What is the diagnosis and recommended therapy for a 66‑year‑old woman with mild thrombocytopenia (platelet count ≈124 × 10⁹/L) and a positive hepatitis C virus antibody?

Diagnosis and Treatment of HCV-Associated Thrombocytopenia

This 66-year-old woman has chronic hepatitis C virus infection with mild thrombocytopenia (platelet count 124,000/µL), and the primary treatment should be antiviral therapy directed at the HCV infection itself, as successful viral eradication addresses both the underlying disease and the associated thrombocytopenia.

Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis with the following steps:

• Verify active HCV infection by testing for HCV RNA using RT-PCR, as a positive HCV antibody alone indicates only past or current infection but does not distinguish between the two 1
• Test for hepatitis B coinfection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc), as HBV reactivation during HCV treatment can cause fulminant hepatitis and death 2
• Assess liver disease severity through clinical evaluation, imaging, and laboratory tests to determine presence and degree of cirrhosis, as this affects treatment duration 2
• Exclude other causes of thrombocytopenia including immune thrombocytopenia (ITP), though HCV itself is a recognized cause of secondary ITP through immune-mediated mechanisms 1, 3

Understanding HCV-Associated Thrombocytopenia

The thrombocytopenia in this patient likely results from multiple mechanisms:

• Immune-mediated platelet destruction via antiplatelet antibodies targeting glycoproteins IIb/IIIa, IIIa, IIb, Ib, and Ia, which occurs in up to 86.7% of thrombocytopenic HCV patients 4
• Direct viral effects on bone marrow and thrombopoiesis 5, 6
• Hypersplenism if cirrhosis with portal hypertension is present 6

Primary Treatment: Antiviral Therapy

The cornerstone of management is treating the HCV infection itself, as this addresses the root cause of the thrombocytopenia 1:

For Patients Without Cirrhosis or With Compensated Cirrhosis (Child-Pugh A):

• Sofosbuvir/velpatasvir 400 mg/100 mg once daily for 12 weeks is the recommended regimen for all HCV genotypes (1-6) 2
• This regimen can be taken with or without food 2
• No ribavirin is needed for compensated disease 2

For Patients With Decompensated Cirrhosis (Child-Pugh B or C):

• Sofosbuvir/velpatasvir plus weight-based ribavirin for 12 weeks 2
• Ribavirin dosing: 1,000 mg/day if <75 kg or 1,200 mg/day if ≥75 kg, divided twice daily with food 2

Critical Safety Consideration:

• Monitor platelet counts closely during interferon-based therapy (if used in older regimens), as interferon can worsen thrombocytopenia through reduced thrombopoietin production 1, 7
• Modern direct-acting antiviral regimens like sofosbuvir/velpatasvir do not carry the same thrombocytopenia risk as interferon-based therapy 2

Management of Thrombocytopenia During Treatment

At a platelet count of 124,000/µL, this patient does not require specific treatment for thrombocytopenia before or during antiviral therapy:

• Platelet counts >100,000/µL are generally safe for initiating antiviral therapy without increased bleeding risk 1
• Even platelet counts of 50,000-100,000/µL rarely cause treatment discontinuation due to thrombocytopenia, and major bleeding episodes do not increase 1
• Severe bleeding is extremely rare even with platelet counts <50,000/µL during peginterferon/ribavirin therapy 8

If Thrombocytopenia Worsens or Bleeding Occurs:

• Do NOT routinely use thrombopoietin receptor agonists for HCV-associated thrombocytopenia, as there is no evidence they improve sustained virological response (SVR), and they carry risk of portal vein thrombosis 1
• If ITP treatment becomes necessary (platelet count <30,000/µL with bleeding risk), use intravenous immunoglobulin (IVIg) 1 g/kg as a one-time dose as first-line therapy 1
• Avoid corticosteroids as first-line in HCV-associated ITP; IVIg is preferred 1

Common Pitfalls to Avoid

• Do not delay antiviral therapy due to mild thrombocytopenia (>100,000/µL), as treating HCV is the definitive solution 1
• Do not confuse HCV antibody positivity with active infection—always confirm with HCV RNA testing 1
• Do not overlook HBV screening—failure to test can result in fatal HBV reactivation during HCV treatment 2
• Do not use thrombopoietin agonists prophylactically—they are not indicated for HCV-associated thrombocytopenia and carry thrombotic risks 1
• Do not assume thrombocytopenia contraindicates treatment—even patients with baseline platelets <50,000/µL can often be safely treated 1, 8

Monitoring During Treatment

• Recheck platelet count at weeks 2,4,8, and 12 during antiviral therapy
• Monitor for signs of bleeding (petechiae, bruising, mucosal bleeding), though risk is low at this platelet level 8
• Assess HCV RNA at week 4 and end of treatment to confirm virological response 2
• Expect platelet count improvement after achieving SVR, as successful viral eradication often resolves immune-mediated thrombocytopenia 4, 6