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Are Direct Oral Anti-Xa Inhibitors Absorbed in Cancer Patients after Gastrectomy? A Case Series

H.C. Puhr1, A. Ilhan-Mutlu1, P. Quehenberger1, P.A. Kyrle1, S. Eichinger1, L. Eischer1

1Medical University of Vienna, Vienna, Austria

Abstract Number: PB0058

Meeting: ISTH 2021 Congress

Theme: Coagulation and Natural Anticoagulants » Coagulation Factors and Inhibitors

Background: Direct oral anticoagulants (DOAC) including the anti-Xa inhibitors apixaban, edoxaban and rivaroxaban are effective and safe for the treatment of venous thromboembolism (VTE) also in cancer patients. DOAC are absorbed predominantly in the upper gastrointestinal tract, which raises concern in cancer patients after gastrectomy regarding achievement of adequate DOAC plasma levels.

Aims: We aimed to evaluate the absorption of oral anti-Xa inhibitors in cancer patients after gastrectomy.

Methods: Using chromogenic anti-Xa assays calibrated for apixaban, edoxaban or rivaroxaban (STA Liquid Anti-Xa, Diagnostica Stago), we measured anti-Xa levels in plasma of eight cancer patients after partial or total gastrectomy who required oral anticoagulation because of VTE or atrial fibrillation. Levels were determined immediately before (trough) and 2-3 hours after drug intake (peak). Rivaroxaban was administered with food.

Results: Patient characteristics including anti-Xa levels and coagulation parameters of eight patient with upper gastrointestinal cancer who underwent total or partial gastrectomy before and after administration of an anti-Xa inhibitor are shown in Table 1 and Table 2. All patients had anti-Xa levels well above the detection limit 2-3 hours after drug intake. In two patients edoxaban trough levels were below the detection limit. One Patient was switched to rivaroxaban with trough levels slightly above the detection limit. One patient discontinued edoxaban and refused further anticoagulation. None of the patients had a thromboembolic event during treatment with DOAC, one patient had major bleeding after brachial artery puncture.
 
Table 1: Patient characteristics and medical history.

Patient number Sex Age Weight in kg Surgery Indication Duration of anticoagulation in months*
1 w 55 70 total gastrectomy PE 8
2 w 37 43 total gastrectomy PE, DVT 8
3 m 76 65 partial gastrectomy DVT 50
4 m 57 65 total gastrectomy Splenic vein thrombosis 26
5 m 76 84 partial gastrectomy PE 11
6 m 76 92 total gastrectomy DVT, PE 4
7 m 80 88 total gastrectomy A-fib 14
8 w 81 39 total gastrectomy A-fib 0,1

Table 1: Patient characteristics and medical history. Abbreviations: PE – pulmonary embolism, DVT – deep vein thrombosis , A-fib – atrial fibrillation; * time from first intake of DOAC until end of observation period
Table 2: Trough and peak anti-Xa levels and coagulation parameters.

trough level peak level
Patient number DOAC Dosage Creatinine Clearance (ml/min) anti-Xa
 (ng/ml)
PT
 (%)
aPTT
 (s)
anti-Xa
 (ng/ml)
PT
 (%)
aPTT
 (s)
1 Rivaroxaban 1x20mg 56,8 45 100 34,1 210 85 44,3
2 Edoxaban 1x30mg 67,9 <20 71 28,8 83 60 33,6
2 Rivaroxaban 1x20mg 75,8 22 65 29,9 39 65 31,2
3 Apixaban 2×2,5mg 57,8 26 87 35,0 65 78 38,0
4 Rivaroxaban 1x20mg 93,7 27 93 30,4 437 72 39,4
5 Rivaroxaban 1x20mg 67,9 65 58 34,5 257 47 43,0
6 Rivaroxaban 1x20mg 54,5 40 80 32,8 228 67 40,8
7 Edoxaban 1x60mg n.a. 51 73 39,5 195 66 47,7
8 Edoxaban 1x30mg 39,9 <20 62 40,4 171 56 49,9

Table 2: Trough and peak anti-Xa levels and coagulation parameters. Abbreviations: DOAC – direct oral anticoagulant, PT – prothrombin time, aPTT – activated partial thromboplastin time, n.a. – not available; Creatinine clearance estimated with the Cockcroft-Gault equation

Conclusions: Direct oral anti-Xa inhibitors are well absorbed in cancer patients after partial or total gastrectomy, but trough and peak levels vary considerably. Studies investigating clinical endpoints are warranted.

To cite this abstract in AMA style:

Puhr HC, Ilhan-Mutlu A, Quehenberger P, Kyrle PA, Eichinger S, Eischer L. Are Direct Oral Anti-Xa Inhibitors Absorbed in Cancer Patients after Gastrectomy? A Case Series [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/are-direct-oral-anti-xa-inhibitors-absorbed-in-cancer-patients-after-gastrectomy-a-case-series/. Accessed May 16, 2022.

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