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

2. 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

3. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 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

4. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 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

5. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 5 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

6. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 Neutropenia  Reduction in circulating neutrophils  Primary Congenital Congenital  Cyclic neutropenia and neutropenia with congenital immunodeficiency diseases  Multiple syndromes Acquired Acquired  Multiple conditions (hypoplastic anemia, aplastic anemia, leukemias, lymphomas [Hodgkin, non-Hodgkin]; myelodysplastic syndrome)  Secondary

7. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Neutropenia  Causes  Prolonged severe infection  Decreased production  Reduced survival  Abnormal neutrophil distribution and sequestration

8. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 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

9. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Eosinophilia  Hypersensitivity reactions trigger the release of eosinophilic chemotactic factor of anaphylaxis from mast cells  Increased in allergic disorders  Increased in parasitic invasions

10. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 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

11. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 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

12. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 Monocytes  Monocytosis  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 Prednisone treatments Hairy cell leukemia Hairy cell leukemia

13. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Lymphocytes  Lymphocytosis  Acute viral infections Epstein-Barr virus Epstein-Barr virus  Lymphocytopenia  Immune deficiencies, drug destruction, viral destruction

14. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 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 Cytomegalovirus (CMV), hepatitis, influenza, HIV

15. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 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

16. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 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

17. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 17 Leukemias  Acute 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

18. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 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)

19. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Leukemias  Chronic myelogenous leukemia (CML)  Usually diagnosed in adults  Chronic lymphocytic leukemia (CLL)  Common in adults (70% asymptomatic at diagnosis) Lymphadenopathy Lymphadenopathy Suppression of humoral immunity Suppression of humoral immunity Increased infection with encapsulated bacteria Increased infection with encapsulated bacteria

20. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 20 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

21. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 21 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

22. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Lymphadenopathy  Causes  Neoplastic disease  Immunologic or inflammatory conditions  Endocrine disorders  Lipid storage diseases

23. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Lymphadenopathy

24. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 24 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 Linked to EBV  Non-Hodgkin lymphoma  Lymphoblastic lymphoma

25. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 25 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

26. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 26 Hodgkin Lymphoma  Physical 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

27. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Hodgkin Lymphoma

28. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 28 Hodgkin Lymphoma

29. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 29 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

30. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 30 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

31. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 31 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

32. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 32 Burkitt Lymphoma

33. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 33 Plasma Cell Malignancies  Multiple Myeloma  Waldenström

34. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 34 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

35. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 35 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

36. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 36 Alterations in Splenic Function  Splenomegaly  Hypersplenism  Congestive splenomegaly  Infiltrative splenomegaly  Removal of the spleen  Increased WBCs and platelets  RBC abnormalities

37. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 37 Disorders of Platelets  Thrombocytopenia  Platelet count <100,000/mm 3 <50,000/mm 3 —hemorrhage from minor trauma <50,000/mm 3 —hemorrhage from minor trauma <15,000/mm 3 —spontaneous bleeding <15,000/mm 3 —spontaneous bleeding <10,000/mm 3 —severe bleeding <10,000/mm 3 —severe bleeding  Causes: Hypersplenism, autoimmune disease, hypothermia, and viral or bacterial infections that cause DIC Hypersplenism, autoimmune disease, hypothermia, and viral or bacterial infections that cause DIC

38. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 38 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 One of the most common childhood bleeding disorders  Manifestations Petechiae and purpura, progressing to major hemorrhage Petechiae and purpura, progressing to major hemorrhage

39. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 39 Disorders of Platelets  Thrombotic thrombocytopenic purpura (TTP)  A thrombotic microangiopathy Platelets aggregate, form microthrombi, and cause occlusion of arterioles and capillaries Platelets aggregate, form microthrombi, and cause occlusion of arterioles and capillaries  Chronic relapsing TTP  Acute idiopathic TTP

40. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 40 Disorders of Platelets  Essential (primary) thrombocythemia  Thrombocythemia is characterized by platelet counts >600,000/mm 3  Myeloproliferative disorder of platelet precursor cells Megakaryocytes in the bone marrow are produced in excess Megakaryocytes in the bone marrow are produced in excess  Microvasculature thrombosis occurs

41. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 41 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

42. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 42 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 Defects in coagulation, fibrinolysis, and platelet number and function

43. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 43 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

44. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 44 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

45. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 45 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

46. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 46 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

47. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 47 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

48. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 48 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