1. Alterations of Leukocyte, Lymphoid, and Hemostatic Function
Chapter 27
Alterations of Leukocyte, Lymphoid, and Hemostatic Function
Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2. Alterations of Leukocyte Function
Deficiencies in the quality and quantity of leukocytes (leukopenia)
Increased numbers of leukocytes (leukocytosis)
Many hematologic disorders are malignancies
Many nonhematologic malignancies metastasize to bone marrow, affecting leukocyte production

4. Alterations of Leukocyte Function
Quantitative disorders
Increases or decreases in cell numbers
Bone marrow disorders or premature destruction of cells
Response to infectious microorganism invasion
Qualitative disorders
Disruption of cellular function

5. Quantitative Alterations of Leukocytes
Leukocytosis
Counts higher than normal
Leukocytosis is a normal protective physiologic response to stressors
Leukopenia
Counts lower than normal
Leukopenia is always abnormal
Low WBC count predisposes to infections

8. Granulocytosis (Neutrophilia)
Evident in first stages of infection/inflammation
If need for neutrophils increases beyond the supply, immature neutrophils (banded neutrophils) released into the blood
Premature release detected in manual WBC differential and is termed a shift to the left
Leukemoid reaction
When the population returns to normal, it is termed a shift to the right

9. Neutropenia Reduction in circulating neutrophils Primary Secondary
Congenital
Cyclic neutropenia and neutropenia with congenital immunodeficiency diseases
Multiple syndromes
Acquired
Multiple conditions (hypoplastic anemia, aplastic anemia, leukemias, lymphomas [Hodgkin, non-Hodgkin]; myelodysplastic syndrome)
Secondary

10. Neutropenia Causes Prolonged severe infection Decreased production
Reduced survival
Abnormal neutrophil distribution and sequestration

11. Granulocytopenia (Agranulocytosis)
Causes
Interference with hematopoiesis
Immune mechanisms
Chemotherapy destruction
Ionizing radiation
Sepsis caused by agranulocytosis often results in death within 3 to 6 days

12. Eosinophilia
Hypersensitivity reactions trigger the release of eosinophilic chemotactic factor of anaphylaxis from mast cells
Increased in allergic disorders
Increased in parasitic invasions

13. Eosinopenia Decrease in circulation numbers of eosinophils
Usually caused by migration of cells to inflammatory sites
Other causes
Surgery, shock, trauma, burns, or mental distress

14. Basophils Basophils account for only up to 1% of the circulating WBCs
Basophilia
Response to inflammation and hypersensitivity reactions
Basopenia
Occurs in acute infections, hyperthyroidism, and long-term steroid therapy

15. Monocytes Monocytosis Monocytopenia Poor correlation with disease
Usually occurs with neutropenia in later stages of infections
Monocytes are needed to phagocytize organisms and debris
Monocytopenia
Very little known about this condition
Prednisone treatments
Hairy cell leukemia

16. Lymphocytes Lymphocytosis Lymphocytopenia Acute viral infections
Epstein-Barr virus
Lymphocytopenia
Immune deficiencies, drug destruction, viral destruction

17. Infectious Mononucleosis (IM)
Acute, self-limiting infection of B lymphocytes transmitted by saliva through personal contact
Commonly caused by the Epstein-Barr virus (EBV)—85%
B cells have an EBV receptor site
Others viral agents resembling IM
Cytomegalovirus (CMV), hepatitis, influenza, HIV

18. Infectious Mononucleosis
Symptoms: fever, sore throat, swollen cervical lymph nodes, increased lymphocyte count, and atypical (activated) lymphocytes; may affect multiple systems
Serious complications are infrequent (<5%)
Splenic rupture is the most common cause of death
Lab values: >50% lymphocytes and at least 10% atypical lymphocytes
Diagnostic test
Monospot qualitative test for heterophilic antibodies
Treatment: symptomatic

20. Infectious Mononucleosis - 1.
Large irregular atypical lymphocytes seen in the peripheral blood of a patient with infectious mononucleosis. The indentation of the cytoplasm of the lymphocyte (arrows) by red blood cells gives rise to the classic "Dutch skirt" appearance of the border.

22. Leukemias Malignant disorder of the blood and blood-forming organs
Uncontrolled proliferation of malignant leukocytes
Overcrowding of bone marrow
Decreased production and function of normal hematopoietic cells

23. Leukemias Acute leukemia Chronic leukemia
Presence of undifferentiated or immature cells, usually blast cells
Rapid onset with short survival
Chronic leukemia
Predominant cell is mature but does not function normally
Slow progression

24. Leukemias Acute lymphocytic leukemia (ALL)
Least common overall but most common childhood leukemia (80%)
Acute myelogenous leukemia (AML)
Most common adult leukemia (mean age, 67)

26. A, Lymphoblasts show significant vacuolation and basophilic cytoplasm
A, Lymphoblasts show significant vacuolation and basophilic cytoplasm. B, Myeloperoxidase stain shows positive staining in most lymphoblasts

27. Leukemias Chronic myelogenous leukemia (CML)
Usually diagnosed in adults
Chronic lymphocytic leukemia (CLL)
Common in adults (70% asymptomatic at diagnosis)
Lymphadenopathy
Suppression of humoral immunity
Increased infection with encapsulated bacteria

28. Leukemias Signs and symptoms of leukemias
Anemia, bleeding purpura, petechiae, ecchymosis, thrombosis, hemorrhage, DIC, infection, weight loss, bone pain, elevated uric acid, and liver, spleen, and lymph node enlargement
Clonal disorder in that a single progenitor cell undergoes malignant transformation

29. Lymphadenopathy Enlarged lymph nodes that become palpable and tender
Local lymphadenopathy
Drainage of an inflammatory lesion located near the enlarged node
General lymphadenopathy
Occurs in the presence of malignant or nonmalignant disease

30. Lymphadenopathy Causes Neoplastic disease
Immunologic or inflammatory conditions
Endocrine disorders
Lipid storage diseases

31. Lymphadenopathy

32. Malignant Lymphomas
Malignant transformation of a lymphocyte and proliferation of lymphocytes, histiocytes, their precursors, and derivatives in lymphoid tissues
Two major categories
Hodgkin lymphoma
Linked to EBV
Non-Hodgkin lymphoma
Lymphoblastic lymphoma

33. Hodgkin Lymphoma Reed-Sternberg cells in the lymph nodes
These cells necessary for diagnosis, but not specific to Hodgkin lymphoma
Classical Hodgkin lymphoma
Nodular lymphocyte predominant Hodgkin lymphoma
B cell in the germinal center that has not undergone successful immunoglobulin gene rearrangement but has undergone apoptosis

34. Hodgkin Lymphoma Physical findings Symptoms Laboratory findings
Adenopathy, mediastinal mass, splenomegaly, and abdominal mass
Symptoms
Fever, weight loss, night sweats, pruritus
Laboratory findings
Thrombocytosis, leukocytosis, eosinophilia, elevated erythrocyte sedimentation rate (ESR), elevated alkaline phosphatase
Paraneoplastic syndromes

35. Hodgkin Lymphoma

36. Hodgkin Lymphoma

37. Non-Hodgkin Lymphoma Generic term for diverse group of lymphomas
The lymphomas can be differentiated based on etiology, unique features, and response to therapies
Non-Hodgkin lymphomas are linked to chromosome translocations, viral and bacterial infections, environmental agents, immunodeficiencies, and autoimmune disorders

38. Non-Hodgkin Lymphoma
Clonal expansion of B cells (85%), T cells, and/or NK cells
Changes in proto-oncogenes and tumor-suppressor genes contribute to cell immortality and thus an increase in malignant cells

39. Burkitt Lymphoma Most common type of non-Hodgkin lymphoma in children
A very fast-growing tumor of the jaw and facial bones
Epstein-Barr virus is found in nasopharyngeal secretions of individuals

40. Burkitt Lymphoma

41. Plasma Cell Malignancies
Multiple Myeloma
Waldenström

42. Multiple Myeloma Proliferation of plasma cells
The tumor may be solitary or multifocal (multiple myeloma)
The malignant plasma cells produce abnormally large amounts of one class of immunoglobulin or incomplete immunoglobulin
The unattached light chains of the immunoglobulins (Bence Jones proteins) can pass through the glomerulus and damage the renal tubular cells

43. Multiple Myeloma Increased osteoclastic bone destruction
Hypercalcemia (13%), renal failure (19%), anemia (72%), bone lesions (80%)
Clinical manifestations
Cortical and medullary bone loss
Skeletal pain
Recurring infections due to loss of the humoral immune response

44. Alterations in Splenic Function
Splenomegaly
Hypersplenism
Congestive splenomegaly
Infiltrative splenomegaly
Removal of the spleen
Increased WBCs and platelets
RBC abnormalities

45. Disorders of Platelets
Thrombocytopenia
Platelet count <100,000/mm3
<50,000/mm3—hemorrhage from minor trauma
<15,000/mm3—spontaneous bleeding
<10,000/mm3—severe bleeding
Causes:
Hypersplenism, autoimmune disease, hypothermia, and viral or bacterial infections that cause DIC

46. Disorders of Platelets
Immune thrombocytopenic purpura (ITP)
IgG antibody targets platelet glycoproteins
Antibody-coated platelets are sequestered and removed from the circulation
Acute form develops after viral infections
One of the most common childhood bleeding disorders
Manifestations
Petechiae and purpura, progressing to major hemorrhage

47. Disorders of Platelets
Thrombotic thrombocytopenic purpura (TTP)
A thrombotic microangiopathy
Platelets aggregate, form microthrombi, and cause occlusion of arterioles and capillaries
Chronic relapsing TTP
Acute idiopathic TTP

48. Disorders of Platelets
Essential (primary) thrombocythemia
Thrombocythemia is characterized by platelet counts >600,000/mm3
Myeloproliferative disorder of platelet precursor cells
Megakaryocytes in the bone marrow are produced in excess
Microvasculature thrombosis occurs

49. Alterations of Platelet Function
Qualitative alterations demonstrate an increased bleeding time in the presence of a normal platelet count
Disorders result from platelet membrane glycoprotein and von Willebrand factor deficiencies
Manifestations
Petechiae, purpura, mucosal bleeding, gingival bleeding, and spontaneous bruising
Disorders can be congenital or acquired

50. Alterations of Coagulation
Vitamin K deficiency
Vitamin K is necessary for synthesis and regulation of prothrombin, the prothrombin factors (II, VII, XI, X), and proteins C and S (anticoagulants)
Liver disease
Causes broad range of hemostasis disorders
Defects in coagulation, fibrinolysis, and platelet number and function

51. Disseminated Intravascular Coagulation (DIC)
Complex, acquired disorder: clotting and hemorrhage simultaneously occur
Sepsis, cancer, trauma, blood transfusion
Result of increased protease activity in the blood caused by unregulated release of thrombin with subsequent fibrin formation and accelerated fibrinolysis
Endothelial damage is primary initiator

52. Disseminated Intravascular Coagulation (DIC)
Blockage of blood flow to organs, resulting in multiple organ failure
Magnitude of clotting may result in consumption of platelets and clotting factors, leading to severe bleeding

53. Disseminated Intravascular Coagulation (DIC)
The amount of activated thrombin exceeds the body’s antithrombins and the thrombin does not remain localized
The widespread thromboses created cause widespread ischemia, infarction, and organ hypoperfusion

54. Disseminated Intravascular Coagulation (DIC)
By activating the fibrinolytic system (plasmin), person’s fibrin degradation product and D-dimer levels increase
Due to the person’s clinical state, the disorder has a high mortality rate
Treatment is to remove the stimulus

55. Disseminated Intravascular Coagulation (DIC)
Clinical signs and symptoms demonstrate wide variability
Bleeding from venipuncture sites
Bleeding from arterial lines
Purpura, petechiae, and hematomas
Symmetric cyanosis of the fingers and toes

56. Thromboembolic Disease
Arterial thrombi
Defects in proteins involved in hemostasis
Venous thrombi
Variety of clinical disorders or conditions
Hypercoagulabilty (thrombophilia)
Acquired
Mutations in coagulation proteins, fibrinolytic proteins, platelet receptors
Triad of Virchow