Targeted Research (March-June 2023)


1.Giving Vit K Does Not Seem To Reduce Bleeding Risk In Patients With Chronic Liver Disease And Elevated INR

ABSTRACT: Limited studies assess the efficacy of vitamin K administration in patients with chronic liver disease (CLD). However, vitamin K is commonly used to treat elevations in international normalized ratio (INR) in these patients with the intended benefit of reducing bleeding risk. This retrospective, single-center cohort study aimed to evaluate the impact of vitamin K administration on INR in patients with CLD. Hospitalized patients ≥ 18 years of age with a diagnosis of CLD or cirrhosis and received vitamin K were included. The primary outcome was the absolute change in INR from baseline to 24 to 48 h after vitamin K administration. Secondary endpoints included subgroup analyses of the primary outcome by route of administration and single versus multi dose administration, and incidence of in-hospital venous thromboembolism (VTE) or major bleeding.

A total of eighty-five patients, primarily with Child–Pugh class C (76.5%), were included. Route of vitamin K administration included oral (PO) (72%) and intravenous (IV) (26%) with a mean daily dose of 8.5 ± 2.3 mg. The absolute change in INR was −0.07 ± −0.35 following vitamin K administration. There was no difference in absolute INR change between single versus multiple dose administration (−0.16 ± −0.35 and −0.03 ± −0.35; P= .13) or between PO versus IV administration (−0.06 ± −0.23 and −0.18 ± −0.48; P = .11). The incidences of in-hospital VTE and major bleeding were 2.4% and 3.5%, respectively. The administration of vitamin K in hospitalized patients with CLD resulted in minimal INR change, suggesting this intervention may not have the intended benefit of reducing bleeding risk.

Smith CB, et al. Impact of Vitamin K Administration on Elevated International Normalized Ratio in Chronic Liver Disease.  Clin Appl Thromb Hemost. 2023 Jan-Dec; 29: 10760296231164642.  Published online 2023 Apr 24. doi: 10.1177/10760296231164642

2. Venous Thromboembolism Risk Assessment And Management Should Probably Be Done Within The First Six Months Of Solid Cancer Diagnosis

ABSTRACT: The aim of this single-center 10-year retrospective observational study was to evaluate the profile of Chinese cancerous patients with venous thromboembolism (VTE) based on demographic features, clinical characteristics, and medication exposure. Consecutive 1482 patients with solid tumors complicated with VTE at a tertiary center between 2012 and 2021 were retrospectively enrolled. Data were collected on demographics, comorbidities, discharge diagnoses, laboratory examination data, treatment details, and imaging description of the lesion.

The overall incidence of clinical VTE was 1.35% in hospitalized patients with cancer in our center. Lung cancer was the most frequent tumor subtype for developing VTE events, accounting for 24.83% of all cases. Over half of the patients (66.60%) were observed to have an increased risk of VTE within the first 6 months of cancer diagnosis. Close to half of the patients (46.49%) had received chemotherapy within 6 months prior to the diagnosis of VTE. The frequency of massive ascites group (>2000 mL) in gynecological patients with VTE was significantly larger than that of non massive ascites group (≤2000 mL) (P < .001).

Patients with ovarian, vulvar, lung cancers were considered at high risk for VTE. The assessment and monitoring of VTE in patients with cancer within the first 6 months of cancer diagnosis should be strengthened. VTE occurrence was closely related to advanced age and stage, adenocarcinoma, obesity and novel anticancer therapies in patients with cancer. Early detection of VTE-related examination may lead to earlier intervention for patients with gynecological tumors with preoperative massive ascites.

Li H, et al. Profile of Solid Tumor Patients Complicated With Venous Thromboembolism: A 10-Year Retrospective Cross-Sectional Study Based on 1482 Cases. Clin Appl Thromb Hemost. 2023 Jan-Dec; 29: 10760296231169514. Published online 2023 Apr 16. doi: 10.1177/10760296231169514

Product Q & A From Our Major Sponsor

Q: A patient of mine is on Warfarin. He told me he added Boluoke® and felt an improvement, and wants more. He says he intends to continue the Warfarin. How serious are the risks of combining Boluoke® with Warfarin? Is there data that support your view, or only caution?  Dr. Allen B., DC (Denver, CO)

A: Boluoke® (lumbrokinase) is a fibrinolytic agent and does not affect PT (INR) or aPTT resting. Thus, it is considered compatible with heparin or warfarin. However, currently there is only one randomized trial that we are aware of, in which warfarin + lumbrokinase was shown to be more effective than warfarin alone in treating patients with acute DVTs.  As a general rule, we recommend that patients should only take Boluoke® with any anticoagulant when under a doctor’s supervision.  

Q: I see a patient who was recently diagnosed with thrombosis (very high platelets), but he also has von Willebrand factor deficiency so he bleeds easily. I would like to give him an enzyme between meals. Would Boluoke® be ok to give him?  He is 31 years old.  I also have another patient with end stage kidney disease.  Are there any contraindications?   Dr. Elizabeth S., ND (Scotlant, ON)

A: In general, patients with VWD have more of an issue with clot initiation (so it takes longer to stop bleeding) and often have minor bleeds (in most cases). Thus, unless there is also low platelet count or a problem with clotting factors, their risk of major bleeds is not high (unless acute trauma).

If hypercoagulation is clinically a more important issue right now, then fibrinolytic enzymes can be helpful. This would be your clinical call.

ESKD is not a contraindication for oral fibrinolytic enzymes. In fact, there is likely a hypercoagulation issue in ESKD and it can be helped by fibrinolytic enzymes. Unfortunately, there is no data showing that oral fibrinolytic enzymes will improve kidney function.