Thrombocytopenia Is Associated With Multi-organ System Failure in Patients With Acute Liver Failure

doi:10.1016/j.cgh.2015.09.029

Clinical Gastroenterology and Hepatology

Volume 14, Issue 4, April 2016, Pages 613-620.e4

https://doi.org/10.1016/j.cgh.2015.09.029 Get rights and content

Background & Aims

Acute liver failure (ALF) is a syndrome characterized by an intense systemic inflammatory response (SIRS) and multi-organ system failure (MOSF). Platelet-derived microparticles increase in proportion to the severity of the SIRS and MOSF, and are associated with poor outcome. We investigated whether patients with ALF develop thrombocytopenia in proportion to the SIRS, MOSF, and poor outcome.

Methods

In a retrospective study, we collected data on the post-admission platelet counts of 1598 patients included in the ALF Study Group Registry from 1998 through October 2012. We investigated correlations between platelet counts and clinical features of ALF, laboratory test results, and outcomes. Of the patients studied, 752 (47%) survived without liver transplantation, 390 (24%) received liver transplants, and 517 (32%) died.

Results

In patients with SIRS, platelet counts decreased 2 to 7 days after admission, compared with patients without SIRS (P ≤ .001). Patients with abnormal levels of creatinine, phosphate, lactate, or bicarbonate had significantly lower platelet counts than patients with normal levels of these laboratory values (all P ≤ .001). The decrease in platelets during days 1 to 7 after admission was proportional to the grade of hepatic encephalopathy and requirement for vasopressor and renal replacement therapy. Although platelet numbers decreased after admission in the overall population, platelets were significantly lower 2 to 7 days after admission in patients with outcomes of death or liver transplantation than in patients who made spontaneous recoveries and survived. In contrast, international normalized ratios over time were not associated with SIRS, laboratory test results associated with poor outcomes, grade of hepatic encephalopathy, or requirement for renal replacement therapy.

Conclusions

The development of thrombocytopenia in patients with ALF is associated with the development of MOSF and poor outcome. We speculate that SIRS-induced activation of platelets, yielding microparticles, results in clearance of platelet remnants and subsequent thrombocytopenia.

Section snippets

Patients and Data Collection

Consecutive participants in the ALF Study Group Registry from its inception in 1998 until October 2012 were assessed for eligibility. Inclusion criteria included acute injury (defined as a jaundice-to-HE interval of < 26 wk), the presence of coagulopathy (defined as INR ≥ 1.5), the presence of HE, and the absence of a previously identified chronic liver disease.¹⁶ Laboratory data and systemic complications were collected for a maximum of 7 days (ie, days 1–7) after enrollment. Data were no

Clinical Characteristics of the Study Population

Baseline demographic and median laboratory values for the 1598 study patients are shown in Table 1. Young Caucasian women dominated the study population (mean age, 41 y; 76% Caucasian, 70% female). Nearly half (47%) of study participants had ALF as a result of acetaminophen (APAP) overdose. Eighty-five percent of study subjects had at least 1 positive element of the SIRS on admission, 32% developed hypotension requiring vasopressors, 33% developed renal failure requiring RRT, 35% developed

Discussion

The current study documents a relationship between a decreasing platelet count, the presence of the SIRS, development of MOSF, and outcome in patients with ALF. We recently showed that plasma microparticles are derived primarily from platelets in patients with ALF, and increase in proportion to the intensity of the same clinical parameters,¹⁵ suggesting that the SIRS drives platelets to generate microparticles, which in turn, play a role in the pathogenesis of the ALF syndrome. The potential

Acknowledgments

The data were presented at the 2013 Annual Meeting of the American Association for the Study of Liver Diseases (plenary session), Washington, DC; November 2013.

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: Conflicts of interest The authors disclose no conflicts.

: Funding Supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (U-01 DK-58369).

View full text

Original articlePancreas, biliary tract, and liverThrombocytopenia Is Associated With Multi-organ System Failure in Patients With Acute Liver Failure

Background & Aims

Methods

Results

Conclusions

Section snippets

Patients and Data Collection

Clinical Characteristics of the Study Population

Discussion

Acknowledgments

Hepatology

Gastroenterology

Lancet

Hepatology

Chest

Thromb Res

Chest

J Thromb Haemost

Thromb Res

Hepatology

Hepatology

J Hepatol

J Thromb Haemost

J Hepatol

Blood

Original article
Pancreas, biliary tract, and liver
Thrombocytopenia Is Associated With Multi-organ System Failure in Patients With Acute Liver Failure