Chapter 12_1 flashcards
(81 cards)
1
Q
White Blood Cells (WBCs) / Leukocytes: Primary Function
A
Protect the body against infection; function within innate and adaptive immune divisions.
2
Q
WBCs of Innate Immune System (First Line of Defense)
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Macrophages (engulf, ingest, enzymatically break down foreign matter), Neutrophils, Eosinophils, Basophils, Natural Killer (NK) cells.
3
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WBCs of Adaptive Immune System
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B lymphocytes (B cells) and T lymphocytes (T cells) - attack specific antigens and maintain memory.
4
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Manufacturing and Maturation Sites of WBCs
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All WBCs manufactured in bone marrow. Lymphocytes mature further in lymphoid tissue (lymph nodes, tonsils, adenoids, thymus gland, spleen).
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Q
Main Disorders Affecting WBCs
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Infections, immune diseases, and hematological neoplasms (leukemias, lymphomas, myelodysplastic syndrome, multiple myeloma).
6
Q
Normal Range of Total WBCs
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4,000 to 10,000 cells per microliter (mcL) (may vary slightly by lab).
7
Q
Three Major Categories of WBCs
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- Monocytes (Macrophages)
- Lymphocytes
- Granulocytes
8
Q
Types of Granulocytes (with granules)
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- Neutrophils (most abundant granulocyte, also called PMNs)
- Eosinophils
- Basophils
9
Q
Agranulocytes (WBCs without granules)
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Monocytes and Lymphocytes.
10
Q
Types of Lymphocytes
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- B lymphocytes (B cells)
- T lymphocytes (T cells)
11
Q
Normal WBC Differential Values (Approximate)
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Neutrophils: 40-80% (Bands: 0-10%)
Lymphocytes: 20-40%
Monocytes: 2-10%
Eosinophils: 1-7%
Basophils: 0-2%
12
Q
Origin of All Blood Cells (Hematopoiesis)
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From pluripotent stem cells in the bone marrow, which can become any type of blood cell.
13
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Two Main Stem Cell Lines for WBC Production
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- Myeloid stem cells: Differentiate into granulocytes (neutrophils, eosinophils, basophils) and monocytes.
- Lymphoid stem cells: Differentiate into lymphocytes (B cells, T cells).
14
Q
Blast Cells
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Immature precursor cells for each WBC cell line.
15
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Maturation of B Lymphocytes
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Mature to a certain extent in bone marrow, then leave and complete maturation in lymphoid tissue (e.g., lymph nodes), where they can develop into plasma cells (antibody-producing cells).
16
Q
Maturation of T Lymphocytes
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Mature to a certain extent in bone marrow, then continue maturation mainly within the thymus gland (become T helper CD4+ and cytotoxic CD8+ cells), then move to lymph nodes for proliferation.
17
Q
Locations of Lymphoid Tissue
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Lymph nodes, spleen, tonsils, adenoids, thymus gland, Peyer’s patches (GI tract), respiratory tract, genitourinary tract.
18
Q
Monocytes: Percentage & Maturation
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Make up 2% to 10% of circulating WBCs. Mature into macrophages when they leave circulation and enter tissue.
19
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Macrophages: Primary Function & System
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Primary function: Phagocytosis (engulf, ingest, enzymatically destroy antigens and cellular debris). Major component of the innate immune system; first responders.
20
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Other Functions of Monocytes/Macrophages
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Synthesize and secrete cytokines (enhance inflammation, stimulate other WBCs). Can become dendritic cells (present antigens to T cells, linking innate and adaptive immunity).
21
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Lymphocytes: Percentage & Main Types
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Make up 20% to 40% of circulating WBCs. Main types: B cells and T cells. Part of the adaptive immune system.
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Function of B Lymphocytes (B cells)
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After antigen exposure, transform into plasma cells, which produce immunoglobulins (antibodies) that attack specific antigens. Provide long-term humoral immunity.
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Function of T Lymphocytes (T cells)
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After antigen exposure, are activated to directly attack specific antigens. Provide long-term cell-mediated immunity.
24
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Granulocytes: General Characteristics
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WBCs with chemical-containing granules in their cytoplasm; granules contain digestive enzymes capable of killing microorganisms and catabolizing debris during phagocytosis.
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Neutrophils (PMNs/Segs): Percentage & Role
Make up 40% to 80% of WBCs. First responders (like macrophages) to infection, stress, inflammation. Lyse bacteria by releasing granule enzymes.
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Neutrophils: Respiratory Burst
When a neutrophil phagocytizes an invader/debris, it releases a respiratory burst of free radicals (superoxides O2-) that contribute to injury of surrounding tissues.
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Mature vs. Immature Neutrophils
Mature neutrophils (Segs): Segmented, multilobed nucleus. Life span 1-2 days.
Immature neutrophils (Bands): Bandlike nucleus. Released by bone marrow when mature supply is exhausted.
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Shift to the Left (Neutrophils)
A laboratory test indicating a high number of bands (immature neutrophils) in circulation. Indicates acute inflammation or infection where bone marrow is working hard to produce WBCs.
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Purulent Exudate (Pus)
Whitish-green discharge from an injury site containing dead neutrophils, infectious material, and cellular debris.
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Eosinophils: Percentage & Primary Roles
Make up 1% to 7% of WBCs. Generated and released mainly during allergic reactions and parasitic infection. Granules contain mediators toxic to parasites and host tissues (histamine, eosinophil peroxidase, etc.).
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Basophils: Percentage & Primary Roles
Make up fewer than 2% of WBCs. Rise in response to infection or allergy, particularly parasitic infection. Granules contain histamine, prostaglandin, leukotrienes, heparin (histamine/heparin assist neutrophil migration).
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Leukocytosis: Definition
A rise in WBC count above 11,000/mcL. Commonly due to infection, inflammation, extreme stress, but also neoplasms or bone marrow disorders.
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Leukemoid Reaction: Definition & Distinction from Leukemia
Leukocytosis in excess of 50,000/mcL due to disorders *other than* leukemia (e.g., hemorrhage, specific infections, splenic dysfunction, organ necrosis). Characterized by excess of normal, early neutrophil precursors (myelocytes, metamyelocytes, promyelocytes), NOT cancerous blasts found in acute leukemia.
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Leukopenia: Definition & Consequences
A decrease in WBC count below 4,000/mcL (general term for decrease in all WBC types). Caused by diminished bone marrow function or WBC destruction. Consequences: Increased risk of infection, decreased signs of infection, diminished healing ability.
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Neutrophilia: Definition & Common Causes
Neutrophil predominance in WBC count; count above 7,000/mcL (with total WBC <11,000/mcL). Commonly occurs in response to bacterial infection, inflammation, malignancy, smoking, stress, certain drugs (glucocorticoids, lithium, epinephrine).
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Neutropenia: Definition, Diagnosis & Common Causes
Lack of sufficient neutrophils; most frequent kind of leukopenia. Diagnosed with <1,500 neutrophils/mcL. Causes: Infections (viral common), medications (chemo, others), vitamin deficiencies, bone marrow diseases, radiation, autoimmune destruction, hypersplenism (see Box 12-1).
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Consequences of Neutropenia & Treatment
Significantly impaired immune defenses (especially if <1,000/mcL). Neutropenia with fever indicates infection. Requires isolation/protective precautions. Filgrastim (Neupogen) can stimulate neutrophil production.
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Monocytosis / Monocytic Leukocytosis: Definition & Causes
Monocytosis: Elevated monocyte count (>800/mcL or >8% of total WBC) with normal total WBC. Monocytic Leukocytosis: Elevated monocyte count with elevated total WBC. Seen in acute/chronic infection/inflammation, malignancy, autoimmune disease.
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Monocytopenia: Definition & Causes
Abnormally low number of monocytes. Can be caused by high-dose steroids or usually a malignancy.
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Eosinophilia: Definition & Causes
Abnormally high number of eosinophils (>600 cells/mcL). Usually result of allergy or parasitic infection. Can also be caused by leukemia, medications, toxins, autoimmune disease.
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Basophilic Leukocytosis / Basopenia: Definitions & Causes
Basophilic Leukocytosis: Rare; often associated with basophilic/mast cell leukemias, hypersensitivity/inflammatory reactions, parasitic infection, hypothyroidism, ulcerative colitis, varicella.
Basopenia: Abnormally low number; usually result of a malignant disorder.
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Lymphocytosis: Definition (Age-Dependent) & Causes
Increase in lymphocytes. Definition varies by age: Infant >9000/mcL, Children >7000/mcL, Adults >4000/mcL. Common sign of infection (especially viral). In older adults, can indicate lymphoproliferative disorders (CLL, lymphomas).
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Lymphocytopenia: Definition (Age-Dependent) & Causes
Decrease in lymphocytes. Definition varies by age: Children <3000/mcL, Adults <1500/mcL, Older adults <1400/mcL. Causes: Decreased bone marrow production (acquired/inherited immunodeficiency), lymphocyte destruction (radiation/chemo).
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Types of Lymphocytopenia
T lymphocytopenia (too few T cells): Caused by HIV, inherited disorder, severe infection, radiation/chemo.
B lymphocytopenia (too few B cells): Caused by immunosuppressive medications.
NK lymphocytopenia (too few NK cells): Rare disorder.
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Hematological Neoplasms: General Definition
Cancers affecting bone marrow, blood cells, lymph nodes, and other parts of the lymphatic system. Include leukemias, lymphomas, multiple myeloma (MM), and myelodysplastic syndrome (MDS).
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Basic Pathophysiology of Hematological Neoplasms
Nonfunctional, cancerous WBCs proliferate, overwhelming bone marrow and lymphoid tissue. They crowd out and suppress development of healthy WBCs, RBCs, and platelets. Leads to bone marrow suppression (anemia, leukopenia/neutropenia, thrombocytopenia).
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General Etiology of Hematological Cancers
Damage to DNA of developing cells in bone marrow (turns on oncogenes, turns off tumor suppressor genes). Can be due to single gene abnormalities (e.g., Ph chromosome) or changes to whole chromosomes (e.g., trisomy, monosomy).
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Ph Chromosome (Philadelphia Chromosome)
Abnormality from translocation between chromosome 9 and 22 (t(9;22)). Fuses BCR gene (chr 22) with ABL gene (chr 9), forming BCR-ABL oncogene. Protein product is enzyme tyrosine kinase, causing leukemia.
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Tyrosine Kinase Inhibitors (TKIs)
Drugs used to treat leukemias (especially CML, some ALL) that target the tyrosine kinase enzyme produced by the BCR-ABL oncogene, preventing its leukemic effects.
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General Risk Factors for Hematological Neoplasms (Box 12-2)
Repeated exposure to benzene (cigarette smoke, industrial), herbicides/pesticides (Agent Orange), certain genetic disorders (Down syndrome), past chemo/radiation, history of other blood cancers/disorders, viral causes (EBV, HIV, HTLV), H. pylori (for MALT lymphoma).
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Common Signs & Symptoms of Hematological Neoplasms (General - Box 12-3)
Anemia (fatigue, SOB, pallor, chest pain), Neutropenia (increased infection susceptibility), Thrombocytopenia (bleeding, bruising, epistaxis, petechiae), Bone pain, Lymphadenopathy, Splenomegaly, Hepatomegaly, Abdominal fullness, Unintentional weight loss, Fever, chills.
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Key Diagnostic Tool: CBC with Differential
Initial test identifying abnormal WBC counts (total and specific types), RBCs, Hgb, Hct, platelets, often prompting further investigation.
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Bone Marrow Aspiration/Biopsy in Hematological Neoplasms
Examines precursor cells and their maturation in bone marrow. Changes in cell types or increased immature cells (blasts) indicate hematological disorders.
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Cytogenetic Testing in Hematological Neoplasms
Analyzes cell’s chromosome number and structure for disorders like aneuploidy, deletions, duplications, translocations, insertions, or inversions. Used for diagnosis, prognosis, and therapy guidance.
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Fluorescence in Situ Hybridization (FISH)
Analyzes cells for chromosome defects (translocations, deletions, extrachromosomal fragments) by using fluorescent probes to detect specific DNA sequences.
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Polymerase Chain Reaction (PCR) in Hematological Neoplasms
Amplifies small sections of DNA for molecular and genetic analysis; used in many lab procedures for cancer diagnosis.
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Flow Cytometry in Hematological Neoplasms
Diagnostic technique examining cells and analyzing DNA by suspending tissue in fluid and passing it through laser light detection. Used in leukemia diagnosis for staging and prognosis.
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Immunophenotyping in Hematological Neoplasms
Analysis of cancer cells to identify specific surface antigens (e.g., CD markers). Results in immunological subtype classification for diagnosis, prognosis, and guiding targeted therapy.
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Lymph Node Biopsy
Microscopic examination of lymphoid tissue (aspirated or surgically removed) for cellular changes. Common in lymphoma diagnosis or assessing metastasis.
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Lumbar Puncture in Hematological Neoplasms
Extracts cerebrospinal fluid (CSF) to check for metastatic cancer cells in the brain/CNS (a sanctuary site).
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General Treatment: Chemotherapy Mechanism & Side Effects
Targets rapidly dividing cells (cancer cells and healthy cells like skin, GI mucosa, bone marrow). Side effects: Hair loss, GI disruption (nausea, vomiting, anorexia), bone marrow suppression (neutropenia, anemia, thrombocytopenia).
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Filgrastim (Neupogen) Use with Chemotherapy
Neutrophil stimulant administered to increase neutrophil production, reducing risk of infection associated with chemotherapy-induced neutropenia.
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General Treatment: Monoclonal Antibodies
Highly specific, lab-synthesized antibodies targeting single antigens on cancer cells. Can destroy cancer cells directly or deliver attached chemotherapeutic agents (antibody-drug conjugates).
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General Treatment: Radiation Therapy
Uses high-dose X-rays to destroy cancer cells, especially those not fully removed by surgery. Can be external (machine-directed) or internal (implanted seeds, wires, catheters).
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General Treatment: Bone Marrow Stem Cell Transplants - Allogeneic
Diseased bone marrow ablated (chemo/radiation). Healthy stem cells from a tissue-matched donor are infused. Risk of rejection. Siblings often best match.
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General Treatment: Bone Marrow Stem Cell Transplants - Autologous
Patient's own healthy stem cells extracted and stored. Patient treated with high-dose chemo/radiation (ablation). Stored cells returned to patient. Lower risk of infection/rejection.
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Umbilical Cord Stem Cells
Used as stem cell transplants; higher concentration of hematopoietic stem cells than adult blood. Small quantity obtained makes it more suitable for children.
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General Treatment: CAR-T Cell Cancer Immunotherapy
Patient’s T cells harvested, genetically engineered in lab to target cancer cell antigens (become chimeric antigen-receptor modified T cells or CAR-T cells). Reinfused to attack and kill tumor cells. Approved for some leukemias/lymphomas.
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Complication of Cancer Treatment: Tumor Lysis Syndrome (TLS)
Results from rapid destruction of many tumor cells at once. Lysed cells release intracellular contents (uric acid, K+, phosphate) into circulation. Causes hyperuricemia, hyperkalemia, hyperphosphatemia (with secondary hypocalcemia). Can lead to acute kidney injury (uric acid crystals damage glomeruli/nephrons). Often seen 48-72h post-treatment initiation.
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Complication of Cancer Treatment: Differentiation Syndrome
Side effect of specific chemotherapy (e.g., retinoic acid in leukemia). Leukemia cells release chemicals. Symptoms: fever, dyspnea (fluid in lungs/around heart), hypotension, kidney damage, severe fluid buildup. Often treated by temporarily stopping drug and giving steroids (e.g., dexamethasone).
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Complication of Cancer Treatment: Cytokine Release Syndrome (CRS)
Toxicity related to T-cell targeting therapies (monoclonal antibodies, CAR-T). Caused by products of immune cells. Clinical signs: fever, hemodynamic instability, capillary leak. Correlates with T-cell activation and elevated cytokine levels. Treated with IL-6 receptor antagonists (tocilizumab) or corticosteroids.
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Hematology vs. Oncology
Hematology: Study of blood cells. Oncology: Study of cancers. Closely related fields for blood cancers.
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Pluripotent Stem Cells
Undeveloped precursor cells in bone marrow with potential to become any type of blood cell.
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Dendritic Cells
Specialized cells (can be derived from monocytes) that present antigens to T cells, linking innate and adaptive immunity.
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Plasma Cells
Antibody-producing cells derived from B lymphocytes, typically within lymph nodes.
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Polymorphonuclear (PMN) WBCs
Another term for neutrophils, referring to their segmented, multilobed nucleus.
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Agranulocytes: Definition
WBCs without granules in their cytoplasm, such as monocytes and lymphocytes.
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Leukapheresis: Definition
A procedure that extracts and removes excess WBCs from the blood. Used when WBC counts are extremely high (e.g., in some leukemias before chemo).
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Basic Pathological Mechanism in Hematological Neoplastic Disease (Objective)
Nonfunctional, cancerous WBCs proliferate and overwhelm the bone marrow and other lymphoid tissue. This crowds out and suppresses the development of healthy WBCs, RBCs, and platelets, leading to immunosuppression, anemia, and thrombocytopenia.
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Clinical Manifestations of Bone Marrow Dysfunction in Hematological Neoplastic Disease (Objective)
Anemia (fatigue, pallor, dyspnea), Leukopenia/Neutropenia (increased susceptibility to infections, fever), Thrombocytopenia (easy bruising, bleeding, petechiae, epistaxis), Bone pain (from marrow expansion).
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Treatment Modalities for Hematological Neoplastic Disease (Objective - General List)
Chemotherapy, Monoclonal Antibodies (Immunotherapy), Radiation Therapy, Stem Cell Transplants (Allogeneic and Autologous), CAR-T Cell Therapy, Targeted Therapies (e.g., TKIs).
