Pathogenesis of Thrombocytopenia in Chronic HCV Infection: A Review

Abstract

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.

Screening varices in patients with HBV‐related cirrhosis on antiviral therapy: Platelet alone or together with LSM

“…Another mechanism might be the increased level of thrombopoietin after effective anti‐HBV treatment, which was thought to be related with improving synthetic liver function. Although an amelioration of virus‐induced immunological mechanisms might be one of the reasons in HCV patients, and there had limited evidence in HBV patients 23 …”

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

“…6,27 As discussed earlier, multiple factors, including potentially reduced thrombin production when platelet counts are <50 × 10 9 /L, 4 contribute to the possibility of increased bleeding risk in CLD patients. [1][2][3] Studies have identified that the risk of procedure-related bleeding is increased when platelet counts fall below approximately 60 to 75 × 10 9 /L, with the highest risk of bleeding occurring when the platelet count is <10 to 20 × 10 9 /L. [28][29][30] In general, CLD patients with platelet counts < − 50 × 10 9 /L are considered to be at high risk for procedurerelated bleeding.…”

“…Patients with thrombocytopaenia associated with chronic liver disease (TCP-CLD) are at risk for both thrombotic and haemorrhagic complications given the complex, altered balance between thrombosis and bleeding in this patient population. [1][2][3] TCP is a reflection of the severity of CLD and contributes to the potential increased risk of bleeding in CLD patients in conjunction with the interplay between multiple elements in the haemostatic system such as platelet dysfunction, anti-platelet antibodies, platelet sequestration and destruction related to hypersplenism, myelosuppression, and alterations in haematopoietic and coagulation factors. [1][2][3] For example, the risk of bleeding in CLD may be affected by decreased thrombin production when platelet counts fall below approximately 50 × 10 9 /L, 4 yet this is countered by an increase in von Willebrand factor.…”

“…[1][2][3] TCP is a reflection of the severity of CLD and contributes to the potential increased risk of bleeding in CLD patients in conjunction with the interplay between multiple elements in the haemostatic system such as platelet dysfunction, anti-platelet antibodies, platelet sequestration and destruction related to hypersplenism, myelosuppression, and alterations in haematopoietic and coagulation factors. [1][2][3] For example, the risk of bleeding in CLD may be affected by decreased thrombin production when platelet counts fall below approximately 50 × 10 9 /L, 4 yet this is countered by an increase in von Willebrand factor. 1,2 Notwithstanding, TCP influences clinical decisions in CLD patients, in particular when weighing the risks vs. benefits of certain diagnostic or therapeutic interventions.…”

“…1,2 Notwithstanding, TCP influences clinical decisions in CLD patients, in particular when weighing the risks vs. benefits of certain diagnostic or therapeutic interventions. [1][2][3] Most clinicians and society guidelines recommend that a patient has a platelet count > − 50 × 10 9 /L before an invasive procedure. [5][6][7][8][9][10][11] Platelet transfusion has been the standard of care to reduce the risk of bleeding in patients with TCP-CLD undergoing invasive procedures.…”