Perioperative Optimisation of Haemostasis and Coagulation

Partial Curriculum Map (2010): 

Partial Curriculum Map (2010) Basic Intermediate Higher IO_BS_09 VS_IK_12 GU_HK_02 OB_BTC_C04 CT_IS_03 GU_HS_03 GU_BK_07 PC_IK_08 OB_HS_06 OB_BK_06 PB_IK_04 MA_HS_02 PB_BK_45 MT_IK_07 CT_HK_08 PB_BK_23 MT_IK_06 CT_HS_08 MT_IS_04 CT_HK_09 OR_IK_04 AD_HS_12 MA_HK_08 MA_HS_09 CCT in Anaesthetics 2010, The Royal College of Anaesthetists

Objectives: 

Objectives List the components of an adequate haemostatic response Describe the pathophysiology of haemorrhagic shock Outline a management plan for haemorrhagic shock Diagnose DIC and list appropriate treatment options Describe risk factors and therapy for hyper-fibrinolysis Outline treatment of bleeding due to antiplatelet therapy Discuss the options to reverse effects of vitamin K antagonists

Clinical Scenarios: 

Clinical Scenarios Laparotomy for perforated viscus + septic shock Rib fractures & head injury in patient on warfarin Traumatic haemorrhagic shock

Scenario 1: 

Scenario 1 67 year old female admitted with a 5 day history of severe abdominal pain, and vomiting. Anuria for 2 days. Hypotensive, peripherally shut-down, confused and lethargic in A&E. Chest x-ray shows air under the diaphragm. Scheduled for emergency laparotomy. Hb 10.3 / WBC 29.8 / platelets 48 PT 24.6 / APTT 43 / Fibrinogen 0.95 Urea 21.8 / Creat 340 Q: How would you prepare this patient for theatre? Q: How would you deal with intraoperative bleeding?

ISTH Scoring system for DIC: 

ISTH Scoring system for DIC Test Score Platelet count > 100,000 = 0 51,000-100,000 = 1 < 50,000 = 2 D-dimer or FDP No increase = 0 Moderate increase = 1 Strong increase = 2 Prolongation of PT < 3 seconds = 0 > 3 but < 6 seconds = 1 > 6 seconds = 2 Fibrinogen g/L > 1 = 0 < 1 = 1 Score > 5 = overt DIC Repeat daily if < 5 Taylor, F.B., Jr, , Toh, C.H., Hoots, W.K., Wada, H. & Levi, M. (2001) Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Journal of Thrombosis and Haemostasis., 86, 1327–1330.

Disseminated intravascular coagulation: 

Disseminated intravascular coagulation

DIC - Treatment: 

DIC - Treatment Treat the underlying condition Platelets if < 50 and bleeding /high risk of bleeding FFP if bleeding or to cover procedure Factor concentrates e.g. PCC instead if volume overload If fibrinogen <1 g/L despite FFP treat with fibrinogen concentrate or cryoprecipitate Heparinise DIC with predominant thrombosis DVT prophylaxis if not bleeding Consider aPC in severe sepsis with DIC Consider tranexamic acid for DIC with primary hyper-fibrinolysis and severe bleeding Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. Brit J Haematol 2009; 145: 24-33.

Scenario 2: 

Scenario 2 You are called to A&E to see a 78 year old male who has fallen of a ladder from a height of 6 feet. He was unconscious for around 10 minutes. He is now drowsy but responsive. He has bruising and pain over his left chest. X-ray demonstrates at least 3 rib fractures and pleural fluid. There is no pneumothorax. CT brain shows a right frontal contusion with a small extradural. He is in atrial fibrillation and takes warfarin. PT 29 (INR 2.8 ), APTT 33, Platelets 145, HB 12.1 Q: How will you manage this man’s coagulation? Q: How will you deal with his pain?

Warfarin reversal: 

Warfarin reversal Assuming bleeding or need for surgery in < 24 h Prothrombin complex concentrate (PCC) + Vitamin K In absence of PCC can use FFP + Vitamin K, or rFVIIa* Vitamin K will reverse high INR within 24 hours INR < 5 will normalise over 4-5 days off warfarin What’s in Octaplex? * In urgent cases or where FFP is not available

PCC (Octaplex): 

PCC (Octaplex) Factor Half-life II 48-60 hours VII 1.5-6 hours IX 20-24 hours X 24-48 hours

Scenario 3: 

Scenario 3 47 year old crushed by forklift truck. Bilateral femoral shaft fractures and unstable pelvic fractures. Left rib fractures. BP 75/30 HR 130 ABG Hb 7.6 lactate 5.9 pH 7.22 2 litres 0.9% saline and 4 units O negative in A&E, taken to theatre for pelvic and femur stabilisation. Ongoing pelvic bleeding ++ Q: What factors are contributing to the bleeding? Q: What do you tell the blood bank (and when)? Q: How would you optimise haemostasis?

Predicting need for massive transfusion in trauma patients…: 

Predicting need for massive transfusion in trauma patients… Cotton BA, Dossett L, Haut E, et al . Multicentre validation of a simplified score to predict massive transfusion in trauma. J Trauma 2010; 69 (Suppl1): S33-39.

Massive transfusion protocols: 

Massive transfusion protocols Issues Activation and transport delays Outdated approaches/missing latest literature Requests for products too slow Product delays (FFP/platelets) Not (patho-)physiological Solutions Products issued as massive transfusion packs E.g. 4-6 PRBC + 4-6 FFP + 1 plts (achieves 1:2:2 RBC:FFP:plt) Use factor concentrates instead (or as well?)

Traumatic coagulopathy: 

Traumatic coagulopathy

Mechanisms of Coagulopathy: 

Mechanisms of Coagulopathy Loss of essential components Absolute Consumption Coagulation activation Relative Dilution Inhibition of haemostatic system Acidosis Hypothermia

Hyperfibrinolysis: 

Hyperfibrinolysis Disinhibition of tPA Consumption of PAI-1 by activated protein C Direct release of tPA from damaged endothelium Settings Cardiopulmonary bypass Major trauma Obstetrics Major urological surgery Major orthopaedic surgery

Slide 20: 

Coagulation and fibrinolysis

The “bloody vicious circle”… The lethal triad…: 

The “bloody vicious circle”… The lethal triad… Acidosis Hypothermia Coagulopathy Lier H, Krep H, Schroeder S, Stuber F. J Trauma. 2008;65:951–960

pH and coagulation: 

pH and coagulation pH < 7.4 - Altered platelet shape and structure pH 7.1 50% reduction in thrombin formation 35% reduction in fibrinogen Reduced platelet count Altered platelet receptor function Correction of acidosis Effectiveness of bicarbonate unclear THAM corrects thrombin and TEG values Aim to buffer to pH > 7.25

Hypothermia and coagulation: 

Hypothermia and coagulation

Calcium and coagulation: 

Calcium and coagulation

Mechanisms of Trauma-induced Coagulopathy: 

Mechanisms of Trauma-induced Coagulopathy Tissue damage Release of tissue factor Vessel damage Initial hypercoagulation Hypoperfusion Endothelial release of tPA => fibrinolysis Initial excessive thrombin burst Increased thrombomodulin and activation of PC Inactivation of Va, VIIIa, and PAI-1 Loss of regulation of tPA Plasmin-mediated hyperfibrinolysis

Mechanisms of Trauma-induced Coagulopathy: 

Mechanisms of Trauma-induced Coagulopathy Acidosis Reduced thrombin generation (50% by pH 7.2) Decreased fibrinogen and platelet levels Decreased clot quality and increased formation time Volume replacement (e.g. 30% dilution) Decreased clot quality (HES/gelatins etc.) Decreased II, VII, VIII, XI, XIII and fibrinogen Thrombin generation maintained Corrected by fibrinogen concentrate

Other issues - platelet margination: 

Other issues - platelet margination At normal Hct: platelets flow near vessel walls RBCs in centre of vessel Exposed to greatest shear force Important in partial activation Important in interaction with vWF on vessel wall As anaemia progresses, more mixing occurs Anaemia reduces platelet/endothelium contact

Key components in haemostasis…: 

Key components in haemostasis… Platelets Fibrinogen Factor XIII (?) – when levels below 60% Innerhofer P, Kienast J. Principles of perioperative coagulopathy. Best Pract Res Anesthesiol 2010; 24: 1-14.

Fibrinogen levels must be protected: 

Fibrinogen levels must be protected

Evolution of fibrinogen targets…: 

Evolution of fibrinogen targets…

Potential Interventions: 

Potential Interventions

Fresh Frozen Plasma: 

Fresh Frozen Plasma Acellular portion of donor blood Frozen to -30 o C with 8 hours of donation Contains near-normal levels of plasma proteins Also lipids, carbohydrates, minerals, anticoagulant components INR of FFP often at upper normal level Quality control is based on Factor VIII levels in Europe Indicated for multiple-factor deficiencies NOT for isolated deficiency (use factor concentrate) Still used too much in USA to correct high INR NOT indicated for fibrinogen replacement alone Viral transmission risk (inactivation lowers factor content)

FFP in massive transfusion: 

FFP in massive transfusion Modern recommendations FFP:RBC 1:1-1:2 Coagulopathy begins after as few as 3 PRBCs Dose = 30 ml/kg “Traditional” recommendation 10-15 ml/kg FFP insufficient Complications Febrile reaction Allergic reaction (1-1.5% per unit, rarely severe) Transfusion associated circulatory overload (TACO!) TRALI

Alternatives to FFP…: 

Alternatives to FFP…

Cryoprecipitate: 

Cryoprecipitate Higher fibrinogen concentration than FFP Fibrinogen concentration is variable 75% of units must have at least 140mg fibrinogen Lower volume Withdrawn from many countries Still available UK and USA No studies looking at perioperative efficacy Viral infection risk as FFP

Infection risks: 

Infection risks FFP HIV: 1 in 10 million Hepatitis C: 1 in 50 million Hepatitis B: 1 in 1.2 million vCJD ? West Nile virus (USA) very rare now Cryoprecipitate Prepared from untreated FFP Similar infection risks Viral inactivation decreases fibrinogen by 16-41%

Other haemostasis options: 

Other haemostasis options

The cell-based coagulation system: 

The cell-based coagulation system

Haemostatic response – cell-based: 

Haemostatic response – cell-based

Haemostatic response – cell-based: 

Haemostatic response – cell-based

Regulation of clot formation: 

Regulation of clot formation Protein C, Protein S, Antithrombin III, tPA, TAFI, TFPI, PAI-1

Questions?: 

Questions?