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Comprehensive Description of Blood Diseases

By Catherine Watson,2014-12-13 13:41
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Comprehensive Description of Blood Diseases

    Comprehensive Description of Blood Diseases

    Hematology/Lymph

    Compiled by Ben Lawner

    UP TO MIDTERM EXAMINATION

References:

    Robbins, Pathologic Basis of Disease

    Hilman, Robert S. Hematology in Clinical Practice th Edition Harrison’s Textbook of Internal Medicine, 15

    Dr. Khin’s handouts

    DISORDERS OF RED BLOOD CELLS, THE ANEMIAS AND THALASSEMIAS, PCV/PRCA Consequences of hemolytic anemia

    1. RBC rupture leads to hemoglobinemia and uria

    2. Haptoglobin decreased

    3. Bilirubin increased, leads to jaundice and gallstones

    4. Bone marrow examination reveals erythroid hyperplasia (ME 1:2) --; INCREASED

    5. Left shift; Increased reticulocytes, Increased normoblasts

    6. Erythroblastosis

    DZ/CLASS MORPHOLOGY PATHOLOGY S/S AND CLINICAL LAB TX

    Normochromic Hemorrhage, hemolysis, excess Weakness HgB decreased Blood replacement Anemia of Blood

    Normocytic demand, malabsorption Fatigue HCT decreased Loss

    Pallor MCV normal

    Cyanosis Reticulocytes increase

    Can give rise to iron

    deficiency if chronic PB: Reticulocytes >

    1%

    Normocytic 50% idiopathic. Unknown why RBC decreased Aplastic anemia NO SPLENOMEGALY-

    Normochromic bone marrow is defective. Can MHC normal If present, reconsider

     be due to: Thrombocytopenia diagnosis.

    Failure of RBC -Stem cell defect Granulocytopenia

    production -T cell mediated attack on bone Associated with hepatitis Hypocellular and

     marrow FATTY bone marrow

     1

     -Drugs Associated with pancreatitis Decreased

    -Chemicals like benzene, reticulocytes

    solvents, insecticides, radiation Poor prognosis in crisis Dry bone marrow tap

    -Pancytopenia that is

    characterized by Decreased or absent

    thrombocytopenia, anemia, reticulocytosis

    neutropenia.

    Two major mechanisms:

    Immunologically mediated

    bone marrow suppression

    Intrinsic stem cell defect

    Associated disease: lupu, PNH,

    hepatitis, Fanconi

    Too few, an anemia Folic acid deficiency, rapid in Weakness HCT decreased Folic acid Folic Acid

    of decreased onset, usually from change in Fatigue MCV increased supplementation Deficiency Anemia

    production diet. Common in nursing home Pallor Hgb decreased

     patients or patients with Cyanosis Macrocytic increased folic acid demand: NO CNS signs

    Megaloblasic pregnancy, etc. Schilling test for DDX

    -Decreased intake Giant metamyelocytes

    -Increased requirements Glossitis

    -Impaired use Stomatitis

    -May occur in chronic

    alcoholics

    Hemolytic anemia G6DPH lacking, this enzyme Weakness Heinz bodies G6PDH deficiency

    protects cells from oxidative Pallor Bite cells (from spleen

    injury. Denatured hemoglobin Jaundice phagocytosis)

    may precipitate as HEINZ Reticulocytosos

    bodies. G6PDH may provide HCT decreased

    X linked modest protection from HgB decreased

    Mediterrean = severe infection with Plasmodium

    Blacks - mild

    Susceptible to drugs:

    Antimalarials / sulfonamides /

    Vit K / DKA

     2

    Fava beans may preciptate

    crisis

    Infections may precipitate

    hemolysis

    Common in American blacks.

    Hemolyic Anemia AR Polychromasia Dx’d in childhood Pyruvic Kinase Def

    (enzyme def) #2 MC Enzyme Def. Anisocytosis (PK)

    Poikilocytosis (burr cells)

    Nucleated RBC’s (d/t BM

    so crowded it pushes cells

    out early)

    Splenomegaly

    Jaundice

    Cholelithasis (gall stones)

     AR Cyanosis (nailbeds) Tx: methylene blue Methemoglobinemia

    Ferrous (Fe2+) to ferric (fe3+) Enzyme Def

    state

    Hemolytic anemia Specrtin deficiency. Cells Anemia Anisocytosis Hereditary

    become spherical. RBC’s Splenomegaly Dark RBCs with loss Spherocytosis

    recognized as foreign in spleen Jaundice of central pallor

    and phagocytized. CAUTION- Aplastic crisis Erythroblastosis

    may result with parvovirus M:E ratio can invert

     (go from 3:1 to 1:3)

    Nucleated RBC’s Hemolytic anemia Formation of antibodies against RAYNAUD’s phenom. COOMBS reagent Prednisone therapy Immune Mediated

    RBCs. positive: If RBCs have Hemolytic Anemia

    WARM: Ab active at body Pallor antibodies on them, Immuno suppressive

    temperature, idiopathic. then agglutination will agents

    Secondary to drugs and Cyanosis be seen during

    neoplasm. laboratory testing

    COLD: Active antibody at 0 to

    4 degrees. Agglutination occurs HgB decreased

    in periphery. Occurs in HCT decreased

    recovery phase of infections.

    Microcytic Excess demand, chronic blood Weakness HgB decreased Iron replacement Iron Deficiency

    Hypochromic loss, depletion of stores, Fatigue HCT decreased Anemia

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    excessive menstruation, GU/GI Pallor MCV decreased

    bleed, dietary. Cyanosis TIBC increased

    *Common in toddlers, Serum Ferretin decr.

    adolescent girls, women of Plummer Vinson IDA: Saturation % decreased

    childbearing age (Per text)

    *Other causes Anemia (Micro/hypo)

    -Impaired absorption Atrophic glossitis

    -Increased requirement Esophageal webs

    -Chronic blood loss

     Dysphagia

    *Iron deficiency in post Koilonychia

    menopausal women or men

    should be considered secondary Most common disorder in

    to GI blood loss until proven world

    otherwise

    Microcytic or Body does not use iron Weakness TIBC normal Treat consequences Sideroblasic

    normochromic or properly to produce Pallor (Adequate iron) and avoid alcholol Anemia

    hypochromic anemia hemoglobin. Looks like IDA in Fatigue HCT decreased

    peripheral blood. HgB decreased

    MCV decreased to

    normal

    Hemolytic anemia Mechanical injury to RBCs Weakness MAHA

    causing fragmentation Pallor Microangiopathic

     Jaundice Hemolytic

    IV hemolysis Anemia

    Jets from AV shunts, cardiac

    problems, mechanical heart

    valves may damage cells.

    DIC causes stricture of

    vasculature and subsequent cell

    lysis.

    Hemolytic anemia Only anemia due to an acquired During exacerbation, Values may be normal PNH

    membrane defect. Deficiency S/S similar to other except during Paroxysmal

    of cell membrane protients. hemolytic anemias. nighttime exacerbation Nocturnal

    Decrease of decay accelerating Hemolytic

     4

    factor (DAF) may be Extremely rare Anemia

    implicated. Bursts of nighttime

    hemolysis that may be

    secondary to decreased pH.

    Mutation in PIGA.

    Increase in RBC’s RELATIVE: Decrease in Thrombosis HgB increased Polycythemia Vera

    proportion of plasma to Infarcts RBC increased

    RBCs… dehydration. Erythematous skin PLT increased

    PRIMARY: Absolute increase Ruddy appearance WBC inceased

    in red cell mass Headache Erythropoetin levels

    SECONDARY: Rare, Increased blood volume decreased

    associated with excessive RBC Increaed blood viscosity

    formation. A Increased bleeding

    myeloproliferative disorder More common in males

    than in females

    Secondary polycythemia

    from COPD, high altitudes,

    and heart disease

    Normocytic Genetic. Weakness Normal granulopoesis PRCA

    Normochromic Failure of erythroid precursors Fatigue Normal platelets

     with no reticulocyte response. Pallor

    Rare form, failure of

    RBC specific Presents as severe precursors normocytic normochronic

    with no reticular response

    (pseudo-HA)

    Bone marrow hypoplasia

    May be secondary to

    thymoma

     Chronic form of Diamond Diamond Blackfan

    Blackfan anemia. Rare form. Anemia

    Chronic form of PRCA

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Microcytic 1- Deletion of one gene, Trait: No anemia, presents HgB decreased Thalassemia, alpha

    Hypochromic- some a silent carrier state. like B thalassemia minor

    subtypes may mimic 2- Deletion of 2 genes, HgB CHAINS may be anemia of iron ext mild. HBH: Seen in Asians, HBH increased

    deficiency 3- Deletion of 3 genes, ineffective for 02 exchange.

     called Hemoglobin H HCT decreased

     disease Heinz bodies Deletion of one gene depending on severity

    and Hemolysis asymptomatic, no anemia

    4- Hydrops fetalis: Crew cut appearance

    DEATH. Deletion of Erythroid hyperplasia, bone on skull forms

    all 4 genes on alpha changes, changes in facial

    locus bones. Crew cut appearance

    due to bone marrow

    activity.

    Mirocytic Error in HgB synthesis. In beta Depends on severity. May Target cells Thalassemia, Beta

    Hypochromic thalassemia, there is an error in be mild or symptomatic. MCV decreased

    B chain synth. O2 carrying HgB decreased or

    capacity reduced. Growth abnormalities from normal

     improper DNA synthesis. HCT decreased or

    COOLEYS: B thal major. normal

    Homozygous form of disease Fatal in life if severe form is HbF increased

    associated with severe anemia. not treated. Crew cut appearance

    Fetal HgB levels increased. of xray due to bone

    Consider genertic marrow hyperplasia

    counseling. THALASSEMIA MINOR:

    Heterozygous. May be mild or Fragmented RBCs

    asymptomatic. Mutation of B

    gene on chromosome 11 locus Increased HbA2 chains

    in Thalassemia minor Too few, an amemia Vitamin B12 deficiency. Loss Weakness HCT down Replacement of Vitamin B12 /

    of decreased of intrinsic factor, gastrectomy, Fatigue MCV increased folic acid AND Pernicious anemia

    production atrophic gastritis, TI resection Pallor Retics decreased B12. Never give Macrocytic (B12 absorbed in terminal Cyanosis Hypersegmented folic acid alone, Megaloblastic ileum), malabsorption, chronic CNS signs PMNs both are necessary

    and long in onset. Pernicious Schilling test: DDx of Low serum B12 for proper DNA

    anemia specifically refers to megaloblastic anemia. Giant metamyelo synthesis

    loss of GIF from mucosal Administration of cytes

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    damage. radioactive B12 and Administration of

    subsequent admin of GIF only folic acid

    will distinguish a B12 results in

    anemia from folic acid persistence of

    deficiency neurological signs

    Pancytopenia and resolution of

    anemia.

DISEASES OF THE WHITE BLOOD CELLS

SOME NOTES:

    Leukocytosis: Increase in total WBC greater than 11,000 per microliter Neutrophilia is greater than 80% of differential

    Neutrophilia may be seen in acute infection

    PB smear may show increased numbers of band cells, a left shift Neutrophilia also seen in tissue necrosis like burnes, stress, exercise, and drug reactions

LEUKEMOID REACTION:

    Resembles leukemia in that it presents with an extreme elevation of peripheral leukocyte count greater than 50,000 with presence of immature neutrophils. Causes include severe infections, severe hemolysis, and malignancy

DDX from leukemia:

    -Immature cells only to myelocyte level.. NO BLASTS!!

    -LAP elevated in granulocytes of LR

    -LAP ABSENT in granulocytes of leukemia

    -Increased basophils in leukemia

    -Basophils normal in leukemoid reaction

    -Philadelphia chromosome is NEGATIVE in leukemoid reaction -Philadelphia chromosome is positive in leukemia

    DISEASE/CLASSIFICAION MORPHOLOGY PATHOLOGY S/S CLINICAL LAB TREATMENT

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    Localized AL seen in lymph nodes in drainage are of infections. Cervical lymph nodes swollen. Acute lymphadenitis

    Generalized AL in bacteremias, viral infections. Nodes enlarged and show microscopically large

    proliferating germinal centers-; abscess formation--;penetration through skin-;draining sinuses.

    TB, syphilis, sacroidosis, cat scratch disease, toxoplasmosis, LGV, viral infections Chronic lymphadenitis

    Follicular hyerplasia: Large germinal centers representing B cell response with proliferating, blast

    transforming lymphocytes. Plasma cells, histiocytes, and neutrophils present in parafollicular regions.

    Two distinct regions are appreciated. 1) A dark zone containing proliferating, blast like B cells. And 2) a

    light zone containing B cells with irregular or cleaved nuclear contours. Also present throughout the

    follicle are phagocytic macrophages. Striking hyperplasia in mononuclear phagocytic cells lining the

    sinuses.

    Paracortical hyperplasia: Proliferation of T cell areas with immunoblast transformation, may efface

    germinal follicles. Seen in drug reactions and viral infections. Hypertrophy of sinusoidal and vascular

    endothelial cells and a mixed cellular infiltrate. Changes are encountered in drug-mediated

    immunogenic reactions, acute viral infections.

    Sinus histiocytosis: Distention of lymphatic sinusoids and infliltration with histiocytes. May be

    particularly prominent in lymph nodes that drain cancers. May represent an immune response on the part

    of the host against the tumor.

    Important to Disease of children and young Abrupt onset with BMA: Hypocellular Aggressive Acute Lymphoblastic

    differentiate ALL from adults. Most common form of fatigue due to anemia, and heavily infiltrated chemotherapy Leukemia, (ALL)

    AML. Relatively leukemia in children, infections due to absence with monomorphic

    condensed chromatin, Approximately 80% are B cell of normal WBCs and poluation of blast Radiation

    presence of scant, type, approximately 20% are T bleeding to to cells. BM elements Intrathecal

    agranular cytoplasm. cell type. Majority of all ALL thrombocytopenia. are markedly reduced. methotrexate

    cells contain deoxynucleotidyl Leukemia infiltrations

    transferase. Etiology is cause bone pain, PB: Moderate to Marrow

    unknown in most cases. splenomegaly, severe anemia transplantation

     hepatomegaly. Leukopenia

    Infiltrations of meninges Thrombocytopenia If 90% or more are BLAST

    cause CNS CELLS-; ACUTE!!!!

     manifestations such as CELLS:

    Majority of ALLs are pre B cell cranial nerve palsies Small size

    tumors that typically manifest High N:C ratio

    as childhood leukemias with Pancytopenia Coarse granules in

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extensive bone marrow and ALL

    variable peripheral blood Thrombocytopenia TdT positive

    involvement. PAS positive

     Elevated LDH and T(9,22) positive

    Onset most common in hyperuricemia

    individuals less than 15 yoa. TdT: Terminal

    Age less than -; poor deoxytransferase is a

    prognosis specialized DNA

     polymerase that is

    Lymphadenopathy expressed by Pre-B

     and Pre-T cells.

    Mediastinal mass

    Presentation in

    adolescene or adulthood-

    ; poorer prognosis

    Philadelphia

    chromosome (T9:22) is

    associated with poor

    prognosis, present in

    about 25% of adult

    cases.

    Diagnosis based on a Malignant neoplastic disorder Anemia Peroxidase positive Tx: Cytotoxic Acute Myeloblastic

    finding of >30% associated with acquired Neutropenia granules. drugs, removal Leukemia, (AML)

    myeloid blasts in bone genetic alterations that result in Thrombocytopenia of the lymphatic

    marrow. replacement of normal marrow Auer rods: Distinctive clone. elements by relatively Prognosis worse than red staining rodlike undifferentiated blast cells. ALL structures which Neoplastic precursor cells represent abnormal accumulate in marrow and Death within months if granules

    suppress remaining normal left untreated

    hematopoeitic progenitor cells. Monoblasts have

    Leukemic organ folded or lobulated

    infiltration nuclei

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    Spontaneous bleeding PB: Occasionally, the

    Fever peripheral smear will

    Fatigue NOT contain blasts.

    Bleeding diathesis Thus, BM aspirate

    Petechiae, ecchymosis necessary to exclude

     AML in patients with

     pancytopenia. Low

    N:C ratio.

    Lymph node Malignant neoplasm of mature Often non-specific BM: Increased Chronic Lymphocytic

    architecture is B cells, unable to differentiate Anemia cellularity. Leukemia

    diffusely effaced by into plasma cells. Hesults in Fatigue Intense lymphocyte small lymphocytes hypogammiglobulinemia. Weight Loss infiltration.

    along with Increase in bacterial infections. Infections Leukocytosis

    prolymphocytes. Bruising

    Proliferation centers Onset in adulthood, median age Lymphadenopathy PB: shows almost all visualized. 60. Splenomegaly mature lymphocytes.

    WBC count increased Absolute

    Most INDOLENT of the lymphocytosis.

    leukemias Smudge cells present:

    Blast crisis rare. fragile lymphocytes

    Survival 4-6 years often rupture during

     preparation.

    *Important factor in

    survival of pt is

    tendency of CLL and

    SLL to transform into

    more aggressive

    neoplasms.

     CML marrows are Malignant neoplastic disorder WBC count markedly PB: predominant Chronic Myeloid Leukemia

    usually 100% cellular. of common hematopoietic elevated neutrophils and Most cells composed precursor cell in which the myelocytees. Entire of maturing granulocute cell series is Splenomegaly due to spectrum of maturing granulocytic predominately affected. 20% of neoplastic granulocyte cells, precursors. Increased all leukemias. extramedullary from myeloblasts to megakaryocytes. hematopoesis. mature neutrophil,

     Onset in adulthood. also basophils and

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