Week 5,6,7 MDL242 ~ reviewed

Which test is increased in a patient with severe hemophilia A?

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 is common in patients with severe hemophilia A?

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

Clot-based mixing studies and Bethesda titers are used to test for:

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.)

Absence of D dimers is useful for ruling out:

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

On what does factor VIII depend for stability?

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

Which assay uses indirect measurement using a chromogenic substrate to quantitate heparin?

Anti-Xa assay (The heparin anti-Xa assay is used to indirectly measure the concentration of heparin. In this system, heparin has an inhibitory effect on the enzyme Xa. Xa normally proteolytically cleaves the chromogenic substrate, releasing the chromogen with a color intensity that is then measured. Because heparin has inhibited some of the Xa, less free Xa will be available to cleave the substrate and less color will be released. Thus the concentration of heparin is inversely proportional to the activity of Xa. This is classified as an indirect measurement.)

A patient is admitted through the hospital emergency department with thrombosis, and heparin is initially begun. Her baseline PTT, before heparin therapy, is prolonged at 68 seconds. Further laboratory studies determine that she has the lupus anticoagulant. What test should be used to monitor her heparin therapy?

Chromogenic anti-Xa assay (The PTT is already prolonged by the lupus anticoagulant, so the heparin therapeutic range for the PTT reagent becomes meaningless. In this case a chromogenic anti-Xa assay should be used.)

Why is it important to monitor patients who are receiving anticoagulant therapy?

Clinical consequences for overdosing are significant. (The clinical consequences for incorrect dosage of anticoagulant drugs are significant. Overanticoagulation can lead to serious bleeding that may even require a visit to the emergency department.)

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

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

Which single-factor inherited deficiencies are most common as the cause for hemophilia?

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

What types of hemostatic complications are found in patients with myeloproliferative disorders?

Hemorrhagic Thrombotic Abnormal platelet function (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.)

Where are most of the plasma procoagulant proteins produced?

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

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?

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

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

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?

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? Thrombin Factor VII Nitric oxide Protein C

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.)

What is the purest form of factor VIII that is available for treating a bleeding patient with hemophilia A?

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

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?

Senile purpura (Senile purpura is the most likely diagnosis for this 78-year-old 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.)

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

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.)

What is the possible mechanism for bleeding in patients with severe liver disease?

Thrombocytopenia Inadequate production of procoagulants Disseminated intravascular coagulation (DIC)

Which is the most common form of von Willebrand disease (VWD)?

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

All of the following serine proteases are bound and inhibited by antithrombin except: Xa. IXa. Correct Answer VIIa. You Answered XIa.

VIIa. (Antithrombin covalently binds and inhibits XIIa, XIa, Xa, IXa, and thrombin. It does not bind VIIa.)

Desmopressin acetate (DDAVP) is used to treat:

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.)

Which is more likely to result from poor absorption than from inadequate nutritional intake in older adults?

Vitamin B12 deficiency (Vitamin B12 deficiency is most likely to develop from inadequate intestinal absorption, rather than an inadequate vitamin intake. This can progressively lead to the development of pernicious anemia.)

Which type of VWD gives a positive response to low-dose ristocetin-induced platelet aggregation?

2B (The low-dose ristocetin-induced platelet aggregometry identifies VWD, subtype 2B.)

Why is the white count in a normal full-term newborn elevated shortly after birth?

An absolute increase in neutrophils occurs. (An absolute increase in neutrophils occurs within hours of birth; this elevates the white count. Bands and occasionally myelocytes may also be present. At day 2, the count begins to drop progressively, primarily because of an absolute decrease in neutrophils.)

What protein does heparin work with to inhibit coagulation?

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 thrombin-antithrombin complex renders thrombin inactive; the complex is taken to the liver and cleared.)

Which is part of primary hemostasis? Fibrinolysis Blood vessels Intrinsic system Inhibitors

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

What is the normal bone marrow cellularity in the population older than 65 years?

Bone marrow cellularity decreases in the older population and is approximately 30%. That of a young adult is 50%. This change may be caused by an increase in the volume of spongy tissue in the bone, as well as an increase in fat, rather than an actual decrease in hematopoietic tissue.

Which is most improved safety for laboratory scientists?

Closed tube sampling (Closed tube sampling has improved the safety and efficiency of coagulation testing. This reduces the chances of the clinical laboratory scientist being exposed to the patient specimen through spillage or aerosol formation.)

Which protein is the best test to distinguish moderate to severe liver disease from vitamin K deficiency?

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.)

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)

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.)

What test is useful for detection of a female carrier of hemophilia A?

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.)

The urea solubility test is used to detect deficiencies in which factor?

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?

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

Which is decreased in DIC? Fibrinogen PT PTT Fibrin degradation products

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

Which is necessary for platelet aggregation? Protein S Kallikrein Vitamin K Fibrinogen

Fibrinogen (Platelet aggregation, the binding of platelets to one another, requires fibrinogen.)

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?

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.)

Which is the most likely diagnosis for an infant who experiences bleeding after circumcision with epistaxis and gingival bleeding?

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.)

A complete blood count (CBC) is requested on a full-term newborn girl, and the following results are obtained: Hemoglobin 14.4 Hematocrit 44.5% MCV 88 fL White blood cells (WBCs) 26.8 × 109/L Platelets 295 × 109/L What conclusion can be made regarding these data for this infant?

Hemoglobin, hematocrit, and MCV are all decreased. (The hemoglobin, hematocrit, and MCV are all low for a full-term newborn (the red count is actually in the reference range). Because the red count is relatively high for the hematocrit and hemoglobin, with the low MCV, thalassemia should be suspected.)

Which single instrument development has been the most important improvement in coagulation instrumentation?

Random access testing (The most significant improvement in automated coagulation analyzers is the ability to provide random access testing. This means that a variety of tests can be run in any order on the same plasma specimen or many specimens within the same testing batch. This vastly improves the efficiency of the clinical laboratory.)

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

activates plasminogen. (Thrombin does not activate plasminogen. It does perform all of the other functions listed.)

Examples of instrument malfunction flags include all except: temperature error. probe not aspirating. mechanical movement. hemolysis.

hemolysis. (The presence of hemolysis is not flagged by the instrument but must be noted by the clinical laboratory scientist. All the other flags are instrument generated.)

Which age-group normally has the lowest mean cell volume?

Newborn (The erythrocytes of newborn infants are markedly macrocytic at birth. The average MCV for full-term infants is 119 ± 9.4 fL; however, a sharp decrease occurs during the first 24 hours of life.1,2 The MCV continues to decrease to 90 ± 12 fL in 3 to 4 months.2,9,17 The more premature the infant, the higher the MCV.)

Which patient group is most susceptible to bleeding because of a deficiency of vitamin K-dependent proteins?

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.

Once a patient is stabilized on warfarin therapy, how often should he or she be monitored?

Once a patient is stabilized on warfarin therapy, monitoring should continue every 4 to 6 weeks until therapy is complete. Changes in diet, metabolism, renal function, other drugs being taken, as well as additional factors all change the response to warfarin and may require making dosage adjustments.

Aspirin-induced bleeding and von Willebrand disease (VWD), type 1, are detected reliably by:

PFA 100 Platelet Function Analyzer. (The PFA 100 Platelet Function Analyzer assesses platelet dysfunction. Aspirin and VWD both negatively affect platelet function, although by entirely different mechanisms. Aspirin acetylates cyclooxygenase, thus preventing the eventual production of thromboxane A2, an important platelet agonist. In type 1 VWD, von Willebrand factor (VWF) is decreased and therefore platelet adhesion is abnormal. The platelet count is not a reliable test for platelet function.)

What coagulation screening test is the most sensitive for detecting mild liver disease?

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.)

A 21-year-old woman has a primary complaint of menorrhagia. Her coagulation screen gives the following results. *Prothrombin time (PT)12.0 seconds (Reference range: 11-15 seconds) *Partial thromboplastin time (PTT)40 seconds (rr: 25-37 seconds) *actor VIII activity 35% (rr: 50%-150%) *Platelet count 225 × 109/L (rr: 150-400 × 109/L) What disorder is most likely? Hemophilia A Hemophilia B VWD, type 1 Factor X deficiency

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%.)

Oral anticoagulation is based on:

Vitamin K antagonism is the basis for oral anticoagulation.

What vitamin is essential for normal synthesis of prothrombin group proteins, thus enabling them to bind Ca2+?

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

Which are components of the contact group of factors? Fibrinogen and thrombin VIII and VWF XII and prekallikrein Calcium and IX

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

An 85-year-old woman has a hemoglobin of 10.5 g/dL. This is:

a sign of an underlying disease that requires further evaluation. (The majority of geriatric individuals maintain a normal hemoglobin for their sex so that this hemoglobin of 10.5 g/dL in an 85-year-old woman is low and a sign of an underlying disease. This requires further work-up. Most anemias in older adults are iron deficiency or the anemia of chronic inflammation (disease). Myelophthisic anemia, in which the bone marrow is invaded by something foreign, such as metastatic malignant cells, certainly occurs but is not the most common cause of anemia in older adults.)

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

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

All are considered routine coagulation tests that are available in most large and small clinical laboratories except: prothrombin time (PT). fibrinogen assay. partial thromboplastin time (PTT). antithrombin assay.

antithrombin assay. (The antithrombin assay traditionally has not been available in most clinical laboratories, and that is still true today in small laboratories.)

Iron deficiency anemia in older adults is most often a result of:

bleeding in the gastrointestinal tract. (Bleeding from the gastrointestinal tract is the most common cause of iron deficiency anemia in older adults.)

Why is the platelet count monitored daily for a patient receiving heparin therapeutically?

A significant decrease in the platelet count is evidence for heparin-induced thrombocytopenia. (A decrease of 40% or greater in the platelet count, even if the platelet count remains in the reference range, is evidence for heparin-induced thrombocytopenia. This is a serious consequence, and unfractionated heparin therapy must be immediately stopped and replaced with a direct thrombin inhibitor.)

What is the role of the thrombin-thrombomodulin complex?

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.)

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

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.)

What substance is known to inactivate arachidonic acid, causing impairment of platelet function?

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.

At what age is it normal for bone marrow cellularity to be 80% to 90% (i.e., has very little fat)?

At the time of birth, the bone marrow is fully active and extremely cellular with very little fat. It contains all hematopoietic cell lineages.

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

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.)

What role do cofactors play in the procoagulant process?

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 is most commonly seen in the population older than70 years? Chronic lymphocytic leukemia Chronic myelogenous leukemia Essential thrombocytosis Acute lymphocytic leukemia

Chronic lymphocytic leukemia (Chronic lymphocytic leukemia is the most common leukemia in the population older than 70 years of age, although acute myeloid leukemia and chronic myelogenous leukemia do show increased age-related incidence. Essential thrombocytosis is rare. Chronic myelogenous leukemia is seen more often in the middle aged, and acute lymphocytic leukemia most commonly occurs in children.)

An INR of 6.5 is obtained on a patient taking warfarin. All quality control is acceptable. What should be done?

Call the clinician immediately. (INRs greater than 5 are associated with increased risk of hemorrhage, and require immediate communication with the clinician who is managing the patient's case.)

What are the primary procoagulant roles of the blood vessel?

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.)

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 × 109/L Platelet function assay- Prolonged Platelet aggregation with epinephrine= Primary but no secondary wave Platelet aggregation with low-dose adenosinediphosphate (ADP)= Primary but no secondary wave Platelet aggregation with ristocetin= Normal What is the most likely diagnosis for this patient?

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.)

What is the most likely reason that the red blood cell (RBC) count remains elevated in a newborn for the first 2 weeks of life?

Hypoxia in utero (Partial hypoxia occurs in utero, which causes the normal physiologic response to increase erythropoietin, which stimulates erythropoiesis. About 2 weeks after birth, as the infant makes the transition from its placenta-dependent oxygenation to the increased tissue oxygenation of the lungs, erythropoietin decreases, and the red cell count begins to decrease.)

Which principle measures the actual coagulation protein rather than fibrin formation?

Immunologic (Immunologic methods measure the actual coagulation protein rather than fibrin formation. These assays are based on antigen-antibody reactions.)

Which is true concerning age-related changes of hemostasis in older adults? Decreased factor VIII Decreased platelet activity Increased fibrinogen Increased fibrinolysis

Increased fibrinogen (Fibrinogen levels, factor VIII, and platelet activity all increase during aging. Plasminogen activator inhibitor, the major inhibitor of fibrinolysis, increases with aging, so fibrinolysis of clots decreases.)

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: *Prothrombin time (PT)12 seconds (rr: 11-15 seconds) *Partial thromboplastin time (PTT)57 seconds (rr: 25-37 seconds) 1:1 mix with normal plasma: 36 seconds (immediate) *Fibrinogen450 mg/dL150-400 mg/dL What would be a reasonable next step to perform?

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 is the greatest disadvantage to photo-optical coagulation instruments?

Interference from lipemia, hemolysis, and hyperbilirubinemia (Possible interference from the presence of lipemia, hemolysis, or hyperbilirubinemia is the greatest disadvantage for photo-optical end-point detection methods.)

Which is true related to the use of aspirin to prevent cardiovascular disease? *It is used to prevent arterial thrombosis. *New studies show it is not effective. *It works well but must be carefully monitored with monthly bleeding times. *Aspirin monitoring tests such as thromboxane B2 are now easy to perform and widely available.

It is used to prevent arterial thrombosis. (Aspirin, as well as other antiplatelet drugs, have been shown to be effective for prevention of arterial thrombosis, especially myocardial infarction, stroke, and peripheral artery occlusion. This therapy is not monitored. However, some individuals are resistant to aspirin therapy, and thromboxane B2 tests are available, although they are not easily performed or widely available.)

Diagnostica Stago coagulation instruments are based on what clot detection principle?

Mechanical (Diagnostica Stago coagulation instruments use a mechanical end-point clot detection principle. These instruments magnetically monitor the movement of a steel ball within plasma. As the clot forms, the sensor detects the slowing of the ball.)

What are the primary roles of VWF?

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.)

Who should select the coagulation instruments for a given laboratory?

Medical staff (The decisions regarding which tests are the most appropriate for the clinical situations encountered by each laboratory should be made in conjunction with the medical staff. When that input has been obtained, the laboratory can determine the availability and cost of instruments that would meet those requirements.)

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

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.)

A clinical laboratory receives a new lot of PTT reagent, so clinical laboratory scientists in the laboratory need to establish the heparin therapeutic range for this new reagent lot. How should this be done?

Perform chromogenic Xa and PTT assays on patient heparinized samples, and do a statistical analysis of result comparisons. (Accrediting agencies for clinical laboratories require that the PTT heparin therapeutic range be determined using samples from patients who are receiving heparin therapeutically; they cannot be receiving simultaneous warfarin therapy (thus their PT must be normal). Both a chromogenic anti-Xa assay and PTT are performed on each patient sample, and the paired results are plotted in a linear graph. The range that corresponds to 0.3 to 0.7 chromogenic anti-Xa is the therapeutic range.)

Using which principle does plasma become more opaque as a clot forms and the amount of light being detected decreases?

Photo-optical (A light source of specified wavelength is made to pass through plasma; some light normally gets through to the detector. As a fibrin clot forms, the amount of light detected decreases. When light decreases to a predetermined deflection from the baseline, the timer stops, indicating clot formation.)

Which is the most common clot detection principle used for coagulation testing?

Photo-optical (The most common clot detection principle used by automated coagulation instruments is photo-optical.)

What substance digests the fibrin clot after healing?

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

The bleeding associated with renal disease is related most to defective:

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

What is the mechanism for the platelet dysfunction in multiple myeloma and Waldenström macroglobulinemia?

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.)

Which is appropriate initial testing for the siblings in Question 23?

Prothrombin time (PT), partial thromboplastin time (PTT), and platelet count

Which is true regarding advances in automated coagulation instrumentation? *Less staff training is required to operate and maintain the equipment than was necessary for earlier semiautomatic instruments. *Single-sample testing is possible because of increased precision. *Newer instruments are less expensive. *Accuracy is so improved that controls do not need to be run.

Single-sample testing is possible because of increased precision. (Increased precision on the new automated coagulation instruments means that single-sample testing is possible. Before this, every sample had to be tested in duplicate and the duplicates had to agree within certain preset limits before they could be averaged and the result reported.)

What is the best test to distinguish hemophilia A from B or C?

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?

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

Which therapy actually lyses the clot rather than prevents future clots?

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 procedure is used to quantitate a factor VIII inhibitor?

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

Which screening test would be normal when the plasma for the patient in Question 48 is analyzed?

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.

Why is there a relative lymphocytosis in a 2 year old?

The absolute number of lymphocytes is increased as the immune system develops. (An absolute increase in lymphocytes occurs, presumably because the immune system is developing as more antigens are encountered; this increases the absolute number of lymphocytes, as well as the relative percent. The number of marginated neutrophils is not increased; lymphocytes do not marginate.)

Patients who have a deficiency of protein C or protein S have which type of disorder?

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.)

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

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.)

A patient is stabilized on warfarin therapy and being monitored using the prothrombin time (PT) followed by calculation of the international normalized ratio (INR). The formula for calculating the INR is: INR = (PTpatient/PTnormal)ISI (where ISI = international sensitivity index)What is used for the PTnormal?

geometric mean PT for the reference population. The PTnormal is the geometric mean for the PT reference interval determined by the clinical laboratory scientists in the laboratory where the testing is being performed. Using the wrong value in this calculation has led to major reporting errors that have resulted in bad patient outcomes.

Clopidogrel (Plavix) is a drug used therapeutically for patients with a risk of arterial thrombi because it:

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.)

A normal 3-month-old boy has a hemoglobin of 11.2 g/dL. Which is true about his hemoglobin? It is: higher than that of a normal full-term newborn. lower than that of an adult of the same age. higher than that of a 14 year old of the same sex. the same as that of an adult of the same sex

lower than that of an adult of the same age. (Hemoglobin is lower in a 3 month old than in an adult of the same sex. It is normally higher at birth but quickly begins to decrease so that by 3 months old this would be a normal hemoglobin (abnormal at birth). It is lower than that of both a 14 year old and an adult of the same sex.)

All are normal peripheral blood RBC findings at birth in a full-term infant except: nucleated RBCs. mean cell volume (MCV) less than 90 fL. reticulocytosis of 5%. hemoglobin of 20.2 g/dL.

mean cell volume (MCV) less than 90 fL. (An MCV of 90 fL in a newborn is abnormal and cause for a thalassemia/iron deficiency work-up. The mean MCV in a full-term newborn is 109 fL; an MCV less than 94 fL is cause for evaluation for alpha-thalassemia or iron deficiency. All the other results given are normal for a full-term newborn.)

Unfractionated heparin is commonly monitored by the:

partial thromboplastin time (PTT). (The PTT is the most commonly used test for monitoring heparin therapy because it responds in a linear fashion over the therapeutic range. The PT is relatively insensitive to heparin, whereas the TT is too sensitive. The kinetic fibrinogen is the least sensitive of these tests to therapeutic heparin.)

Warfarin skin necrosis occurs within the first 2 to 3 days after starting warfarin therapy because:

protein C decreases significantly before full anticoagulation, and skin thrombosis results. (Protein C has a 6-hour half-life, and so it rapidly decreases when warfarin therapy is begun, along with factor VII (both are vitamin K-dependent proteins). Full anticoagulation with warfarin is not obtained until factors X and prothrombin are decreased to less than 50%, requiring 4 to 7 days based on their half-lives. Because protein C is important in controlling clot formation, its decrease actually puts the patient in a prethrombotic state until full anticoagulation is obtained.)

Automatic performance of certain tests based on the results of other tests is called:

reflex testing. (Reflex testing is the automatic ordering of tests based on preset parameters or the results of other tests. These reflex tests must be clearly indicated to the ordering health care provider at the time the initial screening test (or tests) is ordered.)