic granuloma,
Conditions
                     familial eosinophilia
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   Leukemoid Reaction or Leucoerythroblastic Anaemia
Leukemoid Reaction: an increase in white blood cell count (Leukocytosis)
caused by an infection or other disease. (It’s not a sign of cancer)
Leucoerythroblastic Anaemia: appearance of immature myeloid and nucleated
erythrocytes in the blood caused by infiltration of the bone marrow by foreign
or abnormal tissue.
Causes:
                               a. Pneumonia, septicaemia, meningococcal meningitis
Severe infections
especially in children         b. Infectious mononucleosis, pertussis
Intoxications                  Eclampsia, severe burns, mercury poisoning
Neoplasia                      Especially with bone-marrow infiltration
Severe haemorrhage or
haemolysis
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                                  Neutropenia
                         (Decreased number of neutrophils)
Causes:
Drugs                      Selective neutropenia
                           Agranulocytosis (Aplastic anaemia)
Infections                 Viral – including hepatitis, influenza, rubella
                           Bacterial – typhoid fever, brucellosis, military tuberculosis
                           Rickettsial and protozoal infections (Sometimes)
Megaloblastic Anaemia Vitamin B12 or folate deficiency
Chronic neutropenia        Chronic idiopathic neutropenia
                           Immune neutropenia
                           Congenital neutropenias
                           Cyclical neutropenia
Hypersplenism              Primary
                           In association with cirrhosis, Felty’s syndrome, etc…
Ionizing radiation and     Radiotherapy
cytotoxic drugs            Alkylating agents, antimetabolites, others
Malignant disease          Acute leukaemia
                           Leuco-erythroblastic anaemia due to metastatic
                               carcinoma, multiple myeloma or lymphoma
Micscellaneous             Systemic lupus erythematosus, myxoedema,
conditions                 hypopituitrism, iron deficiency, anaphylactic shock
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                                   Lymphopenia
                         (Decreased number of lymphocytes)
Causes:
                                    Mostly from gut as in intestinal lymphangiectasia,
              Loss
                                    Whipple’s disease and rarely Crohn’s disease
                                    Thoracic-duct fistula
                                    Primary, or secondary to gut disease
           Maturation
                                    Vit B12 or folate deficiency
                                    Zinc deficiency
                                    Antilymphocyte globulin
     Pharmacological agents         Corticosteroids
                                    Cytotoxic drugs
                                    Severe septicaemias
            Infections              Influenza, occasionally other virus infections
                                    Colorado tick fever
                                    Miliary tuberculosis
                                    Collagen vascular diseases, especially SLE
  Other miscellaneous conditions    Malignant disease
                                    Other conditions with lymhocytotoxins
                                    Radiotherapy
                                    Graft-versus-host disease
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      Leukocyte Morphological Abnormalities
 Congenital abnormalities
                                       Characterized by giant platelets
                                                    Large granules
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 Acquired anomalies:
                        Indicate bacterial infection
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Additional information
    Complete Blood Count test (CBC)
                                                  Normal Range
         White Blood Cells (WBCs)                4 – 11 x 109 / L
            Hemoglobin (HGB)                     120 – 160 g / L
              Platelets (PLT)                   140 – 450 x109 / L
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                                                             Haematology Team431
                                       Case 1
•   History:
This 20 year old male came to the emergency room with severe abdominal pain in the
right lower quadrant. He had a fever of 39 0C. On examination, he had a rigid abdomen
& rebound tenderness in the right lower quadrant. There were no other abnormalities.
Urinalysis was within normal limits. A CBC showed Hgb 140 g/l, WBC 25 x 109/L,
and platelet count 350 X 109/L.
What are the WBCs predominantly seen?
Mainly neutrophils
Notice that the WBC count is higher than in a normal smear.
In addition a small but increased number of band forms are seen.
The platelets are moderately increased in number.
What is the name for this type of leukocyte reaction?
This reaction is known as Neutrophilia.
What do you think the diagnosis is?
The diagnosis is acute appendicitis.
(Most, but not all, cases of acute appendicitis are associated with Neutrophilia).
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                                       Case 2
•   History:
 This 17 year old female was sent home from summer camp because of
weakness, lassitude, and sore throat. On examination she was found to have an
inflamed pharynx, enlarged tonsils, several enlarged and slightly tender lymph
nodes in the neck, a palpable spleen, and a tender palpable liver edge.
CBC showed Hgb 149 g/l, WBC 12.5 X 109/L, and platelet count 282 X 109/L
What are the WBCs predominantly seen?
The predominant cells are lymphocytes with many atypical lymphocytes.
What is your diagnosis in this case?
Infectious mononucleosis.
What is the differential diagnosis?
- Other viral infections including hepatitis and cytomegalovirus.
- It should not be confused with leukemia.
What other laboratory test that may be helpful in arriving at a specific diagnosis?
Serologic test for infectious mononucleosis like Paul-Bunnell (Monospot) test
     would confirm the diagnosis in most cases.
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Questions:
  1- What is the WBCs abnormality that can be seen in a patient with
     pertussis?
     A –Eosinophilia
     B – Monocytosis
     C –Lymphocytosis
  2- Lymphopenia is found in patients with :
    A – Milliary TB
    B – Acute leukemia
    C – Carcinoma of the ovary
  3- May – Hegglin Anomaly characterized by :
     A- Large granules
     B- Giant platelets
     C- Hyper segmented neutrophil
Answers:
C,A,B
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