Hematology

1. Hematology Mohamad H Qari, MD, FRCPA

2. Hematology • Cellular Components • Components of Blood • Red Blood Cells • White Blood Cells • Inflammatory process • Coagulation • Blood Typing • Clotting disorders

3. Hematology

4. Hematopoeisis • Three developmental periods • Mesoblastic • Blood islands of yolk sac • Primarily RBC production • Embryonic hemoglobin produced • Hepatic • At 6 weeks cell production in liver • Fetal hemoglobin produced • Spleen, thymus, lymph nodes also active prod. • Myeloid • At 5th month Bone Marrow becomes site of prod. • Liver & spleen now Extramedullary • Hemoglobin A (22)

5. Requirements For Hematopoiesis • Stem Cells • Growth Factors • Microenviroment

6. Stem Cell theory • Pluripotent stem cell originator of all cells • Gives rise to cells committed to specific development • Research supporting the theory • PHSC has self-maintaining ability • Committed cells differentiate continuously/ No Reverse Flow

7. Stem cells in Research • Pluripotent cells derived from: • Cell mass of embryos at blastocyst stage (IVF) • Fetal tissue from terminated pregnancy • Application • Identification of factors of cellular decision-making • Development and testing of drugs • Generation of cells and tissue for therapy

10. Cytokines & Growth Factors • Cytokines stimulate or inhibit • Prevent apoptosis • Colony-Stimulating Factors produced by many different cells • Interleukins numbered according to discovery

11. Components of Blood • Plasma • Transport mechanism • 90-92% water. • 6-7% proteins • 2-3% • Fats • Carbohydrates (glucose) • Electrolytes • Gases (O2, CO2) • Chemical messengers

12. Cellular Components WBC’s RBC’s Platelets

13. Components of Blood • Red Blood Cells • Erythrocyte • Hemoglobin – O2 bearing molecule • Comprised of 4 subunits: • Globin (binds to 1 O2 molecule) • Heme (iron) • 100% saturation = 4 globin subunits carrying O2 • Each gram of hemoglobin = 1.34 ml O2 Cellsalive.com

14. Blood Products and Blood Typing • Blood Types • Antigens • A, B, AB, O • Rh factor • Rh+ = ~85% • Rh- = ~15% Blood transfusion

15. Components of Blood • Red Blood Cells (cont.) • Oxygen Transport • Oxy-hemoglobin dissociation curve • 2,3-DPG

16. Components of Blood • White Blood Cells (Leukocytes) • Margination • Phagocytosis The macrophage is using its internal cytoskeleton to envelop cells of the fungus Candida albicans.

17. Components of Blood • Leukocytes (cont.) • White Blood Cell Count • Leukopoiesis • Granulocytes • Neutrophil • Basophil • Eosinophil • Monocytes • Lymphocytes Human Neutrophil: Phagocytosis of Strep pyogenes

18. Components of Blood • Leukocytes (cont.) • Immunity • Subpopulation of lymphocytes known as T cells and B cells • T cells develop cellular immunity. • B cells produce humoral immunity

19. Components of Blood • Inflammatory Process • MAST CELLS. • Immunoglobulin E antibody IgE, • Antigens • Antigens stick to the mast cell IgE antibodies, causing granules in the mast cell to fire their contents into the surrounding tissue. • This releases a host of inflammatory materials - leukotrienes, tumor necrosis factor, interleukin-4 and other cytokines that turn on other inflammatory cells. • These materials cause fluid to leak from the capillaries and white cells including neutrophils, T cells and eosinophils to leave the circulation. The end result is a "local inflammatory response", a red, itchy welt. Cellsalive.com

20. Components of Blood • Hemostasis- • 3 mechanisms • Vascular spasm • Contraction of tunica media • Platelet plug • Platelet aggregation • Coagulation • Formation of fibrin clot

21. Components of Blood • Hemostasis (cont.) • Fibrinolysis • Lysis of clot (plasmin) • Thrombosis • Thrombolytics • Medications affecting clot formation • Alter the enzyme on the platelet. • Affect the coagulation cascade. • Enhance clotting.

22. Coagulation Cascade - Synopsis

23. This scanning electron micrograph shows the fine structure of a blood clot. Platelets released from the circulation and exposed to the air use fibrinogen from the blood plasma to spin a mesh of fibrin.

24. General Assessment - Management • Focused History and Physical Exam • SAMPLE history • Hematological disorders are rarely the chief complaint. • Physical exam • Evaluate nervous system function. • Skin signs

25. General Assessment - Management • Physical Exam (cont.) • Lymphatic signs • Gastrointestinal signs • Epistaxis • Atraumatic bleeding gums • Thrush • Atraumatic splenic/hepatic pain • Musculoskeletal signs • Arthralgia (rheumatoid arthritis) • Hemarthrosis • Cardiorespiratory signs • Tachycardia, cx pn, dyspnea - CHF • Genitourinary signs • Hematuria • Menorrhagia • Infection

26. Blood Products and Blood Typing

27. Blood Products and Blood Typing • = no reaction • + = reaction

28. Blood Products and Blood Typing Brady; Paramedic Care Principles and Practice

29. Diseases of Erythrocytes • Anemias • Anemia is a sign, not a separate disease process. • Signs and symptoms may not be present until the body is stressed. • Differentiate chronic anemia from acute episode. • Treat signs and symptoms. • Maximize oxygenation and limit blood loss. • Establish IV therapy if indicated.

30. Diseases of Erythrocytes Brady; Paramedic Care Principles and Practice

31. Diseases of Erythrocytes • Sickle Cell Disease • Normal red cells maintain their shape as they pass through the capillaries and release oxygen to the peripheral tissues (upper panel). Hemoglobin polymers form in the sickle rell cells with oxygen release, causing them to deform. The deformed cells block the flow of cells and interrupt the delivery of oxygen to the tissues (lower panel).

32. Diseases of Erythrocytes • Sickle Cell Disease (cont.) • Sickle cell crises • Vaso-occlusive • Musculoskeletal/abdominal pain • Priapism • Renal/cerebral infarctions • Hematological • Lowered hemoglobin • Splenic sequestration • Infectious • Management • Follow general treatment guidelines prn. • Consider analgesics.

33. Diseases of Erythrocytes • Polycythemia • Overproduction of erythrocytes. • Occurs in patients > 50 years old or with secondary dehydration. • Most deaths due to thrombosis • Results in bleeding abnormalities: • Epistaxis, spontaneous bruising, GI bleeding. • Management: • Follow general treatment guidelines.

34. Diseases of Leukocytes • Leukopenia/Neutropenia • Too few white blood cells or neutrophils. • Follow general treatment guidelines and provide supportive care. • Leukocytosis • An increase in the number of circulating white blood cells, often due to infection. • Leukemoid reaction

35. Diseases of Leukocytes • Leukemia • Cancer of hematopoietic cells • Initial presentation • Acutely ill, fatigued, febrile and weak, anemic. • Thrombocytopenia • Often have a secondary infection. • Management • Follow general treatment guidelines. • Utilize isolation techniques to limit risk of infection.

36. Diseases of Leukocytes • Lymphomas • Cancers of the lymphatic system • Hodgkin's • Non-Hodgkins • Presentation • Swelling of the lymph nodes • Fever, night sweats, anorexia, weight loss, fatigue, and pruritis • Management • Follow general treatment guidelines. • Utilize isolation techniques to limit risk of infection.

37. Clotting Disorders • Thrombocytosis and Thrombocytopenia • Thrombocytosis • An abnormal increase in the number of platelets • Thrombocytopenia • An abnormal decrease in the number of platelets • Sequestration • Destruction (ITP) • Decreased production • Management • Provide supportive care and follow general treatment guidelines.

38. Clotting Disorders • Hemophilia • Deficiency or absence of a blood clotting factor • Deficiency of factor VIII causes hemophilia A. • Deficiency of factor IX causes hemophilia B. • Deficiency is a sex-linked, inherited disorder. • Defective gene is carried on the X chromosome. • Signs & Symptoms • Numerous bruises, deep muscle bleeding, and joint bleeding.

39. Clotting Disorders • Hemophilia (cont.) • Management • Treat the patient similarly to others. • Administer supplemental oxygen. • Establish IV access. • Be alert for recurrent or prolonged bleeding, and prevent additional trauma. • Von Willebrand’s Disease • Deficient component of factor VIII • Generally results in excessive bleeding. • Generally is not serious; provide supportive care.

40. Clotting Disorders • Disseminated Intravascular Coagulation

41. Components of Blood • Leukocytes (cont.) • Autoimmune disease • May be specific or general • Alterations in the immune process • Immunosuppression • HIV • Anti-rejection medication • Chemotherapy/Cancer • System activation of coagulation cascade. • Results from sepsis, hypotension, OB complications, severe tissue or brain injury, cancer, and major hemolytic reactions. • Multiple Myeloma • Cancerous disorder of plasma cells. • Pathologic fractures are common.

42. Anticoagulants/Antiplatelets • Classifying agents • Anticoagulants • Block synthesis and activation of clotting factors • Antiplatelets • Interfere with platelet aggregation or activation • Fibrinolytics • Dissolve fibrin component of thrombi

43. Anticoagulants/Antiplatelets • Anticoagulants • Warfarin • Blocks activation of Vit K • Interferes w/ coagulation factors II, VII, IX, and X • Unfractionated Heparin • Binds antithrombin III (AT-III) • Inhibits coagulation factors IX and X and thrombin • Hirudin (medicinal leech) • Prevents thrombin binding

44. Anticoagulants/Antiplatelets • Antiplatelets • Aspirin • Prevents platelet activation through cyclooxygenase blockade. • Prevents production of thromboxane A2 • Allows prostacyclin synthesis • Ticlodipine • Deforms platelet membrane fibrinogen receptor

45. Anticoagulants/Antiplatelets • Antiplatelets (cont.) • Glycoprotein IIb-IIIa Receptor Inhibitors • G IIb-IIIa = platelet membrane receptor of fibrinogen • Abciximab • Eptifibatide • Tirofiban • Fibrinolytics • Activate plasminogen to plasmin = fibrinolysis • Streptokinase • Anistreplase • Tissue Plasminogen Activator • Reteplase • Urokinase

46. Hemorrhage

47. Transfusion Reactions • Hemolytic Reaction • Signs & Symptoms • Facial flushing, hyperventilation, tachycardia, hives, chest pain, wheezing, fever, chills, and cyanosis • Treatment • Stop transfusion, change all IV tubing, and initiate IV therapy with normal saline or lactated Ringer’s. • Consider furosemide, dopamine, and diphenhydramine.

48. Transfusion Reactions • Febrile Non-hemolytic Reactions • Signs & Symptoms • Headache, fever, and chills • Treatment • Stop transfusion, change all IV tubing, and initiate IV therapy with normal saline or lactated Ringer’s. • Consider Diphenhydramine and an antipyretic. • Observe closely to ensure reaction is non-hemolytic.