Chapter 104 - Hypercoagulable states

Question 1

What is the Virchow’s triad ?

Answer 1

Predisposition to thrombotic disease when there is:

• endothelial dysfunction,
• hypercoagulability of blood,
• blood stasis or altered blood flow.

Question 2

What are the 4 broad categories of mechanisms that enhance thrombophilia?

Answer 2

• Endothelial disturbances
• Increased procoagulant elements
• Decreased endogenous anticoagulants
• Perturbation in Fibrinolysis

Question 3

When activated or injured, what is the main active factor released by the endothelial cells ?
Where do they store this molecule?

Answer 3

Ultra-Large vWF (UL-vWF), stored in Weibel-Palade bodies (storage ganule)
In health, UL-vWF quickly are cleaved into smaller multimers by ADAMSTS13. When this P is inhibited or decreased, they are not, resulting in high concentrations of UL-vWF causin thrombosis

Question 4

What are the main procoagulant elements that can be increased and be part of a hypercoagulable state?

Answer 4

• Tissue Factor - exposed by endothelial damaged, expressed on activated monocytes/macrophages, on neoplastic cells, on microparticules
• Micoparticules (circulating small vesicles (membrane blebs) released from activated or apoptotic cells)
• Activated platelets
• Content of platelets granules - Ca, serotonin, ADP, fibrinogen, P-selectin, factor Va + in cats, vWF

Question 5

What are the 3 main anticoagulant proteins?

Answer 5

• Antithrombin (AT)
• Activated Protein C (APC)
• Tissue factor pathway inhibitor (TFPI)

Question 6

What molecule, exogenous or endogenous, can increase the efficacy of AT by a 1000 fold ? Where is it found when endogenous ?

Answer 6

Heparin - exogenous, or endogenous (heparin-like GAGs of the glycocalyx (e.g., heparan sulfate))

Question 7

What endogenous molecule can increase the efficacy of AT by a 8-fold, and when ?

Answer 7

Thrombomoduline - AT binds to TM in the presence of thrombin and in the absence of heparin

Question 8

What is the action of antithrombin?

Answer 8

Inhibits FXa and thrombin

Question 9

Who is the main endogenous inhibitor of plasminogen, thus perturbating fibrinolysis?

Answer 9

Plasminogen activator inhibitor (PAI-1)

Question 10

Is thrombosis secondary to cardiac disease frequent in dogs?

When is it seen?

Answer 10

• Infrequent

- Associated with dilated cardiomyopathies and atrial fibrillation

Question 11

What are the 7 most common conditions associated with an hypercoagulable state in veterinary medicine?

Answer 11

• Systemic inflammation
• IMHA
• Protein losing nephropathy
• Hypercorticolemia
• Neoplasia
• Cardiomyopathies
• Isolated brain injury

Question 12

In IMHA in dogs, the hypercoagulable state is wel documented (TEG, elevated FDPs and D-dimer, markedly elevated fibrinogen concentration). What are the mechanisms leading to this hypercoagulable state?

Answer 12

• Low AT activity
• Increase of circulating TF (platelet, MPs, mononuclear cells)
  +/- platelet activation (2 studies in dogs, disparate conclusions)

Question 13

In a predisposed patient, what are two laboratory signs that should raise concerns or the early stages of a consumptive coagulopathy?

Answer 13

• Drop in circulating platelet count

- At least 20% prolongation in aPTT

Question 14

What are the two types of tumors that are most commonly implicated in thrombotic complications?

Answer 14

• Tumors of epithelial cell origin
• Hemic neoplasms (e.g., lymphoma, leukemia, histiocytic sarcoma, hemangiosarcoma)
• (however, any cancer may promote thrombus formation)