Disseminated Intravascular Coagulation (DIC)

The DIC process can be divided into three stages:

• Hypercoagulable (Stage I)
• Secondary fibrinolytic (Stage II)
• Hypocoagulable (Stage III)

Hypercoagulable (Stage I) DIC is commonly initiated through release of tissue factor

(TF) and FVIIa activation of the extrinsic pathway, resulting in a deposition of thrombin in
the microcirculation system. TF is normally contained within the cellular membrane and
encrypted. However, traumatic tissue injury, required major resuscitation, or major surgery,
exposes TF to the bloodstream. TF expression can also occur when monocytes are activated
by sepsis, endotoxin, the presence of cancerous cells, or in pregnancy when amniotic fluid
penetrates the maternal blood stream.

In summary, the release of TF, together with FVIIa, initiates the extrinsic coagulation
cascade and, if it is not anticoagulated accordingly, with heparin low molecular weight
heparin (LMWH), or activated protein C (APC) can result in microthrombosis of the
capillaries of major organs, leading to Acute Respiratory Distress Syndrome (ARDS),
multiple organ failure (MOF), miscarriage, clotted graft, pulmonary embolism (PE), acute
myocardial infarct (AMI), stroke, and deep vein thrombosis (DVT). Fortunately, the high
concentration of thrombin activates the endothelium to release tissue plasminogen activator
(TPA), which activates plasminogen into plasmin -- the enzyme that breaks down the clot
before microthrombotic the capillaries of major organs. This process leads to stage II DIC,
secondary fibrinolysis.

Secondary fibrinolytic (Stage II) The secondary fibrinolytic stage (secondary to a

prothrombotic state) is initiated by the release of TPA by the endothelium system, which
activates plasminogen to plasmin. Plasmin breaks down the clot, releasing fibrinogen
degradation product (FDP). The release of TPA is an attempt to counterbalance the
prothrombotic state into normal hemostasis and to prevent deposition of thrombi into the
microcirculatory system. At the same time FDP, acts as an anticoagulant to inhibit platelet
aggregation and prevent normal cross-linking of fibrin, which is necessary to render clots
insoluble. FDP anticoagulation is enhanced by plasmin's biodegrading of coagulation factors
V, VIII, IX, and XI.

Therefore, secondary fibrinolysis is an attempt to normalize or control the prothrombotic

state by anticoagulating both the enzymatic and platelet aggregation processes to break
down the formed clot. Unfortunately, the source of TF release is not corrected, nor is the
external source of anticoagulation regimen in the form of heparin, LMWH, APC and/or
platelet inhibition by aspirin, Plavix, GPIIb/IIIa inhibitors altered, and so the hemostasis
system enters into a consumptive state, where coagulation proteins and platelets are
consumed leading into the third stage of DCI, Hypocoagulable phase.

Hypocoagulable phase (Stage III) The hypocoagulable phase leads to hemorrhage, but
can be treated by FFP, cryo, and platelets to stop the bleeding. Unfortunately, these
allogenic blood products, in addition to exposing the patient to donor blood products and the
risk of blood-borne diseases, also initiates strong inflammatory reactions and can reinstate
the prothrombotic state of DIC stage I in a much aggravated patient hemostasis state.
Another risk of DIC in secondary fibrinolysis is that a laboratory test panel will be run, and
tests will be normal for PT, PTT, fibrinogen level, platelets, but not for D-DIMER. The
common wisdom is to give Amicar or Aprotinin to normalize D-DIMER, but the doing that
blocks the pathway to breaking down the clot formation.

By identifying DIC in stage I with the Sonoclot Analyzer, then treating according to the
anticoagulation regimen for both enzymatic and platelet activations, and remedying the
source of TF release and balancing the patient's hemostasis, and can stop the initial DIC in
its earliest stage.