Abnormally short activated partial thromboplastin time values are associated with increased risk of recurrence of venous thromboembolism after oral anticoagulation withdrawal

Legnani, Cristina; Mattarozzi, Silvia; Cini, Michela; Cosmi, Benilde; Favaretto, Elisabetta; Palareti, Gualtiero

doi:10.1111/j.1365-2141.2006.06130.x

Cited by 56 publications

(58 citation statements)

References 18 publications

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“…CT may be considered as a conventional coagulation time and was, in fact, correlated with the APTT ratio (rho=0.52, p<0.001). Since shortened APTT has been associated with an increased risk of occurrence 20 and recurrence 21,22 of venous thromboembolism in thrombophilic patients, it is not surprising that shortened CT detects hypercoagulability in splenectomized thalassemic patients. CFT is defined as the time needed for the clot to reach a fixed firmness (20 mm) and MCF is defined as the maximal amplitude of the tracing after the addition of the trigger.…”

Section: Discussionmentioning

confidence: 99%

Hypercoagulability in splenectomized thalassemic patients detected by whole-blood thromboelastometry, but not by thrombin generation in platelet-poor plasma

Tripodi¹,

Cappellini²,

Chantarangkul³

et al. 2009

Haematologica

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BackgroundThe mechanisms responsible for the increased thrombotic risk associated with thalassemia are still unclear. They might be related to the effects of red blood cell or endothelial cell derangements, increased numbers of platelets as well as abnormal plasma coagulation. Design and MethodsTo evaluate the relative role played by cells and plasma we investigated 169 patients with thalassemia by means of thromboelastometry and thrombin generation tests. Thromboelastometry measures indices of the viscoelastic properties of whole blood after activation of coagulation and is characterized by the clotting time, which may be considered as a conventional coagulation time, clot formation time, defined as the time needed for the clot to reach a fixed firmness, and the maximum clot firmness, defined as the maximal amplitude of the tracing. ResultsAll the thromboelastometry parameters determined in whole blood (including shortened clotting time and clot formation time, and increased maximum clot firmness), were consistent with hypercoagulability, especially in splenectomized patients. Conversely, thrombin generation as determined in platelet-poor plasma was not. ConclusionsThese findings point to blood cells and/or platelets rather than to plasma abnormalities as the most important determinants of the thrombotic risk observed in thalassemic patients who had been splenectomized. These results might have important diagnostic and therapeutic implications.

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Section: Discussionmentioning

confidence: 99%

Hypercoagulability in splenectomized thalassemic patients detected by whole-blood thromboelastometry, but not by thrombin generation in platelet-poor plasma

Tripodi¹,

Cappellini²,

Chantarangkul³

et al. 2009

Haematologica

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“…These results suggest that the findings of Hron et al may probably be applied to other commercial APTT reagents, thus making the APTT a simple and inexpensive laboratory tool to stratify patients with VTE with regard to the risk of recurrence. The results stemming from the study of Hron et al published in this issue of the Journal as well as those from Legnani et al published in abstract form [11] are potentially useful to assess the optimal duration of anticoagulation after a first episode of VTE and may pave the way to validate the clinical usefulness of the APTT in prospective intervention studies as it is happening for the D-dimer [12].…”

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confidence: 99%

Activated partial thromboplastin time (APTT). New indications for an old test?

Tripodi

Mannucci

2006

Journal of Thrombosis and Haemostasis

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The activated partial thromboplastin time (APTT) has been designed in 1953 (see Ref.[1] as an historical sketch) and was aimed at assisting the pioneer work of Brinkhous et al. who were purifying factor VIII (FVIII) from plasma. At the very beginning, the APTT was the coagulation time of the test plasma added with exogenous phospholipids (cephalin) as platelet substitutes and calcium chloride [2]. Later on, it was modified by Proctor and Rapaport [3] who added kaolin to optimize the activation of the contact phase of coagulation. This modification was instrumental in making the coagulation times shorter and the results less variable. Since then, the APTT has been extensively used as a research tool that helped discovering many coagulation factors and elucidating their interactions for thrombin generation and fibrin formation. However, the use of the APTT spread widely in the early 1960s of the last century when the availability of commercial kits made it the test of choice to screen patients for congenital and acquired hemorrhagic diseases. Another step forward to the use of the APTT was the incidental discovery made by Conley and Hartmann [4] of patients, with lupus erythematosus, who had frequently prolonged APTTs even upon addition of normal plasma to the test plasma because of the presence of a circulating anticoagulant. At the very beginning, this was considered as a laboratory nuisance as patients bearing the circulating anticoagulant did not have coagulation factor deficiencies and did not present with hemorrhagic problems. Laboratory workers, who had to investigate many prolonged coagulation times without any obvious advantage, began searching for APTT reagents that were less responsive to the useless circulating anticoagulant named Ôlupus anticoagulantÕ. This attitude changed sharply when Bowie et al.[5] described thrombotic events in patients, with systemic lupus erythematosus, who had circulating anticoagulants and prolonged APTT. Since then, the APTT has been extensively used to search for lupus anticoagulants in patients with history of thrombosis or fetal loss [6]. In the early 1970s of the last century, unfractionated heparin started to be the drug of choice for the treatment of acute venous thromboembolism (VTE) and the APTT soon became the test of choice for dose-adjustment [7]. The success of the APTT in this context was high; the therapeutic range 1.5-2.5-fold APTT prolongation over the normal coagulation time, which was established in a clinical study using an APTT reagent of well-defined composition, was adopted indiscriminately regardless of the responsiveness of the reagent used for testing [8]. This problem notwithstanding the APTT has been instrumental for the successful treatment of patients with thrombosis.Looking at the story, one may notice that the APTT results have been taken as an index of loss-of-function and much less as an index of gain-of-function of the coagulation factors. Although studies addressing the significance of shortened APTT have been carried out in the past (revie...

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“…For practical purposes the lag-time may be considered as a conventional coagulation time. Now, it is well known that shortened coagulation times such as, for instance, the activated partial thromboplastin time (APTT) are risk factors for the occurrence [6] and recurrence of VTE [7,8]. Therefore, it is not surprising if shortened lag-times have recently been associated with the risk of VTE [3].…”

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confidence: 99%

More on: high thrombin generation and the risk of recurrent venous thromboembolism

Tripodi

Legnani

Palareti

et al. 2009

Journal of Thrombosis and Haemostasis

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Legnani C, Scharrer I, Schulman S, van der Meer FJ. Increased fetal loss in women with heritable thrombophilia. More on: high thrombin generation and the risk of recurrent venous thromboembolism Recent studies have shown that high thrombin generation is associated with the risk of first [1] and recurrent venous thromboembolism (VTE) [2][3][4]. This is not unexpected as high thrombin generation is a consequence of hypercoagulability due to elevated levels of procoagulant factors or reduced levels of anticoagulant factors. Thrombin generation is measured after activation of coagulation by small amounts of tissue factor as trigger and phospholipids as platelet substitutes [5]. The ensuing thrombin generation curve is defined by many parameters, and those that are mostly used are the lag-time (i.e. the time interval from the addition of the trigger to the start of thrombin generation), the peak thrombin and the area under the thrombin generation curve, also called endogenous thrombin potential (ETP). In principle, each of the above parameters should reflect hypercoagulability. This is obvious for the peak thrombin and the ETP, but less for the lag-time. For practical purposes the lag-time may be considered as a conventional coagulation time. Now, it is well known that shortened coagulation times such as, for instance, the activated partial thromboplastin time (APTT) are risk factors for the occurrence [6] and recurrence of VTE [7,8]. Therefore, it is not surprising if shortened lag-times have recently been associated with the risk of VTE [3]. To our knowledge whilst peak thrombin and ETP have received attention as risk factors of recurrent VTE in some reports, the same attention was not devoted to the lag-time [1,2,4]. Furthermore, it is unknown whether and to what extent the individual parameters of thrombin generation when taken in combination may add clinical value to the risk assessment.To address this issue we reviewed our results of a recent study on the risk of recurrent VTE and thrombin generation [3]. In that study we had found that high thrombin generation when measured in the presence of thrombomodulin was associated with an increased risk of recurrent VTE. The hazard ratio (95% confidence interval) for recurrent VTE in the multivariate analysis was 3.19 (1.29-7.89) for the lag-time, 3.41 (1.34-8.68) for peak thrombin and 4.57 (1.70-12.2) for ETP. In the present analysis patients were allocated according to a score system that took into consideration normal/abnormal values for each of the three parameters.Values for ETP and peak thrombin were considered as normal if they fell within the limits encompassing the first and second tertile of the distribution for all patients.Likewise, values for lag-time were considered normal if they fell within the limits encompassing the second and third tertile. Accordingly, patients had been assigned score 0 if they had all the parameters that were normal, and score 1, 2 or 3 if they had at least 1, 2 or 3 parameters that were abnormal. The distribution of patients acros...

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Abnormally short activated partial thromboplastin time values are associated with increased risk of recurrence of venous thromboembolism after oral anticoagulation withdrawal

Cited by 56 publications

References 18 publications

Hypercoagulability in splenectomized thalassemic patients detected by whole-blood thromboelastometry, but not by thrombin generation in platelet-poor plasma

Hypercoagulability in splenectomized thalassemic patients detected by whole-blood thromboelastometry, but not by thrombin generation in platelet-poor plasma

Activated partial thromboplastin time (APTT). New indications for an old test?

More on: high thrombin generation and the risk of recurrent venous thromboembolism

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