2.5 Hemostasis Problem-Solving

Question 1

Patient History: A 3-year-old male was admitted with scattered petechiae and epistaxis. The patient had normal growth and had no other medical problems expect for chickenpox 3 weeks earlier. His family history was unremarkable.

Laboratory Results:

Patient - PT: 11 sec (Reference Range: 10-13 sec)
Patient - APTT: 32 sec (RR: 28-37 sec)
Patient - PLT count: 18 x 10^3/uL L (RR: 150-450 x 10^3/uL)

These clinical manifestations and laboratory results are consistent with which condition?
A. TTP
B. DIC
C. ITP
D. HUS

Answer 1

C. ITP

Question 2

Patient History: A 12-year-old white male has the following symptoms: visible bruising on arms and legs, bruising after sports activities, and excessive postoperative hemorrhage after 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:

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

A. Factor VII deficiency
B. von Willebrand disease
C. Glanzmann thrombasthenia
D. Bernard-Soulier syndrome

Answer 2

B. von Willebrand disease

Question 3

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

Prolonged PT and APTT
PLT count = 100 x 10^9/L
Fibrinogen = 40 mg/dL

Which of the following blood products should be recommended for transfusion?
A. Factor VIII concentrate
B. PLTs
C. FFP
D. Cryoprecipitate

Answer 3

D. Cryoprecipitate

Question 4

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

Answer 4

C. PLT count

Question 5

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 PLT count; 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 37C caused 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

Answer 5

D. Factor VIII inhibitor

Question 6

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

Peripheral blood smear = macrocytosis, target cells
PLT count = 355 x 10^9/L
PT = 25 sec (reference range = 10-14)
APTT = 65 sec (reference range = 28-36)
Transaminases = elevated (AST: ALT ratio greater than 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 disease

Answer 6

C. Cirrhosis of the liver

Question 7

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 laboratory protocol should be followed for the interpretation of correction
D. A circulating anticoagulant can be ruled out

Answer 7

C. The laboratory protocol should be followed for the interpretation of correction

Question 8

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 was 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 APTT only

Answer 8

C. Check the sample for a clot

Question 9

A plasma sample submitted to the laboratory for PT testing has been stored for 25 hours at 4C. PT is shortened. What is the most probable cause?
A. Factor VII deficiency
B. Activation of factor VII caused by exposure to cold temperature
C. Lupus inhibitor
D. Factor X inhibitor

Answer 9

B. Activation of factor VII caused by exposure to cold temperature

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.

Question 10

APTT is not increased 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. AT deficiency
C. Protein S deficiency
D. Factor VIII deficiency

Answer 10

B. AT deficiency

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

Question 11

A 50-year old patient was admitted to the emergency department with a complaint of pain in the right leg. The leg was red, swollen, and warm to the touch. DVT was suspected, and the patient was started on heparin therapy. Which of the following is (are) the proper protocol(s) to evaluate patients receiving heparin therapy?

A. Baseline APTT and PLT count; APTT testing every 4 to 6 hours after the initial heparin bolus
B. Repeat APTT 5 days after heparin therapy to adjust the therapeutic dose
C. Monitor the PLT count daily and every other day after heparin therapy is completed
D. Monitor PT daily to adjust the therapeutic dose

Answer 11

A. Baseline APTT and PLT count; APTT testing every 4 to 6 hours after the initial heparin bolus

Question 12

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

Admission Complete Blood Count (CBC) Results
Patient:
WBCs: 17.1 x 10^9/L. (RR: 4.8-10.8 x 10^9/L)
RBCs: 2.29 x 10^12/L (RR: 3.80-5.50 x 10^12/L)
Hgb: 8.1 g/dL (RR: 12.0-15.2 g/dL)
Hct: 23%. (RR: 37%-46%)
MCV: 95.7 fL. (RR: 79-101 fL)
MCH: 35.4 pg. (RR: 27-33 pg)
MCHC: 35.0%. (RR: 31%-34%)
RDW: 18.5%. (RR: 11.5-14.5)
PLTs: 48.0 x 10^9/L. (RR: 140-450 x 10^9/L)
MPV: 11.2. (RR: 7.4-9.4)

Differential Counts (%)
Seg neutrophils: 79. (RR: 30%-70%)
Band neutrophils: 3. (RR: 0-10%)
Lymphocytes: 11. (RR: 20-50%)
Monocytes: 6. (RR: 2-12%)
Basophils: 1. (RR: 0-2%)
NRBCs (/100 WBCs): 3. (RR: 0-2%)
Manual platelet count: 18 x 10^/L
(RR: 140 - 450 x 10^9/L)
Marked anisocytosis
Marked RBC fragmentation
PT, APTT, and TT: Normal

Additional Laboratory Data
Urinalysis/Patient/Reference Range

pH: 5.0 (RR: 5-7)
Protein: 30.0. (RR: 0-15 mg/dL)
RBCs: 60-100/u.
Casts: 10/high-power field (hpf) granular/hyaline

Plasma/Patient/Reference Range
Creatinine: 3.1 mg/dL. (RR: 0.7-1.3 mg/dL)
BUN: 39 mg/dL. (RR: 8-12 mg/dL)
Haptoglobin: 5.0 mg/dL. (RR: 50-150 mg/dL)

These clinical manifestations and laboratory results are consistent with:
A. ITP
B. von Willebrand disease
C. TTP
D. DIC

Answer 12

C. TTP

The clinical manifestations and laboratory results in this patient are consistent with TTP. The clinical manifestations of TTP include MAHA, thrombocytopenia, fever, renal failure, and neurological symptoms. The neurological symptoms in this patient are manifested by headache, dizziness, nausea, and vomitting. Weakness and lethargy are signs and symptoms of anemia. Low Hgb and Hct with normal MCV and MCHC indicate a normocytic normochromic anemia. the presence of schistocytes in peripheral blood, with low platelet counts and low haptoglobin, are consistent with MAHA. The high BUN 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 RBCs. The manual platelet count was much lower. The coagulation tests are normal in TTP. In von Willebrand disease, the platelet count is normal and the APTT is usually abnormal. ITP is characterized by thrombocytopenia, but not hemolytic anemia (HA). DIC is associated with a low platelet count, HA, and abnormal coagulation studies. The acute onset of symptoms in this patient may be related to mitomycin used for the treatment of gastric carcinoma in this patient.

Question 13

Patient History: A 1-year-old infant was admitted with recurrent epistaxis for the past 5 days. Past medical history revealed easy bruising and severe nosebleed that had occurred when he was 3 months of age, necessitating transfusion therapy. The mother 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 RBCs on admission.

Admission Laboratory Results (Patient/Reference Range)

Hgb: 4.5 g/dL. (RR: 13-15 g/d:)
Platelet count: 249 x 10^9/L. (RR: 150-450 x 10^9/L)
PT: 11.2 sec. (RR: 11-13 sec)
APTT: 34 sec. (RR: 28-37 sec)

Additional Laboratory tests
Factor VIII assay: 70%. (RR: 50-150%)
PLT aggregation: Abnormal to ADP, EP, and thrombin; normal to ristocetin

These clinical manifestations and laboratory results are consistent with which condition?
A. von Willebrand disease
B. Bernard-Soulier syndrome
C. Glanzmann thrombasthenia
D. Factor VIII deficiency

Answer 13

C. Glanzmann thrombasthenia

These clinical manifestations and laboratory results are consistent with Glanzmann 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 Hgb level caused by epistaxis. The normal platelet count rules out any quantititative platelet disorder. The platelet count is typically low in Bernard-Soulier syndrome. 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 PLT aggregation studies. PLT aggregation is normal to ristocetin and abnormal to ADP, EPI, and thrombin. These results are consistent with Glanzmann thrombasthenia. PLT aggregation is abnormal to ristocetin in von Willebrand disease and Bernard-Soulier syndrome.

Question 14

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. (RR: 11-13 sec)
APTT: 63.0 sec. (RR: 28-37 sec)
TT: 12.0 sec (10-15 sec)
Mixing study APTT.
Preincubation and after 2-hour incub @37: 57.0
Platelet neutralization procedure
Patient plasma + freeze-thawed platelets APTT=35sec
Patient plasma + saline APTT= 59 sec
Anticardiolipin antibody done by ELISA - Neg

These clinical manifestations and laboratory results are consistent with:
A. Factor VIII inhibitor
B. Factor VIII deficiency
C. Anticardiolipin antibodies
D. Lupus anticoagulant

Answer 14

D. Lupus anticoagulant

These clinical manifestations and laboratory results are consistent with lupus anticoagulant. Pain and swelling in the patient’s 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. Normal TT rules out fibrinogen disorders. Prolonged PT and APTT in the absence of bleeding history eliminate the diagnosis of factor deficiency. The APTT test performed on a mixture of patient plasma and normal plasma did not correct the prolonged APTT. This result is indicative of an inhibitor. HOWEVER, because the patient is not bleeding, factor VIII inhibitor is not indicated. A negative anticardiolipin antibody results rules out the possibility of anticardiolipin antibodies being responsible for the patient’s clinical symptoms. The laboratory tests results that confirms the presence of a lupus anticoagulant is prolonged APTT that is not corrected when mixed with normal plasma and that is neutralized by preincubation with platelet phospholipid (an excess of platelet phospholipid neutralizes the antibody, resulting in normal APTT).

Question 15

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 obtained at the time of admission revealed prolonged PT with an INR of 4.5. What is the physician’s most appropriate course of action?
A. Proceed with biopsy because 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 therapy and proceed with the procedure immediately

Answer 15

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

Performing liver biopsy in a patient with a prolonged PT and a high INR could have life-threatening consequences. 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 gastrointestinal tract, and therefore, vitamin K is poorly absorbed. The most logical course of action is 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.

Question 16

A fresh blood sample was sent to the laboratory at 8:00 a.m. for the PT test. At 4:00 p.m. the doctor requested for the APTT test to be done on the same sample. What should the technologist do?
A. Rerun the APTT on the 8:00 a.m. sample and report the result
B. Request a new sample for APTT
C. Run the APTT in duplicate and report the average
D. Mix patient plasma with normal plasma and run the APTT

Answer 16

B. Request a new sample for APTT

According to the 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 4C. 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 medical laboratory scientist should request a new sample for the APTT test.

Question 17

An APTT test is performed on a patient and the result is 50 sec (reference range 27-37 sec). The instrument flags the result because of failure of the delta check. The patient had 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 patient’s family history for 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

Answer 17

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

Traditional anticoagulant drugs, such as heparin and warfarin, are well known. Newer anticoagulant drugs are available for the treatment and prevention of thrombosis. Some of these new drugs have AT or anti-factor Xa effects and, therefore, increase PT, APTT, and TT. Examples of these drugs are argatroban, which inhibits thrombin, and fondaparinux, which inhibits factor Xa.

Question 18

A patient was put on heparin therapy postoperatively for prevention of thrombosis. The patient had the following laboratory results on admission: Platelet count = 350 x 10^9/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 x 10^9/L, and her APTT result was 36 sec. The physician suspected HIT and ordered the PLT aggregation test to be performed immediately. The heparin-induced PLT aggregation test result was negative. Heparin therapy was continued. Several days later, the patient developed a massive clot in her left leg and 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 PLT aggregation does not rule out HIT
D. The patient should have been placed on warfarin therapy

Answer 18

C. The negative PLT aggregation does not rule out HIT

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 because of the neurealization of antibodies by heparin. LMWH should not be used in patients who develop HIT because LMWH can also cause HIT. Warfarin can be started in patients who respond to heparin therapy. Heparin therapy must overlap warfarin therapy until the INR reaches a stable therapeutic range (2.0-3.0). Warfarin therapy cound not be used in this patient because of lack of response to heparin therapy. The first step in the treatment of HIT is discontinuation of heparin, including intravenous catheter flushes, heparin-coated indwelling catheters, UFH, and LMWH.

Question 19

A 50-year-old female was admitted to a hospital for hip replacement surgery. Preoperative tests were performed, and the results showed the following:

Hgb = 13.5 g/dL; Hct = 42%; PT = 12 sec; APTT = 36 sec.

The patient was bleeding during surgery, and postoperative test results revealed the following:

Hgb = 5.0 g/dL; Hct = 16%; PT = 8 sec; 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 result, 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

Answer 19

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

The anticoagulant: blood ratio should be adjusted for the 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 caused by 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 firbinogen and increased factor VIII; however, the preanalytical variables affecting unreliable results should be ruled out first. Heparin therarpy would increase PT and APTT.

Question 20

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 child birth several years earlier or during a tonsillectomy in childhood. her family history was unremarkable.

Laboratory Tests:
PT: 45 sec. / RR: 11-13 sec
APTT: 125 sec. / RR: 28-37 sec
TT: 14 sec. / RR: 10-15 sec
Mixing studies (pt 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

Answer 20

B. Factor V inhibitor

The absence of a positive family history in this patient indicates acquired coagulopathy. Because both the PT and APTT test results 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; exposure 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.