127 Disseminated Intravascular Coagulation Flashcards
(78 cards)
The organs most frequently involved by diffuse microthrombi
Lungs and kidneys
Followed by the brain, heart, liver, spleen, adrenal glands, pancreas, and gut
Acute tubular necrosis is more frequent than renal cortical necrosis
The most important mediators responsible for the imbalance in DIC
Cytokines
The most important interface in which the interaction between inflammation and coagulation takes place
Endothelium of the capillary bed
Constitutes a sine qua non for most patients with DIC
Endothelial perturbation
Plays a central role in the initiation of inflammation-induced coagulation in DIC
Tissue factor (TF)
TF becomes exposed to blood upon disruption of the vascular integrity, or when cells present in the circulation, such as monocytes, are triggered to express TF.
The in vivo expression of TF is dependent on what cytokine
Interleukin (IL)-6
Other cytokines generated during inflammation, impair the physiologic anticoagulant pathways.
Tumor necrosis factor (TNF)-α and IL-1
Thrombin generated by the TF pathway amplifies both clotting and inflammation through the following activities:
- (a) it activates platelets, giving rise to platelet aggregation and augmenting platelet functions in coagulation;
- (b) it activates factors VIII, V, and XI, yielding further thrombin generation;
- (c) it activates proinflammatory factors via protease-activated receptors (PARs) on inflammatory cells;
- (d) it activates factor XIII to factor XIIIa, which crosslinks fibrin clots;
- (e) it activates thrombin-activatable fibrinolysis inhibitor (TAFI), making clots resistant to fibrinolysis; and
- (f) it increases expression of adhesion molecules, such as L-selectin, thereby promoting the inflammatory effects of leukocytes
Serves as an “off switch” for further thrombin generation
Activation of Protein C by Thrombin
Paradoxically, at low concentrations, thrombin exhibits both antiinflammatory and anticoagulant effects because it binds to thrombomodulin and activates protein C to the activated form
The effects of fibrinogen on mononuclear cells seem to be mediated by
Toll-like receptor–4
It is also the receptor of endotoxin.
Procoagulant activity is regulated by three important anticoagulant pathways:
- AT
- Protein C system
- TFPI
Main inhibitor of thrombin and factor Xa
AT
- Without heparin, AT neutralizes coagulation enzymes in a slow, progressive manner.
- Heparin induces conformational changes in AT that result in at least a 1000-fold enhancement of AT activity.
- Thus, the clinical efficacy of heparin is attributed to its interaction with AT.
Acts with its cofactor protein S and degrades the essential cofactors Va and VIIIa, and hence, is an effective anticoagulant
APC
Increased plasma levels of what complement factor results in a relative protein S deficiency during inflammatory diseases
C4bBP
Factor V or factor VIII
Sepsis can also cause resistance toward APC because of a substantial increase in __________levels.
Factor VIII
The main inhibitor of the TF–factor VIIa complex and factor Xa
TFPI
ROLE OF NATURAL ANTICOAGULANT PATHWAYS
(Increased or Decreased) during Inflammation/Sepsis
AT:
Glycosaminoglycans:
Zymogen protein C:
Thrombomodulin:
Plasma levels of C4bBP:
EPCR:
Factor VIII:
AT: decrease
Glycosaminoglycans:decrease
Zymogen protein C: decrease
Thrombomodulin: decrease
Plasma levels of C4bBP: increase
EPCR: decrease
Factor VIII: increase
Inhibits platelet activation and aggregation, blocks neutrophil tethering to blood vessels, and decreases endothelial cell production of various cytokines and chemokines
Prostacyclin
The antiinflammatory effects of APC are mediated by the EPCR.
AT cause induction of prostacyclin release from endothelial cells
In DIC, fibrinolysis is initially activated but subsequently inhibited, because of an increased release of plasminogen activator inhibitor-1 (PAI-1) by endothelial cells.
These effects are mediated by
TNF-α and IL-1
TAFI, like PAI-1, may play a role in impeding fibrinolysis and in augmenting formation of microvascular thrombi.
The most devastating effect of excessive generation of superoxides and associated free radicals may be their role in
Inducing endothelial apoptosis, which exacerbates capillary leak
TRUE OR FALSE
LPS-induced DIC so prominently displays tissue infarction leading to multiorgan dysfunction (eg, sepsis) compared with DIC that is predominately induced by TF exposure (eg, head trauma)
TRUE
LPS-induced DIC so prominently displays tissue infarction leading to multiorgan dysfunction (eg, sepsis) compared with DIC that is predominately induced by TF exposure (eg, head trauma)
mas malala sepsis than trauma
LPS infusion increased both NO and endothelin remarkably, whereas TF infusion increased NO more than did LPS but did not stimulate endothelin significantly.
TRUE OR FALSE
The occurrence of schistocytes in the blood film is uncommon in patients with DIC
FALSE
The occurrence of schistocytes in the blood film is not uncommon in patients with DIC
so common!
Patients with DIC may also display signs of thrombotic microangiopathy, causing further consumption of platelets, and nonimmune hemolysis.
A crucial factor in the pathogenesis of this enhanced platelet–vessel wall interaction is
Release of (ultra-large) von Willebrand factor multimers
Von Willebrand factor is an acute phase protein and markedly upregulated and released during systemic inflammation.
Account for approximately two-thirds of DIC cases in the major series
Infectious diseases and malignant disorders
Infectious diseases: purpura fuminans