A) or FIX (hemophilia B), components of the common pathway. They have an intact extrinsic pathway. Therefore, the PT is unaffected, and the aPTT is prolonged. Patients on aspirin therapy and those with thrombocytopenia have alterations in platelet function and number, respectively, and not in the proteins of the clotting cascade. Therefore, both the PT and the aPTT are unaffected. Patients with end-stage liver disease have decreased ability to synthesize clotting proteins. They show prolonged PT and aPTT.
5.7. Which one of the following can be ruled out in a patient with thrombophilia?
A. A deficiency of antithrombin III
B. A deficiency of FIX
C. A deficiency of protein C
D. An excess of prothrombin
E. Expression of FV Leiden
Correct answer = B. Symptomatic deficiencies in clotting factors will present with a decreased ability to clot (coagulopathy). Thrombophilia, however, is characterized by an increased tendency to clot. Choices A, C, D, and E result in thrombophilia.
5.8. Current guidelines for the treatment of patients with acute ischemic stroke (a stroke caused by a blood clot obstructing a vessel that supplies blood to the brain) include the recommendation that tissue plasminogen activator (TPA) be used shortly after the onset of symptoms. The basis of the recommendation for TPA is that it activates:
A. antithrombin III.
B. the activated protein C complex.
C. the receptor for von Willebrand factor.
D. the serine protease that degrades fibrin.
E. thrombomodulin.
Correct answer = D. TPA converts plasminogen to plasmin. Plasmin (a serine protease) degrades the fibrin meshwork, removing the obstruction to blood flow. Antithrombin III in association with heparin binds thrombin and carries it to the liver, decreasing thrombin's availability in the blood. The activated protein C complex degrades the accessory proteins FV and FVIII. The platelet receptor for von Willebrand factor is not affected by TPA. Thrombomodulin binds thrombin and converts it from a protein of coagulation to one of anticoagulation by decreasing its activation of fibrinogen and increasing its activation of protein C.
5.9. The adhesion, activation, and aggregation of platelets provide the initial plug at the site of vessel injury. Which of the following statements concerning the formation of this platelet plug is correct?
A. Activated platelets undergo a shape change that decreases their surface area.
B. Formation of a platelet plug is prevented in intact vessels by the production of thromboxane A2 by endothelial cells.
C. The activation phase requires production of cyclic adenosine monophosphate.
D. The adhesion phase is mediated by the binding of platelets to von Willebrand factor via glycoprotein Ib.
E. Thrombin activates platelets by binding to a protease-activated G protein–coupled receptor and causing activation of protein kinase A.
Correct answer = D. The adhesion phase of platelet plug formation is initiated by the binding of von Willebrand factor to a receptor (glycoprotein Ib) on the surface of platelets. Shape change from discoidal to spherical with pseudopodia increases the surface area of platelets. Thromboxane A2 is made by platelets. It causes platelet activation and vasoconstriction. Adenosine diphosphate is released from activated platelets, and it itself activates platelets. Thrombin works primarily through receptors coupled to Gq proteins causing activation of phospholipase C.
5.11. Nephrotic syndrome is a kidney disease characterized by protein loss in the urine (≥3 g/day) that is accompanied by edema. The loss of protein results in a hypercoagulable state. Excretion of which of the following proteins would explain the thrombophilia seen in the syndrome?
A. Antithrombin III
B. FV