Semin Thromb Hemost 2019; 45(03): 302-307
DOI: 10.1055/s-0039-1683843
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Novel Coagulation Analyzers in Development: A Glimpse toward the Future of Microfluidics

Sitaram M. Emani
1   Department of Cardiac Surgery, Boston Children's Hospital, Boston, Massachusetts
› Author Affiliations
Further Information

Publication History

Publication Date:
18 March 2019 (online)

Abstract

Coagulation diagnostic testing in pediatric patients currently requires large volume blood sampling and is performed on analyzers that are not well-suited for multiplexed assays on a given sample. For patients who require serial testing at regular intervals, repetitive phlebotomy leads to iatrogenic anemia and need for blood transfusions. Over the past decade, novel microfluidic platforms have been developed that allow for complex multiplexed assays to be performed on small sample volumes, near patient, with high fidelity. In the next few years, these devices will be introduced into clinical trials, and offer the promise of reliable, rapid, multiplexed coagulation assays for pediatric patients who require coagulation diagnostic testing.

 
  • References

  • 1 Hanmod SS, Jesudas R, Kulkarni R, Chitlur M. Neonatal hemostatic disorders: issues and challenges. Semin Thromb Hemost 2016; 42 (07) 741-751
  • 2 Revel-Vilk S. Clinical and laboratory assessment of the bleeding pediatric patient. Semin Thromb Hemost 2011; 37 (07) 756-762
  • 3 Heleen van Ommen C, Middeldorp S. Thrombophilia in childhood: to test or not to test. Semin Thromb Hemost 2011; 37 (07) 794-801
  • 4 Sølbeck S, Ostrowski SR, Johansson PI. A review of the clinical utility of INR to monitor and guide administration of prothrombin complex concentrate to orally anticoagulated patients. Thromb J 2012; 10 (01) 5
  • 5 Radulescu VC, D'Orazio JA. Venous thromboembolic disease in children and adolescents. Adv Exp Med Biol 2017; 906: 149-165
  • 6 Gruenwald CE, Manlhiot C, Crawford-Lean L. , et al. Management and monitoring of anticoagulation for children undergoing cardiopulmonary bypass in cardiac surgery. J Extra Corpor Technol 2010; 42 (01) 9-19
  • 7 van Ommen CH, Sol JJ. Developmental hemostasis and management of central venous catheter thrombosis in neonates. Semin Thromb Hemost 2016; 42 (07) 752-759
  • 8 Thom KE, Hanslik A, Male C. Anticoagulation in children undergoing cardiac surgery. Semin Thromb Hemost 2011; 37 (07) 826-833
  • 9 Kenet G, Aronis S, Berkun Y. , et al. Impact of persistent antiphospholipid antibodies on risk of incident symptomatic thromboembolism in children: a systematic review and meta-analysis. Semin Thromb Hemost 2011; 37 (07) 802-809
  • 10 Ansell J, Zappe S, Jiang X. , et al. A novel whole blood point-of-care coagulometer to measure the effect of direct oral anticoagulants and heparins. Semin Thromb Hemost 2018
  • 11 Nowak-Göttl U, Schneppenheim R, Vielhaber H. APC resistance in childhood thromboembolism: diagnosis and clinical aspects. Semin Thromb Hemost 1997; 23 (03) 253-258
  • 12 Sista R, Hua Z, Thwar P. , et al. Development of a digital microfluidic platform for point of care testing. Lab Chip 2008; 8 (12) 2091-2104
  • 13 Sista RS, Eckhardt AE, Wang T. , et al. Digital microfluidic platform for multiplexing enzyme assays: implications for lysosomal storage disease screening in newborns. Clin Chem 2011; 57 (10) 1444-1451
  • 14 Sista RS, Eckhardt AE, Srinivasan V, Pollack MG, Palanki S, Pamula VK. Heterogeneous immunoassays using magnetic beads on a digital microfluidic platform. Lab Chip 2008; 8 (12) 2188-2196
  • 15 Emani S, Sista R, Loyola H, Trenor III CC, Pamula VK, Emani SM. Novel microfluidic platform for automated lab-on-chip testing of hypercoagulability panel. Blood Coagul Fibrinolysis 2012; 23 (08) 760-768
  • 16 Millington D, Norton S, Singh R, Sista R, Srinivasan V, Pamula V. Digital microfluidics comes of age: high-throughput screening to bedside diagnostic testing for genetic disorders in newborns. Expert Rev Mol Diagn 2018; 18 (08) 701-712
  • 17 Emani S, Nelson LT, Norton S, Singh R, Pamula V, Emani S. Enzymatic functional assays of coagulation using small sample volumes. Lab Med 2017; 49 (01) 47-54
  • 18 Favaloro EJ, McDonald D. Futility of testing for factor V Leiden. Blood Transfus 2012; 10 (03) 260-263
  • 19 Hua Z, Rouse JL, Eckhardt AE. , et al. Multiplexed real-time polymerase chain reaction on a digital microfluidic platform. Anal Chem 2010; 82 (06) 2310-2316
  • 20 Happich D, Schwaab R, Hanfland P, Hoernschemeyer D. Allelic discrimination of factor V Leiden using a 5′ nuclease assay. Thromb Haemost 1999; 82 (04) 1294-1296
  • 21 Happich D, Madlener K, Schwaab R, Hanfland P, Pötzsch B. Application of the TaqMan-PCR for genotyping of the prothrombin G20210A mutation and of the thermolabile methylenetetrahydrofolate reductase mutation. Thromb Haemost 2000; 84 (01) 144-145
  • 22 Monagle P, Chan AKC, Goldenberg NA. , et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e737S-e801S
  • 23 McCrindle BW, Li JS, Manlhiot C. , et al. Challenges and priorities for research: a report from the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH) Working Group on thrombosis in pediatric cardiology and congenital heart disease. Circulation 2014; 130 (14) 1192-1203
  • 24 Newall F, Barnes C, Ignjatovic V, Monagle P. Heparin-induced thrombocytopenia in children. J Paediatr Child Health 2003; 39 (04) 289-292
  • 25 von Vajna E, Alam R, So TY. Current clinical trials on the use of direct oral anticoagulants in the pediatric population. Cardiol Ther 2016; 5 (01) 19-41
  • 26 Hirsh J, Anand SS, Halperin JL, Fuster V. ; American Heart Association. Guide to anticoagulant therapy: heparin: a statement for healthcare professionals from the American Heart Association. Circulation 2001; 103 (24) 2994-3018
  • 27 Baluwala I, Favaloro EJ, Pasalic L. Therapeutic monitoring of unfractionated heparin - trials and tribulations. Expert Rev Hematol 2017; 10 (07) 595-605
  • 28 Oladunjoye OO, Sleeper LA, Nair AG. , et al. Partial thromboplastin time is more predictive of bleeding than anti-Xa levels in heparinized pediatric patients after cardiac surgery. J Thorac Cardiovasc Surg 2018; 156 (01) 332-340.e1
  • 29 Nair AG, Oladunjoye OO, Trenor III CC. , et al. An anticoagulation protocol for use after congenital cardiac surgery. J Thorac Cardiovasc Surg 2018; 156 (01) 343-352.e4
  • 30 Cuker A, Marturano JE, Carinato ME, Lowery TJ, Cines DB. T2 magnetic resonance to monitor hemostasis. Semin Thromb Hemost 2018
  • 31 Gauss T, Hamada S, Jurcisin I. , et al. Limits of agreement between measures obtained from standard laboratory and the point-of-care device Hemochron Signature Elite(R) during acute haemorrhage. Br J Anaesth 2014; 112 (03) 514-520