Heparin-binding proteins are involved in thrombin time variability in normal and patient plasmas.

The ability of plasma proteins to neutralize the anticoagulant activity of heparin was studied using a thrombin time assay with 20 normal adult and 207 patient plasma samples. The thrombin times of normal adult plasmas spiked with the same amount of heparin were found to vary significantly, and this variability was attributed to differences in heparin-binding proteins among individuals. This possibility was investigated by determining thrombin times for a variety of plasma samples following proteolytic digestion. A study of patient pooled plasma showed that incubation with a protease increased the thrombin time from 23 s to > 300 s, suggesting that the anticoagulant activity of heparin could be neutralized by plasma proteins and released with proteolytic digestion. Incubation of the digested plasma with heparinase I returned the thrombin time almost to control values. In addition, patients who received prior heparin injections had different responses to similar dosages of heparin, as indicated by differences in thrombin times. Thus, the anticoagulant activity of heparin may be affected by the balance between free heparin and protein-bound heparin in plasma.     

The relationship between heparin dosage and clotting time

1. The relationship between clotting time and heparin dosage has been studiedin the dog.

2. On the addition of heparin to blood in vitro, a linear relation is found betweenheparin dosage and the logarithm of the clotting time obtained. The sensitivityof the blood sample to the action of added heparin is influenced both by the individual (coagulability of the blood before withdrawal) and by the technics of withdrawal and of determination of the clotting time. It is indicated that alterationsin the latter may be used to extend the range of measurable hypocoagulability dueto heparin. Incubation of heparin with blood for ten minutes increases its anticoagulant effect.

3. When moderate doses of heparin are injected intravenously, five to fifteenminutes are required for the clotting time to reach a maximum. No evidence of abiphasic response was obtained. The maximum clotting time obtained is greaterthan it is with the same amount of heparin added to the blood in vitro, due to theeffect of incubation of heparin with blood on its anticoagulant activity. The in-terval required for the clotting time to return to normal is quite short, and with agiven dosage is constant with different animals. Factors influencing the relationbetween duration of hypocoagulability and dosage are discussed.

4. A test has been devised to determine the sensitivity of the animal to the anticoagulant action of heparin. The clotting time response to certain concentrationsof heparin added to the blood in vitro is determined. A fixed dose of heparin is theninjected intravenously and the clotting time response is again determined. Theresponse in vitro measures the sensitivity of the clotting system to heparin, whilethe in vivo response, when interpreted in the light of the in vitro response, measures the ability of the body to remove heparin from the circulation.

5. By means of this test, it has been determined that anesthesia with pentobarbital decreased the coagulability of the blood, urethane had no effect on coagulability, while the effect of ether was variable. The injection of india ink and evisceration caused a hypercoagulability, while removal of the kidneys had little effect.

6. When the sensitivity of the blood to the anticoagulant action of heparin wastested during these procedures, pentobarbital and nephrectomy had no effect, ethercaused an increase in sensitivity, urethane a decrease. The injection of india inkand also evisceration markedly decreased the sensitivity of the blood to the anticoagulant action of heparin.

7. Anesthesia with pentobarbital, ether or urethane, the injection of india ink,removal of the kidneys, or removal of the gastrointestinal tract, had no effect onthe duration of heparin action in the body.

Note: ACKNOWLEDGMENTWe are greatly indebted to Professor C. H. Best for his interest and encouragement in these studies,and to Dr. J. Markowitz for performing the experimental surgery for us. The study was supported bya grant from the John and Mary R. Markle Foundation.

     

Activated partial thromboplastin time and clinical outcome after thrombin inhibition in unstable coronary artery disease.

Aims Direct thrombin inhibitors have failed to prove superiority over unfractionated heparin in several clinical trials of unstable coronary artery disease. We have investigated the relationship between activated partial thromboplastin time levels and adverse clinical events, i.e. death, myocardial (re-)infarction or refractory angina.Methods and Results One thousand two hundred and nine patients with unstable coronary artery disease were randomized to 72 h infusion with inogatran, a low molecular mass direct thrombin inhibitor, or unfractionated heparin. During 30 days follow-up there was no significant difference between inogatran and unfractionated heparin treatment as regards clinical outcome. 11.6% of the 464 inogatran treated patients with activated partial thromboplastin time above the median at 6 h (44 s) had a clinical event in 7 days, and 6.6% of the 423 patients with activated partial thromboplastin time below the median (P=0.01). After 30 days the event rate was still 41% higher in the inogatran patients with activated partial thromboplastin time above the median (P=0.06). Activated partial thromboplastin time in quartiles indicated a direct relationship between higher activated partial thromboplastin time and worse outcome. In contrast, during heparin infusion there was a trend for improved clinical outcome with activated partial thromboplastin time above the median, but this benefit was lost after cessation of treatment. CONCLUSIONS: Higher activated partial thromboplastin time levels during inogatran treatment are related to increased risk of death, myocardial infarction or refractory angina. This might, at least in part, be explained by differences in anticoagulant mechanisms between direct thrombin inhibitors and heparin, and further emphasizes the poorly defined optimal activated partial thromboplastin time range during treatment with direct thrombin inhibitors in unstable coronary artery disease.     

Evaluation of activated partial thromboplastin time (aPTT) reagents for application in biomedical diagnostic device development

Introduction: The most commonly used test for monitoring heparin therapy is the activated partial thromboplastin time (aPTT). The response of available aPTT reagents to heparin varies significantly. The aim of this study was to highlight the differences between aPTT reagents stored in a dried format to select the most suitable formulations to be used for the development of point‐of‐care diagnostic devices used for monitoring of unfractionated heparin dose response. Methods: Ten reagents were analysed in terms of their performance in liquid and in dried form after storage for 24 h and 14 days. Performance was assessed by measurement of the clotting time (CT) as evidenced by the onset of thrombin formation using a chromogenic thrombin substrate in plasma samples activated with these formulations. Results: Reagents in all of the three forms tested (liquid, 24 h and 14 days) resulted in significant shortening of CTs in comparison with the nonactivated plasma CT. Liquids returned more rapid CTs in comparison with dried reagents. Most of the reagents were more sensitive to heparin in dried, rather than in liquid form. Dried reagents based on kaolin as a surface activator were notably more effective in achieving short CT than others, while dried reagents composed of silica and synthetic phospholipids were the most sensitive to heparin. Conclusion: Two reagents, namely aPTT‐SP and SynthASIL both of which are based on synthetic phospholipids and silica, were identified as promising candidates for incorporation into point‐of‐care diagnostic device platforms as dried reagents.     

Sensitivity of the thrombin clotting time and activated partial thromboplastin time to low level of antithrombin III during heparin therapy

Summary. The thrombin clotting time (TCT) has been used at our institution, along with the activated partial thromboplastin time (aPTT), for monitoring heparin therapy. We have observed that, in some patients, a discrepancy develops between the heparin levels predicted by the TCT and the aPTT with the TCT consistently predicting a lower heparin level than the aPTT. An inverse relationship was noted between the functional antithrombin III (AT-III) level and the magnitude of this discrepancy.     

Monitoring the effect of heparin by measurement of activated clotting time during and after percutaneous transluminal coronary angioplasty

The anticoagulant effect of heparin during percutaneous transluminal coronary angioplasty was monitored by measurements of the activated clotting time in two studies that compared the effects of a single bolus of heparin with those of a bolus of heparin combined with a continuous infusion of the drug. In a preliminary study 40 patients received a single heparin bolus of 10,000 units (protocol I) and a further 40 patients received both a heparin bolus of 10,000 and a continuous infusion of heparin at a rate of 2000 units per hour (protocol II). During the first 45 minutes, nine patients (23%) in protocol I but only two patients (5%) in protocol II were found to be inadequately anticoagulated. For 24 hours after angioplasty both groups received an infusion of heparin at the rate of 2000 units per hour which led to consistent anticoagulation in 73 (91%) of patients. In a subsequent randomised study, 40 patients received heparin according to either protocol I or II. Protocol II was again found to lead to a higher rate of adequate anticoagulation. During the first 60 minutes 11 patients (55%) in protocol I but only three patients (15%) in protocol II were inadequately anticoagulated. In addition, the activated clotting time of arterial blood in the first 30 minutes was significantly higher than that of venous blood in 70% of the patients. A bolus of heparin (10,000 units) together with an infusion of 2000 units per hour should be routinely given during coronary angioplasty. The effects of heparin, which can vary considerably from patient to patient, should be monitored by the measurement of the activated clotting time of arterial blood.     

Heparin kinetics in venous thrombosis and pulmonary embolism.

The response to a standard dose of heparin was studied in 20 patients with venous thromboembolism. The heparin regimen consisted of intravenous injection of 70 units per kg, followed after 90 minutes by a maintenance dose of 400 units per kg per 24 hours given by continuous infusion. Plasma heparin activity and the activated partial thromboplastin time (APTT) were measured at intervals to determine clearance of the initial injection and the response to maintenance dose. Large inter-individual variations were found in the anticoagulant effect and these were due in part to differences in heparin clearance and in part to differences in the APTT response to given amounts of heparin (heparin effect index). The heparin half-life was 63 +/- 15 minutes when plasma heparin activities were used for this calculation and 84 +/- 71.5 minutes when the APTT was used. These results are similar to values previously reported in normal volunteers. Four of the 20 patients had pulmonary embolism and in these heparin half-life was significantly shortened (P less than 0.005).     

Evaluating the optimal activated clotting time during carotid artery stenting

Carotid artery stenting is an alternative to carotid endarterectomy for patients at high risk for surgery for carotid artery stenosis. Although unfractionated heparin is routinely used, there are no published data evaluating the optimal activated clotting time during carotid stenting. In a retrospective analysis of 605 patients who underwent carotid stenting using unfractionated heparin at the Cleveland Clinic Foundation, the optimal peak procedural activated clotting time associated with the lowest combined incidence of death, stroke, or myocardial infarction was 250 to 299 seconds.     

Monitoring the effect of heparin by measurement of activated clotting time during and after percutaneous transluminal coronary angioplasty.

The anticoagulant effect of heparin during percutaneous transluminal coronary angioplasty was monitored by measurements of the activated clotting time in two studies that compared the effects of a single bolus of heparin with those of a bolus of heparin combined with a continuous infusion of the drug. In a preliminary study 40 patients received a single heparin bolus of 10,000 units (protocol I) and a further 40 patients received both a heparin bolus of 10,000 and a continuous infusion of heparin at a rate of 2000 units per hour (protocol II). During the first 45 minutes, nine patients (23%) in protocol I but only two patients (5%) in protocol II were found to be inadequately anticoagulated. For 24 hours after angioplasty both groups received an infusion of heparin at the rate of 2000 units per hour which led to consistent anticoagulation in 73 (91%) of patients. In a subsequent randomised study, 40 patients received heparin according to either protocol I or II. Protocol II was again found to lead to a higher rate of adequate anticoagulation. During the first 60 minutes 11 patients (55%) in protocol I but only three patients (15%) in protocol II were inadequately anticoagulated. In addition, the activated clotting time of arterial blood in the first 30 minutes was significantly higher than that of venous blood in 70% of the patients. A bolus of heparin (10,000 units) together with an infusion of 2000 units per hour should be routinely given during coronary angioplasty. The effects of heparin, which can vary considerably from patient to patient, should be monitored by the measurement of the activated clotting time of arterial blood.     

Clinical experience with routine activated coagulation time monitoring during elective PTCA

Background: Intracoronary thrombosis is an im portant factor in the pathogenesis of acute complications during percutaneous coronary interventions. The activated coagulation time (ACT) is a simple, reproducible bedside test that has become standard as the means of monitoring the anticoagulant effect of heparin during these procedures. To determine if ACT-adjusted heparin dosing reduces the procedure-related complications of elective PTCA, 1200 patients who underwent nonemergent percutaneous transluminal coronary angioplasty (PTCA) between January 1, 1988 and February 26, 1992 were studied.Methods/Results: Two groups were identified based on the use of empirical heparin dosage (group 1, before July 1, 1990) vs. ACT-guided heparin administration strategies (group 2, after July 1, 1990). Group 2 patients were older, had worse left ventricular function, and were more likely to have experienced a prior myocardial infarction than patients in group 1. Patients in group 1 were more likely to have chronic stable angina and a positive exercise test, while group 2 patients were more likely to be undergoing PTCA for post-myocardial infarction (MI) angina. Angiographie characteristics were also consistent with a higher risk profile in group 2 than in group 1 (92.7% vs. 83.4%, p < 0.001). Postprocedural complications, including abrupt closure and late closure, were lower in group 2 patients. The incidence of abrupt vessel closure was decreased by approximately 50% (6.9% vs. 3.5%, p < 0.025), and delayed vessel closure was significantly reduced by over 60% (3.2% vs. 1.0%, p < 0.05). There were no differences in femoral artery complications between the two specified groups.Conclusions: ACTguided heparin therapy during percutaneous coronary interventions decreases acute and delayed vessel closure, even in the presence of clinical and angiographic characteristics that would predict a higher incidence of these events.Presented in part at the 41st Annual Scientific Sessions of the American College of Cardiology, Dallas, TX, April 15, 1992.     

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.     

The internalization and release of heparins by cultured endothelial cells: the process is cell source, heparin source, time and concentration dependent

Endothelial cells in vivo and in vitro take up heparin following administration. In in vitro systems, cellular and pericellular extracts of monolayers exposed to heparin, demonstrate internalization as well as cell surface attachment. To further investigate the characteristics of this exogenous heparin partitioning, we have exposed two types of endothelial cells to media containing cold and 125I labelled bovine lung, porcine mucosal or CY222 heparin. Heparin uptake, in pericellular and intracellular fractions of porcine cells, increased with concentration at 24 hrs exposure for all heparins. Only bovine heparin was preferentialy accumulated intracellularly. Cultured murine LE-II endothelial cells showed a greater accumulation in the intracellular fraction than porcine cells when exposed to porcine heparin. When bovine or CY222 heparin was administered for varying times, total heparin uptake increased with time. Heparin in the pericellular fraction was greater than intracellular at exposure durations from 5 mins to 6 hrs. At 16 hrs intracellular heparin markedly increased and far exceeded pericellular. The possibility of release of previously internalized heparin was studied by washing cultures previously exposed to heparin with heparin-free media. Heparin could be recovered up to 96 hours post exposure. A concurrent decrease in pericellular and cellular heparin was observed. These results show a differing distribution of heparin across endothelial cell membranes that is heparin source, concentration and time dependent. A previously unsuspected gradient-time mechanism is suggested. The degree of internalization differs for different endothelial cell sources. The protracted retention of heparin intracellularly by endothelial cells and subsequent release may be of therapeutic and physiological consequence.     

Percutaneous transluminal coronary angioplasty: Comparison of arterial vs. venous activated clotting time

When arterial blood samples for activated clotting time (ACT) are difficult to obtain from the arterial sheath during coronary intervention, venous ACT serves as a substitute. Data are lacking on whether arterial and venous ACT are identical and whether one can serve as an effective substitute for the other. Forty-eight patients undergoing percutaneous transluminal coronary angioplasty (PTCA) were prospectively evaluated to answer this question. Simultaneous arterial and venous ACT samples were drawn from femoral artery and vein vascular sheaths before and during each procedure, and ACT values were determined with a Hemochron automated electronic timer. Porcine heparin dosing was guided by arterial ACT in the first 25 patients and by venous ACT in the last 23 patients. The target ACT value used for continued heparin dosing was 400 sec. At baseline and throughout the study up to 60 min, venous ACT was slightly and significantly greater than arterial ACT. Despite this statistical difference in ACT values, there was no difference in complication rate between the two groups, and the amount of heparin used during either guiding regimen was the same. Therefore, although venous ACT values are slightly higher than arterial, the more convenient venous ACT can be safely used to guide heparin dosing during PTCA when using a target ACT value of 400 sec. © 1996 Wiley-Liss, Inc.     

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.     

Effects of vitamin K antagonist phenprocoumon on activated partial thromboplastin time measurement of direct thrombin inhibitors.

The activated partial thromboplastin time (aPTT) is currently the most common test used to measure the anticoagulation intensity of heparins and direct thrombin inhibitors (DTIs). Vitamin K antagonists variably affect aPTT reagents. Interactions between heparin and DTIs occur during concurrent therapy. Three DTIs (lepirudin, argatroban, melagatran) and one unfractionated heparin (liquemin) were added to normal plasma (NP) samples (n = 23) and to vitamin K antagonist plasma (VKAP) samples (n = 23) of patients treated with phenprocoumon. Lepirudin and argatroban were added at concentrations from 300 to 3000 ng/ml, melagatran from 30 to 1000 ng/ml, and unfractionated heparin from 0.016 to 0.48 IU/ml. Wave parameters of clotting time and aPTT ratio curves were evaluated by multivariate analysis for inhibitors, aPTT reagents and NP and VKAP samples. Normal ranges resulting from NP samples were 34.5 +/- 1.0 s with Pathromtin SL and 33.9 +/- 0.8 s with Platelin LS. Normal ranges using VKAP were 52.8 +/- 2.6 s (Pathromtin SL) and 44.2 +/- 1.1 s (Platelin LS) (P < 0.0001). Variance analysis showed that inhibitors, plasmas (NP versus VKAP) and reagents influenced the wave characteristics of aPTT (s) (P < 0.0001) and aPTT ratios (P < 0.0001). Distinct statistical differences between aPTT reagents on one hand and normal versus vitamin K antagonist plasma on the other hand make a comparison of reported aPTT results difficult, especially during overlapping therapy with vitamin K antagonists.     

Heparin dosing for percutaneous coronary angioplasty: Use of body surface area to improve initial activated clotting time values

Background: Activated clotting time (ACT) values during percutaneous transluminal coronary angioplasty (PTCA) after the initial 10,000 U heparin bolus are often below target values of 350 or 400 s (Hemochron) and have to be supplemented with additional heparin. This study evaluated the initial 10 min post-heparin bolus clotting time value using a body surface area (BSA)-adjusted heparin bolus versus the traditional 10,000 U heparin bolus. Hypothesis: Body surface area adjustment of initial heparin dosing prior to PTCA will be more effective in reaching target ACT values compared with the 10,000 U heparin bolus method. Methods: Twenty-seven patients receiving the BSA-adjusted heparin bolus were compared with 27 age- and gender-matched controls who had received the traditional heparin bolus. The adjusted heparin bolus formula used was [BSA(m²)/1.3m²] X 10,000 U of heparin. Results: The success rate at reaching the target value of 400 s was 13 of 27 (48.1%) and 2 of 27 (7.4%) for the BSA-guided and 10,000 U heparin-guided groups, respectively (p < 0.01). The success rate at reaching the 350 s target value was 25 of 27 (92.6%) and 6 of 27 (22.2%) for the BSA-guided and 10,000 U heparin-guided groups, respectively (p < 0.01). The 95% confidence intervals for the difference in success between the BSA-guided and 10,000 U heparin-guided groups were 0.19–0.62 and 0.52–0.89 for the 400 s and 350 s ACT targets, respectively. Conclusion: Body surface area adjustment of initial heparin dosing is a more effective method of reaching the initial ACT target values of 350 and 400 s compared with the traditional method prior to PTCA. This conclusion applies to the Hemochron ACT device and arterial samples, and adjustments may need to be made for other devices and/or venous samples.     

Diagnostic uses of the activated partial thromboplastin time and prothrombin time

The activated partial thromboplastin time (APTT) and prothrombin time (PT) have three principal uses. In screening for coagulation disorders (or increased risk of postoperative hemorrhage), the tests add no information to the preoperative care of patients without clinical findings indicative of increased bleeding risk. Furthermore, the prevalence of asymptomatic congenital coagulopathies is so low that false-positive test results greatly outnumber true-positive results. Thus, clinicians may use clinical assessment to screen and should reserve coagulation tests to investigate patients with abnormal findings. In evaluating abnormal bleeding, these tests are sufficiently sensitive that if both are negative, further investigation of the coagulation system is obviated. If one or both tests are positive, the pattern of results directs further attention to limited segments of the coagulation sequence. In monitoring anticoagulation therapy, the APTT and PT tests appear to contribute to the safety and effectiveness of heparin and warfarin therapies, respectively.     

Venous activated clotting time after intra-arterial heparin: Effect of site of administration and timing of sampling

It is not known how the site of arterial administration of heparin and the timing of the activated clotting time (ACT) measurement affect the ACT during coronary interventions. We measured serial femoral venous ACTs after heparin was administered either via the angioplasty guiding catheter into the central aorta or peripherally via a sheath into the femoral artery. When heparin was administered into the central aorta, the ACT rose gradually and by 60 sec plateaued without further increase. When heparin was given into the femoral artery, the ACT displayed a marked “overshoot” early (20–270 sec after heparin) and did not plateau until sometime between 270 and 800 sec after heparin administration. We conclude that the site of administration and timing of venous sampling markedly affect the measured ACT during coronary interventions. Operators should be aware of these effects when assessing the accuracy of the ACT during coronary interventions. © 1996 Wiley-Liss, Inc.     

Heparin Elimination in Uraemic Patients on Haemo-Dialysis

Heparin (100 U/kg bodyweight) was administered as single i.v. injections, and heparin concentration in plasma determined by polybrene titration. Mean concentration half-life was 74.7 min in the normal group (n = 6), 118.6 min in the nephrectomized patients (n = 5), and 97.8 min in the other uraemic patients (n = 6). The differences between the mean values for the normals and for the 2 patient groups were statistically significant (p < 0.001 and p ? 0.2 respectively). Mean anticoagulant half-life (based on thrombin clotting time) was 64.3, 75.8 and 62.7 min in the 3 groups. The differences between heparin concentration half-life and anticoagulant half-life in the 3 groups were statistically significant. These differences may be partly explained by a significant fall in heparin cofactor activity after injection of heparin. There was a strong positive individual correlation between heparin concentration half-life and anticoagulant half-life in the patients (r = 0.94), but not in the normal group (r = 0.31). There was a strong negative individual correlation between heparin tolerance and heparin concentration half-life in the patients (r = -0.84), but no correlation in the normal group. It is concluded that severely impaired renal function has a significant, but moderate influence on heparin elimination.     

Comparison between siliconized evacuated glass and plastic blood collection tubes for prothrombin time and activated partial thromboplastin time assay in normal patients, patients on oral anticoagulant therapy and patients with unfractioned heparin therapy

Introduction: The study was designed to evaluate whether there was a statistically significant effect between evacuated glass tubes and plastic tubes on prothrombin time (PT) and activated partial thromboplastin time (aPTT). Methods: Blood samples were drawn into four different tubes from three patient populations—apparently healthy patients, patients on oral anticoagulant therapy with vitamin K antagonists (OAT‐vka) and patients being treated with unfractioned heparin (UFH). Testing was performed on an automated coagulation analyzer, and statistical analysis was achieved using a test of variance (anova ). Results: For normal patients, there were no statistically significant differences for the aPTT test; however, there were statistically significant differences for the PT test. For patients on OAT‐vka, statistically significant differences were clearly observed between the four tube types for the PT test. For patients treated with UFH, there were no statistically significant differences for the aPTT test. Conclusion: The data showed a statistically significant difference between glass and plastic tubes in the normal population only for the PT test, with consequent repercussions for patients on OAT. This means that appropriate care and validation should take place whenever there is a change in tube type.