Background: Thrombotic disease treatment options are limited when anticoagulation with dose escalation of low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) fail. Fondaparinux is a pure, synthetic pentasaccharide that consists of heparin’s essential five sugar chain that binds antithrombin to inactivate factor Xa. There is scarce data regarding fondaparinux’s use in recurrent thrombosis.
Aims: To highlight fondaparinux’s potential role in anticoagulant-refractory thrombosis.
Methods: Six patients received fondaparinux after thrombosis progression in our center between 2016 and 2021. Their clinical data was retrieved and analysed.
Results: Patient characteristics and evolution on treatment are included in table 1. Of those six patients, two were previously diagnosed with a high-risk thrombophilia (triple positive antiphospholipid syndrome (APS) and homozygous factor V Leiden) and four had an underlying malignancy. Half of the patients were female, and their median age was 52 (range 28-71). Four had thrombosis recurrence on increased LMWH weight-adjusted doses (mean increase of 27.5%, range 15-40%) and two had thrombosis recurrence on therapeutic UFH. While on LMWH or UFH: the APS patient developed a valvular thrombus with arterial microemboli, one patient had progressive upper extremity catheter-related deep vein thrombosis (DVT), another patient developed lower extremity DVT and pulmonary emboli and three others experienced worsening lower extremity DVTs. Heparin-induced thrombocytopenia was considered and ruled out in every case. Hence, all patients were treated with fondaparinux for a duration ranging from 26 days to 16 months. All patients had a normal renal function. No progression of thrombus was observed in 100% of patients. Reduction of valvular thrombus was demonstrated in the APS patient and DVT recanalization either partial or complete was shown on venous duplex in the other five patients. No bleeding complications were documented while on fondaparinux.
Conclusions: In our case series, fondaparinux was a limb-saving and potential life-saving option when other standard methods of anticoagulation failed.
| Patient (sex, age, weight) | High thrombotic risk condition | Thrombotic disease and treatment | Evolution |
| Female, 28y, 64 kg |
Triple positive APS Ischemic toe at 25y, PE (on Warfarin) at 26y, 1st pregnancy at 27y (on LMWH): placental abruption at 28 weeks and HELLP syndrome |
At 33 weeks of 2nd pregnancy: developed a TIA while on LMWH – LMWH dose increased 20% Elective delivery at 36 weeks 2 days post-partum: developed several cerebral microinfarcts – another 20% LMWH increase (total 40%) 4 days post-partum: found to have a large mitral valve thrombus (21 x 9 mm) and worsening neurological symptoms – fondaparinux 10 mg x 1, then 7.5 mg die x 25 days (with Warfarin bridging) |
1 month post fondaparinux initiation: reduction in mass size to 3.4 mm, no further embolic events |
| Female, 30y, 92 kg |
Homozygous factor V Leiden and May-Thurner syndrome diagnosed after post-partum DVT: left common iliac vein stent was inserted |
In-stent left common iliac vein thrombosis on Warfarin (4 months post insertion) – switched to LMWH 30 days later: Left leg DVT progression – LMWH increased 25% 7 days later: Right common femoral DVT – fondaparinux 10 mg die x 14 months, followed by Warfarin |
Duplex 5 months post: patent right leg veins, partial DVT regression on the left |
| Male, 54y, 65 kg |
Testicular metastatic germ cell tumor | Bilateral above-knee DVTs – started on LMWH 15% above weight-adjusted dose 7 months later: acute bilateral above-knee DVTs – fondaparinux 7.5 mg die x 5 months, followed by Apixaban |
Duplex 5 months post: bilateral partial recanalization |
| Male, 50y, 57 kg |
Stage IV Pancreatic cancer | Right above-knee DVT – started on LMWH 3 weeks later: Acute left above-knee DVT – LMWH increased 30% 2 months later: Bilateral PEs – fondaparinux 7.5 mg die x 40 days (then died from cancer) |
Duplex 1 month post: partial recanalization of bilateral DVTs |
| Female, 61y, 63 kg |
Hodgkin’s lymphoma | Catheter-related subclavian DVT – started on UFH (about 40 000 units/24h for therapeutic PTT) After 3 days of UFH: DVT extension in axillary vein – fondaparinux 7.5 mg die x 8 months |
Duplex 2 months later: partial recanalization |
| Male, 71y, 75 kg |
Multiple myeloma | Right above-knee DVT and PEs – started on LMWH 10 months later: spontaneous thigh hematoma requiring transfusion, duplex showed acute right above-knee DVT – IVC filter insertion and stopped anticoagulation 2 weeks later: Left above-knee DVT – started on UFH (about 28 000 units/24h for therapeutic PTT) After 4 days of UFH: Worsening bilateral limb-threatening DVTs – fondaparinux 7.5 mg die x 16 months, followed by Apixaban |
1 week post: near resolution of D-dimers Duplex 3 months post: bilateral partial recanalization |
| APS: antiphospholipid syndrome; PE: pulmonary emboli; LMWH: low-molecular-weight heparin; HELLP: hemolysis, elevated liver enzymes, and low platelets; TIA: transient ischemic attack; DVT: deep vein thrombosis; UFH: unfractionated heparin; PTT: partial thromboplastin time; IVC: inferior vena cava | |||
Patient characteristics and evolution on treatment
To cite this abstract in AMA style:
Tanguay M, Séguin C. Recurrent Thrombosis Rescued by Fondaparinux in High-risk Patients: Case Series and Review of Literature [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/recurrent-thrombosis-rescued-by-fondaparinux-in-high-risk-patients-case-series-and-review-of-literature/. Accessed November 29, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/recurrent-thrombosis-rescued-by-fondaparinux-in-high-risk-patients-case-series-and-review-of-literature/