Thrombocytopenia and Procedural Prophylaxis in the Era of Thrombopoietin Receptor Agonists

Caldwell, Stephen H.; Flamm, Steven L.

doi:10.1002/hep4.1423

Cited by 19 publications

(25 citation statements)

References 53 publications

(109 reference statements)

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“…This lack of association with platelet count also has particular clinical relevance because providers are often reluctant to perform procedures in patients with thrombocytopenia, and several new thrombopoietin agonists have been developed for this purpose. Notably, despite the improvement in platelet counts seen with these agents, more robust outcomes data are needed to establish their efficacy in reducing bleeding ( 30 ). These findings suggest that provider perceptions of bleeding risk due to thrombocytopenia may be disproportionate to the actual risk.…”

Section: Discussionmentioning

confidence: 99%

Bleeding After Elective Interventional Endoscopic Procedures in a Large Cohort of Patients With Cirrhosis

Kundumadam

Phatharacharukul

Reinhart

et al. 2020

Clin Transl Gastroenterol

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INTRODUCTION: Elective therapeutic endoscopy is an important component of care of cirrhotic patients, but there are concerns regarding the risk of bleeding. This study examined the incidence, risk factors, and outcomes of bleeding after endoscopic variceal ligation (EVL), colonoscopic polypectomy, and endoscopic retrograde cholangiopancreatography with sphincterotomy in cirrhotic patients. METHODS: A cohort study of patients with cirrhosis who underwent the above procedures at a single center between 2012 and 2014 was performed. Patients with active bleeding at the time of procedure were excluded. Patients were followed for 30 days to assess for postprocedural bleeding and for 90 days for mortality. RESULTS: A total of 1,324 procedures were performed in 857 patients (886 upper endoscopies, 358 colonoscopies, and 80 endoscopic retrograde cholangiopancreatograpies). After EVL, bleeding occurred in 2.8%; after polypectomy, bleeding occurred in 2.0%; and after sphincterotomy, bleeding occurred in 3.8%. Independent predictors of bleeding after EVL and polypectomy included younger age and lower hemoglobin. For EVL, bleeding was also associated with infection and model for end-stage liver disease-Na. International normalized ratio was associated with bleeding in univariate analysis only, and platelet count was not associated with bleeding in any procedure. Bleeding after EVL was associated with 29% 90-day mortality, and bleeding after polypectomy was associated with 14% mortality. Of the 3 patients with postsphincterotomy bleeding, none were outliers regarding their baseline characteristics. DISCUSSION: In patients with cirrhosis, bleeding occurs infrequently after elective therapeutic endoscopy and is associated with younger age, lower hemoglobin, and high mortality. Consideration of these risk factors may guide appropriate timing and preprocedural management to optimize outcomes.

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Section: Discussionmentioning

confidence: 99%

Bleeding After Elective Interventional Endoscopic Procedures in a Large Cohort of Patients With Cirrhosis

Kundumadam

Phatharacharukul

Reinhart

et al. 2020

Clin Transl Gastroenterol

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“…At present, four TPO-agonists (eltrombopag, romiplostim, avatrombopag and lusutrombopag) have been approved for HCV-related TCP. 34 , 36 – 39 Eltrombopag, as mentioned above, is an orally active TPO-agonist that increases differentiation of bone marrow progenitor cells leading to production of megakaryocytes. 34 , 36 , 40 Romiplostim is a polypeptide composed of four TPO mimetic peptides that dimerize TPO, leading to increase Plt production.…”

Section: Treatmentmentioning

confidence: 99%

“… 36 , 37 The two newest medications, avatrombopag and lusutrombopag, are both non-peptide oral TPO agonists. 39 By July 2019, the USA’s Federal Drug Administration and European Medicines Agency had approved all medications, except romiplostim, for treatment of TCP in chronic HCV patients. 41 – 46 Eltrombopag and romiplostim were additionally approved for ITP.…”

Section: Treatmentmentioning

confidence: 99%

“… 37 There appears to be great potential in the use of TPO-agonists for increasing Plt counts for invasive procedures, and this led to two large randomized control studies that tested the use of avatrombopag and lusutrombopag prior to elective procedures. 39 Avatrombopag and lusutrombopag have been studied for the primary purpose of reducing pre-procedural Plt transfusions. Up to 88% and 65% of patients in each trial reached this goal, respectively.…”

Section: Treatmentmentioning

confidence: 99%

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Pathogenesis of Thrombocytopenia in Chronic HCV Infection: A Review

Rawi¹,

Wu²

2020

Journal of Clinical and Translational Hepatology

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A large proportion of patients with chronic hepatitis C have associated thrombocytopenia (TCP). Due to bleeding risks, TCP, when severe, can limit diagnostic and therapeutic procedures, treatments, and increases risk of complications, especially excessive bleeding. It is important to understand the mechanisms that cause TCP in order to manage it. In general, TCP can be due to increased destruction or decreased production. Proposed mechanisms of increased destruction include autoantibodies to platelets and hypersplenism with sequestration. Proposed mechanisms of decreased production include virus-induced bone marrow suppression and decreased TPO production. Autoantibodies directed against platelet surface antigens have demonstrated an inverse correlation with platelet counts. Hypersplenism with sequestration involves the interaction of portal hypertension, splenomegaly, and platelet destruction. Decreased production mechanisms involve appropriate and inappropriate levels of TPO secretion. There is limited evidence to support viral-induced bone marrow suppression. In contrast, there is strong evidence to support low levels of TPO in liver failure as a major cause of TCP. TPO-agonists, specifically eltrombopag, have been shown in hepatitis C patients to increase platelet counts without reducing portal hypertension or splenomegaly. We conclude that TCP in hepatitis C virusinduced liver disease is often multifactorial, but an understanding of the mechanisms can lead to judicious use of new drugs for treatment.

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“…[28][29][30] In general, CLD patients with platelet counts < − 50 × 10 9 /L are considered to be at high risk for procedurerelated bleeding. 31 In this analysis, more patients in the lusutrombopag group achieved a platelet count > − 50 × 10 9 /L at least once during the study and at the platelet transfusion assessment. The majority of patients in the lusutrombopag group experienced a > − 1.5-fold increase and approximately 50% had at least a doubling in their platelet count from baseline, including those patients with baseline platelet counts <20 × 10 9 /L.…”

Section: Discussionmentioning

confidence: 79%

Assessing the periprocedural magnitude of platelet count change in response to lusutrombopag

Brown

Imawari²,

Izumi

et al. 2021

JHEP Reports

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Thrombocytopaenia is common in patients with chronic liver disease. Lusutrombopag increased platelet count > − 1.5-fold in most patients with chronic liver diseaseinduced thrombocytopaenia. Lusutrombopag doubled platelet count in half of patients treated. Lusutrombopag-induced platelet count increases (without platelet transfusion) lasted for 3 weeks. Lay summary Patients with low platelet counts caused by chronic liver disease may not receive planned invasive procedures or surgeries because of an increased risk of bleeding. Lusutrombopag has previously demonstrated efficacy in raising platelet counts and is approved to treat chronic liver disease patients with low platelet counts in advance of a planned surgery. Physicians need to understand more clearly what to expect in terms of platelet count change when using lusutrombopag; this integrated analysis provides data to help guide its clinical application.

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Thrombocytopenia and Procedural Prophylaxis in the Era of Thrombopoietin Receptor Agonists

Cited by 19 publications

References 53 publications

Bleeding After Elective Interventional Endoscopic Procedures in a Large Cohort of Patients With Cirrhosis

Bleeding After Elective Interventional Endoscopic Procedures in a Large Cohort of Patients With Cirrhosis

Pathogenesis of Thrombocytopenia in Chronic HCV Infection: A Review

Assessing the periprocedural magnitude of platelet count change in response to lusutrombopag

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