Transition from argatroban to oral anticoagulation with phenprocoumon or acenocoumarol: effects on prothrombin time, activated partial thromboplastin time, and Ecarin Clotting Time

2004 ◽  
Vol 91 (06) ◽  
pp. 1137-1145 ◽  
Author(s):  
Jochen Graff ◽  
Ute Klinkhardt ◽  
Nils von Hentig ◽  
Jeanine Walenga ◽  
Hikari Watanabe ◽  
...  
Keyword(s):  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Combined Treatment ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Sensitivity Index ◽  
Clotting Time ◽  
Ecarin Clotting Time

SummaryTreatment with the direct thrombin inhibitor argatroban (ARG) is often followed by vitamin K-antagonist treatment (VKA). Phenprocoumon (PC) and acenocoumarol (AC) are frequently used in Europe. The standard monitoring test for VKA, prothrombin time (PT), is prolonged by direct thrombin inhibitors. Therefore the International Normalized Ratio (INR) obtained during combined treatment does not reflect the true effect of the VKA. A similar interference of the VKA on the activated partial thromboplastin time (aPTT), a monitoring assay for direct thrombin inhibitors, can occur. In 39 healthy volunteers the effect of ARG alone or combined with PC or AC on PT, INR, aPTT, and Ecarin Clotting Time (ECT) was investigated. 6 groups each of 6-8 volunteers received a 5-hour infusion of either 1.0, 2.0 or 3.0 µg/kg/min ARG (days 1, 3, 4 and 5) before initiation of either PC or AC (day 1) and during continued VKA dosing (target INR 2-3). A linear relationship (INR ARG+VKA = intercept + slope * INR VKA alone) was observed between the INR measured “on” and “off” ARG.The slope depended on the argatroban dose and on the International Sensitivity Index (ISI) of the PT reagent, the steepest slope (i.e., the largest difference between INR ARG+VKA and INR VKA alone) was seen with the highest ARG dose and the PT reagent with an ISI of 2.13.There was a close correlation between plasma levels of ARG and aPTT or ECT. Under VKA the ARG-aPTT relationship indicated an increased sensitivity of the aPTT to ARG, VKA treatment had no effect on the prolongation of the ECT induced by argatroban. In conclusion, ARG at doses up to 2 µg/kg/min can be discontinued at an INR of 4.0 on combined therapy with VKA, as this would correspond to an INR between 2.2 and 3.7 for the VKA. If it is necessary to monitor ARG in the critical transition period, the ECT which is not influenced by VKA can be used as an alternative to the aPTT.

Comparison of Activated Partial Thromboplastin Time Ratios with Ecarin Clotting Time Ratios for Monitoring Direct Thrombin Inhibitor Therapy: In-Vitro Study and Case Study of Lepirudin Therapy.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4149-4149
Author(s):  
Harry L. Messmore ◽  
Nancy J. Fabbrini ◽  
Ketty Badrinath ◽  
Richard Harriman ◽  
Omar Iqbal ◽  
...  
Keyword(s):  
Dose Response ◽  
Partial Thromboplastin Time ◽  
Response Curve ◽  
Activated Partial Thromboplastin Time ◽  
Dose Response Curve ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Blood Levels ◽  
Clotting Time

Abstract The direct thrombin inhibitors lepirudin and argatroban are widely used to treat heparin induced thrombocytopenia (HIT). It has been suggested that the Ecarin™ (Echis carinatus venom) clotting time may be superior to the activated partial thromboplastin time (APTT) for monioring purposes. We have prepared standard curves for lepirudin (Refludan™) and Argatroban covering therapeutic drug levels and corresponding APTT ratios (clotting time/control clotting time). Ecarin™ clotting time ratios were performed to demonstrate the practical application of these curves in the clinical care of patients. We report the case of an 80 year old man with HIT/HITT syndrome that occurred during therapy for deep vein thrombosis (DVT) with a low molecular weight heparin (LMWH). His initial coagulation studies were abnormal due to warfarin and LMWH therapy. The patient had a moderate impairment of renal function. Lepirudin therapy in a bolus dose of 14 mg (patient weight: 103.0 kg) resulted in supratherapeutic blood levels of drug and hematuria (Platelet count: 〉200 x 103). Dosage adjustment to maintain an APTT ratio of 1.5 for five days caused no hematuria, but thromboembolic complications occurred at that ratio. The in-vitro dose response curve for Lepirudin was compared with the Ecarin™ clotting time (ECT) ratio at those same concentration ranges in the same plasma. For comparison, Argatroban dose response curves in-vitro were made as well. ECT ratios were very similar to the APTT ratios in the patient’s samples. Representative ratios after the initial bolus, during the infusion period of five days and at the termination of that period are shown in the following table: Comparison of APTT and ECT Ratios APTT Ratio ECT Ratio 1.43 1.07 3.98 3.08 2.91 1.95 2.74 1.95 2.79 1.90 2.58 1.78 2.44 2.42 3.83 4.78 Conclusion: The ECT ratios reflect a steeper dose response curve than that observed with the APTT ratios. This may permit more accurate measurement of blood levels using ECT ratios.

Effect of Melagatran on Prothrombin Time Assays Depends on the Sensitivity of the Thromboplastin and the Final Dilution of the Plasma Sample

2001 ◽  
Vol 86 (08) ◽  
pp. 611-615 ◽  
Author(s):  
Angela Menschiek-Lundin ◽  
Karin Wåhlander ◽  
Tomas Lindahl ◽  
Christer Mattsson
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Plasma Sample ◽  
Anticoagulant Activity ◽  
Vitamin K Antagonists ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Direct Thrombin Inhibitors ◽  
Sensitivity Index ◽  
Response Curves

SummaryProthrombin time (PT) assays are clotting methods that measure the activity of vitamin K-dependent coagulation factors (F) II, VII, and X. There are three main types of PT assays in general usage, namely the Quick assay, Owren’s assay and PT dry chemistry test cards. PT assays were initially developed to monitor dose-adjustments of vitamin K antagonists such as warfarin. The aim of the present study was to investigate whether commercially available PT assays are suitable for evaluating the anticoagulant activity of direct thrombin inhibitors. Melagatran, a reversible direct thrombin inhibitor, was added to human plasma at concentrations ranging from 0.1 to 2.0 μmol/l. Seventeen different commercially available PT kits were used, including thirteen Quick reagents, two Owren reagents and two PT test cards. The sensitivity of the different reagents, expressed as the concentration of melagatran that doubled the prothrombin time (IC50) varied widely, with Thromboplastin S and Thromboplastin HS being the most sensitive (IC50 = 0.9 μmol/l). The reagents with apparently the lowest sensitivity were the two Owren reagents Nycotest PT and SPA 50 with an IC50 of 2.2 and 2.9 μmol/L, respectively. This is most likely due to a higher dilution of melagatran in these assays compared to the dilution in the Quick assays. The results were also dependent on the International Sensitivity Index (ISI) of each reagent. The concentration of melagatran that produced an International Normalized Ratio (INR) of 2 was calculated from dose-response curves for each assay, and these results revealed that reagents with a high ISI value gave an INR of 2 at much lower concentrations of melagatran (0.5-0.7 μmol/L) than those with an ISI-values around one (0.9-1.2 μmol/L). It was found that INR depends not only on the plasma concentration of melagatran, but also on the sensitivity of the PT reagent and on the final dilution of the plasma sample in the prothrombin time assay. Thus, since the same melagatran concentration can be associated with widely varying PT/INR results depending on the specific assay used it is concluded that PT assays and INR can not be used to monitor melagatran activity.

Can RoTEM®analysis be applied for haemostatic monitoring in paediatric congenital heart surgery?

2011 ◽  
Vol 21 (6) ◽  
pp. 684-691 ◽  
Author(s):  
Jo Bønding Andreasen ◽  
Anne-Mette Hvas ◽  
Kirsten Christiansen ◽  
Hanne Berg Ravn
Keyword(s):  
Cardiac Surgery ◽  
Platelet Count ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Congenital Heart ◽  
Heart Surgery ◽  
Congenital Heart Surgery ◽  
Activated Partial Thromboplastin Time ◽  
Clotting Time ◽  
Coagulation Tests

AbstractBackgroundSuccessful management of bleeding disorders after congenital heart surgery requires detection of specific coagulation disturbances. Whole-blood rotation thromboelastometry (RoTEM®) provides continuous qualitative haemostatic profiles, and the technique has shown promising results in adult cardiac surgery.SettingTo compare the performance of RoTEM®with that of conventional coagulation tests in children, we conducted a descriptive study in children undergoing congenital cardiac surgery. For that purpose, 60 children were enrolled and had blood samples taken before, immediately after, and 1 day after surgery. Conventional coagulation tests included: activated partial thromboplastin time, prothrombin time, fibrinogen, fibrin D-dimer, thrombin clotting time, factor XIII, and platelet count.ResultsPost-surgical haemostatic impairment was present to some degree in all children, as seen by pronounced changes in activated partial thromboplastin time, prothrombin time, thrombin clotting time, and platelet count, as well as RoTEM®analysis. RoTEM®showed marked changes in clotting time – prolonged by 7–18% – clot formation time – prolonged by 46–71% – maximum clot firmness – reduced by 10–19%, and maximum velocity – reduced by 29–39%. Comparison of the two techniques showed that conventional coagulation tests and RoTEM®performed equally well with regard to negative predictive values for excessive post-operative drain production – more than 20 millilitres per kilogram per 24 hours after surgery – with an area under the curve of approximately 0.65.ConclusionRoTEM®can detect haemostatic impairments in children undergoing cardiac surgery and the method should be considered as a supplement in the perioperative care of the children where targeted transfusion therapy is necessary to avoid volume overload.

scholarly journals HAEMOPHILIA

2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Diana S Purwanto
Keyword(s):  
Factor Viii ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Activated Partial Thromboplastin Time ◽  
Factor Ix ◽  
Haemophilia A ◽  
Clotting Time ◽  
Serial Test ◽  
Faktor Viii ◽  
Hemofilia A

Abstrak: Hemofilia adalah kelainan perdarahan kongenital yang disebabkan oleh kekurangan faktor VIII (faktor antihemofilik) yang terkait dengan Hemofilia A, atau faktor IX (faktor Christmas) yang terkait dengan Hemofilia B. Kedua hemophilia diturunkan secara X-linked resesif, dan umumnya ditemukan pada laki-laki. Kami melaporkan kasus seorang anak berusia 4 tahun dengan riwayat memar, pendarahan berlebihan, disertai pembengkakan sendi yang nyeri dan hematoma otot, yang dicurigai mengidap hemofilia. Serial tes koagulasi dilakukan dengan hasil: jumlah trombosit, waktu perdarahan, prothrombin time (PT), thrombin clotting time (TCT), dan fibrinogen normal, sedangkan activated partial thromboplastin time (APTT) memanjang. Mixing studies dikoreksi ketika plasma normal dan adsorbed plasma ditambahkan ke plasma pasien, yang menunjukkan defisiensi faktor VIII merupakan penyebab hemofilia ini. Aktivitas faktor VIII 8% menegaskan suatu hemofilia A derajat ringan. Kata kunci: hemofilia, PT, APTT, mixing studies, faktor VIII.   Abstract: Haemophilia is a congenital bleeding disorder caused by a deficiency of factor VIII (antihaemophilic factor), which is related to haemophilia A, or factor IX (Christmast factor), associated with haemophilia B. Both X-linked are recessive, and males are affected mostly. In this case, a four year old boy, who had a history of excessive bruising and bleeding, also suffered from painful swelling of joints and muscle hematoma. He was diagnosed of suspected  haemophilia. A serial test of coagulation studies was performed. The results of platelet count, skin bleeding time, prothrombin time, thrombin clotting time, and fibrinogen were normal; whereas, the activated partial thromboplastin time was prolonged. The mixing studies were corrected when normal plasma and adsorbed plasma were added to the patient plasma, suggesting that the factor VIII deficiency was the cause of this haemophilia. The factor VIII activity was 8% which confirmed the evidence of mild haemophilia A. Keywords: haemophilia, PT, APTT, mixing studies, factor VIII.

Sign in / Sign up

Export Citation Format

Share Document