Management of Thrombocytopenia in Advanced Liver Disease

Thrombocytopenia (defined as a platelet count <150×109/L) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×109/L to 75×109/L) occurs in approximately 13% of patients with cirrhosis. Thrombocytopenia can negatively impact the care of patients with severe liver disease by potentially interfering with diagnostic and therapeutic procedures. Multiple factors can contribute to the development of thrombocytopenia including splenic platelet sequestration, immunological processes, bone marrow suppression by chronic viral infection, and reduced levels or activity of the hematopoietic growth factor thrombopoietin. The present review focuses on the etiologies and management options for severe thrombocytopenia in the setting of advanced liver disease.

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Argatroban Dose Reductions for Suspected Heparin-Induced Thrombocytopenia Complicated by Child-Pugh Class C Liver Disease

Annals of Pharmacotherapy ◽

10.1345/aph.1r226 ◽

2012 ◽

Vol 46 (11) ◽

pp. e30-e30 ◽

Cited By ~ 6

Author(s):

Peter M Yarbrough ◽

Amir Varedi ◽

Amanda Walker ◽

Matthew T Rondina

Keyword(s):

Liver Disease ◽

Bleeding Complications ◽

Severe Liver ◽

Advanced Liver Disease ◽

Heparin Induced Thrombocytopenia ◽

Starting Dose ◽

Severe Liver Disease ◽

Pugh Class ◽

Class C ◽

Dose Reductions

OBJECTIVE: To report our experience of reduced-dose argatroban in a patient with suspected heparin-induced thrombocytopenia (HIT) and Child-Pugh class C liver disease and review the relevant literature to summarize current recommendations on argatroban use in patients with severe liver disease. CASE SUMMARY: A 58-year-old male with Child-Pugh class C liver disease (Model for End-Stage Liver Disease [MELD] score = 31, total bilirubin 4.5 mg/dL) and hemodialysis-dependent renal failure was hospitalized with acute deep vein thrombosis (DVT). Three days after heparin initiation for DVT, he developed thrombocytopenia. Given his heparin exposure (both for treatment of DVT and ongoing hemodialysis), HIT was suspected and all heparinoids were immediately discontinued. Argatroban was initiated for the treatment of HIT while laboratory testing for HIT antibodies and the serotonin release assay were completed. Because of the patient's advanced liver disease, the starting dose of argatroban was reduced to 0.2 μg/kg/min, with frequent monitoring of the activated partial thromboplastin time (aPTT) (goal 60–85 seconds). Despite this dose reduction, the aPTT was supratherapeutic. Following further dose reductions, a final argatroban maintenance dose of 0.05 μg/kg/min was necessary for the attainment of goal aPTTs. DISCUSSION: Reducing the starting dose of argatroban to 0.5 μg/kg/min is recommended in patients with liver disease. Nevertheless, this recommended dose is largely based on data from patients with more moderate liver disease (eg, Child-Pugh class A or B), and dosing in more advanced liver disease remains largely unexplored. Patients with more advanced liver disease may require additional dose reductions to avoid supratherapeutic concentrations of anticoagulation agents and to minimize bleeding risk. CONCLUSIONS: This report illustrates the importance of careful selection of argatroban dosing and appropriate aPTT monitoring in patients with severe liver disease. Excessive anticoagulation may precipitate major bleeding complications, placing patients with this complicated disease at undue risk.

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Safety and efficacy of rituximab in patients with hepatitis C virus–related mixed cryoglobulinemia and severe liver disease

Blood ◽

10.1182/blood-2009-11-253948 ◽

2010 ◽

Vol 116 (3) ◽

pp. 335-342 ◽

Cited By ~ 90

Author(s):

Antonio Petrarca ◽

Luigi Rigacci ◽

Patrizio Caini ◽

Stefano Colagrande ◽

Paolo Romagnoli ◽

...

Keyword(s):

Hepatitis C Virus ◽

Liver Disease ◽

Hepatitis C ◽

Mixed Cryoglobulinemia ◽

Leg Ulcers ◽

Severe Liver ◽

Advanced Liver Disease ◽

End Of Treatment ◽

Severe Liver Disease

Abstract The effectiveness of rituximab in hepatitis C virus (HCV)–related mixed cryoglobulinemia (MC) has been shown. However, the risk of an increase in viral replication limits its use in cirrhosis, a condition frequently observed in patients with MC. In this prospective study, 19 HCV-positive patients with MC and advanced liver disease, who were excluded from antiviral therapy, were treated with rituximab and followed for 6 months. MC symptoms included purpura, arthralgias, weakness, sensory-motor polyneuropathy, nephropathy, and leg ulcers. Liver cirrhosis was observed in 15 of 19 patients, with ascitic decompensation in 6 cases. A consistent improvement in MC syndrome was evident at the end-of-treatment (EOT) and end-of-follow-up (EOF-U). Variable modifications in both mean viral titers and alanine aminotransferase values were observed at admission, EOT, third month of follow-up, and EOF-U (2.62 × 106, 4.28 × 106, 4.82 × 106, and 2.02 × 106 IU/mL and 63.6, 49.1, 56.6, and 51.4 IU/L, respectively). Improvement in liver protidosynthetic activity and ascites degree was observed at EOT and EOF-U, especially in more advanced cases. This study shows the effectiveness and safety of rituximab in MC syndrome with advanced liver disease. Moreover, the depletion of CD20+ B cells was also followed by cirrhosis syndrome improvement despite the possibility of transient increases of viremia titers.

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Thrombotic thrombocytopenic purpura associated with Klebsiella pneumonia in the background of alcoholic liver cirrhosis

Case Reports in Internal Medicine ◽

10.5430/crim.v3n3p30 ◽

2016 ◽

Vol 3 (3) ◽

pp. 30

Author(s):

Satoshi Ichikawa ◽

Keiju Sasaki ◽

Taro Takahashi ◽

Masaki Hayakawa ◽

Masanori Matsumoto ◽

...

Keyword(s):

Liver Cirrhosis ◽

Liver Disease ◽

Klebsiella Pneumonia ◽

Severe Thrombocytopenia ◽

Alcoholic Liver Cirrhosis ◽

Adamts13 Activity ◽

Severe Liver ◽

Laboratory Findings ◽

Thrombocytopenic Purpura ◽

Severe Liver Disease

A 75-year-old male patient with alcoholic liver cirrhosis was emergently admitted due to systemic convulsion and Klebsiella pneumonia. He was referred to us due to severe thrombocytopenia (7,000/μl), and we suspected thrombotic thrombocytopenicpurpura (TTP) considering the coexistence of hemolytic findings and neurological symptoms. We promptly performed plasma exchange and administration of corticosteroids, resulting in full recovery of symptoms and laboratory findings in a week. Thediagnosis of TTP was confirmed by severely decreased ADAMTS13 activity (less than 0.5%) and detection of ADAMTS13 inhibitor. In this case, we speculated that TTP was triggered by Klebsiella pneumonia in the background of advanced alcoholicliver cirrhosis. This is the first report describing the complication of Klebsiella pneumonia and TTP. It is important to be awarethat patients complicated with severe liver disease could be vulnerable to TTP.

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Severe liver disease is caused by HBV rather than HCV in children with hematological malignancies

The Hematology Journal ◽

10.1038/sj.thj.6200300 ◽

2003 ◽

Vol 4 (5) ◽

pp. 321-327 ◽

Cited By ~ 16

Author(s):

Manal H El-Sayed ◽

Magdy M Mohamed ◽

Amr Karim ◽

Anna-Maria Maina ◽

Filippo Oliveri ◽

...

Keyword(s):

Liver Disease ◽

Hematological Malignancies ◽

Severe Liver ◽

Severe Liver Disease

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HÆMORRHAGE IN SEVERE LIVER DISEASE

The Medical Journal of Australia ◽

10.5694/j.1326-5377.1944.tb31157.x ◽

1944 ◽

Vol 2 (4) ◽

pp. 93-93

Keyword(s):

Liver Disease ◽

Severe Liver ◽

Severe Liver Disease

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Hepatitis E and Pregnancy: An Unholy Alliance Unmasked from Kashmir, India

Viruses ◽

10.3390/v13071329 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1329

Author(s):

Mohammad Sultan Khuroo

Keyword(s):

Viral Replication ◽

Pregnant Women ◽

Hepatitis E Virus ◽

Hepatitis E ◽

Polymerase Activity ◽

Severe Liver ◽

Reading Frame ◽

Multiple Factors ◽

Severe Liver Disease ◽

Development And Management

The adverse relationship between viral hepatitis and pregnancy in developing countries had been interpreted as a reflection of retrospectively biased hospital-based data collection by the West. However, the discovery of hepatitis E virus (HEV) as the etiological agent of an epidemic of non-A, non-B hepatitis in Kashmir, and the documenting of the increased incidence and severity of hepatitis E in pregnancy via a house-to-house survey, unmasked this unholy alliance. In the Hepeviridae family, HEV-genotype (gt)1 from genus Orthohepevirus A has a unique open reading frame (ORF)4-encoded protein which enhances viral polymerase activity and viral replication. The epidemics caused by HEV-gt1, but not any other Orthohepevirus A genotype, show an adverse relationship with pregnancy in humans. The pathogenesis of the association is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the pregnant women including infection and damage to the maternal-fetal interface by HEV-gt1; vertical transmission of HEV to fetus causing severe fetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the pregnant women, promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of acute liver failure. (ALF). Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

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Extra Lactate Dehydrogenase Isoenzyme Band in Serum of Patients with Severe Liver Disease

Clinical Chemistry ◽

10.1093/clinchem/17.9.882 ◽

1971 ◽

Vol 17 (9) ◽

pp. 882-885 ◽

Cited By ~ 6

Author(s):

T Lubrano ◽

A A Dietz ◽

H M Rubinstein

Keyword(s):

Liver Disease ◽

Lactate Dehydrogenase ◽

Serum Bilirubin ◽

High Serum ◽

Severe Liver ◽

Additional Band ◽

Dehydrogenase Isoenzyme ◽

Severe Liver Disease ◽

Isoenzyme Patterns ◽

High Serum Bilirubin

Abstract In a study of lactate dehydrogenase isoenzyme patterns in the sera of patients with severe liver disease, who were primarily selected because of an abnormally high serum bilirubin, 42 of 76 patients had an additional band (LDH-T) between isoenzymes 4 and 5 on acrylamide gel. Thirty of the 42 patients died during followup, 24 within a month of recognition of the extra band.

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