This handout is for warfarin-induced skin necrosis (protein c/s deficiency unmasking). Your care team identified this based on: painful erythematous indurated plaque on breast / thigh / buttock / abdomen on warfarin day 3-10 — pre-necrosis warning sign; stat recognition prevents extension.
Other reasons your team may use this plan: hemorrhagic bullae or full-thickness skin necrosis on warfarin days 3-10, areas with abundant subcutaneous fat — established wisn; emergent reversal; warfarin initiated without heparin or lmwh bridge or with high loading dose ≥10 mg/d in patient with known or suspected protein c / s deficiency; family history of warfarin-related skin necrosis or thrombophilia (protein c / s deficiency, factor v leiden) — high pre-test probability for wisn risk on first warfarin exposure.
Take these medications exactly as prescribed. Do not stop or change a dose without talking to your provider.
| Medication | Starting dose | How | When | What it does |
|---|---|---|---|---|
| phytonadione_vitamin_k1 | 5-10 mg IV slow infusion over 30 min | IV | one-time, may repeat once at 12-24h if INR persistently elevated | ASH 2018 (PMID 30482764); ACCP 2021 (PMID 34352295) — restores protein C activity within 6-24h via new hepatic synthesis; IV preferred over PO for emergency due to predictable absorption; avoid IM (hematoma risk on AC); slow IV to avoid anaphylactoid reaction |
| fresh_frozen_plasma | 2-4 units (10-15 mL/kg) IV | IV | one-time, may repeat per clinical response | ASH 2018; ACCP 2021 — FFP contains all coagulation factors INCLUDING protein C and protein S; immediate replacement bridges the kinetic gap until vitamin K-driven hepatic synthesis recovers; volume load consideration in HF / renal failure |
| four_factor_prothrombin_complex_concentrate | 25-50 IU/kg IV (per INR-based protocol; max 5000 IU) | IV | one-time | ASH 2018; ACCP 2021 — 4F-PCC (Kcentra) contains factors II/VII/IX/X PLUS protein C and protein S; rapid reversal of warfarin (faster than FFP); volume-sparing (preferred if HF / renal failure); thrombotic risk manageable in WISN context where reversal is the priority |
| unfractionated_heparin | 80 U/kg IV bolus then 18 U/kg/h titrated to aPTT 1.5-2.5× baseline | IV | continuous infusion | ASH 2018; ACCP 2021 — therapeutic UFH is the bridge AC during warfarin reversal in WISN; heparin/LMWH does not depend on protein C and provides immediate AC; avoid if any HIT history or concurrent thrombocytopenia (separate workup needed) |
| enoxaparin | 1 mg/kg SC q12h (or 1.5 mg/kg SC daily); renal-adjusted to 1 mg/kg SC daily if CrCl <30 | SC | q12h | ASH 2018; ACCP 2021 — LMWH alternative bridge AC; convenient outpatient transition; renal-adjust if CrCl <30; avoid if HIT history |
| fondaparinux | 7.5 mg SC daily (5 mg if <50 kg; 10 mg if >100 kg) | SC | daily | ASH 2018 — fondaparinux alternative bridge AC if heparin / LMWH contraindicated (HIT history); does not cross-react with HIT antibodies; avoid CrCl <30; no antidote |
| apixaban | 10 mg PO BID × 7 d → 5 mg PO BID (or 2.5 mg BID per FDA dose-reduction criteria) | PO | BID indefinite or per VTE duration plan | ASH 2018; ACCP 2021 — DOAC of first choice for long-term AC in protein C / S deficiency to AVOID lifetime warfarin re-challenge; AMPLIFY (Agnelli NEJM 2013 PMID 23808982); preferred over warfarin to eliminate WISN recurrence risk |
| rivaroxaban | 15 mg PO BID × 21 d → 20 mg PO daily with food (15 mg if CrCl 15-50) | PO | BID then daily indefinite | ASH 2018; ACCP 2021 — alternative DOAC for long-term AC; EINSTEIN-DVT (Bauersachs NEJM 2010 PMID 21128814) |
| protein_c_concentrate_ceprotin | 60-80 IU/kg IV initially then 45 IU/kg q6h to maintain protein C activity ≥25% | IV | q6h initially | ASH 2018; rare use case — protein C concentrate (Ceprotin) for severe homozygous protein C deficiency or severe acquired depletion with extensive necrosis; available only at specialized hemophilia centers |
Plan: WISN — STOP warfarin, reverse with vitamin K + FFP/4F-PCC, bridge with heparin/LMWH/fondaparinux, transition to DOAC long-term, lifelong warfarin avoidance (ASH 2018; ACCP 2021)
Contact your care team if any of the following happen:
Call 911 or go to the nearest emergency room right away if you have:
Hematology long-term follow-up; thrombophilia results review at 4 weeks; ≥3 mo AC for VTE indication (longer if ongoing risk); LIFELONG warfarin avoidance education with medical alert bracelet and EHR allergy banner; cascade family screening for protein C / S deficiency; pregnancy planning if applicable (DOAC contraindicated in pregnancy → LMWH for VTE in pregnancy with protein C / S deficiency)
Guideline: ASH 2018 Thrombophilia Guideline (Bates) + ACCP/CHEST 2021 (Stevens) for VTE treatment + ACCP 2016 (Kearon) for warfarin overlap principles