PIVKA­II is associated with liver function, bone metabolism, and muscle function in patients with liver disease.

Protein induced by vitamin K (VK) absence-II (PIVKA-II) is a sensitive marker for diagnosing hepatoma but is occasionally detected in patients without hepatoma Here, the clinical significance of serum PIVKA-II levels in patients who were not administered warfarin and did not have hepatoma or liver disease were evaluated. As VK is related to muscle and bone metabolism, PIVKA-II and clinical factors related to bone and muscle were compared. A total of 441 patients with various liver diseases were evaluated. Of these, 236 patients were female. Clinical factors and anthropometric measurements were obtained for each participant during outpatient visits. Among the clinical factors, type I procollagen N-propeptide (P1NP), a low titer of undercarboxylated osteocalcin (ucOC), and 25(OH) vitamin D (VD) were used as bone metabolic markers, and SARC-F and grip strength were used as muscle-related markers. Serum PIVKA-II levels above the upper limit were associated with Child B/C (Child-Pugh score), high titers of total P1NP, and low titers of ucOC in females, and alcohol-related liver disease and low VD in males. The titer of PIVKA-II were associated with immunoglobulin (Ig) A and prothrombin time (PT)-international normalized ratio (INR) in females, and fibrosis-4-4, IgG, total bilirubin, PT-INR, and SARC-F in males. Elevated PIVKA-II levels were associated with abnormal bone physiology in females, weak muscles in males, and severe liver disease in both sexes. Assessing PIVKA-II may assist in evaluating the clinical and bone-muscle metabolic stages in liver disease. Nutrition and supplementation with fat-soluble vitamins, including VK and VD may thus serve as a potential method to alleviate or prevent bone-muscle pathophysiology in patients with liver disease.

Pre-analytical errors in coagulation testing: a case series.

OBJECTIVES: Prevention of pre-analytical issues in coagulation testing is of paramount importance for good laboratory performance. In addition to common issues like hemolysed, icteric, or lipemic samples, some specific pre-analytical errors of coagulation testing include clotted specimens, improper blood-to-anticoagulant ratio, contamination with other anticoagulants, etc. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are very commonly affected tests due to pre-analytical variables. The impact these parameters possess on surgical decision-making and various life-saving interventions are substantial therefore we cannot afford laxity and casual mistakes in carrying out these critical investigations at all. CASE PRESENTATION: In this case series, a total of 4 cases of unexpectedly deranged coagulation profiles have been described which were reported incorrectly due to the overall casual approach towards these critical investigations. We have also mentioned how the treating clinician and lab physician retrospectively accessed relevant information in the nick of time to bring back reassurance. CONCLUSIONS: Like every other critical investigation, analytical errors can occur in coagulation parameters due to various avoidable pre-analytical variables. The release of spurious results for coagulation parameters sets alarm bells ringing causing much agony to the treating doctor and patient. Only a disciplined and careful approach taken by hospital and lab staff towards each sample regardless of its criticality can negate these stressful errors to a large extent.

A super-geriatric patient with gastrostomy underwent life-threatening prothrombin time-international normalized ratio prolongation by warfarin following fasting and antibiotic therapy.

Key Clinical Message: A 97-year-old woman with gastrostomy had a drastic enhancement for PT-INR after starting antibiotic therapy. Possible causes include (1) vitamin K deficiency due to fasting and (2) a combination of warfarin and antibiotics. Abstract: Geriatric and Asian-descent patients are more sensitive to the effects of warfarin, a key anticoagulant drug. In this report, we present a 97-year-old bedridden woman being treated with warfarin for cardiogenic cerebral infarction and femoral neck replacement as part of in-home medical care with a gastrostomy and was admitted to our hospital after developing pneumonia. We discontinued warfarin and started antibiotics, and her pneumonia-related symptoms improved. Eleven days after restarting warfarin, the patient's PT-INR surpassed the upper limit for measurement (over 10). We considered the mechanism might be triggered by (1) fasting, low nutrition status; and (2) antibiotics secondary to risk factors such as gastrostomy and being a super-geriatric woman. We recommend careful monitoring of PT-INR in patients treated with warfarin and antibiotics, especially in the setting of gastrostomy or older persons.

Comparison of Point-of-Care PT-INR by Hand-Held Device with Conventional PT-INR Testing in Anti-phospholipid Antibody Syndrome Patients on Oral Anticoagulation.

Evidence on agreement of point-of-care (POC) INR testing with laboratory testing in APS patients on oral anticoagulation (OAC), is scarce. This study assessed agreement of paired PT INR testing by a POC device vs. conventional platform-based laboratory test, in APS patients on OAC using a pre-determined definition of agreement. Simultaneous paired PT INR estimation in 92 APS patients was carried out, during October 2020-September 2021. POC INR was performed on capillary blood (pin prick) using the qLabs® PT-INR hand-held device, while laboratory INR estimation was performed using citrated blood (venepuncture) on STA-R Max Analyzer® using STA-NeoPTimal thromboplastin reagent®. Concordance was defined no greater than ± 30% (as per international standards ISO 17593:2007 guidelines) for each paired INR estimation. Agreement between the two was defined as ≥ 90% of paired INR measurements being concordant. 211 paired estimations were performed, within which 190 (90%) were concordant. Good correlation was seen between the 2 methods of INR estimation on Bland Altman plot analysis with an Intra-class correlation coefficient (95% CI) of 0.91(0.882, 0.932). Lab INR range > 4 (P = 0.001) was a significant predictor of higher variability between both methods of INR estimation. Lupus anti-coagulant, other anti-phospholipid antibodies (APL) or triple APL positivity did not result in any statistically significant variation in paired measurements. This study demonstrated good correlation between POC INR measurement and Lab INR estimation and agreement was ascertained between the 2 methods in APS patients on OAC.

Acenocoumarol-Induced Diffuse Alveolar Hemorrhage: A Case Report.

Diffuse alveolar hemorrhage (DAH) is bleeding into the alveolar spaces of the lung. DAH is often associated with systemic autoimmune diseases, coagulation disorders, drugs, inhaled toxins, or transplantation. This study describes a rare case of acenocoumarol-induced DAH, a pulmonary disorder, which has not been reported before. A 48-year-old male presented with a history of rheumatic heart disease with mitral stenosis with moderate mitral regurgitation status post mitral valve replacement. He was taking acenocoumarol but did not keep his prothrombin time-international normalized ratio (PT-INR) monitoring and came to the hospital with complaints of cough, hemoptysis, and breathlessness. Chest x-ray and high-resolution computed tomography (HRCT) thorax were done which revealed diffuse patchy opacities and pulmonary hemorrhage, respectively. After nine days of hospital stay with appropriate management with corticosteroids, antibiotics, and intravenous fluids, the patient was doing well.

Effects of changing the timing of warfarin administration in combination with fluconazole on prolongation of the PT-INR: a case report.

BACKGROUND: Fluconazole (FLCZ) inhibits cytochrome P450 (CYP) 2C9, 2C19, and 3A4 and has a drug-drug interaction that potentiates the effects of warfarin and prolong the prothrombin time-international normalized ratio (PT-INR). Although a drug-drug interaction have been reported between FLCZ and warfarin, the effects of the timing of their administration on this interaction have not yet been investigated. CASE PRESENTATION: A female patient in her 30s with Marfan syndrome had undergone the Bentall procedure with a mechanical valve and total arch replacement for acute aortic dissection Stanford A type and rupture of the ascending aorta. Warfarin was administered to prevent thromboembolism. She was hospitalized 1 year ago for graft infection caused by Candida albicans, and treatment with FLCZ was initiated. She received FLCZ 200 mg once a day in the morning and warfarin 1.75 mg once a day in the evening, and the PT-INR remained stable at approximately 2.0 and within the therapeutic range. However, 42 days after changing the timing of administration of warfarin from evening to morning, the PT-INR was prolonged by approximately 3-fold to 6.25. The PT-INR then decreased to the previous level by changing the timing of administration of warfarin from morning to evening. CONCLUSIONS: The timing of administration of FLCZ and warfarin may affect the magnitude of drug-drug interaction.

Association between PT, PT-INR, and in-hospital mortality in critically ill patients with tumors: A retrospective cohort study.

Objectives: Prothrombin time (PT) and PT-INR are independent predictors of mortality in patients with cancer. The PT and PT-INR of cancer patients are independent predictive variables of mortality. However, whether the PT or PT-INR is related to in-hospital mortality in severely ill patients with tumors remains unknown. Design: This was a case-control study based on a multicenter public database. Settings: This study is a secondary analysis of data extracted from 2014 to 2015 from the Electronic Intensive Care Unit Collaborative Research Database. Participants: The data relevant to seriously ill patients with tumors were obtained from 208 hospitals spread throughout the USA. This research included a total of 200,859 participants. After the samples were screened for patients with combination malignancies and prolonged PT-INR or PT, the remaining 1745 and 1764 participants, respectively, were included in the final data analysis. Primary and secondary outcome measures: The key evaluation methodology was the PT count and PT-INR, and the main outcome was the in-hospital mortality rate. Results: After controlling for confounding variables, we found a curvilinear connection between PT-INR and in-hospital mortality (p < 0.001), and the inflection point was 2.5. When PT-INR was less than 2.5, an increase in PT-INR was positively associated with in-hospital mortality (OR 1.62, 95% CI 1.24 to 2.13), whereas when PT-INR was greater than 2.5, in-hospital mortality was relatively stable and higher than the baseline before the inflection point. Similarly, our study indicated that the PT exhibited a curvilinear connection with in-hospital mortality. On the left side of the inflection point (PT <22), a rise in the PT was positively linked with in-hospital mortality (OR 1.08, 95% CI 1.04 to 1.13, p < 0.001). On the right side of the inflection point, the baseline PT was above 22, and the in-hospital mortality was stable and higher than the PT count in the prior range (OR 1.01, 95% CI 0.97 to 1.04, 0.7056). Conclusion: Our findings revealed that there is a curved rather than a linear link between the PT or PT-INR and in-hospital mortality in critically ill cancer patients. When these two laboratory results are below the inflection point, comprehensive therapy should be employed to reduce the count; when these two laboratory results are above the inflection point, every effort should be made to reduce the numerical value to a value below the inflection point.

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

BACKGROUND: We 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 BODY: Similar 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 (ß, 0.07; 95% CI, 0.02 to 0.13; P = 0.005) and lower platelet count (ß, -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. CONCLUSIONS: In 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.

Post-ovulatory Hemoperitoneum in a Patient on Anticoagulation Therapy for Mitral Valve Replacement.

When a patient is receiving anticoagulant therapy, the rupture of a corpus luteum cyst may go unrecognized in healthy women but becomes clinically relevant as it might exacerbate a hemoperitoneum episode. This report describes the case of a 26-year-old primipara who underwent surgical treatment for a heart defect and later experienced extensive hemoperitoneum. The patient reported to the casualty with symptoms of unstable hemodynamic status such as hypotension 90/60 mmHg and tachycardia 120 beats/minute. A multidisciplinary team decided upon surgical management after stabilizing the coagulation profile and correcting the shock with blood and blood products. The reason was discovered to be a ruptured cyst wall, which was fixed electrosurgically. The patient had a full recovery with no postoperative complications. The most noteworthy aspect of this case was the catastrophic hemoperitoneum caused by improper anticoagulant treatment monitoring. Management of such cases depends on the age of the patient, fertility, and calculating the long-term prognosis of the anticoagulation therapy for the patient.

Relationship between elevated bilirubin levels and enhanced warfarin effects during biliary obstruction.

OBJECTIVES: A marked prolongation of the prothrombin time-international normalized ratio (PT-INR) is frequently observed during biliary obstruction in patients using warfarin. The objective of this study was to identify factors associated with PT-INR prolongation during biliary obstruction in patients using warfarin. METHODS: Among 44 patients using warfarin who had biliary obstruction, we retrospectively investigated warfarin doses and laboratory data before and during biliary obstruction. The primary outcome was the association between changes in PT-INR (ΔPT-INR) and changes in laboratory data before and during biliary obstruction. RESULTS: Median PT-INR was 1.59 (IQR 1.38-1.95) before biliary obstruction and 2.27 (IQR 1.60-3.49) during biliary obstruction, indicating significant prolongation during the obstruction (P < 0.001). ΔPT-INR showed strong positive correlations with change in total bilirubin (ΔT-Bil; ρ = 0.692, P < 0.001) and change in conjugated bilirubin (ΔC-Bil; ρ = 0.731, P < 0.001). ΔPT-INR showed a weak negative correlation with the change in albumin (ΔAlb; ρ = -0.371, P < 0.05). When ΔPT-INR was used as the dependent variable in multiple linear regression analysis, ΔT-Bil, ΔC-Bil, and ΔAlb were significantly associated with ΔPT-INR. CONCLUSIONS: PT-INR was prolonged during biliary obstruction in patients using warfarin, and changes in bilirubin levels were associated with ΔPT-INR. If biliary obstruction with markedly elevated bilirubin levels occurs, measuring PT-INR could lead to safer warfarin therapy.

Diagnostic and Prognostic Significance of the Prothrombin Time/International Normalized Ratio in Sepsis and Septic Shock.

OBJECTIVE: The study investigates the diagnostic and prognostic significance of the prothrombin time/international normalized ratio (PT/INR) in patients with sepsis and septic shock. BACKGROUND: Sepsis may be complicated by disseminated intravascular coagulation (DIC). While the status of coagulopathy of septic patients is represented within the sepsis-3 definition by assessing the platelet count, less data regarding the prognostic impact of the PT/INR in patients admitted with sepsis and septic shock is available. METHODS: Consecutive patients with sepsis and septic shock from 2019 to 2021 were included. Blood samples were retrieved from day of disease onset (ie, day 0), as well as on day 1, 2, 4, 6 and 9 thereafter. Firstly, the diagnostic value of the PT/INR in comparison to the activated partial thromboplastin time (aPTT) was tested for septic shock compared to sepsis without shock. Secondly, the prognostic value of the PT/INR for 30-day all-cause mortality was tested. Statistical analyses included univariable t-tests, Spearman's correlations, C-statistics, Kaplan-Meier analyses and Cox proportional regression analyses. RESULTS: 338 patients were included (56% sepsis without shock, 44% septic shock). The overall rate of all-cause mortality at 30 days was 52%. With an area under the curve (AUC) of 0.682 (p= .001) on day 0, the PT/INR revealed moderate discrimination of septic shock and sepsis without shock. Furthermore, PT/ INR was able to discriminate non-survivors and survivors at 30 days (AUC = 0.612; p = .001). Patients with a PT/INR >1.5 had higher rates of 30-day all-cause mortality than patients with lower values (mortality rate 73% vs 48%; log rank p = .001; HR = 2.129; 95% CI 1.494-3.033; p = .001), even after multivariable adjustment (HR = 1.793; 95% CI 1.343-2.392; p = .001). Increased risk of 30-day all-cause mortality was observed irrespective of concomitant thrombocytopenia. CONCLUSION: The PT/INR revealed moderate diagnostic accuracy for septic shock but was associated with reliable prognostic accuracy with regard to 30-day all-cause mortality in patients admitted with sepsis and septic shock.

Development and validation of a mobile application based on a machine learning model to aid in predicting dosage of vitamin K antagonists among Indian patients post mechanical heart valve replacement.

Patients who undergo heart valve replacements with mechanical valves need to take Vitamin K Antagonists (VKA) drugs (Warfarin, Nicoumalone) which has got a very narrow therapeutic range and needs very close monitoring using PT-INR. Accessibility to physicians to titrate drugs doses is a major problem in low-middle income countries (LMIC) like India. Our work was aimed at predicting the maintenance dosage of these drugs, using the de-identified medical data collected from patients attending an INR Clinic in South India. We used artificial intelligence (AI) - machine learning to develop the algorithm. A Support Vector Machine (SVM) regression model was built to predict the maintenance dosage of warfarin, who have stable INR values between 2.0 and 4.0. We developed a simple user friendly android mobile application for patients to use the algorithm to predict the doses. The algorithm generated drug doses in 1100 patients were compared to cardiologist prescribed doses and found to have an excellent correlation.

Proposal of Quick Diagnostic Criteria for Disseminated Intravascular Coagulation.

BACKGROUND: The diagnostic criteria for disseminated intravascular coagulation (DIC) vary and are complicated and the cut-off values are different. Simple and quick diagnostic criteria for DIC are required in physicians for critical care. MATERIAL AND METHODS: Platelet counts, prothrombin time-international normalized ratio (PT-INR) and D-dimer levels were examined in 1293 critical ill patients. Adequate cut-off values of these parameters were determined and a quick DIC score using these biomarkers was proposed. The quick DIC score was evaluated using a receiver operating characteristic (ROC) analysis. RESULTS: Using the Japanese Ministry of Health, Labor and Welfare diagnostic criteria, 70 and 109 patients were diagnosed with DIC and pre-DIC, respectively. The ROC analysis of factors difference between DIC and non-DIC, revealed the following cut-off values: PT-INR, 1.20; platelet count, 12.0 × 1010/L and D-dimer, 10.0 µg/mL. Based on the above results, the quick DIC score system was proposed. All patients with DIC had a quick DIC score of 3, 4 or 5, and 85.3% of the patients with pre-DIC had a quick DIC score of ≥3 points. All patients with pre-DIC had a score of ≥2 points. In the ROC analysis, the area under the curve was 0.997 for DIC vs. non-DIC, and 0.984 for pre-DIC + DIC vs. non-DIC, and the cut-off value was 3 points for DIC and 2 points for DIC + pre-DIC. The quick DIC scores of non-survivors were significantly higher than those of survivors. CONCLUSIONS: The Quick DIC score system is a simple and useful tool that can be used for the diagnosis of DIC and pre-DIC. Further evaluation of the quick DIC score system in a large-scale study is required.

An increased prothrombin time-international normalized ratio in patients with acute type A aortic dissection: contributing factors and their influence on outcomes.

PURPOSE: We investigated factors contributing to coagulopathy in patients with acute type A aortic dissection (ATAAD) and coagulopathy's influence on patient outcomes. METHODS: We grouped 420 patients who underwent ATAAD repair-none under anticoagulation therapy or with liver disease-by the prothrombin time-international normalized ratio (PT-INR) at admission: < 1.2 (no coagulopathy, n = 371), 1.2-1.49 (mild coagulopathy, n = 33), or ≥ 1.5 (severe coagulopathy, n = 16). We then compared the clinical presentation, dissection morphology, and outcomes among the groups. We assessed the PT-INR in relation to the preoperative hemodynamics and searched for factors predictive of a PT-INR ≥ 1.2. RESULTS: The transfusion volume and operation time were increased among patients with coagulopathy (P < 0.05). The in-hospital mortality (15.2-37.5% vs. 5.1%, P < 0.001) and 5-year survival (61.1-74.4% vs. 87.6%) were relatively poor for these patients. The median PT-INR was 1.03 (0.97-1.1) for patients with stable hemodynamics (n = 318), 1.11 (1.02-1.21) for those in shock (blood pressure < 80 mmHg) not given cardiopulmonary resuscitation (CPR) (n = 81), and 1.1 (1.0-1.54) for those in shock given CPR (n = 21) (P < 0.001). A multivariable analysis identified shock (P < 0.001), a partially thrombosed false lumen (P = 0.006), and mesenteric malperfusion (P = 0.016) as predictive variables. CONCLUSIONS: Shock, a partially thrombosed false lumen, and mesenteric malperfusion appear to be predictive of dissection-related coagulopathy, which influences outcomes negatively.

Effect of Recombinant Human Soluble Thrombomodulin on Coagulation-Related Variables in Patients With Sepsis-Induced Disseminated Intravascular Coagulation: A Retrospective Observational Study.

To evaluate associations among coagulation-related variables, resolution of disseminated intravascular coagulation (DIC) and mortality, we retrospectively investigated 123 patients with sepsis-induced DIC treated with recombinant human soluble thrombomodulin (rTM). Changes in coagulation-related variables before and after treatment with rTM were examined. Further, associations between coagulation-related variables and DIC resolution were evaluated. The platelet count, prothrombin international normalized ratio (PT-INR), and fibrin/fibrinogen degradation products (FDP) significantly (p < .001) improved after rTM administration in survivors (n = 98), but not in nonsurvivors (n = 25). However, the DIC score significantly (p < .001) reduced in survivors and in nonsurvivors. Among coagulation-related variables examined before rTM, only PT-INR was significantly (p = .0395) lower in survivors than in nonsurvivors, and PT-INR before rTM was significantly (p = .0029) lower in patients attaining than not attaining DIC resolution (n = 87 and 36, respectively). The 28-day mortality was significantly lower in patients attaining than not attaining DIC resolution (11.5% vs 41.7%, p = .0001). In conclusion, the initiation of rTM administration before marked PT-INR elevation may be important to induce DIC resolution and thus to decrease mortality in patients with sepsis-induced DIC. Conversely, the treatment with rTM in patients with marked PT-INR elevation may be not so effective in achieving such goals.

Usefulness of Perioperative Laboratory Tests in Total Hip and Knee Arthroplasty: Are They Necessary for All Patients?

BACKGROUND: Laboratory studies are routinely obtained preoperatively and postoperatively for total hip arthroplasty (THA) and total knee arthroplasty (TKA). This study evaluates the necessity of routine, perioperative laboratory tests and identifies risk factors for laboratory-associated interventions. METHODS: This retrospective review evaluated 967 consecutive patients scheduled for primary, unilateral TKAs (n = 593) or THAs (n = 374) over an 18-month period at a single institution. Preoperative prothrombin time (PT) and International Normalized Ratio (INR), complete blood count (CBC), complete metabolic panel (CMP), and postoperative CBC and basic metabolic panel (BMP) were recorded along with any laboratory-associated intervention. Patient demographics and comorbidities identified risk factors for abnormal or actionable laboratory studies. RESULTS: Preoperatively, the actionable rates for PT/INR, CMP, and CBC were 0.3%, 1.4%, and 0.5%, respectively. Vascular, renal, and immunologic diseases were risk factors for an actionable CBC. Risk factors for an actionable CMP include cardiac arrhythmia and diabetes. There were no risk factors for an actionable PT/INR. Postoperatively, only 1.5% of BMPs and 1.5% of CBCs were actionable. Congestive heart failure, renal disease vascular disease, or history of cancer (P = .030) were risk factors for an actionable CBC. There were no risk factors for an actionable BMP. Patients with an abnormal preoperative lab were 2.4 times more likely to have an actionable postoperative lab. Patients with an actionable preoperative lab were 11.3 times more likely to have an actionable postoperative lab. CONCLUSION: Routine preoperative and postoperative labs may not be necessary on all patients undergoing a TKA or THA. Comorbid risk factors and abnormal or actionable preoperative CMPs and CBCs can help determine the usefulness of postoperative laboratory assessments.

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

BACKGROUND: Previous 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. METHODS: Patients 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. RESULTS: Propensity 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). CONCLUSION: In 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.

Fully printed prothrombin time sensor for point-of-care testing.

With an increasing number of patients relying on blood thinners to treat medical conditions, there is a rising need for rapid, low-cost, portable testing of blood coagulation time or prothrombin time (PT). Current methods for measuring PT require regular visits to outpatient clinics, which is cumbersome and time-consuming, decreasing patient quality of life. In this work, we developed a handheld point-of-care test (POCT) to measure PT using electrical transduction. Low-cost PT sensors were fully printed using an aerosol jet printer and conductive inks of Ag nanoparticles, Ag nanowires, and carbon nanotubes. Using benchtop control electronics to test this impedance-based biosensor, it was found that the capacitive nature of blood obscures the clotting response at frequencies below 10 kHz, leading to an optimized operating frequency of 15 kHz. When printed on polyimide, the PT sensor exhibited no variation in the measured clotting time, even when flexed to a 35 mm bend radius. In addition, consistent PT measurements for both chicken and human blood illustrate the versatility of these printed biosensors under disparate operating conditions, where chicken blood clots within 30 min and anticoagulated human blood clots within 20-100 s. Finally, a low-cost, handheld POCT was developed to measure PT for human blood, yielding 70% lower noise compared to measurement with a commercial potentiostat. This POCT with printed PT sensors has the potential to dramatically improve the quality of life for patients on blood thinners and, in the long term, could be incorporated into a fully flexible and wearable sensing platform.

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

BACKGROUND/AIM: The aim of this study was to elucidate the clinical impact of coagulation disorders on outcomes after curative resection of pancreatic ductal adenocarcinoma. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Evaluation of inter-patient variability in the pharmacodynamic indices of warfarin.

OBJECTIVES: Warfarin exhibits huge inter-individual variability in therapeutic response. We assessed the extent and the factors affecting inter-individual variability in the anticoagulation control using pre-validated pharmacodynamic indices. METHODS: Patients receiving warfarin for at least 6 months were recruited. CHA2DS2-VASc, HASBLED, SAMe-TT2R2 scores, warfarin sensitive index (WSI), log-INR variability, and warfarin composite measure (WCM) were assessed. National Institute for Health and Care Excellence (NICE) guideline was adhered for assessing the anticoagulation control using time in therapeutic range (TTR) (TTR < 65%-poor; and TTR ≥ 65%-good). Odds ratio [95% confidence interval] was the effect estimate measure. RESULTS: Eighty-seven (39.5%) of the patients were poorly anticoagulated. Those with lower HASBLED [OR: 0.3; 0.1, 0.6] and SAMe-TT2R2 scores [OR: 0.2; 0.04, 0.7] and higher CHA2DS2-VASc score [OR: 1.8; 1.1, 1.3] predicted good anticoagulation control. Thirty-five (15.9%) patients had high INR variability. Lower TTR, shorter duration of therapy, and higher WSI were observed in patients with high INR variability, and presence of drugs with potential interaction significantly predicted high INR variability. CONCLUSION: Significant numbers of our patients on warfarin had poor anticoagulation control and high INR variability. We have identified duration of therapy, CHA2DS2-VASc score, and WSI as reliable predictors for anticoagulation control and INR variability.