Hemostasis, platelets and Blood management Julie Wegner, PhD, CP Midwestern University Glendale, AZ.
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Transcript of Hemostasis, platelets and Blood management Julie Wegner, PhD, CP Midwestern University Glendale, AZ.
Hemostasis, platelets and Blood management
Julie Wegner, PhD, CP
Midwestern University
Glendale, AZ
None
Why do patients bleed?
• Macrovascular• Microvascular
– Inability to generate thrombin• Insufficient clotting surface (platelets)• Insufficient substrates (clotting factors)• Inhibitors (anticoagulants, antithrombotic agents)
– Clot not strong enough• Insufficient thrombin generation• Weak fibrin-platelet mesh (platelets, fibrinogen)
– Clot vulnerable to lysis
Hemostatic components
Clot location
Substrates for: thrombin generation fibrin formation
Generating environmentProvide substrateProvide protection
Clot formation requirements
PlateletsEndotheliumWBCRBC
Procoagulant factors Intrinsic ExtrinsicAnticoagulant factorsAntithrombotic factors
EndotheliumSubendothelium
Cell-based model
Platelet contributionInitiation and propagation
Serial samplesCancer patients
Correlations: platelet count vs. MA r=0.7 vs. R r=-0.7 vs. r=0.8
Roeloffzen WWH et al. Thrombocytopenia affects plasmatic coagulation as measured bythromboelastography. Blood Coag Fibrinolysis 2010 (in press).
http://www.integrilin.com/popups/platelet2.html
Platelet cascade
Adhesion
Thrombin generation and
hemostasis
Insufficient clotting surface
Insufficient substrates
Presence of inhibitors
Central role of thrombin
From: Crawley JTB et al. The central role of thrombin. J Thromb Haemost. 2007; 5(Suppl 1): 95-101.
Thrombin generationkinetics
T1 = lag phaseT2 = maximum rate of TGT3 = Peak [thrombin]T4 = Total free thrombin (AUC)
Fibrin cross linkingLateral aggregation
TG = thrombin generation, AUC = area under the curve = endogenous thrombin potential (ETP)
from: Wolberg AS. Blood Rev. 2007.
From: Vanschoonbeek K, Feijge MAH, van Kampen RJW et al. Initiating and potentiating role of platelets in tissuefactor-induced thrombin generation in the presence of plasma: subject-dependent variation in thrombogramcharacteristics. J Thromb Haemost. 2004; 2:478-484.
Thrombin generating surfaceThrombin generation and platelet #
Bollinger D et al. Br J Anaesthesiol 2009; 102:793
TG and [substrate]
PPP
(50%)
1. No change in lag time2. Slight decrease rate TG3. Decrease peak TG
1. Decrease coagulation factors• FV and FVII ~ 28% Dilution• FII and FX ~ 44% Dilution + consumption
2. Thrombin potential – [FX] and [FII]-dependent3. Blood loss vs. thrombin potential (r = -0.75*)
Post-op bleeding:Hemodilution vs. consumption?
• Hemodilution global (cells and factors)
• Consumption → global?– Importance of adequate anticoagulation
• ACT @ 480 sec: clots vs consumption?
Heparin and thrombin generation
From: Tanaka KA, Katori N, Szlam F, Sato N, Kelly AB, Levy JH. Effects of tirofiban on haemostatic activation in vitro. Br J Anaesth.2004; 93:263-269.
Peak thrombin Max. rate thrombin generation Lag time
Reversing heparin effectIs more protamine always good?
• Fine tuning protamine– ‘excess’ protamine:
TG– ‘excess’ protamine:
• Increased time to clot• Decreased clot strength • Enhanced vulnerability
to fibrinolysis
Ni Ainle F et al. Blood 2009; 114:1658
TF
Celite
Nielsen VG. Ann Thorac Surg 2006; 81:1720
Weak clots
Insufficient thrombin generation
Insufficient substrate (fibrinogen)
Weak fibrin-platelet mesh (platelets)
Clot quality and [thrombin]
Wolberg, AS. Thrombin generation and fibrin clot structure. Blood Review 2007; 21: 131- 142
Fiber thickness
Fiber weave
Thick Thin
Loose Tight
Clot strengthLow High
Anesth Analg. 2010 In press
Plateau effect1 g/L
120 x 109/L
Bleeding• Depends on clot strength (MA)
• fibrinogen levels• platelet function
100
Clot strengthFibrinogen vs. platelets
Lang T et al. Anesth Analg 2009; 108:751
Velik-Salchner C et al. JTH 2007; 5:1019
Clot vulnerability to lysis
Importance of clot strength in hemostasis
http://www.setma.com/article.cfm?ID=330 Holly, J. Cardiometabolic Risk Syndrome Part V: Fibrinolytic Dysfunction
Fibrinolysis
endothelium
contact activation
TAFI Thrombin
I
Clot quality:Clot structure and local [thrombin]
Wolberg, AS. Thrombin generation and fibrin clot structure. Blood Review 2007; 21: 131- 142
Clot strengthLow High
Fibrinolysis vulnerabilityHigh Low
Colloid solutions (HES) do not activate fibrinolysis, but they do makeclots more vulnerable to fibrinolysis
Summary
• Variability in hemostasis– One size fits all?– Monitoring
• Thrombin generation – Multiple roles– Rate and peak vs. total thrombin
• Clot structure– Thrombin– Platelets– Fibrinogen
• Clot structure and fibrinolysis