8.2.6 Perioperative hypercoagulability

 Blood is kept in balance between procoagulant and anticoagulant trends. This balance can be upset in favour of coagulation by increasing coagulation activity or decreasing fibrinolysis. This may occur in congenital conditions or in acquired diseases [7].

• Congenital hypercoagulability (5-9 times increased thrombotic risk):
  • Procoagulant effect: factor V Leiden (factor V resistant to cleavage by protein C), G20210A mutation in prothrombin, hyperfibrinogenemia.
  • Reduction in anticoagulation efficiency: protein C and S deficiency, antithrombin III deficiency.
  • Reduced fibrinolysis: deficiency of plasminogen inhibitor, lipoprotein (a).
• Acquired hypercoagulability (8-15 times increased thrombotic risk):
  • Antiphospholipid antibodies (lupus erythematosus), cardiolipin.
  • Conditions such as carcinoma, inflammatory conditions, severe burns or major trauma.
  • Heparin-induced thrombocytopenia (see HIT).
  • Pharmacological causes: oral contraceptives, tissue adhesives, excessive use of coagulation factors (rFVIIa, desmopressin).

The origin of a thromboembolism is multifactorial, and the triggering cause is very often surgery. The three elements of Virchow's triad (blood, flow and vascular wall) are severely disrupted by surgical procedure and by tissue damage; coagulation balance is unset by metabolic stress and by systemic inflammatory syndrome in favour of hypercoagulability [4].

• Acceleration of thrombin formation and decrease in antithrombin activity, corresponding to a stimulation of the coagulation cascade.
• Hyperfibrinogenemia (up to 6 g/L). Spontaneous elevation of fibrinogen levels during surgery increases the firmness of clot but also the risk of thrombosis.
• Platelets increase in number and aggregability. This hyperactivity can lead to excessive consumption and reduced functionality postoperatively, particularly important when in contact with foreign surfaces such as in ECC or ventricular assist [5].
• Clot dissolution is delayed.

Coagulation cascade is a very powerful system, as blocking blood loss is crucial during an attack or injury. This phenomenon appeared with the first vertebrates 450 million years ago and has been a definite evolutionary advantage for such animals. Perioperative hypercoagulability, with its attendant arterial occlusions, venous thromboses and embolisms, is the manifestation of a primordial element for survival of complex beings. It is therefore not surprising how difficult to inhibit it properly.

Reviews

The diagnosis of vascular occlusion is obviously based on ischaemia of target organs (infarction, vascular occlusion), venous stasis and embolism (most often pulmonary). The presence of thrombin-antithrombin complexes (TAC) or D-dimer confirms the genesis of a thrombus. But there is no test that can predict which patients are at risk. In the perioperative setting, two types of laboratory tests  can be performed in the operating room (POC test, point-of-care test) give an idea of the degree of coagulation stimulation and its possible deviations.

• Thrombo-elastogram (TEG) (ROTEM™); it assesses time to get a clot, speed of its formation, its firmness, and time for its disappearance.
• Platelet function test (VerifyNow™, Multiplate™, etc).

Unfortunately, these tests are not that standardised and have not been validated by large multicentre studies. There is currently only a narrow consensus on their cut-off values.

Prophylaxis

Deep vein thrombosis and pulmonary embolism are the most common risks of postoperative hypercoagulability. They are favoured by a number of factors.

• Advanced age;
• Coagulopathies;
• Anamnesis of thromboembolism;
• Active cancer disease;
• Obesity;
• Inflammatory syndrome: infection, sepsis, rheumatic disease;
• Orthopaedic surgery, cancer surgery;
• Immobilisation, venous compression;
• Pregnancy and postpartum, prescription of oestrogens;
• Central venous catheter, pacemaker probe.

In addition to early mobilisation and intensive physiotherapy, thromboembolic prophylaxis is based on anticoagulation. Several different regimens are currently considered adequate [2,6].

• Non-fractionated heparin, 5'000 IU 2-3 x/day subcut;
• LMWH: first dose preoperatively or 3-6 hours postoperatively;
  • Enoxaparin (Clexane^® , Lovenox^® ), 40 mg/day or 30 mg 2 x/day subcut;
  • Nadroparin (Fraxiparine^® ) 5700 U/d subcut;
  • Dalteparin (Fragmin^® ) 5'000 U/d subcut;
• Fondaparinux (Arixtra^® ), 2.5 mg/day subcut;
• Dabitagran (Pradaxa^® ), 110 or 220 mg/day po;
• Rivaroxaban (Xarelto^® ), 10 mg/day orally.

Treatment is usually of short duration (7-10 days), but is extended (4-6 weeks) in high-risk situations such as major pelvic or orthopaedic surgery.

A patient's risk of developing thromboembolism can be quantified by various clinical scores, one of the most relevant being Padua Prediction Score [1].

• Active cancer 3 points
• Anamnesis of thromboembolism 3 points
• Reduced mobility 3 points
• Hypercoagulability syndrome 3 points
• Recent trauma or surgery (< 30 days) 2 points
• Age > 70 years 1 point
• Cardiorespiratory failure 1 point
• Heart attack or stroke 1 point
• Inflammatory status 1 point
• Obesity (BMI > 30) 1 point
• Hormone therapy 1 point

Below 4 points, the risk is low; above 4 points, it is high and warrants prophylaxis [1].

The diagnosis of pulmonary embolism is suspected on the basis of its clinical probability, as determined by a score such as revised Geneva score (see Table 17.11) [3].

 © CHASSOT PG, MARCUCCI Carlo, last update November 2019.

References

1. BARBAR S, NOVENTA F, ROSSETTO V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 2010 ; 8 :2450-7
2. GARCIA DA, BAGLIN TP, WEITZ JI, et al. Parenteral anticoagulants: Antithrombotic therapy and prevention of thrombosis, 9^th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (Suppl 2):e24S-e43S
3. LE GAL G, RIGHINI M, ROY PM, et al. Prediction of pulmonary embolism in the emergency department: The revised Geneva score. Ann Intern Med 2006; 144:165-71
4. NIELSEN VG, ASMIS LA. Hypercoagulability in the perioperative period. Best Pract Res Clin Anaesthesiol 2010; 24:133-44
5. NIELSEN VG, STEENWYK BL, HOLMAN WL, et al. Mechanical circulatory device thrombosis: a new paradigm linking hypercoagulation and hypofibrinolysis. Am Soc Artif Int Org J 2008; 54:351-8
6. SINAURIDZE EI, PANTELEEV MA, ATAULLAKHANOV FI. Anticoagulant therapy: basic principles, classic approaches and recent developments. Blood Coag Fibrinol 2012; 23:482-93
7. SNIECINSKI RM, HURSTING MJ, PAIDAS MJ, LEVY JH. Etiology and assessment of hypercoagulability with lessons from heparin-induced thrombocytopenia. Anesth Analg 2011; 112: 46-58