HEMATOLOGIC SYSTEM

1. HEMATOLOGIC SYSTEM Ch. 14 Goodman

2. OVERVIEW • *The hematologic system involves the blood, blood vessels and the associated organs. • *The study of hematology includes the diseases of the hematological system. • * This critical system is tightly integrated with the following systems: lymphatic, immune, circulatory, respiratory. It is also integrated with hormonal and metabolic functions. • ***While there are primary diseases of the hematological system, the most common conditions are most often signs of other conditions

3. COMPONENTS OF BLOOD • *2 components of blood: • Plasma • Formed elements • Erythrocytes (RBCs) • Leukocytes (WBCs) • Thrombocytes (platelets)

4. SIGNS OF HEMATOLOGICALDISORDERS • Edema (sign) Excessive fluid accumulation within the interstitial tissues or within body cavities • Infarction (sign) localized region of necrosis caused by reduction of arterial perfusion • Thrombus (sign) blood clot - solid mass within intact vessel or the heart • Embolus (sign) Thrombus on the move that gets lodged distant from its place of origin

5. MORE SIGNS…. • Lymphedema (sign) Can be a sign of hematologic conditions - increased lymphatic load associated with decreased plasma proteins • Bleeding / bruising (sign) A sign when it happens with minor trauma or if bleeding continues longer than normal • Shock (sign) Inadequate blood pressure to perfuse organs

6. AND STILL MORE… • Lymphedenopathy (sign) Abnormal enlargement of lymph nodes • Splenomegaly enlarged spleen (spleen removes old RBC’s and antibody-laden bacteria or cells)

7. AGING/HEMATOPOIETIC SYSTEM • Aging and the Hematopoietic System • Decreased red marrow • Decreased intestinal iron absorption • Increased fragility of plasma membranes • Increased fibrinogen and platelet adhesiveness • Earlier activation of coagulation system • (ergo…) disturbed blood flow, propensity for anemia (low RBCs) - if nothing else slower RBC recovery from a loss of blood

8. BLOOD TRANSFUSION REACTIONS • Blood Transfusions • Reaction to blood and blood products • 1. Febrile nonhemolytic reaction - most common (.5-1% of transfusions), fever (at least 1 degree rise) but stable cells • 2. Transfusion related acute lung injury - 1 in every 2000 transfusions; initially mild shortness of breath but can progress to appear clinically as acute respiratory distress syndrome (widespread inflammation, low ventilatory volumes, poor oxygenation); with treatment can prevent / minimize permanent lung damage • 3. Acute hemolytic transfusion - 1 in every 25,000 transfusions - severe response due to ABO incompatibility; RBCs are destroyed (lysis) - mortality rate is high (17-60%)

9. BLOOD TRANSFUSION REACTIONS (CONTINUED): • 4. Allergic reactions - 1-3% of all transfusions, most common with fresh frozen plasma and platelet transfusions - allergic reaction • 5. Anaphylaxis - 1 in 20,000 transfusions - acute onset of hypotension, laryngeal edema • 6. Sepsis - very rare; due to bacterial contamination of blood products used in transfusion • Bloodless medicine - goal to reduce blood loss with procedures to avoid need of transfusions

10. DISORDERS of IRON ABSORPTION • Disorders of Iron Absorption • Hereditary Hemochromatosisis an autosomal recessive hereditary disorder characterized by excessive iron absorption by small intestine • Uncoupling of absorption and needs - leads to iron deposition in cells, particularly the liver, pancreas and heart • Early signs include weakness, hepatomegaly, elevated liver enzymes; symptoms include myalgias, joint pain, fatigue

11. Hereditary Hemochromatosis (continued) • Diagnosis-by blood work • Treatment - therapeutic phlebotomy • Prognosis -is good (from a mortality / morbidity perspective) but the condition is not reversible - it is managed

12. DISORDERS OF ERYTHROCYTES • Anemia • 1. Definition • reduction in oxygen carrying capacity of blood due to reduced quantity or quality of • RBCs • HgB < 14 g/100 ml for men; 12 g/ 100 ml for women

13. Anemia (continued) • 2. Overview • Not technically a disease - really a sign of other underlying disorders - including but not limited to: • **dietary (folate, vitamin B12) • **acute or chronic blood loss • **iron deficiency (diet or absorption) • **congenital defects (sickle cell anemia) • **poison exposure • **disease of bone marrow • **chronic inflammatory, infectious or neoplastic disease • **any disorder that upsets the balance between blood loss through bleeding or destruction and production of RBCs

14. Anemia (continued) • 3. Clinical manifestations • Mild - minimal and vague symptoms of fatigue • Moderate to severe progression: weakness, dyspnea on exertion, tachycardia, increased angina in pre existing CAD, dementia • 4. Treatment • a. Underlying problem (cause) if possible • b. Blood transfusions

15. DISORDERS OF LEUKOCYTES • Disorders of Leukocytes A. Leukocytosis **Definition & Etiology • Increased number of leukocytes (WBCs) for a variety of causes - including as a normal response stressors • Common finding with infection - > 10,000 WBCs/mm^3 **Clinical manifestations • Signs and symptoms are usually those of infectious conditions (localized or systemic) - fever, headache, shortness of breath ** Treatment Underlying problem

16. Disorders of Leukocytes • B. Leukopenia **Definition & Etiology Decreased number of WBCs - < 5000 / ml caused by a variety of conditions: *HIV, hepatitis *alcohol *Nutritional deficiencies *connective tissue disorders (SLE) *bone marrow failure (i.e. following antineoplastic chemotherapy) **Clinical manifestations Asymptomatic; increased risk of infection **Treatment Underlying problem

17. NEOPLASTIC DISEASES OF THE BLOOD AND LYMPH SYSTEMS • **** Bone marrow transplant Treatment of choice for any hematologic neoplastic disease • A. Leukemias • Malignant neoplasm of blood forming cells that replaces normal bone marrow with a malignant clone • Acute vs. Chronic • Myeloid vs. Lymphocytic • Blastic vs. cytic • Acute progresses quickly; chronic slowly • Myeloid - bone marrow origin involving hematopoeitic stem cells • Lympho - involving lymphoid or lymphatic system • Blastic - large, immature (functionless) cells • cytic - immature, smaller cells • Immunologically can also classify as T-cell / natural killer cell and B-cell leukemias

18. Leukemia (continued) • Three main clinical consequences: • 1. Anemia • 2. Infection • 3. Bleeding tendencies • Acute myelogenous leukemia - AML - most common leukemia in adults • Acute lymphoblastic leukemia - ALL – diagnosed most commonly in children • Chronic myeloid leukemia - CML – occurs most often in adults • Chronic lymphocytic leukemia - CLL – a common type of adult leukemia

19. MALIGNANT LYMPHOMAS • Malignant Lymphomas • Cancers of lymphatic system • Two groups - Hodgkin’s lymphoma and Non-Hodgkin’s Lymphoma (HL and NHL) - although the distinction has become less clear • More useful to categorize based on cell behavior - indolent vs. aggressive • HL is distinguished from others by presence of a cell known as the Reed-Sternberg cell in the lymph nodes

20. Hodgkin’s Lymphoma • HL - adults and children; B-cell malignancy; Clinical manifestations are variable, Box • 14-6, Ann Arbor Staging Classification for HD (Hodgkin’s Disease) - progresses by increased involvement of lymph nodes and other lymph organs; Stage IV includes involvement of extralymphatic organs (liver, lung, skin)

21. Non-Hodgkin’s Lymphoma • NHL - large group (~30 types) of lymphoid malignancies that present as solid tumors arising from lymphatic cells - 5th most common type of cancer in the US with an incidence of ~67,000 / year; clinical manifestations are variable

22. MULTIPLE MYELOMA • Multiple Myeloma • MM - primary malignant neoplasm of plasma cells arising in bone marrow • Progression causes damage to kidney, recurrent infections, often affects the nervous system • Increased incidence (doubled in past 2 decades) (~16,000 new cases / year) - thought in part to increase in population > 85 years old

23. MYELOPROLIFERATIVE DISORDERS • Myeloproliferative Disorders • Originate from a hematopoietic stem cell that has transformed to allow the cell to mature and function with uncontrolled function - common characteristics include: • 1. hypercellular bone marrow • 2. tendency to thrombosis and hemorrhage • 3. increased risk of evolving into acute leukemia

24. Types of Myeloproliferative Disorders • Polycythemiavera - increased production of RBCs • Essential thrombocythemia - most common - increased platelet count

25. DISORDERS OF HEMOSTASIS • Disorders of Hemostasis • Primary hemostasis - formation of a platelet plug (collagen fibrils and von Willebrand’s factor (vWF) in the subendothelial matrix of the blood vessel gets exposed to blood) • Secondary hemostasis - vascular damage exposes tissue damage

26. Disorders of hemostasis • A. von Willebrandʼs Disease • Most common inherited bleeding disorder - • Disorder of primary hemostasis - mucosal and skin bleeding and prolonged oozing after trauma or surgery • Rx - replacement of vWF

27. Disorders of hemostasis • B. Hemophilia • Deficiency of clotting factors • Disorder of secondary hemostasis - easy bruising, prolonged bleeding • If severe can spontaneously bleed - into joints, muscles, organs • Rx - replacement of clotting factors

28. Disorders of hemostasis • C. Thrombocytopenia • Decreased platelets (< 150,000/mm^3) - caused by either reduced production or increased destruction; usually a sign of other problems • Mucosal bleeding is a common sign • May be presenting sign of aplastic anemia (bone marrow failure) • Rx - underlying cause; platelet transfusions

29. Disorders of hemostasis • D. Aspirin / NSAIDs • Single dose of ASA can impair platelet function for 48 hours • NSAIDs are less potent • ASA and NSAIDs are contraindicated before surgery

30. Disorders of hemostasis • E. Disseminated Intravascular Coagulation • DIC - thrombotic disease caused by overactivation of the coagulation cascade - • Paradoxical in that clotting and hemorrhage occur simultaneously within the vascular system • Widespread clotting and fibrin deposition in circulation, causes backflow and increased pressure which leads to hemorrhage • Common after shock, sepsis, obsteteric / gynecological complications, cancer, massive trauma • Alteration in normal balance of pro and anticoagulant factors • Rx - underlying cause

31. Disorders of hemostasis • F. Hemoglobinopathies • Abnormalities in the formation of HgB • 1. Sickle cell disease (SCD) - • Genetic, result is HgB that changes from biconcave to crescent (sickle) shape once oxygen is released - provides selective immunity to malaria but leads to difficulty in blood flow in microvascular resulting in acute and chronic tissue injury

32. Disorders of hemostasis • Acute crises or episodes - pain caused by blockages of sickled RBCs in any organ, bone or joint; location and severity vary widely • Life threatening crises occur when these occur in chest (heart or lung) or CNS • Bone marrow transplant cures SCD • Sickle Cell trait - makes both types of HgB - rarely symptomatic

33. Disorders of hemostasis • 2. Thalassemias- inherited disorder with abnormalities in one of more of the 4 globin genes; leads to varying degrees of abnormally functioning HgB • Clinical manifestations based on extent to which the globin genes are impacted and are related to: • 1. defective synthesis of HgB • 2. structurally impaired RBCs • 3. hemolysis or destruction of RBCs (anemia) \ impaired oxygen carrying capacity - • Rx - transfusions

34. Created by: Andrea C. Mendes PT, DPT and Sean M. Collins PT, ScD