Global Haemostasis in Critically Ill Patients with Sepsis: Evidence for a Prothrombotic State.

Activation of haemostasis in sepsis may lead to microvascular thrombosis and progression to multiorgan failure (MOF). Almost all critically ill patients with sepsis have abnormal coagulation screens but these are unlikely to adequately represent the state of a patient’s haemostatic system and global assays may be more useful. Normal controls (n=32) and critically ill patients with sepsis (n=39) were recruited. Coagulation factors, antithrombin (AT) and protein C (PC) were measured. Thrombin generation was measured using the calibrated automated thrombogram (CAT) in platelet rich (PRP) and poor (PPP) plasma. Low dose tissue factor (6pM) activated whole blood Rotem® was measured and the first derivative of the trace gave a velocity of clot firmness.

The results show that despite decreased levels of factors II, V, VII, XI and XII (correlation with decreased albumin, P<0.01, suggesting synthetic dysfunction as well as consumption); global measures of haemostasis show delayed but preserved or enhanced overall thrombin generation and clot formation. We hypothesise that the raised FVIII and normal FIX offset the decreased levels of other factors to maintain total thrombin generation which is delayed due to slowed formation of sufficient initial thrombin to activate FV, VIII and XI and stimulate expression of platelet phospholipids. Raised fibrinogen (correlation with CRP, P<0.001), important in the whole blood Rotem-based method, contributes to the prothrombotic state. The global assays are not sensitive to AT and PC and may underestimate the prothrombotic state. These data suggest that haemostatic changes in sepsis are predominantly prothrombotic and may be important in microvascular thrombosis and progression MOF.