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Elevated activated partial thromboplastin time during administration of first-generation adenoviral vectors for gene therapy for prostate cancer: identification of lupus anticoagulants.

OBJECTIVES: To evaluate the cause and significance of elevated activated partial thromboplastin time (aPTT) in a group of patients who received a first-generation adenoviral vector (Ad-OC-TK) delivering a toxic gene to prostate cancer cells as part of a Phase I clinical trial at the University of Virginia. METHODS: Eleven subjects were injected intratumorally to metastatic lesions of prostate cancer in the prostatic fossa, retroperitoneal lymph nodes, or bone (iliac, ischium, or vertebrae). After the initial laboratory evaluation, patients with elevated aPTT underwent a series of additional tests, including mixing studies, coagulation factor, prekallikrein, and high-molecular-weight kininogen, and lupus anticoagulant studies (modified Russell viper venom time) with phospholipid correction, and a Staclot LA assay. RESULTS: Of the 11 subjects who were enrolled in the trial, 6 had elevated aPTT values. Of the 6 patients, 3 had aPTT elevation of more than 10 seconds above normal. Two of the subjects with higher values demonstrated an inhibitory pattern with the factor VIII and XI assays, and the lupus anticoagulant studies were positive. No clinical sequelae to the elevated aPTT values were observed. CONCLUSIONS: This is, to our knowledge, the first formal report of a first-generation adenoviral vector causing a slight transient elevation of the aPTT through the induction of an antiphospholipid antibody. No clinical sequelae related to elevated aPTT values were observed. The adenoviral protocol was safe; similar protocols should be aware of this phenomenon.

Adenoviridae↗

Relation between systemic anticoagulation as determined by activated partial thromboplastin time and heparin measurements and in-hospital clinical events in unstable angina and non-Q wave myocardiaL infarction. Thrombolysis in Myocardial Ischemia III B Investigators.

Although coronary thrombosis is thought to play a pivotal role in the pathogenesis of unstable angina and non-Q wave myocardial infarction and antithrombotic therapy is a mainstay in the early management of these patients, the relation between measures of systemic anticoagulation and clinical events has not been defined clearly. In the Thrombolysis in Myocardial Ischemia III trial, 1473 patients with ischemic chest pain at rest evaluated within 24 hours of symptom onset were randomized to (1) tissue plasminogen activator (TPA) or placebo and (2) an early invasive or an early conservative strategy. All patients received a full complement of anti-ischemic medication, aspirin, and continuous intravenous heparin titrated to an activated partial thromboplastin time (aPTT) of 1.5 to 2.0 times control for 72 to 96 hours. The median aPTT in all study groups exceeded the minimum threshold (45 seconds) by 24 hours and remained within the designated range during the protocol-directed heparin infusion. No differences in median aPTT values for the 72- to 96-hour study period were observed between groups (p=not significant). Median 12-hour heparin concentrations were >0.2 U/ml in all groups; however, values <0.2 U/ml were common thereafter, particularly in TPA-treated patients. Time-dependent covariate analyses failed to identify statistically significant differences in either aPTT or heparin levels between patients with in-hospital clinical events (spontaneous ischemia, myocardial infarction, or death) and those without events (p=0.27). Furthermore, early clinical events occurred in a similar percentage of patients with optimal anticoagulation (all aPTTs >60 seconds, all heparin levels>0.2 U/ml), and those with aPTTs or heparin levels below these thresholds. Aggressive (high-intensity) anticoagulation with heparin to achieve aPTTs >2.0 times control does not appear to offer additional clinical benefit to lower levels (1.5 to 2.0 times control) among patients with unstable angina and non-Q wave myocardial infarction receiving intravenous heparin and oral aspirin. Therefore, the optimal level of anticoagulation in this common clinical setting is between 45 and 60 seconds when heparin is included in the treatment strategy. Direct plasma heparin measurement does not offer an advantage to routine aPTT monitoring. The occurrence of spontaneous ischemia, myocardial infarction, and death in spite of antischemic therapy and optimal anticoagulation (as it is currently defined) with heparin supports ongoing efforts to develop more effective antithrombotic agents.

Aged↗

Use of bedside activated partial thromboplastin time monitor to adjust heparin dosing after thrombolysis for acute myocardial infarction: results of GUSTO-I. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.

BACKGROUND: The safety and efficacy of bedside monitors of activated partial thromboplastin time (aPTT) have not been examined in a large population receiving intravenous heparin after thrombolytic treatment for acute myocardial infarction. We compared outcomes among patients monitored with these devices versus standard monitoring methods. METHODS AND RESULTS: Investigators chose the bedside device (n = 1713 patients) or their standard method (n = 26,162) for all aPTT measurements at their sites. Clinical outcomes at 30 days, 1-year mortality rate, and aPTT levels at 6, 12, and 24 hours were compared. Bedside-monitored patients had significantly less moderate/severe bleeding (10% vs 12%, P < .01), fewer transfusions (7% vs 11%, P < .001), and a smaller decrease in hematocrit (5.5% vs 6.7%, P < .001) but significantly more recurrent ischemia (22% vs 20%, P = .01). Fewer bedside-monitored patients had subtherapeutic aPTT levels at 12 and 24 hours. Among patients with subtherapeutic levels at 6 and 12 hours, more bedside-monitored patients had therapeutic levels when next monitored. After adjustment for baseline differences, no significant difference in mortality rate was observed in bedside-monitored patients at 30 days (4.3% vs 4.8%, P = .27) and at 1 year (7.1% vs 7.7%, P = .38). The groups had similar rates of reinfarction, shock, heart failure, and stroke. CONCLUSIONS: This prospective substudy supports the use of bedside monitoring of heparin anticoagulation after thrombolysis.

Aged↗

Stability of prothrombin time and activated partial thromboplastin time tests under different storage conditions.

Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are common laboratory tests that are useful in the diagnosis of coagulation disorders and monitoring anticoagulant therapy. Recent expansions in the outreach laboratory services at our institution prompted us to investigate the shipping limitations for some tests, including PT and aPTT. Although we followed NCCLS guidelines for the collection of blood specimens, we observed falsely elevated PT and aPTT values due to the different storage conditions. The objective of this study is to determine the effect of conditions and duration of storage on PT and aPTT tests using plasma and whole blood samples, respectively. For this study, 36 plasma samples with normal and prolonged PT and aPTT were exposed to different storage conditions. Blood was centrifuged immediately and plasma was stored at room temperature (RT), refrigerated at 4 degrees C, or frozen at -20 degrees C. The samples were analyzed at 0 h and repeated at 6, 12 and 24 h under various conditions. Although statistically significant differences were observed for plasma samples for normal PT tests after 12 h at refrigerated and frozen storage conditions, the differences would not change the clinical interpretation of the results. On the other hand, samples stored refrigerated or at RT showed significant differences for aPTT at 24 h. These differences would change clinical interpretation, especially for samples with normal or near normal aPTT times. Interestingly, aPTT was significantly higher for samples stored frozen when compared to refrigerated and RT conditions at 6 h. Similar patterns were also observed on ten whole blood samples with normal PT and aPTT values. In conclusion, either plasma or whole blood samples can be accepted for PT testing up to 24 h and for aPTT testing up to 12 h only, when transported either at RT or at 4 degrees C.

Humans↗

Analysis of the activated partial thromboplastin time test using mathematical modeling.

Activated partial thromboplastin time (APTT) is a laboratory test for the diagnosis of blood coagulation disorders. The test consists of two stages: The first one is the preincubation of a plasma sample with negatively charged materials (kaolin, ellagic acid etc.) to activate factors XII and XI; the second stage begins after the addition of calcium ions that triggers a chain of calcium-dependent enzymatic reactions resulting in fibrinogen clotting. Mathematical modeling was used for the analysis of the APTT test. The process of coagulation was described by a set of coupled differential equations that were solved by the numerical method. It was found that as little as 2.3 x 10(-9) microM of factor XIIa (1/10000 of its plasma concentration) is enough to cause the complete activation of factor XII and prekallikrein (PK) during the first 20 s of the preincubation phase. By the end of this phase, kallikrein (K) is completely inhibited, residual activity of factor XIIa is 54%, and factor XI is activated by 26%. Once a clot is formed, factor II is activated by 4%, factor X by 5%, factor IX by 90%, and factor XI by 39%. Calculated clotting time using protein concentrations found in the blood of healthy people was 40.5 s. The most pronounced prolongation of APTT is caused by a decrease in factor X concentration.

Blood Coagulation Disorders↗

Monitoring of unfractionated heparin with the activated partial thromboplastin time: determination of therapeutic ranges.

The purpose of the present study was to determine therapeutic ranges for unfractionated heparin therapy using the activated partial thromboplastin time (APTT) by calibration against anti-Xa concentration. APTT assays were performed locally, i.e. at the institution of blood collection, on fresh plasma samples from patients treated with intravenous unfractionated heparin. The measurements were performed by 25 Dutch clinical laboratories using 11 different APTT reagents and 10 different types of coagulometers. After the local APTT measurement, the samples were frozen and transported to a central laboratory for measurement of anti-Xa activity. The number of samples from the participating laboratories ranged from 10 to 48. Local APTT results were correlated with the central anti-Xa measurements. Orthogonal regression analysis of log-transformed values was used to calculate APTT therapeutic ranges corresponding to anti-Xa concentrations of 0.29-0.47 IU/ml. The calculated APTT ranges were different between laboratories, even when the same reagent was used. In many laboratories, the therapeutic APTT range in use was much wider than the calculated range. Imprecision of the calculated APTT range was influenced by the wide scatter of the measurement points and by the selection of samples for the orthogonal regression equation. The present results show that, if anti-Xa concentrations of 0.29-0.47 IU/ml reflect the true therapeutic range, many laboratories do not use the proper therapeutic APTT range.

Dose-Response Relationship, Drug↗

Antibodies to thromboplastin in systemic lupus erythematosus: isotype distribution and clinical significance in a series of 92 patients.

We determined the prevalence and relationship with clinical manifestations of antibodies to thromboplastin (aTP) in 92 patients with systemic lupus erythematosus (SLE). Thirty-two (35%) patients had aTP: 13 (14%) were positive for IgG aTP, 13 (14%) for IgM aTP, and 6 (7%) for both. Patients with aTP had an increased incidence of thrombosis (p = 0.01), thrombocytopenia (p < 0.001), hemolytic anemia (p < 0.001), and fetal losses (p = 0.03). When the IgG and IgM aTP isotypes were analysed separately, the IgG aTP were found to be associated with thrombosis (p < 0.001), thrombocytopenia (p < 0.001), and fetal losses (p = 0.02). The IgM aTP were associated with hemolytic anemia (p < 0.001). A correlation was found between the titers of aTP and those of anticardiolipin antibodies, in both IgG (p < 0.01, r = 0.6) and IgM (p < 0.01, r = 0.64) isotypes, and between the titers of IgG aTP and the diluted Russell's viper venom time used to detect the lupus anticoagulant (p < 0.001, r = 0.42). This test is a reliable, reproducible and sensitive assay for the detection of antiphospholipid antibodies, specially in those patients under anticoagulant therapy.

Adolescent↗

Measuring partial thromboplastin-time. An international collaborative study.

A series of collaborative exercises on the partial thromboplastin-time (P.T.T.) test, involving over three hundred hospital centres in Britain and overseas, were performed in 1975. Lyophilised test plasmas were issued from the World Health Organisation Collaborating Centre for Anticoagulant Control Reagents to participants, together with a standardised reference P.T.T. reagent and a standard technique. Hospitals were asked to test the plasma samples with the standardised reagent and technique in parallel with their customary local P.T.T. reagent and method. The overall success-rate in detecting the intrinsic clotting abnormality in the eight abnormal test samples was higher with the standardised reagent and technique than with all other reagents. Furthermore, fewer hospitals obtained false positive results when the normal plasma sample was tested with the standardised method rather than with their usual routine reagents. An index was used to measure the success-rate of the P.T.T. reagents in correctly identifying the test plasmas as normal or abnormal. The eight test plasmas showed a varying degree of abnormality. A system of "weighting" was therefore introduced as the failure of a P.T.T. method to detect more severe defects was regarded as more serious. Although hospitals were unfamiliar with the standardised method, the results established its superiority over all other P.T.T. reagents included in the trials in sufficient numbers for analysis. Failures with commercial reagents may have been caused by insensitivity of the cephalin extracts or the unreliability of the manufacturers recommended techniques. Since the same laboratories obtained good results with the standardised method technical failure can be excluded.

Blood Coagulation Disorders↗

The need for routine pre-operative coagulation screening tests (prothrombin time PT/partial thromboplastin time PTT) for healthy children undergoing elective tonsillectomy and/or adenoidectomy.

In some medical centers, the routine pre-operative evaluation of healthy children undergoing elective tonsillectomy and/or adenoidectomy (T and A) includes coagulation screening tests (PT, prothrombin Time; PTT, partial thromboplastin time; and INR, international normalized ratio). In this retrospective study, we determined whether there is a positive correlation between prolonged PT/PTT/INR tests in healthy children, with no prior medical history of coagulation problems, and bleeding during surgery and/or bleeding in the month following surgery. We reviewed the records of 416 elective T and A surgeries performed at the Soroka University Medical Center in Beer-Sheva, Israel, over the course of 1999. One hundred and twenty-one (29.1%) patients had preoperative prolonged PT values but only four (3.3%) of these patients experienced light bleeding during surgery. Seven (5.8%) of the 121 patients with prolonged PT tests experienced bleeding episodes during the 1st month subsequent to the surgery. Of the 65 (15.6%) patients who had prolonged pre-operative INR values, only three (4.6%) experienced light bleeding during surgery. Two (3.1%) patients with prolonged INR values experienced light bleeding during the 1st month subsequent to surgery. Sixty-one (14.7%) patients had prolonged first preoperative PTT values, only five of whom (8.2%) experienced light bleeding during surgery. Two (3.3%) of the 61 with prolonged PTT values experienced light bleeding during the 1st month subsequent to surgery. We therefore concluded that pre-operative coagulation screening tests provide low sensitivity and low bleeding predictive value. As such, routine coagulation tests before T &A are not indicated unless a medical history of bleeding tendency is suspected.

Adenoidectomy↗

Activated partial thromboplastin time (aPTT) monitoring to achieve therapeutic anticoagulation before and after introducing a nomogram for adjunctive heparin treatment with thrombolytic therapy for acute myocardial infarction.

In patients with acute myocardial infarction (AMI) receiving thrombolytic therapy and i.v. unfractionated heparin, anticoagulant levels are frequently outside the target range. We evaluated the effects on anticoagulant levels before (group A) and after (group B) the introduction of a heparin nomogram in consecutive AMI-patients, receiving thrombolytic therapy and adjunctive heparin treatment. The target activated partial thromboplastin time (aPTT) was defined as 60-90 s. During the first 72 h after admission, the total number of aPTTs within the target range and the time taken to achieve the range were compared. The incidence of bleeding complications was assessed. Group A consisted of 56 and group B of 55 patients. The number of patients within the target range at 72 h (44 versus 51; chi2=4.51; P=0.034) was significantly higher in group B. No difference was found between total aPTTs within the target range (26% in group A versus 30% in group B; P=ns). Bleeding complications were slightly less in group B (7 versus in group A versus 2 patients in group B; P=ns). We concluded that the introduction of a nomogram resulted in significantly more patients with aPTTs within the target range. However, a substantial number of aPTTs before and after introduction of the nomogram were outside the target range. Moreover, this retrospective study shows that previously acquired prospective data (which showed a marked improvement of anticoagulation using a heparin nomogram) are not necessarily reproduced in the real life clinical setting.

Aged↗

Value of preoperative prothrombin time/partial thromboplastin time as a predictor of postoperative hemorrhage in pediatric patients undergoing tonsillectomy.

OBJECTIVE: Hemorrhage after tonsillectomy is a potentially lethal complication. Preoperative assessment consisting of prothrombin time (PT) and activated partial thromboplastin time (PTT) has been used to identify patients at risk for hemorrhage after tonsillectomy and adenoidectomy. We sought to assess the value of PT/PTT screening as a predictor of posttonsillectomy hemorrhage. DESIGN: A retrospective chart review was carried out with a minimum of 1 month follow-up. SETTING: Tertiary academic referral center. PATIENTS: Between January 1992 and June 1995, 382 patients undergoing tonsillectomy were examined; 339 patients with a minimum of 1 month follow-up were reviewed for this study. MAIN OUTCOME MEASURE: Normal and prolonged PT/PTT values were examined. Bleeding in the intraoperative, immediate postoperative, and delayed phases of healing was examined. RESULTS: Two-hundred and twenty-two patients had normal PT/PTT, 39 had prolonged PT/PTT, and 78 had no preoperative studies performed. Bleeding occurred in 2.7%, 2.6%, and 3.3%, respectively, of patients. Eight patients had positive family histories of bleeding tendencies. One patient (12.5%) with a normal PT/PTT experienced a delayed posttonsillectomy bleed. Of 39 patients with abnormal coagulation studies, 30 were borderline elevations with no repeat studies done; one patient experienced postoperative hemorrhage. Nine abnormal results were repeated; three returned to normal, three remained prolonged but underwent tonsillectomy with no intervention, and three received hematology consultations. One patient had lupus anticoagulant, one had Hageman Factor deficiency, and one was cleared for surgery with no diagnosis. All patients underwent tonsillectomy with no episodes of postoperative bleeding. CONCLUSIONS: Preoperative PT/PTT provides no additional information than does a bleeding history for the general pediatric population undergoing tonsillectomy. This should only be done in selective cases where warranted by history.

Child↗

Are baseline prothrombin time/partial thromboplastin time values necessary before instituting anticoagulation?

STUDY OBJECTIVES: To determine whether baseline prothrombin time (PT) or partial thromboplastin time (PTT) values provide information that is useful to the clinician before initiating anticoagulation and whether emergency physicians elicit historical information about bleeding disorders before beginning anticoagulant therapy. DESIGN: A three-year retrospective review of the records of 199 patients admitted through the ED with an ICD-9-CM diagnosis of deep-vein thrombosis or pulmonary embolus using a predesigned study sheet that included historical questions, baseline PT and PTT values, treatment given, timing of treatment, and underlying medical problems. SETTING: University-affiliated tertiary-care hospital. MEASUREMENTS AND MAIN RESULTS: Deep-vein thrombosis was the primary diagnosis in 75% of patients. Pertinent historical items were not documented in 92% to 100% of patients. Baseline PT and PTT values were obtained in 94% of patients. An elevated baseline PT was found in 26 patients, all of whom were taking warfarin. An elevated baseline PTT was found in 21 patients. These results were attributed to laboratory error (one), warfarin use (nine), heparin therapy before baseline tests (five), anticardiolipin antibodies (five, one of whom was on warfarin therapy), and unknown causes (three). Heparin therapy was not altered for any patient. CONCLUSION: Emergency physicians rarely document pertinent questions about bleeding disorders before initiating anticoagulation therapy. Baseline PT and PTT values are almost routinely obtained despite the fact that they do not alter therapy or serve as sensitive or specific screening tests. Routine baseline PT and PTT values are rarely needed before initiating anticoagulation. Eliminating such routine testing would result in significant cost savings.

Adolescent↗

Elevated partial thromboplastin time as an indicator of hemorrhagic risk in postoperative patients on warfarin prophylaxis.

Warfarin provides effective prophylaxis against postoperative venous thromboembolic complications in adults undergoing elective hip surgery, but at the risk of increased bleeding complications. Although patients on this drug are routinely monitored by prothrombin time (PT), mild elevations of the partial thromboplastin time (PTT) have been reported with warfarin therapy. In a prospective study of 194 patients undergoing elective hip surgery, the authors assessed the incidence of elevation of the PTT above 50 seconds while the patient was receiving warfarin prophylaxis and the effect of this elevation on bleeding complications. The prophylactic warfarin was begun the night prior to surgery. Thirty-eight patients (19.6%) had a PTT greater than 50 seconds (group 1) and 156 had milder or no elevation of the PTT (group 2). The mean maximum PTT in group 1 was 61.2 ( +/- 12.9), versus 39.9 ( +/- 5.0) seconds in group 2. Major postoperative bleeding complications occurred in 26.3% of group 1 patients, versus 4.5% of group 2 (P less than .01). This subset of patients with an abnormal PTT elevation despite appropriate control of the PT is at a significantly increased risk of major postoperative bleeding. This observation may also prove valuable in reducing bleeding complications from warfarin use in nonsurgical patients.

Blood Coagulation Tests↗

Low-molecular-weight heparin and partial thromboplastin time-adjusted unfractionated heparin in thromboprophylaxis after total knee and total hip arthroplasty.

Thromboprophylaxis with heparins after total hip arthroplasty (THA) and total knee arthroplasty (TKA) is well established. The aim of this study was to compare low-molecular-weight heparin (enoxaparin) with partial thromboplastin time (PTT)-adjusted, unfractionated heparin (heparin sodium). In a prospective study of THA and TKA 246 patients, physical examination and compression and duplex ultrasound were performed 1 day before and 7 and 14 days after surgery. One hundred thirty patients received 40 mg enoxaparin subcutaneously once per day. One hundred sixteen patients received 5,000 IU heparin sodium subcutaneously 3 times daily. As the PTT did not reach 40 seconds, the heparin sodium dosage was increased to 7,500 IU 3 times daily. The overall thrombosis rate was 4% (n = 10). In the enoxaparin group, the rate was 2.9% of the 70 THAs and 10% of the 60 TKAs. Thrombosis also occurred in the group that received heparin sodium: 1.8% of the THAs and 1.7% of the TKAs. For TKA, the difference between the 2 heparin groups was statistically significant. In the thromboprophylaxis of TKA, PTT-adjusted unfractionated heparins are superior to fixed doses of low-molecular-weight heparins.

Aged↗

Activated partial thromboplastin time-protamine dose relation in the presence and absence of heparin.

A protamine titration is one of the methods to determine the protamine dose necessary to neutralize heparin. The protamine dose response was studied with the activated partial thromboplastin time (APTT) in the presence of a known amount of heparin and in the absence of heparin, using freshly prepared human plasma. When heparin was present in the plasma, APTT values plateaued between a minimal neutralizing dose of protamine and a protamine dose five times greater. At doses above the APTT plateau, protamine exerted its own anticoagulant action as evidenced by an increase in APTT values. In the absence of heparin, APTT did not change until the protamine concentration reached 50 micrograms/mL. Then the APTT began to increase above this critical concentration. The increases in APTT values caused by an increase of 50 micrograms/mL of protamine were significantly greater without heparin than they were in the presence of heparin. These results suggest that protamine has a wide safety range when neutralizing heparin without exerting its own anticoagulant action. Although the mechanisms are under speculation, the heparin-protamine complex may inhibit the anticoagulant action of protamine in vitro.

Blood Coagulation↗

The ineffectiveness of a non-weight based heparin regimen in achieving therapeutic activated partial thromboplastin time (aPTT) in acute coronary syndrome.

Although low molecular weight heparin (LMWH) is increasingly being used in the treatment of acute coronary syndrome (ACS), unfractionated intravenous (IV) heparin infusion is still widely used in Australian hospitals for the treatment of ACS. This paper evaluates the effectiveness of a non-weight based heparin regimen in achieving a therapeutic activated partial thromboplastin time (aPTT) within 24 hours of IV heparin commencement. A sequential retrospective chart review of 99 medical records of ACS patients in a district hospital in south western Sydney, Australia, was performed. These patients were prescribed IV heparin and did not receive thrombolytic or warfarin therapy. Only 35 per cent reached a therapeutic aPTT level within 24 hours of commencement of IV heparin therapy. Comparison of therapeutic aPTT and non-therapeutic aPTT groups revealed that body weight was the only factor that was significantly different in the two groups. Patients who reached the therapeutic aPTT threshold within 24 hours weighed significantly less (mean body weight: 70.3 kg versus 80.3 kg) than those who did not reach the therapeutic threshold within 24 hours of heparin commencement (t = 3.80, d.f. = 86, p < 0.001). Given that a significant proportion of patients who require IV heparin therapy exceed the 70 kg body weight, the findings from this study suggest that a non-weight based heparin regimen is ineffective in the rapid achievement of therapeutic aPTT.

Acute Disease↗

Heparin dosing and therapeutic activated partial thromboplastin times (aPTT) in acute coronary syndrome (ACS).

This study assessed the current practices of heparin dosing and determined the extent of therapeutic activated partial thromboplastin times (aPTT) achieved, utilising a standard heparin nomogram in the coronary care unit and step-down cardiac ward of a health care facility in South Australia. The study also examined the effect of actual body weight (ABW), body mass index (BMI), smoking, concomitant intravenous glycerine trinitrate, age, gender and creatinine levels, individually, on the time taken to attain a therapeutic aPTT in acute coronary syndrome (ACS) patients receiving a heparin infusion. A retrospective correlational research design was utilised to include the collection of quantitative data from 66 men and women of all ages and background consecutively admitted into the coronary care unit and the step-down cardiac ward and receiving a continuous heparin infusion. The quantitative data included demographic details plus all information regarding treatment and results of heparin therapy from the patients' medical records. Descriptive analysis of the data revealed 32% of the participants attained a therapeutic level with the first aPTT taken and that, successively, 35% and 45% of the participants attained a therapeutic level with the second and third aPTT taken. The majority of participants were found to be outside of the therapeutic range at any one time during the study. A generalised linear model (log-binomial model) applied to the data revealed that increased ABW (p=0.002), creatinine levels (p=0.033) and, in particular, BMI (p=0.000) were significant risk factors that contributed to the failure of participants attaining a therapeutic aPTT level. Age (p=0.668), gender (p=0.623), smoking (p=0.993) and the use of concomitant intravenous glycerine trinitrate (p=0.897) did not have a significant effect on the time to reach a therapeutic aPTT. The results provide noteworthy information for the re-evaluation of the use of the standard heparin nomogram. A robust randomised clinical trial is required to further examine BMI as the best predictor for heparin requirements in ACS patients receiving a heparin infusion.

Acute Disease↗

Determination of normal versus abnormal activated partial thromboplastin time and prothrombin time after cardiopulmonary bypass.

OBJECTIVE: The study's objective was to determine the prothrombin time (PT) and activated partial thromboplastin time (aPTT) values that differentiated normal from excessively bleeding patients immediately after cardiopulmonary bypass (CPB). DESIGN: A prospective blinded study. SETTING: A large academic medical center. PARTICIPANTS: 148 patients were studied. INTERVENTIONS: aPTT and PT were determined by the hospital laboratory and the Biotrack 512 Coagulation Monitor (Ciba Corning Diagnostics, Medfield, MA) from an arterial whole blood sample obtained 10 minutes after protamine administration. Patients were subjectively and objectively defined as "bleeders" or "nonbleeders" with blinded observers. MEASUREMENTS AND MAIN RESULTS: The specificity and sensitivity were determined by a receiver operating characteristic (ROC) analysis. Twenty-three of 148 patients (14.9%) were characterized as bleeders. The laboratory PT had a maximal specificity and sensitivity of 78% and 75%, respectively, at a value of 15.4 s, with a negative and positive predictive value of 93% and 33%, respectively. The maximal specificity and sensitivity of the laboratory aPTT was 64% and 76%, respectively, at a value of 46 s, with a negative and positive predictive value of 89% and 33%, respectively. aPTT and PT approached normal values after 12 hours in the intensive care unit. CONCLUSION: The aPTT and PT values that produce the maximal sensitivity and specificity in the ROC analysis may be helpful to differentiate patients who are bleeding excessively from those patients who are not after CPB and to guide transfusion of blood products. New whole blood coagulation devices with rapid turn-around times had similar predictive value for bleeding tendency compared with standardized laboratory tests.

Adult↗