MANILA CENTRAL UNIVERSITY

COLLEGE OF MEDICAL TECHNOLOGY / MEDICAL LABORATORY SCIENCE

SEMINAR 2 – Case Studies about Coagulation and Haemostasis

NAME: _________________________________________________________ DATE: ________________________

 INSTRUCTION: Submit this assignment (YOUR ANSWERS, TOGETHER WITH THIS QUESTIONNAIRE) on March 13,
2018 (Tuesday). Submission beyond or after the said date will not be accepted. Your answers to the questions must
be COMPUTERIZED and place all of them in a separate LONG bond paper (Do not forget to write your name and the
date submitted). Your answers together with this questionnaire must be placed in a long VIOLET sliding folder. You
are very free to use different Hematology books as many as you can; but DO NOT use the internet. Kindly indicate the
source of your answers (title of the book you used, edition, author, and page number/s) and the signature of the
librarian if you utilized the Library. Write also your name and the date submitted on this questionnaire. Thank you
very much. Good luck and God bless to all of you.

1. A 17-year-old Jewish woman complains of recurrent episodes of bleeding from the nose and mouth since birth and
heavy menstrual bleeding since menarche. She has never had bleeding into joints or muscles. Her brother also has a
history of nasal bleeding. Physical examination does not reveal any telangiectases of the nose and mouth. Skin and
joints appear normal. Gynaecologic examination is normal. Platelet count is 250 x 10 9/L. bleeding time is prolonged at
18 minutes. Appearance of platelets on the peripheral blood smear is normal.

 QUESTIONS:
a) What conditions should be considered in the differential diagnosis for this bleeding? Why?
b) What additional testing can be performed to evaluate this bleeding tendency?
c) How would each of the possible conditions in the differential diagnosis be treated to minimize
further bleeding episodes?

2. A 67-year-old white man with a history of cigarette smoking developed sudden onset of tingling and weakness of the
left arm that lasted 10 minutes before resolving, consistent with a transient ischemic attack. He was examined soon
afterward in the hospital emergency department and no residual neurologic abnormalities were found. The spleen
was not palpable and no bleeding or bruising were present. Laboratory findings included a hematocrit of 43%, white
blood cell count of 11.2 x 109/L, with a normal white blood cell differential, and platelet count of 760 x 10 9/L. Bone
marrow aspirate and biopsy revealed megakaryocytic hyperplasia with clustering of megakaryocytes but no
granulocytic or erythrocytic hyperplasia, no fibrosis, and normal storage iron. Bone marrow culture exhibited growth
in the absence of added growth factors, consistent with a diagnosis of a myeloproliferative disorder. Smoking
cessation and aspirin were advised to prevent recurrent thrombotic episodes. The patient refused hydroxyurea
treatment.

 QUESTIONS:
a) What conditions are considered in the differential diagnosis of thrombocytosis in this patient?
b) Which characteristics present in this case differentiate myeloproliferative disorders from reactive
causes of thrombocytosis?

3. An obese 36-year-old white female emergency medical technician complains of easy bruising of the arms and legs for
several months. This bruising is episodic and seems unrelated to trauma during work. She reports no stinging or
burning sensations before the appearance of bruises. No bleeding from the nose, mouth, or other mucous membranes
is noted. No bleeding into joints or muscles has occurred. Family history is negative for bleeding or bruising. Physical
examination reveals normal skin turgor with a few discrete fresh ecchymoses on the thighs and forearms but no other
obvious bleeding. Platelet count is 380 x 109/L; bleeding time is 5 minutes, 30 seconds; APTT, PT, and fibrinogen
studies are normal.

 QUESTIONS:
a) What additional information will be helpful in defining a cause for this bruising?
b) What conditions should be considered in the differential diagnosis? Why?
c) What additional testing can be performed to confirm a diagnosis?
a) assay. Erythrocyte sedimentation rate, cryoglobulin testing and serum protein electrophoresis may
uncover a vasculitis, or hypergammaglobulinemic purpura.

4. A 23-year-old African-American woman in the 14 th week of her first pregnancy presents to the hospital with mild
confusion, headaches, nausea, easy bruising, and petechiae. Physical examination reveals a temperature of 37.7°C,
blood pressure of 150/100 mm Hg, pulse of 80 beats per minute, and respirations of 14 per minute. Mild confusion
and decrease in light touch sensation of the right arm are noted. Scattered petechiae cover the inner thighs, and
ecchymoses on the forearms are present. No other bleeding is observed. The uterus is enlarged, and a foetal heartbeat
is detected. The spleen tip is not palpable.
Admission laboratory findings show a hematocrit of 21%, white blood cell count of 10 x 109/L, platelet count 18.0 x
109/L, and reticulocyte count of 7%. PT, APTT, and fibrinogen are normal. FDP is positive with a titer of 32, and D-
dimer is positive at 0.5 to 1.0 μg/mL. The Direct Antiglobulin Test (DAT) is negative. The peripheral blood smear
shows moderate poikilocytosis with schistocytes, nucleated red blood cells, and polychromasia. Serum creatinine is
2.5 mg/dL, blood urea nitrogen is 50 mg/dL, calcium is 7.6 mg/dL, and albumin is 2.4 mg/dL. Urinalysis is remarkable
with 3+ proteinuria and numerous red blood cells. Bone marrow aspiration and biopsy reveal erythroid and
 megakaryocytic hyperplasia. Hyaline thrombi are seen in blood vessels of the biopsy. Electrocardiogram and chest
radiograph are normal.

 QUESTIONS:
a) What is the most likely diagnosis? How should the patient be treated?
b) What other conditions should also be considered in the diagnosis? What additional testing could be
performed to confirm or reject these diagnosis?

5. A 66-year-old-man with a diagnosis of amyloidosis was admitted to the hospital with severe gastrointestinal bleeding.
Admission laboratory data included:

TEST RESULT REFERENCE VALUES

Complete Blood Count (CBC) Anaemia; microcytic/hypochromic Normal
Platelet Count Normal Normal
Prothrombin Time (PT) 45.0 seconds 10.0 to 14.0 seconds
Activated PTT (aPTT) 95 seconds 23 to 36 seconds
Fibrinogen 400 mg/dL 200 to 400 mg/dL
Thrombin Time 5 seconds 4 to 12 seconds
PT mixing study 13 seconds 10.0 to 14.0 seconds
aPTT mixing study 30 seconds 23 to 36 seconds
Stypven Time 55 seconds 14 to 20 seconds
Factor II 75 percent 50 to 150 percent
Factor V 93 percent 50 to 150 percent
Factor VII 90 percent 50 to 150 percent
Factor IX 100 percent 50 to 150 percent
Factor X 5 percent 50 to 150 percent

This patient was determined to have Factor X deficiency secondary to amyloidosis. Other vitamin K-dependent factors
were normal, as was Factor V, which ruled out a nutritional deficit or liver disease.

 QUESTIONS:
a) Why were both the PT and aPTT prolonged in this case?
b) What test results indicate a factor deficiency as opposed to a circulating anticoagulant?

6. A 37-year-old man was seen by his physician for a routine physical examination. A full blood work-up was drawn and
sent to a reference laboratory for analysis. Results were as follows:

TEST RESULT REFERENCE VALUES

CBC and platelet count Normal Normal
Prothrombin Time (PT) 12.0 seconds 10.0 to 14.0 seconds
Activated PTT (aPTT) 60 seconds 23 to 36 seconds
Thrombin Time 5 seconds 4 to 12 seconds

The patient was asymptomatic for any bleeding. Testing continued and produced the following results:

TEST RESULT REFERENCE VALUES

aPTT mixing study 32 seconds 23 to 36 seconds
Factor VIII:C 90 percent 50 to 150 percent
Factor IX 77 percent 50 to 150 percent
Factor XI 45 percent 70 to 130 percent

This patient was found to have Factor XI deficiency. The initial history revealed that he was of Eastern European-
Ashkenazi Jewish background. This factor deficiency is prevalent among this population. The patient’s factor level was
not depressed enough to produce symptoms, but could have posed a significant surgical risk. Heterozygous Factor XI
deficiency has a variable presentation and bleeding risk may not correlate with factor levels.

 QUESTIONS:
a) Why was the aPTT abnormal but the PT remained normal in this case?
b) What does the aPTT mixing study result indicate?
c) What treatment is indicated here?

7. A 60-year-old woman was admitted to the emergency department with haemorrhage into the right arm and right
breast. No previous history of bleeding or medication was indicated. Laboratory data upon admission were as follows:

TEST RESULT REFERENCE VALUES

Prothrombin Time (PT) 12.0 seconds 10.0 to 14.0 seconds
Activated PTT (aPTT) 58 seconds 23 to 36 seconds
Fibrinogen 400 mg/dL 200 to 400 mg/dL
aPTT mixing study 40 seconds 23 to 36 seconds
Diluted Russell’s Viper Venom Time ratio 1.1 Less than 1.2
Platelet Neutralization Procedure difference 1 second Less than 5 seconds
 This patient does not have a lupus anticoagulant, but still does not correct in a mixing study with pooled normal
plasma. Further studies must be performed. Incubation of the patient’s plasma with pooled normal plasma for 2 hours
at 37°C, demonstrates time-and-temperature dependency, indicating the presence of an inhibitor. In addition, factor
assays indicate decreased activity of a single factor.

TEST RESULT REFERENCE VALUES

Factor VIII:C 10 percent 50 to 150 percent
Factor IX 90 percent 50 to 150 percent
Factor XI 95 percent 70 to 130 percent

Factor inhibitor analysis (Bethesda assay) for factor VIII:C produced a titer of 8 Bethesda units of inhibitor activity
(normal is less than 0.5 units). One Bethesda unit of inhibitor is equivalent to 50% residual factor activity after
incubation at 37°C for 2 hours. This patient developed a spontaneous inhibitor to Factor VIII:C that resulted in the
massive bleeding into the tissue of her arm and breast.

 QUESTIONS:
a) Which test(s) rule out the presence of a lupus anticoagulant?
b) What treatment is indicated here?

8. A 65-year-old woman with liver disease was admitted to the medical intensive care unit. Admission laboratory data
were as follows:

TEST RESULT REFERENCE VALUES

Prothrombin Time (PT) 14.5 seconds 10.0 to 14.0 seconds
Activated PTT (aPTT) 39 seconds 23 to 36 seconds
Fibrinogen 190 mg/dL 200 to 400 mg/dL
Thrombin Time 18 seconds 4 to 12 seconds

Prolongation of the aPTT and thrombin time could be caused by the presence of heparin. This could be ruled out
before further testing is performed.
Reptilase time = 29 seconds (reference value: 18 to 22 seconds)
Fibrinogen antigen = 380 mg/dL (reference value: 200 to 400 mg/dL)
A PT and aPTT mixing study produced a correction for both tests.
Factors VIII:C, IX, XI, and XII were within normal limits.
This patient was neither receiving heparin nor was the specimen contaminated by heparin, as evidenced by the
prolonged reptilase time. The combination of a decreased fibrinogen level and prolonged thrombin and reptilase
times are suggestive of a dysfibrinogenemia, especially in patients with liver disease. Slight prolongation of the PT
may also be noted and will not be attributable to any factor deficiency. Antigenic assay of fibrinogen usually results in
higher values than the functional (clottable) assay).

 QUESTIONS:
a) How can it be known that this patient is not on heparin therapy?
b) Differentiate between the thrombin time and reptilase time with regard to heparin.
c) What treatment is indicated here?

9. A 25-year-old man was admitted for hernia repair. Admission laboratory data were as follows:

TEST RESULT REFERENCE VALUES

CBC and platelet count Normal Normal
Prothrombin Time (PT) 12.5 seconds 10.0 to 14.0 seconds
Activated PTT (aPTT) 115 seconds 23 to 36 seconds
aPTT mixing study 25 seconds 23 to 36 seconds
Factor VIII:C 97 percent 50 to 150 percent
Factor IX 104 percent 50 to 150 percent
Factor XI 110 percent 70 to 130 percent
Factor XII 96 percent 70 to 140 percent

Interval incubations of the patient’s plasma with the aPTT reagent, containing silica as the activator, produced the
following results:

TEST RESULT REFERENCE VALUES

5-minutes incubation aPTT 115 seconds 23 to 36 seconds
10-minutes incubation aPTT 57 seconds 23 to 36 seconds
15-minutes incubation aPTT 35 seconds 23 to 36 seconds
Prekallikrein activity Less than 1 percent 30 to 100 percent

This patient has a prekallikrein deficiency. Contact system deficiencies (Factors XII, HMWK, prekallikrein) do not pose
any haemorrhagic risk.
  QUESTIONS:
a) Why was the aPTT abnormal, but the PT remained normal?
b) What treatment would be indicated in this case?

10. A 29-year-old woman was seen by her obstetrician for pre-natal care. She had three previous pregnancies, two
resulting in spontaneous first-trimester miscarriages and the third is foetal demise at 28 weeks’ gestation. Laboratory
values were as follows:

TEST RESULT REFERENCE VALUES

CBC and platelet count Normal Normal
Prothrombin Time (PT) 11.5 seconds 10.0 to 14.0 seconds
Activated PTT (aPTT) 45 seconds 23 to 36 seconds
Fibrinogen 375 mg/dL 200 to 400 mg/dL

Further studies included:

TEST RESULT REFERENCE VALUES

aPTT mixing study 43.0 seconds 23 to 36 seconds
Diluted Russell Viper Venom Time ratio 1.60 seconds Less than 1.20
Platelet Neutralization Procedure 15 seconds Less than 5 seconds
difference
Anti-cardiolipin Antibody Positive Negative

This patient has a lupus anticoagulant with positive anti-cardiolipin antibodies. These are known to cause recurrent
spontaneous abortion, as well as thrombotic events such as strok,e deep vein thromboses, and pulmonary embolism.

 QUESTIONS:
a) What complex is inhibited by lupus anticoagulant (LAC), causing a prolongation of the clotting time?
b) Why does the platelet neutralization procedure (PNP) show a significant difference in this patient?
c) What form of treatment is indicated here?

11. A 40-year-old woman was scheduled for an elective surgical procedure. Pre-admission testing revealed the following
resuts:

TEST RESULT REFERENCE VALUES

CBC and platelet count Normal Normal
Prothrombin Time (PT) 18.0 seconds 10.0 to 14.0 seconds
Activated PTT (aPTT) 30 seconds 23 to 36 seconds

After further examination, the patient stated that she had episodes of epistaxis and easy bruising. Additional
laboratory testing included:

TEST RESULT REFERENCE VALUES

PT 1:1 mix 13.0 seconds 10.0 to 14.0 seconds
Factor VII 30 percent 50 to 150 percent

This patient has Factor VII deficiency. Factor VII is not measured by the aPTT and is normal, whereas the PT is
sensitive to deficiencies of the extrinsic system (factors I, II, V, VII, and X) and is prolonged in these cases.

 QUESTIONS:
a) What material was used to perform the mixing study?
b) What treatment is indicated here?
c) Why was the PT prolonged and the aPTT normal in this case?

12. A 5-year-old boy presented in the emergency department with a hemarthrosis of the right knee after falling off a
playground swing. Physical examination revealed a well-nourished child with no fractures or other ecchymoses. He
was afebrile. Laboratory findings were as follows:

TEST RESULT REFERENCE VALUES

CBC and platelet count Normal Normal
Prothrombin Time (PT) 13.0 seconds 10.0 to 14.0 seconds
Activated PTT (aPTT) 87 seconds 23 to 36 seconds
Fibrinogen 325 mg/dL 200 to 400 mg/dL
Bleeding Time (BT) 6 minutes 2 to 9 minutes

Further studies included:

TEST RESULT REFERENCE VALUES

aPTT 1:1 mix 32 seconds 23 to 36 minutes
Factor VIII:C 10 percent 50 to 150 percent
vWF:Antigen 90 percent 50 to 150 percent
 This patient was known to have haemophilia A.

 QUESTIONS:
a) What material did the laboratory professional use when performing this mixing study?
b) What treatment is indicated for this patient?

13. A full-term male infant was born by normal vaginal delivery. Thirty hours postpartum, there was new onset of oozing
of blood at the umbilical cord stump. Laboratory analysis included:

TEST RESULT REFERENCE VALUES

CBC and platelet count Normal Normal
Prothrombin Time (PT) 14.0 seconds 10.0 to 14.0 seconds
Activated PTT (aPTT) 36 seconds 23 to 36 seconds
Fibrinogen 400 mg/dL 200 to 400 mg/dL

Clinical presentation did not indicate a haemorrhagic tendency. Late onset of umbilical cord stump bleeding prompted
the evaluation of Factor XIII. A re-calcified plasma clot exposed to a 5 M urea solution dissolved within 4 hours. This is
conclusive for Factor XIII deficiency.

 QUESTIONS:
a) Is the 5-molar urea lysis test a qualitative or quantitative determination?
b) What treatment is indicated for this patient?

14. A 12-year-old boy underwent tooth extraction in preparation for orthodontia. Persistent bleeding followed. The
history was remarkable for bruising and frequent epistaxis. The patient’s mother also experienced easy bruising and
menorrhagia. Physical examination revealed several medium-sized ecchymotic lesions on the lower extremities.
Laboratory findings were as follows:

TEST RESULT REFERENCE VALUES

Prothrombin Time (PT) 12.0 seconds 10.0 to 14.0 seconds
Activated Partial Thromboplastin Time (aPTT) 40 seconds 23 to 36 seconds
Bleeding Time (BT) Greater than 15 minutes 2 to 9 minutes
Platelet Count 300 x 109/L 150 to 450 x 109/L
Factor VIII:C 30 percent 50 to 150 percent
vWF: Antigen (vWF:Ag) 45 percent 50 to 150 percent
vWF: Ristocetin Cofactor (vWFR:Co) 41 percent 50 to 150 percent
Ristocetin-Induced Platelet Aggregation (RIPA) Depressed response Normal response
Multimers Normal Normal

The history of bruising, epistaxis, and dental bleeding with a prolonged aPTT, BT, and reduced Factor VIII:C, vWF:Ag,
vWFR:Co, and RIPA are indicative of classic von Willebrand disease (type 1).

 QUESTIONS:
a) Which blood product could correct the RIPA value in this case?
b) Which laboratory values reflect a type 1 von Willebrand disease?
c) What form of therapy would be indicated here?