Heparins have adequate ex vivo anticoagulant effects in hospitalized patients with cirrhosis

Boom, Bente P. van den; Meijenfeldt, Fien A. von; Adelmeijer, Jelle; Roberts, Lara N.; Bernal, William; Lisman, Ton

doi:10.1111/jth.15296

Cited by 3 publications

(4 citation statements)

References 37 publications

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“…Interestingly, however, VTE prophylaxis also does not seem to decrease VTE rates in these retrospective studies, suggesting that the prophylactic regimens administered are suboptimal. Although in vitro studies have suggested a decreased potency of some anticoagulant drugs in patients with liver disease, 61 in a recent prospective study, a single dose of prophylactic heparins led to a similar decrease in thrombin generation in patients with chronic liver disease compared to patients without liver disease 62 . Although future studies on the prolonged use of VTE prophylaxis and its optimal dosages should be performed, VTE prophylaxis should not be withheld from patients with cirrhosis.…”

Section: Haemostatic Complications In Liver Diseasementioning

confidence: 99%

Pathophysiology and management of bleeding and thrombosis in patients with liver disease

Boom

Lisman

2022

Int J Lab Hematology

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Patients with liver disease often develop complex changes in their haemostatic system. Frequently observed changes include thrombocytopaenia and altered plasma levels of most of the proteins involved in haemostasis. Although liver disease was historically classified as a haemostasis-related bleeding disorder, it has now been well established that the antihaemostatic changes that promote bleeding are compensated for by prohaemostatic changes. Conventional coagulation tests however do not accurately reflect these prohaemostatic changes, resulting in an underestimation of haemostatic potential. Novel coagulation tests, such as viscoelastic tests (VETs) and thrombin generation assays (TGAs) better reflect the net result of the haemostatic changes in patients with liver disease, and demonstrate a new, "rebalanced" haemostatic status. Although rebalanced, this haemostatic status is more fragile than in patients without liver disease. Patients with liver disease are therefore not only at risk of bleeding but also at risk of thrombosis. Notably, however, many haemostatic complications in liver disease are not related to the haemostatic failure. It is, therefore, crucial to identify the cause of the bleed or thrombotic complication in order to provide adequate treatment. In this paper, we will elaborate on the haemostatic changes that occur in liver disease, reflect on laboratory and clinical studies over the last few years, and explore the pathophysiologies of bleeding and thrombosis in this specific patient group.

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Section: Haemostatic Complications In Liver Diseasementioning

confidence: 99%

Pathophysiology and management of bleeding and thrombosis in patients with liver disease

Boom

Lisman

2022

Int J Lab Hematology

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“…There have been concerns raised from preclinical studies regarding efficacy of these agents in patients with cirrhosis due to their indirect mechanism of action via potentiation of antithrombin, which is reduced in cirrhosis 53 . However, a recent study comparing the anticoagulant effect of prophylactic LMWH/UFH prescribed to patients with and without cirrhosis suggested a similar anticoagulant effect of heparins in patients with cirrhosis 54 . There is no need for routine laboratory monitoring in this setting.…”

Section: Choice Of Pharmacological Thromboprophylaxis In Patients Wit...mentioning

confidence: 99%

“…53 However, a recent study comparing the anticoagulant effect of prophylactic LMWH/UFH prescribed to patients with and without cirrhosis suggested a similar anticoagulant effect of heparins in patients with cirrhosis. 54 There is no need for routine laboratory monitoring in this setting. As highlighted above and in Table 1, not all studies reported the pharmacological agent and/or doses utilized, so specific recommendations regarding preferred agent/dose cannot be made.…”

Section: Choice Of Pharmacologic Al Thromboprophyla Xis In Patient S ...mentioning

confidence: 99%

Thromboprophylaxis for venous thromboembolism prevention in hospitalized patients with cirrhosis: Guidance from the SSC of the ISTH

Roberts

Hernández‐Gea

Magnusson

et al. 2022

Journal of Thrombosis and Haemostasis

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Hospital‐associated venous thromboembolism (HA‐VTE) is a major cause of morbidity and mortality and is internationally recognized as a significant patient safety issue. While cirrhosis was traditionally considered to predispose to bleeding, these patients are also at an increased risk of VTE, with an associated increase in mortality. Hospitalization rates of patients with cirrhosis are increasing, and decisions regarding thromboprophylaxis are complex due to the uncertain balance between thrombosis and bleeding risk. This is further accentuated by derangements of hemostasis in patients with cirrhosis that are often considered contraindications to pharmacological thromboprophylaxis. Due to the strict inclusion and exclusion criteria of seminal studies of VTE risk assessment and thromboprophylaxis, there is limited data to guide decision making in this patient group. This guidance document reviews the incidence and risk factors for HA‐VTE in patients with cirrhosis, outlines evidence to inform the use of thromboprophylaxis, and provides pragmatic recommendations on VTE prevention for hospitalized patients with cirrhosis. In brief, in hospitalized patients with cirrhosis: We suggest inclusion of portal vein thrombosis as a distinct clinically important endpoint for future studies. We recommend against the use of thrombocytopenia and/or prolongation of prothrombin time/international normalized ratio as absolute contraindications to anticoagulant thromboprophylaxis. We suggest anticoagulant thromboprophylaxis in line with local protocols and suggest low molecular weight heparin (LMWH) or fondaparinux over unfractionated heparin (UFH). In renal impairment, we suggest LMWH over UFH. For critically ill patients, we suggest case‐by‐case consideration of thromboprophylaxis. We recommend research to refine VTE risk stratification, and to establish the optimal dosing and duration of thromboprophylaxis.

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“…97 Nevertheless, in a recent study performed by our group, it was shown that heparins have comparable anticoagulant effects in patients with ACLF as in those with cirrhosis or nonliver hospitalized, suggesting that the doses as currently used in patients without underlying liver disease might equally be suitable for those with ACLF. 99…”

Section: Correction Of Altered Hemostasis In Acutely Ill Liver Patientsmentioning

confidence: 99%

Effects of Inflammation on Hemostasis in Acutely Ill Patients with Liver Disease

Driever

Lisman

2022

Semin Thromb Hemost

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Patients with liver diseases are in a rebalanced state of hemostasis, due to simultaneous decline in pro- and anticoagulant factors. This balance seems to remain even in the sickest patients, but is less stable and might destabilize when patients develop disease complications. Patients with acute decompensation of cirrhosis, acute-on-chronic liver failure, or acute liver failure often develop complications associated with changes in the hemostatic system, such as systemic inflammation. Systemic inflammation causes hemostatic alterations by adhesion and aggregation of platelets, release of von Willebrand factor (VWF), enhanced expression of tissue factor, inhibition of natural anticoagulant pathways, and inhibition of fibrinolysis. Laboratory tests of hemostasis in acutely-ill liver patients may indicate a hypocoagulable state (decreased platelet count, prolongations in prothrombin time and activated partial thromboplastin time, decreased fibrinogen levels) due to decreased synthetic liver capacity or consumption, or a hypercoagulable state (increased VWF levels, hypofibrinolysis in global tests). Whether these changes are clinically relevant and should be corrected with antithrombotic drugs or blood products is incompletely understood. Inflammation and activation of coagulation may cause local ischemia, progression of liver disease, and multiorgan failure. Anti-inflammatory treatment in acutely-ill liver patients may be of potential interest to prevent thrombotic or bleeding complications and halt progression of liver disease.

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Heparins have adequate ex vivo anticoagulant effects in hospitalized patients with cirrhosis

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 3 publications

References 37 publications

Pathophysiology and management of bleeding and thrombosis in patients with liver disease

Pathophysiology and management of bleeding and thrombosis in patients with liver disease

Thromboprophylaxis for venous thromboembolism prevention in hospitalized patients with cirrhosis: Guidance from the SSC of the ISTH

Effects of Inflammation on Hemostasis in Acutely Ill Patients with Liver Disease

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