Lecture 14: Blood Flashcards
What initiates primary hemostasis in the coagulation cascade?
arterial vasoconstriction occurs to reduce blood flow to the site of the injury
What is involved in secondary hemostasis?
the two pathways: intrinsic and extrinsic
What is the intrinsic pathway in the coagulation cascade?
contact activation: the blood is exposed to the surface of the damaged endothelium and collagen within that wall and this contact activated factor XII to XIIa
What is the extrinsic pathway in the coagulation cascade?
traumatized tissue releases tissue factors which complex with factor VIIa
factory I
fibrinogen
factor II
prothrombin
factor III
tissue factor or thromboplastin
factor VIII
antihemophilic factor
factor IX
Christmas factor
What are the vitamin K dependent clotting factors?
II, VII, IX, and X
What is an good indication of the presence of an inherited bleeding disorder?
bleeding after minor surgical procedures especially dental procedures
What is the percent of patients with hemophilia A or B that have a negative family history?
30-40%
What are the indications of a platelet defect?
mucocutaneous bleeding after cuts, increased bleeding after cuts, small areas of superficial bleeding after cuts, variable amounts of bleeding after major surgery
What are the indications of clotting factor deficiencies?
deep tissue bleeding (joint and muscle), large hematomas, can be delayed bleeding post-surgery
What are examples of platelet disorders?
Von Willebrand disease is most common, immune thrombocytopenia
What are examples of clotting deficiencies?
factor VIII (hemophilia A), factor IX (hemophilia B), factor XI (hemophilia C)
What is a hyppercoagulable disorder?
usually results in higher than normal risk for thrombosis formation; also knows as thrombophilia or bleeding diathesis; increased risk involved in pregnancy, cancer, and estrogen therapy
What is antithrombin III?
also known as antithrombin; is an alpha-2 globulin made in the liver; it is an anticoagulant
What happens in the absence of antithrombin III?
coagulation is constant, unchecked and eventually results in depletion of clotting factors -> leading to uncontrolled bleeding
How is antithrombin involved in mediating the balance of clotting and bleeding?
inactivation of thrombin, and inactivation of factor X to Xa
What is an antithrombin III lab test used for?
used to monitor for hyppercoagulable states
What can a decreased antithrombin result in?
deep vein thrombosis, pulmonary embolism, phlebitis, heparin resistance, early age onset of thromboembolic events
What are protein C and protein S?
they are anticoagulants that are synthesized in the liver; protein s is a co-factor to protein c that enhances the function of protein C
What does protein C inhibit?
factor Va and factor VIIIa
What are the outcomes of a decrease in protein C and S?
increased risk 7 fold for venous thromboembolism (VTE), disseminated intravascular coagulation, neonatal purpura fulminans
What is factor V Leiden?
an inherited mutated form of factor V; caused by a single mutation from glutamine to arginine
What is the pathophysiology behind the effect of factor V Leiden?
typically protein C breaks down factor V at one of three cleavage sites; in factor V Leiden protein C cannon break down factor V at one of the normal cleavage sites -> as a result factor V leiden stays in circulation longer increasing coagulation
Who should you test for factor V leiden?
patients who have a thrombotic event without and predisposing factors; strong family history of thrombosis; DVT of pregnancy or w/ oral contraceptive use; arterial clot or thrombosis of unusual location
What is fibrinogen?
produced in liver; involved in hemostasis of blood clotting; fibrinogen is converted to fibrin through the action of thrombin; also is an acute phase reactant and levels increase with tissue inflammation
What is a fibrinogen test primarily used for?
used in the evaluation of bleeding disorders and to monitor for the treatment of DIC and fibrinolysis
dysfibrinogenemia
dysfunctional fibrinogen; bleeding or thrombosis occurs, poor wound healing
hypofibrinogenemia
reduces fibrinogen, usually mild bleeding
hypodysfibrinogenemia
reduced AND dysfunctional fibrinogen, bleeding or thrombosis
Afibrinogenemia
rare genetic condition resulting in lack of fibrinogen (increase in consanguinity); mild to severe bleeding
What causes increase in levels of fibrinogen?
acute inflammation, trauma, acute infection, CVA, CAD, MI, pregnancy, estrogen and oral contraceptive use
What causes a decrease in levels of fibrinogen?
congenital Afibrinogenemia, hypofibrinogenemia, liver disease, disseminated intravascular coagulation