NURS 5315: Advanced Pathophysiology Hematologic Module 4 Questions with 100% Correct Answers

NURS 5315: Advanced Pathophysiology Hematologic Module 4 Questions with 100% Correct Answers What is the peripheral zone of platelet? Outermost layer. Made of phospholipids. Contains many receptors responsible for platelet adhesion and aggregation What is the sol-gel of the platelet It is the outermost layer made of possible if it contains many receptors responsible for platelet adhesion and aggregation What is the organelle zone of platelets Innermost layer contains calcium dense granules and alpha granules What are the four phases of platelet plug formation? Activation, adherence, aggregation, and secretion What is the first step or phase of platelet plug formation and explain Activation is the first step. In physiological states. Platelets circulate without adhering to the intact endothelium. An injury to the endothelium exposes thev WF, fibronectin, collagen and from thrombospondin.. Collagen is a potent activator and when the sub endothelial collagen is exposed by an injury. The platelets become charged AKA activated. Platelets and become aware of the injury and undergo a shape change that increases their ability to adhere to the site of injury. The second step in platelet plug formation is Adherence is a process by which platelets attached to the injured endothelium. Adherence begins with the vWF. Circulating vWF binds to the exposed subendothelial collagen and to the GP Ib/IX/V receptors on circulating platelets. Collagen then binds with the GP VI receptor. The binding of collagen with the GP VI receptor results in the activation of the GPIIb/IIIa and GPIa/IIa receptors. vWF then binds with the GPIIb/IIIa receptors and collagen further binds with the GPIa/IIa receptors. This collective binding anchors the platelets in place The third step in platelet plaque formation is Aggregation- is the process by which platelets bind to one other. There are multiple GPIIb/IIIa receptors on one platelet and when activated (as described above) they have a greater affinity for fibrinogen. Fibrinogen is able to bind to two GPIIb/IIIa receptors simultaneously and thereby bind platelets together The fourth step in platelet plug formation is Secretion- during this phase the platelet granules release their contents. a. ADP- enhances adhesion, activates platelets and recruits platelets b. Serotonin recruits platelets. c. Fibronectin and thrombospondin are proteins which stabilize platelets that are adhered to the site of injury. d. Thromboxane A2- is a product of the arachidonic acid pathway but is stored inside the platelet too. It causes vasoconstriction and enhances platelet aggregation. e. Growth factors promote tissue repair however they have a role in the development of atherosclerosis. The final step in platelet plug formation The platelet plug is stabilized by fibrin and XIIIa which are the end products of the coagulation cascade. What is the extrinsic pathway arms of the coagulation cascade Extrinsic pathway is considered the primary pathway of coagulation. It is activated when Tissue Factor is exposed at the site of injury. The process starts with a vascular injury which results in the exposure of Tissue Factor (III) which has a cell receptor for factor VII. (As a side note lipid filled macrophages in atherosclerotic plaques contain a large amount of tissue factor which increases the likelihood of arterial thrombus formation from plaque ruptures). Once exposed TF binds with VII to form the TF/VIIa complex. TF/VIIa activates X = Xa. Activated factor Xa binds with activated Va and calcium to form the prothrombinase complex. The prothrombinase complex converts factor II (prothrombin) to activated factor IIa (thrombin). Thrombin (activated factor IIa) then moves on to activate 4 factors. It activates factor I (fibrinogen) to activated factor Ia (fibrin) and it also activates factors V, VIII & XIII. You can see the action of thrombin on your screen marked with blue lines. Fibrin (activated factor Ia) is placed over the platelet plug and activated factor XIIIa stabilizes the fibrin. What is the intrinsic pathway arms of the coagulation cascade The clinical significance of the intrinsic pathway is not entirely understood, because a deficiency of factor XII (Hageman factor) does not cause bleeding. As such the intrinsic pathway's main function is thought to be one which enhances the extrinsic pathway. This pathway is activated when the blood is exposed to negative charges which are found on the molecules of ADP and ATP. This exposure activates factor XII (Hageman factor). Activated factor XIIa then activates factor XI. Activated factor XIa activates IX. Activated factor IXa then activates factor X. Activated factor Xa then forms the prothrombinase complex in the common pathway. Coagulation Cascade Key Plasma Proteins 1.Tissue Factor 2.VII 3.X 4 .Prothrombinase Complex 5. Prothrombin 6. Thrombin 7 .Fibrinogen 8. Fibrin 9. XIII 10. XII 11. VIII 12. IX 13. Antithrombin 14. Protein C 15. Protein S 16.t-PA 1. Initiator of extrinsic pathway. 2. Forms complex with tissue factor (III) and activates factors IX and X 3. Activates Prothrombin through activated Xa form 4. (prothrombin and activated factors X and V) that activates prothrombin into thrombin 5. Factor II, source of thrombin that activates fibrinogen 6. cleaves the extracellular domain of G-protein-coupled protease-activated receptors (PARs), thereby initiating transmembrane signaling. 7. moves between the beta and gamma regions but is removed during the formation of serum; precursor of fibrin clot 8. Used to stabilize clot 9. Fibrin - stabilizing factor - cross links fibrin through XIIIa to strengthen clot 10. Hageman Factor. Initiator of intrinsic pathway 11. VIIIa is a component of tenase complex 12. IXa is a component of tenase complex, activates factor X 13. it inhibits thrombin and several activated clotting factors (e.g., VIIa, IXa, Xa, XIa, XIIa). 14. in the circulation binds to thrombomodulin in a thrombin-dependent manner and is converted to activated protein C 15. degrades factors Va and VIIIa 16. a serine protease that reaches maximal enzymatic activity after binding to fibrin and proteolytically activates plasminogen to plasmin What is the coagulation cascade The coagulation cascade is the second arm of hemostasis. This process involves quite a few steps and there are many players involved. It can be difficult to follow and understand. This first slide show the coagulation process in a simplified manner. The two arms of the coagulation cascade are activated, followed by multiple enzymatic processes, the two arms then converge into the common pathway and the final product of this process is the formation of fibrin which stabilizes the platelet plug. There are a total of twelve coagulation factors, and a number of additional proteins which function to control coagulation and dissolve clots. All twelve coagulation factors are plasma proteins and the majority of them are produced by the liver. Because they are produced by the liver individuals with liver disease such as cirrhosis, acute hepatic failure, or hepatocyte damage of any kind (temporary or chronic) are likely to be deficient in these factors and at an increased risk of bleeding. How was the platelet plug process altered with aspirin? Inhibits the formation of TX a two by blocking Cox one pathway of arachidoic pathway How is the platelet plug process altered with clopidogrel? P2Y12 receptor is blocked from ADP - thus allowing cAMP to continue to prevent platelet aggregation How does warfarin altered coagulation? Vitamin K is blocked from becoming vitamin k reductase, and carboxylation of vitamin K dependent clotting factors is unable to occur. How does low molecular weight heparin alter coagulation? -cannot inhibit thrombin, but can only inhibit clotting factor Xa -They inhibit activated Xa and prevent the formation of the prothrombinase complex and consequently thrombin. They do have some effect on antithrombin but to a much lesser extent than heparin. How does factor X a inhibitors alter coagulation These drugs (fondaparinux, apixiban, rivaroxaban) increase antithrombin's affinity for Xa. Antithrombin neutralizes Xa and thereby prevents the formation of the prothrombinase complex and thrombin. How does direct thrombin inhibitors altered coagulation Drugs in this class include dabigatran and argatroban. The inhibition of thrombin prevents the activation of fibrinogen and XIII. The active form of fibrinogen is fibrin which supports the platelet plug. XIIIa cross links with fibrin to provide stabilization to the platelet plug. How does primary view thrombocytopenia purpura altar platelet plug process Process of platelet destruction begins with the phagocytosis of platelets by macrophages. The macrophages then present the digested platelet peptides to the CD4 cells. The CD4 cells believe these peptides are antigens and initiate the immune response. IgG antibodies then bind to platelets most often on the platelet membrane glycoproteins such as GPIIb/IIIa and ultimately platelets are destroyed How is the platelet plug process altered with TTP -ADAMTS13 is a protease that is responsible for the breakdown of von Willebrand factor. • Persons with TTP have large amounts of vWF in their plasma and lack ADAMTS13 protease. • In congenital forms of the disease there is a mutation in the gene responsible for making ADAMTS13, leading to a deficiency of this protease. 5 • The increased levels of vWF leads to platelet aggregation, microthrombi in organs, causing organ failure. The thrombi are mainly made of platelets (lacking RBCs and fibrin). • Antibody to ADAMTS13 has been isolated in most people with acquired TTP. • Other factors o Plasminogen activator inhibitor- levels are increased. Normal function is to inhibit fibrinolytic compound. How is hemophilia a coagulation altered Hemophilia A is a sex linked recessive disease which results in a deficiency of factor VIII. A mutation in the F8 gene leads to the development of hemophilia A. In him and Philip B how is coagulation altered The characteristics of Hemophilia B (Christmas Disease) are very similar to hemophilia A, but the deficiency is related to factor IX. All other characteristics are essentially the same, except that it occurs less commonly than Hemophilia Type A. ==Sex Linked recessive disease, secondary to a mutation in the F9 gene. • Deficiency in factor IX How does DIC alter the platelet plug process The igniting event causes endothelial damage. The endothelial damage exposes the subendothelial tissue factor and activates the inflammatory cascade. The exposed TF activates the coagulation cascade. The activation of the coagulation system leads to a widespread and systemic intravascular fibrin deposition. While this is happening the fibrinolytic system is working to break down the fibrin. The fibrin degradation products (which are present in massive amounts) adhere to platelets and prevent platelet adhesion. Eventually the products of coagulation are consumed, resulting in bleeding. Organ failure may ensue due to micro-thrombi How does DIC alter coagulation The igniting event causes endothelial damage. The endothelial damage exposes the subendothelial tissue factor and activates the inflammatory cascade. The exposed TF activates the coagulation cascade. The activation of the coagulation system leads to a widespread and systemic intravascular fibrin deposition. While this is happening the fibrinolytic system is working to break down the fibrin. The fibrin degradation products (which are present in massive amounts) adhere to platelets and prevent platelet adhesion. Eventually the products of coagulation are consumed, resulting in bleeding. Organ failure may ensue due to micro-thrombi What are the clinical manifestations of coagulopathy heorrhage? Clinical manifestations of a bleed from a coagulopathy include: • joint bleeding • tissue hematomas • large, spontaneous, centrally located ecchymosis • bleeding after trauma, surgery or an injury tends to be delayed What is a example of coagulopathy hemorrhage? Deficiency of Hageman factor (factor XII) Hemophilia A & B What are the clinical manifestations of thrombocytopenia hemorrhage Clinical manifestations of a bleed from a thrombocytopenia include: • Mucosal bleeding such as: • Epistaxis • Oral bleeding • GI or GU bleeding (in the absences of malignancy) • Hemoptysis • Heavy menses • Bleeding occurs immediately after a trauma or injury • Petechiae may be present. What are examples of Thrombocytopenia? Thrombotic Thrombocytopenic Purpura (TTP) Neonatal thrombocytopenia Primary Immune Thrombocytopenic purpura What are the causes of thrombocytopenia? Common causes of thrombocytopenia include: • Hemodilution which tends to occur post-operatively and has a nadir of 2-4 days. A nadir refers to the lowest point. • Splenomegaly which is seen in some cancer patients and patients with cirrhosis. The spleen sequesters platelets. • HIV, bone marrow failure • Hemolysis • Medications cause a lot of issues and thrombocytopenia is one of them. On this slide you see a list of medications which can cause thrombocytopenia: Sulfonamides • Vancomycin, • Quinine -remember tonic water • Linezolid (Zyvox), • Heparin, Abciximab (Reopro) • Eptifibatide (Integrilin), Tirofibab (Aggrastat), • Rifampin (Rifadin), Piperacillin, • Beta Lactam antibiotics (PCN, Cephalosporins), • Valporic acid (Depakote), • Carbamazepine (Tegretol), Phenytoin (Dilantin) What is the etiology of Primary Immune Thrombocytopenic purpura? AKA idiopathic Thrombocytopenic purpura It is acquired. Idiopathic, • Preceding viral infection: HIV, VZV, CMV, HCV, • Disease states (as above) cause secondary ITP. Primary ITP refers to an isolated thrombocytopenia in the absence of another etiology such as SLE, CML, Antiphospholipid syndrome, or medications What is the Clinical manifestations of ITP? Clinical manifestations of ITP include: • Presentation can vary • Petechiae, purpura, and easy bruising are expected.