Success! Hemostasis

A 57-year-old man with prostate cancer is admitted to the intensive care unit with severe bleeding problems. The following laboratory results are obtained: Platelet count= normal Prothrombin time= prolonged aPTT= prolonged Fibrinogen= decreased Thrombin time= prolonged D-dimer= negative FDP= positive Antithrombin= normal RBC morphology= Schistocytes absent These laboratory results are consistent with A. Primary fibrinogenolysis B. DIG with secondary fibrinolysis C. Factor II deficiency D. Coumadin® therap

A. Primary fibrinogenolysis is an unusual disorder in which the fibrinolytic system is activated in the absence of clot formation. Plasmin degrades factors V, VIII, and fibrinogen. The D-dimer test is positive if fibrin degradation products are present; they are absent in this disorder. The FDP test is positive in the presence of either fibrin or fibrinogen degradation products. Tests that are abnormal in DIG due to the systemic clotting are normal in primary fibrinogenolysis.

The main regulatory protein of secondary hemostasis is A. Antithrombin B. Protein C C. alpha2-Antiplasmin D. Tissue plasminogen activator

A. Antithrombin is the most important naturally occurring inhibitor to clotting and accounts for 80% of negative feedback in the coagulation cascade by inhibiting serine proteases. Protein C and its cofactor, protein S, inhibit cofactors V and VIII. a2-Antiplasmin is responsible for neutralizing plasmin once the clot has been lysed. Tissue plasminogen activator activates the fibrinolytic system in response to clot formation.

Of the following therapeutic agents, those considered to be antiplatelet medications are A. Aspirin and Plavix® B. Coumadin® and heparin C. Heparin and protamine sulfate D. Tissue plasminogen activator and streptokinase

A. Aspirin inhibits the enzyme cyclooxygenase in the prostaglandin pathway, preventing platelet aggregation. Plavix® (clopidogrel bisulfate) blocks the Ilb/IIIa fibrinogen-binding platelet receptor, preventing platelet aggregation. Coumadin® and heparin inhibit clotting factors in secondary hemostasis. Protamine sulfate can be used to neutralize heparin. Tissue plasminogen activator and streptokinase are fibrinolytic system activators

Laboratory results on a 6-year-old female with petechiae and severe epistaxis are as follows: Platelet count= 145 x 1 09/L Bleeding time= >1 5 min (reference range </=8.0 min) MPV= 16.0 fL (reference range 8.0-1 0.0 fL) Platelet aggregation= Normal response to ADP, collagen, epinephrine; no response with ristocetin Prothrombin time= 1 1 .5 sec (control 12.0 sec) aPTT= 33.0 sec (control 32.0 sec) These results are consistent with A. Bernard-Soulier syndrome B. von Willebrand disease C. Glanzmann thrombasthenia D. Ehlers-Danlos syndrome

A. Bernard-Soulier syndrome is a platelet adhesion defect that can be mistaken for von Willebrand disease. Platelets in this syndrome lack the glycoprotein Ib receptor, which is necessary for von Willebrand factor to attach to the platelet. Both disorders give identical platelet aggregation patterns. Bernard-Soulier syndrome is noted for giant platelets (note the increased MPV) and varying degrees of thrombocytopenia. Because von Willebrand factor is present in Bernard-Soulier syndrome, the aPTT is normal.

In storage pool disease, platelets are primarily deficient in A. ADP B. Platelet factor 3 C. Thrombasthenin D. Thromboxane A2

A. Platelets in storage pool disease are deficient in dense granules. The platelets in this disorder lack nonmetabolic ADP found in dense granules and normally released when the platelets are stimulated. This accounts for a poor response to aggregating agents

Which of the following best describes protein C? A. Vitamin K-dependent inhibitor to clotting B. Activator of factors V and VIILC C. Inhibitor of fibrinolysis D. Synthesized by endothelial cells

A. Protein C, a glycoprotein produced in the liver, is a potent inhibitor of coagulation. The activation of protein C, by the thrombin/thrombomodulin complex, will cause the inactivation of factors V and VIII:C. Protein C and its cofactor, protein S, are vitamin K-dependent proteins.

The principle of_____ methods depends on cleavage of synthetic substrates by an active serine protease. A. Chromogenic B. Photo-optical C. Mechanical D. Immunodiffusion

A. The proteolytic activity of antithrombin after activation to a serine protease can be assayed via methods that employ synthetic substrates. The cleavage of the synthetic substrate by an active serine protease will yield a chromogenic compound. Chromogenic methods can also be used to assay plasminogen, protein C, and heparin.

A microtainer EDTA sample obtained during a fingerstick puncture is run on an automated cell counter, yielding a platelet count of 178 x 10^9/L. In the erythrocyte monolayer of the stained peripheral blood smear, an average of 9 platelets per field is seen under lOOOx magnification. Based on these data, you should A. Report the results because the platelet count and platelet estimate correlate. B. Recollect a specimen for a repeat platelet count because the platelet count and estimate do not correlate. C. Examine the periphery of the blood smear for clumping because the platelet count and estimate do not correlate. D. Rerun the platelet count on the available specimen to confirm the results.

A. The results should be reported. A platelet estimate is obtained by multiplying the average number of platelets per oil immersion field (in an erythrocyte monolayer) by 20,000. This number is based on a normal erythrocyte count, which must be considered when comparing the platelet count and estimate. The estimate in this example is 180 x 10^9/L. This agrees with the platelet count.

When thrombin binds to thrombomodulin on the endothelial cell surface, thrombin can A. Activate the protein C pathway B. Activate factor V and factor VIII C. Convert fibrinogen to fibrin D. Stimulate platelet aggregation

A. Thrombomodulin, an endothelial cell receptor, has the ability to change the specificity of thrombin from a procoagulant to an anticoagulant. Once bound to thrombomodulin, thrombin has anticoagulant properties because of its activation of protein C. Protein C, along with its cofactor protein S, then exerts negative feedback on the clotting system by inactivating factor V and factor VIII.

The hemorrhagic problems associated with scurvy are due to a deficiency of_____ , which is a cofactor required for collagen synthesis. A. Vitamin C B. Prothrombin C. Vitamin K D. Protein C

A. Vascular integrity is influenced by vitamin C intake. In a deficiency or absence of vitamin C, collagen production is insufficient or abnormal. Vitamin C deficiency is associated with capillary fragility and the primary hemostasis bleeding symptoms of petechiae and mucosal bleeding

Measurement of the time required for fibrin formation when thrombin is added to plasma evaluates the A. Fibrinogen concentration B. Prothrombin concentration C. Extrinsic clotting system D. Intrinsic clotting system

A. When thrombin is added to patient plasma, fibrinogen is converted to fibrin. No factors above fibrinogen in the cascade are measured, including prothrombin. Both the thrombin time and fibrinogen test use thrombin reagent; both tests measure only one factor, fibrinogen.

A 30-year-old female is admitted to the hospital with neurological symptoms. The following results are obtained: Hemoglobin= 60g/L Hematocrit= 0.19L/L Platelet count= 25 x 1 09/L RBC morphology= Many schistocytes ADAMTS-13= Markedly decreased The most likely diagnosis for the patient is A. Thrombotic thrombocytopenic purpura B. Idiopathic thrombocytopenic purpura C. Hemolytic uremic syndrome D. von Willebrand disease

A. With the severe anemia and many schistocytes, a microangiopathic hemolytic anemia should be considered (TTP, HUS). HUS is seen in children after a gastrointestinal infection, frequently caused by E. coli 0157:H7, and results in renal damage. TTP is seen in young adults and is more common in women than men. TTP causes neurological damage. Patients with TTP have unusually large multimers of von Willebrand factor because they have a deficiency of a metalloprotease, ADAMTS-13, responsible for breaking down the multimers. These large multimers of vWF bind strongly to platelets, causing platelet aggregation and thrombotic complications in multiple organs.

A sodium citrate tube is received in the laboratory for PT and aPTT testing. Results are as follows: Prothrombin time= > 1 00.0 sec (control 12.0 sec) aPTT= >200.0 sec (control 32.0 sec) On examination, a large clot is discovered. The abnormal test results are due to deficiencies of factors A. I, V, VIII, IX B. I, II, V, VIII, XIII C. II, VII, IX, X D. VIII, IX, XI, XII

B. A synonym for the fibrinogen group of factors is the consumed factors, because they are totally used up in clot formation. In the conversion of fibrinogen to fibrin, all of prothrombin is converted to thrombin. Thus, factors I, V, VIII, XIII, and II are all missing in serum.

Platelets interacting with and binding to other platelets is referred to as A. Adhesion B. Aggregation C. Release D. Retraction

B. "Adhesion" refers to platelets interacting with something other than platelets. In vivo platelets adhere to collagen that is exposed when vessel damage occurs. "Aggregation" refers to attachment of platelets to other platelets. Release is the process by which platelet granule contents are secreted. Retraction describes one of the final steps in coagulation in which the fibrin-platelet plug contracts, restoring normal blood flow to the vessel.

A specimen is received for a prothrombin time and activated partial thromboplastin time. The 5 mL tube has 2.5 mL of blood in it. Expected test results are A. PT and aPTT both falsely short B. PT and aPTT both falsely long C. PT and aPTT both unaffected D. PT unaffected, aPTT falsely short

B. A 9:1 ratio of blood to anticoagulant is needed for sodium citrate to bind all available calcium in the blood sample and prevent coagulation. When the 9:1 ratio is not maintained due to the tube not being full, excess sodium citrate present will bind reagent calcium in the test system. This will cause falsely prolonged PT and aPTT results.

Blood for an aPTT was collected from a 5year-old boy. During the venipuncture, he had to be restrained by several people and still managed to be a moving target. The result of the child's aPTT was 18.0 sec (reference range 22.0-38.0 sec). The aPTT controls were in range. Which of the following interpretations would apply to the aPTT result? A. aPTT is abnormal because of a hereditary factor deficiency. B. aPTT is invalid because of contamination with tissue factor. C. Tube is probably not full, resulting in a falsely short time. D. Result is within reference range for a patient of this age.

B. A clean venipuncture is required for coagulation testing. The description of the traumatic venipuncture indicates that the result might be invalid because of exposure to tissue thromboplastin/tissue factor, resulting in a falsely short test result. A tube that is not full would cause a falsely long time. A factor deficiency causes long clotting times. This 5-year-old would have the same reference range as adults.

Reversal of a heparin overdose can be achieved by administration of A. Vitamin K B. Protamine sulfate C. Antithrombin D. Warfarin

B. A heparin overdose can result in hemorrhage. If bleeding becomes life threatening, protamine sulfate can be given. Heparin will dissociate from antithrombin if protamine sulfate is administered, because heparin has a higher affinity for protamine sulfate. Vitamin K can be administered in the management of bleeding for patients who overdose with warfarin, which is a synonym for Coumadin®.

Fibrin strands are cross-linked and the fibrin clot is stabilized by the activity of A. alpha2-Antiplasmin B. Factor XHIIIa C. Plasmin D. Thrombin

B. Activated factor XIII is a transglutaminase that cross-links fibrin monomers between glutamine and lysine residues. Fibrin monomers that are not cross-linked lack the stability to maintain the hemostatic plug, as evidenced by the bleeding problems experienced by individuals deficient in factor XIII. Thrombin contributes to the formation of the fibrin clot, which is degraded by plasmin. Once the fibrin clot has been lysed and plasmin is free in circulation, alpha2-antiplasmin quickly neutralizes plasmin.

A 4-year-old child is seen in the emergency department with petechiae and a platelet count of 15 x 10^9/L. She has no previous history of bleeding problems. Three weeks earlier she had chicken pox. The physician advises the parents to keep the child off the playground to avoid injury, and says the child will recover within 2-4 weeks with no further treatment. What condition does this child most likely have? A. Essential thrombocythemia B. Idiopathic thrombocytopenic purpura C. Thrombotic thrombocytopenic purpura D. Glanzmann thrombasthenia

B. Acute idiopathic thrombocytopenic purpura is mainly seen in young children. A viral infection often precedes the onset of symptoms by several weeks. In 90% of patients with acute ITP, there is an increase in IgG immunoglobulin attached to the surface of the platelets. Spontaneous remission occurs in most patients within 2-6 weeks of the onset of the illness. A chronic form of ITP, believed to be a different disease, is seen in adults.

A 25-year-old male presents to his physician complaining of leg pain. The physician diagnoses a deep vein thrombosis and wants to determine the cause of the thrombotic episode. Which of the following conditions would not be associated with such a thrombotic episode? A. Factor V Leiden and Prothrombin 20210 mutations B. Hypofibrinogenemia and hyperhomocysteinemia C. Lupus anticoagulant and anticardiolipin antibodies D. Antithrombin and protein C deficiencies

B. All of the conditions listed are associated with thrombosis except hypofibrinogenemia. Although hereditary dysfibrinogenemia frequently causes thrombosis, hypofibrinogenemia causes bleeding tendencies. The most common hereditary thrombotic disorder, factor V Leiden, is caused by synthesis of an abnormal factor V molecule that is resistant to the inhibitory affects of protein C. The Prothrombin 20210 mutation, in which an abnormal factor II molecule is synthesized, is the second most common hereditary thrombotic disorder.

A clot retraction defect is suspected in a newborn male experiencing severe bleeding following circumcision. The following results are obtained: Platelet count= 320 x 1 0^9/L Bleeding time= >15 min (reference range </ =8.0 min) Platelet aggregation= Normal response to ristocetin; weak response to ADP, collagen, epinephrine Prothrombin time= 1 2.0 sec (control 12.0 sec) aPTT= 31 .0 sec (control 32.0 sec) These results are characteristic of A. von Willebrand disease B. Glanzmann thrombasthenia C. Storage pool disease D. Christmas disease

B. Because the platelet count is within the reference range, the prolonged bleeding time is due to a qualitative platelet disorder. Poor clot retraction is characteristic of Glanzmann thrombasthenia. Clot retraction is normal in storage pool disease and von Willebrand disease. Christmas disease is caused by factor IX deficiency and does not affect platelet function. Glanzmann thrombasthenia can be further differentiated from von Willebrand disease by the platelet aggregation study results. The PT and aPTT results rule out a secondary hemostasis defect

The platelet aggregation pattern drawn below is characteristic of the aggregating agent A. ADP B. Collagen C. Ristocetin D. Thrombin

B. Collagen is the only aggregating agent that includes a single wave response preceded by a lag phase. During the lag phase collagen stimulates platelets to release their granule contents. Endogenous ADP released from the platelets then initiates irreversible platelet aggregation.

An 80-year-old man suffered a heart attack 1 month ago, and after the hospital stay was discharged with instructions to follow an outpatient treatment plan. He arrives at the cardiology clinic today for lab work to monitor the treatment plan. The following results are obtained: PT= 52.0 sec (control 1 2.0 sec) INR= 5.5 (therapeutic range 2.0-3.0) aPTT= 50.0 sec (control 32.0 sec) This patient is most likely on a A. Nontherapeutic dose of unfractionated heparin B. Nontherapeutic dose of coumarin C. Nontherapeutic dose of both unfractionated heparin and coumarin D. Fibrinolytic agent such as tissue plasminogen activator

B. Coumarin interferes with the function of vitamin K in the synthesis of prothrombin group factors II, VII, IX, and X. Tests that measure one or more of these factors will be prolonged. These factors are synthesized but are nonfunctional. Of the factors affected by coumarin, IX, X, and II are measured in the aPTT. VII, X, and II are measured in the PT. The patient is on a nontherapeutic dose of coumarin, and the INR demonstrates this. Unfractionated heparin (administered intravenously) and fibrinolytic activators are not used on an outpatient basis.

A 25-year-old obstetrical patient at 35 weeks gestation is admitted through the emergency room. She has bleeding in the genitourinary tract, and there are visible petechiae and ecchymoses. The following laboratory results are obtained: Platelet count= marked decreased Prothrombin time= prolonged aPTT= prolonged Fibrinogen= decreased Thrombin time= prolonged D-dimer= positive FDP= positive Antithrombin= decreased RBC morphology= schistocytes present These laboratory results are consistent with A. Primary fibrinogenolysis B. DIG with secondary fibrinolysis C. Factor II deficiency D. Heparin therapy

B. DIG is a consumption coagulopathy in which the fibrinogen group of factors I, V, VIII, XIII, as well as II in the prothrombin group, is consumed in systemic clotting faster than the liver can synthesize them. When the clotting system is activated, the fibrinolytic system is simultaneously activated. Degradation products form causing the FDP and D-dimer tests for degradation products to be positive. The thrombin time measures fibrinogen and is prolonged due to low fibrinogen and the presence of degradation products. Antithrombin is quickly depleted in an attempt to stop systemic clotting. Platelets are consumed in clotting, and schistocytes form as red blood cells fragment as they encounter fibrin strands in circulation.

The coagulation factors having a sex-linked recessive inheritance pattern are A. Factor V and factor VIII B. Factor VIII and factor IX C. Factor IX and factor X D. von Willebrand factor and factor VIII

B. Factor VIII and factor IX are the sex-linked recessive hemostatic defects, von Willebrand factor deficiency and dysfibrinogenemia are inherited as autosomal dominant disorders. Factor V, factor X, and most of the other inherited hemostatic disorders have an autosomal recessive inheritance pattern.

A clot retraction defect is most likely due to A. Lack of platelet receptor glycoprotein Ib B. Lack of platelet receptor glycoprotein Ilb/IIIa C. Insufficient ADP in dense bodies D. Absence of von Willebrand factor

B. Glanzmann thrombasthenia is a disorder characterized by absent or defective GP Ilb/IIIa platelet receptors for fibrinogen binding and subsequent platelet aggregation. Clot retraction in these patients is abnormal due to the lack of the contractile protein actomyosin/thrombasthenin. Neither insufficient ADP in dense bodies, absence of von Willebrand factor, nor absence of the platelet receptor glycoprotein Ib affects clot retraction. Lack of glycoprotein Ib, the von Willebrand factor receptor site, causes the platelet adhesion defect seen in Bernard-Soulier disease.

The size threshold range used by electrical impedance methods to count particles as platelets is A. 0-10 fL B. 2-20 fL C. 15-40fL D. 35-90 fL

B. In the electrical impedance method for counting platelets, particles between 2 and 20 fL will be classified as platelets by the analyzer's computer. The normal average platelet volume is 10 fL. One dilution is used for counting and sizing of platelets and red blood cells. In the electrical impedance method, size thresholds differentiate the two.

Which of the following does not contribute to the activation of the fibrinolytic system? A. Xlla B. XIa C. Kallikrein D. Tissue plasminogen activator

B. Once activated, three of the four contact factors activate both the intrinsic clotting system and provide intrinsic activation of the fibrinolytic system. The only contact factor that does not activate the fibrinolytic system is factor XL Extrinsic activation of the fibrinolytic system is achieved by the release of tissue plasminogen activator by damaged endothelial cells.

Which of the following enzymatically degrades the stabilized fibrin clot? A. Plasminogen B. Plasmin C. Prothrombin D. Thrombin

B. Plasmin, the active form of plasminogen, is the enzyme responsible for degrading fibrin into several different fragments. The D-dimer test is abnormal when there is excessive fibrinolytic activity. Prothrombin is the inactive precursor of thrombin that cleaves fibrinogen to form fibrin, which is stabilized by the activity of factor XIII.

A potent inhibitor of platelet aggregation released by endothelial cells is A. Epinephrine B. Prostacyclin C. Ristocetin D. Thromboxane A2

B. Prostacyclin, also referred to as PGI2, is the most potent inhibitor of platelet aggregation known. Injured endothelial cells release prostacyclin. Epinephrine and ristocetin are potent stimulators of platelet aggregation. Thromboxane A2, generated by platelets via the prostaglandin pathway, also stimulates platelets to aggregate.

The anticoagulant required for routine coagulation testing is A. Sodium heparin B. Sodium citrate C. Acid citrate dextrose D. Sodium fluoride

B. The Clinical and Laboratory Standards Institute (CLSI) recommends 3.2% (0.109 M) sodium citrate for coagulation testing. Sodium heparin is used for many chemistry tests, but will cause times that exceed linearity if used for coagulation tests. Acid citrate dextrose (ACD) is used for HLA phenotyping, DNA analysis, and paternity tests. Sodium fluoride is used for glucose testing.

The prothrombin time will detect deficiencies in the_____ pathway(s) when calcium and a tissue factor source such as rabbit brain are added to plasma. A. Extrinsic B. Extrinsic and common C. Intrinsic D. Intrinsic and common

B. The prothrombin time test measures the coagulant activity of the extrinsic and common pathway factors of I, II, V, VII, and X. The reagent used for the prothrombin time test contains calcium and tissue thromboplastin. Thromboplastin is an extract of tissue such as brain or placenta. The activated partial thromboplastin time test measures all coagulation factors present in the intrinsic and common pathways except factor XIII. Calcium, a phospholipid source, and an activating agent, such as kaolin, silica, or celite, are present in the reagents used for the activated partial thromboplastin time.

Why is the activated partial thromboplastin time (aPTT) not the procedure of choice for detecting a platelet factor 3 (PF3) deficiency? A. Platelet-rich plasma is used for this test. B. The reagent contains a phospholipid substitute for PF3. C. PF3 is unstable in the reagent used for this test. D. PF3 does not function in the system being tested.

B. The reagent used in the aPTT procedure is a phospholipid extract that substitutes for platelet factor 3 in coagulation reactions. Platelet-poor plasma is used, so thrombocytopenia does not affect the aPTT. Platelet factor 3 functions in the intrinsic and prothrombin-converting complexes that must form for blood coagulation to occur.

The following results are obtained on a 60-year-old male patient: WBC= 24.7 x 1 09/L RBC= 6.67x1012/L Hgb= 200 g/L Hct= 0.61 L/L Plt= 79 x 1 09/L PT= 19.3 sec(control 1 2.0 sec) aPTT= 8 1.2 sec (control 32.0 sec) The WBC, RBC, Hgb, Hct, and Pit were performed on blood collected in an evacuated tube containing EDTA. The PT and aPTT were performed on blood collected in an evacuated tube containing 3.2% sodium citrate. The standard collection procedure was followed, and all tests were performed within the appropriate time limits. Based on this information, the statement that best explains the prolonged coagulation test results is A. Coagulation reactions require platelet factor 3; availability of this component is insufficient when the platelet count is below 100xl09/L. B. The ratio of anticoagulant to blood is critical; the volume of anticoagulant must be decreased when the Hct is greater than 55%. C. The PT and aPTT evaluate the extrinsic and intrinsic pathways, respectively; prolongation of both tests indicates a deficiency of a factor common to both systems. D. Coagulation reactions are inhibited by a product released by leukocytes; this inhibitory activity becomes significant when the leukocyte count is greater than 20.0 x 109/L.

B. The required blood-to-anticoagulant ratio for coagulation testing is 9:1. If a volume of blood contains an elevated number of RBCs, generally considered to be a hematocrit greater than 55%, this ratio will be affected. Excess sodium citrate in the patient plasma, which acts as an anticoagulant by binding calcium ions, will bind the reagent calcium added back to the test plasma during the procedure. Falsely prolonged results are obtained. The specimen needs to be redrawn using less sodium citrate

A patient on therapeutic warfarin will most likely have a(n) A. Normal PT/INR, increased aPTT, prolonged bleeding time, low platelet count B. Increased PT/INR, increased aPTT, normal bleeding time, normal platelet count C. Normal PT/INR, normal aPTT, normal bleeding time, normal platelet count D. Increased PT/INR, normal aPTT, prolonged bleeding time, low platelet count

B. Warfarin is a vitamin K antagonist and affects liver synthesis of the prothrombin group factors II, VII, IX, and X. The factors are produced but are nonfunctional. Warfarin therapy is monitored with the prothrombin time (PT), which will detect nonfunctional II, VII, and X. The aPTT, though used to monitor heparin therapy, can detect nonfunctional II, IX, and X caused by warfarin therapy. Warfarin does not affect platelet function or quantity. Aspirin and other antiplatelet medications such as clopidogrel bisulfate (Plavix®) will affect platelet function and prolong the bleeding time.

The operating principle of a platelet aggregometer is best described as A. Aggregation on a foreign surface: Platelet aggregation is directly proportional to the difference in platelet counts performed before and after platelet-rich plasma is passed through a column of glass beads. B. Change in optical density: As platelets aggregate, the optical density of the platelet-rich plasma decreases. C. Electrical impedance: Platelet aggregates are counted as they pass through an aperture, temporarily interrupting the flow of current between two electrodes. D. Pulse editing: Editing electronically generated pulses can differentiate the number of free platelets versus platelet aggregates.

B. When an aggregating agent is added to an optically dense suspension of platelet-rich plasma (PRP), the platelets normally stick to each other, forming platelet aggregates. As additional platelets aggregate, the cell suspension becomes clearer and has a few large clumps of cells. At maximum aggregation the specimen is relatively clear, allowing light transmission that is only partially obstructed by a few large platelet aggregates

von Willebrand factor is a A. Phospholipid required for multiple reactions in the coagulation sequence B. Plasma protein that binds platelets to exposed subendothelial collagen C. Plasma protein with procoagulant activity in the intrinsic coagulation system D. Platelet membrane glycoprotein that attaches the platelet to the injured vessel wall

B. von Willebrand factor (vWF) is a portion of the plasma protein known as the factor VHI/von Willebrand factor complex. Its function is to bind to platelet membrane glycoprotein Ib and form a bridge between the platelet and exposed subendothelial collagen. vWF is a carrier protein for factor VIII:C, but vWF does not have coagulant activity in secondary hemostasis as factor VIILC does.

A normal histogram showing platelet size distribution is best described as A. Bimodal, nonskewed peaks B. Left-skewed single peak C. Right-skewed single peak D. Single peak, Gaussian distribution

C. A histogram showing platelet size distribution is made by plotting platelet size (x axis) versus number (y axis). The resulting curve is usually a single, right-skewed peak. This reflects a larger number of platelets in the lower size range with a "tail" of larger cells to the right of the majority

Screening tests for a 46-year-old male patient admitted for minor surgery follow: Platelet count= 325 x 1 0^9/L Bleeding time= 4.5 min (reference range </= 8.0 min) Prothrombin time= 13.0 sec (control 12.0 sec) aPTT= 95.0 sec (control 32.0 sec) aPTT 1:1 mixing study= 32.0 sec The patient has no clinical manifestations of a bleeding problem and has no personal or family history of bleeding problems, even following dental extraction. Several family members have been treated for deep vein thrombosis. Based on these laboratory results and the clinical history, the most likely cause of the prolonged aPTT is A. Heparin present in the sample B. Factor VIII deficiency C. Factor XII deficiency D. Factor XIII deficiency

C. An abnormal aPTT that corrects with a 1:1 mixing study, and a normal PT indicate a deficiency in the intrinsic coagulation pathway. Because factor XII is an activator of the fibrinolytic system, a deficiency can result in thrombosis. Presence of heparin in the sample would cause noncorrection of the mixing study. Factor VIII deficiency causes bleeding into muscles and joints, not thrombosis. Factor XIII can be eliminated because it is not measured in the aPTT or PT, and a deficiency would cause a bleeding disorder.

A prolonged aPTT result is obtained on a patient diagnosed with acute disseminated intravascular coagulation (DIG). The patient has not yet been treated for this disorder. The most likely cause of the prolonged aPTT is A. In addition to DIG, the patient is deficient in a factor required for the extrinsic pathway. B. DIG is characterized by synthesis of less stable coagulation factors, which deteriorate rapidly in the circulation. C. Systemic activation of the coagulation system depletes some factors more rapidly than the liver can synthesize them. D. The patient has been misdiagnosed; a prolonged aPTT indicates that the problem is deficient, not excessive, coagulation.

C. As coagulation occurs in vivo, some factors are consumed just as they are when blood is allowed to clot in a test tube in vitro. The factors consumed during coagulation are I, II, V, VIII, and XIII. Results of laboratory procedures relying on one or more of these factors will be affected. All these factors except factor XIII contribute to the reactions evaluated in the aPTT procedure.

A platelet aggregation agent that characteristically yields a biphasic curve when used in optimal concentration is A. Arachidonic acid B. Collagen C. Epinephrine D. Ristocetin

C. Epinephrine is the only aggregating agent listed that typically gives a biphasic pattern. ADP and thrombin also give biphasic patterns when used in optimal concentrations. Arachidonic acid causes a rapid monophasic platelet aggregation. Collagen and ristocetin also induce monophasic aggregatory responses

Phlebotomist Forgetful Frank collected a tube of blood for an aPTT on John Smith at 10:00 A.M. The blood was collected in a sodium citrate tube. At 4:30 P.M., Frank was getting ready to leave for the day when he discovered Mr. Smith's blood specimen on his blood collection tray. So before leaving, Frank delivered the tube of blood to the laboratory for testing. Which of the following best describes the expected results? A. Sodium citrate is a preservative as well as an anticoagulant, so the aPTT result should be accurate. B. An aPTT collected in sodium citrate will give falsely long results because some factors are unstable in this anticoagulant. C. A falsely long aPTT is expected because some factors deteriorate rapidly at room temperature. D. Exposure of the plasma to erythrocytes for several hours has probably activated the factors, so the aPTT will be falsely short.

C. Factors V and VIII are labile and deteriorate rapidly at room temperature. Blood for aPTT testing should be tested within 4 hours of draw. Sodium citrate is the appropriate anticoagulant for coagulation procedures.

The following results are obtained on a 3-year-old boy with sudden severe hemorrhagic problems: Bleeding time= 5.0 min (reference range </= 8.0 min) Prothrombin time= 13.0 sec (control 12.0 sec) aPTT= 95.0 sec (control 32.0 sec) aPTT1:1 mixing study= 35.0 sec Platelet aggregation= Normal with ristocetin, ADP, collagen, and epinephrine These clinical manifestations and laboratory results are consistent with A. Aspirin therapy B. von Willebrand disease C. Hemophilia A D. Heparin therapy

C. Hemophilia A is inherited as a sex-linked recessive disorder of factor VIII:C. Mothers are carriers who pass the disease on to male offspring. This disorder is strictly a secondary hemostasis defect, so tests for primary hemostasis such as the bleeding time and platelet aggregation studies are normal. Factor deficiencies correct when a 1:1 mixing study is performed; presence of heparin in the sample would result in little or no correction of the mixing study. Aspirin affects platelets in primary hemostasis

In platelet aggregation studies, certain aggregating agents induce a biphasic aggregation curve. This second phase of aggregation is directly related to A. Formation of fibrin B. Changes in platelet shape C. Release of endogenous ADP D. Release of platelet factor 3

C. In platelet aggregation studies, the addition of the aggregating agent may induce an initial aggregation phase followed by a secondary wave. The initial phase is due to the interaction of the aggregating agent with the platelet. The second phase is due to release of nonmetabolic ADP from platelet granules, which promotes the additional wave of aggregation.

Which of the following is not a normal maturation stage for platelets? A. Megakaryoblast B. Promegakaryocyte C. Micromegakaryocyte D. Megakaryocyte

C. Micromegakaryocytes, also known as dwarf megakaryocytes, are thought to be megakaryocytes that have lost their ability to undergo endomitosis. They can be seen in the peripheral blood of patients with myelodysplastic syndromes or myeloproliferative disorders. They may resemble lymphocytes, but cytoplasmic blebs can help to identify them as micromegakaryocytes

Thrombocytosis is a characteristic of A. Disseminated intravascular coagulation B. Splenomegaly C. Polycythemia vera D. Idiopathic thrombocytopenic purpura

C. Polycythemia vera, a hemopoietic stem cell disorder characterized by excessive production of erythrocytic, granulocytic, and megakaryocytic cells in the bone marrow, is usually accompanied by thrombocytosis. ITP, DIG, and splenomegaly are all characterized by thrombocytopenia. In ITP, platelet destruction is mediated by immune mechanisms. Platelets are consumed in DIG and sequestered in an individual with an enlarged spleen.

Prekallikrein deficiency is associated with A. Prolonged aPTT that does not correct with a mixing study B. Autosomal dominant inheritance C. Increased risk of thrombosis D. Delayed bleeding at the incision site following surgery

C. Prekallikrein (Fletcher factor) deficiency is one of the many autosomal recessive disorders. The aPTT will be prolonged and will correct with a mixing study because it is a factor deficiency. Because prekallikrein is an activator of the fibrinolytic system, prekallikrein-deficient patients cannot lyse clots efficiently and are prone to thrombosis. Fibrinolytic and anticoagulant therapies are indicated in patients who develop thrombosis. Delayed post-operative bleeding at the incision site is characteristic of a factor XIII deficiency.

A 65-year-old patient in the emergency department has a normal D-dimer and an elevated FDP result. These results are consistent with the presence of degradation products of A. Non-cross-linked fibrin B. Cross-linked fibrin C. Fibrinogen D. Plasmin

C. The D-dimer is a specific marker of fibrinolysis. A normal D-dimer test can be used to rale out the formation of a clot. The D-dimer test will be elevated when a clot has formed, factor XIII has cross-linked fibrin, and the fibrinolytic system is lysing the clot. The FDP detection test will be abnormal whether fibrin degradation products or fibrinogen degradation products are present. Because the D-dimer is normal in this patient, fibrin degradation products have not formed, but fibrinogen degradation products are present resulting in the elevated FDP result

The reference value for mean platelet volume (MPV) is approximately A. 2-4 fL B. 5-7 fL C. 8-10 fL D. 11-14 fL

C. The average volume of normal platelets is approximately 8-10 fL. This platelet parameter is equivalent to the erythrocyte parameter MCV (mean corpuscular volume). MPV is increased in the hereditary Bernard-Soulier syndrome and May-Hegglin anomaly; also in acquired disorders with increased need for platelet release from the bone marrow.

An aPTT and PT are requested on a patient scheduled for emergency surgery. On an optical density clot detection system, normal and abnormal controls for both tests are within range, but the patient's results exceed the upper limit of linearity. The patient's aPTT and PT have been performed in duplicate, but there still is sufficient plasma, which is grossly lipemic, to repeat the tests. What is the best course of action to follow? A. Report the results immediately by phone, emphasizing that the tests were run in duplicate and the controls are within range. B. Request a new specimen and repeat the aPTT and PT using freshly diluted controls. C. Repeat the aPTT and PT on an instrument that detects clot formation electromechanically. D. Inform the physician that accurate results are impossible.

C. The lipemic plasma may interfere with the detection of fibrin clot formation by instruments measuring a change in optical density. The change in optical density may be insufficient for detection. The most accurate results in this situation can be obtained by performing the procedure on an electromechanical fibrin clot detection instrument, such as a fibrometer. Requesting a new specimen will be of no use because the redraw will most likely also be lipemic.

The coagulation factors referred to as "vitamin K-dependent" are A. I, V, VIII, XIII B. II, V, IX, XII C. II, VII, IX, X D. XI, XII, Fletcher, Fitzgerald

C. The prothrombin group factors II, VII, IX, and X are called vitamin K-dependent factors. Vitamin K is needed by the liver to synthesize functional circulating forms of these factors. In the absence of vitamin K, the liver synthesizes the prothrombin group factors, but they are nonfunctional because they lack the carboxyl (COOH) groups needed for binding to Ca2+ on phospholipid membranes. The oral anticoagulant warfarin is a vitamin K antagonist and causes liver synthesis of these nonfunctional factors.

Which of the following is not a cause of thrombocytopenia? A. Splenomegaly B. Chemotherapy C. Increased thrombopoietin D. Aplastic anemia

C. Thrombopoietin is the major humoral factor involved in platelet production. Increased thrombopoietin results in thrombocytosis; decreased thrombopoietin results in thrombocytopenia. Two-thirds of platelets, once released from the bone marrow, are in circulation. The other onethird of platelets is sequestered in the spleen. Splenomegaly is a cause of thrombocytopenia due to increased sequestration. Chemotherapeutic agents destroy both normal and malignant cells, causing thrombocytopenia, anemia, and leukopenia. Aplastic anemia occurs when the bone marrow fails to produce any of the three cell lines

A patient on warfarin therapy will be deficient in a functional amount of A. Fibrinogen and prothrombin B. Stable and labile factors C. Protein C and protein S D. Fletcher and Fitzgerald factors

C. Vitamin K is required for liver synthesis of regulatory proteins C and S and functional clotting factors II, VII, IX, and X. A deficiency of vitamin K decreases the concentrations of these proteins and subsequently affects test results that measure one or more of them. Fibrinogen, Labile, Fletcher, and Fitzgerald factors do not require vitamin K for their synthesis.

Results on a 35-year-old male presenting with sudden severe hemorrhagic problems are as follows: Platelet count= 225x10^9/L Bleeding time= 6.5 min (reference range </= 8.0 min) Prothrombin time= 12.8 sec (control 12.0 sec) aPTT= 85.0 sec (control 32.0 sec) aPTT1:1 mixing study= 65.0 sec These clinical manifestations and laboratory results are consistent with A. Lupus anticoagulant B. von Willebrand disease C. Hemophilia A D. Factor VIII inhibitor

D. Failure of normal plasma to correct the aPTT indicates the presence of a circulating inhibitor. A factor VIII inhibitor is associated with hemorrhagic problems and would result in noncorrection of the mixing study. Hemophilia A and von Willebrand disease are both caused by factor deficiencies that would result in correction when a 1:1 mixing study is performed. The lupus anticoagulant is a circulating inhibitor that prolongs the aPTT with little or no correction of the mixing study, but it is associated with thrombosis, not severe hemorrhagic problems.

A fibrinogen assay is performed on the fibrometer using the standard 1:10 dilution with Owren's buffer. The seconds obtained do not read on the standard curve. An alternate 1:20 dilution is performed and is 400 mg/dL when read off the curve. The concentration of fibrinogen to be reported in mg/dL is A. 160 mg/dL B. 200 mg/dL C. 400 mg/dL D. 800 mg/d

D. A 1:20 dilution is used when the time obtained on a patient sample is less than the shortest time used in preparation of the standard curve. A 1:20 dilution is diluted by a factor of 2 when compared to the usual 1:10 dilution. The value read off the curve must be multiplied by 2 to take into account the alternate dilution used. 400 x 2 = 800 mg/dL

An 85-year-old male with slurred speech and paralysis on the right side of the body is seen in the emergency department. A stat D-dimer is ordered and is very high. The physician suspects a thromboembolic event based on the D-dimer, and needs to institute clot-dissolving therapy immediately. The most likely diagnosis and appropriate therapy for the patient is A. Myocardial infarction; treat with aspirin B. Pulmonary embolism; treat with warfarin C. Deep vein thrombosis; treat with heparin D. Stroke; treat with tissue plasminogen activator

D. A high D-dimer level indicates the presence of a thrombus (deep vein thrombosis, pulmonary embolism) but is not useful in determining the location. If a thrombus breaks away and travels to the brain, a stroke occurs, causing the symptoms described in this patient. Tissue plasminogen activator will activate the fibrinolytic system to lyse the clot. It should be administered within hours of onset of symptoms to prevent irreversible brain damage. Because of the small window of treatment time, a D-dimer performed on a possible stroke patient should be done STAT. Aspirin, warfarin, and heparin can be administered to prevent the formation of new clots but will not lyse existing clots.

The number of platelets an average megakaryocyte generates is approximately A. 25-50 B. 50-200 C. 200-500 D. 2000-4000

D. Each megakaryocyte produces approximately 2000- 4000 platelets. A single megakaryocyte can generate this large number of cells because platelets are nonnucleated fragments of their cytoplasm. The number of platelets generated by a megakaryocyte depends on its cell size, which is directly related to the number of endomitotic divisions before cytoplasmic fragmentation.

In which of the following functions are the products released by vascular endothelial cells not involved? A. Inhibition of platelet aggregation B. Activation of the fibrinolytic system C. Conversion of thrombin from a procoagulant to an anticoagulant D. Cross-linkage of fibrin monomers

D. Endothelial cells release prostacyclin, which is a potent inhibitor of platelet aggregation. They also release tissue plasminogen activators, which initiate the fibrinolytic system. When thrombin binds with thrombomodulin on the endothelial cell surface, the specificity of thrombin changes. Rather than converting fibrinogen to fibrin, thrombin complexed with thrombomodulin activates protein C. Protein C along with protein S inhibits clotting by "turning off" factors V and VIII. Factor XIII is responsible for cross-linking fibrin monomers but it is not a component of endothelial cells.

Epsilon aminocaproic acid is the treatment of choice for A. von Willebrand disease B. Hemophilia A C. DIG with secondary fibrinolysis D. Primary fibrinogenolysis

D. Epsilon aminocaproic acid (EACA) is a specific inhibitor of plasmin and is used to turn off inappropriate lysing that occurs in primary fibrinogenolysis. Fibrinolysis seen in DIC is an appropriate body response to systemic clotting. If EACA is administered to a patient in DIC, clots that form will not be lysed, and this could be quickly fatal to the patient.

Heparin inhibits clotting by A. Chelating calcium ions B. Preventing activation of prothrombin C. Causing liver synthesis of nonfunctional factors D. Enhancing the action of antithrombin

D. Heparin forms a complex with antithrombin to inhibit coagulation. The heparin-antithrombin complex rapidly inhibits thrombin and other serine proteases. Coagulation may be inhibited by coumarin and related vitamin K antagonists that cause liver synthesis of nonfunctional prothrombin group factors II, VII, IX, and X. Several anticoagulants, such as sodium citrate and EDTA, prevent fibrin formation by chelating calcium ions, which serve as cofactors in several reactions in the coagulation cascade.

The platelet parameter PDW refers to the A. Average platelet volume B. Cell weight versus density C. Capacity to adhere to foreign surfaces D. Variation in platelet cell size

D. PDW is an abbreviation for platelet distribution width. This parameter measures the uniformity of platelet size. It is the platelet equivalent of the red cell parameter RDW. It represents the coefficient of variation of the platelet population

The recommended type of microscopy for the performance of manual platelet counts is A. Electron B. Dark field C. Light D. Phase contrast

D. Phase microscopy is currently recommended for manual platelet counts. This allows satisfactory discrimination between platelets and debris, a major problem in manual counts. Light microscopy may also be used; however, differentiating between platelets and debris is more difficult than with phase microscopy

Laboratory tests requested on a patient scheduled for early morning surgery include a CBC with platelet count. An automated platelet count performed on the specimen is 57 x 10^9/L. In the monolayer area of the peripheral blood smear there are approximately 12 platelets per oil immersion field, many of which are encircling neutrophils. Controls are in range. Based on this information, the best course of action is A. Report all the results because the instrument is functioning properly. B. Alert the physician immediately so cancellation of surgery can be considered. C. Thoroughly mix specimen and repeat platelet count; if results remain the same, report all results and indicate that platelet count has been confirmed by repeat testing. D. Have the specimen redrawn using 3.2% sodium citrate as the anticoagulant.

D. Platelets encircling neutrophils is a phenomenon referred to as platelet satellitosis. This "pseudothrombocytopenia" occurs when the blood of some individuals is anticoagulated with EDTA. Recollecting the specimen using sodium citrate often corrects this problem. If sodium citrate is used, the platelet count obtained must be multiplied by 1.1 for reporting purposes. Multiplying by 1.1 adds back the 10% loss of platelets seen when sodium citrate, with a 9:1 ratio of blood to anticoagulant, is used.

Which of the following test results is not characteristic of DIG? A. Decreased fibrinogen concentration B. Positive test for degradation products C. Decreased platelet count D. Increased antithrombin

D. The PT and aPTT are prolonged in DIG because of consumption of factors I, II, V, and VIII. Platelets are trapped in forming clots and are removed from circulation. The fibrinolytic system is activated by systemic intravascular coagulation; fibrin and fibrinogen degradation products are elevated. FDP and D-dimer tests will both be positive. The regulatory proteins antithrombin, protein C, and protein S are depleted trying to turn off systemic clotting.

If a physician suspects a qualitative platelet defect, the most useful test to order is the A. Platelet count B. Prothrombin time C. 5.OM urea solubility test D. Bleeding tim

D. The bleeding time test is a primary hemostasis screening test for platelet and vascular' function. The platelet count is a quantitative test that cannot be used to determine platelet function. The prothrombin time is a secondary hemostasis screening test and does not evaluate platelet function because platelet-poor plasma is used for testing. The 5 M urea solubility test will detect a factor XIII deficiency.

Which of the following complexes is not needed for blood coagulation to occur? A. Vila, tissue factor, Ca2+ B. IXa, VIII, Ca2+, PF3 C. Xa, V, Ca2+, PF3 D. Xlla, kallikrein, HMWK

D. The intrinsic, extrinsic, and common pathways each have a complex that must form for blood coagulation to occur. The intrinsic complex of IXa, VIII, and Ca2+ forms on the platelet surface (PF3) and activates factor X. The extrinsic complex of Vila, tissue factor, and Ca2+ activates factor X as well as factor IX and is the dominant pathway in vivo. Factor IX activation by the extrinsic complex provides a link between the intrinsic and extrinsic systems and minimizes the importance of the contact factors in vivo. The prothrombin-converting complex of Xa, V, Ca2+, and PF3 is responsible for converting prothrombin to thrombin.

Which of the following is not synthesized in the liver? A. Factor VIII B. Plasminogen C. Protein C D. von Willebrand factor

D. The liver produces most of the clotting factors as well as inhibitors to clotting. A patient with liver disease has impaired synthesis of these clotting factors and inhibitors. One of the few hemostatic proteins not produced by the liver is von Willebrand factor, which is produced by endothelial cells and megakaryocytes.

The activity of the lupus anticoagulant and anticardiolipin antibodies appears to be directed against A. Factor V B. FactorVIII C. Factor IX D. Phospholipid

D. The lupus anticoagulant was first discovered in patients with systemic lupus erythematosus. It is actually seen in more patients without SLE, but the original name remains. Lupus anticoagulant and anticardiolipin antibodies belong to the antiphospholipid antibody family. Their activity appears to be directed against the phospholipid portion of the prothrombinase complex (Xa-Vphospholipid-calcium). The antibodies are usually IgG, but can also be IgM. They are found in autoimmune disorders, neoplasms, and some infections. They can also be medication related and can be found in apparently normal individuals. Their presence is suspected when the patient is experiencing thrombosis and the aPTT is prolonged with no correction of the mixing study.

Laboratory results on a 16-year-old female with frequent nosebleeds and severe menorrhagia are as follows: Platelet count= 250 x 1 09/L Bleeding time= >15 min (reference range <8.0 min) Prothrombin time= 1 3.0 sec (control 1 2.0 sec) aPTT= 75.0 sec (control 32.0 sec) Platelet aggregation= Normal response to ADP, collagen, epinephrine; no response with ristocetin These results are consistent with A. Christmas disease B. Hemophilia A C. Glanzmann thrombasthenia D. von Willebrand disease

D. The patient's platelet count is within the reference range, but the bleeding time is prolonged. This indicates a platelet function problem. The coagulation tests indicate a problem in the intrinsic clotting system (factors XII, XI, IX, VIII, Fitzgerald, and Fletcher). The one disorder in which both platelet function and the coagulant property of factor VIII:C are affected is von Willebrand disease. A synonym for von Willebrand factor is the ristocetin cofactor. In its absence, platelets will not aggregate with ristocetin. The platelet aggregation pattern confirms this diagnosis.

A 24-year-old female with painful swelling in her left leg is seen by her physician, who orders laboratory testing for PT and aPTT. The PT is normal. The aPTT is prolonged, but shortens with a 10-minute incubation of patient plasma with partial thromboplastin reagent that uses kaolin as the activator. A 1:1 aPTT mixing study corrects to normal. The most likely diagnosis is A. Factor II deficiency B. FactorVIII inhibitor C. Factor XIII deficiency D. Prekallikrein deficiency

D. The patient's symptoms suggest a possible deep vein thrombosis. An increased incubation time of patient plasma with aPTT reagent using kaolin is considered to be a screening test for prekallikrein deficiency. The additional incubation time allows for increased activation of the contact factors, thus shortening the aPTT. Because prekallikrein is an activator of fibrinolysis, a deficiency causes an increased thrombotic risk in the patient. A factor II deficiency would not give a normal PT result. A factor XIII deficiency can only be detected by performing a 5.0 M urea solubility test. A factor VIII inhibitor would cause noncorrection of the mixing study. All conditions listed except prekallikrein deficiency would cause bleeding symptoms.

Which of the following will not cause the thrombin time to be prolonged? A. Fibrin degradation products B. Heparin C. Factor I deficiency D. Factor II deficiency

D. The thrombin time is a test that measures fibrinogen. Thrombin reagent is added to undiluted patient plasma, and the time it takes for fibrinogen conversion to fibrin is measured. Anything that interferes with the ability of thrombin to convert fibrinogen to fibrin will prolong the test. Heparin and the degradation products X and E inhibit thrombin. Factor II cannot be measured in the thrombin time because the reagent used is its active form, thrombin (IIa)

The expected screening test results for a patient with a fibrin stabilizing factor deficiency are A. Prolonged prothrombin time B. Prolonged activated partial thromboplastin time C. Prolonged prothrombin time and activated partial thromboplastin time D. Normal prothrombin time and activated partial thromboplastin time

D. Thrombin converts fibrinogen to the fibrin monomer. Fibrin monomers spontaneously polymerize to form the fibrin polymer. This is the endpoint of clot-based PT and aPTT tests. This fibrin polymer is unstable. Once activated, factor XIII, also known as fibrin stabilizing factor, produces strong, covalent bonds to create a stable fibrin polymer. This occurs after the endpoint of the PT and aPTT has been reached. A factor XIII deficiency is suspected when delayed post-operative bleeding occurs at the incision site, and the deficiency can be confirmed with the 5 M urea clot solubility test.

A patient in the hospital for an acute myocardial infarction is placed on standard unfractionated heparin therapy and aspirin. Laboratory results are performed before instituting therapy and then daily as shown: Prothrombin Time= Before Therapy (norm), Day2 (norm), Day3 (norm) aPTT= before therapy (norm), Day2 (prolonged), Day3 (prolonged) Platelet Count=before therapy (325x10^9/L), Day2 ( 160 x 1 0^9/L), Day3 (42 x 1 0^9/L) The most likely complication by Day 3 is A. Disseminated intravascular coagulation B. Primary fibrinogenolysis C. Aspirin-induced thrombocytopenia D. Heparin-induced thrombocytopenia

D. Up to 5% of patients receiving unfractionated heparin therapy for more than 5 days develop an IgG antibody that can cause platelet activation, leading to thrombosis in the microvasculature. If this occurs, the platelet count drops quickly. Patients receiving heparin therapy should be monitored with daily platelet counts. Direct thrombin inhibitors such as lepirudin, bivalirudin, and argatroban can be used in place of heparin. Enoxaparin sodium, a low-molecular-weight heparin, is contraindicated as a treatment for heparin-induced thrombocytopenia. Aspirin therapy causes a qualitative, not quantitative, platelet defect.