Prolonged International Normalized Ratio Research Articles

Effect of High Altitude Environment on Pharmacokinetic and Pharmacodynamic of Warfarin in Rats.

High altitude environment affects the pharmacokinetic (PK) parameters of drugs and the PK parameters are an important theoretical basis for guiding the rational clinical use of drugs. Warfarin is an oral anticoagulant of the coumarin class commonly used in clinical practice, but it has a narrow therapeutic window and wide individual variation. However, the effect of high altitude environment on PK and pharmacodynamic (PD) of warfarin is unclear. The objective of this study is to investigate the effect of a high altitude environment on PK and PD of warfarin in rats. Rats were randomly divided into plain group and high altitude group and blood samples were collected through the orbital venous plexus after administration of 2 mg/kg warfarin. Warfarin concentrations in plasma samples were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and PK parameters were calculated by the non-compartment model using WinNonlin 8.1 software. Meanwhile, the expression of PXR, P-gp and CYP2C9 in liver tissues was also determined by western blotting. The effect of high altitude environment on PD of warfarin was explored by measuring activated partial thromboplastin time (APTT) and prothrombin time (PT) values and then calculated international normalized ratio (INR) values based on PT. Significant changes in PK behaviors and PD of warfarin in high altitude-rats were observed. Compared with the plain-rats, the peak concentration (Cmax) and the area under the plasma concentration-time curve (AUC) increased significantly by 50.9% and 107.46%, respectively. At the same time, high altitude environment significantly inhibited the expression of PXR, P-gp and CYP2C9 in liver tissues. The results of the PD study showed that high altitude environments significantly prolonged PT, APTT and INR values. High altitude environment inhibited the metabolism and increased the absorption of warfarin in rats and increased the effect of anticoagulant effect, suggesting that the optimal dose of warfarin for patients at high altitude should be reassessed.

Liver dysfunction in children with scrub typhus: association with severity of illness and outcome

Background: Liver dysfunction is a common finding in children with scrub typhus. Adult literature has found a significant association between the extent of liver dysfunction and severity of illness and outcome. However, very few studies are available on children.Objectives: To study the extent of liver dysfunction in children with scrub typhus and its association with severity of illness and outcome.Method: It was a retrospective descriptive study conducted on children diagnosed with scrub typhus admitted to a tertiary care centre in south India from January 2016 to December 2020. Children from 1 month to 18 years of age were included. Demographic data, clinical details, laboratory parameters, course of illness and outcome data were collected and analysed. Results: Study population included 143 cases of scrub typhus. Mean age of the study population was 8.4 ± 4.4 years with a male: female ratio of 1.2:1. Fever was present in 100%, myalgia in 54.5%, decreased appetite in 54.5%, jaundice in 8.4% and hepatomegaly in 71.3% of children. Abnormal liver function tests were present in 75.5% children. Elevated aspartate transaminase (AST) was seen in 75.5%, elevated alanine transaminase (ALT) in 67.1%, hypoalbuminaemia in 47.5% and severe hypoalbuminaemia (<2.5g/dL) in 29.4%. Complications included meningitis (13.3%), shock (7.6%), meningoencephalitis (2.7%) and acute respiratory distress syndrome (2%). There were 2 (1.3%) deaths. Children with complications had higher AST (p <0.01), ALT (p = 0.018), low serum albumin (p<0.001) and prolonged international normalised ratio (INR) (p =0.003).Conclusions: Abnormal liver function tests were present in 75.5% of children with scrub typhus. Children with complications of scrub typhus had significantly higher median AST levels, ALT levels, low serum albumin levels and prolonged INR compared to children with no complications

Poor Correlation of Rivaroxaban Concentration with the Routine Coagulation Screening Test in Chinese Patients with Atrial Fibrillation

Aims. The aim of this study is to assess the relationship between rivaroxaban plasma concentration quantified by the gold standard and anticoagulant activities measured by routine coagulation assays in Chinese atrial fibrillation (AF) patients. Whether the normal results of these tests were reliable to rule out clinically relevant rivaroxaban levels at various thresholds was also explored. The effect of clinical drug-drug interactions (DDIs) on the exposure and anticoagulant effect of rivaroxaban were further evaluated. Methods. 116 patients receiving rivaroxaban for the management of nonvalvular AF were recruited. Rivaroxaban concentrations and coagulation tests were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and a blood coagulation analyzer, respectively. Results. The correlation of trough concentration (Ctrough) and prothrombin time (PT) or international normalized ratio (INR) was moderate with Spearman’s correlation coefficient of 0.495 and 0.506, respectively. A normal PT/INR was unable to rule out Ctrough levels of >30 ng/mL and >50 ng/mL, but the negative predictive value reached 100% to exclude Ctrough of >100 ng/mL. Ctrough showed a small correlation with activated partial thromboplastin time (aPTT) (Spearman’s correlation coefficient: 0.241) and no correlation with thrombin time (TT) (Spearman’s correlation coefficient: 0.074). Neither aPTT nor TT accurately predicted Ctrough at any concentration. Peak concentration (Cpeak) did not correlate with any coagulation parameters. The presence of digoxin and febuxostat significantly increased rivaroxaban Ctrough by 2.18 fold and prolonged PT and INR by 44.16% and 43.60%, respectively. Conclusions. Normal routine coagulation assays were insufficient to monitor therapy with rivaroxaban. Poor correlations between rivaroxaban concentration and routine coagulation assays were observed in Chinese AF patients. The use of digoxin/febuxostat alone had no effect on rivaroxaban concentrations; however, combined strong breast cancer resistance protein inhibitor (febuxostat) and P-glycoprotein probe (digoxin) in patients with renal impairment is likely to cause clinically significant DDI with rivaroxaban. More studies are needed to establish routine therapeutic drug monitoring of rivaroxaban in clinical practice.

Overt and Massive Spontaneous Subconjunctival Hemorrhage on a Patient with Prolonged International Normalized Ratio on Therapeutic Warfarin: A Case Report.

Overt and Massive Spontaneous Subconjunctival Hemorrhage on a Patient with Prolonged International Normalized Ratio on Therapeutic Warfarin: A Case Report.

Hypocoagulability in Children With Decompensated Chronic Liver Disease and Sepsis: Assessment by Thromboelastography.

To evaluate the coagulation status of children with decompensated chronic liver disease (DCLD) and infection and factors affecting it using thromboelastography (TEG). Coagulation status of children admitted with DCLD and infection was assessed by international normalized ratio (INR), platelet count, and TEG [reaction time (R), kinetic time (K), α-angle (AA), maximum amplitude (MA), coagulation index (CI), and lysis index (LY30)] at admission and at 7-14 days after treatment. CI < -3 represents hypocoagulable state. Clinical profile including systemic inflammatory response syndrome (SIRS), infection severity, bleeding, treatment response, and outcome were noted. Thirty children (21 boys, median (IQR) age 78 [15.7-180] months) were studied prospectively. At admission, 29 (96.7%) had prolonged INR, 24 (80%) had thrombocytopenia, and 17 (56.6%) were hypocoagulable by TEG. Nine of 30 (30%) had normal TEG but deranged INR and platelets. Nineteen (63.3%) cases had SIRS, 11 (36.6%) had severe sepsis, and 8 (26.6%) had bleeding. Hypocoagulable state was common in severe sepsis than sepsis/infection (81.1% versus 42.1%; P = 0.05) and persistent (n = 4) versus recovered SIRS (n = 15, 100% versus 33%; P = 0.03). Bleeders had prolonged R-time (7.8 versus 5.4 min; P = 0.03), smaller MA (30.2 versus 47 mm; P = 0.05), and α-angle (40.4 versus 62.9; P = 0.03) but similar INR and platelets than nonbleeders. Six patients (20%) had poor in-hospital outcomes; R-time ≥8.5 min predicted mortality with high sensitivity (83%) and specificity (100%). Fifth-seven percent of children with DCLD and infection were hypocoagulable by TEG. Severe sepsis and persistent SIRS worsened the coagulation status. TEG identifies bleeders better than INR and platelet count. R-time ≥8.5 min predicts a poor hospital outcome.

Deficiency of coagulation factors is associated with the bleeding diathesis of severe yellow fever.

Yellow fever (YF) is an acute tropical infectious disease caused by an arbovirus and can manifest as a classic hemorrhagic fever. The mechanism of the bleeding diathesis in YF is not well understood. We assessed clinical and laboratory data (including a panel of coagulation tests) from 46 patients with moderate (M) and severe (S) YF admitted to a local hospital between January 2018 and April 2018. Among 46 patients, 34 had SYF of whom 12 (35%) patients died. A total of 21 (45%) patients developed some type of bleeding manifestation and 15 (32%) presented severe bleeding. Patients with SYF had more severe thrombocytopenia (p = 0.001); prolonged activated partial thromboplastin time (aPTT) and thrombin time (TT) (p = 0.03 and p = 0.005, respectively); reduced plasma levels of coagulation factor (F) II (p < 0.01), FIX (p = 0.01), and FX (p = 0.04); and D-dimer levels almost 10 times higher (p < 0.01) when compared with patients with MYF. Patients who died had more bleeding (p = 0.03), more major bleeding (p = 0.03), prolonged international normalized ratio (INR) and aPTT (p = 0.003 and p = 0.002, respectively), as well as lower activity of FII (p = 0.02), FV (p = 0.001), FVII (p = 0.005), FIX (p = 0.01), and protein C (p = 0.01) than the ones who survived. FVIII levels were either normal or increased in all patients studied. Our results suggest that the bleeding diathesis of SYF is associated with the deficiency of coagulation factors produced by the liver. Prolonged INR and aPTT and reduced FII, FV, FVII, FIX, and protein C were associated with death.

Clinically relevant increases in the international normalized ratio and model of end-stage liver disease score by therapeutic doses of direct oral anticoagulants in patients with cirrhosis

BackgroundPatients with cirrhosis are increasingly using direct oral anticoagulants (DOACs) in therapeutic doses for the treatment of portal vein thrombosis or for concomitant atrial fibrillation. DOACs may affect routine diagnostic tests of coagulation including the international normalized ratio (INR). The INR is a part of the model of end-stage liver disease (MELD) score, a validated score that predicts the mortality risk in patients with cirrhosis and is used to prioritize patients for liver transplantation. DOAC–induced increases in the INR may thus lead to artificial inflation of the MELD score. ObjectiveWe studied the effect of DOACs on INR prolongation in patients with cirrhosis. MethodsWe spiked plasma from 20 healthy individuals and 20 patients at the start of liver transplantation with DOACs in concentrations representing peak therapeutic levels. In addition, we studied INR increases in healthy controls and patients with mild cirrhosis who received the DOAC edoxaban for 1 week for study purposes. ResultsIn controls and patients, the INR increased by an ex vivo addition of a DOAC, and the INR increase in patients was proportional to the baseline INR values. The increase in INR translated to a median increase of between 3 and 10 MELD points, depending on the DOAC used. In controls and patients alike, the INR increased on the ingestion of edoxaban, which translated to an increase in 5 MELD points. ConclusionsTaken together, DOACs result in an INR increase that translates to clinically meaningful increases in MELD points in patients with cirrhosis, and precautions to avoid artificial inflation of the MELD score in these patients are warranted.

Cefazolin-Associated INR Elevation: A Case Report

Purpose: To describe a case of significantly elevated international normalized ratio (INR) in a patient on apixaban receiving treatment with intravenous cefazolin in the setting of coronavirus disease 2019 (COVID-19) infection and malnutrition. Summary: A 74-year-old male patient on apixaban receiving cefazolin for osteomyelitis in the setting of COVID-19 and poor nutritional intake presented with internal jugular tunneled catheter site bleeding and an INR of greater than 22.5. Laboratory abnormalities and bleeding concerns were successfully managed with vitamin K and changing antimicrobial therapy from cefazolin to daptomycin. Follow-up labs one week later demonstrated a sustained improvement in coagulopathy. Conclusion: INR prolongation believed to be secondary to cefazolin can be effectively managed with administration of vitamin K and conversion of antimicrobial therapy to an alternative agent.

SARS-COV-2-INDUCED COAGULOPATHY DEMONSTRATING HEMORRHAGIC CARDIAC TAMPONADE: A TIGHT SQUEEZE

SARS-COV-2-INDUCED COAGULOPATHY DEMONSTRATING HEMORRHAGIC CARDIAC TAMPONADE: A TIGHT SQUEEZE

Risk factors associated with repeated epidural blood patches using autologous blood.

BackgroundAn epidural blood patch (EBP) is a procedure to treat intracranial hypotension that does not respond to conservative treatment. EBPs are commonly repeated when the symptoms persist. In this study, we used a large single-center retrospective cohort and evaluated the factors associated with repeated EBPs.MethodsFrom January 2010 to December 2020, a total of 596 patients were treated with EBPs for intracranial hypotension. We evaluated the factors associated with repeated EBPs in the entire population, in patients with spontaneous intracranial hypotension (SIH), and in those with available myelographies.ResultsIn a total of 596 patients, 125 (21.1%) patients required repeated EBPs, and 96/278 (34.5%) in SIH and 29/314 (9.2%) in iatrogenic population. In patients with SIH, international normalized ratio (INR) and cerebrospinal fluid (CSF) leakage on myelographies consistently exhibited significant associations (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.02–1.87; P = 0.043 and OR, 2.18; 95% CI, 1.28–3.69; P = 0.004). In patients with iatrogenic injury, INR and CSF leakage on myelogram did not show difference in repeated EBPs.ConclusionsRepeated EBPs may be more frequently required in patients with SIH. Prolonged INR and CSF leakage were associated with repeated EBPs in patient with SIH. Further studies are needed to determine factors associated with repeated EBP requirements.

INR and COVID-19 severity and mortality: A systematic review with meta-analysis and meta-regression

ObjectivesD-dimer elevations, suggesting a pro-thrombotic state and coagulopathy, predict adverse outcomes in coronavirus disease 2019 (COVID-19). However, the clinical significance of other coagulation markers, particularly the international normalized ratio (INR), is not well established. We conducted a systematic review and meta-analysis of the INR in COVID-19. MethodsA literature search was conducted in PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting INR values, measures of COVID-19 severity, and mortality (PROSPERO registration number: CRD42021241468). ResultsThirty-eight studies in 7440 COVID-19 patients with low disease severity or survivor status during follow up (50 ​% males, mean age 57 years) and 2331 with high severity or non-survivor status (60 ​% males, mean age 69 years) were identified. The INR was significantly prolonged in patients with severe disease or non-survivor status than in patients with mild disease or survivor status (standard mean difference, SMD, 0.60; 95 ​% confidence interval, CI 0.42 to 0.77; p ​< ​0.001). There was extreme between-study heterogeneity (I2 ​= ​90.2 ​%; p ​< ​0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. The Begg's and Egger's t-tests did not show publication bias. In meta-regression, the SMD of the INR was significantly associated with C-reactive protein (p ​= ​0.048) and D-dimer (p ​= ​0.001). ConclusionsProlonged INR values were significantly associated with COVID-19 severity and mortality. Both INR prolongation and D-dimer elevations can be useful in diagnosing COVID-19-associated coagulopathy and predicting clinical outcomes.

Blood coagulation parameter abnormalities in hospitalized patients with confirmed COVID-19 in Ethiopia.

Coagulopathy and thromboembolic events are among the complications of Corona Virus disease 2019 (COVID-19). Abnormal coagulation parameters in COVID-19 patients are important prognostic factors of disease severity. The aim of this study was to analyze coagulation profiles of hospitalized COVID-19 patients in Addis Ababa, Ethiopia. This prospective cross-sectional study was conducted among 455 Covid-19 patients admitted at Millennium COVID-19 care and treatment center, Addis Ababa, Ethiopia from July 1- October 23, 2020. Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and International normalized ratio (INR) were determined on HUMACLOT DUE PLUS® coagulation analyzer (Wiesbaden, Germany). In all statistical analysis of results, p<0.05 was defined as statistically significant. A prolonged prothrombin time was found in 46.8% of study participants with COVID-19 and a prolonged prothrombin time and elevated INR in 53.3% of study subjects with severe and 51% of critically COVID patients. Thrombocytopenia was detected in 22.1% of COVID-19 patients. 50.5% and 51.3% of COVID-19 patients older than 55 years had thrombocytopenia and prolonged APTT respectively. In this study, prolonged prothrombin time and elevated INR were detected in more than 50% of severe and critical COVID-19 patients. Thrombocytopenia and prolonged APTT were dominant in COVID-19 patients older than 55 years. Thus, we recommend emphasis to be given for monitoring of platelet count, PT, APTT and INR in hospitalized and admitted COVID-19 patients.

Comparison of rotational thromboelastometry parameters with 20-minute whole blood clotting test as a predictor of envenoming in Russell's viper bite patients.

Coagulopathy is an important and common systemic clinical syndrome caused by snake envenoming. The major clinical effect of Russell's viper (RV) envenoming is haematotoxicity. The 20-min whole blood clotting test (WBCT20) is the standard test for identification of envenoming in resource-limited settings. However, its reliability as a diagnostic test has been questioned. Rotational thromboelastometry (ROTEM) assays different phases of clot formation from initiation to fibrinolysis. Our objective was to compare parameters of ROTEM with WBCT20 and the international normalized ratio (INR) as predictors of envenoming in RV bite patients. Fifty-three patents with RV bite presenting to Anuradhapura Hospital, Sri Lanka were recruited. Epidemiological and clinical data were obtained. Venous blood samples were collected at admission for ROTEM, INR and WBCT20. A total of 46 of 53 patients with RV bites received antivenom serum (AVS); 74% had a non-clottable WBCT20. All 46 had at least one abnormal ROTEM parameter and 93% had a prolonged EXTEM clotting time (EXTEM-CT). The sensitivity of a prolonged INR was only 55%. EXTEM-CT is a better predictor of envenoming and the need for AVS than WBCT20 in RV bites (p=0.02). It provides a numerical value that can be used post-AVS to objectively assess the response and decide on further treatment.

Comparisons of Radiological and Clinical Characteristics between Traumatic and Non-traumatic Subdural Hematoma Patients.

ObjectiveSubdural hematoma (SDH) primarily occurs in elderly patients. While most patients have good prognosis, some do not. Hematoma recurrence is one of the factors influencing prognosis. Moreover, some characteristic radiological factors may increase the recurrence rate. The aim of this study was to investigate whether the presence of trauma influenced radiological characteristics and hematoma recurrence in SDH patients treated with burr hole trephination.MethodsFrom January 2012 to December 2014, we selected 83 patients diagnosed with unilateral SDH using computed tomography and/or magnetic resonance imaging. We divided the patients into 2 groups based on the presence of trauma. We compared the 2 groups with multiple parameters, such as patient factors, radiological characteristics, and recurrence rate.ResultsPatients who had a prolonged international normalized ratio (INR) were significantly more common in the non-traumatic SDH group (22.2%:55.2%, p=0.002). There was no statistical difference in radiological parameters between the 2 groups. The recurrence rate was marginally higher in the non-traumatic SDH group (14.8%:17.2%, p=0.502), but this difference was not statistically significant.ConclusionThere were no statistically significant differences in the radiological findings, including brain atrophy, hematoma density, thickness of hematoma, and degree of midline shifting between the 2 groups. The associated trauma history may not influence recurrence. Anticoagulants medication influence INR prolongation, and commonly shown in non-traumatic group, but not statistically. INR prolongation was statistically more common in non-traumatic SDH patients than in traumatic SDH patients. INR prolongation is only a different characteristic between 2 groups.

The effect of warfarin administration on platelet aggregation.

The aim of this study was to assess the effect of anticoagulation treatment on platelet aggregation. The study group consisted of 24 patients on long-term warfarin therapy without any antiaggregation therapy. Platelet aggregation was measured using VerifyNow with arachidonic acid (AA) as an inducer in 23 patients and with light transmission aggregometry (LTA) in 19 patients using four different agonists. All patients had their international normalized ratio (INR) checked regularly. The mean INR value was 2.07 (SD 0.6). The average aggregation measured by VerifyNow was found to be 637.5 (SD 36.6) aspirin reaction units. The values of average aggregability in LTA were 73.3 % (SD 4.5 %), 73.2 % (SD6 %) and 72.1 % (SD 4.8 %) in case of aggregation induced by AA, ADP, and collagen, respectively. Epinephrine‑induced aggregability was 65.3 % (SD 14.7 %). Regression analysis between INR and values of collagen- or epinephrine‑induced aggregability (r = 0.654 and 0.575) was found statistically significant (p = 0.004 and 0.016); every increase in INR by 0,1 brings about an increase in collagen- and epinephrine‑induced aggregation values by 1.5 and 4, respectively. Administration of warfarin does not produce a significant reduction in platelet aggregation. On the contrary, prolonged INR evokes a mild increase in aggregation induced by collagen or epinephrine (Tab. 2, Fig. 3, Ref. 32). Text in PDF www.elis.sk Keywords: platelet aggregation, anticoagulation, warfarin, platelet function tests, chronic ischemic heart disease.

Hemostatic Balance in Pediatric Acute Liver Failure: Epidemiology of Bleeding and Thrombosis, Physiology, and Current Strategies.

Pediatric Acute Liver Failure (PALF) is a rapidly progressive clinical syndrome encountered in the pediatric ICU which may rapidly progress to multi-organ dysfunction, and on occasion to life threatening cerebral edema and hemorrhage. Pediatric Acute Liver Failure is defined as severe acute hepatic dysfunction accompanied by encephalopathy and liver-based coagulopathy defined as prolongation of International Normalized Ratio (INR) >1.5. However, coagulopathy in PALF is complex and warrants a deeper understanding of the hemostatic balance in acute liver failure. Although an INR value of >1.5 is accepted as the evidence of coagulopathy and has historically been viewed as a prognostic factor of PALF, it may not accurately reflect the bleeding risk in PALF since it only measures procoagulant factors. Paradoxically, despite the prolongation of INR, bleeding risk is lower than expected (around 5%). This is due to “rebalanced hemostasis” due to concurrent changes in procoagulant, anticoagulant and fibrinolytic systems. Since the liver is involved in both procoagulant (Factors II, V, IX, XI, and fibrinogen) and anticoagulant (Protein C, Protein S, and antithrombin) protein synthesis, PALF results in “rebalanced hemostasis” or even may shift toward a hypercoagulable state. In addition to rebalanced coagulation there is altered platelet production due to decreased thrombopoietin production by liver, increased von Willebrand factor from low grade endothelial cell activation, and hyperfibrinolysis and dysfibrinogenemia from altered synthetic liver dysfunction. All these alterations contribute to the multifactorial nature of coagulopathy in PALF. Over exuberant use of prophylactic blood products in patients with PALF may contribute to morbidities such as fluid overload, transfusion-associated lung injury, and increased thrombosis risk. It is essential to use caution when using INR values for plasma and factor administration. In this review we will summarize the complexity of coagulation in PALF, explore “rebalanced hemostasis,” and discuss the limitations of current coagulation tests. We will also review strategies to accurately diagnose the coagulopathy of PALF and targeted therapies.

Combined factor V and factor VIII deficiency: A rare case report and literature review

Background: Combined factor V and factor VIII deficiency (F5F8D) is a rare autosomal recessive inherited coagulopathy. It has a higher prevalence in the Mediterranean region (1:100,000) compare to its prevalence in the general population which is estimated to be (1:1000,000). Case report: We report a 59 years old Lebanese lady who was referred from the general surgery clinic with an asymptomatic prolongation of prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (aPTT) detected during preoperative work up for an elective umbilical hernia repair. The patient had history of bleeding following dental procedures since childhood as well as easy bruising with minimal trauma. Physical examination was unremarkable. haematological investigations were normal apart from the prolonged PT, INR and aPTT which were corrected following mixing studies. Factor assay revealed factor V level of 5.5% and factor VIII level of 11.9% with other factors within normal ranges confirming the diagnosis of combined F5F8D. Conclusion: Combined factor V and factor VIII deficiency should be suspected in patients with prolonged PT, INR and aPTT especially if they are of Mediterranean, Middle east or Arabic origin with a history of consanguineous marriages. Treatment is generally not indicated unless the patient has recurrent serious bleeding manifestations.

Prolonged international normalized ratio and vascular injury at divisional level predict embolization failures of patients with iatrogenic renal vascular injuries

Transcatheter arterial embolization (TAE), as an alternative to surgery for iatrogenic renal vascular injury (IRVI), may have unsatisfactory outcomes. Nonetheless, there is inadequate information regarding the predictors of TAE outcomes for IRVI in the literature. The aim of this retrospective study was to investigate the predictors of TAE outcomes for IRVI. Of 47 patients, none had major complications, 17 (36.2%) patients had minor complications, and none suffered significant renal function deterioration after TAE. Technical success and clinical success were 91.5% and 93.6%, respectively. Technical failure was associated with older age, thrombocytopenia, prolonged international normalized ratio (INR) and divisional IRVI. Clinical failure was associated with kidney failure, use of steroids, prolonged INR, and divisional IRVI. In addition, prolonged INR was a significant predictor of technical failure. This implies that aggressive measures to control the INR prior to TAE are warranted to facilitate technical success, and technical success could then be validated on post-TAE images. Furthermore, divisional IRVI was a predictor of clinical failure. Thus, divisional IRVI should undergo surgery first since TAE is prone to clinical failure. The avoidance of clinical failure is validated if divisional IRVI does not need further intervention.

Prognostic significance of a prolonged international normalized ratio in elderly patients in an internal medicine ward

PurposeTo investigate clinical characteristics and the prognostic significance of a prolonged international normalized ratio (INR) without obvious cause or anticoagulant treatment, in elderly inpatients. MethodsDemographic, clinical, and laboratory data, in-hospital death and 30day-mortality were prospectively registered for 100 consecutive patients aged ≥75years admitted to an internal medicine ward for a variety of acute medical disorders, and compared according to normal (≤1.15) and prolonged (>1.15) INR on admission. Exclusion criteria were: anticoagulant therapy, disseminated intravascular coagulopathy, acute bleeding, liver disease, active malignant disorder, and known coagulopathy. ResultsProlonged INR was found in 52% of patients. Patients with prolonged INR tended more likely to present with dementia and pressure sores than patients with normal INR. Moreover, patients with prolonged INR more often needed assisted feeding and presented lower mean levels of serum albumin on admission. In-hospital (21.2% vs. 6.2%) and 30-day (32.7% vs. 6.2%) mortality rates were significantly higher in patients with prolonged INR than those with normal INR. On stepwise logistic regression analysis, prolonged INR strongly predicted 30-day mortality (P=0.004, relative risk 1.67, 95% confidence interval 1.07–2.60). ConclusionsProlonged INR without obvious cause or anticoagulant treatment is common among elderly patients admitted to an internal medicine ward, and is associated with a severe clinical profile. Prolonged INR is a powerful predictor of 30-day mortality. Assessment of INR my improve risk stratification for elderly inpatients.

Menstrual Abnormalities and Gynaecological Problems in Women on Anticoagulant and Antiplatelet Therapy: Management Options

Introduction: The aim of this study was: 1) To study the pattern of menstrual abnormality and severity in women on anticoagulant and antiplatelet drugs. 2) To analyze the correlation of prothrombin time (PT), International Normalised ratio (INR) and the bleeding severity. 3) To discuss the various management options in unexpected emergencies and menstrual complications in this subset of women on anticoagulants. Material & Methods: It is a prospective study, over a period of 18 months from July 2011 to december 2012. We had 44 women on antithrombotic therapy. 32 women were on anticoagulants and 12 were on antiplatelet agents. The severity of bleeding pattern was assessed with pictoral bleeding assessment chart (PBAC). 1) Out of 44 women studied, 32 women were on anticoagulants and 12 were on antiplatelet agents. 26 (81.25%) were on acenocoumarol, 5 (15.62%) on warfarin, 1 (3.12%) on heparin, among the 12 antiplatelet users, 8 (66.66%) were on aspirin and 4 (33.33%) on clopidogrel. 2) The indication for anticoagulants was mitral valve replacement (MVR) in 9, double valve replacement (DVR) in 6, aortic valve replacement (AVR) in 3, severe pulmonary artery hypertension (PAH) in 2, severe mitral stenosis (MS) with atrial thrombus in 2, deep vein thrombosis (DVT) in 5, severe mitral regurgitation (MR) in one, the other indications were subdural hematoma, thromboendarterectomy, chronic kidney disease (CKD) stage V, coarction of aorta, one each. The indication for antiplatelet therapy was percutaneous transluminal coronary angioplasty (PTCA) in 3, Wolf Parkinson White (WPW) syndrome + atrial fibrillation (AF), acute myocardial infarction (AMI), coronary artery bypass graft (CABG), mid basilar artery aneurysm, renal allograft recipient, dialated cardiomyopathy, aortic aneurysm repair, hypertension and unstable angina one each. Results: In women on anticoagulants (32), the main complaint was menorrhagia/heavy menstrual bleeding (HMB) in 20, polymenorrhoea with menorrhagia in 4, continuous per vaginal (PV) bleeding in 6. One lady had postmenopausal bleeding. Among the 12 antiplatelet users the main complaint was menorrhagia in 8, polymenorrhoea with menorrhagia in 2, postmenopausal bleeding in one. While on antithrombotic therapy apart from heavy menstrual bleeding, two women had intraperitoneal bleeding, two had post menopausal bleeding, two had secondary postpartum bleeding (PPH). CVA due to embolic stroke occurred in three, one during the study period. Subchoroidal haemorrhage causing choroidal detachment was noted in one. Conclusions: In patients with prolonged INR, excessive uterine bleeding can be an alerting initial manifestation. Antithrombotic therapy can cause HMB or exaggerate the symptom of HMB due to an underlying gynaec pathology. Mefanamic acid and norethisterone were used to arrest heavy menstrual bleeding. Antithrombotic therapy in women needs special consideration with alterations in menstrual pattern and contraception. Pregnancy and postpartum period present special challenges.