1. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Chapter 10 Alterations in Hemostasis

2. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Hemostasis Stopping blood flow Normal: –Blood usually fluid –Seals broken blood vessels Abnormal: –Inappropriate clotting –Insufficient clotting

3. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Platelets (Thrombocytes) 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

4. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question All but which of the following are true about platelets? a.An enzyme called erythropoietin stimulates their production. b.They are made from megakaryocytes. c.They originate from the bone marrow. d.They are stored in the spleen.

5. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer a.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).

6. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Mediators of Hemostasis 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

7. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Coagulation Factors Plasma proteins –Most are synthesized by liver –von Willebrand factor made by endothelium –Circulate as inactive procoagulation factors Calcium

8. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question What is the effect of von Willebrand disease on the platelets? a.Increased platelet aggregation b.Decreased platelet aggregation c.Increased platelet formation d.Decreased platelet formation

9. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer b.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.

10. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Vessel Spasm

11. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Cyclooxygenase Enzymes (COX) Produce Mediators of Hemostasis Celebrex is a drug that blocks COX-2 People taking Celebrex develop increased TXA 2 levels What problems might they have? COX-1 COX-2 arachidonic acid thromboxane A 2 prostacyclin

12. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Intrinsic and Extrinsic Pathways

13. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Fibrinogen  Fibrin

14. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Scenario 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?

15. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Hypercoagulability Increased platelet number Platelet aggregation Endothelial damage Increased procoagulation factors Decreased anticoagulation factors

16. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Tell whether the following statement is true or false. Hypercoagulability states increase the risk of thrombus formation.

17. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer 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.”

18. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Scenario: 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?

19. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Platelet Disorders Decreased platelet levels (thrombocytopenia) –Decreased production –Increased destruction –Platelets used up in forming clots Impaired platelet function

20. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Tell whether the following statement is true or false. Platelet disorders are bleeding disorders.

21. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer 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.