vitamin-k-semiquinone-radical and Femoral-Fractures

To summarize the clinical features and bone complications in a patient from a large family with X-linked congenital adrenocortical hypoplasia (AHC) and evaluate the efficacy of different treatment regimens on the prognosis of secondary osteoporosis caused by AHC at a 5-year follow-up.. A large family with AHC was recruited, and the causative gene mutation was identified by Sanger sequencing in the proband. Clinical features as well as radiological examinations and laboratory indices of osteoporosis secondary to AHC were analyzed in this study. Meanwhile, the proband was treated with classical antiresorptive drugs (bisphosphonates) for 2 years and switched to a vitamin K. The proband was identified as carrying a homozygous insertion mutation (p. Thr193GlyfsX13) in the. Secondary osteoporosis induced by AHC deserves clinical attention. Unlike in primary osteoporosis, the curative effect of bisphosphonates was unsatisfactory and was more likely to cause atypical femoral fractures in long-term treatment. It is suggested that bone anabolic drugs may be better alternatives.

Topics: Bone Diseases; Diphosphonates; Femoral Fractures; Humans; Mutation; Osteoporosis; Vitamin K

About one third of all patients with proximal femur fractures take oral anticoagulation like aspirin (ASS), direct platelet aggregation inhibitors like Clopidogrel and Ticagrelor (PAI), vitamin-K-antagonists like Warfarin (VKA) and direct oral anticoagulants like Rivaroxaban, Dabigatran and Apixaban (DOAC). The management and timing of fracture stabilization of these patients is a rising challenge in orthopedic trauma. Our objective was to determine the effect of oral anticoagulation on patients with proximal femur fractures, which received a proximal femur nail antirotation (PFNA) within 24 h after trauma.. A retrospective chart review of 327 patients (mean age 80 ± 13 years; 223 women and 104 men) with sub- or intertrochanteric fractures between January 2013 and December 2017 was performed. All patients underwent surgery in the first 24 h after admission. Solely patients without or with only one type of oral anticoagulation were included. There were 74 patients with ASS, 30 with PAI, 52 with DOAC and 25 with VKA medication. All patients taking VKA received high dose Vitamin K or coagulation factors to normalize INR prior to surgery. Primary outcome measures were transfusion rate and pre- and postoperative hemoglobin (Hb) difference. Secondary outcome measures were mortality and complications like infection, hematoma and acute cardiovascular events.. Patients undergoing treatment with DOAC had a 3.4-fold increased risk for intraoperative blood transfusion. The risk for blood transfusion for patients taking ASS, PAI or VKA did no differ from the control group. Patients without an intraoperative blood transfusion on oral anticoagulation showed no increase in pre- and postoperative Hb-difference compared with controls. Anticoagulation showed no significant effect on complication rates and mortality in patients operated within the first 24 h.. Early surgical care of proximal femur fractures is safe even in patients with anticoagulant medication. All patients should be preoperatively prepared for possibly intraoperative transfusion, especially patients on DOAC.

Topics: Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Blood Loss, Surgical; Female; Femoral Fractures; Fracture Fixation, Internal; Humans; Male; Middle Aged; Postoperative Hemorrhage; Preoperative Care; Retrospective Studies; Time Factors; Vitamin K

Clinical use of non-vitamin K antagonist oral anticoagulants is increasingly well established. However, specific agents for reversal of these drugs are not currently available. It was to objective of this study to investigate the impact of activated prothrombin complex concentrate (aPCC) on the anticoagulant effects of dabigatran in a randomised, controlled, porcine trauma model. Twenty-one pigs received oral and intravenous dabigatran, resulting in supratherapeutic plasma concentrations. Twelve minutes after injury (standardised bilateral femur fractures and blunt liver injury), animals (n=7/group) received 25 or 50 U/kg aPCC (aPCC25 and aPCC50) or placebo (control) and were followed for 5 hours. The primary endpoint was total volume of blood loss (BL). Haemodynamic and coagulation variables (prothrombin time [PT], activated partial thromboplastin time, diluted thrombin time, thrombin-antithrombin complexes, thromboelastometry, thrombin generation and D-dimers) were measured. Twelve minutes post-injury, BL was similar between groups. Compared with control (total BL: 3807 ± 570 ml) and aPCC25 (3690 ± 454 ml; p=0.77 vs control), a significant reduction in total BL (1639 ± 276 ml; p< 0.0001) and improved survival (p< 0.05) was observed with aPCC50. Dabigatran's anticoagulant effects were effectively treated in the aPCC50 group, as measured by several parameters including EXTEM clotting time (CT) and PT. In contrast, with aPCC25, laboratory values were initially corrected but subsequently deteriorated due to ongoing blood loss. Thromboembolic or bleeding effects were not detected. In conclusion, blood loss following trauma in dabigatran-anticoagulated pigs was successfully reduced by 50 U/kg aPCC. Optimal methodology for measuring amelioration of dabigatran anticoagulation by aPCC is yet to be determined.

Topics: Administration, Oral; Animals; Antibodies, Monoclonal, Humanized; Anticoagulants; Area Under Curve; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Calibration; Dabigatran; Femoral Fractures; Fibrin Fibrinogen Degradation Products; Hemodynamics; Hemorrhage; Hemostasis; Male; Multiple Trauma; Partial Thromboplastin Time; Platelet Aggregation; Platelet Function Tests; Prothrombin Time; Random Allocation; Swine; Thrombelastography; Thrombin; Time Factors; Vitamin K

Osteocalcin (a vitamin K-dependent, bone-specific protein) is widely accepted as a marker of osteoblastic activity. The present study was conducted to determine if a vitamin K deficiency would affect fracture healing by virtue of an alteration in osteocalcin metabolism. Thirty male Sprague-Dawley rats were divided into two groups. The control group was fed a diet that was lacking in, but offered water replete with vitamin K. The experimental group was fed a vitamin K-deficient diet and was offered water that was lacking in vitamin K. After two weeks, vitamin K deficiency was established in the experimental group as shown by decreased urinary excretion of gamma-carboxyglutamic acid and an elevation of serum prothrombin times to between two to two and one-half times the control values. At this time, a standard, closed femoral fracture was produced. Six weeks later, the animals were killed. The bones were biomechanically tested in torsion. Subsequent to mechanical testing, the calluses were retrieved, and the osteocalcin content and the degree of gamma carboxylation of the osteocalcin in the calluses were measured. The results show that despite significant alterations in the gamma carboxylation of osteocalcin and elevation of prothrombin times to two to two and one-half times the control values, there were no differences in the mechanical properties of the calluses. Furthermore, there were no differences in the content or gamma carboxylation of osteocalcin in these calluses. Apparently, in vitamin K deficiency, fracture callus achieves normal mechanical properties and may have a mechanism for the gamma carboxylation of glutamic acids in osteocalcin despite a substantial depression of this activity in the rest of the body.

Topics: 1-Carboxyglutamic Acid; Animals; Bony Callus; Calcium-Binding Proteins; Femoral Fractures; Male; Osteocalcin; Prothrombin Time; Rats; Rats, Inbred Strains; Vitamin K; Vitamin K Deficiency; Wound Healing

Topics: Femoral Fractures; Humans; Vitamin K

Topics: Femoral Fractures; Humans; Vitamin K