Deck 28: Introduction to Thrombosis and Anticoagulant Therapy

Question 1

Thrombus formation is central to the pathogenesis of all of the following except:

A) Myocardial infarction
B) Ischemic stroke
C) Hepatitis
D) Pulmonary embolism
E) Warfarin-induced skin necrosis

Answer 1

Hepatitis

Question 2

Which function(s) of thrombin cease(s) to occur when thrombin is bound to thrombomodulin?

A) Activation of platelets
B) Activation of factors V, VIII, and XIII
C) Cleavage of fibrinogen
D) All of the above
E) None of the above

Answer 2

All of the above

Question 3

Activated protein C is capable of degrading which activated plasma factors in the presence of its cofactor protein S?

A) Va and VIIa
B) Va and VIIIa
C) IIa and Va
D) IIIa and IVa
E) None of the above

Answer 3

Va and VIIIa

Question 4

Which integral membrane protein present on the surface of endothelial cells serves as a cofactor for thrombin-mediated activation of protein C?

A) Heparin
B) Fibrinogen
C) Plasmin
D) Thrombomodulin
E) None of the above

Question 5

Protein S is a vitamin K-dependent protein that is produced in the __________.

A) Liver
B) Megakaryocytes
C) Endothelial cells
D) All of the above
E) None of the above

Question 6

Naturally occurring substances that limit thrombogenesis include antithrombin, heparin cofactor, and __________.

A) Protein S
B) Protein C
C) Tissue plasminogen activator (t-PA)
D) All of the above
E) None of the above

Question 7

In the activated partial thromboplastin time (APTT)-based screening assay for activated protein C resistance (APC-R), which situation is consistent with a normal result (i.e., the patient does not have APC-R)?

A) Patient clot time with added APC is longer than the patient clot time without added APC.
B) Patient clot time with added APC is shorter than patient clot time without added APC.
C) Patient clot time with added APC is the same as patient clot time without added APC.

Question 8

Protein C function is significantly increased in the presence of:

A) Calcium
B) Protein S
C) Phospholipids
D) A and B
E) B and C

Question 9

Which form of protein S functions as the cofactor for protein C?

A) Free form
B) C4BbP bound
C) C5 convertase bound
D) C3 convertase bound
E) None of the above

Question 10

The quantity of __________ present regulates the rate of formation of activated protein C.

A) XIIIa
B) Va
C) IIIa
D) VIIIa
E) IXa

Question 11

Which anticoagulant protein interacts with heparin resulting in conformational changes and the formation of a complex between itself and factors IIa, Xa, and heparin?

A) Heparin cofactor
B) Antithrombin
C) Protein C
D) Protein S
E) None of the above

Question 12

All of the following influence clot formation except:

A) Characteristics of the vessel wall (especially the endothelium)
B) Turbulence of blood flow
C) Procoagulant and anticoagulant factors in the blood
D) Speed of blood flow
E) Height

Question 13

Thrombin binds to platelets at low concentration to initiate:

A) Shape change
B) Secretion
C) Aggregation
D) All of the above
E) None of the above

Question 14

Which of the following is not a characteristic of thrombin?

A) Cleavage of fibrinogen to form polymerizable fibrin monomers
B) Direct lysis of a clot
C) Converts factor XIII to an active transglutaminase which then cross-links polymerized fibrin, rendering it insoluble
D) Activates factors VIII and V
E) None of the above

Question 15

Physiologic activation of plasminogen by the extrinsic pathway of coagulation is initiated by the stimulation of endothelial cells and subsequent release of _____________________.

A) Tissue thromboplastin
B) t-PA
C) Factor XIIa
D) All of the above
E) None of the above

Question 16

Why is thrombogenesis greatly accelerated by the presence of platelets?

A) The phospholipid platelet membrane offers support for the surface-dependent activation process of coagulation.
B) Thrombin can stimulate the platelet release reaction.
C) Alpha granules contain, among other things, fibrinogen, factor V, and von Willebrand's factor (vWF)
D) All of the above
E) None of the above

Question 17

Activated protein C (APC):

A) Cleaves and inactivates factor Va
B) Cleaves and activates factor Va
C) Is an inhibitor of coagulation
D) A and C
E) B and C

Question 18

Which of the following is/are true regarding inherited thrombophilia?

A) The majority of people who carry heterozygous mutations that have been associated with thrombosis do not manifest a thrombotic disease.
B) Activated protein C resistance, protein C deficiency, protein S deficiency, and antithrombin deficiency are all examples of inherited thrombophilic disorders.
C) Prothrombin nucleotide G20210A mutation, hyperhomocysteinemia, and some forms of dysfibrinogenemia are associated with thrombotic disease.
D) A and B only
E) A, B, and C

Question 19

Physiologic fibrinolysis results in the proteolytic degradation of polymerized __________.

A) Fibrin
B) Plasmin
C) Fibrinogen
D) Thrombin
E) None of the above

Question 20

The central reaction in the fibrinolytic system is the conversion of:

A) Fibrinogen to fibrin
B) Prothrombin to thrombin
C) Plasminogen to plasmin
D) Plasmin to plasminogen
E) None of the above

Question 21

Which of the following statements about hyperhomocysteinemia is/are true?

A) Hyperhomocysteinemia can be inherited or acquired.
B) Deficiencies of folate, vitamin B₆, and vitamin B₁₂ can cause hyperhomocysteinemia.
C) Mutation in the methylene tetrahydrofolate reductase (MTHFR) gene is responsible for some forms of hyperhomocysteinemia.
D) Mild to moderate hyperhomocysteinemia is an independent risk factor for arterial thrombotic diseases such as stroke, myocardial infarction, and peripheral vascular disease.
E) All of the above

Question 22

Which type of protein C deficiency is associated with normal antigenic levels of protein C but low functional activity of protein C?

A) Type I
B) Type II
C) Type III
D) Type IV
E) None of the above

Question 23

Which autosomal dominant thrombotic disorder is associated with an increased risk of warfarin-induced skin necrosis?

A) Protein C deficiency
B) Protein S deficiency
C) Antithrombin deficiency
D) A and B
E) All of the above

Question 24

How is a deficiency of protein S different from other vitamin K-dependent plasma protein deficiencies?

A) Deficiency may involve abnormality of the protein S antigen.
B) The quantitative distribution of protein S between free and bound forms may contribute to functional deficiency.
C) Deficiency may involve abnormally low levels of protein S.
D) All of the above
E) None of the above

Question 25

Which type of assay is preferable for initial detection of protein C deficiency but insufficient for complete characterization of the type of deficiency?

A) Chromogenic assay
B) Clot-based (functional) assay
C) Immunologic assay
D) All of the above
E) None of the above

Question 26

The most frequently encountered inherited thrombotic disorder in Caucasians (people of European descent) is _____________________.

A) Protein C deficiency
B) Protein S deficiency
C) Antithrombin deficiency
D) APC-R
E) None of the above

Question 27

Which statement is true regarding monitoring anticoagulant therapy in patients with a LA?

A) If the patient's PT and international normalized ratio (INR) were within normal range before starting warfarin, then the INR can be used for therapeutic monitoring.
B) Because the APTT is prolonged in people with LA, the PT has to be used to monitor heparin therapy.
C) Because the patient has an LA, if he or she is receiving warfarin therapy, an INR of no more than 2.0 is adequate.
D) If the patient is receiving warfarin, then a chromogenic factor X assay may be needed. If the patient is receiving heparin, then a chromogenic anti-factor Xa (heparin assay) should be used if monitoring is required.
E) The physician should use his or her best judgment regarding dosing of anticoagulants because it is impossible to monitor anticoagulant therapy in people with LA.

Question 28

Clinical manifestations of heterozygous AT-III deficiency (such as thrombotic episodes before age 40) may occur in association with:

A) Surgery
B) Pregnancy
C) Oral contraceptives
D) Trauma
E) All of the above

Question 29

Which of the following is NOT among the standard criteria for aPL syndrome?

A) Arterial thrombosis
B) Venous thrombosis
C) The patient must have systemic lupus erythematosus
D) Certain patterns of pregnancy loss
E) LA or medium to high aCL titer on at least two occasions at least 6 weeks apart

Question 30

The laboratory's algorithm for excluding or diagnosing aPL syndrome may include the following except:

A) Platelet neutralization test
B) Dilute Russell viper venom time
C) Anticardiolipin ELISA
D) t-PA assay
E) APTT mixing study

Question 31

In trying to explain a prolonged APTT, the following should be considered:

A) The possibility that there is heparin in the specimen
B) Hypofibrinogenemia and/or DIC
C) Elevated hematocrit resulting in too much anticoagulant in the tube for the amount of plasma present and/or traumatic venipuncture
D) Specific factor deficiency or an inhibitor
E) All of the above

Question 32

Which type of protein S deficiency contains low levels of free, bound, and total protein S?

A) Type I
B) Type IIa
C) Type IIb
D) All of the above
E) None of the above

Question 33

Which inherited thrombotic disorder may present clinically as neonatal purpura fulminans and with coagulation test results indicative of disseminated intravascular coagulation (DIC)?

A) Homozygous protein C deficiency
B) Activated protein C resistance
C) Heterozygous protein C deficiency
D) Heterozygous protein S deficiency
E) None of the above

Question 34

Which statement about lupus anticoagulants (LAs) and antiphospholipid (aPL) syndrome is true?

A) LAs are best detected by enzyme-linked immunosorbent assay (ELISA) for anticardiolipin (aCL) antibodies.
B) All prolongations of the APTT are caused by LAs.
C) The presence of either a positive ELISA for aCL or an LA is sufficient to label a patient as having aPL syndrome.
D) aPL syndrome is associated only with arterial thrombosis.
E) The term "LA" is inherently confusing, because although LAs prolong coagulation tests, they are known for their association with thrombotic disease, not bleeding.

Question 35

APC-R:

A) Is most often caused by a defect in the factor V gene.
B) Is an extremely common cause of thrombophilia in Asian populations.
C) Can be detected only by genetic testing, not by any coagulation tests.
D) Is only caused by factor V Leiden.
E) Goes away when the patient is pregnant.

Question 36

The APTT-based screening test for APC-R involves:

A) Using reagent plasma with excess factor V
B) Diluting patient plasma with factor V-deficient plasma
C) Making a ratio of two clotting times, one with added APC and one without
D) A and B
E) B and C

Question 37

Which of the following is not one of the criteria recommended by the International Society on Thrombosis and Hemostasis for the diagnosis of LA?

A) Prolongation of at least one phospholipid-dependent clotting assay
B) Prolongation of at least one non-phospholipid-dependent clotting assay
C) Inhibition of clotting is seen in mixing studies.
D) Evidence that the clotting abnormality is phospholipid dependent
E) The diagnosis of LA makes sense based on the patient's clinical presentation and there is no reason to suspect a specific factor inhibitor.

Question 38

A doctor is concerned about the possibility of aPL syndrome in her patient, who had a stroke when she was 23 years old. Which of the following lab results is consistent with aPL syndrome?

A) APTT prolonged but corrects with both an immediate and an incubated mixing study. Dilute Russell viper venom time (dRVVT) within normal range.
B) APTT within normal range, dRVVT within normal range, prothrombin time (PT) within normal range, aCL high titer once but normal 6 weeks later.
C) APTT prolonged, APTT prolonged on mixing study, normal dRVVT, normal dilute prothrombin time (dPT), APTT corrects with addition of excess phospholipid. The same results occur with repeat testing 8 weeks later.
D) Prolonged PT, prolonged APTT, both correct on their respective immediate and incubated mixing studies.
E) Normal APTT and dRVVT, prolonged dPT. dPT still prolonged after addition of excess phospholipid.

Question 39

Which autosomal dominant thrombotic disorder may present with deep venous thrombosis complicated by pulmonary embolism?

A) Activated protein C resistance
B) Antithrombin III (AT-III) deficiency
C) Protein C deficiency
D) Protein S deficiency
E) All of the above

Question 40

As part of a preoperative work up, a patient has a prolonged APTT. Because of this, you are certain that:

A) The patient will bleed excessively during surgery.
B) The patient is receiving heparin.
C) The patient is therapeutically anticoagulated with warfarin.
D) The patient has a LA and is at higher risk for thrombosis than most people while recovering from surgery.
E) None of the above; clinical information and additional testing are needed.

Question 41

Regarding assays used to diagnose HIT:

A) They are so reliable that a negative result absolutely excludes the diagnosis of HIT.
B) Functional assays require the use of patient serum and reagent platelets known to react to HIT sera.
C) Functional assays require the use of patient platelets and reagent sera known to react to HIT platelets.
D) A and B
E) A and C

Question 42

What is the target INR for oral anticoagulant therapy in the treatment of venous thrombosis (except possibly patients with LA)?

A) 2.0-3.0
B) 3.0-4.5
C) 1.0-2.0
D) 3.0-4.0
E) None of the above

Question 43

There is increased risk of thrombosis during pregnancy because of all of the following factors except:

A) Significant decline in plasma levels of free and total protein S
B) Increased production of most procoagulant proteins
C) Absorption of activated protein C from the mother by the fetus
D) The placenta is rich in tissue factor that may produce increased thrombin.
E) Mechanical factors such as venous stasis of the lower extremities caused by the gravid uterus and trauma to pelvic veins during delivery

Question 44

Which laboratory test is used to monitor low-molecular-weight heparin therapy?

A) FDP
B) Anti-Xa chromogenic assay
C) Thrombin time
D) PT
E) APTT

Question 45

Warfarin is used clinically for the prevention of all except:

A) Deep venous thrombosis
B) Pulmonary embolism
C) Bleeding after tooth extraction
D) Acute myocardial infarction
E) Arterial emboli originating from the heart and causing stroke

Question 46

Regarding laboratory testing to detect known causes of thrombosis:

A) Testing is best performed as soon as possible after the thrombosis is diagnosed, but before the patient receives anticoagulants.
B) It is best to test using plasma drawn after the patient has begun anticoagulant therapy, so the effects of the thrombus are masked.
C) Testing during the acute thrombotic event can result in false positives and false negatives
D) Genetically based tests, such as those for MTHFR, prothrombin G20210A, and factor V Leiden, are affected by anticoagulant therapy and the presence of thrombus.
E) It is acceptable to test for inherited causes of thrombophilia during the acute event, but not for acquired causes.

Question 47

Which of the following is true about heparin-induced thrombocytopenia (HIT)?

A) It is heralded by a sudden unexplained decrease in platelets on the first day of heparin therapy.
B) Because HIT patients are thrombocytopenic, they are all at high risk for bleeding complications.
C) It appears to be caused by an immune response related to heparin exposure.
D) If a patient did not develop HIT the first time he or she was ever exposed to heparin, then he or she has no risk of developing HIT on subsequent exposures to heparin.
E) All of the above

Question 48

All of the following are true about low-molecular-weight heparin therapy except:

A) It can be easier for both the physician and patient and therapeutic monitoring is not always required.
B) It can be given subcutaneously, and patients can administer it to themselves.
C) It is much less expensive than unfractionated heparin therapy and never causes HIT.
D) If monitoring is required, it cannot be monitored via the APTT.
E) It requires monitoring by a target concentration strategy.

Question 49

Advantages of the APTT over the anti-factor Xa chromogenic assay for monitoring intravenous heparin therapy include all of the following except:

A) The technique is quick, familiar, and easy for laboratorians.
B) It is inexpensive.
C) It correlates in a linear fashion, across many patient samples, with the actual concentration (U/mL) of heparin in the patient's plasma.
D) It reflects the anticoagulant activity of the heparin in the patient's plasma.

Question 50

The PT evaluates the __________ pathway of coagulation.

A) Intrinsic
B) Extrinsic
C) Common
D) All of the above
E) None of the above

Question 51

Which of the following clinical features is not significant when evaluating a patient with suspected thrombophilia?

A) History of recurrent fetal loss
B) Age at which thrombotic event occurred
C) History of myocardial infection (MI)
D) Chemotherapy
E) Height

Question 52

Which laboratory test is used to monitor oral anticoagulant (warfarin) therapy?

A) APTT
B) PT
C) TT
D) Fibrinogen
E) None of the above

Question 53

Unfractionated heparin (UH) therapy:

A) Uses the same dose of heparin for all adult patients
B) Cannot be given by any route except intravenously
C) Requires monitoring approximately every 6 hours after dosing until the therapeutic interval has been achieved, after which daily monitoring is adequate
D) Has a wide therapeutic interval so there is little risk of bleeding or thrombosis if the dose is too high or too low
E) Can be monitored only via the APTT

Question 54

What is the usual treatment for patients presenting with deep venous thrombosis?

A) Administration of oral anticoagulant (warfarin) followed by heparin therapy
B) Administration of lupus anticoagulants followed by heparin therapy
C) Administration of intravenous heparin, followed by several months of oral anticoagulant (warfarin) therapy
D) All of the above
E) None of the above

Question 55

Why would a patient given only warfarin (oral vitamin K antagonist) therapy initially be at risk for thrombosis rather than bleeding for the first 3 or 4 days of therapy?

A) Factor VIII levels increase initially.
B) Factor VII has a short half-life.
C) Warfarin is absorbed by the intestine only after several days.
D) Protein C and S have short half-lives and decrease sooner than factors II, IX, and X do after beginning therapy.
E) None of the above

Question 56

The most popular laboratory test used in monitoring UH therapy is the __________.

A) PT
B) APTT
C) Thrombin time (TT)
D) Fibrinogen degradation product (FDP)
E) Anti-Xa assay

Question 57

What is the target of the anticoagulant mechanism of heparin?

A) Thrombin inhibition
B) Thrombin synthesis
C) Plasmin inhibition
D) Plasmin synthesis
E) None of the above

Question 58

A reasonable panel of laboratory tests to screen for the more common causes of thrombophilia in a patient with recurrent thrombosis could include any of the following except:

A) Protein C, protein S, and antithrombin functional (activity level) assays
B) Screening test for APC resistance
C) Two screening tests for lupus anticoagulant, for example, dRVVT and APTT
D) vWF assay
E) aCL antibody ELISA

Question 59

Which functional assay result is positive for HIT? (high concentration of heparin = 100 U/mL, low concentration = 0.1 U/mL)

A) Platelet aggregation is absent in the saline control and with the high concentration of heparin, but does occur with the low concentration of heparin.
B) Platelet aggregation occurs in the saline control and the high and the low concentrations of heparin.
C) Platelet aggregation is absent in the saline control but does occur in the high and low concentrations of heparin.
D) Platelet aggregation is absent in the saline control and the low concentration of heparin, but does occur in the high concentration of heparin.
E) A and D

Question 60

Which of the following is/are true regarding HIT?

A) If a patient is suspected of having HIT, it is safe for the doctor to wait until he or she has the results of a HIT assay before stopping all of the patient's exposure to heparin.
B) Patients with HIT should not be given any other anticoagulants since they are thrombocytopenic.
C) All patients with antibodies to heparin-platelet factor 4 (PF4) complexes have HIT.
D) The most important step in preventing or limiting thrombosis in patients with HIT is stopping all exposure to heparin.
E) Only unfractionated heparin is associated with HIT.

Question 61

The INR value for plasma depends on the international sensitivity index (ISI) of the __________ used.

A) Controls
B) Thromboplastin reagents
C) Calibrators
D) Thromboplastin reagent and instrument combination
E) Instruments

Question 62

Which of the following is/are affected by the vitamin K antagonist warfarin, which is used for oral anticoagulant therapy?

A) Factor XII
B) Protein C
C) Protein S
D) A and B
E) B and C

Question 63

Studies that should be performed before administering fibrinolytic therapy include:

A) PT
B) APTT
C) Complete blood count (CBC) with platelet count
D) Fibrinogen assay
E) All of the above

Question 64

The INR is calculated by:

A) Patient value in seconds divided by control value in seconds
B) Patient value in seconds divided by the mean of the reference range in seconds
C) Control value in seconds divided by patient value in seconds
D) Patient value in minutes divided by mean of the reference range in minutes, raised to the ISI
E) Patient value in seconds divided by mean of the reference range in seconds, raised to the ISI

Question 65

Streptokinase and urokinase are __________ plasminogen activators.

A) Fibrin specific
B) Non-fibrin-specific
C) Thrombin nonspecific
D) Thrombin specific
E) None of the above

Question 66

The primary aim of thrombolytic therapy is to activate __________.

A) Plasminogen into plasmin
B) Prothrombin into thrombin
C) Fibrinogen to fibrin
D) Factor VIII into hemophilia factor
E) Factor V into activated protein C