Successful Warfarin Anticoagulation Despite Protein C Deficiency and a History of Warfarin Necrosis

Zauber, N. Peter

doi:10.7326/0003-4819-104-5-659

Cited by 82 publications

(29 citation statements)

References 7 publications

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“…This approach should avoid an abrupt fall in protein C levels before reduction in levels of factors II, IX, and X occurs, and several case reports have suggested that warfarin can be resumed in this way without recurrence of skin necrosis. 184,185 Clinical Applications of Oral Anticoagulant Therapy…”

Section: Nonhemorrhagic Adverse Effects Of Warfarinmentioning

confidence: 99%

American Heart Association/American College of Cardiology Foundation Guide to Warfarin Therapy

Hirsh¹,

Fuster²,

Ansell³

et al. 2003

Circulation

711

542

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Section: Nonhemorrhagic Adverse Effects Of Warfarinmentioning

confidence: 99%

American Heart Association/American College of Cardiology Foundation Guide to Warfarin Therapy

Hirsh¹,

Fuster²,

Ansell³

et al. 2003

Circulation

711

542

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“…Therefore, in these subjects the suggested regimen for starting vitamin K antagonists consisted of low progressively increasing doses of oral anticoagulants associated with heparin in order to reach a therapeutic INR level within 10-14 days [7,16] . Nevertheless, heparin has been reported to be ineffective in preventing skin necrosis during initiation of oral anticoagulant, even in the absence of a loading dose [7,17,18] . Fresh frozen plasma as a source of PC has been successfully employed for this clinical indication [18] , but its use has several disadvantages, such as fluid overload with potential life-threatening complications [19] .…”

Section: Discussionmentioning

confidence: 99%

Successful Protein C Concentrate Administration during Initiation of Oral Anticoagulation in Adult Patients with Severe Congenital Protein C Deficiency: Report of Two Cases

Imberti

Giorgi‐Pierfranceschi²

2007

Pathophysiol Haemos Thromb

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Protein C (PC) is a vitamin K-dependent proenzyme with anticoagulant activity, and patients with congenital PC deficiency are at high risk for thrombotic episodes. In patients with PC deficiency, starting treatment with oral anticoagulant drugs is associated with a transient hypercoagulable state and clinically overt thromboembolic complications before reaching a full anticoagulant effect. This report describes a successful supplementation with PC concentrate in two adult patients with moderately severe PC deficiency during the initiation of oral anticoagulation and a course of therapeutic dose of low-molecular-weight heparin for acute venous thromboembolism. Plasma PC levels above 50% were observed in both patients and maintained during the entire supplementation treatment period with PC concentrate until a stable therapeutic anticoagulation level has been reached. These results have been obtained within a short time, thus allowing a safe administration of a loading dose of warfarin. No adverse reactions to the PC concentrate, i.e. skin necrosis and other thromboembolic complications, bleedings or allergic reactions, were observed. We conclude that PC concentrate seems to be effective for the prevention of thromboembolic complications and safe in patients with congenital PC deficiency while initiating oral anticoagulants.

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“…Nevertheless, based on the widely accepted pathophysiol ogy of warfarin-induced skin necrosis, the ap proach we used is rational and has been used successfully by other clinicians managing pa tients with prior histories of warfarin-induced skin necrosis [14,15].…”

Section: Discussionmentioning

confidence: 99%

“…Warfa rin has been generally considered contra-indi cated and heparin used in the long term is inconvenient and associated with the risk of osteoporosis. Recent reports have suggested that it is possible to prevent the recurrence of warfarin-induced skin necrosis by providing anticoagulant coverage with therapeutic doses of heparin during the critical intitial period of oral anticoagulant treatment and by com mencing low doses of warfarin with gradual increments to prevent an abrupt fall in the protein C level before there is a reduction in the levels of factors II, IX and X [ 14,15]. This report cites 2 cases of warfarin-induced skin necrosis in patients with protein S deficiency who were successfully treated with warfarin using the combination of heparin, low-dose warfarin and long periods of overlap of these anticoagulant agents.…”

mentioning

confidence: 99%

Warfarin-Induced Skin Necrosis in 2 Patients with Protein S Deficiency: Successful Reinstatement of Warfarin Therapy

Anderson

Brill-Edwards²,

Walker³

1992

Pathophysiol Haemos Thromb

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Warfarin-induced skin necrosis is a rare but serious complication of oral anticoagulant therapy. This condition has been associated with protein C deficiency but only rarely reported in patients with a deficiency of protein S. We have managed 2 patients with a history of warfarin-induced skin necrosis who were diagnosed as being protein-S-deficient. Since both patients were candidates for long-term anticoagulant therapy we elected to reintroduce warfarin using a regimen designed to minimize the risk of recurrent skin necrosis. While they were therapeutically anticoagulated with heparin, warfarin was started at 1 mg/day and the dose was increased gradually. Heparin was not discontinued until the prothrombin times were in the therapeutic range for at least 72 h. Both patients tolerated the reinstitution of warfarin without difficulty and they have now been followed for over 2 years on oral anticoagulants without complication.

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Successful Warfarin Anticoagulation Despite Protein C Deficiency and a History of Warfarin Necrosis

Cited by 82 publications

References 7 publications

American Heart Association/American College of Cardiology Foundation Guide to Warfarin Therapy

American Heart Association/American College of Cardiology Foundation Guide to Warfarin Therapy

Successful Protein C Concentrate Administration during Initiation of Oral Anticoagulation in Adult Patients with Severe Congenital Protein C Deficiency: Report of Two Cases

Warfarin-Induced Skin Necrosis in 2 Patients with Protein S Deficiency: Successful Reinstatement of Warfarin Therapy

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