Mazzeffi: Management of Bleeding in Patients on Mechanical Circulatory Support

Clinical Pearls (assisted by Jessica Buchner, MD)

Bleeding events on ECMO: Mazzeffi et al.

• 1/2 of all patients have a serious bleeding event while on VV or VA ECMO
  • Defined as event that leads to ≥2U PRBC transfusion
    • Highest risk in post-cardiotomy shock patients
  • VA>VV ECMO
  • Overall: 10 events per 100 ECMO days
• Bleeding impacts survival
  • ~20% difference in mortality rates
• Predicting who will bleed: HTN, Age>65, ECMO Type (all 3=HAT score)
  • Absolute risk of bleeding not as high if platelets >50,000

LVAD patients

• Predominant risk is for GI bleeding, especially with newer non-pulsatile devices
  • Harvey et al.: bleeding risk 15-40%

• In addition, LVAD patients are at risk for ICH
  • Wilson et al.: ICH risk 30%, possibly related to HTN
  • 33% mortality with ICH

Why do patients on mechanical circulatory support bleed more?

• Shear stress and blood trauma
  • 2400 RPM = 5X the normal physiology shear stress
• Change in platelet morphology, not platelet numbers
  • More lysis and platelet fragmentation
  • Increased platelet activation
• Loss of VWF multimers
  • Change in conformation of multimer causing poor platelet adhesiveness
  • VWF is stored in endothelial cells & alpha granules of platelets and subendothelial connective tissues
    • Alpha 1 domain binds platelets (GP1b), alpha 3 binds collagen
  • Change in conformation makes them non-functional
    • Makes it easier for ADAMTS13 to cleave multimers, leading to break down
  • Type O blood has less vWF at baseline
    • ABO type doesn’t make difference in overall bleeding events
    • Massive transfusions are more often in the type O group

Coagulation profile is affected on ECMO: Days 1, 3, 5, 7, 12, 16 Nair

• Slight drop to plt count
• Supernormal intrinsic pathway due to up-regulation of factor VIII
• ROTEM
  • EXTEM normal to slightly increased
  • INTEM mostly normal

How should we anticoagulate?

• ECMO
  • High vs low ACT group- Yao
    • Significantly higher rates of major bleeding in high group (70% vs 20%)
    • No difference in thrombosis rate (high ACT group actually had more thromboses)
• LVAD
  • Standard is warfarin + aspirin
    • Goal INR 1.5-2.5
  • Alternative: Dipyridamole (shorter half life)

Management of bleeding

Pratt

• Hemostatic agents
  • DDVAP: 0.3-0.4 ug/kg
    • Increases release of endogenous vWF
    • No RCTs exist to prove benefit in mechanical circulatory support
  • VWF-factor VIII concentrate: 40-80 IU
    • Factor VIII has longer half life than vWF (risk thrombosis)
    • Expensive
    • No RCTS exist to prove benefit in mechanical circulatory support
  • Cryoprecipitate
    • Exposes the patient to multiple donors and therefore risk for antibody formation (transplants)
    • Most device patients also have increased fibrinogen levels
  • Platelets
    • Optimal count not known
    • Uncertain how to monitor
      • PFA 100? Platelet mapping?
  • Antifibrinolytics
    • Data sparse
    • One large observational study in pediatric EMCO patients showed decreased bleeding events
  • rFVIIa
    • 15 patient case series (11 VA ECMO patients, 4 VV ECMO patients)
      • Only 1 patient had major stroke
• Airway Bleeding
  • Can use Fogarty balloon or grasper
    • IP is critical
  • Argon plasma coagulation or cryotherapy for clot removal
  • In an RVAD, perhaps too much flow?
• Nose bleeds
  • Common in VA ECMO
    • Continue AC
  • Pack with polyvinyl alcohol or oxidized cellulose + wait! (can be weeks)
    • Add prophylactic abx and correct thrombocytopenia (if needed)