Dr.TH De Klerk

Definition: The process of blood clot formation through a controlled sequence of events, at the site of vessel injury.

Phases:

Initiation (adhesion)and formation (aggregation) of the platelet plug.

Propagation of clotting process.

Termination of clotting by antithrombotic control mechanisms.

Removal by fibrinolysis.

The Big Question around the Bleeding Patient: Haemostatic Disorder or Surgical Problem? Chicken or Egg....or Both! Both occur together especially with

haemodynamically significant bleeding. This leads to the next question: Haemostatic therapy or re-operation? Rather both together! In terms of haemostatic therapy: How much? Of what? What is the end-points?

Peri- and postoperative PT, aPTT, INR, platelet count and even PFA-100® are typically to some extent abnormal in most patients.

These abnormalities occur in those who bleed and those who don’t- Poor ability to predict who will bleed.

European Resuscitation protocols currently favour ratio FFP:PRC:Platelets of 1:1:1 for massive blood loss. Expensive!

European Trauma Bleeding Guidelines updated for 2013,recommend that all patients should get thromboelastometry together with above mentioned blood tests.

25-35% of civilian trauma patients. Higher- traumatic brain injury. Either hyper- or hypocoagulability.

Vicious triad: Acidosis, hypothermia and coagulopathy.

Perpetuate each other.

pH<7.2- interferes with assembly of coagulation factors.

Hypothermia- platelet dysfunction, impaired enzymatic function. (Remember coagulation cascade sequence of pro-enzymes activated).

Hemodilution- Resuscitation-associated coagulopathy. 50% of patients received >3 litres resuscitation fluid prior to arrival to casualty.

Mechanism: HYPOPERFUSION!

Increased levels of activated protein C and thrombomodulin→↓thrombin generation→ hypocoagulability.

Activated protein C→consumption plasminogen activator inhibitor-1→ fibrinolysis.

Depletion of activated protein C stores→rebound prothrombotic state.

Hypocoagulability→ Hyperfibrinolysis→ Prothrombotic state.

Each of these 3 phases require different treatment- wrong treatment ↑ mortality.

Why Thromboelastometry? 1. Gives a dynamic real-time overview of the

whole haemostatic process and the sequential interaction between the various components.

2. Makes treatment of bleeding more specific, resulting in a saving on blood products.

3. It is not only hypocoagulability which is demonstrated by the ROTEM but also hypercoagulability!

4. Prognostic marker.

Whole Blood Impedance Aggregometry.

Measurement of the elasticity of blood clot.

Small cylindrical cup with oscillating pin around a vertical axis.

Clotting retards rotation- inhibits torque (rotational force) of pin- mechano-transducer to give electrical impulse.

NB: r = CT; k = CFT; MA = MCF

ROTEM® parameters

CFT = Clot Formation Time (sec)

α- angle (°)

MCF = Maximum Clot Firmness (mm)

Clot Quality

Maximum Lysis (%)

CT = Clotting Time (sec)

CT (clotting time): time from start of measurement until initiation of clotting=> initiation of clotting, thrombin formation, start of clot polymerisationr

CFT (clot formation time): time from initiation of clotting until a clot firmness of 20mm is detected=> fibrin polymerisation, stabilisation of the clot with thrombocytes and F XIIIr

MCF (maximum clot firmness): firmness of the clot=> increasing stabilisation of the clot by the polymerised fibrin, thrombocytes as well as F XIIIr

ML (maximum lysis): reduction of the clot firmness after MCF in relation to MCF=> stability of the clot (ML < 15% ) or fibrinolysis (ML > 15% within 1h)

A5 = Clot Firmness (mm)

5 minutes after CT

AX = Clot Firmness (mm)

x minutes after CT

NATEM compares with original TEG- Hellige Thrombelastograph instrument.

NATEM- reflection of interaction of both coagulation pathways and other coagulation components in action

EXTEM: Activation of clot formation by thromboplastin (tissue factor). Assessment of clotting factors: I, II, V, VII, X, platelets, fibrinolysis.

INTEM: Activation of clot formation via the contact phase. Clotting factors: I, II, V, VIII, IX, X, XI, XII, platelets,fibrinolysis.

FIBTEM: Activation as with EXTEM with addition of cytochalasin D, a platelet blocking substance. Fibrinogen levels and fibrin polymerisation assessed.

Other specialized HEPTEM, APTEM.

Mr. BC 62yr Male, Caucasian, single, pensioner, Waterkloof.

Admitted 22/02/2014. Problem: Decompensated heart failure, Warfarin toxicity- INR 9.12 Precipitant: Septic left foot.

Background: Morbidly Obese (BMI>50m²/Kg), T2DM- on insulin, Hypertension, Aortic Valve Replacement-metal valve (2008) on warfarin, intermittend atrial fibrillation, GERD. Strong suspicion of obstructive sleep apnoea.

Current medication: Furosemide, enalapril, simvastatin, nifedipine, omeprazole, actraphane.

In hospital course: Initiated on anti-cardiac failure therapy, clindamycin and vancomycin- septic foot. Secondarily infected pulmonary edema- imipenem. Vancomycin stopped- as d/w Infectious Diseases Unit. Cardiac echo: Normal systolic function, left ventricular hypertrophy. Severe aortic stenosis- pannus formation. Arterial dopplers bilateral legs: Severe atherosclerotic disease bilateral, monophasic flow below knees. Admitted to high care 24/02/2014. Developed acute kidney injury due to myoglobinemia- managed conservatively. 27/02/2014 Above knee Guillotine amputation, for later formalization. Continuously oozing from stump. 01/03/2014 episode bleeding- requiring transfusion 3u packed cells, as well as FFP’s. DDAVP 450mcg tds intranasal given. Wound exposed bleeding vessel tied off. 06/03/2014 formalization/closure wound.

27/02 28/02 01/03 02/03

Urea 21.8 28.5 40.5 41.7

Creatinine 169 239 280 229

Platelets 81 162 148 113

INR 1.54 1.58 1.69 1.52

PT 18.8 N 19.3 N 20.7 N 18.5 N

FFP’S 4U GIVEN

DDAVP 450MCG TDS INTRANASAL

Me. BM, 34 yr, female, African, single, unemployed, Waterkloof.

Admitted on 07/02/2014. Collateral history from her brother that she fell from bed while having generalized tonic-clonic seizure. Was unable to move limbs since injury.

Known with epilepsy since childhood- Carbamazepine 400mg bd po. Poorly controlled- compliance? No other co-morbidities.

Sustained C5/C6 bilateral facet dislocation- with corresponding neurological level- motor + sensory. 10/02/2014 Anterior discectomy and fusion.

Recurrent episodes of segmental lung collapse- secondary to mucous plugs, as consequence of poor cough effort due to nature of spinal cord injury. Recurrent bronchoscopic intervention with removal plugs.

Episode of ventilator associated pneumonia- initiated on Piperacillin/Tazobactam. Patient at this stage seems to have depressed mood – initiated on fluoxetine, 18/02/2014. 19/02/2014 bleeding PV- Hb 9.8 to 4.9. Transfused 4u packed cells, FFP’s.

B-HCG negative, endovaginal and pelvic ultrasound normal.

Clotting profile showed marginally increased PT, with normal PTT and INR. Normal liver and kidney function tests. Prophylactic dose enoxaparin 4omg dly sc. Platelet number 261, Normal PFA-100®. Fibrinogen level ↑ 9.0. These parameters remained like this for the next 5days.

Patient ID Sample ID Patient name Sex Birth date Comment Test name Start time Run time Channel Error code CT A5 A10 A15 A20 A25 A30 CFT MCF MCF-t alpha LI30 LI45 LI60 ML CFR LOT CLR AR5 AR10 AR15 AR20 AR25 AR30 MCE ACF G TPI MAXV MAXV-t AUC LT Image filenameGT63973100 --- BOITSHOKO, MONTSHO F 1979-06-13 --- natem 2014-03-01T15:34:47 01:00:20 1 0 *3,614 --- --- --- --- --- --- --- --- --- --- --- --- --- --- --- --- --- --- --- --- --- --- --- --- *0 --- --- --- --- *27 --- BOITSHOKOMONTSH_natem_140301153447000GT63973100 --- BOITSHOKO, MONTSHO F 1979-06-13 --- intem 2014-03-01T15:35:36 01:00:18 2 0 228 72 79 80 80 80 79 48 80 941 82 98 95 --- *7 83 --- 5 498 1,258 2,054 2,858 3,659 4,452 409 *75 20,438 255 35 280 7,992 --- BOITSHOKOMONTSH_intem_140301153536000GT63973100 --- BOITSHOKO, MONTSHO F 1979-06-13 --- extem 2014-03-01T15:36:23 01:00:18 3 0 321 59 78 82 83 83 82 132 83 1,187 71 99 97 --- *4 76 --- 4 268 985 1,791 2,616 3,445 4,271 484 *79 24,203 110 16 478 8,274 --- BOITSHOKOMONTSH_extem_140301153623000GT63973100 --- BOITSHOKO, MONTSHO F 1979-06-13 --- fibtem 2014-03-01T15:37:12 01:00:18 4 0 1,590 4 8 12 17 21 25 1,429 *27 *2,015 *11 100 --- --- *0 --- --- --- 31 93 194 338 526 756 --- *28 --- --- 2 2,398 *2,772 --- BOITSHOKOMONTSH_fibtem_140301153712000

Cryoprecipitate 8u

Drugs withdrawn

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