Question 1

You are examining a 9-year-old boy who is brought in by his parents for unexplained bleeding problems from birth. He experiences easy bruising, bleeding from the gums, and frequent epitaxis. His parents were first cousins, but they showed no bleeding problems. Hemostatic analysis of the boy's blood showed dramatically prolonged plasma prothrombin clotting time. Given the limited data in this case, a defect/deficiency in which of the following is most likely in this patient?

A) factor VIII
B) factor XI
C) factor XIII
D) fibrinogen
E) high-molecular-weight kininogen, HMWK

fibrinogen

Accepted Answer

The dramatically prolonged plasma prothrombin clotting time suggests a deficiency in fibrinogen, which is essential for clot formation.  Defects associated with factors of the pathways of blood coagulation can also be assessed with specific assays. The prothrombin time (PT) is an assay designed to screen for defects in fibrinogen, prothrombin, and factors V, VII, and X and thus measures activities of the extrinsic pathway of coagulation. When any of these factors is deficient then the PT is prolonged. A normal PT is 11.0 to 12.5 seconds. A PT greater than 20 seconds is indicative of coagulation deficit.

Question 2

You are tending to a 5-year-old boy with a suspected case of congenital deficiency in coagulation. He had bled from the umbilical and circumcision sites during his first week of life. He experiences frequent ecchymoses and hematomas within 12 to 24 hoursafter trauma. His parents are first cousins, but there is no family history of bleeding disorders. A bleeding disorder workup was initiated and the results indicated that PT, PTT, fibrinogen, platelet aggregation studies, and von Willebrand factor were normal. The patient's plasma was incubated with thrombin and Ca²⁺ and the resultant clot dissolved in the presence of urea. Given these findings, which of the following is most likely defective/deficient in this patient?

A) factor VII
B) factor VIII
C) factor XIII
D) tissue factor pathway inhibitor, TFPI
E) prothrombin

Accepted Answer

Factor XIII deficiency is characterized by normal PT, PTT, fibrinogen, and platelet function tests, but the clot dissolves in the presence of urea due to defective cross-linking of fibrin.

Question 3

A 66-year-old Caucasian man of Italian decent was admitted to the hospital for a grade III draining ulceration and underlying osteomyelitis of the left fifth metatarsal head. Past medical history was significant for Type 1 diabetes. Past surgical history was significant for a resection of an infected tibial sesamoid of the right foot. Prior to treatment of the ulceration routine clotting tests were performed and showed significantly prolonged activated partial thromboplastin (aPTT) time (69.5 second; normal 30-40 second), while prothrombin time (PT) was normal. Given these findings, which of the following factors of coagulation is most likely to be defective in this patient?

A) factor VII
B) factor XI
C) prekallikrein
D) tissue factor
E) tissue factor pathway inhibitor, TFPI

factor XI

Accepted Answer

The prolonged aPTT with normal PT suggests a defect in the intrinsic pathway of coagulation, which involves factors VIII, IX, XI, and XII. Factor XI deficiency is a common cause of prolonged aPTT with normal PT. The partial thromboplastin time (PTT) is used to assay for defects in the intrinsic pathway of coagulation. The PTT assay has been modified by the addition of activators that shorten the normal clotting time and this form of the assay is referred to as the activated partial thromboplastin time (aPTT). The PTT is normally prescribed in patients with unexplained bleeding or clotting. The assay will evaluate the function of fibrinogen, prothrombin, and factors V, VIII, IX, X, XI, and XII. A defect in any of these factors will result in a prolonged PTT (or aPTT). A normal PTT is 60 to 70 seconds, whereas for the aPTT the normal range is 30 to 40 seconds. The PTT is a standard assay used to assess the efficacy of heparin anticoagulant therapy. Prolonged PTTs are associated with acquired or congenital bleeding disorders associated with coagulation factor deficiency, vitamin K deficiency, liver disease, DIC, von Willebrand disease, leukemia, hemophilia, and heparin administration

Question 4

You are examining the processes of blood coagulation utilizing in vitro assays involving the addition of potential inhibitory compounds. In your control assay the rate of fibrin clot formation, following addition of whole blood, takes 16 seconds. The addition of your compound results in fibrin clot formation in 3 seconds. Given the observed results, which of the following proteins is most likely targeted for inhibition by the test compound?

A) factor V
B) factor XIII
C) fibrinogen
D) protein C
E) thrombin

Accepted Answer

Protein C (PC) is a trypsin-like serine protease that serves as a major regulator of the coagulation process. Thrombin cleavage of PC removes the activation peptide generating aPC. When activated through cleavage by thrombin, aPC cleaves both factor Va and factor VIIIa into inactive enzymes. This results in the termination of the role of VIIIa as the scaffold for the formation of the tenase complex and Va as a cofactor in the conversion of prothrombin to thrombin in the prothrombinase complex. The net effect, at the level of coagulation, of the activation of PC is termination of further increases in thrombin production and a halt to further fibrin clot formation. A lack of aPC activity would be apparent if fibrin clotting was accelerated due to lack of inhibition of factors Va and VIIIa

Question 5

Although the role of aPC in the termination of coagulation is extremely important, it also serves many additional functions that alter the inflammator processes occurring in the vasculature. The antiinflammatory functions of aPC are, in part, due to the activation of which of the following?

A) antithrombin III
B) protease activated receptor-1, PAR-1
C) thrombin
D) thrombomodulin
E) tissue plasminogen activator, tPA

Accepted Answer

Activated protein C (aPC) exerts its anti-inflammatory effects partly through the activation of protease activated receptor-1 (PAR-1). Activated PC binds to the endothelial protein C receptor (EPCR) and leads to the activation of PAR-1 which elicits cytoprotective and anti-inflammatory responses within endothelial cells. The cytoprotective effects elicited via aPC activation of PAR-1 include protection of the endothelial cell barrier and induction of antiapoptotic signaling pathways as well as expression of eNOS. Additional endothelial responses to aPC activation of PAR-1 occur via inhibition of the expression and actions of the potent pro-inflammatory transcription factor NFκB. The suppression of NFκB action results in downregulation of the synthesis of endothelial pro-inflammatory cytokines such as IL-6 and IL-8, the chemokine MCP-1 (monocyte chemoattractant protein-1), and the cell adhesion molecule ICAM-1 (intercellular adhesion molecule-1).

Question 6

Although the role of aPC in the termination of coagulation is extremely important, it also serves many additional functions that alter the inflammator processes occurring in the vasculature. The antiinflammatory functions of aPC are, in part, due to the activation of which of the following?

A) antithrombin III
B) protease activated receptor-1, PAR-1
C) thrombin
D) thrombomodulin
E) tissue plasminogen activator, tPA

Accepted Answer

von Willebrand disease (vWD) results from defects in von Willebrand factor (vWF). The disorder is characterized by bleeding from mucocutaneous sites (typical skin and mucous membranes) rather than from deep tissues and joints. vWF is involved in 2 important reactions of blood coagulation. The first is the interaction of vWF with specific receptors on the surface of platelets and the subendothelial connective tissue. This interaction allows platelets to adhere to areas of vascular injury. The second role of vWF is to bind to and stabilize factor VIII allowing factor VIII to survive in the blood. As a consequence of these roles for vWF, deficiencies result in defective platelet adhesion and to secondary deficiencies in factor VIII. Since factor VIII deficiency results in hemophilia A, vWF deficiencies can manifest with clinical symptoms that appear to be hemophilia A.

Question 7

You are treating a patient manifesting with a hypercoagulopathy evident by frequent deep vein thrombosis (DVTs) and pulmonary emboli. This patient most likely suffers from which of the following disorders?

A) antithrombin III deficiency
B) Bernard-Soulier syndrome
C) factor V Leiden
D) hemophilia A
E) von Willebrand disease

Accepted Answer

Factor V Leiden is a genetic disorder that increases the risk of blood clots. It is the most common inherited cause of hypercoagulopathy.  The hypercoagulopathy (thrombophilia) referred to as factor V Leiden is caused by a mutation in the factor V gene resulting in a protein that is not effectively degraded by aPC. Factor V Leiden is the most common inherited thrombophilia in Caucasian populations of European descent. Overall, 5% of the world population harbors the factor V Leiden mutation. The symptoms of factor V Leiden are deep vein thrombosis (DVT) and pulmonary embolism, both of which can be fatal. In fact, it is estimated that in as many as 30% of patients who experience DVT and/or pulmonary embolisms are carriers of the factor V Leiden mutation.

Question 8

A deficiency in which of the following blood coagulation factors could most likely be suspected in a patient exhibiting a prolonged aPTT time?&#10;A) factor VII&#10;B) factor XIII&#10;C) factor IX&#10;D) protein C&#10;E) tissue factor pathway inhibitor, TFPI

Accepted Answer

Factor IX deficiency, also known as Hemophilia B, leads to a prolonged activated partial thromboplastin time (aPTT) because it is part of the intrinsic pathway of the coagulation cascade.  The partial thromboplastin time (PTT) is used to assay for defects in the intrinsic pathway of coagulation. The PTT assay has been modified by the addition of activators that shorten the normal clotting time and this form of the assay is referred to as the activated partial thromboplastin time (aPTT). The assay will evaluate the function of fibrinogen, prothrombin, and factors V, VIII, IX, X, XI, and XII. A defect in any of these factors will result in a prolonged PTT (or aPTT).

Question 9

The mother of a 4-year-old boy brings her son to his pediatrician for a repeated episodes of easy bruising and epistaxis. Blood work reveals a prolonged PTT, a normal PT, and a prolonged bleeding time. Platelet count is 285,000/uL. Based on these laboratory findings, what is the most likely diagnosis?

A) disseminated intravascular coagulation
B) hemophilia B
C) primary fibrinolysis
D) vitamin K deficiency
E) von Willebrand disease

Accepted Answer

The laboratory findings of prolonged PTT, normal PT, prolonged bleeding time, and normal platelet count are consistent with von Willebrand disease, which affects both platelet function and the intrinsic coagulation pathway.  Partial thromboplastin time (PTT), prothrombin time (PT), bleeding time, and platelet count are key laboratory tests used to differentiate between bleeding disorders. PTT measures plasma clotting time to assess the integrity of the intrinsic coagulation pathway (factors XII, XI, IX, VIII, X, V; prothrombin; and fibrinogen). PT measures plasma clotting time to assess the integrity of the extrinsic pathway (factors VII, V, X; prothrombin; and fibrinogen). Bleeding time measures the time needed for a standard skin puncture to stop bleeding and assesses platelet ability to form a hemostatic plug. von Willebrand disease results from deficiencies in both factor VIII and in von Willebrand factor (vWF), which combine to form a circulating complex. Synthesized by endothelial cells, vWF is important in the facilitation of platelet adhesion to subendothelial collagen. As a constituent in the factor VIII-vWF circulating complex, it serves to stabilize factor VIII and significantly increase its half-life; thus, a deficiency in vWF will cause a secondary decrease in factor VIII levels. von Willebrand disease demonstrates autosomal dominant inheritance and is believed to be one of the most common inherited bleeding disorders. Patients show bleeding after minor trauma, with the most common sites including skin (easy bruising) and mucous membranes (epistaxis). Coagulation tests reveal a prolonged PTT, a normal PT, and a prolonged bleeding time with normal platelet count.

Question 10

A 47-year-old fireman is admitted to the emergency room for extensive burns received while battling a fire. A few hours after admission, he develops pregangrenous changes in multiple digits of hands, his left foot, and his nose. A short time later, he experiences bleeding from his mucous membranes and IV site, as well as the development of multiple petechiae. Which of the following is the major initiating mechanism of this clinical scenario?

A) antithrombin III deficiency
B) multiple air emboli
C) release of thromboplastin
D) supervening infection
E) tissue hypoxemia

Accepted Answer

The clinical scenario describes disseminated intravascular coagulation (DIC), which is often initiated by the release of thromboplastin (tissue factor) into the circulation, leading to widespread clotting and subsequent bleeding. This patient is exhibiting the typical findings of disseminated intravascular coagulation. This is initiated by the release of tissue factor or thromboplastic substance (either exogenous, eg, amniotic fluid, or endogenous, eg, tissue damage as in this case) into the circulation. This activated the coagulation cascade, resulting in the formation of multiple thrombi that can block the microcirculation and produce ischemia and necrosis in vulnerable tissues. As thrombus formation continues, platelets and clotting factors can be exhausted, allowing hemorrhage to occur. The ischemic changes and hemorrhage are both apparent in this patient. Given the history and timing of this case, trauma leading to the release of tissue factor is more likely. However, endothelial injury may also initiate disseminated intravascular coagulation (DIC) by the release of tissue factor.

Question 11

A 6-year-old boy has a long history of a hereditary bleeding disorder characterized by spontaneous nontraumatic hemorrhages into joint spaces, skeletal muscle, and mucous membranes. Laboratory studies reveal a normal prothrombin time, elevated partial thromboplastin time, very low factor VIII, normal factor X, normal factor XI, and normal platelet aggregation studies with ristocetin. Which of the following is the most likely diagnosis?

A) Christmas disease
B) hemophilia A
C) hemophilia B
D) Rosenthal syndrome
E) von Willebrand disease

Accepted Answer

The answer of A 6-year-old boy has a long history...

Question 12

A 26-year-old woman complains of the acute onset of anuria, purpura, and mental confusion. Her peripheral blood film displays marked thrombocytopenia and abundant schistocytes. Laboratory studies reveal elevations of bilirubin, creatinine, and lactose dehydrogenase. A skin biopsy shows numerous intravascular thrombi within the dermal microvasculature. What is the most likely diagnosis?

A) acute idiopathic thrombocytopenia purpura
B) Bernard-Soulier syndrome
C) Glanzmann thrombasthenia
D) May-Hegglin anomaly
E) thrombotic thrombocytopenic purpura

Accepted Answer

The answer of A 26-year-old woman complains of the acute...

Question 13

You are tending to a patient with a high tendency to bleeding. He bruises easily and has bleeding from his gums. Analysis of coagulation factors in his blood shows normal levels of factor V but low levels of factor VIII. Injection of factor VIII provides only minimal benefit and you find that the injected protein is rapidly degraded. Using a platelet aggregation test you find that combination of your patients serum with normal platelets results in only 20% of the platelet aggregation seen with both samples from a normal individual. Based on these findings you determine that your patient is deficient in which of the following factors of coagulation?

A) factor X
B) factor XII
C) fibrinogen
D) thrombin
E) von Willebrand factor

Accepted Answer

The answer of You are tending to a patient with...

Question 14

Which of the following represents a critical role of thrombin in the promotion of coagulation?&#10;A) activation of protein C&#10;B) activation of thrombin-activatable fibrinolysis inhibitor, TAFI&#10;C) cleavage, leading to activation, of PAR-1&#10;D) cleavage of factor X to Xa&#10;E) cleavage of factor XIII to XIIIa

Accepted Answer

The answer of Which of the following represents a critical...

Question 15

Which of the following is the final step in the coagulation cascade, leading to clot formation?&#10;A) conversion of thrombin to prothrombin&#10;B) plasmin catalyzed degradation of fibrin fibers&#10;C) polymerization of prothrombin&#10;D) release of tissue factor&#10;E) thrombin catalyzed conversion of fibrinogen to fibrin

Accepted Answer

The answer of Which of the following is the final...

Question 16

ReoPro (abciximab) is a member of a class of anticoagulant drugs that function by inhibiting the role of platelets in hemostasis. Which of the following protein complexes is the target of ReoPro action?

A) GPIa-GPIIa
B) GPIb-GPIX-GPV
C) GPIIb-GPIIIa
D) prothrombinase complex
E) tenase complex

Accepted Answer

The answer of ReoPro (abciximab) is a member of a...

Question 17

Accumulating evidence indicates that the nonsteroidal anti-inflammatory (NSAID) aspirin is effective in the control of numerous chronic conditions such as atherosclerosis. The principal cardiovascular benefit from aspirin is due to its ability to reduce the incidence and severity of thrombotic episodes. The anticoagulant effect of aspirin occurs through its ability to inhibit which of the following activities?

A) cyclooxygenase
B) fibrin cross-linking by factor XIIIa
C) phospholipase A₂
D) thrombin binding to activated platelets
E) von Willebrand factor

Accepted Answer

The answer of Accumulating evidence indicates that the nonsteroidal anti-inflammatory...

Question 18

Which of the following proteins of the coagulation cascade forms an active complex with tissue factor to initiate the extrinsic clotting cascade?&#10;A) factor VII&#10;B) factor VIII&#10;C) factor IX&#10;D) fibrinogen&#10;E) protein S

Accepted Answer

The answer of Which of the following proteins of the...

Question 19

Hemophilia B results from a deficiency in which of the following proteins?&#10;A) factor VIII&#10;B) factor IX&#10;C) fibrinogen&#10;D) thrombin&#10;E) von Willebrand factor

Accepted Answer

The answer of Hemophilia B results from a deficiency in...

Question 20

Hemophilia A results from a deficiency in which of the following proteins?&#10;A) factor VIII&#10;B) factor IX&#10;C) fibrinogen&#10;D) thrombin&#10;E) von Willebrand factor

Accepted Answer

The answer of Hemophilia A results from a deficiency in...

Question 21

Which of the following factors of blood coagulation is the major inhibitor of the extrinsic clotting cascade? A) antithrombin III B) high-molecular-weight kininogen (HMWK) C) lipoprotein-associated coagulation factor (LACI) D) α₂-macroglobulin E) protein S

Accepted Answer

The answer of Which of the following factors of blood...

Question 22

Patients who exhibit a prolonged mucocutaneous bleeding time with a normal coagulation time, clot retraction, and platelet count and have reduced levels of the coagulation factor VIII have a deficiency in which protein involved in hemostasis?

A) factor IX
B) fibrinogen
C) thrombin
D) tissue factor
E) von Willebrand factor

Accepted Answer

The answer of Patients who exhibit a prolonged mucocutaneous bleeding...

Question 23

Presentation of the platelet membrane protein complex, GPIIb-GPIIIa, which binds with von Willebrand factor, is necessary for which of the following?&#10;A) activation of PKC leading to phosphorylation of myosin light chain and platelet morphology changes&#10;B) cleavage and activation of high-molecularweight kininogen&#10;C) inducing platelet cross-linking&#10;D) release of thrombin from platelet granules&#10;E) stimulation of endothelial and smooth muscle cell interaction resulting in vasoconstriction

Accepted Answer

The answer of Presentation of the platelet membrane protein complex,...

Question 24

Which of the following is the final step in the coagulation cascade, leading to clot formation?&#10;A) conversion of thrombin to prothrombin&#10;B) plasmin-catalyzed degradation of fibrin fibers&#10;C) polymerization of prothrombin&#10;D) release of tissue factor&#10;E) thrombin-catalyzed conversion of fibrinogen to fibrin

Accepted Answer

The answer of Which of the following is the final...

Question 25

A deficiency in which of the following factors of hemostasis, whose symptoms generally do not appear prior to age 15, would manifest with recurrent deep vein thrombosis, pulmonary embolism and cerebral vein thrombosis?

A) antithrombin III
B) factor VIII
C) fibrinogen
D) protein C
E) von Willebrand factor

Accepted Answer

The answer of A deficiency in which of the following...

Question 26

Which of the following factors is present only in the intrinsic pathway of blood coagulation?&#10;A) factor I (fibrinogen)&#10;B) factor II (prothrombin)&#10;C) factor V&#10;D) factor VIII&#10;E) factor X

Accepted Answer

The answer of Which of the following factors is present...

Question 27

Heparin is a rapidly acting, potent anticoagulant that has many important clinical uses. Which of the following is an action of heparin?&#10;A) activates antithrombin III&#10;B) activates prothrombin&#10;C) decreases prothrombin time&#10;D) inhibits calcium action&#10;E) promotes vitamin K activity

Accepted Answer

The answer of Heparin is a rapidly acting, potent anticoagulant...

Question 28

Platelet aggregation requires the interaction of fibrinogen with a receptor on activated platelets. Which of the following is the most likely composition of this receptor?&#10;A) factor XII (Hageman factor)&#10;B) GPIb-GPIX-GPV&#10;C) GPIIb-GPIIIa&#10;D) thrombin&#10;E) von Willebrand factor

Accepted Answer

The answer of Platelet aggregation requires the interaction of fibrinogen...

Question 29

Activated platelets stimulate vasoconstriction through the production of which of the following? A) leukotriene C₄ B) platelet-activating factor (PAF) C) prostacyclin (PGI₂) D) prostaglandin E₂ (PGE₂) E) thromboxane A₂ (TXA₂)

Accepted Answer

The answer of Activated platelets stimulate vasoconstriction through the production...

Deck 51: Hemostasis: Blood Coagulation