Decrease In International Normalized Ratio Research Articles

Futility of fresh frozen plasma in the correction of coagulopathy prior to image-guided drainage of infected collections: Results from a prospective case–control study

Abstract BACKGROUND: Fresh frozen plasma (FFP) is frequently used as prophylactic hemostatic therapy for correction of periprocedural coagulopathy. This practice is frequently based on the assumption that deranged international normalized ratio (INR) predicts the risk of periprocedural bleeding and that FFP transfusion is effective in mitigating the procedure-associated bleeding risks. There is limited evidence to support both these assumptions in the context of image-guided drainage of infected collections. AIMS: The study aimed to analyze the efficacy of weight-based standard FFP dose for correction of infection-associated coagulopathy in patients with clinicoradiologically diagnosed infected collections planned for image-guided drainage. MATERIALS AND METHODS: In this prospective case–control study, 229 patients with clinicoradiologically diagnosed infected abdominal collection(s) planned to undergo image-guided drainage were included. Cases and controls were defined as patients with baseline INR >1.2–3 (in the absence of any other bleeding diathesis) and INR ≤1.2, respectively. Cases received 10–15 mL/kg of FFP before drainage. Costs and time delays in drainage among the two groups, efficacy of plasma transfusion in the correction of coagulopathy, incidence of transfusion reactions, bleeding complications, and inhospital mortality were analyzed. RESULTS: There were 117 cases and 112 controls. A total of 445 FFP units were utilized. The median (interquartile range) time required from diagnosis of collection to the procedure was 25.3 (20.8–40.3) hours among cases and 16.4 (8.7–20.1) hours among controls (P < 0.001). FFP transfusion resulted in INR normalization (≤1.2) only in 7.9% of cases (n = 9). Among the 81 cases who had pretransfusion INR ≥1.5, INR improved to ≤1.5 in 49 (60.4%) patients. There was an average of 2.9% decrease in INR per unit of FFP transfused. No bleeding complications were noted in patients undergoing drainage despite a persistent deranged INR (>1.5) postplasma transfusion. Transfusion reactions occurred in 17/117 (14.5%) patients. There were no deaths among the controls while five patients died among the cases. CONCLUSION: Prophylactic FFP transfusion for infection-associated coagulopathy leads to a significant delay in lifesaving drainage procedures. Minority of patients attain normalization of INR with FFP transfusion.

Impact of enteral administration of sodium hypochlorite on the mechanisms of inflammation and hemostasis in cancer patients with enteral insufficiency syndrome after multi-organ surgeries

Background. Enteral insufficiency syndrome is a complicated and multifactorial symptom complex that is accompanied with impaired functions of the gastrointestinal tract and is also one of the main causes of the development of endotoxicosis, systemic inflammatory response syndrome, abdominal sepsis, septic shock, and multi-organ failure. Thrombosis, which is associated with oncological diseases, is another common cause of death among patients with cancer after the progression of the disease. Development and implementation of new methods of detoxification in cancer patients in clinical practice after multi-organ surgeries is a major problem in intensive care. Purpose – to study the effectiveness of the enteral administration of sodium hypochlorite in cancer patients after multi-organ surgeries with systemic inflammatory response syndrome and to monitor the dynamics of certain markers of inflammation. Materials and methods. 53 patients with cancer were observed after having undergone multi-organ surgeries on the abdominal organs. The patients were divided into two groups: the main group (n=27), in which indirect electrochemical detoxification with sodium hypochlorite at a concentration of 0,06% was carried out by the drip infusion method through a gastrointestinal tube, and the comparison group (n=26), in which the treatment was performed according to standard treatment regimens. The examination was carried out at 3 stages – before NaClO infusion, on the 1st and the 7th day after the indirect electrochemical detoxification. Groups were compared according to age and anatomical and functional zones of the surgery (the surgery was performed on the abdominal organs). Results. Patients with stage 2/3 enteral insufficiency syndrome were treated with the method of electrochemical detoxification with sodium hypochlorite, which led to the inflammation reduction and normalization of the hemostatic system parameters. In patients, who were receiving sodium hypochlorite (the main group), the reduction in inflammatory mediators was observed: C-reactive protein (CRP) – from 22.1 to 5.6 mg/l, interleukin-6 (IL-6) – from 14,36 to 1.55 pg/ml, and also hemostatic parameters were improved. A decrease in the international normalized ratio (INR), fibrin, activated partial thromboplastin time (APTT), D-dimer level, blood clotting time, and an increase in prothrombin index were observed. Analyzing the effectiveness, it should be noted that the correction of the hemostatic system and the development of inflammation are significantly faster (on the 1st day after the NaClO infusion) compared with standard treatment methods while also ensuring plasma preservation. Conclusions. The use of the method of electrochemical detoxification with 0,06% NaClO in postoperative intensive therapy in enteral insufficiency syndrome prevents the development of systemic inflammation and hypocoagulation. The inclusion of sodium hypochlorite in the complex postoperative therapy during the day allowed the development of inflammation (a decrease in the expression of IL-6 and CRP) to be halted and procoagulative changes (a decrease in INR, fibrin, APTT, D-dimer level, blood clotting time, and an increase in prothrombin index) to be achieved.

Evaluation of Response to High-Dose Intravenous Vitamin K Administration.

Essential to the coagulation pathway, vitamin K (phytonadione) is used to correct clotting factor deficiencies and for reversal of warfarin-induced bleeding. In practice, high-dose intravenous (IV) vitamin K is often used, despite limited evidence supporting repeated dosing. This study sought to characterize differences in responders and nonresponders to high-dose vitamin K to guide dosing strategies. This was a case-control study of hospitalized adults who received vitamin K 10 mg IV daily for 3 days. Cases were represented by patients who responded to the first dose of IV vitamin K and controls were nonresponders. The primary outcome was change in international normalized ratio (INR) over time with subsequent vitamin K doses. Secondary outcomes included factors associated with response to vitamin K and incidence of safety events. The Cleveland Clinic Institutional Review Board approved this study. There were 497 patients included, and 182 were responders. Most patients had underlying cirrhosis (91.5%). In responders, the INR decreased from 1.89 at baseline (95% CI = [1.74-2.04]) to 1.40 on day 3 (95% CI = [1.30-1.50]). In nonresponders, the INR decreased from 1.97 (95% CI = [1.83-2.13]) to 1.85 ([1.72-1.99]). Factors associated with response included lower body weight, absence of cirrhosis, and lower bilirubin. There was a low incidence of safety events observed. In this study of mainly patients with cirrhosis, the overall adjusted decrease in INR over 3 days was 0.3, which may have minimal clinical impact. Additional studies are needed to identify populations who may benefit from repeated daily doses of high-dose IV vitamin K.

Опыт применения рекомбинантного активированного фактора свертывания VII в лечении массивных акушерских кровотечений

This article presents the results of a retrospective observational study on the use of recombinant activated coagulation factor VII (Eptacog alfa [activated], Coagil-VII) to evaluate its efficacy and safety in the treatment of massive obstetric hemorrhage (MOH) in 30 women with volume of circulating blood loss over 25%; 90% of women delivered by cesarean section, and 10% of women delivered by vaginal birth. The efficacy and safety of Coagil-VII as a hemostatic agent in intensive therapy for MOH were evaluated using clinical, laboratory and statistical research methods. The administration of Eptacog alfa [activated] (Coagil-VII) helped to significantly reduce the volume of blood loss, duration, time and rate of bleeding, and the amount of blood component transfusion. The total dose of the drug was 3.68 mg. The analysis of laboratory parameters (hemogram, blood biochemistry tests) in patients of the study group with MOH did not reveal any negative effect of Coagil-VII according to the parameters. The results of the hemostatic system assessment showed that after administration of Coagil-VII there was an increase in blood coagulation potential, as evidenced by a decrease in International Normalized Ratio, shortened prothrombin and thrombin time, activated partial thromboplastin time. All parameters were within the reference range, without increasing the risk of thrombotic complications. No thrombotic complications in the early and late postoperative/postpartum period were detected in any patient. Hysterectomy in this study group was performed in 7 (23.3%) patients; the uterus was preserved in 23 (76.7%) women with MOH. The use of modern hemostatic drug Coagil-VII in the complex treatment of MOH under the control of clinical laboratory testing helped to stop (in 86.6% of women) or reduce the intensity of hemorrhage (in 13.3% of patients), reduce the amount of transfused blood components, improve the patients’ condition without thrombotic complications, reduce possible complications associated with transfusions and the cost of therapy, and implement organ preservation tactics in 76.7% of women. Key words: pregnancy, safety, massive hemorrhage, patient blood management, fertility, efficacy

Utility of 4-Factor Prothrombin Complex Concentrate in Trauma and Acute-Care Surgical Patients.

Since 2013, prothrombin complex concentrate (PCCs) have been approved in the United States for the reversal of anticoagulation induced by vitamin K antagonists. However, there has been limited investigation into their use in trauma and acute-care surgery (ACS). To investigate the role that 4-factor PCC may have in reversing anticoagulation in the setting of trauma and ACS. All trauma and ACS patients who presented between March 14, 2014, and August 1, 2015, were included in this retrospective descriptive analysis. Patients receiving 4-factor PCC were compared with patients receiving fresh frozen plasma (FFP) alone. The following data were collected from medical records: age, sex, race, international normalized ratio (INR) at admission (baseline) and after reversal, blood products given, dosing of medication, injury severity score, length of stay, thromboembolic event, death during admission, and death within 90 days after admission. There were 188 trauma and ACS patients who required reversal of anticoagulation. Of these, 98 patients received FFP and 90 received PCC. Patients who received PCC were at increased risk for death during admission (20% vs 9.2% for FFP group) or within 90 days (39% vs 15%, respectively). Patients in the PCC group had a higher median baseline INR (2.9 vs 2.5 in the FFP group) and a lower postintervention INR (1.4 vs 1.8); consequently, the decrease in INR was greater in the PCC group than in the FFP group (1.5 vs 0.7, respectively). The number of total units of packed red blood cells transfused was significantly higher in patients receiving PCC. Patients receiving PCC had worse outcomes than those who received FFP. Given that these differences may have resulted from baseline differences between groups, these results mandate further prospective analysis of the use of PCC in trauma and ACS patients.

Prothrombin Complex Concentrate for Warfarin-Associated Intracranial Bleeding in Neurosurgical Patients: A Single-Center Experience.

Objective: The number of patients presenting with warfarin-associated intracranial bleeding and needing neurosurgical intervention is growing. Prothrombin complex concentrate (PCC) is commonly used for anti-coagulation reversal before emergent surgery. We present our experience with PCC use in patients presenting with coagulopathy and needing urgent craniotomy. Methods: We retrospectively identified all patients presenting with intracranial bleeding and coagulopathy due to warfarin use, requiring urgent neurosurgical procedures, from January, 2014 (implementation of 4-PCC therapy) until December, 2016. For coagulation reversal, all patients received 4-PCC (Octaplex) and vitamin K. Results: Thirty-five consecutive patients (17 men; median age 72 years) were administered 4-PCC before emergent neurosurgical procedures. The majority of patients presented with traumatic subdural hematoma (62%) and spontaneous intracerebral hemorrhage (32%). All patients were taking warfarin. Median international normalized ratio (INR) on admission was 2.94 (range: 1.20 to 8.60). Median 4-PCC dose was 2000 I.U. (range: 500 I.U. to 3000 I.U.). There was a statically significant decrease in INR (p < 0.01), PT (p < 0.01), and PTT (p = 0.02) after 4-PCC administration. Postoperative INR values were ≤3.00 in all patients, and seven (20%) patients had normal INR values. There were no 4-PCC related complications. Four (11%) patients developed subdural/epidural hematoma and 20 (57%) patients died. Mortality was associated with lower Glasgow coma scale (GCS) score. Conclusions: The 4-PCC facilitates INR reversal and surgery in patients presenting with warfarin-associated coagulopathy and intracranial bleeding requiring urgent neurosurgical intervention.

Effect of vitamin K2 on the anticoagulant activity of warfarin during the perioperative period of catheter ablation: Population analysis of retrospective clinical data.

BackgroundCatheter ablation is a non-medication therapy for atrial fibrillation, and during the procedure, warfarin is withdrawn in the preoperative period to prevent the risk of bleeding. In case of emergency, vitamin K2 can be intravenously administered to antagonize the anticoagulant activity of warfarin. The aims of this study were to conduct population pharmacokinetic/pharmacodynamic modeling for retrospective clinical data and to investigate the effect of vitamin K2 on the anticoagulant activity of warfarin in the perioperative period of catheter ablation.MethodsA total of 579 international normalized ratio (INR) values of prothrombin time from 100 patients were analyzed using the nonlinear mixed-effects modeling program NONMEM. A 1-compartment model was adapted to the pharmacokinetics of warfarin and vitamin K2, and the indirect response model was used to investigate the relationship between plasma concentration and the pharmacodynamic response of warfarin and vitamin K2. Since no plasma concentration data for warfarin and vitamin K2 were available, 3 literally available pharmacokinetic parameters were used to simultaneously estimate 1 pharmacokinetic parameter and 5 pharmacodynamic parameters.ResultsThe population parameters obtained not only successfully explained the observed INR values, but also indicated an increase in sensitivity to warfarin in patients with reduced renal function. Simulations using these parameters indicated that vitamin K2 administration of more than 20 mg caused a slight dose-dependent decrease in INR on the day of catheter ablation and a delayed INR elevation after warfarin re-initiation.ConclusionsA pharmacokinetic/pharmacodynamic model was successfully built to explain the retrospective INR data during catheter ablation. Simulation studies suggest that vitamin K2 should be administered with care and that more than 20 mg is unnecessary in the preoperative period of catheter ablation.

Retrospective study of rFVIIa, 4-factor PCC, and a rFVIIa and 3-factor PCC combination in improving bleeding outcomes in the warfarin and non-warfarin patient.

In case of severe bleeding, the physician must rapidly and effectively halt bleeding without the risk of thromboembolic complications. Despite widespread use, no study has directly compared recombinant activated factor VII (rFVIIa), the rFVIIa and 3-factor prothrombin complex concentrate (PCC) combination ("combination"), and 4-factor PCC on their effectiveness in improving patient outcomes. This study examined the medical records of 299 patients, 65.2% on warfarin prior to admission, who received these hemostatic agents and were admitted to an ICU or through the emergency department at Oregon Health & Science University. Mortality, length of stay, change in international normalized ratio (INR), plasma use, and number of thromboembolic complications were used to assess effectiveness. In patients receiving warfarin, the combination group had the greatest decrease in INR as well as lowest overall INR, but experienced a higher number of clotting complications, while the rFVIIa group used the most plasma. Non-warfarin patients in the combination group had the shortest length of stay among survivors, but the rFVIIa group had the lowest mortality. Based on this data, it may be prudent to further study the use of rFVIIa in treating extreme bleeding in the non-warfarin patient, while this study supports other data that 4-factor PCC may be the most prudent for the warfarin patient. Am. J. Hematol. 91:705-708, 2016. © 2016 Wiley Periodicals, Inc.

Emergent reversal of vitamin K antagonists: addressing all the factors

BackgroundReversal of warfarin-induced coagulopathy after traumatic injury may be done exclusively with prothrombin complex concentrates (PCCs). No direct comparisons between different PCC regimens exist to guide clinical decision-making. Our institution has used 2 distinct PCC strategies for warfarin reversal; a 3-Factor PCC (Profilnine) combined with activated Factor VII (3F-PCC+rVIIa), and a 4-Factor PCC (Kcentra) given without additional factor supplementation. MethodsRetrospective review of all PCC administrations to trauma patients with acute bleeding who were taking warfarin before injury. Primary endpoints were international normalized ratio (INR) reduction, in-hospital mortality, and diagnosis of deep venous thrombosis (DVT). ResultsEighty-seven patients were identified from 2011 to 2015. Fifty-three were treated with 3F-PCC+rVIIa and 34 with 4F-PCC. Patient demographics, injury severity, and presenting laboratory data were similar. The 3F-PCC+rVIIa produced a lower median (IQR) INR postreversal compared with 4F-PCC (.75 (.69, 1.00) vs 1.28 (1.13, 1.36), P<.001). Both regimens were able to obtain an INR lower than 1.5 immediately after administration (3F+rVIIA 93.9% vs 4F 97.1%, P =.51). In the 4F-PCC group, there was a significant decrease in the incidence of DVT (2.9% vs 22.6%), P < .01), and a nonsignificant reduction in mortality (2.9% vs 17.0%, P = .08). ConclusionsUse of 4F-PCC for warfarin reversal after traumatic hemorrhage is associated with a less severe decrease in INR, a significant reduction in DVT rates and a trend toward reduced mortality when compared with similar patients treated with 3F-PCC+rVIIa.

Modelling of vitamin K half-life in patients treated with vitamin K antagonists before hip fracture surgery

BackgroundGuidelines recommend treatment with vitamin K in patients requiring reversal of the effect of vitamin K antagonists (VKA) before semi-urgent surgery. In clinical practice, the time for reversal of the international normalized ratio (INR) to values adequate for surgery is often reported longer than the expected 12–24hours, which may delay surgery and increase the risk of complications. MethodsIn order to optimize the management of elderly patients treated with VKA and undergoing hip fracture surgery, we aimed to model the vitamin K half-life in this specific population. Files for patients admitted between 2006 and 2008 for hip fracture surgery and chronically treated with VKA were retrospectively studied. Only patients with an INR superior to 1.5 upon arrival were included in the study. The effect of vitamin K on the decrease in INR was modelled after a PK/PD analysis using NONMEM. Thirty-one patients’ files were analysed. ResultsDespite management in accordance with guidelines, 31% of the patients had a delayed return to INR values<1.5 resulting in delayed surgery. Time to INR<1.5 was longer than 24hours in 50% of the patients. The calculated half-life of vitamin K was 24.7hours in this population. ConclusionThe vitamin K half-life in elderly patients treated with VKA and undergoing hip fracture surgery was prolonged. The use of vitamin K or of a more rapid acting alternative should be discussed, depending on the urgency of the surgery.

Alterations in Blood Coagulation and Viscosity Among Young Male Cigarette Smokers of Al-Jouf Region in Saudi Arabia.

Hemorheology, a measure of rheological properties of blood, is often correlated with cerebral blood flow and cardiac output; an increased blood viscosity may increase the risk of thrombosis or thromboembolic events. Previous studies have reported a large variation in hemorheological properties of blood among smokers. This prompted us to conduct coagulation experiments to evaluate the effect of cigarette smoking on hematological parameters, like cell counts, and coagulation parameters among young males in Al-Jouf region, Saudi Arabia. The hematological and coagulation parameters were used to relate the changes in viscosity and coagulation to smoking. A total of 321 male participants (126 nonsmokers and 195 smokers) were enrolled into the study as randomized sample. Complete blood count was measured by hematology analyzer, and coagulation tests were performed by coagulation analyzer. Thettest analysis was performed to compare the relationships of variables between the 2 groups. The results confirmed that smoking alters some hematology parameters leading to significant deterioration in blood flow properties. Smoking also increased the hematocrit (HCT), whole blood viscosity (WBV), and plasma viscosity (PV) but decreased the international normalized ratio (INR). The decrease in INR was found to be associated with the increase in WBV, PV, and HCT. Further investigations are necessary to assess the reversibility of such changes in cessation of smoking or other elements of influence.

Short‐term warfarin reversal for elective surgery – using low‐dose intravenous vitamin K: safe, reliable and convenient*

Peri-procedural management of warfarin reflects an intricate balance between the restoration of haemostasis and appropriate thromboprophylaxis. This prospective single-arm study assessed the safety and efficacy of a convenient schedule, incorporating low-dose intravenous vitamin K (vitK(IV) ) for short-term warfarin reversal prior to elective surgery, as well as vitK-dependent factor levels (vitK-Factors) and International Normalized Ratio (INR) pre- and post-vitK(IV) . One seventy eight patients on long-term warfarin received 3mg vitK(IV) 12-18 h pre-procedure with no adverse reactions. 167/178 (94%) achieved an INR≤1·5 post-vitK(IV) on the day of surgery, while all achieved INR≤1·7. Four patients had procedure-associated major bleeding, but importantly had achieved a pre-procedure INR<1·5 and vitK-Factors >0·30iu/ml. No patient suffered a symptomatic thromboembolism during the 6-week follow-up. Median days to re-establish a therapeutic INR were 4 (range 2-11). VitK(IV) near normalized all vitK-Factors, with a uniform pattern of depletion and repletion in association with an increase and decrease in INR, respectively; and from the data, INR<1·5 correlated with vitK-Factors >0·30iu/ml. Low-dose vitK(IV) for short-term warfarin reversal was reliable and safe, and successfully lowered the INR to an acceptable level for planned surgery, with no excess of bleeding, thromboembolism, delayed discharge, or resistance to warfarin. The protocol was simple and convenient for both the patients and the healthcare institution.

Potential Glucosamine‐Warfarin Interaction Resulting in Increased International Normalized Ratio: Case Report and Review of the Literature and MedWatch Database

We describe a 71-year-old man who had received warfarin 7.5 mg/day for 5 years for atrial fibrillation, which had maintained his international normalized ratio (INR) within a narrow range of 2.5-3.2. During this 5-year period, he had also been treating himself with the supplement glucosamine hydrochloride 500 mg-chondroitin sulfate 400 mg twice/day for arthritis. The patient then increased his dosage of glucosamine to 1500 mg and chondroitin to 1200 mg twice/day; his INR previous to this change was 2.3. Approximately 3 weeks later, his INR increased to 3.9. His supplement dosage was reduced to glucosamine 750 mg-chondroitin 600 mg/day; a repeat INR done 16 days later was 4.7. The supplement was then stopped, and his warfarin schedule was changed to 7.5 mg every other day alternating with 3.75 mg every other day. Sixteen days later, his INR was 2.6. This case report suggests that a potential interaction exists between warfarin and glucosamine that is associated with an increase in the INR. We therefore performed a pharmacovigilance survey of spontaneously reported adverse events in warfarin-treated patients concomitantly exposed to glucosamine, glucosamine-chondroitin sulfate, or chondroitin sulfate and present a literature review of this apparent drug-drug interaction. Using the United States Food and Drug Administration (FDA) MedWatch database, 20 reports of glucosamine or glucosamine-chondroitin sulfate use with warfarin associated with altered coagulation (manifested by increased INR, or increased bleeding or bruising) were identified. In some cases, a decrease in the supplement dosage was followed by a return of the INR to the previous therapeutic range. Similarly, a decrease in warfarin dosage was followed by a decrease in INR in one patient who received long-term warfarin therapy. One report described an intraventricular bleed and subdural hematoma, which resulted in a persistent vegetative state. The World Health Organization (WHO) adverse drug reactions database documented 21 spontaneous reports of increased INR associated with glucosamine use, 17 of which resolved when glucosamine was stopped. We located one published case report of concomitant use of glucosamine-chondroitin sulfate potentiating the effect of warfarin. In aggregate, the reports from the FDA and WHO, the published case report, and our case report suggest that the use of warfarin and glucosamine may lead to an increased INR. Patients should be advised that the use of the two products may cause an increase in INR, and they should inform their health care provider if they consume glucosamine. More information is necessary to define this interaction.

Potential Interaction Between Warfarin and High Dietary Protein Intake

A 55-year-old Caucasian man was receiving warfarin therapy after undergoing aortic valve replacement. His international normalized ratio (INR) was stabilized with warfarin 95 mg/week for 5 weeks. Commencement of a low-carbohydrate, high-protein diet resulted in a series of subtherapeutic INRs that led to a 16% increase in the dosage requirement to maintain therapeutic INRs. After the patient discontinued the diet, his INR increased, and several dosage reductions were required until his INR stabilized with his original dosage of 95 mg/week. Two additional case reports have described a possible interaction between warfarin and a high-protein diet. The potential for increased dietary protein intake to raise serum albumin levels and/or cytochrome P450 activity has been postulated as mechanisms for the resulting decrease in INRs. Given the available animal and human data that demonstrate alterations in drug metabolism in the presence of altered dietary protein intake, an increase in warfarin metabolism due to cytochrome P450 activation appears to be the most likely cause. In addition to the previously reported cases, this case indicates a potential interaction between warfarin and a high-protein diet. Because of the popularity of high-protein diets and because of the risks associated with inadequate or excessive warfarin anticoagulation, patients and health care providers should be aware of this interaction to ensure appropriate monitoring when warranted.

Toward Rational Fresh Frozen Plasma Transfusion

Numerous published guidelines encourage appropriate use of fresh frozen plasma (FFP). However, adherence is documented as poor. Therefore, we sought to determine the laboratory effect of FFP administration to patients with an international normalized ratio (INR) less than 1.6 (prothrombin time <1.6 times normal). We found minimally prolonged INRs decreased with treatment of the underlying disease alone. Adding FFP to the treatment failed to change the decrease in INR over time. In addition, we observed that the change in the INR per unit of FFP transfused can be predicted by the pretransfusion INR (INR change = 0.37 [pretransfusion INR] – 0.47; r 2 = 0.82). With an observed analytic variation of 3.2%, a significant amount of change in the INR following FFP transfusion is expected at an INR of more than 1.7. Indeed, only 50% of patients with an INR of 1.7 showed a significant change in INR with FFP transfusion. Therefore, transfusion for patients not meeting current FFP guidelines does not reliably reduce the INR and exposes patients to unnecessary risk.

Toward Rational Fresh Frozen Plasma Transfusion The Effect of Plasma Transfusion on Coagulation Test Results

Numerous published guidelines encourage appropriate use of fresh frozen plasma (FFP). However, adherence is documented as poor. Therefore, we sought to determine the laboratory effect of FFP administration to patients with an international normalized ratio (INR) less than 1.6 (prothrombin time < 1.6 times normal). We found minimally prolonged INRs decreased with treatment of the underlying disease alone. Adding FFP to the treatment failed to change the decrease in INR over time. In addition, we observed that the change in the INR per unit of FFP transfused can be predicted by the pretransfusion INR (INR change = 0.37 [pretransfusion INR] - 0.47; r2 = 0.82). With an observed analytic variation of 3.2%, a significant amount of change in the INR following FFP transfusion is expected at an INR of more than 1.7. Indeed, only 50% of patients with an INR of 1.7 showed a significant change in INR with FFP transfusion. Therefore, transfusion for patients not meeting current FFP guidelines does not reliably reduce the INR and exposes patients to unnecessary risk.

Rosuvastatin-acenocoumarol interaction

Background:Previous evidence suggests that hydroxymethylglutaryl coenzyme A-reductase inhibitors (statins) might potentiate the effect of oral anticoagulants, but a MEDLINE search (key terms: stains, rosuvastatin, anticoagulants, acenocoumarol, and interaction; years: 1980–2005) revealed no reports of an interaction between rosuvastatin and acenocoumarol. Objective:The aim of this article was to describe a case of possible interaction between rosuvastatin and acenocoumarol. Methods:We report the case of a 36-year-old male patient receiving long-term oral treatment with acenocoumarol, a synthetic coumarin anticoagulant, who experienced an increase in international normalized ratio (INR) and a hematoma in the left leg ∼45 days after the initiation of treatment with rosuvastatin. Results:After discontinuation of both drugs, an unexpectedly rapid decrease in INR was observed. Conclusions:Based on the results of this case, a possible pharmacologic interaction between rosuvastatin and acenocoumarol should be considered. Rosuvastatin might enhance the anticoagulant effect of acenocoumarol, and a rebound effect in cases of simultaneous discontinuation of both drugs might occur. Rosuvastatin should be administered with extreme caution in patients receiving long-term acenocoumarol therapy.

Fulminant hepatic failure

Abstract Analysis of the first 150 cases collected from 73 centers reporting to the Fulminant Hepatic Failure Surveillance Study showed that 80 patients had presumable viral hepatitis, of whom 62 died. Of 41 patients who had recent surgery, 36 died. In 35 patients massive liver necrosis developed less than three weeks after halothane anesthesia, and 27 (77 per cent) of these had multiple exposures to halothane. The risk from halothane is small, but this complication was present in nearly one quarter of the cases reported in our study. When the use of halothane is desired, multiple exposure should be avoided, if possible. Moreover, postoperative fever after exposure to halothane, otherwise "unexplained," is an important warning sign, and should be thoroughly investigated and taken into consideration when further exposure to this anesthetic is contemplated. The physician prescribing halothane must balance need against risk.

Simple and Safe Method to Prepare Patients With Prosthetic Heart Valves for Surgical Dental Procedures

Temporary discontinuation of high-intensity oral anticoagulant treatment is not recommended in patients undergoing dental surgery. This policy is not based on solid data from randomized clinical trials but on expert consensus. The alternative, i.e., to continue treatment and treat patients with tranexamic acid mouthwash, often is not applicable. A prospective cohort study was carried out to evaluate bleeding and thromboembolic complications in patients bearing prosthetic heart valves and registering International Normalized Ratio (INR) values between 2.0 and 4.5, who underwent dental procedures after a 2-day suspension of warfarin treatment. One hundred four consecutive patients receiving high-intensity anticoagulation underwent 123 dental procedures after 2 days' warfarin withdrawal. No major bleeding complications occurred in the week after the procedure; minor bleeding requiring local measures occurred in two patients. No thromboembolic events and no cases of bacterial endocarditis were recorded in the 3 months after the procedure. A mean decrease in INR by approximately 1.0 U (from 2.95+/-0,59 to 1.87+/-0,46) occurred after 2 days' warfarin suspension. Seven days after reinitiation of warfarin, INR values returned to the therapeutic range in 90% of cases. The calculated average time spent at INR less than 2.0 (critical value) was 28 hours. Two days' warfarin suspension is a simple and safe policy for patients with prosthetic heart valves undergoing dental surgery.