Non-anticoagulation options (generally empirical) for potential use in anticoagulant-refractory thrombotic APS
| When to consider . | Options . | Caveats and comments . |
|---|---|---|
| Rethrombosis despite standard-intensity VKA: increase to high-intensity VKA | Vitamin D: correct vitamin D deficiency based on general population guidelines in patients with thrombotic APS | Theoretical reasons for using vitamin D are compelling, but clinical data are limited |
| Statins: correct hyperlipidemia/dyslipidemia based on general population guidelines | Good theoretical reasons for using statins but be mindful of myalgia (∼10%) and (rarely) myositis | |
| Hydroxychloroquine | Good theoretical support from animal models and some clinical data | |
| Very few side effects but long-term use warrants regular ophthalmic examination for rare “bullseye maculopathy” | ||
| Antiplatelet agents | Paucity of evidence for addition of low-dose aspirin to standard-intensity VKA vs switch to high-intensity VKA | |
| Associated with increased bleeding risk | ||
| Rethrombosis despite high-intensity VKA and subsequent high-intensity LMWH (∼20% above standard-therapeutic dose): increase to escalated-dose LMWH (∼30% above standard-therapeutic dose), then fondaparinux | B-cell inhibition | May be particularly useful if concomitant thrombocytopenia is present |
| Approximately 10% of patients with SLE develop hypogammaglobulinemia with consequent infection risk | ||
| IVIG | May be particularly useful if concomitant thrombocytopenia refractory to rituximab but also potentially prothrombotic; therefore, cautious dosing is advised | |
| Plasma exchange | Suggest replacement with 100% FFP to minimize coagulopathy and bleeding risk with anticoagulation | |
| SD-FFP preferable because of reduced potential for adverse events | ||
| Complement inhibition | May be beneficial in APS-related refractory microvascular thrombotic states, including thrombotic microangiopathy or chronic persistent microvascular thrombosis | |
| Vaccinate against meningococcal infections | ||
| Vasodilators | The potential benefit of sildenafil and iloprost may exceed their vasodilatory effect, possibly mediated by platelet function inhibition and endothelial stabilization | |
| Surgical interventions to achieve vasodilation: lumbar sympathectomy, digital sympathectomy, sacral nerve stimulation | The principle is to block/reduce sympathetic mediated vasoconstriction of arterioles permanently | |
| Epidermal grafting | Autologous skin grafting in which the epidermal layer of the skin is harvested from the donor site, then excised and transferred onto the wound | |
| Hyperbaric oxygen therapy | This may be an option for patients with dermal ulceration or tissue loss secondary to ischemic APS | |
| Inferior vena cava filters | Mounting evidence shows little benefit |
| When to consider . | Options . | Caveats and comments . |
|---|---|---|
| Rethrombosis despite standard-intensity VKA: increase to high-intensity VKA | Vitamin D: correct vitamin D deficiency based on general population guidelines in patients with thrombotic APS | Theoretical reasons for using vitamin D are compelling, but clinical data are limited |
| Statins: correct hyperlipidemia/dyslipidemia based on general population guidelines | Good theoretical reasons for using statins but be mindful of myalgia (∼10%) and (rarely) myositis | |
| Hydroxychloroquine | Good theoretical support from animal models and some clinical data | |
| Very few side effects but long-term use warrants regular ophthalmic examination for rare “bullseye maculopathy” | ||
| Antiplatelet agents | Paucity of evidence for addition of low-dose aspirin to standard-intensity VKA vs switch to high-intensity VKA | |
| Associated with increased bleeding risk | ||
| Rethrombosis despite high-intensity VKA and subsequent high-intensity LMWH (∼20% above standard-therapeutic dose): increase to escalated-dose LMWH (∼30% above standard-therapeutic dose), then fondaparinux | B-cell inhibition | May be particularly useful if concomitant thrombocytopenia is present |
| Approximately 10% of patients with SLE develop hypogammaglobulinemia with consequent infection risk | ||
| IVIG | May be particularly useful if concomitant thrombocytopenia refractory to rituximab but also potentially prothrombotic; therefore, cautious dosing is advised | |
| Plasma exchange | Suggest replacement with 100% FFP to minimize coagulopathy and bleeding risk with anticoagulation | |
| SD-FFP preferable because of reduced potential for adverse events | ||
| Complement inhibition | May be beneficial in APS-related refractory microvascular thrombotic states, including thrombotic microangiopathy or chronic persistent microvascular thrombosis | |
| Vaccinate against meningococcal infections | ||
| Vasodilators | The potential benefit of sildenafil and iloprost may exceed their vasodilatory effect, possibly mediated by platelet function inhibition and endothelial stabilization | |
| Surgical interventions to achieve vasodilation: lumbar sympathectomy, digital sympathectomy, sacral nerve stimulation | The principle is to block/reduce sympathetic mediated vasoconstriction of arterioles permanently | |
| Epidermal grafting | Autologous skin grafting in which the epidermal layer of the skin is harvested from the donor site, then excised and transferred onto the wound | |
| Hyperbaric oxygen therapy | This may be an option for patients with dermal ulceration or tissue loss secondary to ischemic APS | |
| Inferior vena cava filters | Mounting evidence shows little benefit |
FFP, fresh frozen plasma; SD-FFP, solvent-detergent fresh frozen plasma.