Coag 2.5 Hemostasis Problem-Solving Flashcards
- 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 except for chickenpox 3 weeks earlier. His family history was unremarkable.
PT: 11 sec (Ref: 10-13 sec)
APTT: 32 sec (Ref: 28–37 sec)
PLT count: 18 × 10^3/µL (Ref: 150–450 × 10^3/μL)
These clinical manifestations and laboratory results are consistent with which condition?
A. TTP
B. DIC
C. ITP
D. HUS
C. ITP
These clinical manifestations and laboratory results are consistent with ITP. ITP is an autoimmune thrombocytopenia. In children, acute ITP occurs after a viral infection, as was the case in this 3-year-old patient. Clinical manifestations are associated with petechiae, purpura, and mucous membrane bleeding, such as epistaxis and gingival bleeding. Abnormal laboratory tests include a very low PLT count, and other causes of thrombocytopenia should be ruled out in patients with suspected ITP.
- 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.
PLT count: 350 × 10^3/μL (Ref: 200–450 × 10^3/μL)
PT: 11 sec (Ref: 10–12 sec)
APTT: 70 sec (Ref: 28–37 sec)
TT: 13 sec (Ref: 10–15 sec)
PLT AGGREGATION
-Normal aggregation with collagen, EPI, ADP
-Abnormal aggregation with ristocetin
CONFIRMATORY TESTS
VWF:Rco: 25% (Ref: 45%–140%)
VIII:C: 20% (Ref: 50%–150%)
VWF:antigen: 10% (Ref: 45%–185%)
These clinical manifestations and laboratory results are consistent with which diagnosis?
A. Factor VIII deficiency
B. von Willebrand disease
C. Glanzmann thrombasthenia
D. Bernard-Soulier syndrome
B. von Willebrand disease
von Willebrand disease is an inherited bleeding disorder caused by abnormal PLT adhesion and aggregation. In von Willebrand disease, VWF is deficient or dysfunctional. VWF enhances the release of factor VIII from the liver, and it also forms a complex with factor VIII in the circulation. Deficient or dysfunctional VWF results in decreased factor VIII as well and, therefore, an increase in APTT values. The clinical manifestations associated with von Willebrand disease are easy bruising, epistaxis, and bleeding after surgery. The diagnostic laboratory test shows abnormal PLT aggregation to ristocetin, which is corrected by addition of normal plasma containing VWF. 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 abnormal. The PLT count and PT are normal in von Willebrand disease.
- The following results are obtained from a patient who developed severe bleeding:
Prolonged PT and APTT
PLT count = 100 × 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
D. Cryoprecipitate
Cryoprecipitate contains fibrinogen, factor VIII, and VWF. FFP has all of the clotting factors; however, it is not the best choice if cryoprecipitate is available.
- 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
C. PLT count
The PLT count should be checked every other day in patients receiving heparin therapy. 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.
- 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 37°C
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
D. Factor VIII inhibitor
Factor VIII inhibitor is found in 20% to 25% of patients with hemophilia 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 with an inhibitory effect that is time and temperature dependent. The presence of factor
VIII inhibitor causes elevated APTT in the face of a normal PT. 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. APTT would not be corrected by mixing
studies in the presence of factor VIII inhibitor. In addition, factor VIII inhibitor is associated with bleeding. Lupus anticoagulant is associated with thrombosis and not
bleeding unless it coexists with thrombocytopenia, which is not the case in this patient.
- A 62-year-old female presents with jaundice and the following laboratory data:
Peripheral blood smear = macrocytosis, target cells
PLT count = 355 × 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
C. Cirrhosis of the liver
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 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 bilirubin is converted to urobilinogen and excreted into feces. In cirrhosis of the liver, both necrosis and obstruction caused by scarring produce increases in unconjugated and conjugated bilirubin, respectively. In addition, the liver enzymes are elevated (the AST:ALT ratio is less than 1 in necrotic liver diseases, such as hepatitis, but not in cirrhosis).
- 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
C. The laboratory protocol should be followed for the interpretation of correction
- 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
C. Check the sample for a clot
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 PT and APTT. Checking the sample for a clot is the most reasonable step in this case.
- A plasma sample submitted to the laboratory for PT testing has been stored for 25 hours at 4°C. 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
B. Activation of factor VII caused by exposure to cold temperature
- 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
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.
- 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
A. Baseline APTT and PLT count; APTT testing every 4 to 6 hours after the initial heparin bolus
Baseline PLT count and APTT should be performed on all patients prior to administration of heparin. APTT should be repeated every 4 to 6 hours after bolus injection (high dose). Response to heparin therapy varies among patients for the following reasons: heparin half-life is decreased in extended thrombosis, and the anticoagulant activities of heparin change based on nonspecific binding of heparin to plasma proteins. Therefore, heparin therapy should be closely monitored. Heparin dosage can be adjusted based on the anti–factor Xa assay. In addition, the PLT count should be monitored regularly during heparin therapy because decrease of the PLT count to 50% below the baseline value is significant and may be associated with HIT. PT is not used to monitor heparin therapy.
- 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.
WBCs :17.1 × 10^9/L (Ref: 4.8–10.8 × 10^9/L)
RBCs: 2.29 × 10^12/L (Ref: 3.80–5.50 × 10^12/L)
Hgb: 8.1 g/dL (Ref: 12.0–15.2 g/dL)
Hct: 23% (Ref: 37%–46%)
MCV: 95.7 fL (Ref: 79–101 fL)
MCH: 35.4 pg (Ref: 27–33 pg)
MCHC: 35.0 % (Ref: 31%–34%)
RDW: 18.5 (Ref: 11.5–14.5)
PLTs: 48.0 × 10^9/L (Ref: 140–450 × 10^9/L)
MPV: 11.2 (Ref: 7.4–9.4)
DIFERENTIAL COUNTS (%):
Segmented neutrophils: 79 (Ref: 30%–70%)
Band neutrophils: 3 (Ref: 0%–10%)
Lymphocytes: 11 (Ref: 20%–50%)
Monocytes: 6 (Ref: 2%–12%)
Basophils: 1 (Ref: 0%–2%)
NRBCs (/100 WBCs): 3 (Ref: 0)
Manual platelet count: 18 × 10^9/L (Ref: 140–450 × 10^9/L)
Marked anisocytosis: None
Marked RBC fragmentation: None
PT, APTT, and TT: Normal
ADDITIONAL LABORATORY DATA
URINALYSIS:
pH: 5.0 (Ref: 5–7)
Protein: 30.0 mg/dL (Ref: 0–15 mg/dL)
RBCs: 60–100/μl
Casts: granular/hyaline 10/high-power field (hpf)
PLASMA:
Creatinine: 3.1 mg/dL (Ref: 0.7–1.3 mg/dL)
BUN: 39 mg/dL (Ref: 8–22 mg/dL)
Haptoglobin: 5.0 mg/dL (Ref: 50–150 mg/dL)
These clinical manifestations and laboratory results are consistent with:
A. ITP
B. von Willebrand disease
C. TTP
D. DIC
C. 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 vomiting. 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.
- Patient History
A 1-year-old infant was admitted with recurrent epistaxis for the past 5 days. Past medical history revealed easy bruising and a 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
Hgb 4.5 g/dL (Ref: 13–15 g/dL)
Platelet count 249 × 10^9/L (Ref: 150–450 × 10^9/L)
PT 11.2 sec (Ref: 11–13 sec)
APTT 34 sec (Ref: 28–37 sec)
ADDITIONAL LABORATORY TESTS
Factor VIII assay 70% (Ref: 50%–150%)
PLT aggregation: Abnormal to ADP, EPI, 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
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 quantitative 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.
- 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.
PT 14.5 sec (Ref: 11–13 sec)
APTT 63.0 sec (Ref: 28–37 sec)
TT 12.0 sec (Ref: 10–15 sec)
Mixing Study APTT:
Preincubation & after 2-hour incubation at 37°C: 57.0 sec
Platelet neutralization procedure:
Patient plasma + freeze-thawed platelets: APTT = 35 sec
Patient plasma + saline: APTT = 59 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
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 result rules out the possibility of anticardiolipin antibodies being responsible for the patient’s clinical symptoms. The laboratory test result 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).
- 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
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.
