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PubMed1997

Properties of optical data from activated partial thromboplastin time and prothrombin time assays.

Changes in characteristics of optical transmittance data from coagulation assays were examined as a function of concentration of coagulation proteins or anticoagulants. Transmittance data were collected for activated partial thromboplastin time (APTT) and prothrombin time (PT) assays from: 1) plasmas prepared by mixing normal plasmas with deficient plasmas to give varying levels of coagulation proteins; 2) plasmas containing added heparin; and 3) 200 specimen plasmas that were also assayed for fibrinogen, coagulation factors, and other components. Optical profiles were characterized using a set of parameters describing onset and completion of coagulation, magnitude of signal change, rate of coagulation and other properties. Results indicated that parameters other than those typically reported for APTT and PT are associated with individual deficiencies, but that diagnosis of specimen status on the basis of optical data is complex. These results suggest possibilities for expanded interpretation of PT/APTT optical data for clinical or research applications.

Antithrombin III↗
PubMed1998

Effect of warfarin on activated partial thromboplastin time in patients receiving heparin.

BACKGROUND: The activated partial thromboplastin time (APTT) is used to adjust heparin sodium dosage. However, warfarin sodium is often administered concomitantly with heparin and may also affect the APTT and, therefore, heparin dose. We performed a prospective cohort study to quantify the effect of warfarin on the APTT in patients who are being treated with heparin. METHODS: Serial assays of APTT, international normalized ratio, heparin levels, and functional levels of prothrombin (factor II) and factors VII and X were performed in 24 patients with acute venous thromboembolism who were treated with concomitant continuous intravenous heparin and warfarin. The effects of warfarin, as expressed by international normalized ratio and coagulation factor levels, on APTT were determined. RESULTS: Warfarin markedly affected APTT; for each increase of 1.0 in the international normalized ratio, the APTT increased 16 seconds (95% confidence interval, 10-22 seconds). The effects of warfarin and heparin on APTT were additive. Consequently, warfarin markedly altered the relationship between APTT and heparin levels; of the 29 blood samples with supratherapeutic APTT, 13 had a therapeutic heparin level and 10 had a subtherapeutic heparin level. CONCLUSIONS: In patients receiving concomitant heparin and warfarin therapy, APTT reflects the combined effects of both drugs. Because of the marked effect of warfarin on the APTT, decreasing heparin dose in response to a high APTT frequently results in subtherapeutic heparin levels.

Anticoagulants↗
PubMed1999

Recurrent venous thrombosis and heparin therapy: an evaluation of the importance of early activated partial thromboplastin times.

BACKGROUND: The presence of an association between early subtherapeutic activated partial thromboplastin times (aPTTs) and recurrent venous thromboembolism (VTE) remains controversial. OBJECTIVE: To determine the relation between early subtherapeutic aPTTs and recurrent VTE in patients who were treated with intravenous (i.v.) unfractionated heparin (UFH). PATIENTS AND METHODS: We studied 961 patients with acute VTE who received i.v. UFH in 3 randomized trials that compared the use of i.v. UFH (loading dose: 5000 U i.v.; initial infusion, 1250-1280 U/h) with that of subcutaneous low-molecular-weight heparin. According to aPTT criteria, patients were classified as being in a subtherapeutic or a therapeutic state during the first 24 and 48 hours of treatment. All episodes of possible recurrent VTE were adjudicated by an independent committee that was unaware of the aPTTs. RESULTS: At 24 hours, in 886 patients who were eligible for the analysis, the rate of recurrent VTE in the subtherapeutic group was 6.7% (11/163) compared with 5.3% (38/723) in the therapeutic group. The odds ratio for recurrence in patients in the subtherapeutic vs the therapeutic group at 24 hours was 1.30 (95% confidence interval: 0.64-2.63; P = .46). At 48 hours, in 917 patients who were eligible for the analysis, the rate of recurrent VTE in the subtherapeutic group was 7.8% (5/64) compared with 5.7% (49/853) in the therapeutic group. The odds ratio for recurrence in patients in the subtherapeutic vs the therapeutic group at 48 hours was 1.32 (95% confidence interval: 0.51-3.44; P = .56). CONCLUSION: In patients with acute VTE who receive an i.v. bolus of 5000 U, followed by a starting dose of at least 1250 U/h of UFH, a subtherapeutic aPTT response during the first 48 hours of treatment is not associated with a large increase in the risk of recurrent VTE.

Aged↗
PubMedDate not supplied

Partial thromboplastin time: prediction of adverse events and poor prognosis by low abnormal values.

BACKGROUND: Clinical observations suggest an increased incidence of bleeding and thrombosis in association with a shortened partial thromboplastin time (PTT). OBJECTIVE: To determine whether abnormally fast PTTs are associated with an increased risk of death, thromboses, bleeding, and the overall occurrence of morbid events. METHODS: The medical records of 199 patients admitted in a 1-year period to a Veterans Affairs medical center were reviewed for PTTs and the events of death, thromboses, and severe bleeding. Group 0 (n = 49) consisted of patients with abnormally fast PTTs (<23 seconds). Group 1 (n = 50) consisted of patients with fast normal PTTs (23-25 seconds), and the control group, group 2 (n = 100), contained patients with PTTs from 28 to 31 seconds. The Cox proportional hazards regression was used to analyze the time-independent covariates of PTT groups, surgery, cancer, and other clinical variables as predictors of 3 outcome variables: bleeding, thrombosis, and death. RESULTS: Of the covariates examined, the PTT was found to be the most significant predictor of poor outcome. A statistically significant association was found between the PTT and time to death (P<.001), thrombotic events (P<.001), and bleeding (P<.006), and between the PTT and overall occurrence of morbid events (P<.001). Furthermore, survival curves showed that the greatest hazards of death, thrombosis, bleeding, and overall morbidity consistently occurred in group 0 compared with groups 1 and 2. CONCLUSIONS: Abnormally fast PTTs, particularly if confirmed on repeated testing, indicate a significant risk of subsequent death, thrombosis, bleeding, and overall morbidity. Careful examination of patients with low PTTs may reduce such associated morbidity and mortality.

Case-Control Studies↗
PubMed2001

Use of a fixed activated partial thromboplastin time ratio to establish a therapeutic range for unfractionated heparin.

BACKGROUND: The commonly recommended therapeutic range for patients receiving unfractionated heparin of 1.5 to 2.5 times the control activated partial thromboplastin time (aPTT) is not universally applicable. It has been suggested that the therapeutic range for each aPTT reagent should be based on plasma heparin levels. We sought to identify an aPTT ratio that corresponds to therapeutic anti--factor Xa heparin levels for combinations of several reagents and coagulometers that are commonly used. METHODS: Citrated plasma was collected from 126 unselected patients receiving unfractionated heparin. Four automated coagulometers and 6 commercial aPTT reagents were used to measure the aPTT. Plasma anti--factor Xa levels were measured by means of a commercially available assay. The relationship between the aPTT results and anti-factor Xa heparin levels for each reagent-coagulometer combination was determined by linear regression analysis, and the aPTT results corresponding to therapeutic anti--factor Xa heparin levels were calculated. RESULTS: For all reagent-coagulometer combinations studied, an aPTT ratio of 1.5 resulted in anti--factor Xa heparin levels considerably below the lower limit of the therapeutic range. When the aPTT was performed on any of the coagulometers assessed with the use of Actin (Dade Diagnostics, Aguada, Puerto Rico) and IL Test (Instrumentation Laboratories, Fisher Scientific, Unionville, Ontario) reagents, aPTT ratios necessary to achieve therapeutic anti--factor Xa heparin levels approximated 2.0 to 3.5. CONCLUSION: For laboratories that cannot perform heparin levels, the use of less responsive reagents and any of the coagulometers studied, along with target aPTT ratio between 2.0 and 3.5, appears to be a reasonable alternative.

Antithrombin III↗
PubMed1982

Prothrombin and partial thromboplastin times as preoperative screening tests.

Preoperative tests of coagulation function have been suggested to detect patients who are likely to have abnormal bleeding during and after surgery. A study was designed to determine the yield of prothrombin time (PT) and partial thromboplastin time (PTT), both in discovering patients who are at risk for abnormal bleeding and in inducing changes in patient care or outcome. Of 750 patients on three surgical services, 611 (81%) patients had no indication of a bleeding disorder on history or physical examination. Of the 139 patients who had clinical indications, 25 (18.0%) patients had an abnormal PT or PTT. Of the 611 patients without clinical indications, 480 patients had the PT or PTT determined, and 13 (2.7%) patients had abnormal results. One (0.2%) of the 480 patients might have benefited from the test result (this patient required a second operation to control arterial bleeding). The prolonged PT or PTT was of no apparent clinical importance in the remaining 12 patients without indications of bleeding disorders preoperatively. The low yield of the PT and PTT in detecting unsuspected bleeding disorders preoperatively was further obscured by the larger number of apparently false-positive results.

Blood Coagulation Tests↗
PubMed1982

Activated partial thromboplastin time after heparin removal (aPTT/HR) in a new scheme of anticoagulant monitoring.

Activated partial thromboplastin time after heparin removal (aPTT/HR), a test employing anion exchange chromatography, was devised as an alternative to the prothrombin time after heparin removal (PT/HR) to monitor simultaneous anticoagulation with heparin and coumarins. The potential utility of the aPTT/HR was assessed by performing parallel PTs and aPTTs on 62 consecutive plasmas from coumarin-treated outpatients. All samples had 0.2 units/ml of heparin added and then removed to see if the maneuver influenced therapeutic group assignment. In no instance did reassignment occur. A conditional Irwin-Fisher test (P = 0.000604) and a special multinomial trial analysis (P = 0.002) indicated that the aPTT would be at least comparable to the PT for following coumarin antithrombotic prophylaxis. Since the heparin removal procedure had no influence on therapeutic categorization, the same statistical proof could be applied to the relationship between aPTT/HR and PT/HR. This study indicates that the aPTT can be used to monitor all stages of heparin and /or coumarin anticoagulation.

Anticoagulants↗
PubMed1988

Prolonged activated partial thromboplastin time of unknown etiology: a prospective study of 100 consecutive cases referred for consultation.

The activated partial thromboplastin time (aPTT) is frequently used to assess overall competency of the intrinsic pathway of coagulation. An abnormal value may be caused by any of several abnormalities along this pathway or by many other variables including the presence of inhibitors, poor collection of the sample, or variables in the laboratory. When the cause for the prolongation is unknown to the requesting physician, the hematologist may be consulted. In this prospective study, the cause and perceived hemostatic risk to 100 consecutive patients referred to use for consultation regarding a prolonged aPTT of previous unknown cause were evaluated. We found that these abnormal aPTTs may be either indicative of a hemostatic defect, in 50% of the cases, or of no particular risk, in 36% of the cases. In 14%, the aPTT was artifactually prolonged. Most (81%) patients with a prolonged aPTT due to a hemostatic defect had an abnormal hemostatic history but some (19%) did not. Even among true abnormal tests, the degree of abnormality indicated little or nothing about hemostatic competency. We conclude that the cause of an abnormal aPTT is more important than the result itself. These data may be of use to those who consult on such matters.

Adult↗
PubMed1992

Activated clotting times and activated partial thromboplastin times in patients undergoing coronary angioplasty who receive bolus doses of heparin.

The accurate assessment of coagulation status is an important part of interventional procedures performed in the cardiac catheterization laboratory. While the traditional clinical means of assessing heparin anticoagulation has been with the activated partial thromboplastin time (APTT), the activated coagulation time (ACT) has come into widespread use in the catheterization laboratory as an assay of whole blood clotting time which can be performed rapidly at the bedside. The purpose of the present study was to (1) assess the anticoagulant effect of a 10,000 U bolus of heparin in PTCA patients and (2) document the relationship between ACTs and APTTs in a subset of these patients. Baseline and postheparin ACTs were measured using a HemoTec coagulation timer in 545 unselected PTCA patients. The average baseline ACT was 120 +/- 22 sec. After a 10,000 U bolus of heparin the average ACT was 249 +/- 44 sec; 58% of patients had an ACT less than 250 sec, 17% had an ACT between 250 and 275 sec, 12% had an ACT between 275 and 300 sec, and 13% had an ACT greater than 300 sec. A total of 175 paired ACT and APTT measurements were obtained in a random subset of these patients at baseline, after heparinization, and at 4-6 hr intervals after the procedure. The APTT was limited by absolute upper and lower limits of 150 and 22 sec; there were no such limits on the ACT. When limiting values were excluded, there was a strong overall correlation between ACT and APTT measurements (r = 0.92, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Bedside monitoring of heparin therapy: comparison of activated clotting time to activated partial thromboplastin time.

Heparin anticoagulation is utilized during and after interventional cardiac catheterization procedures to reduce the risk of acute thrombotic coronary artery occlusion. The short half-life of heparin, the importance of maintaining therapeutic anticoagulation, and the time delay inherent in the processing and retrieval of the activated partial thromboplastin time (aPTT) by the hospital laboratory has generated interest in point-of-care heparin monitoring. The activated clotting time (ACT), the aPTT as assessed by both a new portable device, as well as the hospital laboratory, and heparin levels (H) were obtained from the same sample of blood in 100 patients receiving intravenous heparin. There was an excellent correlation between the aPTT determined at the bedside and by the hospital laboratory (r = .89). The ACT did not correlate well with either the laboratory or bedside aPTT (r = .63, .68 respectively). In the sub-therapeutic and therapeutic range, there was essentially no correlation between ACT and H. Only ACT values > 225 sec were predictive of therapeutic or supra-therapeutic aPTTs. ACT values < 225 sec, however, were not useful in predicting degree of anticoagulation. In situations in which the maintenance of therapeutic anticoagulation is critical as well as those in which the determination of lack of anticoagulation is required, the bedside determination of aPTT appears to be a useful tool.

Cardiac Catheterization↗
PubMed1981

Enhancement of monocyte thromboplastin activity by antigenically stimulated lymphocytes: a link between immune reactivity and blood coagulation.

Immune reactions are often associated with fibrin deposition. The mechanisms that lead to this fibrin formation have not yet been clarified. In this study, we show that mononuclear leukocytes (MNL) from donors with a high proliferative response to protein derivative of tuberculin (PPD) have on average 2.5 to 15-fold more thromboplastin (TP) activity, both exposed and intracellularly, compared with MNL from low responder after 4, 7 and 11 days of culture in the presence of PPD. This difference was not observed between the two groups of donors when PPD was omitted from the culture medium. Further evidence for a specific enhancement of the leukocyte TP activity can be derived from the about 4-fold increase in TP activity of the bilateral mixed leukocyte culture relative to the individually cultured controls after 7 days of incubation. TP activity was associated selectively with the monocytes in a PPD-stimulated culture of MNL. The PPD-specific enhancing effect on the leukocyte TP activity could be transferred by soluble factor(s) from stimulated lymphocytes to purified monocytes, which suggests that the effect is, at least partially, mediated by lymphokine(s).

Blood Coagulation↗
PubMed2006

Prolongation of the prothrombin time and activated partial thromboplastin time in children with sickle cell disease.

BACKGROUND: Patients with sickle cell disease (SCD) have high rates of perioperative complications, including bleeding 1,2. PROCEDURES: We conducted a retrospective review of pre-operative coagulation studies in pediatric patients with SCD followed by a prospective study of 100 well children with SCD to determine the prevalence of abnormal coagulation screening tests, and to evaluate potential etiologies. RESULTS: In the retrospective study, 32/84 (38.1%) had a prolonged prothrombin time (PT), compared to 8/100 in the prospective study. Prolongations of the activated partial thromboplastin time (aPTT) were less common. Children in the prospective study with prolonged PTs had significantly lower levels of Factor V and VII compared to those with normal PTs. Factor VII levels were <50% in 4/8 with long PTs, compared to 3/92 with normal PTs, P=0.001. Though retrospectively, several patients had normalization of their PT with vitamin K, there was no laboratory evidence of vitamin K deficiency in the prospective study. In the retrospective analysis, six of seven children who had pre-operative coagulation studies and significant intraoperative blood loss had prolonged PTs (P=0.04). CONCLUSIONS: Children with SCD admitted for surgical procedures were more likely to have prolonged PTs than those tested at a well visit. There was intra-patient variability in coagulation studies that may be related to clinical status, hepatocellular dysfunction, and/or increased clotting factor consumption. Future well-designed prospective studies to determine whether abnormal coagulation studies are associated with an increased risk of perioperative bleeding in children with SCD are necessary.

Adolescent↗
PubMed1982

Establishment of a human renal pelvic cancer cell line producing tissue thromboplastin and plasminogen activator.

A new epithelial cell line derived from undifferentiated carcinoma of human renal pelvis, designated KP 1, was established in vitro. The cell line has been passaged 190 times in vitro for 5 years and 9 months. The predominant cell in KP 1 was a tear-drop-shaped cell. Doubling time of the cell line was 35 h. The malignant epithelial character of this line was verified by carcinogenicity in the subcuticular layer of nude mice and by karyotypic analysis which revealed the cells to be completely aneuploid with a model chromosome number in the hypertriploid range. KP 1 cells were shown to produce both tissue thromboplastin and plasminogen activator which was immunologically identical to urokinase, the plasminogen activator in urine.

Animals↗
PubMedDate not supplied

Use of the activated partial thromboplastin time for the diagnosis of congenital coagulation disorders: problems and possible solutions.

The activated partial thromboplastin time (APTT) is a commonly performed laboratory procedure which is used for multiple purposes including monitoring of heparin therapy, detection of coagulation factor deficiency, and detection of lupus anticoagulants. Among the hereditary coagulation deficiencies, factor VIII and factor IX are the most common. APTT reagents differ widely in both their sensitivity to factor VIII and factor IX deficiencies as well as their responsiveness. Sensitivity may be defined as the ability to identify a deficiency state while responsiveness is indicated by the degree of prolongation of the APTT result as compared to the upper limit of normal. Reagents may be both sensitive and responsive or alternatively sensitive and relatively nonresponsive. Consequently, it is extremely important for each laboratory to carefully identify the upper limit of the normal range. A variety of preanalytical variables will also effect the sensitivity of the APTT to factor deficiency states. These variables include specimen handling and the preparation of platelet poor plasma. The instrument effect is also of importance. Selection of the reagent tends to have the most impact on sensitivity and responsiveness while instrumentation affects the precision of a given APTT. The composition and concentration of phospholipid in APTT reagents does have an effect on reagent responsiveness and sensitivity. Sensitivity to factor deficiencies does not necessarily parallel sensitivity to lupus anticoagulants.

Blood Coagulation Disorders↗
PubMedDate not supplied

Chromogenic substrates for activated partial thromboplastin time testing: are they worth using?

In hemostasis testing the development of chromogenic substrates provides an alternative to the traditional methods based on the detection of forming clots. The new technology has often replaced the clotting tests, especially in the area of single clotting factor and inhibitor assay, less frequently for global screening tests. We report studies of the validity and clinical application of two reagents for activated partial thromboplastin time (APTT) testing with chromogenic substrates in comparison with the conventional clotting method. Congenital deficiencies of the intrinsic coagulation pathway, other than hypo- and dysfibrinogenemia detected by chromogenic APTT, agreed with those detected by the clotting APTT. The results with the two methods for plasma under heparin treatment suggest a lesser responsiveness of the chromogenic methods to heparinization. The chromogenic methods demonstrated the presence of the lupus anticoagulant in the majority of tested samples of known lupus subjects, but with a lower responsiveness than the clotting method. In conclusion, we found chromogenic APTT suitable for hemostasis testing because it generally gives the same information as the conventional clotting method with the exception of heparin monitoring and lupus anticoagulant detection, where an improved sensitivity would be desirable.

Blood Coagulation Disorders↗
PubMedDate not supplied

Performance guidelines for the partial thromboplastin time test.

The partial thromboplastin time (PTT) test is widely used as a screening test for the detection of hemophilia. It is also used to monitor patients on heparin anticoagulation. These proposed guidelines for the performance of this test, including comparable reference ranges, precision and sensitivity requirements are felt to be reasonable and attainable. Whether further progress will occur depends upon a perceived need by laboratorians, instrument and reagent manufacturers and government regulators that standardization of the PTT is desirable.

Blood Coagulation Tests↗
PubMedDate not supplied

Use of the activated partial thromboplastin time for monitoring heparin therapy: problems and possible solutions.

There is considerable variation in available methods for the activated partial thromboplastin time (APTT), giving widely differing results with patients on heparin treatment. The study is primarily concerned with the assessment of five of the widest used APTT reagents. The heparin response of these reagents has been related to their lipid composition and physical properties. Of the various correlations between lipid composition of the reagents and clotting performance only electrophoretic mobility was associated with the APTT response to heparin. There was a highly significant negative correlation between the APTT prolongation with heparin and electrophoretic mobility. When plasma is heparinized in vitro a differing order of ranking for APTT reagents is obtained than when heparinized patients are tested. The APTT response in patients with recent thrombosis must therefore be the best guide to the clinical dose of heparin. The therapeutic range of conventional heparin therapy is generally regarded as 1.5-2.5 times the control. External quality assessment programmes in the UK and USA have shown considerable differences between heparin dosage according to the APTT test systems. The definition of the therapeutic range must be derived from randomized clinical studies. The need for progress in standardization of the APTT monitoring of heparin is demonstrated.

Blood Coagulation Tests↗