Disorders of Fibrinolysis

Question 1

increased fibrinolysis occurs for 2 reasons

Answer 1

• increased activation of plasminogen = primary

- in response to increased coagulation (secondary to clot formation)

Question 2

primary fibrinolysis

Answer 2

• increased plasmin in the circulation
  > plasmin formed without coag activation (not due to clot formation); normally through thrombin triggers release of TPA
  > due to increased plasminogen activators or decreased plasmin inhibitors
• free plasmin degrades fibrinogen, factors V, VIII, and XIII
  > results increased FDPs

Question 3

causes of chronic DIC

Answer 3

• cancers of pancreas, prostate, ovaries, lungs
• liver and renal disease
• liver and BM may compensate for consumption in chronic DIC
• *slowly evolving overtime; dominant process = clotting; no imbalance to bleeding side of things**

Question 4

causes of acute DIC

Answer 4

• obstetric emergencies
• intravascular hemolysis
• septicemia
• crush injuries
• *must be treated right away!! often fatal**

Question 5

“consumption coagulopathy”

Answer 5

• DIC
• coag factors and PLTs are consumed
• coag inhibitors are also activated and used up

Question 6

secondary fibrinolysis

Answer 6

response to increased coagulation

- thrombotic disorders = deep vein thrombosis, pulmonary embolism, disseminated intravascular coag, etc.

Question 7

venous thromboembolism

Answer 7

• formation of blood clots in veins
• deep vein thrombosis: in veins deep in the legs, groins, or arms (below muscles)
• pulmonary embolism: clot that travelled to lungs (FATAL)

Question 8

arterial thrombosis

Answer 8

• clot formation in artery
• often due to rupture of atherosclerotic laque
• triggers PLT activation
• = myocardial infarctions or ischemic strokes

Question 9

DIC

Answer 9

• pathological activation of coag system
• imbalance between coag, inhibition, and fibrinolytic systems; overwhelms!!
• coag factors and platelets consumed
• thrombus formation throughout microcirculation (not localized, ineffective)
• fibrinolytic system, activated
• acute and uncompensated or chronic

Question 10

DIC causes:

Answer 10

• activation of extrinsic pathway by release of TG or a tissue thromboplastin-like substance
• direct activation of factors X or prothrombin
• activation o the intrinsic pathway

Question 11

TF can be released into circulation due to: (4)

Answer 11

• injury (placenta, prostate, lungs, brain)
• expression of TF by monocytes
• bacteria sepsis
• tumors rich in TF
• release of tissue factor-like substances*
• APL
• transfusion rxns
• toxins*
• bacterial endotoxins
• snake venoms

Question 12

fibrinolysis secondary to coagulation

Answer 12

• secondary response to DIC
  > fibrin breakdown results in formation of FDPs
  > D-dimers present along with X, Y, D, E
• free plasmin in circulation digests all fibrinogen and fibrin; and factors V, VIII, IX, and XI
• excess FDPs inhibit clot formation by:
  > inhibiting thrombin, fibrin monomer polymerization and impairing PLT aggregation
  > results in more bleeding

Question 13

how to treat DIC

Answer 13

• chronic: treat the underlying cause

- acute: treat dominant process = usually bleeding; replace missing hemostatic processes = transfusion