1. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Chapter 26 Disorders of Hemostasis

2. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Five Stages of Hemostasis 1.Vessel spasm 2.Formation of the platelet plug 3.Blood coagulation or development of an insoluble fibrin clot 4.Clot retraction 5.Clot dissolution

3. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Categories of Disorders of Hemostasis Thrombosis –The inappropriate formation of clots within the vascular system Bleeding –Failure of blood to clot in response to appropriate stimulus

4. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Vascular Constriction Vessel spasm constricts the vessel and reduces blood flow. It is a transient event that usually lasts minutes or hours. Vessel spasm is initiated by endothelial injury and caused by local and humoral mechanisms.

5. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Platelet Plug Formation Adhesion and aggregation 1.Attracted to a damaged vessel wall 2.Activation by subendothelial tissue 3.Change from smooth disks to spiny spheres 4.Exposing glycoprotein receptors on their surfaces

6. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Requirements for Blood Clotting Process Presence of platelets produced in the bone marrow Von Willebrand factor generated by the vessel endothelium Clotting factors synthesized in the liver using vitamin K

7. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Why should blood clot? Hemostasis is designed to maintain the integrity of the vascular compartment. –Infection –Volume –Oxygen production –Tissue damage –Healing

8. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Clot Retraction and Dissolution Clot retraction and clot dissolution are also significant to hemostasis. The process involves the interaction of substrates, enzymes, protein cofactors, and calcium ions that circulate in the blood or are released from platelets and cells in the vessel wall.

9. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Intrinsic and Extrinsic Coagulation Pathways Terminal steps in both pathways are the same. –Calcium, factors X and V, and platelet phospholipids combine to form prothrombin activator. –Prothrombin activator converts prothrombin to thrombin. –This interaction causes conversion of fibrinogen in fibrin stands that create the insoluble blood clot.

10. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Regulation of Blood Coagulation Antithrombin III inactivates coagulation factors and neutralizes thrombin. When antithrombin III is complexed with naturally occurring heparin, its action is accelerated, and provides protection against uncontrolled thrombus formation on the endothelial surface. Protein C, a plasma protein, acts as an anticoagulant by inactivating factors V and VIII.

11. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Regulation of Blood Coagulation (cont.) Protein S, another plasma protein, accelerates the action of protein C. Plasmin breaks down fibrin into fibrin degradation products that act as anticoagulants.

12. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins General Forms of Hypercoagulability States Conditions that create increased platelet function –Atherosclerosis –Diabetes mellitus –Smoking –Elevated blood lipoid and cholesterol levels –Increased platelet levels

13. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins General Forms of Hypercoagulability States (cont.) Conditions that cause accelerated activity of the coagulation system –Pregnancy and the puerperium –Use of oral contraceptives –Postsurgical state –Immobility –Congestive heart failure –Malignant diseases

14. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Hypercoagulability States Increase the risk of clot or thrombus formation in the arterial or venous circulations –Arterial thrombi are associated with conditions that produce turbulent blood flow and platelet adherence. –Venous thrombi are associated with conditions that cause stasis of blood flow with increased concentrations of coagulation factors.

15. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Causes of Bleeding Decrease in the number of circulating platelets –Depletion of platelets must be relatively severe before hemorrhagic tendencies of spontaneous bleeding occur. Impaired platelet function –Bleeding resulting from platelet deficiency commonly occurs in small vessels and is characterized by petechiae and purpura.

16. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Increased Platelet Function Hypercoagulability due to increased platelet function results in platelet adhesion, formation of platelet clots, and disruption of blood flow. The causes of increased platelet function are disturbances in flow, endothelial damage, and increased sensitivity of platelets to factors that cause adhesiveness and aggregation.

17. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Atherosclerotic Plaques and Platelets Atherosclerotic plaques disturb blood flow, causing endothelial damage and promoting platelet adherence. Platelets that adhere to the vessel wall release growth factors, which cause proliferation of smooth muscle and thereby contribute to the development of atherosclerosi. Smoking, elevated levels of blood lipids and cholesterol, hemodynamic stress, and diabetes mellitus predispose to vessel damage, platelet adherence, and eventual thrombosis.

18. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Platelet Defects Thrombocytopenia –Results from a decrease in platelet production, increased sequestration of platelets in the spleen, or decreased platelet survival –Types Drug-induced thrombocytopenia Idiopathic thrombocytopenic purpura Thrombotic thrombocytopenic purpura Impaired platelet function

19. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Manifestations of Thrombocytopenia Bleeding –Mucous membranes Nose, mouth, gastrointestinal tract, and uterine cavity Commonly occurs in small vessels –Petechiae—pinpoint purplish-red spots Seen almost exclusively in conditions of platelet deficiency –Purpura—purple areas of bruising

20. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Thrombocytopenia may be caused by all of the following except: –A. Auto antibodies –B. Drug hypersensitivities –C. Viral stimulation of platelet production –D. Bacterial infections that decrease platelet production

21. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer C. Viral stimulation of platelet production Rationale: Thrombocytopenia is an essential reduction of platelets.

22. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Coagulation and Vitamin K Vitamin K is an essential cofactor for synthesis of clotting factors. –Fat-soluble vitamin synthesized by intestinal bacteria –In vitamin K deficiency, the liver produces inactive clotting factor resulting in abnormal bleeding.

23. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Coagulation Defects Deficiencies can arise because of defective synthesis, inherited disease, or increased consumption of the clotting factors – Hereditary disorders –Hemophilia A –Hemophilia B –Von Willebrand disease –Any genetic disruption of the production of clotting factor

24. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Von Willebrand disease is caused by which of the following? –A. Deficiency of clotting factors VIII and IX –B. Lack of factor IX and poor platelet function –C. Deficiency of factor VIII and poor platelet function

25. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer C. Deficiency of factor VIII and poor platelet function Rationale: These two conditions come together to cause the disseminated bleeding.

26. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Vascular Disorders that Cause Bleeding Hemorrhagic telangiectasia –An uncommon autosomal dominant disorder characterized by thin-walled, dilated capillaries and arterioles Vitamin C deficiency (scurvy) –Results in poor collagen synthesis and failure of the endothelial cells to be cemented together properly, causing a fragile wall

27. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Vascular Disorders that Cause Bleeding (cont.) Cushing disease –Causes protein wasting and loss of vessel tissue support because of excess cortisol Senile purpura (bruising in elderly persons) –Caused by the aging process

28. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Conditions Associated with Disseminated Intravascular Coagulation Obstetric conditions Cancers Infections Shock Trauma or surgery Hematologic conditions

29. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Question DIC is associated with which of the following? –A. Endothelial damage –B. Activation of factor X –C. Release of tissue factor –D. A, B, and C are all correct.

30. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer D: A, B, and C are all correct. Rationale: A, B, and C are all correct and can lead to the bleeding and clotting seen in DIC.