Prolonged Prothrombin Time-international Normalized Ratio Research Articles

Clinical and Epidemiological Characteristics of 30 Fatal Cases of Crimean-Congo Hemorrhagic Fever in Kabul, Afghanistan: A Retrospective Observational Study.

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease associated with a high fatality rate. CCHF is endemic in Afghanistan, and its morbidity and mortality have increased recently but there is limited data about the characteristics of fatal cases. We aimed to report the clinical and epidemiological features of fatal CCHF cases who were admitted to Kabul Referral Infectious Diseases (Antani) Hospital. This is a retrospective cross-sectional study. The demographic and presenting clinical and laboratory features of 30 fatal CCHF cases diagnosed by reverse transcription polymerase chain reaction (RT-PCR) or enzyme-linked immunosorbent assay (ELISA) tests were collected from the patients' records between March 2021 and March 2023. During the study period, a total of 118 laboratory-confirmed CCHF patients were admitted to Kabul Antani Hospital of whom 30 patients (25 males, 5 females) consequently died, indicating a 25.4% case fatality rate (CFR). The age of the fatal cases ranged from 15 to 62 years and their mean age was 36.6 ± 11.7 years. Concerning occupation, the patients were butchers (23.3%), animal dealers (20%), shepherds (16.6%), housewives (16.6%), farmers (10%), student (3.3%), and others (10%). The clinical symptoms of the patients on admission were fever (100%), generalized body pain (100%), fatigue (90%), bleeding (any type) (86.6%), headache (80%), nausea/vomiting (73.3%), and diarrhea (70%). The initial abnormal laboratory findings were leukopenia (80%), leukocytosis (6.6%), anemia (73.3%), and thrombocytopenia (100%), raised hepatic enzymes (ALT & AST) (96.6%) and prolonged prothrombin time/international normalized ratio (PT/INR) (100%). The hemorrhagic manifestations associated with low platelet and raised PT/INR levels are linked with fatal outcomes. A high index of clinical suspicion is required to recognize the disease at an early stage and to begin the treatment promptly for reducing mortality.

Thrombocytopenia and PT-INR in patients with anorexia nervosa and severe liver dysfunction

BackgroundWe previously reported a case that led us to hypothesize that decreased production of thrombopoietin (TPO) leads to thrombocytopenia in patients with anorexia nervosa (AN) with severe liver dysfunction and that prolonged prothrombin time-international normalized ratio (PT-INR) predicts thrombocytopenia in such cases. To validate this hypothesis, we report another case in which TPO levels were measured. In addition, we examined the association between prolonged PT-INR and thrombocytopenia in such patients.Main bodySimilar to the previously reported patient, a patient with AN with severe liver dysfunction showed that TPO levels increased after improvements in liver enzyme levels and PT-INR, followed by recovery of platelet count. In addition, a retrospective study was also conducted to review patients with AN whose liver enzyme levels were > 3 × the upper limit of normal (aspartate aminotransferase > 120 U/L or alanine aminotransferase > 135 U/L). The study included 58 patients and showed a correlation coefficient of -0.486 (95% confidence interval [CI], -0.661 to -0.260; P < 0.001) between maximum PT-INR and minimum platelet count. These patients showed higher PT-INR (β, 0.07; 95% CI, 0.02 to 0.13; P = 0.005) and lower platelet count (β, -5.49; 95% CI, -7.47 to -3.52; P < 0.001) than the 58 matched control patients without severe liver dysfunction, even after adjusting for body mass index.ConclusionsIn patients with AN with severe liver dysfunction, prolongation of PT-INR could predict thrombocytopenia, which may be mediated by decreased TPO production due to decreased hepatic synthetic function.

Supra-therapeutic Anticoagulation with Warfarin: A Cross-sectional Study.

To identify the extent and associated factors for patients with prolonged prothrombin time, international normalized ratio (PT-INR), and the dosage modifications were carried out with warfarin. Studies evaluating patients on warfarin with supratherapeutic anticoagulation are limited. It is vital to understand the management strategies for patients receiving warfarin who are bleeding and those with only supratherapeutic PT-INR. To evaluate the factors associated with supratherapeutic anticoagulation without bleeding with warfarin. A cross-sectional study was carried out on patients receiving long-term warfarin with at least one PT-INR value > 3.2. Percent time in therapeutic range (TTR) was calculated and National Institute for Health and Care Excellence (NICE) guidelines were adhered to defining anticoagulation control into good (> 65%) and poor (< 65%). One hundred and forty-four patients were recruited. Nearly half of the study population had PT-INR values between 3.2 and 3.9. On average, individuals had at least 4 times PT-INR values in the supratherapeutic range. Elderly patients were observed with a significant trend of supratherapeutic INR. Duration of therapy was significantly correlated with the risk of PT-INR > 4. Lower TTR was observed in patients with frequent PT-INR > 4 and those patients had significantly poor anticoagulation control. Duration of warfarin therapy and HAS-BLED scores were observed to be significant predictors of supratherapeutic INR. Large variations were observed in the modifications of warfarin dose carried out at various supratherapeutic INR values and consequently PTINR values. We observed that the majority of patients with supratherapeutic INR had their INR values between 3.2 and 3.9. Elderly patients, with higher HAS-BLED scores and prolonged duration of warfarin therapy, were observed with an increased risk of supratherapeutic anticoagulation. Careful dosage modifications are needed particularly in high-risk categories as mentioned above.

The effect of vitamin K on prothrombin time in critically ill patients: an observational registry study

BackgroundPrevious studies have indicated that vitamin K deficiency is common in non-bleeding critically ill patients with slightly prolonged prothrombin time-international normalized ratio (PT-INR). It has never been investigated thoroughly whether the administration of vitamin K to these patients could affect their PT-INR. Therefore, the aim of this registry study was to evaluate changes in PT-INR in response to vitamin K in critically ill patients with PT-INR in the range of 1.3–1.9.MethodsPatients admitted to a mixed 9-bed general intensive care unit at a University Hospital, between 2013 and 2019 (n = 4541) with a PT-INR between 1.3 and 1.9 at any time during the stay were identified. Patients who received vitamin K with appropriate sampling times for PT-INR and without exclusion criteria were matched with propensity score to patients from the same cohort who did not receive vitamin K (controls). PT-INR was measured at admission, within 12 h before vitamin K administration and 12–36 h following vitamin K administration. Exclusion criteria included pre-existing liver cirrhosis, any plasma or platelet transfusion, or > 1 unit red blood cell transfusion between PT-INR samplings.ResultsPropensity score matching resulted in two groups of patients with 129 patients in each group. PT-INR decreased in both groups (1.4 [1.3–1.4] in the vitamin K group and 1.4 [1.3–1.6] in the controls, p < 0.001 and p = 0.004, respectively). The decrease in PT-INR was slightly more pronounced in patients who received vitamin K (delta PT-INR − 0.10 [− 0.30 to − 0.10] in the vitamin K group and − 0.10 [− 0.20 to 0.10] in the controls, p = 0.01).ConclusionIn critically ill patients with a PT-INR of 1.3–1.9, the administration of vitamin K resulted in a slightly larger decrease of PT-INR 12–36 h after administration compared to controls. Future studies should focus on identifying which patient populations may benefit most from vitamin K administration as well as whether vitamin K could be a better alternative than plasma or prothrombin complex concentrate to improve PT-INR before non-emergent invasive procedures.

Factors influencing the effectiveness of recombinant human soluble thrombomodulin on disseminated intravascular coagulation: a retrospective study

BackgroundAlthough recombinant human soluble thrombomodulin (rTM) has been widely used to treat disseminated intravascular coagulation (DIC) in Japan, there is no consensus regarding rTM efficacy. Therefore, if the factors influencing rTM efficacy is revealed, it may be possible to demonstrate the effectiveness of rTM by limiting the patients who use rTM. This study investigated the factors of rTM treatment which influence DIC status.MethodsThis retrospective case-control study enrolled hospitalized adult patients treated with rTM from October 2010 to May 2020. Among these patients, 227 who were diagnosed with DIC according to the Japanese Association for Acute Medicine DIC scoring system were assessed. The primary endpoint was the 28-day mortality after rTM treatment. For Cox-proportional hazards model, explanatory factors determined using univariate analysis with p < 0.1 were used. In addition, some factors considered to affect DIC-related mortality such as age ≥ 75 years, rTM dose ≥380 U/kg, antithrombin III treatment, and diseases with a poor prognosis (sepsis, solid tumors, and trauma) were added as covariates.ResultsUnivariate analyses suggested that male sex (p = 0.029), treatment in intensive care unit (p = 0.061), and prothrombin time-international normalized ratio (PT-INR) (p < 0.001) were the factors influencing DIC-related 28-day mortality after rTM treatment. According to Cox-proportional hazard analysis, the adjusted odds ratio for DIC-related 28-day mortality in patients with PT-INR ≥ 1.67 was 2.23 (95% confidence interval: 1.451–3.433, p < 0.001), age ≥ 75 years was 1.57 (95% confidence interval: 1.009–2.439, p = 0.046), and male sex was 1.66 (95% confidence interval: 1.065–2.573, p = 0.025), respectively. As life-threatening bleeding events were not observed, prolonged PT-INR might directly or indirectly affect DIC-related mortality caused by rTM treatment.ConclusionrTM treatment for DIC was less effective in male patients with PT-INR ≥ 1.67 and age ≥ 75 years.

Prognostic factors for the short-term mortality of patients with rheumatoid arthritis admitted to intensive care units

BackgroundPatients with rheumatoid arthritis (RA) have high mortality risk and are frequently treated in intensive care units (ICUs).MethodsThis was a retrospective observational study. This study included 67 patients (20 males, 47 females) with RA who were admitted at the ICU of our institution for ≥48 h between January 2008 and December 2017. We analyzed the 30-day mortality of these patients and the investigated prognostic factors in RA patients admitted to our ICU.ResultsUpon admission, the median age was 70 (range, 33–96) years, and RA duration was 10 (range, 0–61) years. The 5-year survival after ICU admission was 47%, and 30-day, 90-day, and 1-year mortality rates were 22, 27, and 37%, respectively. The major reasons for ICU admission were cardiovascular complications (24%) and infection (40%) and the most common ICU treatments were mechanical ventilation (69%), renal replacement (25%), and vasopressor (78%). In the 30-day mortality group, infection led to a fatal outcome in most cases (67%), and nonsurvival was associated with a significantly higher glucocorticoid dose, updated Charlson’s comorbidity index (CCI), and acute physiology and chronic health evaluation (APACHE) II score. Laboratory data obtained at ICU admission showed that lower platelet number and total protein and higher creatinine and prothrombin time international normalized ratio (PT-INR) indicated significantly poorer prognosis. The multivariate Cox proportional hazard model revealed that nonuse of csDMARDs, high updated CCI, increased APACHE II score, and prolonged PT-INR were associated with a higher risk of mortality after ICU admission.ConclusionOur study demonstrated that the nonuse of csDMARDs, high updated CCI, elevated APACHE II score, and coagulation abnormalities predicted poorer prognosis in RA patients admitted to the ICU.

The prognostic value of routine coagulation tests for patients with heat stroke

To evaluate the prognostic value of routine coagulation tests for patients with heat stroke. This was a multi-center retrospective study. Patients who arrived at the hospital <24h after the onset of Heat Stroke (HS) were included. The routine coagulation variables were detected within 24h after the onset, including the lowest platelet count (PLC). 60-day mortality rate was 20.9%. The median Prothrombin Time-International Normalized Ratio (PT-INR) of the non-surviving patients was significantly higher than that of the survivors (P<0.01). The median Activated Partial Thromboplastin Time (APTT) in non-surviving patients was significantly higher than in the surviving patients (P<0.01). A Cox regression analysis revealed that 60-day mortality was associated with PT-INR (P=0.032) and APTT (P=0.004). The optimal PT-INR point for predicting 60-day mortality rate was 1.7. The optimal APTT point for predicting 60-day mortality was 51.45. Patients with increased PT-INR (≥1.7) levels had, overall, a significantly reduced survival time (P<0.01). Patients with elevated APTT (≥51.45) also had a decrease in survival time (P<0.01). The prognostic scoring, with increased PT-INR (≥1.7) and prolonged APTT (≥51.45) at one point each, was also demonstrated to be useful in predicting 60-day mortality. Patients whose temperature fell to 38.9°C within 30min had significantly lower levels of PT-INR and APTT within 24h than those who took longer to cool down. A prolonged APTT and elevated PT-INR within 24h are independent prognostic factors of 60-day mortality in HS.

Prognostic Impact of Coagulation Activity in Patients Undergoing Curative Resection for Pancreatic Ductal Adenocarcinoma.

The aim of this study was to elucidate the clinical impact of coagulation disorders on outcomes after curative resection of pancreatic ductal adenocarcinoma. Preoperative coagulation activity in 135 patients, who had undergone curative resections for pancreatic ductal adenocarcinoma was retrospectively evaluated and the impact on survival outcomes analyzed. A prolonged prothrombin time-international normalized ratio (PT-INR) (≥1.1) was detected in 23/135 patients (17%). Univariate analysis that showed prolonged PT-INR was associated with worse relapse-free (hazard ratio=1.79, p=0.044) and overall (hazard ratio=2.18, p=0.004) survival. Multivariate analyses showed prolonged PT-INR, large tumor (>30 mm), and lymph node metastasis were independent predictors of poor overall survival. Prolonged PT-INR may be a predictor of poor prognosis in patients with pancreatic ductal adenocarcinoma who have undergone curative resection. Coagulation disorders may be a therapeutic target for improving outcomes of pancreatic ductal adenocarcinoma.

Predictive factors of therapeutic intervention in on-call endoscopy for suspected gastrointestinal bleeding

Background and Aims: Performing an endoscopy out of hours confer significant burdens on limited health-care resources. However, not all on-call endoscopies lead to therapeutic interventions. The purpose of the present study was to analyze predictive factors for performing therapeutic intervention in patients with suspected gastrointestinal bleeding.Methods: We reviewed and analyzed electronic medical records regarding on-call endoscopy that were prospectively collected for quality control. The subjects were patients with suspected gastrointestinal bleeding who underwent on-call endoscopies at night, on weekends and on holidays between April 2013 and January 2017 in Seoul National University Bundang Hospital. To determine predictive factors for performing therapeutic intervention, the following variables were analyzed: symptoms, patient status, coexisting disease, laboratory findings and medications. To clarify the association between the likelihood of therapeutic intervention in on-call endoscopy and AIMS65 score, the included variables were divided by cutoffs.Results: A total of 270 patients (male: 72.6%, mean age: 62.6 years) with suspected gastrointestinal bleeding had on-call endoscopies and 153 (56.7%) patients had therapeutic intervention. Gastroscopy, colonoscopy and both endoscopic techniques were performed in 215, 42 and 13 patients, respectively. In the multivariate analysis, hematemesis (p < .001, odds ratio [OR], 2.484) and prolonged prothrombin time-international normalized ratio (PT-INR) (p = .033; OR, 1.958) were correlated with performing therapeutic intervention in on-call endoscopy. AIMS65 score with a cutoff of 2 was associated with the likelihood of intervention (p = .043).Conclusions: Hematemesis and prolonged PT-INR were predictive factors of therapeutic intervention when on-call endoscopy was performed in patients with suspected gastrointestinal bleeding.

Gastrointestinal intramural hematoma—Analysis of clinical and radiological features for early differentiation from mesenteric ischemia

Long-term anticoagulation is associated with hemorrhage at various sites. Gastrointestinal intramural bleeds and hematomas (IMH) often mimic mesenteric ischemia (MI) due to similar clinical settings and imaging features, making early differentiation difficult. To compare the demography, clinical features and imaging characteristics of patients presenting with IMH with those of MI, so as to help in evolving clinical and imaging guidelines to differentiate both early in the course of the disease. All radiologically (contrast-enhanced computed tomogram [CT]) diagnosed cases of gastrointestinal IMH from the hospital database during the period between 2006 and 2012 were retrospectively analyzed. This data was compared with the clinical and imaging features of a group of surgically confirmed MI during the same period. Patients not on anticoagulation therapy at the time of presentation and those with incomplete clinical or radiological data were excluded from the study. There were 16 patients in IMH group and 54 patients in MI group. Clinical features like overt rectal bleeding or melena, and prolonged prothrombin time-international normalized ratio (PT-INR) more than three, and CT features like proximal location in the bowel, increased bowel wall thickness, hyperdensity on plain scan (>40 Hounsfield units (HU)), and short segment bowel involvement were significantly associated with IMH. Visualization of embolus and absent mesenteric vasculature to a segment of intestine in CT was significantly associated with MI. Attention to clinical features and early CT scan can aid in early differentiation of IMH from MI, facilitating appropriate intervention early in the course of disease.

Phase I study of LY2181308, an antisense oligonucleotide against survivin, in patients with advanced solid tumors

LY2181308 is an antisense oligonucleotide that complementarily binds to survivin mRNA and inhibits its expression in tumor tissue. This phase I dose escalation study evaluated the tolerability, pharmacokinetics, and anticancer activity of LY2181308 in Japanese. Patients with solid tumors refractory to standard therapy received LY2181308 (400, 600, or 750 mg) as a 3-h intravenous infusion for 3 consecutive days and thereafter once a week. LY2181308 was administered to 14 patients, aged 44-73 (median 60) years. Flu-like syndrome, prolonged prothrombin time-international normalized ratio (PT-INR), thrombocytopenia, and fatigue were common reversible grade 1/2 toxicities. The dose-limiting toxicity was reversible grade 3 elevation of ALT/AST/γ-GTP in 1 patient treated at the 750-mg dose. Pharmacokinetic analysis showed a long terminal half-life of 21 days and an extensive tissue distribution of LY2181308. In 12 evaluable patients, one patient had stable disease, while the remaining 11 patients had progressive disease. LY2181308 monotherapy is well tolerated up to 750 mg with a manageable toxicity, the pharmacokinetic profile warrants further evaluation of LY2181308 in combination with cytotoxic agents or radiotherapy.

Defining effective therapies in transfusion medicine and hemostasis: new opportunities with the TMH Network

Defining effective therapies in transfusion medicine and hemostasis: new opportunities with the TMH Network