aPTT In Patients Research Articles

Unresponsiveness of Activated Partial Thromboplastin Time to Bivalirudin in Adults Receiving Extracorporeal Membrane Oxygenation.

Activated partial thromboplastin time (aPTT) is the standard for monitoring bivalirudin but demonstrates a nonlinear response at higher drug concentrations. The objective of this study was to assess the relationship between bivalirudin dose and aPTT in patients receiving extracorporeal membrane oxygenation (ECMO) to determine a threshold where aPTT unresponsiveness occurs. Two hundred fourteen adults receiving bivalirudin during ECMO between 2018 and 2022 were included. Piecewise regression in a linear mixed effects model was used to determine a bivalirudin dose threshold of 0.21 mg/kg/hr for aPTT unresponsiveness. For doses of less than 0.21 mg/kg/hr (n = 135), every 0.1 mg/kg/hr dose increase led to an aPTT increase of 11.53 (95% confidence interval [CI] = 9.85-13.20) seconds compared to only a 3.81 (95% CI = 1.55-6.06) seconds increase when dose was greater than or equal to 0.21 mg/kg/hr (n = 79) ( pinteraction < 0.001). In multivariable logistic regression, venovenous configuration (odds ratio [OR] = 2.83, 95% CI = 1.38-5.77) and higher fibrinogen concentration (OR = 1.22, 95% CI = 1.05-1.42) were associated with greater odds of unresponsiveness, whereas older age (OR = 0.79, 95% CI = 0.63-0.98), kidney dysfunction (OR = 0.48, 95% CI = 0.25-0.92), and a higher baseline aPTT (OR = 0.89, 95% CI = 0.82-0.97) were associated with lower odds. Alternative methods are necessary to ascertain bivalirudin's hemostatic impact when doses exceed 0.21 mg/kg/hr during ECMO.

From Activated Partial Thromboplastin Time to Antifactor Xa and Back Again.

Monitoring is essential to safe anticoagulation prescribing and requires close collaboration among pathologists, clinicians, and pharmacists. We describe our experience in the evolving strategy for laboratory testing of unfractionated heparin (UFH). An intrainstitutional investigation revealed significant discordance between activated partial thromboplastin time (aPTT) and antifactor Xa (anti-Xa) assays, prompting a transition from the former to the latter in 2013. With the increasing use of oral factor Xa inhibitors (eg, apixaban, rivaroxaban, edoxaban, betrixaban), which interfere with the anti-Xa assay, we adapted our protocol again to incorporate aPTT in patients admitted on oral Xa inhibitors who require transition to UFH. Our experience demonstrates key challenges in anticoagulation and highlights the importance of clinical pathologists in helping health systems adapt to the changing anticoagulation landscape.

Usefulness of Routine Coagulation Tests in Healthy Children Undergoing Elective Minor Surgery: a 12-Year Retrospective Study.

Although routine coagulation tests, such as prothrombin time (PT) and activated partial thromboplastin time (aPTT) are performed before surgery to identify the risk of perioperative bleeding, bleeding complications are rare in minor surgeries, and false-positive results are often observed. Therefore, this study aimed to analyze the common causes of abnormal results of preoperative coagulation tests in previously healthy children undergoing elective minor surgery and determine the usefulness of performing these tests. Additionally, it aimed to identify the distribution of factor XII activity in children with prolonged aPTT. The medical records of 363 pediatric patients aged 0 - 18 years, who were referred to the pediatric hematology-oncology department due to abnormal preoperative coagulation tests prior to undergoing minor surgery at the Kyung Hee University Medical Center between March 2008 and October 2020, were retrospectively review-ed. The majority of patients (n = 348, 96%) had prolonged aPTT, few (n = 29, 8%) had a prolonged PT international normalized ratio, and a small number (n = 14, 4%) had both prolonged PT and aPTT. On repeating the coagulation tests, 194 children showed persistent abnormal results. Of these, 184 patients underwent mixing tests, and 176 showed correction for factor deficiency (n = 26) and lupus anticoagulant positive (n = 14). Factor deficiencies included factor XII (n = 16), possibility of von Willebrand disease (vWD; n = 4), factor XI (n = 2), factor VIII (n = 1), factors IX and XII (n = 1), factor VII (n = 1), and factor V (n = 1). The severity of factor deficiency was mild (25 - 38%). One patient with factor VII deficiency received preoperative clotting factors but had postoperative bleeding requiring clotting factor replacement. Another patient with possible vWD received fresh frozen plasma after surgery and had mild symptoms. Linear regression showed no significant correlation between factor XII activity and aPTT in patients with prolonged aPTT (R2 = 0.0002, p = 0.84) or factor XII activity according to aPTT results in those with factor XII deficiency (R2 = 0.04749, p = 0.40). These results suggest that coagulation tests may be selectively performed in previously healthy children undergoing minor surgery with positive bleeding and/or family history. The distribution of factor XII should be investigated further.

Emicizumab treatment: Impact on coagulation tests and biological monitoring of haemostasis according to clinical situations (BIMHO group proposals).

Emicizumab, a bispecific humanised monoclonal antibody restoring to some extent the function of activated FVIII deficient in haemophilia A, represents a major therapeutic advance in the management of haemophilia A patients. No dosage adjustment is required, which leads to a major change for patients used to regular biological monitoring which is particularly burdensome in the case of substitution therapy. In some circumstances, such as before an invasive procedure or in case of bleeding, biological monitoring will be necessary and emicizumab's interference with haemostasis tests, particularly those based on an activated partial thromboplastin times (aPTT), must be known to best interpret the tests and to select the most appropriate methods to guide therapy. The normalisation of aPTT in patients treated with emicizumab is not sufficient to consider haemostasis as normalised. In the event of administration of FVIII to a patient receiving emicizumab, the determination of FVIII should use a chromogenic method using non-human reagents. Coagulation global tests have been proposed to evaluate the biological response when using bypassing agents in patients treated with emicizumab, but the usefulness must be confirmed. The French group BIMHO presents proposals for biological monitoring of a patient treated with emicizumab according to clinical situations.

Coagulation profile in patients with chronic liver disease

Background: Chronic liver disease (CLD) is defined as a process of slow and continuous destruction and regeneration of the hepatic parenchyma giving rise to fibrosis and cirrhosis. When it has markedly progressed, it may present with clinical bleeding due to reduction in levels of procoagulant factors, barring some like factor VIII and von Willebrand factor, which are elevated. It is essential to observe that reduced levels of the procoagulants are accompanied by decrease in levels of anticoagulants such as antithrombin and protein C. Under normal conditions, the coagulation machinery is balanced, but the phenomenon of the simultaneous reduction of procoagulants as well as anticoagulants in patients with CLD has been an unsolved puzzle since long. Objective: This study was undertaken to study the relevance and significance of first-line coagulation tests (prothrombin time [PT] and activated partial thromboplastin time [aPTT]) in relation to bleeding manifestations in patients with CLD, to classify the cases of CLD enrolled on the basis of etiology, to study the platelet count, PT, and aPTT values of the cases, and to calculate the Child–Pugh (CP) and model for end-stage liver disease (MELD) scores for all the patients and stratify them accordingly. Materials and Methods: It was a prospective observational study including 40 patients known to be diagnosed with CLD. CP score and MELD were calculated for all. Values of coagulation parameters were compared in patients with and without cirrhosis, in patients belonging to different CP classes, those with low and high MELD scores, and patients with or without upper gastrointestinal (UGI) bleed. Results: Means of PT and aPTT were compared in patients with and without cirrhosis where it was found that there was no statistically significant prolongation of PT or aPTT in patients with cirrhosis compared to those without. We also studied the values of PT and aPTT through increasing grades of CP score and found statistically significant difference between values of PT between those belonging to Class A versus Class C. It was observed that the difference of the mean of PT of the two groups (with MELD

The Use of Point of Care Testing for Monitoring of APTT in Patients Receiving Heparin Infusion

Background: There is a high risk of thromboembolic events among patients undergoing cardiac surgery, and perioperative anticoagulation is sometimes required. The time taken for laboratory based APTT blood sampling results and adjustments may compromise patient safety. There is evidence in the literature to suggest that bedside testing turnaround times is of benefit to inpatient care, and conversely that POCT is inaccurate. The primary aim of this study was to determine if point of care testing of APTT was accurate when compared to laboratory based APTT measurements. The secondary aim was to identify if there was a correlation between operator experience and accuracy of results. Methods: Following full ethics approval by the Royal Adelaide Hospital, Human Research Ethics Committee (HREC), current Cardiothoracic Surgery Unit inpatients were enrolled in the study over a period from July 2016-March 2017. A total of 50 samples were obtained from the minimum number of patients required and separated into three tiers; point of care testing group from finger prick test, point of care testing group from standard postoperative blood sample, and laboratory based testing of standard postoperative blood sample. Results were correlated with Central Adelaide Local Health Network (CALHN) heparin infusion protocols. Clinically significant samples were those which POCT IV and laboratory IV results varied enough to alter the heparin infusion protocol rate change. Results: Demographics showed 83% of patients were male, 67% were receiving IV heparin preoperatively for unstable coronary artery disease, and the mean age of participants was 66 years. Of the 50 collected samples, 17/50 (34%) were recorded as being clinically significant. On the adjusted POCT protocol, 14/50 (28%) of samples were clinically significant. There was a statistically significant difference between POCT IV and laboratory IV results; p = 0.02 and mean difference between values was 19.1. Linear regression analysis showed a poor correlation between POCT IV and laboratory IV samples. There was no relationship between preoperative and postoperative samples. Conclusions: Point of care testing in our study of 50 patient samples shows that there is a poor correlation between POCT and laboratory based testing. Additionally, there is a steep learning curve for those performing the test with no marked improvement following progressive samples. Accordingly, POCT testing in cardiac surgery patients is not recommended for clinical use until further research is completed showing improved correlation between tests, and methods to overcome the steep learning curve are identified.

Establishment and assessment of APTT assay based on the combinations of Mg2+ and Ca2+ for lupus anticoagulants measurements

Objective To establish and assess the new method of APTT assay based on the combinations of Mg2+ and Ca2+ for lupus anticoagulants (LA) measurements. Methods This prospective study included 309 trisodium citrate anticoagulated plasma samples from 244 random patients and 65 patients with different autoimmune diseases (AID) to establish and assess the method of LA measurement, respectively. Final concentrations of 0, 2.0, 4.0, 8.0, 16.0 mmol/L Mg2+ were added into 25 mmol/L Ca2+ solution, and Actin reagent was used to measured plasma APTT of 94 patients. The applied concentration of Mg2+ -Ca2+ solution was confirmed through the special and significant alteration of APTT from LA-positive and -negative plasma observed in the presence of Mg2+ (test solution). Based on Actin reagent use, the test solution and 25 mmol/L Ca2+ solution were applied to measure APTT of patients and normal individuals, respectively, and the ratio of Mg2+ -Ca2+ -APTT to Ca2+ -APTT (Mg2+ -Ca2+ -APTT indices) and normalized Mg2+ -Ca2+ -APTT indices (NAR) were calculated, respectively. Mixed plasma NAR was measured, and CV% was calculated to evaluate the repeatability and stability of Mg2+ -Ca2+ -APTT method. APTT of 150 patients was measured with the test solution and Actin reagent to calculate Mg2+ -Ca2+ -APTT indices, and normalized LA ratio was determined with dRVVT method. The applicability of Mg2+ -Ca2+ -APTT assay was assessed through comparisons of the results from the two methods. Finally, NAR and NLR of 65 patients with AID (including 26 SLE patients) were measured with Mg2+ -Ca2+ -APTT assay and dRVVT method, respectively, and ROC curve was also used to assess the efficacy of the two methods for LA measurements. Results In all LA-negative plasma, APTT increased from 28.1±4.5 s to 61.2±7.9 s in normal APTT group , 47.2±8.9 s to 97.5±10.3 s in increased APTT group, and 27.6±5.1 s to 61.2±7.9 s in ACA-positive group when Mg2+ increased from 0 to 8 mmol/L in Mg2+ -Ca2+ solution (F=34.12, 38.9 and 28.35, P 1.034 of Mg2+ /Ca2+ indices, there was 141 patients with increased indices and NLR<1.20, and 9 patients with decreased ones and NLR≥1.20 in all 150 patients. The area under ROC curve of NAR and NLR for LA detection was 0.913 (95% CI: 0.848-0.978) and 0.892(95% CI: 0.817-0.966), respectively, and the cut-off value was 0.87 and 1.13, respectively. The sensitivity and specificity of NAR (85% and 77%) was higher than that of NLR (81% and 74%), respectively. The accordant rate of positive, negative, and total results between NAR and NLR was 94.4%, 98.5%, and 98%, respectively. Conclusion The method of APTT assay based on Mg2+ combining Ca2+ for LA measurements is feasible, and can be used to detect plasma LA of patients.(Chin J Lab Med, 2018, 41: 165-170) Key words: Magnesium; Calcium; Partial thromboplastin time; Lupus coagulation inhibitor

Utility of Clot Waveform Analysis in Russell's Viper Bite Victims with Hematotoxicity.

Introduction:In Russell's viper bites, due to the lack of a better alternative, whole blood clotting test (WBCT) remains the standard test even though its reliability and sensitivity has been shown to be low. Activated partial thromboplastin time (aPTT)-based clot waveform analysis (CWA) is an optic absorbance assay that can be used as a global clotting test. In this study, the objective was to assess the changes in CWA and to compare CWA to WBCT and aPTT in patients with Russell's viper envenomation.Methods:The datum was collected prospectively over 2 months as a pilot observational study in a tertiary care center. All proven cases of Russell's viper-envenomated individuals with preliminary CWA data and WBCT were included in the study. The clot wave (CW) of the five individuals, which met all the stringent inclusion criteria, was analyzed and interpreted.Results:CW absorbance sigmoid waveform was deranged in all 5 cases, of which 4 showed a change in CWA even before an abnormal aPTT. Three of the 5 had a normal WBCT but showed early changes in CWA. Atypical biphasic waveform reported in disseminated intravascular coagulation in other prior studies is seen in venom-induced consumptive coagulopathy also. In all patients where a second derivative was plotted, the second (lower) phase of the second derivative showed a slow rise to baseline.Conclusion:CWA showed changes which provided information earlier than the conventional coagulation studies in the snakebite victims studied. While aPTT or WBCT reflects clotting time, CWA conveys the dynamic process of clot formation and stabilization. CWA may reveal disorders of clotting in snakebite victims before the conventional tests become abnormal. Future research should assess the speed and accuracy of the test in diagnosing hemotoxic envenomation and its potential role in guiding antivenom therapy.

Point of Care Testing for APTT in Patients on Heparin Infusion – Beneficial or Not?

Point of Care Testing for APTT in Patients on Heparin Infusion – Beneficial or Not?

Comparison of Time to Therapeutic aPTT in Patients Who Received Continuous Unfractionated Heparin After Implementation of Pharmacy-wide Intervention Alerts.

Background: For patients on continuous IV unfractionated heparin (UFH), failing to achieve a therapeutic aPTT by 24 hours can be associated with increased morbidity. A pharmacy clinical surveillance system (PCSS) subtherapeutic aPTT alert was implemented at our institution to improve achievement of therapeutic aPTT goals by 24 hours. Objective: The primary objective was the time to achieve the minimum goal aPTT before and after the alert implementation. The secondary objectives were to examine the percentage of patients who achieved the minimum goal aPTT by 24 hours and the number of dose changes to achieve the minimum goal aPTT. Methods: A single-center retrospective study was conducted to include all adult inpatients receiving a continuous UFH infusion during a 3-month period prior to the implementation of a subtherapeutic aPTT alert and a 3-month period after implementation. Results: 317 patients were included in the analysis. The average time to achieve the minimum goal aPTT was 21.8 hours prior to alert implementation and 15.4 hours after implementation (p = .002). The percent of patients who achieved the minimum goal aPTT by 24 hours was 65.7% prior to alert implementation and 82.4% after implementation (p = .035). The average number of dose changes necessary to achieve aPTT value to the minimum goal aPTT prior to alert implementation was 1.67 and 1. 98 after implementation (p = .68). Conclusion: This analysis showed that implementation of a PCSS subtherapeutic aPTT alert for patients on continuous UFH infusions may ensure patients reach goal aPTT faster and facilitate a higher percent of patients who achieve the minimum goal aPTT by 24 hours.

Clinical implication of monitoring rivaroxaban and apixaban by using anti-factor Xa assay in patients with non-valvular atrial fibrillation

BackgroundAlthough patients taking non-vitamin K antagonist oral anticoagulants (NOACs) do not require routine coagulation monitoring, high-risk patients require monitoring to assess pharmacodynamics. MethodsWe measured (1) anti-factor Xa activity (AXA), using chromogenic assay with the HemosIL Liquid Heparin kit, (2) prothrombin time (PT), and (3) activated partial thromboplastin time (aPTT) in 188 blood samples from 70 patients with non-valvular atrial fibrillation, of whom 36 received rivaroxaban once daily and 34 received apixaban twice daily. ResultsAfter the rivaroxaban therapy, AXA ranged from 0 to 3.65IU/mL; PT, from 9.6 to 44.5s; and APTT, from 19.3 to 69.7s. After the apixaban therapy, AXA ranged from 0.02 to 3.18IU/mL; PT, from 10.2 to 20.8s; and APTT, from 21.8 to 59.8s. At peak time, the AXA of patients who received rivaroxaban and apixaban were almost the same (2.08±0.91IU/mL vs. 1.71±0.57IU/mL), but the PT and APTT of patients who received rivaroxaban were more prolonged than those of patients who received apixaban (18.1±5.6s vs. 13.8±0.9s, p<0.001 and 40.9±7.3s vs. 35.5±7.5s, p<0.01, respectively). At trough time, the AXA and PT of patients who received rivaroxaban were respectively lower and shorter than those of patients who received apixaban (0.28±0.31IU/mL vs. 1.04±0.72IU/mL, p<0.001 and 11.9±2.0s vs. 13.7±2.4s, p<0.01, respectively), but the APTT of patients who received rivaroxaban and apixaban did not significantly differ (32.3±4.3s vs. 34.3±3.8s). ConclusionsMeasurement of AXA might be useful to assess the pharmacodynamics of high-risk patients, such as high age, low body weight, and/or low renal function, and to assess the intensity of anticoagulation by using different methods of administration, such as crushed tablet via the nasogastric tube.

(507) - Comparison of Monitoring Unfractionated Heparin Using Anti-Xa vs. aPTT in Patients With Ventricular Assist Devices

(507) - Comparison of Monitoring Unfractionated Heparin Using Anti-Xa vs. aPTT in Patients With Ventricular Assist Devices

Monitoring of Unfractionated Heparin Using Activated Partial Thromboplastin Time

We frequently encounter high levels of activated partial thromboplastin time (aPTT) during heparin anticoagulation. The purpose of this study is, first, to investigate the rate of achieving and maintaining therapeutic aPTT in patients treated with heparin anticoagulation and second, to assess the adequacy the current nomogram. We included 197 patients who underwent anticoagulation with unfractionated heparin (UFH) according to the standard nomogram between September 2008 and May 2010. The primary endpoints were the rate of achieving a therapeutic range (TR) at the first sample, 24 hours, or 48 hours. We also compared heparin nomograms according to age (<70 years vs ≥70 years). Of the 197 patients, 131 had heparin loading. In the heparin loading group, there were 19.1% (n=25), 69.5% (n=91), and 90.1% (n=18) achieving TR at the first aPTT, 24 hours, and 48 hours, respectively. The therapeutic aPTT proportion was 39.2%, and the rate of peak level above 90 seconds was 93.1%. Peak levels of aPTT were higher in the older age group than in the younger age group (202.3 ± 124.2 versus 152.0 ± 78.9, p=0.007). Our results indicate a high rate of achieving therapeutic aPTT at 24 hous and 48 hours, but a low success rate for maintenance within the TR. Most patients had supratherapeutic aPTT of more than 90 seconds. Therefore, the TR of aPTT that matches heparin levels of 0.3 to 0.7 IU/mL measured by antifactor Xa assay should be determined. If not, we should consider adopting a new heparin dosing nomogram.

Prognostic value of post-procedural aPTT in patients with ST-elevation myocardial infarction treated with primary PCI

Unfractionated heparin is the most commonly used anticoagulant in ST-elevation myocardial infarction (STEMI) and its effect can be monitored with activated partial thromboplastin time (aPTT). However, the optimal aPTT range during heparin therapy after primary percutaneous coronary intervention (PCI) is yet to be defined. A mean aPTT was calculated of all aPTT measurements in the first 24 hours after pPCI in a total of 1,876 STEMI patients. Mean aPTT measurements were stratified into four categories; < 1.5 times the upper limit of normal (ULN), 1.5 - 2.0 times ULN (the therapeutic group), 2.01 - 3.99 times ULN, and ≥ 4 times ULN. Compared to patients with a therapeutic aPTT, patients with aPTTs < 1.5 times ULN had no increase in recurrent ischaemic events and had similar rates of bleeding complications. Patients with a mean aPTT ≥ 4 times ULN had higher rates recurrent ischaemic and haemorrhagic complications. After multivariable analyses, aPTT ratios ≥ 4 times ULN were no longer associated with recurrent ischaemic events, but remained a strong predictor of severe and moderate bleeding (hazard ratio [HR] 4.64, p = 0.016 and HR 2.27, p = 0.052). In conclusion, in 1,876 STEMI patients treated with pPCI, low aPTTs in the first 24 hours after PCI were not associated with an increase in ischaemic events, whereas high aPTT values were associated with more frequent bleeding complications. These results indicate no clear benefit as well as a safety concern with heparin treatment after primary PCI.

Suboptimal monitoring and dosing of unfractionated heparin in comparative studies with low-molecular-weight heparin.

Site-specific validation of the activated partial thromboplastin time (aPTT) therapeutic range is required to ensure administration of the optimal dose of unfractionated heparin. Therapeutic ranges of 1.5 to 2.5 times the control value are subtherapeutic for most modern aPTT reagents. To audit the appropriateness of aPTT monitoring in clinical trials comparing unfractionated heparin and low-molecular-weight heparin in patients with venous thromboembolism. Search of PubMed database from 1984 to 2001. Randomized, controlled trials that compared unfractionated and low-molecular-weight heparin for the treatment of venous thromboembolism. Use of unvalidated and potentially suboptimal therapeutic ranges for aPTT in patients assigned to receive unfractionated heparin. Fifteen studies met inclusion criteria. Only 3 studies used a validated aPTT therapeutic range, and 11 studies used a range that included aPTT values 1.5 times the control value. Ten studies reported unfractionated heparin doses, and 7 of these documented a reduction to less than 30 000 U/d in response to aPTT results. Most studies monitored unfractionated heparin inappropriately. This shortcoming could be responsible for the reduced efficacy of unfractionated heparin in clinical trials.

A new regimen for heparin use in acute coronary syndromes

Background Recent trials have demonstrated an association between high activated partial thromboplastin time (aPTT) and bleeding, intracranial hemorrhage, reinfarction, and death in patients with acute coronary syndromes treated with heparin. Of all the factors that affect aPTT in patients treated with heparin, body weight is most strongly correlated. Methods We compared the efficacy of 2 weight-adjusted heparin regimens (groups 2 and 3) and the standard (group 1) non–weight-adjusted 5000-U intravenous bolus/1000 U/hr infusion to achieve an aPTT between 45 and 70 seconds in a nonrandomized prospective cohort of 80 patients admitted with unstable angina and non-ST elevation myocardial infarction. Results Patients treated with the lower dose of weight-adjusted heparin (60 U/kg intravenous bolus, maximum of 4000 U; 12 U/kg/hr, maximum 900 U/kg), group 3, were more often within the target range for aPTT at 6 hours (34% vs 5% vs 0%) and required fewer heparin infusion changes (1.0 ± 1.0 vs 1.9 ± 1.0 vs 2.0 ± 0.9) within the first 24 hours compared with the other regimens. Patients in groups 1 and 2 were overwhelmingly above target range at 6 hours (95% and 84%, respectively, compared with 48% in group 3). Conclusions Traditional heparin dosing regimens result in marked initial overanticoagulation in patients with acute coronary syndromes, which may place these patients at higher risk of adverse outcomes. A lower dose weight-adjusted heparin regimen is superior in achieving early aPTTs within the target range and reducing the need for infusion changes over the ensuing 24 hours. (Am Heart J 1999;138:313-8.)

Comparison of activated partial thromboplastin time to activated clotting time for adequacy of heparin anticoagulation just before percutaneous transluminal coronary angioplasty

Patients must undergo systemic anticoagulation with heparin before undergoing percutaneous transluminal coronary angioplasty (PTCA) to minimize the risk of intracoronary thrombus formation and acute vessel occlusion. Although most patients undergo anticoagulation just before PTCA, a subset consisting of those who have received thrombolytic therapy and those with unstable angina are frequently brought to the interventional laboratory already being treated with a continuous heparin infusion. Such anticoagulation is thought to reduce the risk of spontaneous coronary thrombosis. Heparin anticoagulation is typically monitored using activated partial thromboplastin time (aPTT). There are several other laboratory methods, however, available for evaluating the anticoagulant effect of heparin. The activated clotting time (ACT) is another frequently used parameter 1 that is rapidly obtainable in an on-line fashion. Bedside kits have also become available for the rapid determination of aPTT. This study determines if therapeutic aPTT in patients maintained on a continuous heparin infusion for > 24 hours before PTCA is indicative of an adequate level of preprocedural anticoagulation as assessed by ACT.

Pharmacology of r-hirudin in renal impairment

The pharmacokinetic properties of r-hirudin were studied in nine patients suffering from different degrees of renal insufficiency. To this end, r-hirudin was administered intravenously at dosages of 0.1 mg/kg. The elimination half-life t 1 2β was determined in blood plasma and the cumulative r-hirudin excretion in urine was measured over 48 h. In healthy volunteers t 1 2β was 0.9 ± 0.2 h; the cumulative r-hirudin excretion in urine after 48 h amounted to 38 ± 10 % of the dose administered, most of this quantity was excreted during the first hours. In seven patients with chronic renal failure, t 1 2β was 15 to 41 h; in three of these patients cumulative urinary r-hirudin excretion was increased to 70 – 80 %, in four patients cumulative r-hirudin excretion in urine within 48 h amounted to 39 ± 8 %, but was delayed in time. In 2 bilaterally nephrectomized patients, t 1 2β was 168 and 316 h, resp. The renal clearance of hirudin was significantly and linearly correlated with the creatinine clearance (r=0.872). In all patients aPTT and bleeding time were only moderately prolonged. Because of the modified pharmacokinetic behaviour the administration of hirudin in patients with impaired renal function requires individually adjusted dosages or prolonged administration intervals.