Hypercoagulable States and CPB / Test 3/3 Flashcards Preview

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Flashcards in Hypercoagulable States and CPB / Test 3/3 Deck (63):
1

“Hypercoagulability” can be broadly defined as a risk of ______1_______ in circumstances that would not cause thrombosis in a normal subject.
It can be either ____2____ or ___3_____.

1.) Thrombosis
2.) Inherited
3.) Acquired

2

A hereditary tendency to thrombosis, irrespective of its cause has been referred to as ?

Thrombophilia

3

2 factors that accelerate clot formation ?

Factor VIII & Factor V

4

3 factors that Inhibit clot formation ?

Protein C, Protein S, Thrombomodulin
Antithrombin III

5

What inhibits thrombin and other serine proteases ?

Natural Anticoagulant Antithrombin III

6

What inhibits Factor V and VIII ?

Natural Anticoagulant
Protein C

7

Cofactor for protein C ?

Natural Anticoagulant
Protein S

8

What does the (Natural Anticoagulant) Tissue Factor Pathway Inhibitor bind to ?

binds factor Xa and VII-tissue complex

9

True hypercoaguable states can only be determined after RULING OUT other causes…

Pregnancy
Recent surgery Immobilization (stasis)
Obesity
Malignancy

Fracture

Heart failure
Oral contraceptive use

10

CRITERIA for True hypercoaguable state ?

- Recurrent thrombosis
- thrombosis in Unusual sites (cerebral veins, hepatic veins, renal veins, IVC, mesenteric veins)

- First time thrombosis at age

- Family history of thrombosis

11

What can make a patient PRONE to coagulability ?

-Protein C deficiency
-AT III deficiency
-Protein S deficiency
-Activated Protein C (APC) resistance
- Mutation of factor V that makes it resistant

12

Quantitative or Qualitative abnormalities of individual, specific coagulation factors that directly produce a pro-thrombotic state describes what state of hypercoagulability ?

Primary Hypercoagulable State

13

Represents a diverse group of clinical disorders that are associated with a thrombotic tendency

Secondary Hypercoagulable State

14

Mutations of one of the physiological antithrombotic factors which leads to a quantitative deficiency or loss of function?

Inherited

15

Hypercoagulable States
that are sometimes inherited, but are more commonly ACQUIRED ?

Acquired:

Cancer
Liver Problems
Birth Control Pills > PE

16

Antithrombin/Heparin Disorder ?

Antithrombin deficiency

17

Protein C/Protein S Disorders
?

Protein C deficiency
Protein S deficiency
Resistance to activated protein C

18

Fibrinolytic Disorders

Hypoplasminogenemia
or
Dysplasminogenemia

19

Prevalence of deficiencies of hemostatic factors responsible for hereditary thrombotic disease.

AT III
Protein C
Protein S
APC Resistance

AT III 1%
Protein C 8%
Protein S 10%
APC Resistance 17%

20

Characterized by proportionate reductions in activity and antigen levels, each to about 50% of normal in heterozygous individuals, indicating synthetic abnormality of a functionally normal molecule describes what deficiency ?

Antithrombin III Deficiency Type 1

21

Normal or near normal antigen levels are accompanied by low activity levels, indicating a functionally defective molecule.
- Affecting heparin binding
- impaired reactive site function
- multiple abnormalities
causing both abnormal
heparin binding and
abnormal protease inhibition

Antithrombin III Deficiency
Type 2

22

Suspected ATIII DefieciencyCPB Management & Action.
ACT

Repeat Bolus
ACT still low
- Give 2 units FFP … or
- Give Thrombate
Recheck ACT

23

A naturally occurring anticoagulant which preserves blood fluidity and limits clot formation to the sites of vascular injury.

Protein C

24

Rare but fatal hereditary condition (Inherited autosomal disease) manifested by massive disseminated intravascular coagulaopathy and purpura fulminans in the neonatal period?

Homozygous Protein C deficiency

25

Prevalence is 0.1 to 0.5% in the general population, the vast majority remain symptom free.

Inherited autosomal disease
Heterozygous Protein C deficiency

26

Patients with heterozygous PC deficiency are at lifelong risk for thrombosis, but the episodic nature of clinical thrombosis suggests that an _____ ______ _____ may be necessary to trigger a clinically significant thrombotic event.

acquired thrombogenic stimulus

27

Protein C is activated upon

the production of thrombin.

28

Thrombin generation promotes clot formation by

cleaving fibrinogen into fibrin
and also activates the protein C system.

29

Activated protein C subsequently suppresses further thrombin generation and enhances what?

fibrinolytic potential

30

Activated protein C, along with protein S, act to inhibit the intrinsic coagulation pathway by inactivating what factors?

factors Va and XIIa

31

Activated PC also neutralizes

Plasminogen Activator Inhibitor, which enhances fibrinolysis

32

Is Protein C Deficiency a problem for Perfusionists?

Kinda bu not really, Patients’ should still achieve anticoagulation with heparin

33

“Protein C deficiency is associated with what, following open heart surgery"?

massive cerebral thrombosis

34

The possibility of an abnormally low anticoagulant potential at the time when the patient is separated from bypass and heparinization is reversed may be an important factor in what ?

subsequent morbidity associated with thrombotic complications

35

How do you restore normal levels Protein C Pre-CPB ?

Prime- As per protocol with the addition of one unit of FFP to normalize Protein C levels

36

What is the concentration of Protein C in FFP ?

87 ±15 U/dL

37

As a general rule- 2 units of PC per kg. of body weight will give what ?

1% rise in Protein C levels

38

What are 2 Other Protein C Sources ?

Cryoprecipitate
Protein C Concentrates

39

Why is the long term use of FFP or Protein C concentrates not a reasonable alternative ?

1/2 life of Protein C is ~ 8 hrs

40

Suspected Protein C Deficiency CPB Management & Action

Pre-CPB
Restore normal levels
- FFP
- Cryoprecipitate

Slow, conservative heparin reversal

41

Activated Protein C Resistance is present in what percentage of the population ?

3 - 7 %

42

Factor V Leiden is produced by a single point mutation at position 1691 with a substitution of ___ _ ___, which eliminates the protein C cleavage site on activated or functional factor V.

glycine for arginine

43

A Factor V Leiden abnormality results in a ?

prothrombotic state

44

Protein S, a cofactor
Enhances the effect of activated protein C by a factor of ?

10

45

Protein S Is down regulated by compliment regulatory protein ?

(C4bBP)

46

Protein S Deficiency Type I =

Quantitative

47

Protein S Deficiency Type II =

Qualitative

48

Dysfunctional Thrombomodulin
can result from ?

structural or conformational changes that alter the expression or function of the molecule.

49

Quantitative Fibrinolytic Disorder ?

Hypoplasminogenemia

50

Qualitative Fibrinolytic Disorder ?

Dysplasminogenemia

51

Name 2 Fibrinolytic Disorders
AKA
Plasminogen activator deficiency ?

- Decreased TPA
- Increased plasminogen activator inhibitor

52

Hypercoagulable States such as
Dysfibrinogenemias
which is a qualitative abnormality of fibrinogen, can be detected by what ?

- Prolongation of thrombin
time.
- Prolongation of Reptilase
time.
- Disproportionately lower
levels of fibrinogen

53

What does Fibren degradation products (FDP) tell us?

If were clotting or breaking down clots.

54

Dysfibrinogenemia with a defective thrombin binding to the abnormal fibrinogen would lead to what ?

increased circulating thrombin which would be a prothrombotic stimulus for processes such as platelet aggregation.

55

Resistant lysis of the abnormal fibrin, is possibly the result of ?

defective binding of t-PA or plasminogen to the abnormal fibrin

56

By itself, is not associated with clinical bleeding.
It is associated with a predisposition to thrombosis

Lupus-like Anticoagulant

Antibody to phospholipid which causes an increased APTT

57

APL antibodies often interfere with in vitro tests of hemostasis by ?

impeding the anchoring of coagulation proteins to phospholipid surfaces

58

An autoimmune disorder associated with lupus ?

erythematosus

59

Antiphospholipid antibody Syndrome =

inhibits the protein C system

60

Thrombosis-prone due to multiple and often complex abnormalities of the hemostatic system.
-Abnormalities of blood flow.
-Abnormalities of blood composition.
-Abnormalities of the vessel wall.

Secondary Hypercoagulable States

61

In patients with a diagnosed hypercoagulable state undergoing CPB, normalize with the deficient product if possible.
Monitor closely during heparin reversal and into the post-operative period. The use of the following is suggested ?

TEG

62

Vasculitis and homocystinuria describes what ?

Abnormalities of the blood vessel wall

63

Oral contraceptives, nephrotic syndrome, paroxysmal nocturnal hemoglobinuria, and hyperlipidemia describes what ?

Abnormalities of blood composition.