A #hemetwitter #tweetorial

DIC.

In med school, we were taught that DIC stood for disseminated intravascular coagulation.

Or...

Death. Is. Coming.

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This is severe and may be a bit hyperbolic.

But DIC is nothing to mess around with.

So what is it exactly?

At its core, DIC is coagulation gone rogue.

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For those that aren't coagulation nerds, a quick primer.

Following blood vessel injury, primary hemostasis occurs involving collagen, VWF, platelets.

Secondary hemostasis is comprised of the intrinsic (PTT) and extrinsic (PT) pathways which converge at the common pathway.
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The common pathway generates thrombin, which converts fibrinogen to fibrin.

So where does this go wrong?

First, it is important to note that DIC is not an independent disorder. It is ALWAYS a complication of another issue.
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The 1st report of DIC was back in 1834 by Dupuy who described what occurred when brain material was injected intravenously into animals. Yikes.

The animals died quickly and widespread clots were found throughout their bodies.

Glad I didn't have to do those experiments..
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Causes of DIC in people include:
-Infections (occurring in up to 30% of septic pts)
-Polytrauma
-Scary OB stuff (retained fetus, placental abruption, amniotic fluid embolism)
-Malignancy
-Vascular malformations
-Burns
-Snake bites
-Hopefully not brain injection

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All involve systemic inflammatory responses, a crucial factor in the pathogenesis of DIC.

The initiator of coagulation in DIC is tissue factor (TF), an extrinsic pathway component. TF is on the surface of many cell types but generally not in contact with circulating blood.

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TF is normally exposed after vascular damage but is released in response to cytokines, TNF, and endotoxin.

It is abundant in tissue of lung, brain and placenta, explaining DIC in response to polytrauma (and IV brain injection).

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Platelet activation (also 2/2 inflammation) greatly facilitates coagulation activation. interaction btw platelets/vessel wall can lead to a thrombotic microangiopathy in some pts!

VWF is involved as an acute phase reactant and ultra large (UL) multimers are released.

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This is why pts with severe inflammatory responses frequently have ADAMTS13!

ADAMTS13 is an important protease responsible for cleaving VWF. UL VWF leads to
consumption of ADAMTS13.

ADAMTS13 has been shown to be as predictive of mortality as APACHE
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Normally, coagulation is balanced by anticoagulants (proteins C,S, TFPI and AT). In DIC these controls are dysfunctional, allowing unchecked activation.

Fibrinolysis is also inhibited due to levels of PAI-1 (an inhibitor of plasmin, the key factor in fibrinolysis)

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Evidence now suggests that cell free DNA, extracellular histones and DNA binding proteins play a key role, contributing to NETosis which is highly procoagulant.

plasma levels of DNA-histone complexes and double-stranded DNA correlate with DIC severity.
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So..
Fibrin clots in circulationtrap platelets to make bigger clots micro and macro-vascular thrombosis

ischemia, inadequate perfusion, and end organ damage.

Diagnosis of DIC is based on laboratory testing in the right clinical context.

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Lab criteria for DIC include

PT, PTT (factor consumption)
platelets (consumption)
fibrinogen (consumption)
D-dimer or fibrin degradation products (formed during fibrin formation and subsequent degradation)

ISTH's helpful scoring algorithm
https://cdn.ymaws.com/www.isth.org/resource/group/1188b45f-809f-4e2d-b3ef-c6836c51440b/official_communications/definitionofdic.pdf

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It's important to recognize that fibrinogen is an acute phase reactant and given inflammation may be .

One study found that only 8.6% of pts with DIC have fibrinogen and recommended using a fibrinogen/CRP ratio instead.
https://www-karger-com.proxy.lib.umich.edu/Article/Pdf/96786
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The ISTH score (which uses fibrinogen) has NPV and PPV of ~95% and is predictive of mortality with a diagnosis of overt DIC doubling risk.

Given fibrin deposition then factor consumption, patients with DIC are at risk for bleeding and thrombosis.

So how do we treat?

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Tx of DIC is focused on treating the UNDERLYING problem.

Optimal tx of coagulation derangements is controversial.

Heparin blocks experimental DIC but clinical evidence is mixed.

Activated protein C was tried due to its anti-inflammatory and anticoagulant properties..
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Results were disappointing. Data on AT has been mixed although a few meta analyses have shown some survival benefit.

Thrombomodulin (TM) has also been studied. TM is a cofactor in the activation of protein C but more importantly has anti-thrombotic, anti-inflammatory..
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and cyto-protective properties.

Trial data has been favorable with decreased mortality but has not been statistically significant.

Recombinant ADAMTS13 is also being explored.

Antifibrinolytics and PCCs are generally avoided due to risk of thrombosis.

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Tx is indicated for symptomatic patients with bleeding or thrombosis.

Tx should not be withheld due to fear of "feeding the fire." But the goal should not be to normalize laboratory values. However, most groups agree on a minimum platelet threshold of 10-20K.

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Many pts with vascular malformations have chronic DIC for years.

For these pts, I can assure you, death is NOT coming.

For severe sepsis, trauma, burns, mortality rates are 40-80% andwith patient age and severity of derangements.

Yikes. Scary stuff.
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