Medical Laboratory Science Review Harr 2.5 Coagulation: Hemostsis Problem Solving

C. ITP

C These clinical manifestations and laboratory results are consistent with ITP. ITP is an autoimmune thrombocytopenia. In children, acute ITP thrombocytopenia occurs following a viral infection, as is the case in this 3-year-old patient. Clinical manifestations are associated with petechiae, purpura, and mucous membrane bleedings such as epistaxis and gingival bleeding. Abnormal laboratory tests include a very low platelet count and a prolonged bleeding time. Other causes of thrombocytopenia should be ruled out in patients with ITP.

Patient History

A 3-year-old male was admitted to a hospital with scattered petechiae and epistaxis. The patient had normal growth and had no other medical problems except for chickenpox 3 weeks earlier. His family history was unremarkable. Laboratory Results

Patient; Reference Range

PT: 11 sec; 10-13 sec

APTT: 32 sec; 28-37 sec

Platelet count: 18 × 103/µL; 150-450 × 103/µL

These clinical manifestations and laboratory results are consistent with which condition?

A. TTP

B. DIC

C. ITP

D. HUS

B. von Willebrand's disease

B These clinical manifestations and laboratory results are consistent with von Willebrand's disease. Von Willebrand's disease is an inherited bleeding disorder caused by abnormal platelet adhesion. Platelet adhesion depends on VWF and glycoprotein Ib. In von Willebrand's disease, VWF is deficient or dysfunctional. VWF promotes secondary hemostasis by acting as a carrier for factor VIII. Deficient or dysfunctional VWF results in decreased factor VIII and therefore abnormal secondary hemostasis. The clinical manifestations associated with von Willebrand's disease are easy bruising, epistaxis, and bleeding after surgery. Abnormal laboratory test results are increased bleeding time and abnormal platelet aggregation to ristocetin, which is corrected on addition of normal plasma containing VWF. Activated partial thromboplastin time (APTT) is prolonged as a result of the deficiency of factor VIII. Factor VIII activity (VIII:C), VWF ristocetin cofactor activity (VWF:Rco), and VWF:antigenic activity (VWF:antigen) are all abnormal. The platelet count and prothrombin time are normal in von Willebrand's disease.

A 12-year-old white male has the following symptoms: visible bruising on arms and legs, bruising after sports activities, and excessive postoperative hemorrhage following tonsillectomy 3 months ago. His family history revealed that his mother suffers from heavy menstrual bleeding, and his maternal grandfather had recurrent nosebleeds and bruising.

Laboratory Results

Patient; Reference Range

Platelet Count: 350 × 103/µL; 200-450 × 103/µL

PT: 11.0 sec; 10-12 sec

APTT: 70 sec; 28-37 sec

TT: 13 sec; 10-15 sec

Platelet Aggregation:

Normal aggregation with collagen, epinephrine, ADP

Abnormal aggregation with ristocetin

Confirmatory Tests:

Patient; Range Reference

VWF:Rco 25%; 45%-140%

VIII:C 20%; 50%-150%

vWF:antigen 10%; 45%-185%

These clinical manifestations and laboratory results are consistent with which diagnosis?

A. Factor VIII deficiency

B. von Willebrand's disease

C. Glanzmann's thrombasthenia

D. Bernard-Soulier syndrome

D. Cryoprecipitate

D Cryoprecipitate contains fibrinogen, factor VIII, and VWF. Fresh frozen plasma has all of the clotting factors; however, it is not the best choice if cryoprecipitate is available

The following results are obtained from a patient who developed severe bleeding:

Prolonged PT and APTT

Platelet count = 100 × 109 /L

Fibrinogen = 40 mg/dL

Which of the following blood products should be recommended for transfusion?

A. Factor VIII concentrate

B. Platelets

C. Fresh frozen plasma

D. Cryoprecipitate

C. Platelet counts

C The platelet count should be checked every other day in patients receiving heparin therapy. Heparin-induced thrombocytopenia (HIT) should be suspected in patients who are not responding to heparin therapy and/or are developing thrombocytopenia (50% below the baseline value) and thrombotic complications while on heparin therapy. Increase in heparin dose should be avoided in patients with the clinical symptoms of thrombosis while they are receiving heparin. Fibrinogen assay and PT are not the appropriate assays for monitoring heparin therapy, nor are they used to test for HIT.

A 30-year-old woman develops signs and symptoms of thrombosis in her left lower leg following 5 days of heparin therapy. The patient had open-heart surgery 3 days previously and has been on heparin ever since. Which of the following would be the most helpful in making the diagnosis?

A. Fibrinogen assay

B. Prothrombin time

C. Platelet counts

D. Increased heparin dose

D. Factor VIII inhibitor

D Factor VIII inhibitor is found in 10%-20% of hemophilia patients receiving replacement therapy. It may also develop in patients with immunologic problems, women after childbirth, and patients with lymphoproliferative and plasma cell disorders, or it may develop in response to medications. Factor VIII inhibitor is an IgG immunoglobulin with an inhibitory effect that is time and temperature dependent. The presence of factor VIII inhibitor causes an elevated APTT in the face of a normal prothrombin time. Mixing studies in factors VIII and IX deficiencies will correct the prolonged APTT both at the immediate mixing stage and after incubation for 2 hours. The APTT would not be corrected by mixing studies if lupus anticoagulant was present. In addition, lupus anticoagulant is not associated with bleeding unless it coexists with thrombocytopenia.

The following laboratory results were obtained on a 25-year-old woman with menorrhagia after delivery of her second son. The patient has no

previous bleeding history.

Normal platelet count; normal bleeding time; normal PT; prolonged APTT Mixing of the patient's plasma with normal plasma corrected the prolonged APTT on immediate testing. However, mixing followed by 2-hour incubation at 37°C caused a prolonged APTT. What is the most probable cause of these laboratory results?

A. Lupus anticoagulant

B. Factor VIII deficiency

C. Factor IX deficiency

D. Factor VIII inhibitor

C. Cirrhosis of the liver

C The clinical presentation and laboratory results in this patient are indicative of cirrhosis of the liver. Most of the clotting factors are made in the liver. A decrease in multiple clotting factors is associated with a prolonged PT and APTT. Macrocytosis and target cells are present in liver disease. The liver changes the unconjugated bilirubin to conjugated bilirubin. Conjugated bilirubin is excreted into the intestines, where the bilirubin is then converted to urobilinogen and excreted into the stool. In cirrhosis of the liver, both necrosis and obstruction caused by scarring produce an increase in unconjugated and conjugated bilirubin, respectively. In addition, the liver enzymes are elevated (the AST:ALT ratio is <1 in necrotic liver diseases such as hepatitis but not in cirrhosis).

A 62-year-old female presents with jaundice and the following laboratory data:

Peripheral blood smear: macrocytosis, target cells

Platelet count: 355 × 109/L

PT: 25 sec (reference range =10-14)

APTT: 65 sec (reference range = 28-36)

Transaminases: elevated (AST:ALT>1)

Total and direct bilirubin: elevated

These clinical presentations and laboratory results are consistent with:

A. Inherited factor VII deficiency

B. DIC

C. Cirrhosis of the liver

D. von Willebrand's disease

C. The mixing study needs to be repeated

C In mixing studies, correction occurs if a prolonged APTT result drops to within 10% of the result of normal human plasma. Only 50% factor activity is required for a normal PT or APTT. Clotting results >15% are not considered corrected, and results between 10%-15% should be repeated. A circulating anticoagulant typically results in failure to correct the APTT with normal plasma

When performing a mixing study, the patient's APTT is corrected to 12% of normal. What is the most appropriate interpretation of these findings?

A. The APTT is considered corrected

B. The APTT is considered uncorrected

C. The mixing study needs to be repeated

D. A circulating anticoagulant can be ruled out

C. Check the sample for a clot

C A clot can form because of inadequate mixing of the sample after venipuncture, if the blood fills the evacuated tube at a slow rate, or with traumatic venipuncture. In vitro, blood clots result in consumption of the clotting factors and therefore prolongation of PT, APTT, and other clot-based assays. If the clotting factors have been activated but the clot formation is incomplete, it may result in shortening of the PT and APTT. Checking the sample for a clot is the most reasonable step in this case.

A standard blue-top tube filled appropriately (with 4.5 mL blood) was submitted to the laboratory for preoperative PT and APTT testing. The results of both tests were elevated. The patient's PT and APTT from the previous day were within normal limits, and he is not on heparin therapy. Which is the most appropriate first step to investigate the abnormal results?

A. Report the result as obtained

B. Perform a mixing study

C. Check the sample for a clot

D. Report the APTT only

B. Activation of factor VII due to exposure to cold temperature

B Samples for evaluation of PT are stable for 24 hours if kept at room temperature. Prolonged exposure to cold will activate factor VII, resulting in decreased PT results

A plasma sample submitted to the lab for PT testing has been stored for 25 hours at 4°C. The PT result is shortened. What is the most probable cause?

A. Factor VII deficiency

B. Activation of factor VII due to exposure to cold temperature

C. Lupus inhibitor

D. Factor X inhibitor

B. Antithrombin deficiency

B Antithrombin deficiency in patients receiving heparin therapy may lead to heparin resistance, and therefore, lack of prolongation of APTT results. Antithrombin is a heparin cofactor and as such increases heparin activity by 1,000-fold. The deficiency of AT is associated with a poor response to heparin therapy

The APTT results are not elevated in a patient receiving heparin. Which of the following factors may be associated with the lack of response to heparin therapy in this patient?

A. Protein C deficiency

B. Antithrombin deficiency

C. Protein S deficiency

D. Factor VIII deficiency

A. A baseline APTT and platelet count; APTT testing every 6 hours until the target is reached

A The baseline platelet count and APTT should be performed on all patients prior to administration of heparin. The response to heparin therapy varies among different patients for the following reasons: Heparin half-life is decreased in extended thrombosis, and the anticoagulant activities of heparin change based upon nonspecific binding of heparin to plasma proteins. Therefore, heparin therapy should be closely monitored. Heparin dosage can be monitored by an APTT or activated clotting time (ACT) test but not by the PT. In addition, the platelet count should be monitored regularly during heparin therapy, because a decrease of the platelet count to 50% below the baseline value is significant and may be associated with HIT.

A 50-year-old patient was admitted to the emergency department complaining of pain in her right leg. Her leg was red, swollen, and warm to the touch. Deep venous thrombosis was suspected, and the patient was started on heparin therapy. Which of the following is (are) the proper protocol to evaluate patients receiving heparin therapy?

A. A baseline APTT and platelet count; APTT testing every 6 hours until the target is reached

B. Repeat APTT after 5 days postheparin therapy to adjust the therapeutic dose

C. Monitor the platelet count daily and every other day after heparin therapy is completed

D. Monitor PT daily to adjust the therapeutic dose

C. TTP

C The clinical manifestations and laboratory results in this patient are consistent with TTP. The clinical manifestations of TTP include microangiopathic hemolytic anemia (MAHA), thrombocytopenia, fever, renal failure, and neurological symptoms. The neurological symptoms in this patient are manifested by headache, dizziness, nausea, and vomiting. Weakness and lethargy are signs and symptoms of anemia. Low hemoglobin and hematocrit with normal MCV and MCHC indicate a normocytic/normochromic anemia. The presence of schistocytes on the peripheral blood with low platelet counts and low haptoglobin are consistent with microangiopathic hemolytic anemia. The high blood urea nitrogen and creatinine levels are characteristic of renal failure. The platelet count, performed on admission, was done on a hematology analyzer and was falsely elevated because of the presence of microcytes or fragmented red cells. The manual platelet count was much lower. The coagulation tests are normal in TTP. In von Willebrand's disease, the platelet count is normal and the APTT is usually abnormal. ITP is characterized by thrombocytopenia but not HA. Although DIC is associated with a low platelet count and HA, it is characterized by abnormal coagulation studies. The acute onset of symptoms may be related to mitomycin used for the treatment of gastric carcinoma in this patient

A 46-year-old female was admitted to the emergency department with complaints of headache, dizziness, lethargy, nausea, vomiting, and weakness. The patient had a gastrectomy procedure 4 months earlier to remove adenocarcinoma of the stomach. She was placed on mitomycin therapy. Diagnostic procedures indicated recurrence of the carcinoma.

Admission CBC Results

Patient; Reference Range

WBC 17.1 × 109/L; 4.8-10.8 × 109/L

RBC 2.29 × 1012/L; 3.80-5.50 × 1012/L

Hgb 8.1 g/dL ;12.0-15.2 g/dL

Hct 23%; 37%-46%

MCV 95.7 fL; 79-101 fL

MCH 35.4 pg; 27-33 pg

MCHC 35.0 g/dL; 31-34 g/dL

RDW 18.5; 11.5-14.5

PLT 48.0 × 109/L; 140-450 × 109/L

MPV 11.2; 7.4-9.4

DIFFERENTIAL COUNTS (%)

Segmented neutrophils 79; 30%-70%

Band neutrophils 3; 0%-10%

Lymphocytes 11; 20%-50%

Monocytes 6; 2%-12%

Basophils 1; 0%-2%

NRBCs (/100 WBCs) 3; 0

Manual platelet count: 18 × 109/L; 140-450 × 109/L

Marked anisocytosis none

Marked RBC fragmentation: none

PT, APTT, and TT: Normal

ADDITIONAL LABORATORY DATA

Urinalysis; Patient; Reference Range

pH; 5.0; 5-7

Protein; 30.0 mg/dL; 0-15 mg/dL

RBC; 60-100/µL; 0-5/µL

Casts; 10/hpf granular/ hyaline; Not detectable

Creatinine; 3.1 mg/dL; 0.7-1.3 mg/dL

BUN; 39 mg/dL; 8-22 mg/dL

Haptoglobin; 5.0 mg/dL; 50-150 mg/dL

These clinical manifestations and laboratory results are consistent with:

A. ITP

B. von Willebrand's disease

C. TTP

D. DIC

C. Glanzmann's thrombasthenia

C These clinical manifestations and laboratory results are consistent with Glanzmann's thrombasthenia. Epistaxis and easy bruising are characteristics of platelet disorders. The positive family history is indicative of an inherited bleeding disorder. Laboratory tests reveal a low hemoglobin level due to epistaxis. The normal platelet count rules out any quantitative platelet disorder. The platelet count is typically low in Bernard-Soulier syndrome. The bleeding time test evaluates in vivo platelet function and number. Normal PT and APTT combined with a normal factor VIII assay rule out coagulation disorders. The laboratory tests that confirm an inherited platelet disorder are platelet aggregation studies. Platelet aggregation is normal to ristocetin and abnormal to ADP, epinephrine, and thrombin. These results are consistent with Glanzmann's thrombasthenia. Platelet aggregation is abnormal to ristocetin in von Willebrand's disease and Bernard-Soulier syndrome

Patient History

A 1-year-old infant was admitted to the hospital with recurrent epistaxis for the past 5 days. The past medical history revealed easy bruising and a severe nosebleed at 3 months of age, necessitating transfusion therapy. Te mother had had a severe nosebleed 8 years ago. The father was reported to bleed easily after lacerations. The patient was transfused with 2 units of packed red cells upon admission.

Admission Laboratory Results

Patient; Reference Range

Hgb: 4.5 g/dL; 13-15 g/dL

Platelet count: 249 × 109/L; 150-450 × 109/L

PT: 11.2 sec; 11-13 sec

APTT: 34 sec; 28-37 sec

ADDITIONAL LABORATORY TESTS

Factor VIII assay 70%; 50%-150%

Platelet Abnormal to aggregation: ADP, epinephrine, and thrombin; normal to

ristocetin

These clinical manifestations and laboratory results are consistent with which condition?

A. von Willebrand's disease

B. Bernard-Soulier syndrome

C. Glanzmann's thrombasthenia

D. Factor VIII deficiency

D. Lupus anticoagulant

D These clinical manifestations and laboratory results are consistent with lupus anticoagulant. Pain and swelling in her right leg may be indicative of thrombosis. As many as 48% of women with repeated spontaneous abortions have lupus anticoagulant or/and antibody to phospholipid such as anticardiolipin antibodies. The unremarkable family history in this patient rules out an inherited thrombotic disorder. A normal TT rules out fibrinogen disorders. A prolonged PT and APTT in the absence of bleeding history eliminate the diagnosis of factor deficiency, including factor VIII deficiency. The APTT performed on a mixture of patient plasma and normal plasma did not correct. This result is indicative of an inhibitor. However, because the patient is not bleeding, factor VIII inhibitor is not indicated. A negative anticardiolipin antibody result rules out the possibility of anticardiolipin antibodies being responsible for the patient's clinical symptoms. The laboratory test that confirms the presence of a lupus anticoagulant is a prolonged APTT that is not corrected when mixed with normal plasma and that is neutralized by preincubation with platelets (an excess of platelet phospholipid neutralizes the antibody, resulting in a normal APTT).

Patient History:

A 30-year-old female was referred to the hospital for evaluation for multiple spontaneous abortions and current complaint of pain and swelling in her right leg. Her family history is unremarkable.

Laboratory Tests; Patient; Reference Range

PT: 14.5 sec; 11-13 sec

APTT: 63.0 sec; 28-37 sec

Thrombin time: 12.0 sec; 10-15 sec

Mixing Study APTT:

Preincubation and after 2-hour incubation at 37°C; 57.0 sec

Platelet Neutralization Procedure:

Patient plasma + freeze-thawed platelets; APTT: 35.0 sec

Patient plasma + saline; APTT: 59.0 sec

Anticardiolipin antibodies done by ELISA: Negative

These clinical manifestations and laboratory results are consistent with:

A. Factor VIII inhibitor

B. Factor VIII deficiency

C. Anticardiolipin antibodies

D. Lupus anticoagulant

C. Cancel the procedure and start the patient on vitamin K therapy

C Liver biopsy in a patient with a prolonged PT and a high INR could be life threatening. In this patient, the prolonged PT is likely caused by liver disease. Vitamin K is stored in the liver and is essential for activation of factors II, VII, IX, and X. Vitamin K needs bile (secreted by the liver) for its absorption. In liver disease characterized by obstruction, bile is not secreted into the GI tract, and therefore, vitamin K is poorly absorbed. The most logical course of action is to recommend the following: Start the patient on vitamin K therapy, repeat the PT test 4 days after starting vitamin K administration, and cancel the biopsy until the patient's PT returns to normal.

A 60-year-old patient was admitted to a hospital for a liver biopsy. The biopsy was scheduled for 11:00 a.m. The coagulation results performed at the time of admission revealed a prolonged PT with an INR of 4.5. What is the physician's most appropriate course of action?

A. Proceed with biopsy, because a prolonged PT is expected in liver disease

B. Postpone the procedure for a couple of days

C. Cancel the procedure and start the patient on vitamin K therapy

D. Put patient on vitamin K and proceed with the procedure immediately

B. Request a new sample for APTT

B According to Clinical Laboratory Standards Institute (CLSI) guidelines, samples for APTT should be centrifuged and tested within 2 hours after collection. However, the sample is stable for 4 hours if stored at 4oC. APTT evaluates the clotting factors in the intrinsic and common coagulation pathways, including factor VIII (intrinsic) and factor V (common). Factors VIII and V are cofactors necessary for fibrin formation. However, they are both labile. Storage beyond 4 hours causes falsely elevated APTT results. The technologist should request a new sample for the APTT.

A fresh blood sample was sent to the laboratory at 8:00 a.m. for a PT test. At 4:00 p.m., the doctor requested an APTT test to be done on the same sample. What should the technologist do?

A. Rerun APTT on the 8:00 a.m. sample and report the result

B. Request a new sample for APTT

C. Run APTT in duplicate and report the average

D. Mix the patient plasma with normal plasma and run the APTT

B. Check to see if the patient has received any other anticoagulant medications

B Traditional anticoagulant drugs such as heparin and warfarin are well known. There are new anticoagulant drugs available for the treatment and prevention of thrombosis. Some of these new drugs have antithrombin effects and therefore increase PT, APTT, and TT results. Examples of these drugs are hirudin, which inhibits thrombin; and danaparoid, which inhibits factor Xa.

An APTT test is performed on a patient and the result is 50 sec (reference range 27-37 sec). The instrument flags the result owing to failure of the delta check. The patient had an APTT of 35 sec the previous day. The technologist calls the nursing unit to check whether the patient is on heparin therapy. The patient is not receiving heparin. What is the next appropriate step?

A. Check the family history for an inherited factor VIII deficiency

B. Check to see if the patient has received any other anticoagulant medications

C. Perform mixing studies

D. Perform a factor VIII assay

C. The negative platelet aggregation does not rule out HIT

C Heparin therapy should be stopped immediately when clinical symptoms indicate HIT. The blood sample should be tested at least 4 hours after heparin therapy is discontinued. Early sampling for HIT testing may give a false-negative result due to the neutralization of antibody by heparin. LMWH should not be used in patients who develop HIT, because LMWH drugs can also cause HIT. Warfarin therapy can be started in patients who respond to heparin therapy as soon as the APTT is increased to 1.5 times the baseline APTT. Heparin therapy must overlap warfarin therapy until the INR reaches a stable therapeutic range (2.0-3.0). Warfarin therapy could not be used in this patient because she did not respond to heparin therapy. The first step in the treatment of HIT is discontinuation of heparin, including intravenous catheter flushes, heparincoated indwelling catheters, unfractionated heparin, and LMWH.

A patient was put on heparin therapy postoperatively for prevention of thrombosis. The patient had the following laboratory results on admission: Platelet count = 350 × 109/L; PT = 12 sec (reference: 10-13 sec); APTT = 35 sec

(reference: 28-37). After 6 days of heparin therapy, the patient complained of pain and swelling in her left leg. Her platelet count dropped to 85 × 109/L and her APTT result was 36 sec. The physician suspected heparin-induced thrombocytopenia (HIT) and ordered a platelet aggregation test to be performed immediately. The heparin-induced platelet aggregation test result was negative. Heparin therapy was continued. Several days later, the patient developed a massive clot in her left leg that necessitated amputation. Which of the following should have been recognized or initiated?

A. The patient should have been placed on LMWH

B. The heparin dose should have been increased

C. The negative platelet aggregation does not rule out HIT

D. The patient should have been placed on warfarin therapy

B. Report Hgb and Hct results, adjust the anticoagulant volume, and redraw a new sample for PT and APTT

B The anticoagulant-to-blood ratio should be adjusted for PT and APTT tests in patients with a severe anemia. The standard anticoagulant volume (0.5 mL) is not sufficient for the large quantity of plasma in these patients, causing unreliable PT and APTT results. The low Hgb and Hct in this patient were due to severe bleeding during surgery. To get accurate PT and APTT results, the amount of anticoagulant is adjusted according to the following formula: (0.00185)(V)(100-H) = C, where V = blood volume in mL; H = patient's Hct; and C = volume of anticoagulant in mL. A new sample should be drawn to rerun the PT and APTT. There are other causes for decreased PT and APTT, such as increased fibrinogen and increased factor VIII; however, the preanalytical variables affecting unreliable results should be ruled out first. Heparin therapy would increase PT and APTT

A 50-year-old female was admitted to a hospital for hip replacement surgery. The preoperative tests were performed and the results showed an Hgb of 13.5 g/dL; Hct = 42%; PT = 12 sec; APTT = 36 sec. The patient was bleeding during surgery and the postoperative test results revealed an Hgb = 5.0 g/dL; Hct = 16%; PT = 8 sec; and

APTT = 25 sec. What steps should be taken before releasing these results?

A. No follow-up steps are needed; report the results as obtained

B. Report Hgb and Hct results, adjust the anticoagulant volume, and redraw a new sample for PT and APTT

C. Call the nurse and ask if the patient is receiving heparin

D. Because the patient is severely anemic, multiply the PT and APTT results by two and report the results

B. Factor V inhibitor

B The lack of a positive family history in this patient indicates the presence of an acquired coagulopathy. Because both PT and APTT tests are abnormal, the clotting factor involved is most probably in the common pathway. The lack of correction by mixing studies suggests the presence of an inhibitor. Factor V antibodies are the most common antibodies among the clotting factors of the common pathway (I, II, V, and X). Factor V antibodies are reported to be associated with surgery, some antibiotics such as streptomycin, patients who are exposed to blood products, or the bovine form of "fibrin glue." Patients with antibodies to factor V may require long-term therapy with immunosuppressive drugs. Acute bleeding episodes may be treated by platelet transfusions. The PT test is normal in patients with factor VIII deficiency and factor VIII inhibitor. Lupus anticoagulant is not present with bleeding unless associated with coexisting thrombocytopenia.

Patient and Family History

A 45-year-old woman visited her doctor complaining of easy bruising and menorrhagia occurring for the past few weeks. The patient had no history of excessive bleeding during childbirth several years earlier nor during a tonsillectomy in childhood. Her family history was unremarkable.

Laboratory Reference

Tests Patient Range

PT 45 sec 11-13 sec

APTT 125 sec 28-37 sec

Thrombin Time 14.0 sec 10-15 sec

Mixing studies (patient plasma + normal plasma): PT = 40 sec; APTT = 90 sec

Platelet count and morphology = normal

Liver function tests = normal

These clinical manifestations and laboratory results

are consistent with:

A. Factor VIII inhibitor

B. Factor V inhibitor

C. Factor VIII deficiency

D. Lupus anticoagulant