Bank Hemostasis (Coagulation) - All Questions

Chemotherapy results in which condition? a. Acquired thrombocytopenia b. Inherited thrombocytopenia c. Acquired splenic sequestration d. Inherited thrombocythemia

*a. Acquired thrombocytopenia Wide arrays of chemotherapeutic agents used for the treatment of hematologic and nonhematologic malignancies suppress bone marrow megakaryocyte production and the production of other hematopoietic cells. Drug-induced thrombocytopenia is often the dose-limiting factor for many chemotherapeutic agents.

What substance is known to inactivate arachidonic acid, causing impairment of platelet function? a. Aspirin b. Calcium c. Tylenol d. Vitamin K

*a. Aspirin Aspirin inactivates the enzyme cyclooxygenase, blocking thromboxane A2 production and causing impairment of platelet function (called aspirin effect). Thromboxane A2 causes Ca+2 to be released and promotes platelet aggregation and vasoconstriction.

What procedure is used to quantitate a factor VIII inhibitor? a. Bethesda assay b. Reptilase time c. Factor VIII concentration d. VWF assay

*a. Bethesda assay The Bethesda assay is used to quantitate a factor VIII inhibitor.

A 28-year-old woman sees her family physician complaining of easy bruising and menorrhagia. She has a platelet count of 60 × 10^9/L. All other hematology and routine coagulation tests are normal. She has a platelet-associated immunoglobulin G (IgG) autoantibody in her serum. Which is most likely? a. Chronic immune thrombocytopenic purpura b. Thrombotic thrombocytopenic purpura c. Acute immune thrombocytopenic purpura d. Hemolytic uremic syndrome

*a. Chronic immune thrombocytopenic purpura Chronic immune thrombocytopenic purpura is most often seen in women between the ages of 20 and 50 years of age. Patients most often complain of easy bruising, recurrent epistaxis, and menorrhagia. Platelet destruction in chronic immune thrombocytopenic purpura is the result of an IgG autoantibody, with various membrane glycoproteins being the most frequent targets.

What are the primary procoagulant roles of the blood vessel? a. Constrict and provide collagen and other compounds to activate clotting. b. Prevent the blood from escaping and promote fibrinolysis. c. Secrete platelet growth factors and manufacture calcium. d. Constrict and synthesize most plasma coagulation factors.

*a. Constrict and provide collagen and other compounds to activate clotting. Blood vessels play a role in constriction of the vessel once it has been damaged. Collagen is located in the subendothelial tissue and is exposed once a vessel is damaged. They also provide other compounds, such as von Willebrand factor (VWF), which is necessary for platelet adhesion.

Which protein is the best test to distinguish moderate to severe liver disease from vitamin K deficiency? a. Factor V concentration b. Factor VII concentration c. Factor VIII concentration d. Factor IX concentration

*a. Factor V concentration Factor V is not vitamin K dependent, but it is produced in the liver, so it is decreased in moderate to severe liver disease. Factors VII and IX are both vitamin K dependent, so they are decreased in both liver disease and vitamin K deficiency. Factor VIII is not decreased in either liver disease or vitamin K deficiency; in fact, because it is an acute phase reactant, it may actually be elevated in mild to moderate liver disease.

Which is decreased in DIC? a. Fibrinogen b. PT c. PTT d. Fibrin degradation products

*a. Fibrinogen Fibrinogen is decreased in DIC. The PT and PTT are both increased (prolonged), whereas fibrin degradation products are increased.

Where are most of the plasma procoagulant proteins produced? a. Liver b. Megakaryocytes c. Endothelial cells d. Spleen

*a. Liver Most of the procoagulant proteins found in plasma are synthesized in the liver.

What kind of antibody causes neonatal alloimmune thrombocytopenia? a. Maternal antibody against a fetal platelet antigen inherited from the father b. Fetal antibody directed against maternal platelet antigen c. Fetal antibody against a fetal platelet antigen inherited from the father d. Maternal autoantibody against a mother's platelet antigen

*a. Maternal antibody against a fetal platelet antigen inherited from the father Neonatal alloimmune thrombocytopenia develops when a mother develops an alloantibody against a platelet antigen inherited by the fetus from the father. These antibodies cross the placenta, bind to the antigen-bearing fetal platelets, and cause their premature destruction.

What are the primary roles of VWF? a. Mediates platelet adhesion and carrier molecule for factor VIII. b. Mediates platelet aggregation and carrier molecule for factor IX. c. Inhibits excess coagulation and activates protein C. d. Activates plasmin and enhances vitamin K factors.

*a. Mediates platelet adhesion and carrier molecule for factor VIII. VWF is required for normal platelet adhesion; it is also the carrier protein for factor VIII, protecting it from proteolysis and thus prolonging the in vivo half-life from just a few minutes (in the absence of VWF) to 8 to 12 hours.

Which is true regarding testing for the diagnosis of vascular disorders? a. Most do not have abnormal clinical laboratory tests. b. The platelet count and aggregometry are useful. c. The prothrombin time (PT) and partial thromboplastin time (PTT) are most useful. d. Evaluation of von Willebrand factor (VWF) is useful.

*a. Most do not have abnormal clinical laboratory tests. Clinical laboratory tests are not available for evaluation and diagnosis of vascular disorders. Ruling out other sources of bleeding disorders often makes the diagnosis. The usual clinical signs are easy bruising and spontaneous bleeding, especially from mucosal surfaces. In that respect they are similar to platelet dysfunction disorders.

Which test is increased in a patient with severe hemophilia A? a. PTT b. Thrombin time (TT) c. PT d. Factor VIII assay

*a. PTT The PTT is increased (prolonged) in patients with severe hemophilia A because of a significant decrease in factor VIII. The PT and TT are both normal.

What substance digests the fibrin clot after healing? a. Plasmin b. Activated protein C c. TPA d. alpha2-antiplasmin

*a. Plasmin Plasmin is the active form of the zymogen plasminogen. Plasmin systematically digests (i.e., degrades, lyses) the fibrin clot after healing.

What is the best test to distinguish hemophilia A from B or C? a. Specific factor assays b. PTT c. TT d. Bleeding time

*a. Specific factor assays Hemophilia A (factor VIII deficiency), hemophilia B (factor IX deficiency), and hemophilia C (factor XI deficiency) are differentiated from one another using specific factor assays.

The qualitative platelet disorders and vascular disorders typically exhibit what type of symptoms? a. Superficial bleeding b. Deep tissue bleeding c. Hemarthrosis d. Thrombosis

*a. Superficial bleeding Superficial bleeding, including petechiae, epistaxis (nose bleeds), and gingival (gum) bleeding, is characteristic of qualitative bleeding disorders.

Which is the most important protease of the coagulation pathway because of its role in so many different catalytic functions? a. Thrombin b. Factor XIa c. Plasmin d. Factor VIIa

*a. Thrombin Thrombin is considered the most important protease of the coagulation pathway because of its multiple functions. These include splitting fibrinogen to form fibrin monomers; activating the cofactors V and VIII; activating factor XIII; binding to thrombomodulin to activate protein C; and aggregating platelets, to name just a few.

Which is the most common form of von Willebrand disease (VWD)? a. Type 1 b. Type 2A c. Type 3 d. Acquired

*a. Type 1 Type 1 VWD is seen in more than 70% of patients with VWD.

On what does factor VIII depend for stability? a. VWF b. Platelets c. Thrombin d. Protein S

*a. VWF Factor VIII circulates bound to VWF. Free factor VIII is unstable in plasma, so much so that it cannot even be detected.

What vitamin is essential for normal synthesis of prothrombin group proteins, thus enabling them to bind Ca2+? a. Vitamin K b. Vitamin B12 c. Vitamin C d. Vitamin D

*a. Vitamin K Vitamin K is necessary for carboxylation of glutamic acid residues on the precursor prothrombin group proteins. This carboxylation enables these proteins to bind Ca2+.

All can mask a deficiency of VWF and thus of type 1 VWD except: a. fibrinogen levels. b. pregnancy. c. acute stress. d. type ABO blood group.

*a. fibrinogen levels. The concentration of VWF is low in VWD, type 1. VWF is an acute-phase reactant and is thus elevated in acute stress. Higher estrogen levels during pregnancy also elevate VWF. Individuals with type ABO blood type have higher levels of VWF. All these can thus mask VWD.

Absence of D dimers is useful for ruling out: a. thromboembolism. b. von Willebrand disease (vWD). c. protein C deficiency. d. factor VII deficiency.

*a. thromboembolism. The D dimer is a specific marker for thrombosis; when the assay is negative, it is useful for ruling out thromboembolism.

What protein does heparin work with to inhibit coagulation? a. Protein S b. Antithrombin c. Vitamin K d. Factor VII

*b. Antithrombin Heparin binds to antithrombin, thus bringing thrombin in close proximity to antithrombin. It also changes the configuration of antithrombin so that it can effectively bind thrombin. The thrombinantithrombin complex renders thrombin inactive; the complex is taken to the liver and cleared.

Which is true regarding the plasma coagulation zymogens? a. Circulate normally in their active form. b. Are serine proteases that form complexes to activate other zymogens to ultimately generate thrombin. c. Activation normally occurs throughout the body when vascular injury occurs. d. Are cofactors that induce peptide bonding to make larger active molecules.

*b. Are serine proteases that form complexes to activate other zymogens to ultimately generate thrombin. Zymogens are the inactive forms of the procoagulant enzymes. They are serine proteases that form complexes to activate other zymogens. The end result of this process is to generate thrombin.

Which is an autosomal recessive disorder in which the GP Ib/IXI/V complex is missing from the platelet surface? a. von Willebrand disorder (VWD) b. Bernard-Soulier syndrome c. Glanzmann thrombasthenia d. Dense granule deficiency

*b. Bernard-Soulier syndrome Bernard-Soulier syndrome is inherited as an autosomal recessive disorder in which the GP Ib/IX/V complex is missing from the platelet surface or exhibits abnormal function. Inability to bind to VWF accounts for the inability of platelets to adhere to exposed subendothelium and the resultant bleeding characteristic of this disorder.

Which is part of primary hemostasis? a. Fibrinolysis b. Blood vessels c. Intrinsic system d. Inhibitors

*b. Blood vessels Blood vessels and platelets are important in primary hemostasis, where they play roles in forming the primary hemostatic plug.

Platelet count and function studies are performed on a patient with a history of easy bruising, and the following results are obtained: Platelet count = 295 × 10^9/L Platelet function assay = Prolonged Platelet aggregation with epinephrine = Primary but no secondary wave Platelet aggregation with low-dose ADP = Primary but no secondary wave Platelet aggregation with ristocetin = Normal What is the most likely diagnosis for this patient? a. Bernard-Soulier disease b. Dense granule deficiency c. Glanzmann thrombasthenia d. Gray platelet syndrome

*b. Dense granule deficiency The platelet count on this patient is normal; however, the platelet function assay is abnormal, which suggests platelet dysfunction. Of the disorders listed, only dense granule deficiency has the platelet aggregation results that are listed. Patients with Bernard-Soulier disease have normal aggregation studies with every agonist except ristocetin, which is abnormal. The reverse is true for Glanzmann thrombasthenia—they have normal aggregation with ristocetin but have no primary wave, as well as no secondary wave with other agonists. Patients with gray platelet syndrome have a moderate thrombocytopenia, prolonged bleeding time, and large platelets that appear gray on a Wright-stained blood film because of the absence of alpha-granules. Platelet aggregation studies are unremarkable.

In which substance is a patient with the following coagulation test results most likely deficient? Prothrombin time (PT) = 17 seconds (RR: 11-15 seconds) Partial thromboplastin time (PTT) = 31 seconds (RR: 25-37 seconds) Thrombin time (TT) 16 seconds (RR: 15-21 seconds) a. Fibrinogen b. Factor VII c. Factor VIII d. Factor X

*b. Factor VII Factor VII deficiency shows a prolonged PT with a normal PTT result. A deficiency of fibrinogen ideally should prolong the PT, PTT, and TT. Factor VIII deficiency prolongs the PTT but not the PT and TT, whereas a factor X deficiency should prolong both the PT and PTT but not the TT.

Which single-factor inherited deficiencies are most common as the cause for hemophilia? a. Factor V b. Factor VIII c. Factor IX d. Factor XI

*b. Factor VIII Eighty-five percent of congenital single-factor deficiencies are of factor VIII. This results in hemophilia A.

What is the mechanism for the platelet dysfunction in multiple myeloma and Waldenström macroglobulinemia? a. Granules become deficient. b. Platelets are coated with paraprotein. c. Nitric oxide is not produced. d. Cyclooxygenase is acetylated.

*b. Platelets are coated with paraprotein. Platelet dysfunction results from coating of the platelet membranes by paraprotein and does not depend on the type of paraprotein present. In addition to interacting with platelets, the paraprotein likely interferes with fibrin polymerization and the function of other coagulation proteins.

What is the purest form of factor VIII that is available for treating a bleeding patient with hemophilia A? a. Cryoprecipitate b. Recombinant factor VIII concentrate c. Fresh frozen plasma d. Factor VIII concentrate prepared by chemical concentration

*b. Recombinant factor VIII concentrate Recombinant deoxyribonucleic acid (DNA) technology provides a high-purity factor VIII concentrate.

What is the correct term to describe a platelet count of 550 × 10^9/L when all other complete blood count (CBC) results are basically normal? a. Normal b. Thrombocytosis c. Thrombocytopenia d. Essential thrombocythemia

*b. Thrombocytosis This platelet count is elevated, so the correct terminology to describe it is thrombocytosis; this is most probably a reactive thrombocytosis. Platelets are also elevated in essential thrombocythemia, but they usually exceed 1 million/mL (1000 × 10^9/L), and other abnormalities would also be seen in the CBC.

Patients who have a deficiency of protein C or protein S have which type of disorder? a. Bleeding disorder b. Thrombotic disorder c. Bruising disorder d. Hypercalcemia

*b. Thrombotic disorder Patients with a deficiency of either protein C or protein S have a thrombotic disorder. These two proteins are important in regulating, by downgrading, thrombin generation and thus clotting. Activated protein C binds free protein S to form a complex that inactivates factors Va and VIIIa.

A 35-year-old woman with neurologic symptoms presents with a markedly decreased platelet count. She has moderate anemia with many red cell fragments on the blood film, as well as polychromasia and nucleated red blood cells (RBCs). The prothrombin time (PT) and partial thromboplastin time (PTT) are both normal. Which is the most likely diagnosis? a. Immune thrombocytopenic purpura b. Thrombotic thrombocytopenic purpura c. Hemolytic uremic syndrome d. DIC

*b. Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura is characterized by thrombocytopenia, a microangiopathic hemolytic anemia with schistocytes (red cell fragments), and neurologic abnormalities. It is most common in women 30 to 40 years of age.

All are functions of thrombin except: a. activates factors V and VIII. b. activates plasminogen. c. activates factor XIII. d. initiates platelet aggregation.

*b. activates plasminogen. Thrombin does not activate plasminogen. It does perform all of the other functions listed.

Clot-based mixing studies and Bethesda titers are used to test for: a. vitamin K deficiency. b. inhibitors (antibodies) against coagulation factors. c. DIC. d. hemophilia.

*b. inhibitors (antibodies) against coagulation factors. An inhibitor against a coagulation protein is confirmed using clot-based mixing studies. The Bethesda titer is then performed to determine the concentration of the inhibitor.

Which type of VWD gives a positive response to low-dose ristocetin-induced platelet aggregation? a. 1 b. 2A c. 2B d. 2N

*c. 2B The low-dose ristocetin-induced platelet aggregometry identifies VWD, subtype 2B.

What role do cofactors play in the procoagulant process? a. Bind fibrinolytic factors to slow down lysis of the clot. b. Bind Ca2+ to form a bridge with platelet phospholipids. c. Bind to their specific activated serine protease to stabilize the protease and increase its activity. d. Bind to collagen to aid in platelet adhesion.

*c. Bind to their specific activated serine protease to stabilize the protease and increase its activity. Cofactors bind to their specific activated serine protease to stabilize the protease and increase its activity. One example is the binding of the cofactor Va to factor Xa, which then magnifies the activity of factor Xa to activate prothrombin.

Which patient group is most commonly diagnosed with acute immune thrombocytopenic purpura? a. Older men after an infection b. Infants born to women who had eclampsia c. Children after having an infection d. Adult patients with enlarged spleens

*c. Children after having an infection Acute immune thrombocytopenic purpura is primarily a disorder of children. It frequently occurs 1 to 3 weeks after an infection.

Which is the most common cause of acquired platelet dysfunction? a. Myeloproliferative disorders b. Wiskott-Aldrich syndrome c. Drugs, especially aspirin d. Afibrinogenemia

*c. Drugs, especially aspirin Aspirin and other drugs are the most common causes of acquired platelet dysfunction.

What test is useful for detection of a female carrier of hemophilia A? a. PTT b. PT c. Factor VIII to VWF ratio d. VWF antigen test

*c. Factor VIII to VWF ratio Approximately 90% of female carriers of hemophilia A are detected using the ratio of factor VIII activity to VWF antigen. This is because VWF production is unaffected by factor VIII deficiency, so it should be normal in a female hemophilia A carrier, whereas the factor VIII activity will be less than that of VWF. Thus a discrepancy exists in the concentration of these two proteins.

Two children in the same family have recurrent, chronic bruising in multiple sites, repeated long-lasting epistaxis, and minor bleeding after dental work. Which type of disorder is most likely? a. Localized, acquired, anatomic b. Localized, congenital, anatomic c. Generalized, congenital, systemic d. Generalized, acquired, systemic

*c. Generalized, congenital, systemic Because the two affected children are in the same family, this is most likely congenital. Recurrent, chronic bruising in multiple sites, along with long-lasting epistaxis and minor bleeding after dental work, make this generalized and systemic rather than localized and anatomic.

A 4-year-old child becomes very sick after drinking contaminated water. Kidney function tests are markedly elevated. Thrombocytopenia is mild, and a few schistocytes are noted on the blood film. Which is most likely the diagnosis? a. Immune thrombocytopenic purpura b. Thrombotic thrombocytopenic purpura c. Hemolytic uremic syndrome d. DIC

*c. Hemolytic uremic syndrome Hemolytic uremic syndrome is found primarily in children between the ages of 6 months to 4 years. In outbreaks of HUS associated with consumption of E. coli-contaminated water, both children and adults have developed HUS.

A 67-year-old woman arrives at the emergency department with acute bleeding into the back of the throat. A coagulation screen is ordered with the following results: PT = 12 sec (RR: 11-15 sec) PTT = 57 sec (RR: 25-37 sec) PTT 1:1 mix w/ normal plasma = 36 seconds (immediate) Fibrinogen = 450 mg/dL (RR: 150-400 mg/dL) What would be a reasonable next step to perform? a. Perform factor IX assay. b. Perform factor VII assay. c. Incubate the 1:1 mix at 37°C for 1 hour. d. Perform TT.

*c. Incubate the 1:1 mix at 37°C for 1 hour. Factor VIII autoantibodies are usually time and temperature dependent. Thus the 1:1 mix must be incubated at 37°C for 1 to 2 hours to give the antibody time to react with the factor VIII added by the normal plasma. Prolongation of the PTT on this incubated 1:1 mix indicates that an antibody to VIII is present. A factor VIII assay, when performed, will show a low factor VIII (less than 30%).

What coagulation screening test is the most sensitive for detecting mild liver disease? a. Fibrinogen b. PTT c. PT d. TT

*c. PT Liver disease particularly affects production of the vitamin K-dependent proteins. Because the PT is sensitive to factor VII activity and it (factor VII) has a short half-life of 3 to 5 hours, the PT is the most sensitive for detecting mild liver disease.

Which therapy actually lyses the clot rather than prevents future clots? a. Aspirin b. Heparin c. TPA d. Coumadin

*c. TPA TPA is normally released from endothelial cells and activates plasminogen, which then gradually lyses the fibrin clot. TPA is used therapeutically to lyse pathologic clots in thrombotic disease. Aspirin inhibits platelet function, heparin binds to antithrombin to inhibit thrombin, and Coumadin interferes with normal synthesis of the vitamin K-dependent proteins.

What is the single most common cause of clinically important bleeding? a. Hemophilia b. Fibrinogen deficiency c. Thrombocytopenia d. Qualitative platelet disorders

*c. Thrombocytopenia The single most common cause of clinically important bleeding is thrombocytopenia with a platelet count less than 100 × 10^9/L.

A 21-year-old woman has a primary complaint of menorrhagia. Her coagulation screen gives the following results. Prothrombin time (PT) = 12.0 seconds (11-15 seconds) Partial thromboplastin time (PTT) = 40 seconds (25-37 seconds) Factor VIII activity = 35% (50%-150%) Platelet count = 225 × 10^9/L (150-400 × 10^9/L) What disorder is most likely? a. Hemophilia A b. Hemophilia B c. VWD, type 1 d. Factor X deficiency

*c. VWD, type 1 VWD is the most prevalent of the congenital bleeding disorders, affecting both female and male subjects; hemophilia A and B both affect primarily male subjects. Female patients with VWD often complain of menorrhagia. Most patients with VWD have factor VIII levels in the range of 35% to 50%.

Which are components of the contact group of factors? a. Fibrinogen and thrombin b. VIII and VWF c. XII and prekallikrein d. Calcium and IX

*c. XII and prekallikrein The contact factors include factor XII, prekallikrein (Fletcher factor), and high-molecular-weight kininogen (Fitzgerald factor).

All are common conditions or situations that interfere with platelet function except: a. liver disease. b. uremia. c. allergic purpura. d. cardiopulmonary bypass surgery.

*c. allergic purpura. Allergic purpura does not interfere with platelet function. All of the other listed conditions or situations can affect platelet function.

Clopidogrel (Plavix) is a drug used therapeutically for patients with a risk of arterial thrombi because it: a. inhibits thrombin. b. activates the protein C pathway. c. inhibits platelet function. d. activates plasminogen.

*c. inhibits platelet function. Clopidogrel is an antiplatelet function drug used for three reasons: (1) to treat patients with arterial occlusive disease; (2) for prevention of myocardial infarction; and (3) to decrease the risk of thrombotic stroke in patients with cerebrovascular disease and in patients who are intolerant of aspirin.

The bleeding associated with renal disease is related most to defective: a. blood vessels. b. plasma procoagulants. c. platelets. d. inhibitors.

*c. platelets. Platelet dysfunction is the primary cause for prolonged bleeding in patients with renal failure.

What is the role of the thrombin-thrombomodulin complex? a. Initiates vasoconstriction. b. Activates thrombin. c. Inhibits factor Xa. d. Activates protein C.

*d. Activates protein C. Thrombin binds the endothelial cell membrane protein thrombomodulin, and the complex then activates protein C. Activated protein C complexes with protein S, and the complex degrades factors Va and VIIIa, which downregulates thrombin generation.

What is the possible mechanism for bleeding in patients with severe liver disease? a. Thrombocytopenia b. Inadequate production of procoagulants c. Disseminated intravascular coagulation (DIC) d. All of the options

*d. All of the options All of the findings listed are possible causes for bleeding in patients with severe liver disease.

What types of hemostatic complications are found in patients with myeloproliferative disorders? a. Hemorrhagic b. Thrombotic c. Abnormal platelet function d. All of the options

*d. All of the options Patients with one of the chronic myeloproliferative disorders, such as polycythemia vera and essential thrombocythemia, may have abnormal platelet function; clinically, they may result in either abnormal bleeding or abnormal thrombosis. Some patients develop both, although this is rare.

Which screening test would be normal when the plasma for the patient in Question 26 is analyzed? A 39-year-old male patient shows evidence of poor wound healing and a history of joint bleeding. What protein deficiency is most likely present? a. PT b. PTT c. TT d. All of the options

*d. All of the options The PT, PTT, and TT are all normal in a patient with factor XIII deficiency. Factor XIII deficiency is evaluated by placing the clot in 5M urea; the uncross-linked clot is weak and dissolves within 2 hours in this solution.

A 39-year-old male patient shows evidence of poor wound healing and a history of joint bleeding. What protein deficiency is most likely present? a. Factor VIII b. Factor IX c. Factor V d. Factor XIII

*d. Factor XIII Patients with a deficiency of factor XIII have evidence of poor wound healing and anatomic bleeds.

The urea solubility test is used to detect deficiencies in which factor? a. Fibrinogen b. Factor V c. Factor XII d. Factor XIII

*d. Factor XIII The plasma from patients with a factor XIII deficiency forms weak clots that dissolve within 2 hours when suspended in a 5M urea solution because the clot has not been cross-linked by XIIIa.

What plasma protein is important for normal wound healing and stabilization of the fibrin clot? a. Tissue factor b. Prothrombin c. Factor Xa d. Factor XIIIa

*d. Factor XIIIa Factor XIIIa stabilizes the fibrin polymer and is essential for normal wound healing, as well as tissue integrity.

Which is necessary for platelet aggregation? a. Protein S b. Kallikrein c. Vitamin K d. Fibrinogen

*d. Fibrinogen Platelet aggregation, the binding of platelets to one another, requires fibrinogen.

Which is the most likely diagnosis for an infant who experiences bleeding after circumcision with epistaxis and gingival bleeding? a. Aspirin ingestion b. Gray platelet syndrome c. Vitamin C deficiency d. Glanzmann thrombasthenia

*d. Glanzmann thrombasthenia Glad Glanzman thombobasthenia is a rare disorder which manifests itself clinically in the neonatal period or infancy, occasionally with bleeding after circumcision and frequently with epistaxis and gingival bleeding. Hemorrhagic manifestations include petechiae, purpura, menorrhagia, gastrointestinal bleeding, and hematuria.

Which is a commonly used drug that can cause thrombocytopenia? a. Warfarin b. Aspirin c. Ibuprofen d. Heparin

*d. Heparin Heparin is associated with drug-induced thrombocytopenia; this is called heparin-induced thrombocytopenia, and it can have serious thrombotic complications. Warfarin does not affect the platelet count. Aspirin and ibuprofen both affect platelet function.

Which results in ineffective thrombopoiesis? a. Immune thrombocytopenic purpura b. Thrombotic thrombocytopenic purpura c. Disseminated intravascular coagulation (DIC) d. Megaloblastic anemia

*d. Megaloblastic anemia Thrombocytopenia because of ineffective thrombopoiesis is one of the usual features of megaloblastic anemias. Vitamin B12 and folic acid are both required for normal maturation of megakaryocytes in the bone marrow.

Which patient group is most susceptible to bleeding because of a deficiency of vitamin K-dependent proteins? a. Those with poor diets b. Those on antibiotic agents c. Pregnant women d. Newborns

*d. Newborns Newborns are the most susceptible to vitamin K protein deficiency because the levels of the vitamin K-dependent proteins at birth are significantly lower than those for adults, and they drop even further the first few days of life. Breastfeeding prolongs the deficiency because passively acquired maternal antibodies delay establishment of the gut flora.

Which is normal in a patient regularly taking aspirin? a. Platelet aggregation b. Platelet cyclooxygenase function c. Synthesis of thromboxane A2 d. Platelet count

*d. Platelet count Only the platelet count, of those evaluations listed, is normal in a patient who regularly takes aspirin. Aspirin acetylates cyclooxygenase, which is necessary for the synthesis of thromboxane A2.

What happens to the fibrin monomers created when thrombin cleaves fibrinopeptides A and B from fibrinogen? a. Immediately inactivated to prevent excess clotting b. Converted to plasminogen c. Digested quickly by tissue plasminogen activator (TPA) d. Polymerized and are stabilized by factor XIIIa

*d. Polymerized and are stabilized by factor XIIIa Once thrombin splits fibrinopeptides A and B from fibrinogen, the fibrin monomers are formed. These spontaneously polymerize to form the initial soluble fibrin polymer, which is cross-linked by XIIIa and then becomes insoluble. Fibrin monomers spontaneously polymerize to form the fibrin clot, which is then stabilized by factor XIIIa. TPA activates plasminogen to plasmin, which lyses the clot.

Which aids in preventing excess clotting? a. Thrombin b. Factor VII c. Nitric oxide d. Protein C

*d. Protein C The protein C pathway helps regulate the coagulation mechanism by digesting activated coagulation factors V and VIII. Thrombin is the activated form of prothrombin; it plays a number of roles in promoting coagulation, including the splitting of fibrinogen to form fibrin. Nitric oxide counteracts vasoconstriction.

Which is appropriate initial testing for the siblings in Question 1? a. Fibrinogen, D-dimer, and platelet aggregation studies b. Factor VIII assay, liver function tests, and vitamin K level c. von Willebrand factor (VWF) antigen, Bethesda titer, and reptilase time d. Prothrombin time (PT), partial thromboplastin time (PTT), and platelet count

*d. Prothrombin time (PT), partial thromboplastin time (PTT), and platelet count The initial hemostasis profile should consist of the PT, PTT, and platelet count.

A 78-year-old patient recently noticed dark blotches on his forearms and on the backs of his hands. He seems to bruise even when a phlebotomy is performed using excellent technique with no problems encountered. No other symptoms exist, and all laboratory tests are normal. Which is the most likely diagnosis? a. Hereditary hemorrhagic telangiectasia b. Ehlers-Danlos syndrome c. Paraproteinemia and amyloidosis d. Senile purpura

*d. Senile purpura Senile purpura is the most likely diagnosis for this 78-yearold man who only recently began to notice abnormal bruising and/or bleeding. The hereditary abnormalities would have presented earlier in life. Paraproteinemia and amyloidosis would demonstrate other abnormal clinical laboratory testing.

What is common in patients with severe hemophilia A? a. Generalized bleeding after trauma or dental work b. Generalized hemorrhage c. Major bruising on extremities and chronic nosebleeds d. Serious anatomic bleeds into joints

*d. Serious anatomic bleeds into joints Hemophilia A causes anatomic bleeds, including deep muscle and joint bleeds. Major bruising is associated with platelet abnormalities.

Desmopressin acetate (DDAVP) is used to treat: a. dysfibrinogenemia. b. warfarin overdose. c. vitamin K deficiency. d. VWD, type 1.

*d. VWD, type 1. DDAVP, which triggers the release of VWF from storage organelles, is used to treat type 1 VWD. It is also useful in type 2A, but it is contraindicated in type 2B.

Oral anticoagulation is based on: a. increasing plasminogen. b. activating plasmin. c. combining with antithrombin. d. vitamin K antagonism.

*d. vitamin K antagonism. Vitamin K antagonism is the basis for oral anticoagulation.

An elevated tissue plasminogen activator (TPA) is associated with: a. abnormal bleeding. b. aspirin use. c. DIC. d. decreased fibrinolysis.

a. An elevated TPA is associated with abnormal bleeding. TPA activates plasminogen to plasmin, which lyses a clot; when TPA is elevated, this occurs prematurely and bleeding ensues.

Which practice is necessary when collecting blood specimen from a heparin or saline lock? a. Flush the IV line with 5-mL saline before collecting the specimen. b. The first 5 mL of blood that is collected must be immediately inserted into the blood tube for testing. c. Flush the IV line with heparin before collecting the specimen. d. Collect the blood directly into an evacuated tube.

a. Collection of blood from a heparin or saline lock is usually performed by physicians or nursing staff. The IV line must be flushed with 5-mL saline before the blood draw to avoid specimen contamination. The first 5 mL of blood that is collected should be discarded. IV lines should never be flushed with heparin before collecting blood for coagulation testing. Blood should be collected into a syringe, and a transfer device is used to transfer the blood to an evacuated tube.

A patient is positive for fibrin degradation products and negative for D dimers. Which condition is most likely? a. Systemic fibrinolysis b. DIC c. Hypofibrinogenemia d. Deep vein thrombosis (DVT)

a. Fibrin degradation products are positive and D dimers are negative in systemic (also called primary) fibrinolysis. Plasmin is present, which degrades fibrinogen so that it is decreased. However, thrombin is not present, so no D dimers are formed. They are both elevated in DIC and DVT. Neither is useful for hypofibrinogenemia, which is diagnosed using a fibrinogen assay.

Which will cause spuriously prolonged clot-based coagulation tests? a. An evacuated 3.2% sodium citrate tube filled to 50% capacity b. An evacuated 3.2% sodium citrate tube filled to 90% capacity c. Prolonged tourniquet application d. Plasma collected from a traumatic tap

a. Filling an evacuated 3.2% sodium citrate only halfway (50%) will lead to falsely prolonged clot-based coagulation test results. The relative excess anticoagulant will bind (some) of the calcium added in the test system. A 90% fill gives valid results and can be used. Prolonged tourniquet application and plasma collected from a traumatic tap both have the potential of activating coagulation, thus leading to shortened, not prolonged, results.

A patient has an elevated thrombin time and normal reptilase time. Which situation is most likely? a. Heparin therapy b. Low fibrinogen c. Elevated fibrin split products d. Dysfibrinogenemia

a. Heparin prolongs the thrombin time but does not prolong the reptilase time. A low fibrinogen, elevated fibrin split products, and dysfibrinogenemia prolong both, although differences exist in sensitivity to some of these between the two tests.

Which laboratory test identifies genetic variants in platelet-related bleeding disorders? a. HTS b. Sanger c. TEG d. ROTEM

a. High-throughput genetic sequencing (HTS) has become the reference approach to identifying the genetic variants that underlie platelet-related and coagulopathy-related bleeding disorders, having replaced the pioneering but less precise Sanger sequencing. Thromboelastography (TEG) and modification rotational thromboelastometry (ROTEM) measure clotting time and the dynamics of clot formation and dissolution as effected by the kinetics of thrombin generation, platelet activation, fibrin generation, clot strength, clot stability, and inhibitory effects on any aspect.

Which is the purpose ristocetin? a. Checks for plasma abnormalities in VWD. b. Provides info about platelet secretion conditions. c. Cleaves two protease-activatable receptors. d. Binds P2Y1 and P2Y12.

a. Ristocetin is used to check for abnormalities of plasma VWF in VWD. Lumiaggregometry provides more definitive information for conditions where recording platelet secretion, in addition to platelet aggregation, is an important diagnostic factor. Thrombin (or TRAP) cleaves two platelet membrane protease-activatable receptors (PARs), PAR-1 and PAR-2, both members of the seven-transmembrane repeat receptor family. ADP binds platelet membrane receptors P2Y1 and P2Y12, also members of the seven-transmembrane repeat receptor family.

Which is an acceptable sample for a prothrombin time (PT) test? a. One that was collected 24 hours before testing. b. One with a very small clot that was easily removed. c. 3.2% sodium citrate blood sample immediately collected following a serum separator tube. d. Blood anticoagulated with heparin and brought to the laboratory within 1 hour.

a. Specimens collected for PTs may be held uncentrifuged or centrifuged at 15° to 25°C and tested within 24 hours of the time of collection. Any clot in a specimen makes the sample useless for coagulation testing. Serum separator tubes contain a clot activator; this can contaminate the next tube drawn, and, for coagulation, is the same as having a clot. Heparinized samples are not used for coagulation testing.

What is the test commonly used to monitor the high heparin doses used in cardiac bypass surgery? a. PTT b. Prothrombin time c. Thrombin clotting time d. Fibrinogen

a. The high heparin doses used in cardiac bypass surgery can be monitored using the PTT.

Which patient would likely have a normal PT? a. Patient with a factor VII deficiency b. Patient with a factor VIII deficiency c. Patient on warfarin d. Clotted blood

b. A patient with a factor VIII deficiency would have a normal PT. All the others listed would have a prolonged PT.

Which condition is associated with an elevated fibrinogen? a. Acute DIC b. Chronic inflammation c. Severe liver disease d. Increased plasmin levels

b. An elevated fibrinogen is present in chronic inflammation because fibrinogen is an acute phase protein. It is decreased in all the other situations listed.

A patient admitted to the hospital with thrombosis is given the standard heparin dosage. Twenty-four hours after the heparin is started, the PTT is 38 seconds (reference range, 25 to 37 seconds). Both normal and abnormal controls are within their limits. Which is most likely? a. Laboratory error b. Patient has low antithrombin c. Heparin-induced thrombocytopenia d. Patient should be switched to low-molecular-weight heparin (LMWH)

b. When a patient has a deficiency of antithrombin, heparin may be administered in therapeutic or even higher dosages, but it will not exert an anticoagulant effect in vivo or be detected by the PTT. This is called heparin resistance.

Which condition would have a normal PTT? a. Lupus anticoagulant b. Fibrinogen of 50 mg/dL c. Factor VII deficiency d. Heparin therapy

c. Factor VII deficiency would have a normal PTT. All the other listed conditions would have a prolonged PTT.

How often must the partial thromboplastin time (PTT) reference interval be determined? a. Only when both the normal and abnormal controls are outside their acceptable limits b. At least every 6 months c. With each new lot of reagent d. Only when the normal control is outside its acceptable limits

c. The PTT reference interval must be determined with each new lot of reagent and at least once per year.

A patient has a hematocrit of 65%. Which is true related to coagulation testing? a. Hematocrit does not affect coagulation testing. b. Tube must be recollected with heparin as the anticoagulant. c. Tube must be recollected using 0.34 mL of sodium citrate to 4.5 mL of blood. d. Tube must be recollected using 0.62 mL of sodium citrate to 4.5 mL of blood.

c. The plasma volume is relatively low in a patient who has a high hematocrit. This unacceptably raises the anticoagulant-to-plasma ratio, invalidating test results that become falsely prolonged. When the hematocrit is greater than 55%, the volume of citrate must be decreased to optimize the anticoagulant-to-plasma ratio. Blood is not collected in heparin for coagulation tests.

Which deficiency prolongs the PTT but does not lead to abnormal bleeding? a. Factor V b. Factor VIII c. Factor XI d. Factor XII

d. A deficiency of factor XII prolongs the PTT. However, patients with this deficiency do not have abnormal bleeding.

A prolonged bleed time could signal: a. Glanzmann thrombasthenia. b. von Willebrand disease. c. scurvy. d. all of the options.

d. A prolonged bleeding time could theoretically signal von Willebrand disease (VWD), a functional platelet disorder such as Glanzmann thrombasthenia, or a vascular disorder such as scurvy or vasculitis, and was thought to have a predictable result in therapy using aspirin and other nonsteroidal anti inflammatory drugs (NSAIDs).

A patient undergoing thrombolytic therapy has a plasminogen level of 3.5 mg/dL. Which condition does this patient most likely have? a. Pregnancy b. Hemorrhage c. Acute inflammation d. Hepatitis

d. A typical plasminogen reference interval is 5 to 13.5 mg/dL. Plasminogen levels are decreased in thrombolytic therapy, DIC, hepatitis, and cancer, or may be hereditary. Decreased plasminogen is associated with thrombosis. Plasminogen rises in systemic fibrinolysis, acute inflammation, and during pregnancy, and high levels may be associated with hemorrhage.

Which is good practice in regard to phlebotomy on patients with hemostasis testing ordered? a. Make sure the patient is fasting. b. Always draw the sodium citrate tube last. c. Collect the blood in a glass syringe. d. Use a 20- or 21-gauge needle.

d. For routine coagulation draws, a 20- or 21-gauge needle is used. The patient does not need to be fasting, the sodium citrate tube should be drawn first, and glass (syringe) should never be used for coagulation specimens because glass activates the contact phase.

Which is necessary for normal platelet aggregation? a. Ristocetin b. von Willebrand factor (VWF) c. Epinephrine d. Fibrinogen

d. Normal platelet aggregation requires fibrinogen. Ristocetin is a substance added in vitro that causes platelet to clump. VWF is needed for normal platelet adhesion. Epinephrine is a platelet agonist stimulating platelet aggregation, but it is not necessary.

Patients with which condition would have a normal PT? a. Liver disease b. Disseminated intravascular coagulation (DIC) c. Factor VII deficiency d. Factor IX deficiency

d. Patients with a deficiency of factor IX will have a normal PT. The PT does not require this protein.

Which is an acceptable sample for testing on a photo-optical clot-detecting instrument? a. Lipemic plasma b. Hemolyzed plasma c. Serum d. Plasma collected using a 9:1 ratio of whole blood to 3.2% sodium citrate

d. Plasma should be collected at a 9:1 ratio of blood to anticoagulant (3.2% sodium citrate). Lipemia and hemolysis are possible interfering substances when using an instrument that uses the photo-optical principle for end-point detection. Serum cannot be used for coagulation testing because the sample has already clotted, with resultant loss of several coagulation proteins.

Which specimen would be acceptable for platelet aggregation studies? a. Blood drawn in ethylenediaminetetraacetic acid (EDTA) and kept at room temperature for 6 hours. b. Blood drawn in 3.2% sodium citrate and transported to the laboratory on ice (2° to 4°C). c. Blood drawn in a serum separator tube. d. Blood drawn in 3.2% sodium citrate and kept at room temperature for 2 hours after drawing.

d. Platelet function studies must be performed within 3 hours of drawing, and the specimen must be kept at room temperature because chilling damages platelets. The blood sample must be drawn in 3.2% sodium citrate.

The platelet function test will be normal and is no value to perform in patients who have: a. a qualitative platelet disorder. b. von Willebrand disease (VWD). c. Glanzmann thrombasthenia. d. factor VIII deficiency.

d. The platelet function test will be normal in patients with a factor VIII deficiency. It ideally will be prolonged in all the other listed settings. The bleeding time test is being used less often because it has poor predictive value and leaves scarring.

A patient has a factor VIII level of 50% activity. Which is most likely true regarding what can be expected for this patient's clinical situation? a. Severe bleeding b. Moderate bleeding c. Mild bleeding d. Normal with respect to factor VIII

d. The reference range for factor VIII activity is 50% to 150%. Thus this patient is normal.

A patient is stabilized on warfarin with an international normalized ratio (INR) of 2.7. He develops pneumonia and is admitted to the hospital. His appetite is depressed and he is placed on broad-spectrum antibiotic agents. At 1 week after the admission, his INR is 5.0. What is the most likely interpretation? a. The patient should be given more warfarin. b. A PTT should be performed to rule out heparin administration. c. A new sample should be collected to rule out a clotted specimen. d. Vitamin K is reduced, increasing the effects of warfarin.

d. This elevated INR is probably the result of a deficiency of vitamin K, which increases the effects of warfarin. Vitamin K deficiency is seen during use of broad-spectrum antibiotic agents that destroy gut flora and in people with a poor diet, both of which are present in this patient.

A 53-year-old woman arrives at the hospital with bleeding into the back of the throat and has a coagulation screen performed. She has no history of abnormal bleeding before this despite major stress to hemostasis in the past—she was in a major automobile accident at age 37 and has had impacted wisdom teeth extracted. Her coagulation results follow: Prothrombin time (PT) - 13.1 seconds Reference range: 11-15 seconds Partial thromboplastin time (PTT) - 87 seconds (35 with 1:1 mix with normal plasma) Reference range: 25-37 seconds Fibrinogen 380 mg/dL Reference range: 200-400 mg/dL Which is the most likely cause for her bleeding? a. Factor XII deficiency b. Factor IX deficiency c. Factor VIII deficiency d. Factor VIII inhibitor

d. This patient is bleeding abnormally. However, she has had major trauma in the past with no abnormal bleeding; this suggests the problem is acquired, not congenital. The PTT is prolonged, so the common pathway appears to be intact. The prolonged PTT fully corrects on a 1:1 mix, although at the upper end of the reference range. Putting all of this together, the most likely problem is an acquired factor VIII inhibitor.

A prolonged PTT is corrected when mixed with normal plasma and tested immediately and after a 2-hour incubation. Which test (or tests) should be performed next? a. Bethesda titer b. High-phospholipid PTT c. Anti-Xa assay d. Factor VIII assays

d. This pattern suggests a factor deficiency, and factor VIII assay should be performed. The Bethesda titer is performed when a specific factor inhibitor is present; no evidence exists for this because the PTT on the incubated 1:1 mix did not prolong. Highphospholipid PTT testing is done to confirm the lupus anticoagulant; this is not present because the immediate 1:1 mix on this sample corrected. No reason exists to perform an anti-Xa assay, often used to monitor LMWH.

A patient's platelet count drops 4 days after being placed on heparin. Select the correct interpretation. a. The patient has heparin-induced thrombocytopenia. b. The patient has benign, limited thrombocytopenia related to heparin. c. A bleeding time should be performed to evaluate qualitative platelet disorders. d. An immunoassay for heparin-dependent anti-platelet factor 4 (PF4) should be performed to distinguish heparin-induced thrombocytopenia from benign, limited thrombocytopenia related to heparin.

d. This pattern, a drop in the platelet count 4 days after being placed on heparin, suggests heparin-induced thrombocytopenia. It could also be a benign, limited thrombocytopenia related to heparin. Assays such as the immunoassay for heparin-dependent anti-PF4 can distinguish the two.