›Desmopressin 0.3 microg/kg IV over 30 minutes for uremic platelet dysfunction, given once only to avoid tachyphylaxis and hyponatremia
›Anticoagulant reversal
›Warfarin: vitamin K 10 mg IV plus 4-factor prothrombin complex concentrate 25 to 50 units/kg
›Dabigatran: idarucizumab 5 g IV
›Factor Xa inhibitor: andexanet alfa by the low- or high-dose protocol, or 4-factor prothrombin complex concentrate 50 units/kg
›Heparin: protamine 1 mg per 100 units given in the preceding 2 to 3 hours, single dose maximum 50 mg
›Tranexamic acid
›Nebulized tranexamic acid 500 mg every 6 to 8 hours as an adjunct for ongoing alveolar hemorrhage
›Intravenous tranexamic acid 1 g over 10 minutes then 1 g over 8 hours may be added
›Avoid in known active thromboembolic disease and reduce the dose in severe renal impairment
›Stop once alveolar hemorrhage has settled to limit thrombotic risk during active vasculitis
›Recombinant activated factor VII
›Off-label rescue only for refractory life-threatening hemorrhage after conventional measures have failed
›Reported as intravenous doses around 90 microg/kg, or as endobronchial administration
›Carries arterial and venous thrombotic risk; use only with hematology input
›Not a substitute for immunosuppression or plasma exchange
Pulse and oral glucocorticoids
›Methylprednisolone pulse
›Methylprednisolone IV 500 to 1000 mg once daily for 3 consecutive days
›Follow with oral prednisone 1 mg/kg once daily, usual maximum 60 to 80 mg per day
›Taper on the PEXIVAS reduced-dose schedule, reaching roughly 5 mg per day by month 4 to 5
›The reduced-dose oral schedule lowers serious infection without a survival or kidney penalty
›Maximum single pulse 1000 mg per day
›Start empiric antimicrobials alongside the pulse if infection cannot be excluded
›Adjuncts to glucocorticoid
›Gastric protection with pantoprazole 40 mg daily while on high-dose steroid and possibly bleeding
›Monitor capillary glucose every 4 to 6 hours and treat to 6 to 10 mmol/l with a variable-rate insulin infusion
›Accept a higher permissive range in longstanding poorly controlled diabetes to avoid hypoglycemia
›Hyperglycemia is expected and is not a reason to withhold the pulse
›What glucocorticoid does not do
›It does not replace induction immunosuppression or plasma exchange in organ-threatening disease
›It does not need to wait for tissue confirmation when alveolar hemorrhage is already clinical
›Abrupt cessation risks adrenal crisis after only days of high-dose exposure
›Indications
›Coexisting anti-glomerular basement membrane antibody, treated as anti-glomerular basement membrane disease with daily exchange
›Severe alveolar hemorrhage with hypoxemia or ventilator dependence
›Severe or dialysis-requiring acute kidney injury, where exchange improves renal recovery even though the PEXIVAS trial did not reduce death or end-stage kidney disease overall
›Prescription
›One plasma volume, about 60 ml/kg, exchanged per session for roughly 7 sessions over 14 days
›Replace with 5% albumin; switch to fresh frozen plasma if actively bleeding or within 72 hours of biopsy or surgery
›Give immunosuppressive drugs after a session, never before, so they are not removed
›Monitoring during exchange
›Ionized calcium each session; replace calcium for citrate-induced levels below 1.0 mmol/l
›Fibrinogen and platelets each session; hold or space sessions if fibrinogen falls below 1.0 g/l
›Potassium and magnesium in mmol/l, with a post-session electrocardiogram when levels shift
Induction immunosuppression
›Rituximab
›Rituximab IV 375 mg/m2 once weekly for 4 weeks, or 1 g on day 0 and day 15
›Premedicate with methylprednisolone, acetaminophen 1 g, and an antihistamine
›Slow or pause the infusion for a reaction, then restart at half the rate
›Screen hepatitis B surface antigen and core antibody first, and give antiviral prophylaxis if positive
›No adjustment for renal function is required
›In pregnancy it crosses the placenta after the first trimester and depletes neonatal B cells; see Special Populations
›Preferred in relapsing disease and where preserving fertility matters
›Cyclophosphamide
›Cyclophosphamide IV 15 mg/kg per pulse, single-dose maximum 1.2 g
›First 3 pulses every 2 weeks, then every 3 weeks
›Reduce by about 2.5 mg/kg for age over 60, and further for age over 70
›Reduce for an estimated glomerular filtration rate under 30 ml/min/1.73 m2, for example to about 10 mg/kg
›Give mesna and ondansetron 8 mg IV with each pulse and maintain a high urine output
›Check the complete blood count at the day 10 to 14 nadir and hold or cut the next pulse for neutropenia
›Teratogenic: avoid in the first trimester and use in later pregnancy only if immediately life-threatening; see Special Populations
›Oral cyclophosphamide 2 mg/kg per day is an alternative with a higher cumulative dose
›Avacopan
›Avacopan 30 mg orally twice daily as a glucocorticoid-sparing adjunct started by the specialist
›It blocks the complement C5a receptor and does not substitute for rituximab or cyclophosphamide
›It is not an acute-phase or emergency department drug
›Monitor liver enzymes and avoid strong CYP3A4 inducers
›Sequencing
›Pulse glucocorticoid first, then plasma exchange if indicated, then the induction agent timed after exchange
›Do not give live vaccines around induction
›Confirm no untreated tuberculosis or hepatitis B before the first dose
Infection prophylaxis, cardiovascular control, and thromboprophylaxis
›Pneumocystis prophylaxis
›Trimethoprim-sulfamethoxazole 160/800 mg orally three times weekly during induction
›Alternatives are dapsone 100 mg daily, atovaquone 1500 mg daily, or inhaled pentamidine 300 mg monthly if sulfa-intolerant
›It also reduces Staphylococcus aureus carriage relevant to granulomatosis with polyangiitis
›Empiric antimicrobials
›Cover community-acquired pneumonia until cultures and lavage exclude infection, given the near-identical presentation
›Add antifungal or antiviral cover only on a specific risk or a positive test
›Blood pressure control
›For a hypertensive emergency with acute kidney injury, lower mean arterial pressure by no more than about 20 to 25% in the first hour; in chronic hypertension, dialysis dependence, or older adults use the conservative end and avoid rapid normalization
›Labetalol 10 to 20 mg IV every 10 minutes, or a nicardipine infusion 5 mg/h titrated by 2.5 mg/h every 5 to 15 minutes to a maximum 15 mg/h
›Nicardipine is a dihydropyridine arterial vasodilator; reflex tachycardia is expected and acceptable here because the goal is afterload and pressure reduction, not rate control
›Hold renin-angiotensin blockers during acute kidney injury and active bleeding
›Venous thromboembolism
›Active vasculitis raises thrombosis risk, but active alveolar hemorrhage contraindicates pharmacologic prophylaxis
›Use intermittent pneumatic compression until bleeding has stopped for 24 to 48 hours
›If proximal deep vein thrombosis or pulmonary embolism is confirmed during active hemorrhage, a retrievable inferior vena cava filter is preferred and fibrinolysis is contraindicated
›Analgesia and antipyresis
›Acetaminophen 1 g every 6 hours, maximum 4 g in 24 hours, and no more than 3 g in 24 hours if body weight is under 50 kg, hepatic impairment, or chronic high alcohol use
›Avoid non-steroidal anti-inflammatory drugs such as ibuprofen 400 to 600 mg every 6 to 8 hours because they worsen renal function and impair platelets
›Fentanyl 25 to 50 microg IV, an opioid cleared independently of the kidney, is preferred over morphine when renal function is impaired
Monitoring, iatrogenic harms, and failing therapy
›Monitoring cadence for titrated therapy
›Continuous pulse oximetry and telemetry; an arterial line when on vasoactive drugs or during plasma exchange
›Hemoglobin every 4 to 6 hours during active bleeding, then every 12 hours
›Hourly urine output; creatinine and electrolytes in mmol/l at least daily
›Ionized calcium, fibrinogen, and platelets each plasma exchange session
›How routine interventions harm this patient
›Liberal fluid loading floods already-hemorrhagic alveoli and precipitates oliguric renal failure; keep balance neutral to negative
›Therapeutic anticoagulation and fibrinolysis convert survivable alveolar hemorrhage into fatal hemorrhage and are contraindicated during active bleeding
›A small endotracheal tube precludes therapeutic bronchoscopy; positive pressure and PEEP help by tamponade, but excess plateau pressure causes barotrauma
›Non-steroidal anti-inflammatory drugs and iodinated contrast accelerate the renal injury, and aminoglycosides compound it
›Etomidate 0.3 mg/kg IV adds adrenal suppression to the illness; it is acceptable as a single induction dose, but ketamine 1 to 2 mg/kg IV is preferred when perfusion is marginal
›Hyperoxia offers no benefit once SpO2 reaches 96%; wean FiO2 back to the target range
›Intra-aortic balloon counterpulsation and other mechanical circulatory support that requires systemic anticoagulation are contraindicated during active hemorrhage; venovenous ECMO is the exception and is run with minimal or no anticoagulation
›Electrocardiogram and electrolyte surveillance
›Pulse glucocorticoid shifts potassium into cells, plasma exchange chelates calcium, and ondansetron 8 mg with azole antifungals prolongs the QT interval
›Obtain an electrocardiogram after each glucocorticoid pulse and each exchange session and correct potassium and magnesium in mmol/l
›New conduction disease, low voltage, or arrhythmia raises eosinophilic myocarditis in eosinophilic granulomatosis with polyangiitis
›When therapy is not working
›Persisting or worsening hypoxemia 24 to 48 hours after the glucocorticoid pulse: escalate to or intensify plasma exchange and confirm the induction agent has been given
›Repeat bronchoscopy and cross-sectional imaging to find superimposed infection or a missed second diagnosis
›Reconsider anti-glomerular basement membrane disease, antiphospholipid syndrome, mitral stenosis, and occult anticoagulant effect
›A rising transfusion requirement despite immunosuppression is the trigger for venovenous ECMO and rescue hemostatic measures