Martinelli et al. reported a case of a 6-year old girl with severe protein S deficiency who experienced recurrent skin necrosis when her INR was below 4.0 with warfarin therapy. She was started on rivaroxaban and did not have any further skin necrosis after 1 year, suggesting it may be an alternative to warfarin for those with severe protein S deficiency. De Kort et al. described a case using subcutaneous protein C concentrate injections daily for long-term treatment of severe congenital protein C deficiency, which appeared safe and effective despite subtherapeutic levels. Monagle et al. presented a case using low molecular weight heparin subcutaneously twice daily for 6 months then once daily that was

1. Megan Handley
Drug information question: anticoagulant treatment protein C & S deficiency
 Martinelli et al. reported a case of a 6-year old girl with severe protein S
deficiency. She was on long-term anticoagulant therapy with warfarin with a
therapeutic INR of 2.0-3.0. Unfortunately, this range was not sufficient
because the girl experienced recurrent episodes of warfarin-induced skin
necrosis developed if the INR was <4.0. The patient was started on
rivaroxaban and the skin necrosis ceased at 1 year of follow-up. The authors
believe that rivaroxaban may be considered as a valid anticoagulant
alternative to vitamin K antagonists in patients with severe inherited protein
S deficiency because it does not reduce the anticoagulant function of
activated protein C. (Martinelli I, Bucciarelli P, Artoni A, et al. Anticoagulant
treatment with rivaroxaban in severe protein S deficiency. Pediatrics.
2013;1156:e1435-8)
 Protein C concentrate (Ceprotin) is indicated for severe congenital protein C
deficiency. It is most commonly administered intravenously, however a case
report by de Kort et al. described its use subcutaneously in long-term
treatment. The dosage used was 750 IU once daily. Trough levels were
monitored, and despite subtherapeutic levels, there was no recurrent
thrombosis and D-dimer levels were normal. More studies need to be
conducted. (de Kort EHM, Vrancken S, van Heijst AFJ, et al. Long-term
subcutaneous protein C replacement in neonatal severe protein C deficiency.
Pediatrics. 2009;29:e1338-42)
 Monagle, et al. presented a case report that used low molecular weight
heparin as a treatment option for protein C deficiency. The dose
administered was 1mg/kg subcutaneously twice daily for 6 months, then
1mg/kg once daily thereafter. Treatment appeared safe and effective as a
treatment option. (Monagle P, Andrew M, Halton J, et al. Homozygous protein
C deficiency: description of a new mutation and successful treatment with
low molecular weight heparin. Thromb Haemost. 1998;79:756-61)
Conclusions: There is limited data on alternative treatments for protein C and S
deficiency. The target-specific oral anticoagulants seem to be undergoing further
investigation into this indication. I would recommend continuation of warfarin
treatment until further evidence is presented.