Prothrombin International Normalized Ratio Research Articles

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.

EFFECTS OF SUBCUTANEOUS C1-ESTERASE INHIBITOR ON COAGULATION AND FIBRINOLYTIC PARAMETERS

Introduction Replacement therapy with subcutaneous C1-esterase inhibitor (C1-INH[SC]) 60 IU/kg twice weekly is approved for routine prophylaxis to prevent hereditary angioedema (HAE) attacks. Coagulation and fibrinolytic parameters levels tend to be elevated in HAE patients. We evaluated the effects of C1-INH(SC) on these parameters. Methods In the COMPACT study, subjects received 40 IU/kg or 60 IU/kg of plasma-derived C1-INH(SC) and a corresponding placebo, as prophylaxis over 16 weeks each. In the open-label extension (OLE), subjects received 40 IU/kg or 60 IU/kg of C1-INH(SC) for up to 140 weeks. Exploratory analyses included the assessment of coagulation and fibrinolytic parameters (D-dimer, Prothrombin Fragments [PF] 1+2, activated Partial Thromboplastin Time [aPTT], Fibrinogen, and Prothrombin International Normalized Ratio [PT-INR]) at prescheduled visits. Results Coagulation and fibrinolytic parameters were reported above the normal range at baseline. Treatment with C1-INH(SC) 60 IU/kg resulted in median decrease from baseline for D-dimer (COMPACT [baseline to Week 14]: 605.0 to 330.0 ng/mL; OLE [baseline to Week 140]: 510.0 to 330.0 ng/mL) and PF 1+2 (COMPACT [baseline to Week 14]: 264.0 to 185.0 pmol/L; OLE [baseline to Week 140]: 218.5 to 159.0 pmol/L). The aPTT, Fibrinogen, and PT-INR levels were stable relative to baseline over the treatment period. Results refer only to the Food and Drug Administration (FDA) approved 60 IU/kg dose. Conclusions A reduction or stabilization in coagulation and fibrinolytic parameters was observed in HAE patients treated prophylactically with C1-INH(SC). No related thromboembolic events were reported during treatment with C1-INH (SC).

Pre- to postoperative coagulation profile of 307 patients undergoing oesophageal resection with epidural blockade over a 10-year period in a single hospital: implications for the risk of spinal haematoma

BackgroundEpidural anaesthesia and analgesia are indicated for oesophageal surgery. A rare but serious complication is spinal haematoma, which can occur on insertion, manipulation or withdrawal of catheters. Evidence and guidelines are vague regarding which tests are appropriate and how to interpret their results. We aimed to describe how routine coagulation test results change during oesophagectomy’s perioperative course.MethodsFollowing ethical approval, we retrospectively identified patients who had undergone oesophagectomy between 2002 and 2012. Blood test results and details of operations, haemorrhage and complications were recorded and analysed with Excel and R. A literature search was conducted using the PubMed terms ‘epidural’ AND ‘coagulation’ AND English language. Relevant articles published in 2000 and after were included.ResultsThree hundred and seven patients received a thoracic epidural infusion with bupivacaine and morphine while 51 received an intravenous morphine infusion. Tests taken preoperatively and before the planned withdrawal of the epidural catheter demonstrated increases in all three measures: aPTT (activated partial thromboplastin time), PT-INR (prothrombin international normalised ratio) and platelet count (Plc). Postoperative thrombocytopenia was almost non-existent while aPTT or PT-INR was elevated above the reference range in 129/307 patients: aPTT was elevated in 116/307 while PT-INR was elevated in 32/307. This is too small a sample to allow meaningful estimation of risk of spinal haematoma: it may be as high as 2.3%. The literature search returned 275 articles, of which 57 were relevant. Twenty-one concerned the natural history of postoperative coagulation; 16, the incidence of and risk factors for spinal haematoma; and 5, evaluation of specific blood tests. Postoperative coagulation is characterised by thrombocytosis and transient moderately abnormal routine coagulation test results. Viscoelastic tests are not validated in the stable postoperative setting.ConclusionsScreening for coagulopathy before removal of epidural catheters is of unclear benefit since elevated aPTT and PT-INR are usual and may not indicate hypocoagulation. A thorough clinical assessment is important. We nevertheless recommend caution when being presented with elevated routine tests of coagulation before withdrawing an epidural catheter: viscoelastic haemostatic tests may have a role in testing before withdrawal of epidural catheters but they are so far not validated. Future research should include advanced coagulation analysis as soon as a patient is unfortunate enough to have a spinal haematoma.

Safety assessment of phacoemulsification combined with warfarin therapy

Objective To evaluate the safety of taking warfarin in phacoemulsification surgery for patients with cartaract. Methods The patients of prothrombin international normalized ratio (INR)>3.0 were ruled out according to the exclusive criteria. Ninty-four eyes of 91 patients were divided into group A, B and C. Group A, 33 eyes of 33 cases without history of cardiovascular clisease ware control group; group B, 30 eyes of 28 cases were suspended taking warferin before surgery; group C, 31 eyes of 30 cases received surgeries and took warferin continuously. Incidence of intraocular hemorrhages intraoperative and postoperative were compared among three groups. Results All surgeries were successfully performed. No intraocular hemorrhage occurred among three groups during and after operation. Conclusion Phacoemulsification could be safely performed without discontinuing warfarin in the case of prothrombin INR<3.0. Key words: Warfarin; Cartaract; Hemorrhage, intraocular; Phacoemulsification

Colloid osmotic pressure and extravasation of plasma proteins following infusion of Ringer's acetate and hydroxyethyl starch 130/0.4.

During fluid infusion therapy, plasma proteins are diluted and leak from the intravascular space, which alters the colloid osmotic pressure (COP) and potentially affects coagulation. We hypothesised that acetated Ringer's and starch solution, alone or in combination, influence these mechanisms differently. On different occasions, 10 male volunteers were infused with 20ml/kg acetated Ringer's and 10ml/kg 6% hyroxyethyl starch 130/0.4 (Voluven(®) ) alone or in combination (first with starch solution followed by Ringer's solution). Blood samples were collected every 30-min for measurements of COP, blood haemoglobin, platelets, and plasma concentrations of albumin, immunoglobulins (IgG and IgM), coagulation factor VII (FVII), fibrinogen, cystatin C, activated partial thromboplastin time (APTT) and prothrombin international normalised ratio (PT-INR). Changes were compared with the haemoglobin-derived plasma dilution. The COP increased by 8.4% (SD 3) with starch and decreased by 26.2% (7.9) with Ringer's. These infusions diluted the plasma by 23.4% (5.3) and 18.7% (4.9) respectively. The COP changes in the combined experiment followed the same pattern as the individual infusions. Albumin and IgG changes in excess of the plasma dilution were very subtle. The intravascular contents of the IgM and platelets decreased, whereas FVII, fibrinogen and cystatin C increased. PT-INR increased by 1/3 of the plasma dilution, whereas changes in APTT did not correlate with the plasma dilution. The starch increased COP and only minor capillary leak occurred in healthy volunteers. The fluid-induced plasma dilution correlated with mild impairment of the extrinsic coagulation pathway but not of the intrinsic pathway.

Hydroxyethyl starches and dextran during hip replacement surgery: effects on blood volume and coagulation

Colloid fluids influence the coagulation system by diluting the plasma and, potentially, by exerting other effects that are unique for each fluid product. We hypothesised that changes in the coagulation measured at the end of surgery would be mainly governed by differences in half-life between the colloid fluids. Eighty-four patients were randomised to receive one of four colloids: HES 130/0.42/6:1 (Venofundin(®)), 130/0.4/9:1 (Voluven(®)), 200/0.5/5:1 (Haes-steril(®)) and 6% dextran 70 (Macrodex(®)). Blood samples were taken just before and after a preoperative 500 ml bolus, and also after subsequent elective hip replacement surgery. Volume expansion was estimated from the blood dilution and coagulation assessed by ROTEM, activated partial thromboplastin time, prothrombin international normalised ratio (PT-INR), D-dimer and thrombin-antithrombin complex (TAT). The blood volume expansion amounted to approximately 600 ml for all four colloids directly after infusion. Voluven(®) and Haes-steril(®) prolonged the aPT time and Venofundin(®) increased TAT. Although all colloids increased PT-INR and D-dimer, the ROTEM analyses showed that they consistently shortened the clotting time and weakened the clot strength. These effects were mainly unchanged after surgery, during which the haemorrhage averaged 500-600 ml. Macrodex(®) produced a stronger volume support at the end of the surgery (91% of infused volume; P<0.001) than the three starch solutions (42-60%). All tested colloid fluids induced a mild hypercoagulable state with faster clotting, but with weaker clot strength. The additive influence of surgery was relatively small, and postoperative changes in coagulation were mainly due to differences in the half-life of each colloid.

Acute liver failure in Lithuania

Acute liver failure (ALF) is a life-threatening condition that can rapidly progress into coma and death due to the cerebral edema and multi-organ dysfunction. The ALF etiology and risk factors have been investigated in West Europe, North America, and Asia; however, there are still no published data about the causes and prognosis of ALF in Central and East European countries. The aim of our study was to analyze the causes, outcomes, and prognostic factors of ALF in patients referred to tertiary care center in Lithuania. A total of 28 consecutive patients admitted to the tertiary care center (one of two university-level medical centers in Lithuania) over the period of January 1996 and December 2004 and who fulfilled the entry criteria of ALF (presence of hepatic encephalopathy (HE) and prothrombin international normalized ratio (INR) >1.5) were included into a prospective study. In our study the most frequent causes of ALF were acute viral hepatitis B (21.4 %), drug-induced hepatitis (21.4%), and indeterminate hepatitis (17.9%); other etiologies included Budd-Chiari syndrome (10.7%), ischemic hepatitis (10.7%), Wilson's disease (7.1%), Amanita phalloides-induced liver damage (3.6%), acute fatty liver of pregnancy (3.6%), and malignant infiltration of the liver (3.6%). Among patients with drug-induced liver injury, only one case of acetaminophen poisoning was diagnosed. Clinical status of 9 persons in all patients with ALF corresponded to criteria for liver transplantation (LT) (one liver transplantation was performed), 6 of them had contraindications, and 13 patients did not fulfill requirements for urgent LT. The patients' survival rate in these groups was 11.1%, 16.7% and 69.2%, respectively. In 27 non-transplanted patients univariate analysis revealed the grade of HE on the day of enrolment, total serum bilirubin, pH, and prothrombin INR as risk factors for death from ALF. Multivariate logistic regressive analysis determined only prothrombin INR >3.24 and serum pH <or=7.29 as independent predictors of lethal outcome in ALF. Acute viral hepatitis B, drug-induced liver injury, and indeterminate hepatitis are the main ALF causes in Lithuania. In non-transplanted patients, the main predictors of lethal outcome were severe coagulopathy and metabolic acidosis. Improvement of liver donation system for urgent liver transplantation is essential requirement for amelioration of ALF patient's survival.

ワルファリン服用患者の抜歯後における抗凝固状態回復期間に影響する因子について

We statistically analyzed factors that influence anticoagulant effect after tooth extraction in patients receiving oral warfarin therapy. The study group comprised 60 of 109 patients who were receiving warfarin and presented at our hospitalfor tooth extraction from August 1991 through December 2001. The Prothrombin International Normalized Ratio (PT INR) of these 60 patients was measured and followed up until 4 weeks after tooth extraction. Multiple linear regression based on AMOS was used for statistical analysis. The dependent variable was the period oftime required after tooth extraction for the PT INR (cardiologist-determined PT INR), a cardiologist-determined coagulation index for the purpose of cardiovascular therapy, to recover to its pre-extraction level. Our study revealed that anticoagulant effect after tooth extraction was influenced by a history of prosthetic heart valve placement (prosthetic valve), the dosage of warfarin administered (the dosage), the numbers of days of treatment cessation and of administering a reduced dose of warfarin, and the cardiologist-determined PT INR. The effects of prosthetic valve and the number of days of cessation of warfarin treatment were statistically significant (partial regression coefficient, 0.31). The influence of the number of days of treatment cessation was indirectly, affected by the prosthetic valve, the dosage, and the cardiologist-determined PT INR.

Minimising Medication Mishap: Introducing a Warfarin Safety Strategy

ABSTRACTAnticoagulants have been implicated in up to 10% of all adverse drug events. In 2001, The Alfred established a Medication Safety Committee and identified warfarin therapy as a patient safety priority. Through process mapping and consultation, opportunities for error were identified throughout the warfarin prescribing, dispensing and administration processes. Clinicians considered review of prothrombin international normalised ratio results and routine warfarin dosing at 2000 hours as the most significant risk to patients. This was because warfarin was frequently prescribed by after‐hours staff who were not familiar with the patient's history or changes in their clinical condition or medication. Clinicians participated in the development and implementation of a warfarin safety strategy that involved changing the dosing to 1600 hours and alert stickers affixed to drug charts by pharmacists to identify patients prescribed warfarin. This program was effective in improving staff management of inpatients receiving warfarin. It also demonstrated the importance of an effective change management strategy in establishing a sense of urgency in clinicians regarding safety, and engagement in process analysis, risk identification and the development of simple and practical safety strategies.