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Slide Notes

After seeing a couple of patients in the ER with coagulopathy, I realized that at times where the coagulopathy is an emergency, having a mental algorithm on hand to evaluate whether action is needed, could prevent a patient from bleeding out. I decided I would put together this Haiku Deck to teach, via a monologue, how to think about TTP in the ER.
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TTP in the ER

Published on Apr 27, 2016

After seeing a couple of patients in the ER with coagulopathy, I realized that at times where the coagulopathy is an emergency, having a mental algorithm on hand to evaluate whether action is needed, could prevent a patient from bleeding out. I decided I would put together this Haiku Deck to teach, via either a monologue for personal review or a full presentation with a script, how to think about TTP in the ER.

PRESENTATION OUTLINE

Thrombotic Thrombocytopenic Purpura in the ER

Nikita Consul, Columbia Univ. College P&S 2017
After seeing a couple of patients in the ER with coagulopathy, I realized that at times where the coagulopathy is an emergency, having a mental algorithm on hand to evaluate whether action is needed, could prevent a patient from bleeding out. I decided I would put together this Haiku Deck to teach, via a monologue, how to think about TTP in the ER.

REVIEW of TTP:
ADAMST13 plasma protein deficiency prevents platelet clumping

To review, TTP, or Thrombotic Thrombocytopenic Purpura, is a coagulopathy wherein the ADAMST13 plasma protein is deficient, either due to congenital or acquired etiologies.

The protein normally cleaves von Willebrand Factor, enabling platelet "sticking" to the endothelium, required for initiation of platelet-fibrin aggregate deposition, or clot deposition. This deficiency of the plasma protein leads to a lack of platelet binding to damaged endothelial tissue.
Photo by Ivy Dawned

THIS.

in the ED, we see
When we see patients with TTP, in the ER, we may not have time to look up previous history before we make a split-second decision on which laboratory tests to order.

A patient who presents with non-blanching petechiae, purpura, or ecchymoses, may look like this patient here, with red-purple lesions on his/her skin.

blood smear:

CBC:
Our first step should be to get a CBC with differential, accompanied by a blood smear.

The blood smear will be read (by a Hematologist) as sparse platelets among RBCs and some WBCs, that will most likely be normal. The platelets that do show up on the blood smear may or may not be damaged. In the case of TTP, platelets should not be damaged, but rather just low in number.

A CBC with platelet count

we don't know whether it's TTP

or HIT or HUS or DIC or ITP...
From the CBC count and blood smear alone, we don't have enough information yet to decide whether it's TTP or some other coagulopathy, and because each has a different emergency treatment approach, it would be *nice* to figure out what the patient actually has. However, waiting for additional lab measurements to return is not a great plan of action in this potentially emergent situation.
Photo by jenny downing

but plasmapheresis is complicated...

we can do plasma exchange to increase ADAMST13
TTP treatment requires emergent plasma exchange to increase the plasma protein ADAMST13, but executing plasmapheresis emergently is not wise, due to the resources involved and the potential risks to the patient involved with the process

yup, complicated

Obvious from this slide, the complexity and immensity of the plasmapheresis equipment.

furthermore, other pathways could be involved

Additionally, plasmapheresis without significant pre-test probability of TTP is not warranted, due to the significant delays it can cause in implementing other treatment options for other causes of purpura.
Photo by jenny downing

But no matter the cause,

why not just increase platelet count, anyway?
Platelet transfusion upon seeing low platelet count is an intuitive response. However, in multiple coagulopathies, it does not help, and delays proper treatments, while exposing the patient to significant risk.
Photo by Sandra Gama

Well,
for TTP:
Transfusion doesn't increase platelet clumping

In TTP the platelet count is low due to thromboses forming intravascularly, and increasing the platelet count, though has not been shown to overtly cause harm, certainly does not alleviate the symptoms. This is because the underlying problem is in ADAMST13 plasma protein deficiency, and so transfusion is not needed.

Transfusion will only provide fresh platelets, but without fresh ADAMST13, the fibrin-platelet clots cannot deposit onto von Willebrand Factor.
Photo by Thomas Hawk

for some etiologies,
we do transfuse directly

For some etiologies, platelet transfusion is the mainstay of therapy, such as....
Photo by 3water

Such as,
for ITP:
Transfuse platelets + IVIg + Steroids

For ITP, where platelet transfusion replenishes platelets that are lost. IVIg distracts autoimmune response by overflooding the blood with antibodies, and Steroids dampen the autoimmune response.
Photo by Naccarato

...because immune destruction of platelets can be treated with transfusion!

These are appropriate treatment steps for known ITP, by alleviating immune destruction of platelets. ITP can be supported as the leading diagnosis, often by the WBC count.

for other thrombocytopenias,

we need to diagnose the underlying cause
Photo by Minette Layne

getting coags only helps with diagnosis, if it is DIC

DIC is rare in the outpatient setting, but more common in the inpatient and ICU setting. In DIC, PT and PTT are both increased. In other acute presentations of coagulopathy, PT and PTT are not as useful.
Photo by SkyFireXII

DIC, being overactive coagulation factors,

leading to consumptive coagulopathy
The underlying cause of DIC is overactivation of the coagulation cascade via tissue factor release, which leads to widespread consumption of clotting factors involved in the cascade. Therefore, areas of the vasculature dependent upon hemostatic clotting mechanisms are subject to free bleeding, presenting as thrombocytopenic coagulopathy with increased D-dimer and decreased fibrinogen.

Treatment involves addressing the underlying cause, whether or not FFP/cryoprecipitate are available for delivery.

for TTP and HIT,
we rely on the H&P

History of Heparin Dose?

"4Ts Score"
Patients should be asked about history of heparin dose, especially in the last 30 days. Criteria based on the "4T Score" help to calculate a score that evaluates pre-test probability for HIT, which uses percentage of platelet count decrease, timing of platelet count drop relative to heparin exposure, thrombosis symptoms, and whether an alternative diagnosis is most likely.

Tx: stop the heparin

start the alternative
Most emergently, management of HIT involves removing heparin and replacing with an alternative anticoagulant.
Photo by minghan

Remember TTP
by thinking FRANTIC

TTP, which is not as straightforward to diagnose via H&P, can only be confirmed with a serum ADAMST13 plasma protein level, which often does not arrive in adequate time for performing first steps of an intervention.
Photo by KylaBorg

F ever
R eticulocytosis
A nemia
N eurological change
T hromboses
I ndirect bilirubinemia
C reatinine elevation

Labs and symptoms with TTP amy or may not reflect a collection of signs consistent with fever, microangiopathic hemolytic anemia, brain injury, and renal injury.
Photo by KylaBorg

If FRANTIC, start patient on
Plasmapheresis + Steroids

High pre-test probability, in our current day, is what is used to warrant plasmapheresis and steroids.

Plasmapheresis will delay other interventions if it's not TTP, so try to be sure

However, it is important to remember that plasmapheresis can delay implementing other interventions, and may expose the patient to unnecessary risks. Therefore, high clinical suspicion is a must.

Coming Soon:
Plasmic Score to help decide on benefit of plasma exchange, in TTP not yet diagnosed with ADAMST13 activity level

"High clinical suspicion" is better supported with POC labs, which may be clustered to reflect the unique symptoms/signs associated with TTP. A Plasmic Score has undergone some investigation for validity as a possible tool for indexing clinical suspicion in a more standardized way.

Plasmic Score calculates pre-test probability:
Creatinine >2.0
Platelets
D-dimer >4.0
Reticulocytes >2.5%
Indirect Bilirubin >1.5

Of note, the Plasmic score utilizes criteria including abnormal levels of serum creatinine, platelets, D-dimer, reticulocytes, and indirect bilirubin. The score has been to shown to, in over 200 patient cases, effectively recognize patients with high risk of TTP with low ADAMST13 level in over 95%.

If investigated more thoroughly for robustness, this score could allow for earlier diagnosis of high risk of TTP and therefore earlier intervention, whereas in low-risk cases, the provider can investigate other possible causes.

But for now... Just H&P :)

Whether or not you use the PLASMIC score, is up to you. For now, PLASMIC is not used widely, but we can implement the concepts of the score in our H&P and POC lab assessments.
Photo by FrankGuido

Thank You.



References:

Bendapudi et al. "Derivation and Prospective Validation of a Predictive Score for the Rapid Diagnosis of Thrombotic Thrombocytopenic Purpura: The Plasmic Score." Blood. 2014.

Bentley et al. "Performance of a clinical prediction score for thrombotic thrombocytopenic purpura in an independent cohort.". Vox Sang. 2013.

Kessler et al. "Thrombotic thrombocytopenic purpura: a hematological emergency." J Emerg Med. 2012.

Staudinger et al. "Management of acquired coagulation disorders in emergency and intensive-care medicine." Seminars Thromb Hem. 1996.

Stella et al. "The diagnostic dilemma of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in the obstetric triage and emergency department: lessons from 4 tertiary hospitals." Am J Ob Gyn. 2009.

Photo by djniks