scholarly journals Falsely prolonged activated partial thromboplastin time – a pre- and post-analytical issue

2018 ◽  
Vol 29 (1) ◽  
pp. 157-161
Author(s):  
Charlotte Gils ◽  
Pernille Just Vinholt ◽  
Mads Nybo
Keyword(s):  
Gastrointestinal Bleeding ◽  
Partial Thromboplastin Time ◽  
Coagulation Factors ◽  
Activated Partial Thromboplastin Time ◽  
Coagulation Testing ◽  
Prolonged Aptt ◽  
Viii And Ix ◽  
Analytical Issue ◽  
Analytical Phase ◽  
Routine Coagulation

This case highlights two common pre-analytical problems identified in routine coagulation testing of activated partial thromboplastin time (aPTT), which were overlooked because of a concurrent flag code indicating no coagulation and the result was replaced by asterisks. It concerns a boy with gastrointestinal bleeding and prolonged aPTT > 300 seconds, which raised the suspicion of haemophilia. When all other coagulation parameters (including specific coagulation factors VIII and IX) turned out to be normal, aPTT was re-measured using another analysis principle, which revealed a normal aPTT. The primary aPTT result turned out to be aborted due to concurrent haemolysis and lipaemia, but was erroneously interpreted as prolonged coagulation. The lesson is awareness of the possibility of numerous flag codes on the same sample overruling each other, and awareness on the responsibility in the post-analytical phase that must be carried by increased educational focus and by the manufacturers.

Interference of Blood Cell Lysis on Routine Coagulation Testing

2006 ◽  
Vol 130 (2) ◽  
pp. 181-184 ◽  
Author(s):  
Giuseppe Lippi ◽  
Martina Montagnana ◽  
Gian Luca Salvagno ◽  
Gian Cesare Guidi
Keyword(s):  
Blood Cell ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Cell Lysis ◽  
Activated Partial Thromboplastin Time ◽  
Analytical Quality ◽  
Coagulation Assays ◽  
Coagulation Testing ◽  
Quality Specifications ◽  
Routine Coagulation

Abstract Context.—Preanalytical factors influencing the reliability of laboratory testing are commonplace. It is traditionally accepted that hemolytic samples are unsuitable for coagulation assays because of the release of hemoglobin, intracellular components, and thromboplastic substances from damaged blood cells. Objective.—To evaluate the influence of blood cell lysis on routine coagulation testing. Design.—Twelve aliquots prepared by serial dilutions of homologous lysated samples collected from 10 different subjects, and displaying a final percentage of lysis ranging from 0% to 9.1%, were tested for prothrombin time, activated partial thromboplastin time, fibrinogen, and dimerized plasmin fragment D. Lysis was achieved by subjecting citrated whole blood to a freeze-thaw cycle. Outcome Measures.—Interference from blood cell lysis on routine coagulation testing. Results.—Statistically significant increases in prothrombin time and dimerized plasmin fragment D were observed in samples containing final lysate concentrations of 0.5% and 2.7% respectively, whereas significant decreases were observed in activated partial thromboplastin time and fibrinogen in samples containing a final lysate concentration of 0.9%. The current analytical quality specifications for desirable bias are ±2.0% for prothrombin time, ±2.3% for activated partial thromboplastin time, and ±4.8% for fibrinogen. Percent variations from the baseline values exceeding the current analytical quality specifications for desirable bias were achieved for lysate concentrations of 0.9% (prothrombin time and activated partial thromboplastin time) and 1.8% (fibrinogen), corresponding to average free plasma hemoglobin concentrations of 1.7 and 3.4 g/L, respectively. Conclusion.—Our results confirm that, although slightly hemolyzed specimens might still be analyzable, a moderate blood cell lysis, as low as 0.9%, influences the reliability of routine coagulation testing. Because the interference in coagulation assays has a wide interindividual bias, we do not recommend lysis correction and we suggest that the most appropriate corrective measure should be free hemoglobin quantification and sample recollection.

Comparison of Reagents for Determining the Activated Partial Thromboplastin Time

1978 ◽  
Vol 39 (03) ◽  
pp. 640-645 ◽  
Author(s):  
J J M L Hoffmann ◽  
P N Meulendijk
Keyword(s):  
Partial Thromboplastin Time ◽  
Coagulation Factors ◽  
Activated Partial Thromboplastin Time ◽  
Factor Xi ◽  
Viii And Ix

SummarySix commercially available reagents for the determination of the activated partial thromboplastin time have been evaluated and compared with respect to their sensitivity to the coagulation factors VIII, IX and XI and to their response to heparin. Some variation was observed among the reagents regarding their sensitivity to factor XI and even greater differences were obtained with factors VIII and IX. It was also clear that none of the reagents was sensitive to the same extent to the factors tested. The sensitivity to heparin shows considerable variation, in terms of time as well as mode of response to increasing heparin levels. In four reagents this response is linear, it is logarithmic in one and the remaining one is yet again different.It seems unlikely that any standardization of the APTT determination is at present possible with the reagents studied.

scholarly journals A Rare Cause of Isolated Prolonged Activated Partial Thromboplastin Time: An Overview of Prekallikrein Deficiency and the Contact System

2021 ◽  
Vol 9 ◽  
pp. 232470962110121
Author(s):  
Ivy Riano ◽  
Klaorat Prasongdee
Keyword(s):  
Partial Thromboplastin Time ◽  
Normal Activity ◽  
Fresh Frozen Plasma ◽  
Activated Partial Thromboplastin Time ◽  
Recessive Trait ◽  
Bleeding Tendency ◽  
Contact Activation ◽  
Asymptomatic Patients ◽  
Prolonged Aptt ◽  
Fresh Frozen

Prekallikrein (PK) deficiency, also known as Fletcher factor deficiency, is a very rare disorder inherited as an autosomal recessive trait. It is usually identified incidentally in asymptomatic patients with a prolonged activated partial thromboplastin time (aPTT). In this article, we present the case of a 52-year-old woman, with no prior personal or family history of thrombotic or hemorrhagic disorders, who was noted to have substantial protracted aPTT through the routine coagulation assessment before a kidney biopsy. The patient had an uneventful biopsy course after receiving fresh frozen plasma (FFP). Laboratory investigations performed before the biopsy indicated normal activity for factors VIII, IX, XI, XII, and von Willebrand factor (vWF) as well as negative lupus anticoagulant (LA) screen. The plasma PK assay revealed low activity at 15% consistent with mild PK deficiency. The deficit of PK is characterized by a severely prolonged aPTT and normal prothrombin time (PT) in the absence of bleeding tendency. PK plays a role in the contact-activated coagulation pathway and the inflammatory response. Thus, other differential diagnoses of isolated prolonged aPTT include intrinsic pathway factor deficiencies and nonspecific inhibitors such as LA. We concluded that the initial evaluation of a prolonged aPTT with normal PT should appraise the measurement of contact activation factors and factor inhibitors. PK deficiency should be considered in asymptomatic patients with isolated aPTT prolongation, which corrects on incubation, with normal levels of the contact activation factors and factor inhibitors.

scholarly journals Breakfast can Affect Routine Hematology and Coagulation Laboratory Testing: An Evaluation on Behalf of COLABIOCLI WG-PRE-LATAM

TH Open ◽  
2019 ◽  
Vol 03 (04) ◽  
pp. e367-e376 ◽  
Author(s):  
Maria Elena Arredondo ◽  
Eduardo Aranda ◽  
Rubén Astorga ◽  
Lorena Michele Brennan-Bourdon ◽  
Marise Danielle Campelo ◽  
...  
Keyword(s):  
Latin American ◽  
Health Care Professionals ◽  
Partial Thromboplastin Time ◽  
Blood Cells ◽  
Laboratory Testing ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Activated Partial Thromboplastin Time ◽  
Coagulation Testing ◽  
Fasting Time

AbstractLaboratories worldwide perform both hematological and coagulation testing on patients avoiding fasting time. In 2017, the Latin America Confederation of Clinical Biochemistry (COLABIOCLI) commissioned the Latin American Working Group for Preanalytical Phase (WG-PRE-LATAM) to study preanalytical variability and establish guidelines for preanalytical procedures to be applied by clinical laboratories and health care professionals. This study, on behalf of COLABIOCLI WG-PRE-LATAM, aims to evaluate the effect of the breakfast on routine hematology and coagulation laboratory testing. We studied 20 healthy volunteers who consumed a breakfast containing a standardized amount of carbohydrates, proteins, and lipids. We collected blood specimens for routine hematology and coagulation laboratory testing before breakfast and 1, 2, and 4 hours thereafter. Significant differences between samples were assessed by the Wilcoxon ranked-pairs test. Statistically significant differences (p < 0.05) between basal and 4 hours after the breakfast were observed for red blood cells, hemoglobin, hematocrit, mean corpuscular volume, white blood cells, neutrophils, lymphocytes, monocytes, mean platelet volume, and activated partial thromboplastin time. In conclusion, the significant variations observed in several hematological parameters, and activated partial thromboplastin time due to breakfast feeding demonstrate that the fasting time needs to be carefully considered prior to performing routine hematological and coagulation testing to avoid interpretive mistakes of test results, and to guarantee patient safety. Therefore, COLABIOCLI WG-PRE-LATAM encourages laboratory quality managers to standardize the fasting requirements in their laboratory, i.e., 12 hours.

A shortened activated partial thromboplastin time is associated with the risk of venous thromboembolism

Blood ◽  
2004 ◽  
Vol 104 (12) ◽  
pp. 3631-3634 ◽  
Author(s):  
Armando Tripodi ◽  
Veena Chantarangkul ◽  
Ida Martinelli ◽  
Paolo Bucciarelli ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Venous Thromboembolism ◽  
Partial Thromboplastin Time ◽  
Odds Ratio ◽  
Case Control Study ◽  
Coagulation Factors ◽  
Case Control ◽  
Activated Partial Thromboplastin Time ◽  
Simple Test ◽  
Coagulation Time ◽  
Control Study

Hypercoagulability due to high coagulation factors XI, VIII, IX, II, and fibrinogen is recognized as a risk factor of venous thromboembolism (VTE). These factors are cumulatively explored by the activated partial thromboplastin time (APTT). To test the hypothesis that a short APTT increases the risk of VTE, a case-control study was carried out in 605 patients referred for thrombophilia testing after documented VTE and in 1290 controls. Median APTT ratio (coagulation time of test-to-reference plasma) values were 0.97 (range: 0.75-1.41) for patients and 1.00 (range: 0.72-1.33) for controls (P &lt; .001). In patients who had an APTT ratio smaller than the fifth percentile of the distribution in controls, the odds ratio (OR) for VTE was 2.4 (95% confidence interval [CI]: 1.7-3.6) and was independent of inherited thrombophilic abnormalities. Further statistical analyses in 193 patients and 259 controls for whom factor VIII (FVIII) levels were available showed a decrease of the OR from 2.7 (95% CI: 1.4-5.3) to 2.1 (95% CI: 1.0-4.2), indicating that the risk was only partially mediated by high FVIII levels. In conclusion, hypercoagulability detected by a shortened APTT is independently associated with VTE. This inexpensive and simple test should be considered in the evaluation of the risk of VTE.

Comparison Between a One-Point Dilute Phospholipid APTT and the Dilute Russell Viper Venom Time for Verification of Lupus Anticoagulants

1992 ◽  
Vol 67 (06) ◽  
pp. 672-678 ◽  
Author(s):  
Barbara M Alving ◽  
Charles F Barr ◽  
Lawrence E Johansen ◽  
Douglas B Tang
Keyword(s):  
Partial Thromboplastin Time ◽  
Antiphospholipid Antibodies ◽  
Test System ◽  
Bovine Brain ◽  
Activated Partial Thromboplastin Time ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Normal Plasma ◽  
Prolonged Aptt ◽  
Higher Sensitivity

SummaryIn the present study, the dilute Russell viper venom time (RVVT) and the dilute phospholipid activated partial thromboplastin time (PL-APTT), which are two assays used for the verification of lupus anticoagulants (LA), were modified to increase standardization. The modified assays were then compared with respect to sensitivity and specificity in detecting LA in plasmas from 72 patients with a prolonged APTT. Modifications included utilizing a single dilution of phospholipid that was either bovine brain thromboplastin (Thrombofax) or liposomes comprised of phosphatidylcholine/phosphatidylserine, and expressing the results as a ratio of the clotting times of the mixture of patient and normal plasma/clotting time of normal plasma. In the RWT, the correlation coefficient between assay results for liposomes and Thrombofax was 0.88 and in the PL-APTT, the correlation was 0.68. A positive test for LA was defined as a ratio of ≥1.3 for the PL-APTT with liposomes and ≥1.2 for the PL-APTT with Thrombofax and the RWT with Thrombofax or liposomes. Regardless of the phospholipid source in the test system, the PL-APTT demonstrated higher sensitivity and the RWT showed greater specificity in detecting patient plasmas that contained antiphospholipid antibodies.

Properties of Optical Data from Activated Partial Thromboplastin Time and Prothrombin Time Assays

1997 ◽  
Vol 78 (03) ◽  
pp. 1079-1087 ◽  
Author(s):  
Paul J Braun ◽  
Thomas B Givens ◽  
Andrew G Stead ◽  
Lisa R Beck ◽  
Sheila A Gooch ◽  
...  
Keyword(s):  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Optical Transmittance ◽  
Coagulation Factors ◽  
Activated Partial Thromboplastin Time ◽  
Optical Data ◽  
Change Rate ◽  
Coagulation Assays ◽  
Signal Change ◽  
Coagulation Proteins

SummaryChanges 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.

The influence of acetaldehyde and glycosaminoglycans upon Factor Xa- and Factor X-deficient plasma

2002 ◽  
Vol 80 (9) ◽  
pp. 879-886 ◽  
Author(s):  
Arthur S Brecher ◽  
Eric L Hommema
Keyword(s):  
Blood Coagulation ◽  
Partial Thromboplastin Time ◽  
Factor Xa ◽  
Activated Partial Thromboplastin Time ◽  
Clotting Factor ◽  
Factor X ◽  
Chondroitin Sulfates ◽  
Prolonged Aptt ◽  
Subsequent Addition ◽  
Three Components

The comparative effects of glycosaminoglycans and acetaldehyde (AcH) – glycosaminoglycan (GAG) mixtures upon Factor Xa- (FXa) and Factor X-deficient plasma (FXDP) have been studied by activated partial thromboplastin time (APTT) studies. Heparin at 0.025, 0.030, 0.04, and 0.05 U statistically prolonged the APTT when pre-incubated with FXa at 37°C for 3 min prior to addition to FXDP and subsequent addition of Ca2+. Upon addition of 0.25, 0.375, and 0.5 µg heparin-6000 (H6k) to FXa, significant increases in APTT were observed. Similarly, profound increases in APTT were observed when 0.5, 0.75, and 1.0 µg heparin-3000 (H3k) was added to FXa. The chondroitin sulfates (CSA, CSB, CSC) had far less impact upon APTT with the FXa–FXDP system. In examining the effects of AcH–GAG mixtures upon the clotting factor, it was observed that 44.3 and 443 mM AcH synergistically prolonged the APTT in a statistically significant manner regardless of the order of premixing the three components. Hence, AcH may play a role in prolonging APTT in alcoholics. It synergistically prolonged APTT in concert with GAGs and FXa at the AcH levels used in this study. The effect of the GAGs upon FXDP is far less than its effect upon FXa.Key words: Factor Xa, acetaldehyde, heparin, glycosaminoglycans, blood coagulation.

scholarly journals Influence of dabigatran and rivaroxaban on routine coagulation assays

2015 ◽  
Vol 113 (01) ◽  
pp. 154-164 ◽  
Author(s):  
Els Bailleul ◽  
Bernard Chatelain ◽  
Anne Demulder ◽  
Katrien Devreese ◽  
Jonathan Douxfils ◽  
...  
Keyword(s):  
External Quality Assessment ◽  
Nationwide Survey ◽  
Activated Partial Thromboplastin Time ◽  
Dependent Manner ◽  
Activity Assay ◽  
External Quality ◽  
External Quality Assessment Scheme ◽  
Coagulation Assays ◽  
Coagulation Testing ◽  
Routine Coagulation

SummaryThe Belgian national External Quality Assessment Scheme performed a nationwide survey using lyophilised plasma samples spiked with dabigatran or rivaroxaban to demonstrate to the Belgian clinical laboratories how these drugs affect their routine coagulation assays prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and antithrombin. Virtually all Belgian laboratories performing routine coagulation testing (189/192) participated in the survey. Both, dabigatran and rivaroxaban significantly prolonged the PT and aPTT in a concentration- and reagent-dependent manner. PT reagents were more influenced by rivaroxaban than by dabigatran and aPTT reagents more influenced by dabigatran than by rivaroxaban. Among PT reagents, Neoplastin R® was the most sensitive to rivaroxaban and Innovin ® and Thromborel S® the least sensitive. Converting PT results to INR only increased the variability between reagents. Among aPTT reagents, Actin FSL® was the least sensitive to dabigatran while the other aPTT reagents showed slightly higher sensitivities. The presence of dabigatran led to falsely reduced fibrinogen concentrations when measured with a low thrombin concentration reagent. The presence of dabigatran caused an overestimation of the antithrombin level when measured with a thrombin-based activity assay and the presence of rivaroxaban an overestimation of the antithrombin level when measured with a FXa-based assay. Instrument-related differences were found for all tested parameters. In conclusion, this paper provides detailed information on the effect of dabigatran and rivaroxaban on routine coagulation assays as performed with a large number of reagent/instrument combinations.

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