Four factor prothrombin complex concentrate (human): review of the pharmacology and clinical application for vitamin K antagonist reversal

Vitamin K antagonists (VKAs) have been used for decades for the treatment and prophylaxis of thromboembolic events. Due to their wide range of therapeutic indications, they are the most prescribed oral anticoagulant worldwide. However, they are associated with bleeding complications due to their narrow therapeutic range, variability in individual dose responses and laboratory monitoring, and overdoses. Despite off-label use of 3-factor prothrombin complex concentrates and recombinant activated factor VII, until recently, vitamin K and plasma were the only recommended therapeutic options for reversing VKAs in the USA. In 2013, a 4-factor prothrombin complex concentrate (4F-PCC) was approved in the USA for VKA reversal in patients with bleeding or requiring emergency surgery and invasive procedure. Recent randomized controlled clinical trials have shown that 4F-PCC (Kcentra?) is non-inferior for hemostatic efficacy and superior for international normalized ratio correction as compared to plasma and has a similar safety profile.     

Recombinant activated factor VII administration in a patient with congenital lack of factor VII undergoing laparoscopic hysterectomy: A case report

Introduction and importanceCase report of patient with congenital lack of factor VII, suffering from recurrent hematomas and massive menstrual bleedings resulting in severe anemia and multiple hospitalization.Case presentationPatient was diagnosed with endometrial hyperplasia and not responding to hormonal treatment and substitution with recombinant factor VII was not effective to reduce the bleedings. This case describes successful laparoscopic technique of using bipolar coagulation and non-absorbable clips.Clinical discussionWe describe premedication and post-surgical management – which we had to modify from this found in very scarce literature. Despite previous vaginal deliveries without any complications during the puerperium, 20 days after the surgery patient presented with intraperitoneal bleeding after stopping rFVIIa therapy. It was treated medically without the need for re-laparoscopy.ConclusionLaparoscopic surgery is possible in patients with lack and deficiency of FVIIa, but they need close post-operative surveillance and prolonged supplementation with recombinant FVIIa.     

Dosing Strategies for Antiplatelet Therapy in Percutaneous Coronary Intervention

Abstract

Both clopidogrel and aspirin have been shown to decrease the rate of cardiovascular events and especially stent thrombosis in patients undergoing percutaneous coronary intervention (PCI). However, recent studies have suggested that there is large inter-individual response variability to these drugs (especially to clopidogrel) and that improved inhibition of platelet reactivity using higher doses or new, more potent agents would further reduce the occurrence of cardiovascular events, but may also increase the risk of bleeding. Many different protocols of antiplatelet therapy have been studied and have shown benefit in reducing the rate of major adverse cardiovascular events after PCI. Therefore, the choice of an appropriate antiplatelet therapy protocol is sometimes difficult for the clinician and should be individualized as per the particular patient risk, accounting for both the risk of recurrent cardiovascular events and bleeding. We review the recent data on efficacy and safety of dosing strategies for antiplatelet therapy in PCI.     

Thrombin generation in patients with factor XI deficiency and clinical bleeding risk

Summary. Factor XI (FXI) deficiency is a rare bleeding disorder. Most patients with FXI deficiency are mild bleeders but certain patients with similar FXI activity exhibit different bleeding phenotype. Routine laboratory assays do not help physicians to estimate the individual bleeding risk in these patients. Thrombin generation test (TGT) is a more comprehensive, global function test of the clotting system. We investigated whether or not the bleeding tendency of patients with FXI deficiency is correlated with features of the TGT. Twenty‐four patients with FXI deficiency were divided in two groups: (i) severe bleeders (n = 9) and (ii) mild or non‐bleeders (n = 15). All severe bleeders had a personal history of surgery‐related severe bleeding. Thrombin generation (TG) was measured in platelet‐rich plasma (PRP) using a low concentration of tissue factor 0.5 pm . In patients exhibiting severe bleeding tendency, independently of their FXI level, a dramatically impaired TG was observed. For example, despite a low plasma FXI = 1 IU dl^?1, a clinically non‐bleeding individual exhibited normal TG results whereas another patient with severe bleeding history and FXI = 40 IU dl^–1 had a very low TG capacity. Low velocity and delayed TG were the main parameters suggesting a higher bleeding risk. DNA analysis of patients reported eight novel mutations of the FXI gene but neither mutation location nor secretion or not of the variant correlated with the bleeding tendency. The results of this study suggest that TG measurement in PRP may be a useful tool to predict bleeding risk in FXI deficiency and should be studied further in larger prospective clinical studies.     

von Willebrand disease: still an intriguing disorder in the era of molecular medicine

von Willebrand disease (vWD) is a single-locus disorder resulting from a deficiency of von Willebrand factor (vWF): a multimeric multifunctional protein involved in platelet adhesion and platelet-to-platelet cohesion in high shear stress vessels, and in protecting from proteolysis and directing circulating factor VIII (FVIII) to the site of injury. vWD is the most frequent bleeding disorder, with an estimated prevalence in the general population of 1%. Almost all these cases are represented by a partial quantitative deficiency of von Willebrand factor (vWF) (type 1 vWD). Type 1 is transmitted as an autosomal dominant trait with an extremely variable penetrance and expressivity. A consensus figure for the prevalence of cases with significant bleeding symptoms, requiring some form of treatment, is approximately 100 cases million-1. Among these cases, more than 70-80% are represented by type 1 and respond to deamino-D-arginine vasopressin (DDAVP; desmopressin) administration. The remaining cases are represented by type 2 vWD (qualitative), some of which require substitutive treatment. Only 3-5 cases million-1 result from a total deficiency of vWF in plasma and platelets because of the recessive inheritance of two defective alleles. These cases may have severe bleeding episodes and may require frequent substitutive treatment. The molecular basis of type 2 (missense mutation in the functional domains of the vWF subunit) and type 3 (nonsense or large deletions) is quite well understood. On the contrary the molecular basis for most type 1 cases remains largely unknown, and many genetic factors (e.g. ABO blood group) and environmental or circumstantial factors (e.g. age, stress, drugs, pregnancy, and inflammation) are superimposed on to the genetic background determined by the vWF gene to produce a continuous spectrum from normality to mild type 1 cases. It is extremely difficult to make a clear distinction between mild type 1 cases and normal people because of the wide 'normal' range of laboratory measurements (e.g. length of bleeding time, and levels of vWF and FVIII) and of bleeding symptoms. Molecular testing is useless in this situation, and only good history-taking and repeated laboratory testing of vWF-related measurements in the propositus and his/her family members can help in clinical diagnosis, albeit imprecisely. This difficult task is the main focus of this review which is aimed at alerting the physician toward a balanced approach that should take into consideration both the risk of over- and under-diagnosis of this frequent disorder and the unavoidable production of a number of false positive and false negative cases.     

~(99m)锝标记红细胞腹部γ-闪烁扫描捡测胃肠道出血

本文报告用~(99m)锝标记红细胞腹部γ-闪烁扫描检测胃肠道出血患者26例,敏感性为94％,假阴性率6％,特异性87.5％,假阳性率12.5％,定位精确性90.9％。~(99m)锝标记红细胞注入人体一周内对造血系统及肝肾功能均无明显损害。此法可持续检测24h或36h,因此对间歇性和自限性胃肠道出血有独特的诊断价值。     

A combined treatment regimen for desquamative gingivitis in patients with oral lichen planus

BACKGROUND: Chronic desquamative gingivitis (DG) is a condition characterized by erythema, ulceration, and desquamation of the free and attached gingiva, usually expression of a district-systemic disease, such as oral lichen planus (OLP). METHODS: A combined protocol of oral hygiene and topic corticosteroid therapy was applied in 30 patients with DG associated with OLP. Plaque index (PI) and bleeding on probing (BoP) were evaluated at baseline and after 3 months. RESULTS: PI scoring was significantly lower after treatment in anterior, posterior, and all sites (P < 0.0001) as well as in vestibular and lingual ones (P < 0.0001 and P = 0.0001, respectively). BoP measures were found to be reduced significantly to 22.94% in a full-mouth evaluation (P < 0.0001; OR = 2.633; 95% CI: 2.2685-3.0561) as well as in each specific site (P < 0.0001). CONCLUSION: This clinical trial validated the efficacy, in patients with DG associated with OLP, of a protocol based on professional oral hygiene and self-performed plaque control measures in improving of gingival health status.