Background Due to the smaller size of the molecule and low affinity for platelet factor (f) 4, fondaparinux (F) does not cross react with heparin-induced-thrombocytopenia- antibodies . Also F has some more beneficial mechanisms: reduction of aPl-production (BAFF/Blys) and tissue f expression, C3/C5-inactivation, fXa-C3 cleavage blocking, increase of angiogenic process . This can lead to classify F as pathogenic treatment option for rheumatic diseases (RD) as well as anticoagulant.
Objectives To evaluate the affectivity and safety of F in treatment and prevention of thromboses in patients (pts) with RD.
Methods The study included 54 pts suffered from the next RD: 8 systemic lupus erythematosus (SLE), 7 rheumatoid arthritis (RA), 4 antiphospholipid syndrome (APS), 25 SLE+APS, 4 systemic sclerosis, 1 osteoarthritis, 2 ANCA-associated vasculitis and 1 Behcet`s disease. All the pts were treated with anticoagulants - 24 pts with F, 25 pts with nadroparin, 1 pts with enoxaparin and 4 pts with rivaroxaban - for different reasons: deep vein thrombosis (DVT), trophic ulcer, thrombotic cerebral microangiopathy, postthrombotic pulmonary hypertension, hypercoagulability due to nephritis, thrombosis prevention in SLE+APS pts with low platelets. Incidences of thrombosis, bleeding events and platelets levels were monitored. 10 pts (RA + vasculitis) had initial high fibrinogen levels. 12 pts with SLE+APS had baseline aPTT elevation from lupus anticoagulant (LA). Direct anti-fXa level monitoring (anti-Xa) was performed.
Results All the pts demonstrated clinical improvement. Low anti-Xa was registered in 6 (12%) pts, normal anti-Xa – in 37 (69%) pts and high anti-Xa – in 11 (19%) pts. Pts with low anti-Xa underwent dose correction and none of them had new incidence of thrombosis. Most of pts did not have bleeding complications. Only 1 pt with SLE+APS treated with F developed multiple cutaneous haemorrhages. We discharged F for 24 hours and started again in a half dose. anti-Xa monitoring showed level decrease from 1.73 to 1.3 units/mL. In pts with APS and/or SLE F did not influence on aPL, fibrinogen and aPTT. 3 SLE+APS pts who had distal gangrene and cutaneous necrosis intentionally were treated with high dose of F with anti-Xa ∼2 units/mL. That led to a good clinical response and blood flow recovery in ischemic tissues. There were no any signs and symptoms of bleeding.
Conclusions Fondaparinux is an effective and save drug for the treatment and prevention of thrombosis in pts with RD. During the therapy routine coagulation monitoring is not representative because of LA and inflammation. We recommend to monitor signs of bleeding and anti-Xa and to expand its normal rate up to 2 units/mL in pts with distal gangrene and cutaneous necrosis due to SLE and APS.
Smythe MA, Priziola J, Dobesh PP et al. Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism. J Thromb Thrombolysis. 2016 Jan;41(1):165–86. doi: 10.1007/s11239-015-1315-2.
Alijotas-Reig J, Ferrer-Oliveras R. Management of refractory obstetric antiphospholipid syndrome: from pathogenesis to novel immunomodulatory therapies. Proceeding of the 9th Meeting of the European Forum on Antiphospholipid Antibodies; 2013 May 16–18; Krakow, Poland. Krakow: Medycyna praktyczna; 2013.
Disclosure of Interest None declared
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