7.6.7 Haemostasis and coagulation

Preoperative treatment, heparinisation, bleeding and ECC coagulopathy all combine to increase blood loss after weaning. This area is discussed in detail in Chapters 8 (Coagulation) and 28 (Transfusions). Only a brief review of the main guidelines will be shared here.

Transfusion

Red cell transfusion is only one component of an integrated blood saving strategy that considers the patient's blood as an irreplaceable asset deserving maximum protection: it is based on several principles [9,26].

• Saving the patient's blood cells and coagulation factors, limiting blood loss (rigorous haemostasis, normovolaemic pre-ECC haemodilution, blood recovery, ultrafiltration, tissue adhesives).
• Rational administration of blood products, restrictive transfusion thresholds.
• Prevention of intraoperative coagulopathy (normothermia, acid-base balance, calcium, antifibrinolytics).
• Improvement of tissue DO₂ by haemodynamic and ventilatory optimisation (FiO₂ 0.8-1.0, muscle relaxation, deep anaesthesia, normovolaemia, inotropic support).
• Use of algorithms based on laboratory tests performed in the operating room.

Provided the patient is normovolaemic and the source of bleeding is controlled, transfusion is indicated for the following Hb values [1,3,4,5,12,14].

• On bypass surgery if Hb < 60 g/L (or Ht < 20-24% depending on comorbidities).
• Outside of bypass surgery, an Hb value of 70-80 g/L is a reasonable threshold for transfusion.
• In at-risk populations (coronary ischaemia, ventricular failure, stroke, nephropathy, advanced age, ARDS), the threshold for transfusion may be raised to 80-90 g/L.
• Transfusion is unlikely to improve DO₂ when Hb is ≥ 100 g/L, except in cyanotic heart disease (R-L shunt, pulmonary hypertension).

Transfusion of platelet concentrates during cardiac procedures should be restricted to the following conditions, as it is associated with excess stroke, arterial thrombosis and mortality [3,22].

• Thrombocytopenia < 50,000/mcL.
• Platelet dysfunction proven by functional testing (Multiplate™, VerifyNow™, etc).
• Hemorrhage on uninterrupted preoperative antiplatelet therapy.
• Hemorrhage not controlled by standard measures with evidence of platelet consumption.

Coagulation factors

Many coagulation factors are available in isolated or combined form (Table 8.10). Their primary indication is the treatment of congenital coagulopathies and bleeding on anti-vitamin K (AVK) agents. However, their most frequent use is related to their potential effect on consumption coagulopathies encountered in massive bleeding. Most of these factors show some efficacy in reducing blood loss, but large controlled studies tend to show that this effect is rather modest, and that it comes along with a certain thrombotic risk, particularly with activated factors; this risk ranges from 0.1% to 24% depending on the substance and the series [20].

Fresh frozen plasma (FFP) is  good at preserving oncotic pressure in polytransfused patients, but it is not an effective way of administering clotting factors. The low concentration of clotting factors in FFP (about 0.5 g of fibrinogen per vial) means that a considerable amount must be infused to restore balance (30 mL/kg, or about 2 L for an adult) [6]. In addition to hypervolaemia, FFP is associated with febrile and allergic reactions, infectious contamination and lung injury [13]. The accepted indications for FFP are massive transfusions (blood bag: FFP ratio 1:1 to 2:1), unavailability of isolated coagulation factors and plasma exchange [18]. In other situations, the risks are likely to outweigh the benefits.

Fibrinogen is the first element to be lowered by blood loss: it reaches the critical level of 1.5 g/L when circulating volume loss is 50% [10]. Several studies in cardiac surgery have shown a reduction in the need for allologous blood bags, platelets and plasma in patients who have received fibrinogen [16,17]. Current recommendations consider a level of < 2 g/L as hypofibrinogenemia [14,21]. The administration of 3 gm fibrinogen to a 70 kg patient increases the plasma level by approximately 1 g/L [15]. The most accurate management is based on FIBTEM results: 25-50 mg/kg are required to maintain CMF > 10 mm [24].

Lyophilised prothrombin complex concentrates (PCCs, formerly PPSBs) can be divided into 3 categories [20].

• Concentrates of 3 factors: factors II, IX, X (Prothromplex HT^® ); used mainly in North America to antagonise VKAs.
• Concentrates of 4 factors: factors II, VII, IX, X (Prothromplex T^® , Kanokad^® , Kaskadil^® , Cofact^® , Beriplex^® , Octaplex^® ); dosage: 20-25 IU/kg in case of persistent bleeding, 30-50 IU/kg in case of intracranial bleeding on VKA.
• Activated concentrates: factors II, VII, IX, X, some of which are in activated form (FEIBA^® , Factor eight inhibitor bypassing activity, Autoplex-T^® ); dosage: 50-100 IU/kg. Indicated in the presence of inhibition of factors VIII and IX.

The concentration of each factor varies greatly between preparations. Factor consumption due to massive haemorrhage requires replacement when the loss exceeds 200-250% of the blood volume [2]. Non-activated PCCs are relatively safe, whereas activated concentrates (FEIBA^® ) present a significant risk of thromboembolism [20]. PCCs are only fully active if temperature, blood calcium and acid-base balance are optimal.

Recombinant factor VIIa (rFVIIa, NovoSeven^® , 90 mcg/kg repeated after 2 hours) is indicated for congenital haemophilia A and B, Glanzmann thrombasthenia, and factor VII deficiency. However, there are no data from controlled trials showing a significant gain in mortality in indications related to difficult to control bleeding in cardiac surgery [14,25]. In any case, the substance can only be effective if four elements are controlled [11].

• Platelet count > 70,000/mcL;
• Blood calcium > 1 mmol/L;
• Fibrinogenemia ≥ 2 g/L;
• Haemoglobin ≥ 80 g/L.

Activated factors such as FEIBA and rFVIIa carry a significant risk of generalised arterial and venous thrombosis, probably around 3-10%. They are only recommended as a life-saving measure in cases of potentially lethal haemorrhage refractory to standard therapies, including surgical and endovascular therapies [20].

Factor XIII is responsible for the strength of the fibrin polymer network and has anti-fibrinolytic properties. In cardiac surgery, administration of FXIII (Fibrogammin P^® 10-30 IU/kg) after protamine reduces postoperative blood loss, but it appears to be effective only in patients with lowered factor XIII levels (decreased peak clot firmness on thromboelastogram), which frequently occurs with significant blood loss [8,19]. As in the previous case, it is only appropriate when other treatments have failed to stop bleeding.

Pharmacological agents

In addition to tranexamic acid (see Antifibrinolytics), desmopressin (Octostim^® , Minirin^® ) may have a haemostatic effect because it stimulates the production of factor VIII and von Willebrand factor by the endothelium. It is useful in cases of inhibition by antiplatelet drugs or new oral anticoagulants [23]. It reduces blood loss by 23% and transfusions by 25% during coronary revascularisation in bypass surgery in patients on antiplatelet agents; the rate of re-intervention for haemostasis is reduced (OR 0.39) [7]. The dose is 0.3 mcg/kg IV over 30 minutes (half-life 4-5 hours). Simultaneous administration of tranexamic acid is recommended as desmopressin also stimulates fibrinolysis.

Without being linked to pharmacological agents, three elements are of primary importance in the management of bleeding situations: normocalcaemia, acid-base balance and normothermia.

© CHASSOT PG, GRONCHI F, April 2008, last update, December 2019

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