Neurotrauma en bloeding

ROTEM user meeting

10 november 2015

Victor Viersen AIOS anesthesiologie

VU medisch centrum, Amsterdam

Conflict of interest

• geen

Neuro Trauma en coagulopathie

The New England Journal of Medicine Downloaded from nejm.org at VRIJE UNIVERSITEIT on March 23, 2014. For personal use only. No other uses without permission.

From the NEJM Archive. Copyright © 2010 Massachusetts Medical Society. All rights reserved.

Neurotrauma en Coagulopathie

• ongeveer 30% van alle neurotrauma’s 24% bij binnenkomst, 54% binnen 24 uur 1

• Geassocieerd met progressie van ischemische en hemorrhagische laesies 2

• Geassocieerd met verhoogde morbiditeit en mortaliteit 2

1. Greuters et al. Acute and delayed mild coagulopathy are related to outcome in patients with isolated traumatic brain injury. Critical Care 2011 15:R2.

2. Laroche et al. Coagulopathy After Traumatic Brain Injury. Neurosurgery 70:1334–1345, 2012

Mechanisme

either the activated platelets or the damaged cellular membranes.Negative feedback loops, circulating inhibitors, and both endog-enous and inducible fibrinolytic activity strictly control theinitiation and extent of fibrin deposition. The activation of thefibrinolysis system ensures that the newly formed clot affects onlythe underlying injured tissue. For more details, readers areencouraged to read the excellent review article about thehemostatic and hemorrhagic problems in neurosurgical patientsby Gerlach et al.35

COAGULOPATHY AFTER TBI

The loss of equilibrium among the tightly regulated coagulationfactors can lead either to hypercoagulable states with micro-thrombosis and ischemia or to hypocoagulable states withpossible progression of hemorrhagic lesions (Figure 2). In general,alterations in coagulation parameters, as detected by elevationsin thromboplastin time (PT) and partial PT (PTT) anddecreased platelet count/function, represent increased risks ofbleeding. Hypercoagulability is more difficult to define becausethere is no specific routine laboratory assessment. Currently,there is no precise definition of what constitutes a coagulopathyafter TBI.

LABORATORY TESTING

Standard laboratory tests measure individual component ofcoagulation such as the enzymatic coagulation activity, plateletcounts and function, and byproducts of the fibrinolysis system.Currently, some centers use thromboelastography to assess theoverall viscoelastic properties of blood. This allows real-timeassessment of both hypocoagulable and hypercoagulable stateswith a single test (Table).

Enzymatic Coagulation

The classic test of the extrinsic, or TF, pathway is the PT,measured by the addition of calcium and TF containing extractthromboplastin to plasma. The PT is sensitive to the depletionand/or dysfunction of factors VII, V, X, and II and fibrinogen andis commonly monitored during warfarin therapy. The standardtest of the intrinsic, or contact activation, pathway is the PTT,which is uniquely sensitive to the depletion and/or dysfunction offactors XI, IX, and VIII. Thrombin levels are difficult to measure,and thrombin generation is commonly assessed indirectly byquantification of either enzyme-inhibitor complexes such as thethrombin–antithrombin III complex or prothrombin cleavagefragments liberated during thrombin activation such as pro-thrombin fragments 1 and 2. Fibrin deposition is assessed bythrombin time, measured as the time to fibrin deposition afterthe addition of thrombin to plasma. The thrombin time is sensitiveto the presence of heparin and the depletion or dysfunction offibrinogen. Serum fibrinogen levels may also be quantified directlyto detect deficiencies.

Platelets

In the absence of frank thrombocytopenia, little informationabout platelet function can be derived from a platelet count.Traditionally, platelet function is reported as the bleeding time, inwhich fibrin clot formation is measured as the time to cessation ofbleeding from a controlled superficial wound. The widespread useof antiplatelet therapy for cardiovascular and cerebrovascularindications has increased the interest in point-of-care assessmentof platelet function. Platelet function analyzer (PFA-100), rapidplatelet function assay (VerifyNow), and whole-blood impedanceaggregometry (Multiplate) have been developed to monitor thecapacity of the platelets to form a primary clot in differentconditions. The goal is to quickly identify the inhibition of plateletfunction to diagnose and to adjust the effect of antiplatelet therapyin the perioperative or emergency setting.36-41 Finally, the plateletfunction in whole blood can also be assessed by thromboelastog-raphy in real time.42 Other laboratory tests such as plateletaggregation and flow cytometry are used to determine plateletfunction and activation, respectively. These tests, however, havelimited clinical application, because they are extremely laborintensive and require specialized material.

Fibrinolysis System

The principal measurement of fibrinolytic activity is thedetection of fibrinogen degradation products, themost commonlymeasured of which is D-dimer. Although D-dimer is sensitive foractive fibrinolysis, tissue injury makes D-dimer nearly universallyelevated in trauma patients and therefore of limited value.43 Theacute hyperfibrinolysis seen in trauma patients correlates withelevated tissue-type plasminogen activator (tPA), elevatedD-dimer, and reduced plasminogen activator inhibitor-1 levels.44

Unfortunately, these are specialized tests with limited availability.However, accurate point-of-care diagnosis of hyperfibrinolysishas been recently demonstrated in trauma patients using

FIGURE 1. Current hypothesis for the development of coagulopathy after blunttraumatic brain injury. A combination of hypocoagulable and hypercoagulablestated triggered by the extent of brain injury will lead to secondary injury by wayof ischemic and hemorrhagic lesions.

COAGULOPATHY AND TBI

NEUROSURGERY VOLUME 70 | NUMBER 6 | JUNE 2012 | 1335

Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited.

Tissue Factor Hypothese

Fibrinolyse en Hyperfibrinolyse

• Fibrinolyse door aPC activatie

• Hyperfibrinolyse bij Shock en hypoperfusie niet alleen bij trauma/neurotrauma

Hyperfibrinolyse• Met name geassocieerd met shock & hypoperfusie • Zeer hoge mortaliteit (tot 100%) • Geen standaard laboratorium test beschikbaar • ROTEM

Coagulopathie in de dagelijkse praktijk

• Wat is een coagulopathie; INR waarde, ROTEM, klinisch beeld?

• Verschillende soorten stollingsdefecten

Casus - 1• M: 63 jarige man op een scooter aangereden door

een auto en met zijn hoofd (zonder helm) tegen een hek gekomen

• I: Neurotrauma en open cruris fractuur

• S: E1M1V1, SpO2 70%, NiBP 100/70

• T: RSI etomidaat/sux, intubatie, 1000ml NaCl, 500ml Mannitol 10%, 250ml Hyperhaes (NaCl 7,2%)

Greuters et al. Secondary bleeding in traumatic brain injury: A case reportNederlands Tijdschrift voor Anesthesiologie, Jan 2010 18-20

januari '10 | nederlands tijdschrift voor anesthesiologie

α

α

α

Fibrinogeen: T= 0 1,9 g/LT= 2 uur 1,3 g/L T= 4 uur 1,0 g/L

Casus - 2• M: 76 jarige vrouw als voetganger aangereden

door auto

• I: geisoleerd neurotrauma

• S: bradycardie 40/min, Hypotensie, gaspende ademhaling,

• T: RSI etomidaat/sux, geintubeerd, 500ml gelofusine, 250ml Hyperhaes (7,2% NaCl)

Laboratory

Hemoglobin (mmol/l) 5.3

Hematocrit 0.27

Platelet count (*109/l) 59

aPTT (s) 96

PT (INR) 2.1

Fibrinogen (g/l) 1.2

D-dimer (mg/l) 131

Sodium (mmol/l) 150

Potassium (mmol/l) 3.1

Lactate (mmol/l) 7.2

pH 7.11

pCO2 (mmHg) 47

pO2 (mmHg) 435

HCO3 (mmol/l) 14.3

Base excess (mmol/l) -14.1

Casus - 3

• 93 jarige dame met Blanco voorgeschiedenis

• Gevallen met de fiets, geisoleerd neurotrauma

• Bij opname op de SEH INR 1,36

• Op OK ongeveer een uur na opname INR<6 en diffuus bloeden uit operatiegebied

Probleem ?

Fibrinogeen: 0,5 g/L

ROTEM & (neuro)trauma

• Wanneer een ROTEM?

• Hoe vaak?

Conclusie• Stollingsstoornissen komen vaak voor bij

patiënten met een neurotrauma

• Niet altijd meteen evident bij opname, blijf alert en blijf meten!

• coagulopathie is meer dan alleen gestoord INR (hypofibrinogemie, hyperfibrinolyse, thrombopenie, thrombopatie)

• Laag fibrinogeen is in de praktijk veruit de meest voorkomende stollingsstoornis

Referenties• Acute and delayed mild coagulopathy are related to outcome in patients with

isolated traumatic brain injury. Greuters et al. Critical Care 2011 15:R2.

• Coagulopathy After Traumatic Brain Injury. Laroche et al. Neurosurgery 70:1334–1345, 2012

• Secondary bleeding in traumatic brain injury: A case reportGreuters et al. Nederlands Tijdschrift voor Anesthesiologie, Jan 2010 18-20

• Detection of acute traumatic coagulopathy and massive transfusion requirements by means of rotational thromboelastometry: an international prospective validation study. Hagemo et al. Critical Care 2015, 19:97