Liver Cirrhosis, Portal Vein Thrombosis
Conditions
Keywords
Liver cirrhosis, Portal vein thrombosis, Warfarin
Brief summary
This was a prospective, open-label, pilot interventional clinical study conducted on Egyptian patients with liver cirrhosis complicated by portal vein thrombosis (PVT) who were indicated for anticoagulation therapy. The study aimed to evaluate the clinical applicability of Simcyp®-guided warfarin initiation doses according to Child-Pugh class, focusing on the time required to achieve a therapeutic INR and the safety of anticoagulation during the initiation phase.
Detailed description
This was a prospective, open-label, pilot interventional clinical study conducted on adult cirrhotic patients with radiologically confirmed portal vein thrombosis. A total of twenty-one patients were enrolled from the outpatient clinics of the Hepatology, Gastroenterology, and Infectious Diseases Department at Kafrelsheikh University Hospital between March 2024 and March 2025. Before initiation of anticoagulation therapy, all participants underwent comprehensive baseline clinical and laboratory assessments, including detailed medical history with emphasis on bleeding and thrombotic risk, physical examination, complete blood count, liver and renal function tests, and baseline coagulation profile. Eligible patients were classified according to Child-Pugh score into class A or B. Patients with Child-Pugh class A (n = 10) received warfarin 3 mg once daily, while patients with Child-Pugh class B (n = 11) received warfarin 2 mg once daily. Initial dosing was guided by Simcyp® model predictions and the closest commercially available strengths. Enoxaparin was administered as bridging therapy at a therapeutic dose of 1 mg/kg twice daily until achievement of the target INR. During the warfarin initiation phase, daily INR monitoring was performed, and dose adjustments were carried out using standardized clinical titration principles until a stable therapeutic INR (2.0-3.0) was achieved on two consecutive measurements. Patients were closely monitored throughout the follow-up period for treatment-related adverse events, with particular emphasis on bleeding complications. Bleeding events were systematically assessed and classified as minor or major, in addition to monitoring for any thromboembolic events.
Interventions
DRUGWarfarin 3 mg
Warfarin is a vitamin K antagonist approved for the treatment of thromboembolic disorders and was used in this study for anticoagulation in cirrhotic patients with portal vein thrombosis.
DRUGWarfarin 2 mg
Warfarin is a vitamin K antagonist approved for the treatment of thromboembolic disorders and was used in this study for anticoagulation in cirrhotic patients with portal vein thrombosis.
Sponsors
Kafrelsheikh University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Diagnosed liver cirrhosis (Child-Pugh A or B) * Radiologically confirmed portal venous thrombosis * No prior exposure to warfarin (for initial dose simulation) * No pervious history of variceal bleeding
Exclusion criteria
* Child-Pugh C cirrhosis * Platelets \< 50,000/mm³ * Severe renal impairment (eGFR \< 30 mL/min) * Use of strong CYP2C9/CYP3A4 inhibitors or inducers * Pregnancy or breastfeeding * Active malignancy, especially hepatocellular carcinoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Achieve Therapeutic INR | From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days) | The number of days from initiation of warfarin therapy until an INR value within the therapeutic range (≥ 2.0) was documented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Warfarin Dose During Initiation Phase | From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days) | The mean daily warfarin dose required to achieve therapeutic anticoagulation during the initiation phase. |
| Proportion of Patients Achieving Therapeutic INR Within 3-5 Days | Within 3-5 days after warfarin initiation | The percentage of patients who achieved therapeutic INR (≥ 2.0) within 3 to 5 days after initiation of warfarin therapy. |
| Follow-up Duration During Warfarin Initiation Phase | From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days) | The duration of patient follow-up during the warfarin initiation phase, measured in days. |
| Incidence of Over-Anticoagulation | From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days) | The occurrence of excessive anticoagulation, defined as an international normalized ratio (INR) value greater than 4 during the initiation phase. |
| Incidence of Bleeding Events | From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days) | The occurrence of bleeding complications during the study follow-up period, classified as minor or major according to standard clinical criteria. |
| Incidence of Thromboembolic Events | From initiation of warfarin therapy until achievement of therapeutic INR (up to 14 days) | The occurrence of any new thromboembolic events during the follow-up period after initiation of warfarin therapy. |
Countries
Egypt
Contacts
PRINCIPAL_INVESTIGATORNaira Galal, BSc Pharm
Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
STUDY_DIRECTORNoha Mahmoud El-khodary, PhD
Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University
Outcome results
None listed