Rare coagulation factor deficiency (RFD) is characterized by a deficiency of factor (F) I, FII, FV, FVII, FX, FXI, FXII, FXIII, or a combined deficiency of FV + FVIII or vitamin K-dependent factors and accounts for approximately 5% of all bleeding disorders. The prevalence of RFD in the general population can range from 1 in 1,000,000 for FX to 1 in 2–3 million for FXIII. Combined deficiencies of vitamin K-related factors have been reported in 30 families worldwide. These patients can present with a wide range of clinical symptoms, from mucocutaneous bleeding to life-threatening symptoms such as central nervous system and gastrointestinal bleeding. Treatment of these disorders is primarily based on the replacement of the deficient factor. In this retrospective study, data from 92 children with RFDs were analyzed to describe the distribution, clinical features, treatment patterns, and outcomes of RFDs. The most common factor deficiencies were F VII and F XII deficiency and while combined vitamin-K dependent coagulation factor was found in 3 patients. Of the 92 patients included in the study, 72 exhibited bruising and/or bleeding. The most common type of bleeding was oral and nasal mucosal bleeding. Factor activity was ≤ 5% in 22 patients, 6–20% in 12 patients, and 20–50% in the remaining 60 patients. Among patients with factor levels < 5%, there were both patients without bleeding and patients with recurrent cerebral hemorrhage. Similarly, when factor levels reached 50%, some patients experienced bleeding while others remained asymptomatic. Acute and severe bleeding was controlled with treatment in nine patients. Twenty-seven patients with recurrent bleeding symptoms received prophylaxis. RFDs are more common in regions with high rates of consanguineous marriage, which was 29% in our study. No significant results were obtained regarding an increased risk of bleeding as factor plasmatic levels decreased in patients with RFD. Because of its autosomal recessive inheritance, improving access to genetic counseling and testing is important. Delays in diagnosis and treatment and lack of appropriate prevention are important risk factors that increase life-threatening bleeding.

Prothrombin complex concentrate (PCC) is used to boost thrombin potential, support clot formation, and aid in the treatment and prophylaxis of bleeding. The two main forms of PCC are three-factor (3 F-PCC; comprising coagulation factors II, IX, and X) and four-factor (4F-PCC; factors II, VII, IX, X), which contain 25 times the clotting factors found in human plasma. This narrative review summarizes published efficacy and safety data on one 4F-PCC (Octaplex/Balfaxar, Octapharma) within its recognized uses and explores potential applications across different clinical contexts. Clinically available for > 20 years, Octaplex/Balfaxar is supplied as a freeze-dried powder for reconstitution and intravenous infusion. This 4F-PCC contains non-activated forms of coagulation factors as well as anticoagulant proteins C and S, potentially affording a balanced hemostatic effect and mitigating thrombosis risk. Production involves two virus inactivation/removal steps: solvent/detergent treatment and nanofiltration. 4F-PCC is approved for acquired deficiency of vitamin K-dependent clotting factors, such as those induced by vitamin K antagonists (VKAs, e.g., warfarin), and for congenital deficiency of factors II and X. Five published trials in 444 adult patients demonstrated the efficacy of 4F-PCC in VKA reversal, reducing the international normalized ratio (INR) with only two potentially treatment-related thrombotic events reported. While 4F-PCC dosing is currently indicated to be INR-guided, emerging evidence supports fixed dosing as an alternative to conventional weight-based dosing for VKA reversal. Recent guidelines support 4F-PCC use for direct oral anticoagulant-associated bleeding, cardiac surgery and trauma/emergencies. Ongoing studies will further clarify the efficacy and safety of 4F-PCC beyond its approved indications.

Symptoms of bleeding caused by vitamin K-dependent coagulation factor deficiency (VKCFD) are rare in adults. We present two Japanese cases of adult-onset VKCFD, in which the cause of vitamin K deficiency remains unknown despite comprehensive evaluation. Both patients showed markedly decreased levels of coagulation factors (F) VII, FIX, FX, FII, protein C (PC), and protein S (PS), along with elevated levels of protein induced by vitamin K absence/antagonist II (PIVKA-II). The clinical course in both cases ruled out congenital VKCFD. Based on these findings and a similar case in the relevant literature, we propose a new disease entity, idiopathic acquired VKCFD.

A 4-month-old male born with a Binder Phenotype was admitted for the evacuation of a large subdural hematoma. The blood analysis revealed a prolonged prothrombin time due to vitamin K-dependent coagulation factor deficiency. Vitamin K participates in the embryonic development of the nasal cartilage. The genetic analysis of our patient revealed a rare genetic cause, responsible for the congenital Binder phenotype associated with a defect in the vitamin K metabolism, a pathogenic variant in the GGCX gene that has not been previously reported in the literature. All neonates presenting a Binder Phenotype would benefit from coagulation screening, an easy-access exam, in order to prevent severe and potentially dreadful hemorrhagic events.

Rare coagulation disorders (RCDs) constitute an important health risk. Data on epidemiology, quality of life (QoL), access to care, and impact of the ongoing economic crisis on RCDs in Lebanon is limited. We aimed to address these gaps by evaluating effect of the crisis on the management of RCDs. We performed a retrospective chart review of RCD pediatric patients in a tertiary hospital between 2003 and 2023. Patients with deficiencies of fibrinogen, factor (F)II, FV, combined FV and FVIII, FVII, FXI, FXII, FXIII, and congenital deficiency of vitamin K-dependent factors (VKCFDs) underwent a qualitative assessment of the impact of the economic crisis on care and quality of life by an interview aimed at investigating obstacles to diagnosis, disparities in access to treatment, impact of the crisis on QoL and disease management, and opinion on governmental efforts to solve the health crisis. 46 patients were included. The response rate for the interview was 63%. Among the cohort, 21 (72.4%) reported difficulty accessing treatment since the start of the crisis and 18 (62%) reported "lack of healthcare coverage for necessary treatments" as the main issue. Most participants reported that the Lebanese government did not adequately address their needs during the crisis. Our study showcased that management of RCD patients in Lebanon has been severely affected by the economic crisis. Combined efforts by public and private sectors are needed to appropriately address this issue. Lessons can be learned from the Lebanese experience to appropriately screen for actionable factors in vulnerable populations.