Abnormal clotting

There are a number of inherited disorders that can affect coagulation. The most common of these are haemophilia A and B and von Willebrand disease (VWD), which are X-linked disorders and therefore primarily affect males.^1,2 Haemophilia A and B are caused by deficiencies in factors VIII and IX, respectively, and are associated with excessive and spontaneous bleeding.³ VWD is caused by a deficiency and/or an abnormality in von Willebrand factor (VWF), which is necessary for platelet-to-platelet cohesion and aggregation and adhesion of platelets to the blood vessel wall.⁴ 

Defects linked to other coagulation factors are much rarer and are generally autosomal recessive conditions.^1,2 They affect both males and females, and there is more variability and less predictability in bleeding manifestations compared with haemophilia. 

Assessment of congenital clotting disorders is a complex process requiring a number of different laboratory tests to analyse.^2,3

Direct oral anticoagulants (DOACs) may be used as an alternative to the traditional use of VKAs, such as warfarin, for treatment and prevention of thrombosis in some circumstances,^12,13 although they are not licensed for use in patients requiring anticoagulation for mechanical heart valves.  Rather than targeting the synthesis of vitamin K-dependent clotting factors,  DOACs inhibit specific components of the coagulation cascade directly (Figure 1).¹² There are currently five Food and Drug Administration (FDA)-approved DOACs available: the factor Xa inhibitors rivaroxaban, apixaban, edoxaban and betrixaban, and the thrombin inhibitor dabigatran.¹³ Advantages compared with VKAs include a quicker onset of action and fewer drug-drug interactions, with a subsequent lower need for monitoring or follow-up.¹³

However, there is evidence to suggest that DOACs can indirectly inhibit thrombin-induced platelet aggregation through their inhibition of thrombin generation.^14–16 Due to their direct mode of action on factors involved in the coagulation cascade, DOACs can also affect the interpretation of many laboratory clotting tests; they generally prolong clotting tests, as their inhibition of thrombin or factor Xa disrupts the clotting process.¹⁷ 

In addition to the impact of pharmacotherapy on haemostasis, surgical procedures also carry a risk of bleeding (Figure 3). Although some perioperative blood loss is unavoidable, excessive bleeding is a major complication associated with increased morbidity and mortality.²⁷ Blood loss during surgery can be due to bleeding directly at the site of surgery or an undetected coagulation disorder and can be exacerbated by the effect of the procedure and the subsequent blood loss on haemostasis.²⁷ 

This is a well-recognised challenge in heart surgery with cardiopulmonary bypass (CPB), where abnormalities in platelets, fibrinolysis and a number of coagulation factors can occur.^29,30 During CPB, blood is passed through an extra-corporeal circulation. The blood is in  prolonged contact with an artificial surface and the oxygenator, both of which lead to the induction of a pro-thrombotic state.³¹ This, along with the subsequent high doses of heparin required, and any trauma or hypothermia related to the surgical procedure, can contribute to coagulation dysfunction.²⁸ Fibrinolysis is also activated due to an increase in tissue plasminogen activator (tPA), and haemodilution results in a reduction in platelets and coagulation factors in the blood.²⁷

Extracorporeal membrane oxygenation (ECMO) is another therapy that exposes the blood to a foreign surface, stimulating inflammation and coagulation and inducing a pro-thrombotic state that can lead to fibrin deposition and thrombus formation.^32,33 Moreover, sepsis and inflammation mostly characterise patients with severe respiratory failure on ECMO, complicating anticoagulation management and monitoring. Haemorrhage can also occur through continuous activation of the coagulation cascade, low-level fibrinolysis and consumption of platelets.³²