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PubMed1993

Prothrombin time and partial thromboplastin time as a predictor of bleeding in patients with dengue hemorrhagic fever.

Eighty-nine pediatric patients admitted at the University of Santo Tomas Hospital from June to December 1992, with the clinical diagnosis of dengue hemorrhagic fever (DHF) were studied with the following objectives: To determine the possible use of hematocrit, platelet count, prothrombin time (PT) and partial thromboplastin time (PTT) as predictors of bleeding and outcome in patient with DHF. The following were established: PTT can be an index in predicting bleeding in DHF. The tendency to bleed is greater with prolongation of > 30 seconds; platelet count can be a predictor of mortality, with death six times greater among those platelet count < 50,000/microliters than those whose platelet count was > 50,000/microliters. PT can also predict bleeding in patients with DHF.

Adolescent↗
PubMed1994

Long-term stability studies on the WHO IRP for thromboplastin (human plain BCT/253).

Long-term stability studies on the WHO second primary International Reference Preparation (IRP) for thromboplastin (human plain BCT/253) stored at -20 degrees C have been conducted for ten years. Three centres took part in the exercise using frozen normal and coumarinised plasma samples which were tested throughout. There has been no measurable change in the prothrombin time performance of the human plain IRP over the ten-year period. It can therefore be concluded that new IRP may continue to be calibrated against this preparation in accord with WHO recommendations.

Analysis of Variance↗
PubMed1994

Monitoring anticoagulant therapy by activated partial thromboplastin time: hirudin assessment. An evaluation of native blood and plasma assays.

BACKGROUND: Recombinant hirudin (RH) is a new anticoagulant for prophylaxis and treatment of venous and arterial thrombosis. To which extent the activated partial thromboplastin time (APTT) is suitable for monitoring of RH has not been properly evaluated. Recently, a capillary whole blood device was developed for bed-side monitoring of the APTT and it was demonstrated that this device was suitable to monitor heparin therapy. However, monitoring of RH was not evaluated. STUDY OBJECTIVES: To evaluate in vitro and ex vivo the responsiveness and reproducibility for hirudin monitoring of the whole blood monitor and of plasma APTT assays, which were performed with several reagents and two conventional coagulometers. RESULTS: Large interindividual differences in hirudin responsiveness were noted in both the in vitro and the ex vivo experiments. The relationship between the APTT, expressed as clotting time or ratio of initial and prolonged APTT, and the hirudin concentration was nonlinear. A 1.5-fold increase of the clotting times was obtained at 150-200 ng/ml plasma. However, only a 2-fold increase was obtained at hirudin levels varying from 300 ng to more than 750 ng RH/ml plasma regardless of the assays. The relationship linearized upon logarithmic conversion of the ratio and the hirudin concentration. Disregarding the interindividual differences, and presuming full linearity of the relationship, all combinations were equally responsive to hirudin. CONCLUSIONS: All assays were equally responsive to hirudin. Levels up to 300 ng/ml plasma can be reliably estimated with each assay. The manual device may be preferable in situations where rapid availability of test results is necessary.

Adult↗
PubMed1994

[Utility of measuring prothrombin and activated partial thromboplastin times in a community hospital].

PURPOSE: To prove an excessive use of prothrombin-time (PT) and activated partial thromboplastin time (APTT) in a regional hospital of A-B nivel with 168 beds. MATERIAL AND METHODS: All studies of PT and APTT were compiled during one month. In accordance with assistance type (emergency, inpatient or outpatient), the following parameters were analysed: services distribution and assistance type, justification of haemostasis studies, according to the American Medical Association criteria modified for Erban et al., abnormal findings appeared and economical cost study of the tests, according to the justification request. RESULTS: The total number of haemostasis tests performed in that month was 706, with a daily mean of 22.7. Seven hundred and six were PT analysis and 606 APTT. Fifty-six percent were not adequate. This corresponded to 82.5% of the requests in inpatients, 56% of the outpatients and 33.5% of emergency patients. Only 51 analyses were abnormal, that means 7.4% of all studies. From these, 13 were in inpatients (7.64% from the whole of the patients requests), 11 were outpatients (3.52%) and 27 emergencies (12.8%). The economical burden within the month studied amounted up to 629.760 ptas. CONCLUSIONS: The number of haemostasis screening tests was excessive. The correction of this inappropriate use could improve the patient assistance and could decrease the cost, without impairing, and perhaps increasing, the assistential quality.

Anticoagulants↗
PubMed1993

Effect of synthetic phospholipids on the response of the activated partial thromboplastin time to heparin.

The activated partial thromboplastin time (aPTT) is the most popular test for monitoring of heparin therapy. The purpose of the present study was to show that an aPTT reagent with good response to heparin can be prepared from synthetic phosphoglycerides. Mixed liposomes were prepared from synthetic dioleoylphosphatidylserine (DOPS), dioleoylphosphatidylcholine (DOPC), and dioleoylphosphatidylethanolamine (DOPE). These liposomes were used in an aPTT test system with kaolin as activator, to evaluate their procoagulant activity in the absence and presence of heparin. For comparison, mixtures of purified non-synthetic phospholipids were prepared and tested with the same systems. The aPTT and its response to heparin were influenced by the phospholipid class composition and concentration. The presence of phosphatidylserine (PS) was required to reduce the aPTT of normal plasma to values between 30 and 40s. The presence of phosphatidylethanolamine (PE) in mixed liposomes could modulate the response to heparin. At low PE/PS liposome concentrations (approximately 40 microM), a relatively low response was observed. At high liposome concentrations (approximately 1 mM), the response to heparin increased with the mole fraction of phosphatidylethanolamine. The results obtained with non-synthetic phospholipid mixtures were similar to those obtained with the synthetic phosphoglycerides. Optimal concentrations of DOPS, DOPE and DOPC were found with which an almost linear response to heparin and to low molecular weight heparin (Fragmin) was observed. Using a mixed liposome consisting of 12 microM DOPS/12 microM DOPC/16 microM DOPE, a doubling of the base-line aPTT was achieved at approximately 0.2 IU/ml of heparin, and at approximately 1.0 IU/ml of Fragmin.(ABSTRACT TRUNCATED AT 250 WORDS)

Dalteparin↗
PubMed1993

Lipopolysaccharide induced monocyte thromboplastin synthesis and coagulation responses in patients undergoing coronary bypass surgery after preoperative supplementation with n-3 fatty acids.

Twenty patients with coronary heart disease (CHD) and elevated serum lipids were randomized into 2 groups of 10 to receive encapsulated preparations of either a concentrated ethylester form of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or corn oil in doses of 6 g per day, given double blindly for approximately two months prior to coronary bypass surgery. Lipopolysaccharide (LPS) induced monocyte thromboplastin synthesis was studied during the preoperative period and one week following surgery. The ability of n-3 fatty acids to modify tissue factor pathway inhibitor (TFPI) and tissue plasminogen activator inhibitor (PAI-1) was also evaluated along with fibrinogen and thrombin-antithrombin III (TAT) complexes. No significant changes were noted preoperatively. Monocyte reactivity, PAI-1, fibrinogen and TAT increased significantly after surgery. These changes were not modified by preoperative loading with n-3 fatty acids.

Acute-Phase Reaction↗
PubMed1994

[Is the activated partial thromboplastin time suitable for monitoring of thrombosis therapy with high-dose standard heparin?].

The activated partial thromboplastin time (aPTT, PTT) is widely used to monitor therapeutic anticoagulation with standard heparin. However, it has been known for some time that PTT reagents obtained from various manufacturers display different sensitivities to heparin--a fact which often is not taken into account. The study deals with the question whether the sensitivity of the PTT to heparin is additionally influenced by the decrease in the vitamin K-dependent coagulation factors such as occurs after starting oral anticoagulation (OAC). In in-vitro studies the reaction of the PTT was observed after addition of different amounts of heparin to normal plasma, to plasma taken after the start of OAC and during stable OAC. The results show that the PTT tends to be more sensitive to heparin as soon as oral anticoagulation is initiated. This phenomenon already occurs at an early stage of anticoagulant intake where only factor VII is markedly reduced but prothrombin concentration is still in an almost normal range and therefore a clinically sufficient effect of OAC is not to be expected. Identical results are obtained with plasma samples of heparin treated patients before and after the start of OAC; in addition, a scattering of the PTTs is obvious. This leads to overestimation of heparin concentrations and a consequent reduction of dosage at an early, still insufficient stage of OAC. In contrast, the thrombin time shows--independently of OAC--a good correlation to heparin concentrations. Therefore the thrombin time is more appropriate to monitor heparin therapy in the phase when oral anticoagulation is started.

Blood Coagulation Factors↗
PubMed1993

Activated partial thromboplastin time reagents: an evaluation.

Nine automated, activated partial thromboplastin time (APTT) reagents were evaluated on an automated coagulometer, in comparison with a manual reagent. The study consisted of three separate stages: 1) to choose a reagent that had a working stability between 4 degrees C and 8 degrees C for seven days and heparin sensitivity between 0 and 0.8 iu/ml; ii) assessment of sensitivity to specific factor deficiencies, particularly factors VIII, IX, XI and XII using standardised plasma serially diluted with factor-deficient plasma; and iii) assessment of sensitivity to the presence of a lupus anticoagulant, from a known positive panel. Only one reagent fulfilled all the essential criteria as an acceptable replacement for the manual reagent.

Blood Coagulation Factors↗
PubMed1993

Lupus anticoagulant testing: effect of the platelet count on the activated partial thromboplastin time.

The activated partial thromboplastin time (APTT) is often used as a test to diagnose patients with lupus anticoagulants. It is recommended that platelet-poor plasma be used in the APTT test. In this study the effects of residual platelet contamination on lupus anticoagulant and antiphospholipid antibody testing are described. In fresh samples the residual platelet contamination has no significant effect whereas in frozen samples the effect of residual platelet contamination can have a significant effect on the APTT testing.

Antibodies, Antiphospholipid↗
PubMed1994

A randomized trial comparing activated thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin.

BACKGROUND: The management of heparin therapy in patients who have a subtherapeutic activated partial thromboplastin time (APTT) despite high doses of heparin is problematic because the risk of heparin-associated bleeding increases with dose. Results of experimental studies in animals indicate that when the APTT response to heparin is blunted by infusion of procoagulants, dose escalation can be avoided without compromising efficacy, by monitoring treatment with a heparin assay. METHODS: A randomized, controlled trial was conducted in which patients with acute deep vein thrombosis, pulmonary embolism, or axillary vein thrombosis who required 35,000 U or more of intravenous heparin by continuous infusion during the previous 24 hours were allocated to have their heparin therapy monitored either by anti-factor Xa levels (targeted range, 0.35 to 0.67 U/mL) or by the APTT (targeted range, 60 to 85 seconds). Both ranges were equivalent to a heparin level of 0.2 to 0.4 U/mL by protamine titration. RESULTS: Three (4.6%) of 65 patients in the anti-factor Xa group experienced recurrent venous thromboembolism compared with four (6.1%) of 66 patients in the APTT group (difference, 1.5%; confidence interval, -6.7% to 8.4%) (P = .7). There were four bleeding events (6.1%) in the APTT group compared with one (1.5%) in the anti-factor Xa group (difference, 4.6%; confidence interval, -3.3% to 7.5%) (P = .4). During the period of heparin therapy before warfarin treatment was begun, the patients in the APTT group required a statistically significantly greater amount of heparin compared with the patients in the anti-factor Xa group. The daily mean APTT was subtherapeutic in patients in the anti-factor Xa group, and it was within the therapeutic range in the APTT group. The daily mean anti-factor Xa levels for both groups were within the therapeutic range. CONCLUSION: The heparin assay is a safe and effective method for monitoring heparin treatment in patients with acute venous thromboembolism whose APTT remains subtherapeutic despite large daily doses of heparin. In such patients, dosage escalation can be avoided if the heparin level is therapeutic.

Acute Disease↗
PubMed1993

Heparin monitoring during coronary intervention: activated clotting time versus activated partial thromboplastin time.

Activated clotting time (ACT) and activated partial thromboplastin time (APTT) are used for monitoring heparin therapy during coronary angioplasty. The purpose of this study was to determine which parameter is more useful clinically, and to assess the correlation between ACT and APTT. The authors measured these parameters at fixed intervals (0, 15, 30, 60, 150 and 240 mins) following intravenous heparin administration (12,500 +/- 3100 U) during coronary intervention in 39 patients. APTT rose to 'therapeutic' levels (true therapeutic levels have not been defined for these coagulation tests) more rapidly and fell to subtherapeutic levels more slowly than did ACT. The combination of a subtherapeutic ACT with a therapeutic APTT occurred far more often than did concordant therapeutic ACT and APTT values (69% versus 31%, P < 0.0004). There was a relatively poor correlation between ACT and APTT (r = 0.76). There were no abrupt closures in the study patients. It was concluded that subthreshold ACTs with high APTTs occur frequently, suggesting the improved suitability of ACT for intraprocedural monitoring of anticoagulation status. If one accepts the minimum amount of anticoagulation for prevention of thrombosis to be that which produces an ACT of greater than 300 s, then an APTT of greater than 90 s does not predict adequate anticoagulation.

Adult↗
PubMed1993

The effect of low dose nitroglycerin on plasma heparin concentrations and activated partial thromboplastin times.

We have investigated the effects of low dose nitroglycerin on the activated partial thromboplastin time (APTT), plasma heparin concentration, antithrombin III activity (AT-III) and platelet factor 4 (PF4) levels in a group of 42 patients receiving intravenous heparin and low dose nitroglycerin (GTN) following percutaneous transluminal coronary angioplasty (PTCA). Venous samples were taken before PTCA and at 2, 4 and 24 h after the start of the infusions. Despite the heparin infusion being constant, the median APTT ratio (interquartile range) was significantly lower at the 4 h sample time compared to the 2 h sample time (4.4 [3.8-4.5] vs 2.6 [1.8-4.0], P < 0.05). At this time there was also a significantly lower median plasma heparin concentration compared to the 2 h sample (0.35 [0.2-0.7] vs 0.17 [0.1-0.3] P < 0.05). There were no significant differences in AT-III activity or PF4 levels at 4 h compared to the 2 h sampling time. In another group of patients (n = 20) who received intravenous heparin alone following PTCA also at 1000 U/h there were no significant differences in median APTT ratios (4.4 [4.3-4.5] vs 4.2 [2.9-4.5]), or in median plasma heparin concentrations (0.26 [0.14-0.96] vs 0.22 [0.18-0.87]) at 4 h compared to 2 h. Our observations confirm that nitroglycerin can interfere with the anticoagulant effect of heparin even at low doses. Although the exact mechanism involved remains unknown, this study suggests it is likely to be a result of a reduction in plasma heparin levels, perhaps through acceleration of normal heparin elimination.

Angioplasty, Balloon, Coronary↗
PubMed1993

[Activated partial thromboplastin time. Evaluation of sensitivity and validity for determination of factor VIII coagulant activity].

The authors evaluate the sensibility and validity of some reagents for activated partial thromboplastin time during construction of a curve for measurement of factor VIII coagulant activity. For every reagent three clotting factor VIII deficient plasmas have been used; Baldacci, Dade and Behering. Significant differences in results between every reagent for aPTT and laboratory have been observed. By these results the Authors show the best reagent for aPTT. Future fields of research have been analyzed.

Adolescent↗
PubMed1977

Detection of factor VIII inhibitors with the partial thromboplastin time.

Variations of the partial thromboplastin time (PTT) were tested to determine the best screening method for detection of inhibitors of factor VIII. Variables tested included the duration of preincubation of a mixture of patient plasma and factor VIII source (normal plasma), the ratio of the patient plasma to the normal plasma, and the duration of incubation of the normal plasma-patient plasma mixture with kaolin-cephalin suspension prior to recalcification. The following conclusions were reached: (1) The PTT performed on a mixture of equal amounts of patient and normal plasma without preincubation of the mixture was inadequate to detect many factor VIII inhibitors. (2) Factor VIII inhibitors of more than 0.5 Bethesda units could be detected if the PTT was performed on a mixture of four parts patient plasma and one part normal plasma, with preincubation of the mixture for 60 min at 37 degrees C. (3) Factor VIII inhibitors as weak as 0.1 Bethesda units could be detected if the PTT was performed on a mixture of four parts patient plasma and one part normal plasma incubated with kaolin-cephalin suspension for 120 min at 37 degrees C before recalcification. The last method may make detection of mild factor VIII inhibitors possible in routine clinical laboratories not equipped to perform the more technically difficult Bethesda inhibitor assays.

Factor VIII↗
PubMed1977

The activated partial thromboplastin time as a monitor of heparin therapy: a warning.

The degree of correlation between the whole blood clotting time (WBCT) and the activated partial thromboplastin time (APTT) was evaluated in 42 patients receiving intermittent intravenous heparin therapy. Correlation between the two tests was found to be poor (correlation coefficient 0.52), primarily for reasons related to characteristics of the APTT system employed. The relationship in vitro between the APTT and the level of heparin was evaluated and found to vary widely over a range of heparin concentrations. This study emphasizes the marked variability between various APTT systems and the dangers involved with substituting the APTT for the WBCT to monitor heparin without appropriate initial evaluation.

Blood Coagulation Tests↗
PubMed1996

Deceptive prothrombin and activated partial thromboplastin times in alcoholic cirrhosis.

It is believed that perioperative hemorrhage, in the hepatoportal area, results from a coagulopathy. This study determined if this could be quantitated by a modified recalcification time (MRT) test developed in our laboratory. Unlike prothrombin (PT) and activated partial thromboplastin times (APTT), the MRT is performed with whole blood to ensure the role of blood cells and chemicals (particularly tissue factor, a potent procoagulant) in the coagulation process. Candidates for liver transplantation (n = 11) were studied. Samples (5 mL) of citrated venous blood were obtained from the patients. Aliquots (1 mL) from these samples were divided into groups of vials labeled C, S, and E. Groups C and S received 20 microL saline and group E, 20 microL of saline containing 10 micrograms of Escherichia coli endotoxin (055: B5W). Vial C was incubated for 10 minutes and vials S and E for 120 minutes, all at 37 degrees C. Then, the MRT was determined on 300 microL of blood from each vial after adding 40 microL of 0.1M calcium chloride. Mean MRT values (minutes +/- standard deviation) for C (MRTC), for S (MRTS), and for E (MRTE) were compared with like values from healthy controls (n = 29). Despite prolonged PT and APTT values, MRT values were shortened in patients with cirrhosis. This hypercoagulability detected by the MRT exonerates a hemorrhagic coagulopathy and possibly implicates widened and thinned gaps in the walls of the portal venous tributaries as the cause of perioperative hemorrhage.

Blood Coagulation Disorders↗
PubMedDate not supplied

The relation between the activated partial thromboplastin time response and recurrence in patients with venous thrombosis treated with continuous intravenous heparin.

BACKGROUND: It is unknown whether the true risk of recurrent venous thromboembolism (VTE) is increased in patients with proximal deep vein thrombosis who are treated with continuous intravenous heparin and fail to reach a therapeutic activated partial thromboplastin time (APTT) within 24 to 48 hours of initiation of treatment. METHODS: To compare the risk of recurrent VTE in patients with early subtherapeutic APTT results and those with APTT results above the lower limit of the therapeutic range, we performed a formal review of the literature. We examined all available studies that provided information on the relation between the risk of recurrent VTE and the APTT response to heparin when initiated as a bolus followed by a continuous intravenous infusion of at least 30 000 U/24 h. RESULTS: Five studies were included in the final analysis. The overall recurrence rate was 6.3% in patients whose APTT results were subtherapeutic for the first 24 to 48 hours and 7% in patients whose APTT results were above the lower limit of the therapeutic range, providing a pooled odds ratio of 0.89 with a 95% confidence interval of 0.2 to 4.0. CONCLUSIONS: In patients with VTE who are treated with a bolus of heparin followed by a continuous intravenous infusion of at least 30 000 U/24 h, no convincing evidence shows that the risk of recurrent VTE is critically dependent on achieving a therapeutic APTT result at 24 to 48 hours.

Heparin↗
PubMed1996

The therapeutic range for heparin therapy: relationship between six activated partial thromboplastin time reagents and two heparin assays.

The activated partial thromboplastin time (APTT) is the most commonly used test for laboratory monitoring of unfractionated heparin therapy. Since there are differences between APTT reagents in respect of responsiveness to heparin the widely used therapeutic range of 1.5-2.5 (APTT ratios) may not be appropriate for all reagents. The aim of this study was to assess the relationship between 6 different APTT reagents using a manual technique, 2 of these reagents used in combination with a coagulometer, a heparin assay by protamine titration and a chromogenic anti-Xa assay. Samples from 42 patients treated with unfractionated heparin for thromboembolic disease were studied, 12 of whom were receiving warfarin therapy with International Normalised Ratios (INR) of > 1.3. For normal subjects, APTT results were highly dependent on the method used and statistically significant differences were noted. The ratio of patient to mean normal APTT was calculated for each APTT method. When 30 samples from heparinised patients (with INRs of < 1.3) were analysed manually, the APTT ranges equivalent to 0.2-0.4 u/ml heparin by protamine titration (by regression analysis) were 1.6-1.9 for Boehringer reagent (the least responsive) up to 2.2-2.9 for Instrumentation Laboratory reagent (the most responsive). The concentration of heparin associated on average with APTT ratios of 1.5-2.5 varied approximately twofold to threefold between reagents.

Adult↗