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TBL 3 > Coagulation Assays > Flashcards

Coagulation Assays Flashcards

1
Q

what two major components of clotting do we want to be able to asses if we suspect someone has a bleeding disorder?

A
  1. primary hemostasis, involving platelets

2. secondary hemostasis, involving formation of fibrin

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2
Q

what’s the process of a test that looks at how well a patient can form fibrin?

A
  1. draw blood into a specially prepared tube containing citrate, which removes calcium from the blood to prevent clotting before the sample reaches the lab
  2. the blood is spun down and the red blood cell and buffy coat layers removed before the assays are performed
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3
Q

what tests are used to asses the coagulation cascade?

A
  • PT
  • INR
  • PTT
  • TT
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4
Q

what is PT?

A

prothrombin time

used to assess the extrinsic and common pathways of the coagulation cascade

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5
Q

how do you determine PT?

A

take the patient’s plasma, add thromboplastin (a tissue factor-like substance and phospholipid) and calcium

then measure the time (in seconds) it takes to form fibrin

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6
Q

what’s the normal PT range?

A

11-14 seconds

The problem with this test is that PT values can fluctuate between hospitals because thromboplastin reagents vary a lot from manufacturer to manufacturer

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7
Q

what is INR?

A

International Normalized Ratio

was developed to standardize the method of presenting the PT value

INR is derived from a formula using the ratio of the patient’s PT to a standard PT

so this way the INR value of the patient will be similar at any hospital

INR = 0.8-1.2

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8
Q

what is PTT?

A

partial thromboplastin time

used to assess the intrinsic and common pathways of the coagulation cascade

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9
Q

how did PTT get its name?

A

it was discovered that fibrin could form by just using part of the thromboplastin reagent.

It is now known that the part of the thromboplastin reagent used is the phospholipid (no tissue-factor-like substance is present)

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10
Q

how do you determine PTT?

A

take the patient’s plasma, add phospholipid and calcium

then measuring the time (in seconds) it takes to form fibrin

makes sense because normally in the body tissue factor is necessary to activate the extrinsic pathway, but it is not necessary to activate the intrinsic pathway

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11
Q

what is aPTT?

A

activated partial thromboplastin time

similar to the PTT except that an activator is added to the PTT assay, which helps to speed up clot formation and results in a narrower reference range

aPTT is considered to be more sensitive than the PTT and is used to monitor heparin therapy

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12
Q

what’s the normal aPTT range?

A

25-35 seconds

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13
Q

what is TT?

A

thrombin time

assesses the conversion of fibrinogen to fibrin

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14
Q

how do you determine TT?

A

take the patient’s plasma, adding thrombin, and measuring the time (in seconds) it takes to form fibrin

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15
Q

what’s the normal TT range?

A

12-14 seconds

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16
Q

Which pathways of the clotting cascade do the PT and PTT assess?

A

PT is used to assess the extrinsic pathway

PTT is used to
assess the intrinsic pathway

both assess the common pathway

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17
Q

what are coagulation assays used for?

A

used to evaluate patients with bleeding of unknown etiology or to monitor anticoagulant therapy

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18
Q

what are examples of acquired bleeding disorders?

A
  • liver disease
  • vitamin K deficiency
  • disseminated intravascular coagulation
19
Q

where are coagulation factors involved in the coagulation cascade produced?

A

they’re all produced in the liver!

20
Q

what happens to coagulation if there is liver disease?

A

all coagulation factors are made in the liver so patients with cirrhosis or other advanced liver diseases have an especially high risk of bleeding because they are unable to make coagulation factors at a normal rate

all coagulation assays are prolonged (PT/INR, PTT, TT) since all the coagulation factors are decreased

21
Q

which drugs are anticoagulation drugs?

A

warfarin

heparin

22
Q

what does warfarin do?

A

anticoagulant

acts as a vitamin K antagonist, decreasing production of vitamin K dependent clotting factors II, VII, IX, X

factor IX is part of the intrinsic cascade, while factor VII is part of the extrinsic cascade, thus both the PT and the PTT will be prolonged

23
Q

what test do you use to monitor warfarin therapy?

A

PT/INR study

warfarin decreases production of factors II, VII, IX, X

you use this test because factor VII has the shortest half-life of all the vitamin-K-dependent factors

so the effects of warfarin on coagulation are reflected by the PT/INR before the PTT

24
Q

what does heparin do?

A

heparin indirectly binds to antithrombin to enable antithrombin to inactivate multiple clotting factors, including IIa, VIIa, IXa, Xa, and XIa

antithrombin acts on both the intrinsic and the extrinsic arms of the clotting cascade

however, heparin has more of an effect on the intrinsic arm than it does on the extrinsic arm

25
Q

what test do you do to monitor heparin therapy?

A

PTT testing

this is because heparin has more of an effect on the intrinsic arm than it does on the extrinsic arm

26
Q

what diseases are due to factor deficiency?

A

hemophilia A and hemophilia b

27
Q

what is a mixing study?

A

mixing study can help figure out why the PTT is prolonged

If the PTT comes back prolonged with an unclear etiology, a mixing study can be done to determine if the prolongation is due to factor deficiency (e.g., hemophilia A or B) or the presence of antiphospholipid antibodies (also sometimes called inhibitors)

28
Q

when are anti-phospholipid antibodies made?

A
  • after starting a new drug

- in patients with lupus

29
Q

what are the effects of anti-phospholipid antibodies?

A

most have no clinical effect

some cause thrombosis

30
Q

what do anti-phospholipid antibodies do?

A

in laboratory tests, anti-phospholipid antibodies can bind to, and inactivate, reagents that contain phospholipids (like the thromboplastin reagent that is used in the PTT assay)

this makes less reagent available, and in the case of the PTT, it leads to a prolonged PTT

31
Q

What do anti-phospholipid antibodies do in a patient? And what do they do to a PTT?

A

In a patient, anti-phospholipid antibodies sometimes cause thrombosis.

in the PTT, they bind to the PTT reagent, inactivate it, and cause a falsely prolonged PTT

This looks weird if you don’t know what’s going on: the patient may have thromboses, but the PTT is prolonged (making it seem like the patient is at risk for bleeding)

THIS IS IMPORTANT!! It’s super weird but you need to remember it

32
Q

how do you do a mixing study?

A

you mix the patient’s plasma with normal plasma, and then running the PTT again

33
Q

explain the results of a mixing study

A

you mix the patient’s plasma with normal plasma, and then running the PTT

if the new PTT is normal (if it “corrects”), that means you added something to the mixture (a coagulation factor) that was missing in the patient

if the new PTT is still prolonged (if it “doesn’t correct”), that means there is something in the patient’s blood (aka an anti- phospholipid antibody) that is binding up the PTT reagent and falsely prolonging the PTT

34
Q

If you do a mixing study, and the PTT is still prolonged (it doesn’t correct), what does that mean?

A

It means the patient has anti-phospholipid antibodies

these bind to the PTT reagent, causing a falsely prolonged PTT

35
Q

what is a fibrin degradation product assay used for?

A

FDP is used to measure the amount of fibrin degradation products present

36
Q

what does an elevated FDP indicate?

A

Elevated FDPs indicate that fibrinolysis (breaking down of clots) is occurring in the body

37
Q

what does a D-dimer assay measure?

A

measures only chunks of fibrin that have been crosslinked in a clot

so it’s a little more specific for fibrin in actual clots than the FDP assay is

38
Q

what are FDP and D-dimer assays useful for?

A

evaluating for disorders with increased clotting and breakdown

  1. deep vein thromboses (DVT)
  2. pulmonary embolism (PE),
  3. disseminated intravascular coagulation (DIC)
39
Q

what is DIC?

A

disseminated intravascular coagulation

disorder in which there is abnormal activation of the coagulation cascade, resulting in widespread microthrombi throughout the vessels

however, due to such massive activation of the coagulation pathway, clotting factors, fibrin, and platelets are consumed at a fast rate, resulting in hemorrhage, thrombocytopenia, factor deficiencies, and vessel injuries

so this means that both hemorrhage and thrombosis occur simultaneously

40
Q

in what patient population do you usually see DIC?

A

most commonly seen in critically ill people

41
Q

what are the results from a coagulation study that would indicate DIC?

A

prolonged PT, PTT, and TT

elevated FDP or d-dimer assay

decreased platelet count

42
Q

A patient in the ICU suddenly starts to ooze blood from his central venous line. Lab studies show acute kidney failure. Which of the following lab studies most likely supports the diagnosis?

A. High Platelet Count

B. High PTT

C. Low D-Dimer

D. Mixing study that does not correct

E. Normal PT

A

high PTT

patient’s symptoms with acute kidney failure and oozing blood point to DIC, where thrombosis is causing significant end organ infarction

Patients with DIC will have high PTT and high PT because there is severe thrombocytopenia.

DIC also leads to a high plasma D-dimer level and low platelet counts

A mixing study will actually correct this patient’s abnormal PT and PTT levels because the mixing study will replenish factor deficiencies associated with DIC

43
Q

A patient who is a chronic alcohol abuser arrives to the ED intoxicated with a protuberant abdomen. Patient states that he has been drinking for weeks without a break. Labs show prolonged PT, INR, and thrombocytopenia. What is the likely cause of the prolonged PT and INR?

A

cirrhosis

likely has cirrhosis as indicated by the protuberant abdomen and chronic alcohol use

44
Q

A patient has been started on warfarin for his DVT. Laboratory tests to monitor his warfarin therapy show elevated INR of 2.3. Which of the following clotting factors is associated with the prolonged INR?

A. Factor I
B. Factor V
C. Factor VII
D. Factor XI
E. Factor XII
A

Factor VII

Warfarin inhibits factors II, VII, IX, and X, leading to inhibition of the extrinsic pathway and thus prolonged PT and INR

INR is a common method of monitoring warfarin therapy

TBL 3 (17 decks)

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