International Normalized Ratio Levels Research Articles

Nonalcoholic fatty liver disease-related cirrhosis is commonly unrecognized and associated with hepatocellular carcinoma.

Determination of cirrhosis in nonalcoholic fatty liver disease (NAFLD) is important as it alters prognosis and management. We aimed to examine whether cirrhosis was diagnosed incidentally or intentionally in patients with NAFLD. We reviewed 100 patients with NAFLD cirrhosis to determine mode of cirrhosis diagnosis (incidental or by intent), severity of liver disease at diagnosis, diagnostician, and previous clinical imaging or laboratory evidence of unrecognized cirrhosis. The majority (66/100) of patients with NAFLD cirrhosis were diagnosed incidentally, with the majority of these (74%) diagnosed with NAFLD simultaneously. Those with incidental cirrhosis diagnoses had more deranged platelet and international normalized ratio levels (P < 0.05) and were more likely to have concomitant hepatocellular carcinoma (HCC) (12% versus 0%, P < 0.05). Incidental cirrhosis was diagnosed following imaging (32%) or liver tests (26%) performed for reasons unrelated to liver disease, following unexpected endoscopic finding of varices (21%) or an unexpected surgical finding (14%). Diagnoses by intent were predominantly made by gastroenterologists/hepatologists, whereas general practitioners, surgeons, and physicians tended to diagnose cirrhosis incidentally (P < 0.001). The majority of patients diagnosed incidentally (n = 48/66, 73%) had previous thrombocytopenia, splenomegaly, or high noninvasive fibrosis scores. Following diagnosis, patients diagnosed incidentally were less likely to undergo HCC screening. Conclusion: The majority of patients with NAFLD cirrhosis are diagnosed incidentally. These patients are more likely to have advanced liver disease and HCC. Increased awareness of screening for cirrhosis is needed in patients with NAFLD. (Hepatology Communications 2017;1:53–60)

BIOMARKERS OF COAGULATION ACTIVATION IN CHILDREN WITH SICKLE CELL DISEASE

Sickle cell disease (SCD) is a multisystem disease, characterized by its multi-phenotypic diversity although being a disease caused by a single nucleotide substitution.In the present study, we measured biomarkers of coagulation activation in children with SCD. The study was performed on 50 Egyptian children with SCD and 41 age- and sex-matched controls. Complete blood picture (CBC), International normalized ratio (INR)and Partial thromboplastin time (PTT) levels were measured. Thrombin-antithrombin (TAT) plasma levels was estimated by enzyme-linked immunosorbent assay (ELISA). A statically significant increase in all of INR, PTT and TAT plasma levels were detected. We agree with the previous studies that children with SCD exhibit a hypercoagulable state.

The safety and efficacy of vitamin K antagonist in atrial fibrillation patients with previous ulcer bleeding: Long-term results from a multicenter study.

This study aimed to evaluate the safety and efficacy of vitamin K antagonist (VKA) in atrial fibrillation (AF) patients with previous ulcer bleeding.In this multicenter, retrospective analysis, clinical outcomes of 754 AF patients with a history of ulcer bleeding were evaluated. After ulcer treatment, 458 patients (61%) were treated with VKA, and the outcomes were compared to 296 patients (39%) without VKA.VKA treatment significantly increased major bleeding (7.3%/year vs 3.2%/year, P < 0.001), and reduced major adverse cardiac events (MACE) (5.4%/year vs 10.0%/year, P < 0.001). Specifically, risk of gastrointestinal bleeding was significantly higher in the VKA group than no-VKA group (5.7%/year vs 2.6%/year, P < 0.001). Consequently, there was no difference in the incidence of composite of a MACE and major bleeding, between the 2 groups. In patients with time in the therapeutic range (TTR) ≥65%, VKA significantly decreased MACE (2.8%/year vs 10.0%/year, P < 0.001) without increasing major bleeding. Net clinical benefit model showed beneficial effects of VKA in patients with TTR ≥65%, and harmful effects in those with TTR < 55%.In AF patients with previous ulcer bleeding, VKA treatment did not improve clinical outcomes unless the international normalized ratio level was constantly maintained (TTR ≥65%), as the gastrointestinal bleeding (GIB) risk significantly increased.

A Korean Multi-Center Survey about Warfarin Management before Gastroenterological Endoscopy in Patients with a History of Mechanical Valve Replacement Surgery.

BackgroundGuidelines for esophagogastroduodenoscopy (EGD) in the West allow the continued use of warfarin under therapeutic international normalized ratio (INR) level. In Korea, no guidelines have been issued regarding warfarin treatment before EGD. The authors surveyed Korean cardiac surgeons about how Korean cardiac surgeons handle warfarin therapy before EGD using a questionnaire. Participants were requested to make decisions regarding the continuation of warfarin therapy in two hypothetical cases.MethodsThe questionnaire was administered to cardiac surgeons and consisted of eight questions, including two case scenarios.ResultsThirty-six cardiac surgeons at 28 hospitals participated in the survey, and 52.7% of the participants chose to stop warfarin before EGD in aortic valve replacement patients without risk factors for thromboembolism. When the patient’s INR level was 2, 31% of the participants indicated that they would choose to continue warfarin therapy. For EGD with biopsy, 72.2% of the participants chose warfarin withdrawal, and 25% of the participants chose heparin replacement. In mitral valve replacement patients, 47.2% of the participants chose to discontinue warfarin, and 22.2% of the participants chose heparin replacement. For EGD with biopsy in patients with a mitral valve replacement, 58.3% of the participants chose to stop warfarin, and 41.7% of the participants chose heparin replacement.ConclusionThis study demonstrated that attitudes regarding warfarin treatment for EGD are very different among Korean surgeons. Guidelines specific to the Korean population are required.

Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation in Hepatitis B Virus Related Acute-on-Chronic Liver Failure Treated with Plasma Exchange and Entecavir: a 24-Month Prospective Study.

Search for an effective therapy for patients with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) remains an important issue. This study investigated the efficacy of umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation in patients with HBV-ACLF. 45 consecutive entecavir-treated HBV-ACLF patients were prospectively studied. Among these patients, 11 received both plasma exchange (PE) and a single transplantation of UC-MSCs (group A), while 34 received only PE (group B). The primary endpoint was survival at 24months. Compared with group B, levels of albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin time (PT), international normalized ratio (INR) and model for end-stage liver disease score in group A improved significantly at 4weeks after transplantation (p<0.05). Levels of albumin, PT and INR in group A were also markedly improved at 24months (p<0.05). Group A had significantly higher cumulative survival rate at 24months (54.5% v.s. 26.5%, p=0.015 by log rank test). Between the two groups, levels of creatinine, White blood cell, hemoglobin and platelet were similar. HBeAg loss and hepatocellular carcinoma incidence were similar at 24months. Group assignment (relative risk: 2.926, 95%confidence interval: 1.043-8.203, p=0.041) was an independent predictor for survival at 24months. Success rate of UC-MSC transplantation was 100% in group A. No severe adverse event was observed in any patient. UC-MSC transplantation is safe and effective for HBV-ACLF patients treated with PE and entecavir. It further improves the hepatic function and survival.

Warfarin treatment quality and prognosis in patients with mechanical heart valve prosthesis

ObjectivesTo study the impact of time in therapeutic range (TTR) and international normalised ratio (INR) variability on the risk of thromboembolic events, major bleeding complications and death after mechanical heart...

Gene polymorphisms and the risk of warfarin-induced bleeding complications at therapeutic international normalized ratio (INR)

BackgroundBleeding episodes commonly occur in patients on warfarin treatment even in those within therapeutic range of international normalized ratio (INR). The objective of this study was to investigate the effects of the 8 examined polymorphisms on the risk of bleeding complications in a sample of Iranian patients. MethodsA total of 552 warfarin treated patients who maintained on a target INR level of 2.0–3.5 for at least three consecutive intervals were enrolled from those attended our anticoagulation clinics. Ninety-two bleeding events were observed in 87 patients. The presences of the examined polymorphisms were analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). ResultsPatients with the T allele in NQO1*2 (CT or TT genotypes) had a higher risk of bleeding than patients with the CC genotype (adjusted OR: 2.25, 95% CI: 1.37 to 3.70, P=0.001). Those who were carriers of CYP2C9 one-variant haplotypes (*1/*2 or *1/*3) were also found to be associated with the higher risk of bleeding events. Compared to reference group (*1/*1), the odds of bleeding increased for carriers of one variant allele (*1/*2 or *1/*3) (adjusted OR: 1.75, 95% CI: 1.03 to 2.97, P=0.039). Variant VKORC1, Factor VII, and EPHX1 genotypes were not significantly associated with the risk of bleeding events. ConclusionThe SNP C609T within NQO1 and haplotypes of CYP2C9 (1*2 or 1*3) are independently associated to bleeding complications of warfarin at normal INR. Further studies are required to confirm such associations in diverse racial and ethnic populations.

Implementation of a Simplistic Bivalirudin-Warfarin Transition Protocol Is Associated With Improved Achievement of INR Values Within the Therapeutic Range.

Transition from bivalirudin to long-term warfarin therapy is often difficult to execute due to bivalirudin prolongation of the international normalized ratio (INR), and literature to help guide this transition is extremely limited. To assess the transition from bivalirudin to warfarin after implementation of an institution-wide transition protocol. In this retrospective quasiexperimental study, adult patients receiving bivalirudin directly followed by warfarin for nonprocedural systemic anticoagulation were evaluated to determine the frequency of successful transition to warfarin. Participants were compared before (preprotocol) and after (postprotocol) the implementation of the transition protocol. A total of 39 patients met inclusion criteria and were included in the analysis (preprotocol = 19; postprotocol = 20). The percentage of patients achieving a successful transition was significantly higher in the postprotocol group compared with the preprotocol group (80.0% vs 42.1%, P = 0.015). Bleeding events were similar between the 2 groups (23.1% vs 16.7%, P = 0.689). Withholding of warfarin doses or the use of anticoagulant reversal agents or blood transfusions for supratherapeutic INR levels, surgical procedures, or drop in hemoglobin was numerically lower in the postprotocol group compared with the preprotocol group (16.7% vs 46.2%, P = 0.202). Implementation of a simplistic bivalirudin-warfarin transition protocol significantly increased the frequency of therapeutic INR results on bivalirudin discontinuation. Additionally, patients treated according to this protocol were less likely to have warfarin doses withheld or require reversal agents. Larger studies testing this transition strategy are warranted.

Seasonal variation in the international normalized ratio of neonates and its relationship with ambient temperature.

BackgroundThe morbidity and mortality rates due to cardiovascular events such as myocardial infarction are known to exhibit seasonal variations. Moreover, changes in the ambient temperature are reportedly associated with an increase in these events, which may potentially involve blood coagulation markers. Bleeding due to vitamin K deficiency in neonates, which is associated with high mortality and a high frequency of neurological sequelae, is more commonly observed during the summer season and in warm regions in Japan. To determine the presence of seasonal variation and the influence of ambient temperature on blood coagulation markers in healthy term neonates, we assessed the international normalized ratio (INR) values measured using CoaguChek XS.MethodsWe studied 488 consecutive healthy term neonates who were born at a perinatal center between July 2012 and June 2013. The INR values were measured using CoaguChek XS in 4-day-old neonates who received nursing care in the newborn nursery throughout the duration of hospitalization. The seasonal variations in the INR values and environmental effects on the INR were assessed.ResultsThe mean monthly INR values peaked in July (1.13 ± 0.08), whereas the lowest values were observed in January (1.05 ± 0.08). Higher levels of INR were observed during the summer season (June to August) than during the winter season (December to February). Simple linear regression analysis indicated the presence of weakly positive but significant correlations between INR and outdoor temperature (r = 0.25, p < 0.001), outdoor relative humidity (r = 0.19, p < 0.001), and room relative humidity (r = 0.24, p < 0.001), and the presence of a significant negative correlation between INR and room temperature (r = −0.13, p = 0.02). Furthermore, multiple linear regression analysis showed that only outdoor temperature significantly influenced the INR.ConclusionsA seasonal variation in the INR values was observed among neonates, possibly due to the variation in ambient temperature. Even though the neonates received nursing care in the newborn nursery that was constantly air-conditioned, the outdoor temperature was the most influential factor on INR.

Intraperitoneal Hemorrhage in a Peritoneal Dialysis Patient Using Dabigatran: A Case Report

Dabigatran is used for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. It is still unclear whether the use of dabigatran leads to more bleeding compared with warfarin. In this paper, we present a case of intraperitoneal hemorrhage in a 54-years-old male peritoneal dialysis patient using dabigatran for paroxysmal atrial fibrillation because international normalized ratio level could not be kept at target levels during follow-up. The use of dabigatran in atrial fibrillation has become widespread in recent years. Despite the low risk of intracranial hemorrhage, clinicians should be careful in patients with chronic kidney disease because coagulation monitoring is not possible.

Therapeutic Review of Methylprednisolone Acetate Intra-Articular Injection in the Management of Osteoarthritis of the Knee - Part 2: Clinical and Procedural Considerations.

The use of an intra-articular methylprednisolone acetate (MPA) injection has been shown to have benefits for symptoms of knee osteoarthritis (OA). However, considerations beyond drug efficacy can influence the appropriateness, clinical effectiveness and potential harm of an injection. A review of research evidence and published literature on clinical and procedural factors influencing the effectiveness and safety of a knee injection has been undertaken. Factors include dose, frequency, contraindications, precautions, drug interactions, side-effects, and procedural and patient-related considerations. An evaluation of evidence indicated that a 40 mg dose provides clinical benefit. No strong predictors of response were evident, with the exception of pain severity. Additional benefit for outcomes from higher doses, local anaesthetic, ultrasound guidance or particular anatomical approaches is yet to be demonstrated. Evidence for dose- and duration-related detrimental effects suggests judicious use and frequency. The evaluation showed that there are a number of contraindications and precautions arising from the drug pharmacology, concurrent medications, comorbidities and adverse events which need consideration and monitoring. There was limited safety evidence concerning anticoagulation. The review found that specialist guidance and limited evidence suggests that injection safety concerning warfarin may be enhanced by ensuring that the international normalized ratio level is within therapeutic range. However, the risk-benefit evaluation concerning non vitamin K antagonist oral anticoagulants remains challenging. Although there is published guidance, a lack of clinical studies, safety evidence and reversibility advocates caution. Overall, the review indicates that injection decisions and procedures need an individualized approach and supporting evidence is limited in many areas. Evaluation and discussion of benefits and risks, peri-procedural and post-injection management, and tailoring to the context and individuals' preferences are important in optimizing the benefits and safety of a knee injection.

Prolonged effects of miconazole oral gel on warfarin anticoagulation even after treatment withdrawal.

We investigated the effect of terminating miconazole oral gel (MOG) treatment on the anticoagulant activity of warfarin by evaluating changes in international normalized ratio levels (INR). Data were collected from the medical records of 6 patients treated with warfarin and MOG. Following cessation of MOG treatment, increased INR and INR/dose levels were observed for an average of 15 days, showing that the anticoagulant activity of warfarin was increased for ~ 2 weeks. Closer monitoring of INR levels for at least 2 weeks may be required upon withdrawal of MOG treatment in patients treated with warfarin.

Diagnostic criteria for HBV-related acute-on-chronic pre-liver failure

To investigate the diagnostic criteria for HBV-related acute-on-chronic pre-liver failure (pre-ACLF) which can effectively predict the risk of liver failure. A total of 1279 patients with severe icteric chronic hepatitis B (CHB) and/or severe acute exacerbation of CHB were enrolled. The influence of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil), international normalized ratio (INR) of prothrombin time, sex, and age on the incidence rate of acute-on-chronic liver failure (ACLF) was analyzed, the diagnostic criteria for pre-ACLF and predictive model for ACLF were developed. The chi-square test was used for comparison of categorical variables, and the independent samples t-test was used for continuous data; multivariate logistic regression analysis was performed to evaluate the risk of liver failure. The baseline serum levels of ALT, AST, and TBil, and INR were independent risk factors for liver failure (P < 0.05). The diagnostic criteria for pre-ACLF were as follows: (1) INR≥1.30; (2) AST≥10×upper limit of normal (ULN) and obvious jaundice (TBil≥51.3 μmol/L), or TBil≥342.0 μmol/L. These criteria had a positive predictive value of 45.9%, a negative predictive value of 89.8%, a sensitivity of 69.1%, and a specificity of 76.9%. The predictive model for the risk of ACLF was PY = 1=e(X)/(1+e(X)) (PY represented positive results of logistic regression analysis), X = -10.245+0.026×AST(ULN)-0.025×AST(ULN)+0.046×TBil(mg/dl) + 4.642×INR+0.049×age(years). The patients with higher PY values tended to have a higher incidence rate of ACLF. The incidence rate of ACLF was 75.3% in patients with PY≥0.60, more than 50% in patients with a PY value of 0.40-0.59, and 1.8% in patients with PY < 0.10 (P < 0.01). The diagnostic criteria for pre-ACLF and predictive model can effectively evaluate the risk of HBV-related ACLF.

The importance of MELD after liver transplantation to predict early allograft dysfunction

Early allograft dysfunction (EAD) is a serious complication of liver transplantation (LT). EAD is often multifactorial and The Model for End-Stage Liver Disease (MELD) has the unique ability to incorporate many variables and reflect the overall status of the graft. The MELD score is estimated based on the following variables: creatinine level, total bilirubin level and International normalized ratio (INR). The MELD score is extensively used preoperatively but little is known about the course of the MELD score after LT. The aim of this study was to demonstrate the ideal cut off MELD score for predicting early graft failure in order to re-list the patient as soon as possible. In this single-center, retrospective study, the INR, total bilirubin and creatinine levels were used to calculate the MELD scores within 7 days after LT for a 100 patients. Aspartame aminotransferase (AST) and alkaline phosphatase (ALT) within 7 days after LT were also measured and used as parameters to predict allograft dysfunction.

The effect of carbamazepine on warfarin anticoagulation: a register‐based nationwide cohort study involving the Swedish population

There are data indicating that the interaction between warfarin and carbamazepine results in decreased warfarin efficacy. However, the evidence on the magnitude of and interindividual differences in susceptibility to this interaction has remained scarce. To investigate the effect of carbamazepine on warfarin anticoagulation and warfarin maintenance doses by the use of data from three nationwide registries. In a retrospective cohort study including 166 patients, warfarin doses were compared 2-4 weeks before and 10-13 weeks after initiation of cotreatment with carbamazepine. In addition, warfarin doses and International Normalized Ratio (INR) values were calculated week-by-week during cotreatment. Data on prescribed warfarin doses and INR measurements were obtained from two large Swedish warfarin registers. Data on carbamazepine use were retrieved from the Swedish Prescribed Drug Register. The average warfarin doses were 49% (95% confidence interval 43-56) higher during carbamazepine treatment. The INR decreased upon carbamazepine initiation, and subtherapeutic INR levels were observed in 79% of all patients during the fifth week of cotreatment. Warfarin maintenance dose increases exceeding 50% and 100% were observed in 59% and 17% of patients, respectively. Four of five warfarin-treated patients in whom cotreatment with carbamazepine was initiated experienced subtherapeutic anticoagulative effect within 3-5 weeks. The warfarin dose was subsequently increased by 49%, a change that differed widely between patients. In order to avoid thrombosis and ischemic stroke, carbamazepine initiation should be accompanied by close INR monitoring to better meet the anticipated increase in dose demand.

Should We Use Bridging Therapy during Switching Patients from Warfarin to Novel Oral Anticoagulants?

Rivaroxaban is a new anticoagulant that was approved by the Food and Drug Administration in 2011 for stroke and systemic embolism prophylaxis in patients with nonvalvular atrial fibrillation. Several characteristics have made rivaroxaban an attractive alternative to warfarin: once-daily dosing, obviating the need for monitoring the international normalized ratio (INR), noninferiority to warfarin for preventing stroke in patients with atrial fibrillation, and comparatively lower risk of intracranial hemorrhage. Both The European Summary of Product Characteristics and the US Prescribing Information recommend to discontinue warfarin and to start rivaroxaban on the following day if the initial INR level is below 3.0, yet many clinics convert patient from warfarin to rivaroxaban when INR level is <2.0 due to increased risk of hemorrhage. Since there are no conventional coagulation measures to reliably demonstrate the level of anticoagulation in patients on rivaroxaban, there is an increased risk of adverse events, especially for patients with high ischemic burden. We report a case of acute ischemic stroke in a patient who switched from warfarin to rivaroxaban (20 mg once daily). A 68-year-old female patient with multiple co-morbidities was admitted to our clinic with ischemic stroke. After 1 week follow-up with parenteral anticoagulation in the neurology clinic, she was discharged with mild deficits and with dabigatran treatment (150 mg twice daily). Novel oral anticoagulants are attractive options for anticoagulation particularly in patients who are incompatible with warfarin therapy. On the other hand, physicians should be alert during switching patients from warfarin to novel oral anticoagulants.

Anticoagulation in Patients With Cirrhosis

To review current literature for anticoagulation in patients with cirrhosis and provide a summary of the effects of cirrhosis on the coagulation cascade, therapeutic monitoring through interpretation of antifactor Xa (anti-Xa), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) as well as current prophylaxis and treatment recommendations in cirrhotic patients. A systematic electronic literature search was conducted in PubMed using the key termsanticoagulation, warfarin, low-molecular-weight heparin(LMWH),unfractionated heparin(UFH),target-specific oral anticoagulants, deep-vein thrombosis(DVT),pulmonary embolism(PE),portal vein thrombosis(PVT),venous thromboembolism, anti-Xa, activated partial thromboplastin time, anticoagulation therapeutic monitoring, coagulopathy, coagulation cascade, chronic liver disease, cirrhosis, anddecompensated liver disease Studies written in the English language from January 2000 to December 2015 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by authors independently. Patients with cirrhosis are at higher risk for both bleeding and thrombosis-related complications. Cirrhosis affects production of both procoagulant and anticoagulant factors, thus resulting in increased INR and aPTT levels and decreased anti-Xa levels. LMWH is the treatment of choice for the prevention and treatment of DVT/PE/PVT in patients with cirrhosis, and monitoring with anti-Xa levels for dose adjustment is not recommended. UFH is an alternative in cirrhotic patients for shorter-term use and in cases of severe renal dysfunction and/or hemodynamic instability. Cirrhotic patients on anticoagulation therapy should be monitored closely for signs and symptoms of bleeding and thrombosis.

Quality of anticoagulation therapy in neurological patients in a tertiary care hospital in north India.

Background & objectives:There is paucity of studies on the quality of anticoagulation in neurological patients from India. This study evaluates the quality of oral anticoagulation therapy in neurology patients.Methods:Consecutive patients attending a tertiary care neurology service in north India who were prescribed oral anticoagulant (OAC), were included. Their international normalized ratio (INR) values were prospectively monitored and the earlier INR values of the patients who were already on OAC were retrospectively analyzed. The patients with multi-organ dysfunction, pregnancy and those below 18 yr of age were excluded. The therapeutic INR range was defined as per standard recommendations. The level of anticoagulation, factors interfering with OAC and complications were noted.Results:The results were based on 77 patients with median age 40 yr. Fifty one patients received OAC for secondary stroke prevention, 23 for cerebral venous sinus thrombosis (CVST) and three for deep vein thrombosis (DVT). A total 167.9 person-years of follow up was done with a median of 1.2 (0.3-9.3) years. Of the 1287 INR reports, 505 (39.3%) reports were in the therapeutic range, 496 (38.5%) were below and 282 (21.91%) were above the therapeutic level. Stable INR was obtained in 33 (42.86%) patients only. INR level was improved by dose adjustment in 20 (26%), drug modification in two (2.6%), and dietary adjustment in six (7.8%) patients. Three patients were sensitive and five were resistant to OAC. Complications were noted in 28 instances; thromboembolic in 16 and haemorrhagic stroke in 12. The overall complication rate was 16.7 per 100 person-years.Interpretation & conclusions:It may be concluded that stable therapeutic INR is difficult to maintain in neurological patients. Optimal modification of diet, drug and dose of oral anticoagulant may help in stabilization of INR.

Warfarin- and aspirin-associated fetal intracranial haemorrhage

Warfarin can cross the placental barrier and can cause perinatal intraventricular haemorrhage irrespective of maternal INR (international normalized ratio) level. The prevalence of perinatal intraventricular haemorrhage related to maternal warfarin is 4.6– 5.1% in autopsy studies of stillbirth. Previously reported cases of warfarin-associated fetal intracranial haemorrhage in pregnant women with a mechanical heart valve are shown in Table 1. This is a case report of a neonate who experienced perinatal intraventricular haemorrhage related to maternal warfarin.

A novel point for warfarin usage in ACCP Guidelines, 2012 and its importance for quality of anticoagulation. Commentary on the article by Dr. Ciurus et al. (Kardiochir Torakochir Pol 2015; 12 (4): 334-340).

We have read with great interest the article about the factors affecting the quality of anticoagulation with warfarin by Ciurus et al. [1]. The authors implicate the importance of predictors of controlling the anticoagulation. They aim to assess the quality of anticoagulant therapy in patients on warfarin and evaluate the factors affecting its deterioration. We thank the authors for their well-designed study. Regarding the current guidelines concerning anticoagulant therapy, we detected some contradictory and overlooked points that should be highlighted. We want to make some contributions to the report by Ciurus et al. [1] about the warfarin usage introduction update and education change according to current guidelines. Despite the presentation of new anticoagulants, vitamin K antagonists (VKA) still maintain their importance in clinical administration [2]. Unfortunately, this wide use of VKA is still associated with a wide spectrum of complications. Particular concerns have been raised regarding prevention of these complications. As one of them, the Ciurus et al. emphasized that maximizing the time in the optimum therapeutic range has great importance for avoiding adverse clinical outcomes [1]. To attain this goal, controlling the patient-specific factors such as adherence to the therapeutic plan, appropriate dosing, and reliable international normalized ratio (INR) control are very important. Among such patient-related factors, the feeding habit of the patients is a special issue. Many doctors and patients remember the wide VKA interaction food list containing dietary vitamin K. It has been a frequent practice to limit or alter dietary habits of the patients according to those food lists. But this clinical advice has been changed by the American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines, 2012 [3]. It is suggested in the abovementioned document that limitations of diet deteriorate the therapeutic INR levels. Because most people have long-lasting dietary habits, which are very difficult to change, attempts to change any dietary habit may result in uncontrolled alterations of oral vitamin K intake, resulting in difficulties sustaining the therapeutic INR levels. The ACCP guidelines recommend that “A consistent intake of vitamin K-containing foods is advisable, but neither specific restrictions nor additions seem necessary in patients with stable anticoagulant control. Patients should be informed of possible changes in INR, in particular in response to the use of dietary supplements or herbs, or alcohol used chronically or ingested in large quantities.” The authors reported that, “The participants were informed about the diet limitations required in order to improve the effectiveness of the anticoagulant therapy.” Although this suggestion is valid for attaining a therapeutic level, it is very difficult to maintain this level in therapeutic doses. That is why we think the ACCP guidelines made a modification on warfarin use in 2012, which we cannot see in the previous guidelines from 2008 [4]. We also agree with the suggestion that the patient should be informed about the food and drug interactions but no suggestion should be made on limiting dietary intake, in order to maintain therapeutic INR levels.