systemic intravascular coagulation
coagulation first, then intravascular thrombosis
thrombomodulin
tissue plasminogen activator
intrinsic pathway
extrinsic pathway
common pathway
contact pathway
tissue factor pathway - primary factor in DIC
-antithrombin III - pathway enhanced by heparin
- TFPI
- protein C, S
balance between procoagulant vs. anticoagulant
procoagulant
PAI-1, antiplasmin, tissue factor, clotting factor
vs.
anticoagulant
protein S, C, TFPI, fibrinolytic system, ATIII
systemic activation coagulation
- depletion of platelet, coagulation factors
- bleeding
-death
- intravascular deposition of fibrin
- thrombosis of small vessel
- organ failure
- death
DIC
- reduced antithrombin III levels
- reduced activity of protein C - protein S system
- insufficient regulation of tissue factor activity by TFP2
- impaired fibrinolysis
- cytokines - coagulation activation
- TNF-alpha
- IL-10 coagulation
inflammation overlaps with coagulation
Clinical evidence of thrombosis, hemorrhage or both
*DIC associated condition
malignancy
cardiovascular
hypothermia / hyperthermia
pulmonary
acidosis
anoxia
collagen vascular
anasphysis
infections septicemia
intravascular hemolysis
acute liver disease
tissue injury
obstetrics
fragment
schistocytes
paucity of platelets
lab tests for DIC
D-dimer
antithrombin III
fibrin degradation prod
platelet count
prothrombin time
activated PTT
coagulation factor levels
localized DIC vs. systemic DIC
thrombocytopenia
prolonged clotting times
presence of fibrin degradation products
severe liver failure
vitamin K deficiency
liver disease
HELLP syndrome
treatment of DIC
- stop the triggerring process
- supportive therapy
- plasma & platelet substitution therapy
FFP(fresh frozen plasma)
retroperitoneum - may harbor massive amount of blood without seeing the signs
retroperitoneal bleeding
Coagulation inhibition therapy
- antithrombin III
- protein C concentrate
- tissue factor pathway inhibitor
- heprain? controversial
- antithrombolytic therapy
=> can lead to fatal disseminated thrombosis, tranexamic acid, EACA,
- evidence that intravascular coagulation ceased
- lab of overwhelming fibrinolysis
- bleeding not responding to therapy
microthrombi, consumptive coagulative
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Disseminated intravascular coagulation (DIC) is a pathological process in the body where the blood starts to coagulate throughout the whole body. This depletes the body of its platelets and coagulation factors, and there is a paradoxically increased risk of hemorrhage. It occurs in critically ill patients, especially those with Gram-negative sepsis (particularly meningococcal sepsis) and acute promyelocytic leukemia.
Causes
There are a variety of causes of DIC, all usually causing the release of chemicals into the blood that instigates the coagulation.
- Sepsis, particularly with gram-negative bacteria.
- Obstetric complications (most common cause), with chemicals from the uterus being released into the blood, or from amniotic fluid embolisms, and eclampsia can be causes. Another obstetric condition which can cause DIC is abruptio placentae.
- Tissue trauma such as burns, accidents, surgery or shock.
- Liver disease
- Incompatible blood transfusion reactions or massive blood transfusion (more than the total circulatory volume)
- Malignant cancers, or widespread tissue damage (e.g. burns), or hypersensitivity reactions all can produce the chemicals leading to a DIC.
- Acute promyelocytic leukemia
- Viral hemorrhagic fevers bring about their frank effects, paradoxically, by causing DIC.
- Envenomation by some venomous snakes such as the Stephens Banded Snake, Hoplocephalus stephensi (from the family of Elapidae).
Diagnosis
Although numerous blood tests are often performed on patients prone to DIC, the important measures are: full blood count (especially the platelet count), fibrin degradation products or D-dimer tests (markers of fibrinolysis), bleeding time and fibrinogen levels. Decreased platelets, elevated FDPs or D-dimers, prolonged bleeding time and decreased fibrinogen are markers of DIC.
[edit] Pathophysiology
Various factors can activate the system of coagulation, but the end result is formation of fibrin, a mesh-like protein. The fibrin deposition can block blood vessels, leading to ischemic damage to some tissues. Red blood cells are damaged as well as they get shredded by the fibrin, leading to microangiopathic hemolytic anemia (MAHA). Platelets are consumed in the formation of clots, leading to thrombocytopenia. Due to consumption of both platelets and coagulation factors, DIC paradoxically predisposes to hemorrhage.
[edit] Treatment
The underlying cause must be treated initially. Anticoagulants are only given when indicated (development of thrombotic renal complications) as patients with DIC are prone to bleeding. Platelets may be transfused if counts are very low, and fresh frozen plasma may be administered.
DIC results in lower fibrinogen (as it has all been converted to fibrin), and this can be tested for in the hospital lab. A more specific test is for "fibrin split products" (FSPs) or "fibrin degradation products" (FDPs) which are produced when fibrin undergoes degradation when blood clots are dissolved by fibrinolysis.
In some situations, infusion with antithrombin may be necessary. A new development is drotrecogin alfa (Xigris®), a recombinant activated protein C product. Activated Protein C (APC) deactivates clotting factors V and VIII, and the presumed mechanism of action of drotrecogin is the cessation of the intravascular coagulation. Due to its high cost, it is only used strictly on indication in intensive care patients.[1]
The prognosis for those with DIC, depending on its cause, is often grim, leading the acronym to be known colloquially as "death is coming".
