COAG Review

1
COAG Review
2
BOR Exam
Thrombocytes and hemostasis will comprise 29 of
the subtest and 5 of the total exam (ASCP).
3
NCA EXAM

• 9 questions on 100 question test
• 2 recall
• 5 application
• 2 analysis

4
Basic Cascade
HMWK PK XII XI IX
VII Ca
Ca TT PF3
VIII X Ca PF3 V
II I XIII

 
 
 
5
There are many cascades to use. Some are highly
complex and contain the anticoagulant aspects of
the pathway as well as clotting components. Be
sure you can use the pathway you choose to learn.
6
Correction Studies There are many questions that
will require you to know what is in aged serum
and adsorbed plasma. Aged serum 2 7 9 10
11 12 Adsorbed plasma 1 5 8 13 11 12
7
Correction study questions will also use normal
plasma, and corrections with factor deficient
plasma. The next several slides will be
examples of registry questions that require a an
understanding of the Pathway and correction
studies
8

• Example 1
• A 56 year old woman was admitted to a hospital
  with a history of moderate to severe bleeding
  tendency of several years duration. Epistaxis and
  menorrhagia were reported. Prolonged APTT was
  corrected with fresh normal plasma, adsorbed
  plasma, and aged serum. Deficiency of the
  following is most likely?
• Factor XII
• Factor VIII
• Factor XI
• Factor IX

9

• Example 2
• A patient has a history of mild hemorrhagic
  episodes. Laboratory results include prolonged PT
  and APTT. The abnormal APTT was corrected by
  normal and adsorbed plasma, but not aged serum.
  Which of the following coagulation factors is
  deficient?
• Prothrombin
• Factor V
• Factor X
• Factor VII

10

• Example 3
• A patient with a history of frequent mild
  bleeding episodes has a normal PT and a
  moderately prolonged APTT, which is corrected by
  the addition of each of the following normal
  plasma, factor VIII deficient plasma, factor IX
  deficient plasma. Which factor assay(s) should be
  run?
• VIII
• IX
• XI and XII
• None a circulating inhibitor is present

11
Know your factor groups. What factors are labile,
and how long are labile Factors stable at room
temp? What factors are vitamin K dependent,
produced in the liver, affected by coumadin, and
are stabile at room temp? What factors are
considered contact factors?
12

• Example
• Coagulation factors affected by coumadin drugs
  are
• VII,IX, and X
• I, II, V, and VII
• II, VII, IX, and X
• II,V and VII
• Which of the following factors is considered to
  be labile?
• II
• V
• VII
• X

13
Labile factors I V VIII and XIII Liver
dependent, Vitamin K dependent, Stable, and
affected by Coumadin II VII IX and
X Contact factors PK HMWK XI XII
14
Know your factor deficiencies, especially the
hempohilias (A,B and C). Hemophila A Factor VIII
Hemophilia B Factor IX Hemophilia C Factor
XI Be familiar with the clinical presentations
and lab findings.
15

• Example
• Which of the following is most useful in
  differentiating hemophilias A and
• B?
• Pattern of inheritance
• Clinical history
• APTT
• Mixing studies (Substitution study)
• A hemophiliac male and a normal female can
  produce a
• Female carrier
• Male carrier
• Male hemophiliac
• Normal female

16
Know Von Willebrands disease. You need to know
the clinical presentation and lab findings.
Von Willebrands
Hemophilia A Deficiency VIIIvWF
VIIIC VIII
AHF Inheritance Dominant
autosomal Recessive Sex-linked Clinical
Bleeding Gums, GI, Mucous
Hemarthrosis,muscle
membranes
visceral Lab tests BT/PFA100 A
N Clot
retraction N
N Plt count
N
N Ristocetin A
N PT
N
N APTT A
A VIII
A
A vWFAG A
N
17
Example The following lab data were obtained
from a 40-year old woman with a long history of
abnormal bleeding PT Normal APTT
Prolonged VIII coagulant activity
Decreased VIII-related antigen Markedly
decreased Plt count Normal Bleeding
Time Prolonged Which of the following disorders
does this woman most likely have? a.classic
hemophilia b.Von Willebrands disease c.
Christmas disease d. DIC
18

• Know the role of platelets in coagulation.
• Topics frequently covered in review books include
• Reagent added to platelet aggregation studies to
  test
• for release of dense granules as well as
  aggregation
• -firefly luciferase- (lumiaggregometry)
• When performing plt aggregation studies, the
  instrument
• should be set on 100 transmittance using
  patient plt
• poor plasma
• Plt aggregation pattern expected from patient
  with Bernard-
• Soulier if ristocetin is the agonist-
• This would be a flatline pattern or no
  aggregation
• On patients plt rich plasma sample used to set
  0
• baseline for aggregation studies, what should
  the plt count
• be? 300 x 109/L (we use 250 or 50)

19
5. What is the most common cause of an
abnormality in hemostasis quantitative
abnormality of platelets 6. Plt aggregation is
dependent in vitro on the presence of calcium
ions 7. A bleeding time is used to evaluate the
activity of platelets This would also be
true for PFA100 studies 8. A patient taking
aspirin for pain would have an abnormal
bleeding time. 9. In Von Willebrands disease,
platelets give an abnormal aggregation in the
presence of ristocetin 10. In the performance
of a bleeding time test, the blood
pressure cuff should be inflated to 40mm Hg
20
Know the collection and storage requirements for
Coagulation examples of questions 1.
Anticoagulant of choice 3.2 sodium citrate
Order of draw red, blue, purple 2. Thawing of
platelet-poor plasma that has been stored At
-40C should be perfomred at 35-38 C 3.
Collection on patients with Hcts lt20 and gt55
Formula to adjust anticoagulate C1.85 X
10-3(100-H) x V C volume of sodium citrate in
ml Vvolume of whole blood H hematocrit
21
4. Specimen for APTT in sodium citrate is
collected at 930 am and allowed to remain at
room temp until 330- How will this effect
results-Prolonged due to loss of VIII 5. The tech
notes an APTT was at room temp for 3 hours.
The tech should request a new sample 6. Blood
for coag studies must be centrifuged - with the
top on. 7. A sample was drawn in sodium
citrate. It has approximately 90 of the expected
amount. The specimen should be deemed -
acceptable
22

• There are several questions in current review
  books
• That relate to quality control. Need to know
  basic
• QC procedures and guidelines. Examples.
• Mean of PT control is 12.2. One SD is 0.2.
  According to
• Gaussian distribution, 95 will fall in what
  range
• Upward trend observed over 6 days in QC plot for
  PT on a
• Photo-optical analyzer. This indicates-loss of
  precision
• Abnormal QC is out for PT and APTT. The normal
  control
• is in range. The appropriate action is Repeat
  abnormal
• control on a new bottle before proceeding.

23

• Know basics of testing procedures (photo-optical
  vs
• mechanical) and basic instrumentation guidelines.
• Examples
• Specimen from a patient with severe jaundice. PT
  on a
• photo-optical analyzer is 7.4 seconds. The tech
  should-
• Perform test on a electromechanical instrument
• Patient with increased cryoglobulin is evaluated
  for bleeding
• disorder. Which instrument will give accurate
  results
• - electromechanical
• On automated analyzers, duplication of normal
  results is not
• appropriate because-lab can document precision
  to reflect
• analyzer performance

24

• Five preoperative patients and QC for APTT were
• prolonged on an optical density analyzer.
  Results were
• confirmed using an alternate method
  (mechanical).What would be explanation- reagent
  contamination
• If the automatic pipette is left on after each
  use on an
• electromechanical system what will happen-probe
  will
• fall into reactor when you pick up next sample

25

• Be familiar with the basic tests and what
  information they
• Provide. Examples
• The PT requires that patient citrated plasma be
  combined
• with---Ca and thromboplastin
• A bedside test for monitoring heparin isACT
• The APTT monitors Heparin therapy
• Plasma is diluted in a fibrinogen-activity
  determination to
• decrease the --- influence of inhibitors
• 5. Common test for monitoring Coumadin --PTINR

26

• Questions dealing with Factor XII
• Patient has a normal PT and a prolonged APTT
  using
• a kaolin activator. The APTT corrects to normal
  when the
• incubation is increased---This suggests Hageman
  factor (XII)
• Factor XII is associated with a negative bleeding
  history
• Factor XII is involved in the following
• Activating C1 to C1 esterase
• Activation of Plasminogen
• Activation of XI

27

• DIC
• Know the clinical presentations and lab findings
  in DIC.
• Clinical Manifestations
• Hemmorhaging usually from 3 unrelated sites
• Petechiae, purpura, gangrene, wound bleeding,
• veni-puncture bleeding, subcutaneous hematoma
• Microthrombi
• End-organ dysfunction

28

• DIC
• Lab Findings
• Hypofibrinogenemia
• Abnormal PT
• Abnormal APTT
• Abnormal Thrombin Time
• Abnormal PLT count
• Abnormal tourniquet test and clot retraction
• Positive FDP, Ddimer, and protamine sulfate
• ATIII consumption
• Leukocystosis
• Schistocytes

29

• Some conditions associated with DIC
• Obstetric accidents
• Intravascular hemolysis
• Septicemia
• Viremia (varicella)
• Leukemias Acute Promyelocytic
• Malignancy
• Burns
• Crush injury

30

• Examples of DIC questions and FDP questions
• A patient with severe DIC has an FDP of gt200
  ug/ml
• and a clottable fibrinogen of 50mg/dl. The
  fibrinogen level
• may have been affected by -- Interference from
  elevated
• FDP products
• A test used to monitor streptokinase therapy is
  fibrin
• split products
• In latex agglutination method for determining
  serum
• fibrin/fibrinogen degredation products, which of
  the
• following can be a cause of false positive
  results
• The specimen is collected in a regular red-top
  tube instead
• of special FDP tubes.
• 4. Acute DIC is characterized by
  -hypofibrinogenemia

31
5. A patient develops severe unexpected bleeding
and the following test results are
obtained PT and APTT Prolonged PLTS 50 x
10-3/uL Fib 30 mg/dl FDP Increased Most
probable cause DIC
32

• Know what effect inhibitors will have on basic
  coag
• Tests, and how to identify and confirm them.
• Examples
• Patient has a normal PT and a prolonged APTT. To
• determine if the prolongation is due to a factor
  deficiency
• or a circulating inhibitor the CLS should-Mix 1
  part
• patient plasma with 1 part normal reagent plasma
  and repeat
• APTT
• A patient's thrombin time is 25.5 seconds. The
  control is
• 11.5 seconds. The patients plasma is mixed with
  an equal
• part of normal plasma. The thrombin time is
  rerun and is
• 28 seconds. This indicates----circulating
  anticoagulant
• Plasma from a patient with a Lupus inhibitor can
  show-
• A prolonged APTT and a normal PT
• An abnormal APTT that does not correct when mixed
  with
• equal parts of normal plasma indicates a
  circulating
• inhibitor

33

• Thrombin time is used to detect dysfunctional
  fibrinogens and
• Is very sensitive to anticoagulant therapy.
  Examples of
• questions
• A 54 year old man was admitted with pulmonary
  embolism
• and given streptokinase. What would be most
  useful in
• monitoring this therapy?
• a. APTT
• b. Bleeding time
• c. PT
• d. Thrombin time
• All of the following cause an increase in the
  thrombin
• time except
• a. hypofibrinogenemia
• b. increased FDP
• c. heparin therapy
• d. prothrombin time

34

• Anticoagulant Therapy
• Coumadin degrades vitamin K and thus lowers
  factors II,VII,
• IX, and X
• Heparin binds to ATIII to inhibit thrombin
• Examples of questions
• The first step in the determination of functional
  ATIII is to
• a. neutralize plasma ATIII
• b. Neutralize thrombin with test plasma
• c. incubate plasma with anti-ATIII
• d. Precipitate ATIII with plasma

35

• Biological assays for ATIII based on inhibition
  of
• a. Factor VIII
• b. Heparin
• c. serine proteases
• d. Anti-ATIII globulin
• Decreased response to heparin therapy may be
  caused by decreased
• levels of
• a. ATIII
• b. Platelet factor 4
• c. Factor XIIII
• d. thromboxane
• Enzymes measured in chromogenic substrate assays
  are of what class?
• Serine proteases
• Lysine arginases
• Carboxyl anhydrases
• Lysases

36

• The last examples are in a miscellaneous
  category.
• Questions on these types of topics were rare in
  the review books.
• Clot incubated at 37C dissolves in 24 hours you
  suspect what-
• Fibrinolysis
• Low fibrinogen level
• Factor VII deficiency
• Thrombocytopenia

37

• MISC continued
• Results on newborn were
• PT 12.8 (9.5-14.5)
• APTT 34.5 (20-35 sec)
• TT 14.0 (9-13)
• Fib 380 mg/dl (200-400)
• This suggests
• a. Factor VII
• b. Normal newborn results
• c. hyperfibrinogenemia
• d. Vitamin K deficiency
• Most potent plasminogen activator in contact
  phase is-
• kalikrein

38

• Misc Continued
• Protein C and S are part of anticoagulant
  process.
• Protein C with the cofactor protein S
  inactivate V and VIII.
• Deficiencies of either will increase the risk of
  thrombosis.
• Factor XIII- Associated with delayed bleeding and
  5M
• urea solubility test