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Fibrinolysis
Pathogenesis of DIC
(Porth, 2001)
Pathophysiology
Thrombosis-hypercoagulability Fibrinolysis-hypocoagulability
(the hemorrhagic phase)
1) Coagulation cascade is
initiated, causing 1) Activates the complement
widespread fibrin formation system
2) Microthrombi deposited 2) By products of fibrinolysis
throughout the (fibrin/fibrin degradation
microcirculatory products(FDP)) further
enhance bleeding by
3) Fibrin deposits result in
interfering with platelet
tissue ischemia, hypoxia,
aggregation, fibrin
necrosis
polymerization, & thrombin
4) Multi organ dysfunction activity
3) Leads to Hemorrhage
(Porth, 2004) & (Otto, 2001)
Mechanism
XI XIa
VIII VIIIa
X Xa
V Va
II IIa (Thrombin)
Fibrinogen Fibrin
PAI-1 Prot. S
Prot. C
Antiplasmin
Tissue factor* TFPI
Fibrinolytic
Clotting Factors System
ATIII
Procoagulant Anticoagulant
Diagnosis of DIC
Laboratory studies
no single test is accurate
serial test are more helpful than single test
Conditions Associated With DIC
Malignancy Pulmonary
Leukemia ARDS/RDS
Metastatic disease Pulmonary embolism
Cardiovascular Severe acidosis
Post cardiac arrest Severe anoxia
Acute MI Collagen vascular disease
Prosthetic devices Anaphylaxis
Hypothermia/Hyperthermia
Conditions Associated With DIC
http://tutorial on inflammation
P.Bowne, Alverno College
Incidence
Frachini, Massimo. Thrombosis Journal “Recent acquisitions in the pathophysiology, diagnosis and treatment of
disseminated intravascular coagulation” Feb 2006, 4:4.
Davis-Jackson, Rachel. Thrombosis Journal “Antithrombin III and R-TPA used singly and in combination vs.
supportive care for treatment of endotoxin-induce DIC in the neonatal pig” May 18, 2006, 4:7.
Antifibrinolytic Therapy
2 mechanism :
The first pathway is tissue factor (TF) dependent
following a vessel injury TF–activated factor VII complex
activate factorX leading to conversion of prothrombin
to thrombin.
‘thrombin burst’ formation of a stable fibrin clot that is
resistant to premature fibrinolysis reliable and maintained
hemostasis
The second pathway involves a TF-independent mechanism
In fact, recent data suggest that rFVIIa can directly activate
factor X on phospholipid vesicles and on the surface of
activated platelets and monocytes [11–13]. This mechanism,
which is the most important mode of action of rFVIIa at
pharmacologic doses, optimizes thrombin generation
independently of the presence of TF.
The Use
The dose of rFVIIa was 90 mg/kg and the median number of doses
administered was five (range, 3–10). Of the 18 patients, 15 (83.3%)
responded with cessation of bleeding and improvement in coagulation data.
No thromboembolic complications were observed following rFVIIa
administration
In conclusion, it could be a paradox to use rFVIIa in a clinical
setting characterized by systemic activation of
coagulation.Comprehension of the molecular mechanisms of
action of rFVIIa and the clinical evidence from the literature,
however, suggest the potential role of this bypassing hemostatic
agent in the treatment of refractory bleeding associated with DIC.
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