Ecmo e gestione coagulazione

Systemic anticoagulation during ECMO is intended

to control thrombin generation and limit the risk

for thrombotic and hemorrhagic complications.

Unfractionated heparin (UFH) is the most

commonly used anticoagulant.

UFH acts by binding and inactivating factor Xa and

thrombin.

UFH increases the kinetic of the natural

thrombin-antithrombin binding by 2,000–4,000 times.

As a consequence, chronic heparin administration consumes the

endothelial and circulating pool of AT.

Additionally, heparin may be bound and inactivated by plasma

proteins, endothelial surface, and most of all by circulating platelets,

which scavenge heparin by releasing PF4.

Due to this complex scenario, the exact dose required to correctly

blunt thrombin generation is undefined and may greatly vary during

the course of an ECMO.

The classical dose range is reported between

20 and 70 IU/kg/h

.

AT and number of platelets variations may profoundly vary the

sensitivity to UFH.

This leads to the need for continuous adjustments of the UFH dose,

even if in general there is a trend for larger doses the longer the

The classical dose range is reported between 20 and 70 IU/kg/h.

No-anticoagulation-based ECMO is a strategy may be considered in case of excessive bleeding risk, like for trauma patients.

To achieve peripheral vessels cannulation, a small (50–100 IU/kg) bolus dose of heparin is usually administered.

In postcardiotomy ECMO, full heparinization is usually already achieved. After cannulation and onset of ECMO, heparin should be fully antagonized with

protamine sulfate.

Subsequently, given the residual effects of CPB and surgery, no heparinization is usually undertaken for the first 12–24 h, to avoid massive postoperative bleeding.

Once bleeding is under control, heparin infusion should be started at a low dose (20 IU/kg/h) and subsequently adjusted to the desired level of anticoagulation.

Alternatives to Heparin

Bivalirudin

is a direct thrombin inhibitor with a

short half-life

of

about 25 min and partial (20 %) kidney clearance

The dose of

bivalirudin

is usually reported around

0.03–0.2

mg/kg/h

, with or without an initial bolus of

0.5 mg/kg

Other direct thrombin inhibitors proposed for ECMO in case

of HIT include

argatroban

(0.1–0.4 μg/kg/min) while

danaparoid and lepirudin have been used in the past but are

presently abandoned.

AT

Inevitably, AT is consumed during ECMO, and

the majority of the authors suggest purified AT

supplementation aimed to maintain AT activity

at the lower normal range of 70 %

Of notice, when bivalirudin is used, AT

Monitoring the Hemostatic System During ECMO

Activated Clotting Time (ACT)

ACT

remains the standard of monitoring during heparin

anticoagulation in ECMO.

The ACT provides a bedside assessment of the intrinsic and

common pathway integrity.

Conventional Laboratory Tests

Activated partial thromboplastin time (APTT) explores the intrinsic and common

pathways of coagulation and is the classical measure for heparin therapy.

An APTT of 1.5 times the baseline APTT (50–80 s) is considered the target value

during ECMO and corresponds to a heparin concentration of 0.2–0.3 IU/mL.

Prothrombin time (PT) is a marker of the extrinsic and common coagulation

pathways and should be performed in order to detect the level of coagulation

factors and to guide their supplementation with fresh frozen plasma (FFP),

prothrombin complex concentrates (PCC), or cryoprecipitates.

Platelet count, fibrinogen levels, and d -dimers assays should be performed

daily.

Thromboelastography and Thromboelastometry

The r time and coagulation time are surrogates for thrombin

generation and may guide the UFH infusion rate during ECMO.

There is not a universally accepted value of r time for optimal UFH

dose, but the majority of the authors report an optimal window

between two and three times the upper normal limit (16–25 min)

The anti-Xa UFH assay measures the anti-Xa activity of heparin in plasma.

An optimal value, corresponding to an APTT 1.5–2 times the baseline, is between 0.3 and 0.7 IU/mL.

At present, there is a gap in knowledge about platelet function and antiplatelet drugs use during ECMO.

Adjusting the Coagulation

Profile Guiding the patient into the framework of this optimal pattern is one of the most tricky steps during an ECMO management.

UFH or bivalirudin dose should be adjusted based on ACT, APTT, and TEG/TEM. The other issues can be adjusted using allogeneic blood products or substitutes.

Purified AT is available for AT supplementation.

A severe gap in plasma coagulation factors (INR >3) can be corrected with PCC or cryoprecipitates, whereas minor gaps (INR 2–3) could even be treated with FFP. Suggested values of fibrinogen should be at least 100 g/dL, which approximately

correspond to a maximum clot firmness >10 mm at TEM. Fibrinogen concentrate is available for supplementation;

Antifibrinolytic therapy

with

epsilon-aminocaproic

acid or

tranexamic

acid

should be initiated in presence of signs of ongoing hyperfibrinolysis at TEG/TEM or conventional tests.

A certain degree of fibrinolysis is always present during ECMO;

values of

d -dimers around 300 μg/L

are acceptable, but signs of progressive increase suggest a prompt intervention.

Platelet

count should be maintained above 80,000 cells/mmc in a patient with active bleeding or at high risk for bleeding, with platelet concentrate transfusions.

Conversely, lower values (however >45,000 cells/mmc) may be accepted in non bleeding patients or patients at low risk for bleeding.

Finally,

red blood cells

should be administered to maintain a hemoglobin level at a minimal value of

8 g/dL

;

A bleeding patient requires a prompt and aggressive approach, with allogeneic blood products and substitutes therapy guided by the whole set of coagulation tests.

Conversely, a non-bleeding patient should be treated more conservatively, trying not to treat numbers instead of the patient