This handout is for dvt in paroxysmal nocturnal hemoglobinuria (pnh). Your care team identified this based on: unilateral leg swelling in patient with dark / cola-colored morning urine, episodic abdominal pain, dysphagia, erectile dysfunction, or fatigue out of proportion — consider pnh.
Other reasons your team may use this plan: budd-chiari, portal, mesenteric, splenic, or cerebral venous sinus thrombosis as index event — flow cytometry for pnh clones is mandatory regardless of cbc; cbc with cytopenias plus elevated ldh 5-10× normal, low haptoglobin, indirect hyperbilirubinemia, urine hemosiderin — classic pnh biochemical profile; patient with known aplastic anemia or low-risk mds who develops new venous thrombosis — repeat pnh flow cytometry; pnh clones evolve in 30-50% of aplastic anemia.
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 |
|---|---|---|---|---|
| apixaban | 10 mg BID × 7 d → 5 mg BID full-dose; 2.5 mg BID extended-phase after first 6 mo if continuing indefinite | PO | BID × ≥3 months minimum, indefinite for any thrombotic event in PNH per expert consensus | AMPLIFY (Agnelli NEJM 2013 PMID 23808982) — apixaban first-line for VTE; AMPLIFY-EXT supports 2.5 mg BID extended-phase; expert consensus accepts DOAC for PNH VTE layered on complement inhibition |
| rivaroxaban | 15 mg BID × 21 d → 20 mg daily; 10 mg daily extended-phase after first 6 mo if continuing indefinite | PO | BID then daily ≥3 months, indefinite per criteria | EINSTEIN-DVT (Bauersachs NEJM 2010 PMID 21128814) |
| edoxaban | 60 mg PO daily (30 mg if CrCl 15-50, weight ≤60 kg, or with strong P-gp inhibitor) after 5-10 d LMWH bridge | PO | daily × ≥3 months, indefinite per criteria | Hokusai-VTE (Büller NEJM 2013 PMID 23991958) |
| warfarin | 5 mg daily; INR target 2-3 | PO | daily ≥3 months, indefinite per criteria | TRAPS (Pengo Blood 2018 PMID 30002145) — warfarin > rivaroxaban in triple-positive APS; preferred when DOAC clearance unpredictable |
| enoxaparin | 1 mg/kg SC BID; reduce to 1 mg/kg daily if CrCl <30 | SC | BID | ASH 2020 (PMID 33007077); ASH 2018 pregnancy (PMID 30482767) — LMWH first-line in pregnancy and as bridge during workup |
| eculizumab | 600 mg IV weekly × 4 weeks → 900 mg IV q14d maintenance | IV | weekly × 4 then q14d indefinite | TRIUMPH (Hillmen NEJM 2006 PMID 16990386); Hillmen Blood 2007 (PMID 17716988) — eculizumab reduces thromboembolic events ~85% in PNH; foundational therapy |
| ravulizumab | 2400-3000 mg IV loading weight-based then maintenance q8w | IV | q8w | Lee Blood 2019 / Kulasekararaj — ravulizumab non-inferior to eculizumab with less breakthrough hemolysis and longer dosing interval |
| pegcetacoplan | 1080 mg SC twice weekly | SC | twice weekly | PEGASUS (Hillmen NEJM 2021 PMID 33730455) — pegcetacoplan superior to eculizumab in patients with persistent anemia; addresses extravascular hemolysis on C5 inhibitor |
| meningococcal-acwy-conjugate-vaccine | 0.5 mL IM single dose with booster q5y | IM | ≥2 weeks before C5 inhibitor; booster q5y | CDC ACIP and FDA REMS — Neisseria meningitidis infection risk dramatically increased on C5 inhibitor; vaccination ≥2 weeks before therapy mandatory |
| meningococcal-b-vaccine | 0.5 mL IM 2-dose series | IM | 0 + 6 months ≥2 weeks before C5 inhibitor | CDC ACIP — serogroup B coverage required in addition to ACWY conjugate for complement-deficient patients |
| ciprofloxacin | 500 mg PO daily as prophylaxis if vaccination cannot precede C5 inhibitor by 2 weeks | PO | daily until 2 weeks post-vaccination | Bridge prophylaxis until meningococcal vaccine immunity develops; expert consensus |
Plan: PNH VTE — acute AC + complement inhibition + meningococcal vaccination + transplant consideration (TRIUMPH; PEGASUS; ASH 2020; 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:
Long-term hematology + thrombosis clinic co-management; annual bone marrow if disease progression suspected; pregnancy planning (eculizumab safe; LMWH preferred over DOAC / warfarin for thrombosis); transplant evaluation if severe aplastic anemia; PNH transformation to MDS / AML surveillance; cardiovascular risk factor optimisation; education on breakthrough hemolysis recognition and meningococcal infection symptoms (fever / headache / petechiae / neck stiffness → ED immediately)
Guideline: TRIUMPH eculizumab in PNH + PEGASUS pegcetacoplan + Schrezenmeier international PNH registry + ASH 2018 thrombophilia + ACCP/CHEST 2021