Chapter 12 Disorders of Hemostasis

1. Essentials of Pathophysiology Chapter 12 Disorders of Hemostasis

2. Platelets are also known as leukocytes. • Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder that affects the normal function and formation of platelets. • Disseminated intravascular coagulation is a condition that results in massive systemic bleeding, but coagulation function remains normal. • The use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been identified as a cause of impaired platelet function. • Bleeding can occur as a result of a decrease in the number of circulating platelets or because of impaired platelet function. PRE LECTURE QUIZ (TRUE/FALSE) F T T T T

3. _________________ is the orderly, stepwise process for stopping bleeding that involves vasospasm, formation of a platelet plug, and development of a fibrin clot. • A decrease in the number of circulating platelets is known as _________________________. • Hemophilia A is an X-linked recessive disorder that involves a deficiency of factor _________________. • ________________ disorders are caused by defects associated with platelets, coagulation factors, and vessel integrity. • Vitamin _______________, a fat-soluble vitamin that is continuously being synthesized by intestinal bacteria, is necessary for normal activity of factors VII, IX, and X and prothrombin. PRE LECTURE QUIZ Bleeding  K  Hemostasis thrombocytopenia VIII 

4. Stopping blood flow • Normal: • Blood usually fluid • Seals broken blood vessels • Abnormal: • Inappropriate clotting • Insufficient clotting Hemostasis

5. Thrombopoietin • Made in liver, kidney, smooth muscle, bone marrow • Megakaryocytes formed in bone marrow • Break apart to form many platelets • Platelets live 8–9 days in circulation • Many are stored in spleen • Released when needed Platelets (Thrombocytes)

6. Platelet Structure

7. All but which of the following are true about platelets? • An enzyme called erythropoietin stimulates their production. • They are made from megakaryocytes. • They originate from the bone marrow. • They are stored in the spleen. Question

8. An enzyme called erythropoietin stimulates their production. Rationale:Erythropoietin stimulates the production of RBCs (erythrocytes). The word literally means erythrocyte production. Platelet formation is stimulated by thrombopoietin (thrombus/clot production). Answer

9. CLOTTING CASCADE

10. Chemicals produced by platelets • Released at an injury to: • Start clotting by reacting with blood proteins • Help platelets stick together • Stimulate wound healing • Help platelets stick to vessel wall • Constrict blood vessels Mediators of Hemostasis

11. Plasma proteins • Most are synthesized by liver • von Willebrand factor made by endothelium • Circulate as inactive procoagulation factors • Calcium Coagulation Factors

12. What is the effect of von Willebrand disease on the platelets? • Increased platelet aggregation • Decreased platelet aggregation • Increased platelet formation • Decreased platelet formation Question

13. Decreased platelet aggregation Rationale:Von Willebrand disease is the most common hereditary bleeding disorder. It is caused by a deficiency or defect in vWF (which carries a clotting factor). The result of less clotting factor is an inability to clot. Answer

14. Vessel Spasm

15. Celebrex is a drug that blocks COX-2 Given to block inflamation People taking Celebrex develop increased TXA2 levels What problems might they have? Cyclooxygenase Enzymes (COX) Produce Mediators of Hemostasis arachidonic acid COX-1 COX-2 thromboxane A Prostacyclin Macrophage Activation & Inflamation mediation 2 NSAIDs inhibit both COX 1 &2 COX 1 is needed for intestinal mucosa Problems here?

16. Intrinsic and Extrinsic Pathways Common Pathway

17. Platelets Activated platelets Non activated platelet Platelet aggregate with fibrin threads

18. Fibrinogen  Fibrin

19. A man had a stroke and the doctor gave him tissue plasminogen activator (TPA). • Why? What is the doctor trying to accomplish? • One of the man’s relatives wondered why they did not give him heparin or warfarin instead • What is the difference? Why might TPA be more appropriate? Scenario

20. Increased platelet number Platelet aggregation Endothelial damage Increased procoagulation factors Decreased anticoagulation factors Hypercoagulability

21. True or False. Hypercoagulability states increase the risk of thrombus formation. Question

22. True Rationale:Hyper- as a prefix means “over” or “too much.” Coagulation/coagulability means “clotting/the ability to clot.” Hypercoagulability means “increased ability to clot or form thrombi.” Answer

23. A woman with lupus develops breast cancer. • She is given radiation therapy • She begins to develop nosebleeds and bruising • Her menstrual period is abnormally heavy Question: Why did this happen? Scenario:

24. Decreased platelet levels (thrombocytopenia) • Decreased production • Increased destruction • Platelets used up in forming clots • Impaired platelet function Platelet Disorders

25. DIC

26. True or False. Platelet disorders are bleeding disorders. Question

27. True Rationale:Because the platelet’s job is to clot, platelet disorders mean that the platelets cannot do that job. An inability to clot results in bleeding/bleeding disorders. Answer