Netherlands Journal of Critical Care Submitted November 2015; Accepted March 2016 REVIEW Risk estimation and management of coagulopathy in ICU patients in need of an invasive procedure M.C.A. Müller1,2, N.P. Juffermans2 1Department of Intensive Care, Medical Center Haaglanden-Bronovo, The Hague, the Netherlands 2Department of Intensive Care, Academic Medical Center, Amsterdam, the Netherlands Correspondence M.C.A. Müller - [email protected] Keywords - coagulopathy, bleeding, plasma, viscoelastic tests Abstract Coagulation abnormalities have a high prevalence in critically ill intervention-related bleeding complications is limited. In this patients. The most commonly used tests to assess coagulation narrative review, we discuss the assessment of bleeding risk and status include assessment of the platelet count, prothrombin management of coagulopathy in critically ill patients in need of time, fibrinogen and d-dimer. However, as these tests do not an invasive procedure. A practical recommendation is given. reflect in vivo haemostatic potential, their ability to assess a potential risk of bleeding is limited. Viscoelastic tests evaluate Introduction the whole process of clot formation and degradation, but Coagulopathy has a high prevalence among critically ill their value in the assessment of bleeding risk remains to be patients,[1] and is the result of the derangement of both established. procoagulant and anticoagulant components of the coagulation Despite their limitations, increased prothrombin time/ system (figure 1).[2] The procoagulant elements include the international normalised ratio values or decreased platelet endothelium, thrombocytes, individual coagulation factors and counts are the most important reasons to prophylactically fibrinogen. The anticoagulant system includes proteins C and administer plasma or platelets to critically ill patients prior S and antithrombin. The third component of coagulation is to undergoing an invasive procedure. However, evidence that the fibrinolytic system. The inflammatory response in critical prophylactic correction of coagulation abnormalities prevents illness results in activation of the coagulation system with enhanced thrombin generation, accompanied by attenuated Thrombosis Bleeding fibrinolysis and reduced levels of anticoagulants. Altogether, this leads to a hypercoagulable state with the formation of Increased levels of VWF (micro) thrombi, associated with impaired organ perfusion Decreased levels of ADAMTS-13 Thrombocytopenia Increased levels of factor VIII Vitamin K deciency and subsequent organ failure. Ongoing coagulation processes Reduced proteins C and S and antithrombin Reduced levels of during this hypercoagulable state result in consumption of Downregulation of thrombomodulin factors II, V, VII, IX, X, XI Reduced capacity of TFPI Reduced brinogen clotting factors and thrombocytes, with ensuing deficiencies. Impaired brinolysis (increased PAI-1 and TAFI) Hereby, haemostatic balance will shift to a hypocoagulable state with an increased bleeding tendency. The most common causes of deranged coagulation in the critically ill are summarised in table 1.[2] Assessment of coagulopathy in critically ill patients is a highly relevant clinical need; however, it is characterised by multiple Figure 1. Factors influencing the haemostatic balance in critically ill limitations. The most commonly used tests, including platelet patients count and coagulation times, only reflect a limited part of the ADAMTS-13 = a disintegrin and metalloproteinase with thrombospondin haemostatic process and thus cannot reliably predict potential type 1, motif 13; PAI-1 = plasminogen activator inhibitor type I; TAFI = bleeding risk.[3] The international normalised ratio (INR) was thrombin activatable fibrinolysis inhibitor; TFPI = tissue factor pathway developed to monitor therapy with vitamin K antagonists as inhibitor; VWF= von Willebrand factor it reflects a deficiency of vitamin K dependent coagulation 6 NETH J CRIT CARE - VOLUME 24 - NO 3 - MAY 2016 Netherlands Journal of Critical Care Risk estimation and management of coagulopathy in ICU patients in need of an invasive procedure Table 1. Causes of coagulopathy in critically ill patients Procedures were diverse and included kidney and liver biopsy, PT prolongation Thrombocytopenia as well as abdominal and thoracic drainage.[3] Results of this Consumption review were confirmed in two more recent observational Sepsis Sepsis DIC DIC studies of central venous catheter (CVC) insertion in patients [16,17] Cardiac surgery Extracorporeal circuits with increased INR values. In three studies evaluating the risk Enlarged spleen of chest tube placement in patients with coagulopathy, observed Drug-induced [18-20] Blood loss bleeding rates were low and not related to INR or PT values. The Multiple trauma Multiple trauma same applies to patients undergoing percutaneous insertion of a [21,22] Major blood loss Major blood loss tracheostomy. Also, in trauma patients needing placement Decreased generation of an intracranial pressure monitor, INR was not predictive for Vitamin K deficiency Bone marrow dysfunction the occurrence of bleeding complications.[23] These results are Use of vitamin K antagonists in line with a recent clinical trial in critically ill patients with Renal failure coagulopathy, in which INR/ PT values did not differ between Liver disease patients with and without minor bleeding after undergoing an intervention.[14] Taken together, in critically ill patients undergoing an invasive factors.[4] However, this test was not intended nor validated to procedure, PT or INR values are not predictive of the risk of assess global haemostatic potential. Viscoelastic tests such as bleeding. An explanation may be that the PT/INR provides rotational thromboelastography assess the whole process of clot information on only part of the coagulation process. Thereby, formation and degradation. Thromboelastography has shown other than to detect or estimate the level of vitamin K deficiency, to detect coagulopathy in massive bleeding.[5-10] However, it is questionable whether PT/INR should be measured prior to thromboelastography data derived from critically ill patients are invasive procedures. scarce and reference standards for this population are lacking.[11] To date, these limitations preclude the incorporation of these Platelet count tests into the standard diagnostic evaluation of critically ill Overall, studies on the predictive ability of platelet count to patients with suspected coagulopathy. Other global tests of identify patients at risk of bleeding after invasive procedures haemostasis may include thrombin generation tests. However, are limited. In addition, probably not only the count but also these tests are not available at the bedside. Also, there is a lack the platelet function determines the risk of bleeding. Tests to of available tests for clinical use to detect a defective natural determine platelet function are either cumbersome or not yet anticoagulant system, and the same applies to markers of validated (such as the platelet function analyser, bleeding time fibrinolysis.[12] and rotational thromboelastometry (ROTEM) with a multiplate Altogether, due to the above-mentioned limitations, reliable functionality). Here, we will only discuss the platelet count. identification of critically ill patients with coagulopathy In retrospective studies in patients undergoing tracheotomy is difficult. In clinical practice, platelet count, prolonged or liver biopsy, an inverse relationship was found between prothrombin time (PT) or an increased INR are most frequently the platelet count and risk of bleeding, although a specific used to identify patients with coagulopathy[1] and serve as the threshold value could not be given.[24,25] Using multivariate most important trigger to prophylactically correct a suspected modelling, a retrospective study in patients undergoing CVC coagulopathy.[13] However, the efficacy of blood products to placement suggested a cut-off level of a platelet count of less correct coagulopathy is also a matter of debate,[14,15] in particular than 20,000 as an independent risk factor for bleeding.[26] In for the use of plasma. another single-centre study, bleeding outcomes were reported In the current review, we discuss the ability of these tests to predict after placement of tunnelled CVCs using ultrasonography the risk of bleeding. Also, we discuss management of coagulopathy guidance.[27] During 344 procedures performed in patients that results from critical illness, reviewing both guidelines and with a platelet count less than 50,000, including 42 cases with existing data. A practical recommendation on the assessment and a platelet count less than 25,000, no bleeding complications treatment of coagulopathy in critically ill patients is given. occurred. Of note, all practitioners in this study had extensive experience in image-guided catheter insertion, which limits Value of haemostatic tests to predict bleeding following an the generalisation of these results to settings in which invasive procedure in patients with critical illness-related operators are less experienced. coagulopathy Taken together, for commonly performed procedures on the PT/INR ICU, there seems to be a relation between platelet count and A review of 25 studies, performed in 2005, showed that an risk of bleeding after a procedure, with a possible cut-off value elevated INR was not predictive of periprocedural bleeding. of 20,000. NETH J CRIT CARE - VOLUME 24