Antiviral therapy decreases GpIIb/IIIa activation of platelets in patients with chronic hepatitis C

Summary Interferon alpha (IFN-α) is used to treat haematological and solid malignancies and is the gold standard therapy for chronic hepatitisC infection in combination with ribavirin. It has a well known platelet lowering effect and was recently shown to impair platelet aggregation in the presence of various agonists and has been accused to increase patients’ bleeding risk during IFN-α therapy. Thus, we hypothesised that antiviral treatment decreases GpIIb/IIIa activation and affects global platelet function. In a prospective clinical trial, we examined the effects of combination therapy with pegylated IFN-α 2a (PegIFN-α 2a) and ribavirin on platelet GpIIb/IIIa activation and platelet secretion in 20 patients with chronic hepatitis C at week 2, 4, 8 and 12 after the beginning of therapy. In addition, we determined global platelet function (CEPI-CT) with the PFA-100 and vWF-Ag levels. Antiviral therapy significantly decreased GpIIb/IIIa activation in a time dependent manner, whereas markers of platelet secretion (P-selectin, β-thromboglobulin) remained unchanged. Despite a marked elevation of vWF-Ag levels, CEPI-CT did not change compared to baseline levels. Antiviral therapy significantly decreases GpIIb/IIIa activation in patients with chronic hepatitis C, while vWG-Antigen levels are markedly increased and α-granule secretion is not affected. This does not result in an alteration of global platelet function as assessed by the PFA-100, because elevated vWF-Antigen levels might compensate for the acquired defect.

[1]  Y. Nakatomi,et al.  Von Willebrand factor accelerates platelet adhesion and thrombus formation on a collagen surface in platelet-reduced blood under flow conditions. , 2005, Blood.

[2]  M. Samama,et al.  In vitro aspirin resistance detected by PFA‐100TM closure time: pivotal role of plasma von Willebrand factor , 2004, British journal of haematology.

[3]  B. Jilma,et al.  Desmopressin antagonizes the in vitro platelet dysfunction induced by GPIIb/IIIa inhibitors and aspirin. , 2003, Blood.

[4]  S. Panzer,et al.  Is there an Increased Frequency of Autoimmune Thrombocytopenia in Hepatitis C Infection? A Review , 2003, Wiener Medizinische Wochenschrift.

[5]  B. Jilma,et al.  Activation of calcium-dependent calmodulin by calcium(II)3(3,5-diisopropylsalicylate)6(H2O)6 decreases thrombin receptor activating peptide-induced P-selectin expression , 2003, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[6]  M. Fried,et al.  Side effects of therapy of hepatitis C and their management , 2002, Hepatology.

[7]  J. McHutchison,et al.  Immune thrombocytopenic purpura in patients with chronic hepatitis C virus infection , 2002, American Journal of Gastroenterology.

[8]  H. Gutman,et al.  Impaired platelet aggregation in melanoma patients treated with interferon‐α‐2b adjuvant therapy , 2002 .

[9]  Kenneth Koury,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[10]  B. Jilma.  Platelet function analyzer (PFA-100): a tool to quantify congenital or acquired platelet dysfunction. , 2001, The Journal of laboratory and clinical medicine.

[11]  V. Kretschmer,et al.  Influence of ABO blood groups on primary hemostasis , 2001, Transfusion.

[12]  Pille Harrison,et al.  Progress in the assessment of platelet function. , 2000, British journal of haematology.

[13]  H. Eichler,et al.  Systemic inflammation increases shear stress-induced platelet plug formation measured by the PFA-100 , 2000 .

[14]  H. Eichler,et al.  Effects of erythropoietin on platelet reactivity and thrombopoiesis in humans. , 2000, Blood.

[15]  M. Furman,et al.  Laboratory markers of platelet activation and their clinical significance. , 1999, Current opinion in hematology.

[16]  S. Shattil.  Signaling Through Platelet Integrin αIIbβ3: Inside-out, Outside-in, and Sideways , 1999, Thrombosis and Haemostasis.

[17]  H. Eichler,et al.  Effects of nitric oxide on platelet activation during plateletpheresis and in vivo tracking of biotinylated platelets in humans , 1999, Transfusion.

[18]  C. Datz,et al.  Blunted thrombopoietin response to interferon alfa–induced thrombocytopenia during treatment for hepatitis C , 1998, Hepatology.

[19]  C. Verfaillie,et al.  Interferon-α restores β1-integrin-dependent, collagen-mediated platelet aggregation in a patient with chronic myelogenous leukemia , 1998 .

[20]  G. Everson,et al.  Possible idiopathic thrombocytopenic purpura associated with natural alpha interferon therapy for chronic hepatitis C infection. , 1995, The American journal of gastroenterology.

[21]  K. Ishak,et al.  Histological grading and staging of chronic hepatitis. , 1995 .

[22]  D. Rampton,et al.  Circulating von Willebrand factor in inflammatory bowel disease. , 1992, Gut.

[23]  S. Tura,et al.  Platelet function and interferon alpha‐2a treatment in essential thrombocythaemia , 1991, European journal of haematology.

[24]  A. Michelson,et al.  Downregulation of the platelet surface glycoprotein Ib-IX complex in whole blood stimulated by thrombin, adenosine diphosphate, or an in vivo wound. , 1991, Blood.

[25]  M. Dewanjee,et al.  Viability and functional integrity of washed platelets , 1989, Transfusion.

[26]  J. Hoxie,et al.  Changes in the platelet membrane glycoprotein IIb.IIIa complex during platelet activation. , 1985, The Journal of biological chemistry.

[27]  A. Federici,et al.  Increased von Willebrand factor antigen in the plasma of patients with vasculitis. , 1984, Arthritis and rheumatism.

[28]  M. G. Lötter,et al.  Kinetics, Distribution and Sites of Destruction of 111Indium‐labelled Human Platelets , 1980, British journal of haematology.

[29]  R. Seymour,et al.  A comparative study of the effects of aspirin and paracetamol (acetaminophen) on platelet aggregation and bleeding time , 2004, European Journal of Clinical Pharmacology.

[30]  C. Perry,et al.  Peginterferon-alpha-2a (40 kD): a review of its use in the management of chronic hepatitis C. , 2001, Drugs.

[31]  P. Nurden,et al.  Ultrastructural analysis of the distribution of von Willebrand factor and fibrinogen in platelet aggregates formed in the PFA-100. , 1998, Platelets.