CHAPTER 22.pdf

‭CHAPTER 22: ALTERATION OF HEMOSTASIS‬ ‭Blood = plasma + formed elements (erythrocytes, leukocytes thrombocytes)‬ ‭ emostasis is a term that refers to the cessation of blood flow, particularly through the action of coagulation (clotting)‬ H ‭mechanisms‬ ‭Hemorrhage refers to copious bleeding which c...

‭CHAPTER 22: ALTERATION OF HEMOSTASIS‬ ‭Blood = plasma + formed elements (erythrocytes, leukocytes thrombocytes)‬ ‭ emostasis is a term that refers to the cessation of blood flow, particularly through the action of coagulation (clotting)‬ H ‭mechanisms‬ ‭Hemorrhage refers to copious bleeding which can be outside the skin (from laceration) or in the skin (ecchymoses)‬ ‭Disorders of hemostasis are related to excessive coagulation or excessive bleeding - disruption of homeostasis can occur at any‬ ‭point of coagulation‬ ‭1.‬ ‭Vascular phase (initiation)‬ ‭a.‬ ‭Spasm of blood vessels (injury to blood vessel causes a reactive constriction of spasm of the blood vessels, and‬ ‭platelets are activated and travel to site)‬ ‭2.‬ ‭Aggregation phase (amplification)‬ ‭a.‬ ‭Platelets form a plug (clump together)‬ ‭3.‬ ‭Coagulation phase (propagation)‬ ‭a.‬ ‭Formation of fibrin (platelets release immune proteins+ forms film over platelet)‬ ‭Clotting is caused by intrinsic, extrinsic, and a common pathways‬ ‭Intrinsic‬ ‭Extrinsic‬ ‭Common Pathway‬ ‭ ctivated by trauma‬ A ‭inside the vascular‬ ‭system‬ ‭Activated by platelets,‬ ‭exposed endothelium,‬ ‭chemicals, or collagen‬ ‭ ctivated by‬ A ‭external trauma‬ ‭that causes blood to‬ ‭escape from the‬ ‭vascular system‬ ‭This pathway is‬ ‭much quicker‬ F‭ actor X is a vitamin K-dependent clotting factor and plays a central role in‬ ‭the coagulation cascade at the point of convergence of the intrinsic and‬ ‭extrinsic pathway‬ ‭Factors XII, IX, VII‬ ‭Factors VII, III‬ ‭ ctivated factor X causes a set of reaction resulting in the inactive enzyme‬ A ‭prothrombin (factor II) being converted in the active form thrombin‬ ‭Thrombin then converts soluble fibrinogen (factor I) into insoluble‬ ‭fibrin strands‬ ‭The fibrin strands compromising the clots are then stabilized by factor XIII‬ ‭ lotting cascade is similar to the complement system and each enzyme of the pathway is present in the plasm in an inactive form‬ C ‭The coagulation pathway is a series of + and - feedback loops that control the activation process with the end goal being to reduce‬ ‭thrombin‬ ‭‬ ‭Thrombin alters the structure of fibrinogen, transforming it into fibrin‬ ‭‬ ‭Fibrin provides a mesh like framework on which platelets can clump‬ ‭ ofactors include‬‭calcium‬‭, which serves to bind the‬‭clotting factors together for coagulation to occur while and‬‭vitamin K‬‭is‬ C ‭essential for the functioning of several proteins involved in the regulation of blood clotting‬ ‭Both are required for the synthesis of protein c, an anticoagulant that prevents excessive coagulation after the coagulation cascade‬ ‭occurs. Deficiency of any of these clotting cofactors will cause an impaired ability for blood to coagulate and can contribute to‬ ‭excessive bleeding and hemorrhage‬ ‭ reaking down clots involves primary fibrinolysis, the body’s normal process and secondary fibrinolysis, caused by medication or‬ B ‭disease process‬ ‭Plasmin is the main enzyme that cuts the fibrin mesh at various places‬ ‭‬ ‭Leads to the production of circulating fragments‬ ‭○‬ ‭Fibrin degradation produce‬ ‭○‬ ‭This number is reflected in the D-dimer‬ ‭‬ D ‭ -dimer is a product of fibrin degradation that is present after blood clots are broken down. An elevated‬ ‭result may imply the presence of significant clotting propensity. Elevated levels can also be found in a‬ ‭number of other medical conditions and states.‬ ‭ ‬ ‭Plasminogen is the inactive from of plasmin produced in the liver‬ ‭○‬ ‭Required tissue plasminogen activator (T-PA) and urokinase to be converted to the active form of plasm‬ ‭○‬ ‭T-PA can be made in the lab and is known as recombinant r-PA‬ ‭‬ ‭Clot buster‬ ‭Various type of test for coagulation and bleeding‬ ‭‬ ‭D-dimer - fragment of fibrin degradation‬ ‭○‬ ‭D-dimer is a product of fibrin degradation that is present after blood clots are broken down. An elevated result‬ ‭may imply the presence of significant clotting propensity. Elevated levels can also be found in a number of other‬ ‭medical conditions and states.‬ ‭‬ ‭Activated partial thromboplastin time (aPTT) - same parameters as PTT, with clotting activator‬ ‭○‬ ‭Increased levels indicate prolonged bleeding. Particularly prolonged bleeding is associated with changes in the‬ ‭levels of select clotting factors, primarily factors II, V, IX, X, XI, and XII‬ ‭‬ ‭Fibrinogen - presence of soluble protein necessary for formation of fibrin‬ ‭‬ ‭Partial thromboplastin time (PTT) - functional ability of clotting pathway‬ ‭‬ ‭Vitamin k - vitamin essential to formation of several clotting factors‬ ‭Primary disorders‬ ‭Secondary disorders‬ ‭ ssociated with abnormalities in number or function of‬ A ‭platelets‬ ‭ ssociated with lack of, or reduction in, factors tied to‬ A ‭coagulation‬ ‭May occur as a result of genetic factors, liver dysfunction,‬ ‭dietary deficiency‬ ‭ ON WILLEBRAND DISEASE‬ V ‭Most common genetic bleeding disorder involving partial or‬ ‭complete deficiency in clotting factors (in which a lack of a‬ ‭certain factor prevents platelets from adhering to the site of‬ ‭injury, preventing the formation of a blood clot)‬ ‭‬ ‭Type 1 - most frequent and least severe, often‬ ‭asymptomatic‬ ‭‬ ‭Type 2 - some bleeding issues‬ ‭‬ ‭Type 3 - significant blood loss, internal bleeding, similar‬ ‭to hemophilia‬ ‭Treatments for spontaneous bleeding episode include‬ ‭desmopressin and transfusion with plasma derived vWF‬ ‭products‬ T‭ HROMBOCYTOPENIA‬ ‭Most common cause of abnormal bleeding involving a‬ ‭decrease in number of circulating blood platelets‬ ‭ auses not well understood, infection and other inflammatory‬ C ‭states. artifact, deficient production, increase destruction,‬ ‭consumption or both, abnormal distribution or pooling‬ ‭ linical manifestation include purpura (easy or excessive‬ C ‭bruising), ecchymoses, epistaxis (bleeding from nose), serious‬ ‭hemorrhages, petechiae (superficial bleeding into the skin that‬ ‭appears as a rash or pinpoint sized reddish purple spots,‬ ‭usually on lower legs)‬ ‭Treatment include plasmapheresis (plasma exchange), TTP‬ ‭ EMOPHILIA‬ H ‭Hereditary genetic bleeding disorder associated with the‬ ‭loss of select clotting factors and significant bleeding or‬ ‭soft tissues or joints‬ ‭‬ ‭Hemophilia A - factor VIII‬ ‭‬ ‭Hemophilia B - factor IX‬ ‭ an also be acquired from autoimmune disease, cancer,‬ C ‭pregnancy‬ ‭ linical manifestation‬ C ‭(infants) excessive bleeding after circumcision‬ ‭(adults) severe mucosal bleeding from tongue or hum‬ ‭injuries, permanent bruising over trunk and extremities‬ L‭ ab test would should prolong PTT, normal PT, platelet‬ ‭counts, bleeding time, platelet function assays,‬ ‭Diagnosis involves analysis of factor VIII and IX activity‬ T‭ reatment involves episodic or prophylactic‬ ‭administration of factor VII or XI concentrates‬ ‭therapy, infusion of fresh frozen plasma‬ ‭Issues of hypercoagulopathy in sickle cell disease‬ ‭‬ ‭Clinical manifestation include hypoxia and tissue ischemia‬ ‭‬ ‭Diagnosis involves increase concentration of thrombin with corresponding loss of anticoagulant proteins‬ ‭‬ ‭Treatment includes pharmacological treatments that reduce platelet binding and inhibit platelet activation‬ ‭ isseminated intravascular coagulation (DIC) is a life threatening condition that involves protein that control clotting becoming‬ D ‭overreacting‬ ‭‬ ‭Causes include sepsis, shock, or damage to blood vessels‬ ‭○‬ ‭3 can increase tissue factor and cause systemic activation of coagulation pathways‬ ‭‬ ‭Clinical manifestations - clots cause organ dysfunction, difficulty breathing, hemoptysis, tachycardia‬ ‭‬ ‭Diagnosis - low platelet and fibrinogen levels, prolongation of PT and aPTT results, with elevation in D-dimer values‬ ‭‬ ‭Treatment involves monitoring for blood loss and signs of organ failure due to ischemic damage or administration of‬ ‭platelet and other blood factors‬ ‭Patient education‬ ‭‬ ‭Patient who are at risk of excessive bleeding need to be educated about their condition and provided with instruction‬ ‭about preventing bleeding‬ ‭‬ ‭Bleeding precaution include using a soft toothbrush, wearing shoes at all times, avoiding contact sports, using stool‬ ‭softener to prevent straining‬