Chapter 7: Bleeding and Hemostasis

Question 1

What are three naturally occurring anticoagulants?

Answer 1

• Antithrombin (activated x1000 by heparin)
• Activated protein C
• Tissue factor pathway inhibitor (increased by heparin)
  AAT

Question 2

Normal endothelium controls platelet reactivity through what 3 known inhibitors?

Answer 2

Prostacyclin (PGI2) -> limits platelet response to thromboxane-A2
Ecto-ADPase
Nitric Oxide (decreases IC calcium flux, reducing receptors and affinity of fibrinogen binding sites)

Question 3

What is the life span of a platelet?

Answer 3

6-8 days

Question 4

Activated platelets release secondary agonists – notably which two?

Answer 4

Thromboxane A2
adenosine diphosphase (ADP)

Question 5

Secondary platelet agonist binding does what to platelets at the end of the primary haemostasis?

Answer 5

Agonist binding exposes binding domains for fibrinogen – binding results in interplatelet cohesion and aggregation.

Question 6

The extrinsic pathway is initiated by what?
Intrinsic?

Answer 6

Extrinsic pathway – initiated by tissue factor (Factor 3)
Intrinsic: Contact activation of Factor 12

Question 7

What are the two main “paradigm shifts” when referring to the cell-based model of coagulation?

Answer 7

That tissue factor is the primary physiologic initiator of coagulation
That coagulation is localized to and controlled by cellular surfaces

There are three overlapping phases: initiation, amplification, and propagation.

Question 8

What are the three overlapping phases of the cell-based coagulation model?

Answer 8

Initiation (on TF bearing cells)
Amplification
Propagation (on platelets)

Question 9

PT prolongation means what?

Answer 9

defective extrinsic and / or common pathway

Question 10

APTT prolongation means what?

Answer 10

defective intrinsic and /or common pathway

Question 11

Isolated coagulation factor deficiency generally does not occur until that factor is decreased to less than what % of normal?

Answer 11

25-30%

Question 12

What are three described methods of platelet function testing in dogs/cats? (3)

Answer 12

Platelet aggregometry
platelet function analyzer (PFA-100)
flow cytometry

Question 13

What is the normal BMBT for a dog?
For a sedated cat?

Answer 13

dog < 3 mins
cat 34-105 seconds

Question 14

Prolonged BMBT could mean what? (3)

Answer 14

Thrombocytopenia
Thrombopathia
Vasculopathy

Question 15

What can influence BMBT?

Answer 15

age, skin temp, device used, hct%, blood viscosity, skin thickness, sex, person doing test

Question 16

what is ACT in terms of clotting test?
Contents of tube act as an activator of what factor?
is it more or less sensitive to intrinsic and common pathway defects than APTT

Answer 16

Activated clotting time
factor 12 (intrinsic pathway)
Less sensitive

(Influenced by variables such as severe thrombocytopenia, thrombopathia, anemia, altered viscosity and incubation temperature)

Question 17

Fibrin split products are produced when?

Answer 17

Plasmin lyses fibrinogen

Question 18

What is the most common primary hemostatic defect?

Answer 18

Thrombocytopenia

Question 19

What is the most common cause of platelet counts <50k?

Answer 19

IMTP

Question 20

What are the three types of von Willebrands?

Answer 20

Type 1: All multimers of vWF but reduced concentration (<20% normal = severely affected)
Type 2: Disproportionate decrease or absence of the high-molecular weight multimers - causes severe bleeds, DDAVP can’t help (the big boys are just not there to be released)
Type 3: Almost complete absence of vWF (<1%) often severe bleeds before 1yr of age)

Question 21

vWF levels below what % on ELISA are confirmatory(“deficient”) for diagnosis of von Willebrands?

Answer 21

<50% is deficient

Question 22

How long does it take for cryoprecipitate to have an effect and how long does it last?

Answer 22

Takes 30 min, lasts 4 hours

Question 23

Desmopressin (DDDAVP) is useful for which type of vWD? Is it helpful for clotting an an animal that doesn’t have vWD?

Answer 23

Type 1
No, it doesn’t help a normal dog

Question 24

What test is most diagnostic for a thromboembolism?

Answer 24

Selective pulmonary angiography

D-dimers are sensitive so if normal/<250ng/mL can rule PTE out but not specific so can’t diagnose on that alone.

Question 25

Describe the disease course of DIC:
Are these patients clinically hyper or hypo-coagulable?
What is mortality?
What natural anticoagulant pathway is affected?

Answer 25

Systemic activation of coagulation -> microvascular thrombosis -> compromise of organ perfusion -> organ failure
Ongoing exhaustion of platelets and factors = hypocoagulable state
50-77% mortality in dogs, 93% in cats
Protein C pathway is profoundly decreased

Question 26

Platelets make what via COX-1 from arachidonic acid?

Answer 26

Thromboxane A2

Question 27

What are the two receptors that platelets bind to become activated?

Answer 27

Platelet glycoprotein VI receptor on exposed collagen
or
vWF via the 2whglycoprotein 1b (GPIba) receptor

Question 28

What is the most important activator of platelets?

Answer 28

Thrombin (Factor II)