Improvement in long-term ECMO by detailed monitoring of anticoagulation: a case report

Abstract

Introduction: The use of unfractionated heparin (UFH) as an anticoagulant during long-term extracorporeal support presents a unique challenge for the clinician in balancing the amount of anticoagulant to maintain adequate anticoagulation without causing excessive bleeding. Activated clotting times (ACT) and activated partial thromboplastin times (aPTT) are the most common modality to monitor UFH on extracorporeal membrane oxygenation (ECMO). Limitations to these tests include consumptive coagulopathies, clotting factor deficiencies, platelet dysfunction, and fibrinolysis. The following case report describes the use of alternative monitoring strategies to assess more accurately anticoagulation during ECMO. Case Report: A 20-month-old female presented to the emergency department with a 5-6 day history of cough, fever, tachypnea, and respiratory distress. She was diagnosed with influenza A and B with pneumonia. The patient was placed on veno-venous ECMO (V-V ECMO) after mechanical ventilation failed. On ECMO day eight, the patient developed a thrombus in her inferior vena cava and pleural effusions, obstructing cannula flow. Laboratory tests revealed the ACT was within range, yet the aPTT was dropping, despite increased heparin. Heparin levels were low and antithrombin-III (AT) concentrations were 40%. Recombinant AT was given and subsequent aPTTs were within the therapeutic range. Later, the aPTT decreased to <50 sec, heparin levels were within the therapeutic range, while fibrinogen was >475 mg/ dL, and Factor VIII >150 IU/dL, suggesting an acute phase reaction or ongoing systemic inflammation, increasing the risk for thrombosis. We maintained heparin assays between 0.5-0.7 IU/mL and AT >60% to assure heparin’s effect. The patient showed no signs of excess bleeding, blood product administration, or clots in the circuit, suggesting proper anticoagulation. The patient was successfully weaned on day 33 and is currently alive and at home. Conclusion: Monitoring of anti-Xa UFH and AT proved effective for measuring anticoagulation and detecting inconsistencies in other anticoagulation parameters, leading to steady levels of heparin without further complications.

Keywords

extracorporeal membrane oxygenation anticoagulation anti-Xa unfractionated heparin antithrombin-III activated clotting time

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References

Baird CW , Zurakowski D. , Robinson B. , et al. Anticoagulation and pediatric extracorporeal membrane oxygenation: impact of activated clotting time and heparin dose on survival. Ann Thorac Surg 2007; 26: 231-240.

Sievert AN , Shackelford AG , McCall MM

Trends and emerging technologies in extracorporeal life support: results of the

2006 ECLS Survey. J Extracorp Circ Tech 2009; 41: 73-78.

Haines NM , Rycus PT , Zwischenberger JB , Bartlett RH , Undar A. Extracorporeal Life Support Registry Report 2008; neonatal and pediatric cases. ASAIO J 2009; 55: 111-116.

Gruenwald C. , deSouza V. , Chan AK , Andrew M. Whole blood heparin concentrations do not correlate with plasma anti-factor Xa heparin concentrations in pediatric patients undergoing cardiopulmonary bypass. Perfusion 2000; 15: 203-209.

Chan AK , Leaker M. , Burrows FA , et al. Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass. Thromb Haemost 1997; 77: 270-277.

Owings JT , Pollock ME , Gosselin RC , et al. Anticoagulation of children undergoing cardiopulmonary bypass is overestimated by current monitoring techniques. Arch Surg 2000; 135: 1042-1047.

Bull BS , Korpman RA , Huse WM , Briggs, BD Heparin therapy during extracorporeal circulation: II The use of a dose response curve to individualize heparin and protamine dosage. J Thorac Cardiovasc Surg 1975; 69: 685-689.

Cheung AT , Levin SK , Weiss SJ , et al. Intracardiac thrombus: a risk of incomplete anticoagulation for cardiac operations. Ann Thorac Surg 1994 ; 58: 541-542.

Despotis GJ , Joist JH , Hogue CW , et al. The impact of heparin concentration and activated clotting time monitoring on blood conservation. A prospective randomized evaluation in patients undergoing cardiac operation. J Thorac Cardiovasc Surg 1995; 110: 46-54.

10.

Newall F. , Ignjatovic V. , Summerhayes R. , et al. In vivo age dependency of unfractionated heparin in infants and children. Thrombosis Research 2009; 123: 710-714.

11.

Olson, JD , Arkin, CF , Brandt, JT , et al. College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy: laboratory monitoring of unfractionated heparin therapy. Arch Pathol Lab Med 1998; 122: 782-798.

12.

Bates, SM , Weitz, JI , Johnston, M. , et al. Use of a fixed activated partial thromboplastin time ratio to establish a therapeutic range for unfractionated heparin. Arch Intern Med 2001; 161: 385-391.

13.

Marci CD , Prager D. A review of the clinical indications for the plasma heparin assay . Am J Clin Pathol 1993; 99: 546-550.

14.

Muntean W. Coagulation and anticoagulation in extracorporeal membrane oxygenation . Artif Organs 1999; 23: 979-983.

15.

Hirsh J. , Raschke R. , Warkentin TE , et al. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring efficacy, and safety. Chest 1995 ; 108(suppl 4): 258S-275S.

16.

Kovacs MJ , Keeney M. , MacKinnon K. , Boyle E. Three different chromogenic methods do not give equivalent anti-Xa levels for patients on therapeutic low molecular weight heparin (dalteparin) or unfractionated heparin. Clin Lab Haem 1999 ; 21: 55-60.

17.

Ignjatovic V. , Summerhayes R. , Gan A. , et al. Monitoring unfractionated heparin (UFH) therapy: which anti factor Xa assay is appropriate? Thromb Res 2007; 120: 347-351.

18.

[AQ 2] Christensen RD Hematologic problems of the neonate. WB Saunders, Philadelphia PA, 2000; 1: 246.

19.

Zavadil DP , Stammers AH , Willett LD , et al. Hematological abnormalities in neonatal patients treated with extracorporeal membrane oxygenation (ECMO). J Extracorp Circ Tech 1998; 30: 83-90.

20.

Luddington RJ Thrombelastography/thromboelastometry. Clin Lab Haematol 2005; 27: 81-90.

21.

Urlesberger B. , Zobel G. , Zenz W. , et al. Activation of the clotting system during extracorporeal membrane oxygenation in term newborn infants. J Pediatrics 1996; 129: 264-268.

22.

Chalmers E. , Bonduel M. Antithrombotic therapy in children . Progress in Pediatric Cardiology 2005; 21: 31-43.

23.

Gruys E. , Toussaint MJM , Niewold TA , Koopmans SJ Acute phase reaction and acute phase proteins. J Zhejiang Univ Science 2005: 6B: 1045-1056.

24.

Gabay C. , Kushner I. Acute-phase proteins and other systemic responses to inflammation . N Engl J Med 1999; 340: 448-454.

25.

Koster T. , Blann AD , Briet E. , et al. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep vein thrombosis. Lancet 1995; 345: 152-155.