Neurocritical Care

, Volume 20, Issue 1, pp 84–90 | Cite as

Red Blood Cell Transfusion Increases the Risk of Thrombotic Events in Patients with Subarachnoid Hemorrhage

  • Monisha A. Kumar
  • Torrey A. Boland
  • Mohamed Baiou
  • Michael Moussouttas
  • Jay H. Herman
  • Rodney D. Bell
  • Robert H. Rosenwasser
  • Scott E. Kasner
  • Valerie E. Dechant


Background and Purpose

Red blood cell transfusion (RBCT) may increase the risk of thrombotic events (TE) in patients with subarachnoid hemorrhage (SAH) through changes induced by storage coupled with SAH-related hypercoagulability. We sought to investigate the association between RBCT and the risk of TE in patients with SAH.


205 consecutive patients with acute, aneurysmal SAH admitted to the neurovascular intensive care unit of a tertiary care, academic medical center between 3/2008 and 7/2009 were enrolled in a retrospective, observational cohort study. TE were defined as the composite of venous thromboembolism (VTE), myocardial infarction (MI), and cerebral infarction noted on brain CT scan. Secondary endpoints included the risk of VTE, poor outcome (modified Rankin score 3–6 at discharge), and in-hospital mortality.


86/205 (42 %) received RBCT. Eighty-eight (43 %) had a thrombotic complication. Forty (34 %) of 119 non-transfused and 48/86 (56 %) transfused patients had a TE (p = 0.002). In multivariate analysis, RBCT was associated with more TE by [OR 2.4; 95 % CI (1.2, 4.6); p = 0.01], VTE [OR 2.3; 95 % CI (1.0, 5.2); p = 0.04], and poor outcome [OR 5.0; 95 % CI (1.9, 12.8); p < 0.01]. The risk of TE increased by 55 % per unit transfused when controlling for univariate variables. Neither mean nor maximum age of blood was significantly associated with thrombotic risk.


RBCT is associated with an increased risk of TE and VTE in SAH patients. A dose-dependent relationship exists between number of units transfused and thrombosis. Age of blood does not appear to play a role.


Subarachnoid hemorrhage Hypercoagulable Vasospasm Delayed cerebral ischemia Transfusion Red blood cell Venous thromboembolism 



We would like to thank Barbara Alberto, MS RVT, of the Neurovascular Laboratory and the neurocritical care nurses of the Jefferson Hospital for Neuroscience for their dedication to patient care. This study received no financial support.


There are no disclosures.


  1. 1.
    Marik PE, Sibbald WJ. Effect of stored-blood transfusion on oxygen delivery in patients with sepsis. JAMA. 1993;269:3024–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Dietrich KA, Conrad SA, Hebert CA, Levy GL, Romero MD. Cardiovascular and metabolic response to red blood cell transfusion in critically ill volume-resuscitated nonsurgical patients. Crit Care Med. 1990;18:940–4.PubMedCrossRefGoogle Scholar
  3. 3.
    Marik PE, Corwin HL. Acute lung injury following blood transfusion: expanding the definition. Crit Care Med. 2008;36:3080–4.PubMedCrossRefGoogle Scholar
  4. 4.
    Claridge JA, Sawyer RG, Schulman AM, McLemore EC, Young JS. Blood transfusions correlate with infections in trauma patients in a dose-dependent manner. Am Surg. 2002;68:566–72.PubMedGoogle Scholar
  5. 5.
    Bochicchio GV, Napolitano L, Joshi M, Bochicchio K, Shih D, Meyer W, et al. Blood product transfusion and ventilator-associated pneumonia in trauma patients. Surg Infect (Larchmt). 2008;9:415–22.PubMedCrossRefGoogle Scholar
  6. 6.
    Card RT, Mohandas N, Mollison PL. Relationship of post-transfusion viability to deformability of stored red cells. Br J Haematol. 1983;53:237–40.PubMedCrossRefGoogle Scholar
  7. 7.
    Ho J, Sibbald WJ, Chin-Yee IH. Effects of storage on efficacy of red cell transfusion: when is it not safe? Crit Care Med. 2003;31:S687–97.PubMedCrossRefGoogle Scholar
  8. 8.
    Sugerman HJ, Davidson DT, Vibul S, Delivoria-Papadopoulos M, Miller LD, Oski FA. The basis of defective oxygen delivery from stored blood. Surg Gynecol Obstet. 1970;131:733–41.PubMedGoogle Scholar
  9. 9.
    Valeri CR, Collins FB. The physiologic effect of transfusing preserved red cells with low 2,3-diphosphoglycerate and high affinity for oxygen. Vox Sang. 1971;20:397–403.PubMedCrossRefGoogle Scholar
  10. 10.
    Hovav T, Yedgar S, Manny N, Barshtein G. Alteration of red cell aggregability and shape during blood storage. Transfusion. 1999;39:277–81.PubMedCrossRefGoogle Scholar
  11. 11.
    Jia L, Bonaventura C, Bonaventura J, Stamler JS. S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature. 1996;380:221–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Vamvakas EC, Carven JH. Length of storage of transfused red cells and postoperative morbidity in patients undergoing coronary artery bypass graft surgery. Transfusion. 2000;40:101–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Nina P, Schisano G, Chiappetta F. Luisa Papa M, Maddaloni E, Brunori A, et al. A study of blood coagulation and fibrinolytic system in spontaneous subarachnoid hemorrhage. Correlation with hunt-hess grade and outcome. Surg Neurol. 2001;55:197–203.PubMedCrossRefGoogle Scholar
  14. 14.
    Peltonen S, Juvela S, Kaste M, Lassila R. Hemostasis and fibrinolysis activation after subarachnoid hemorrhage. J Neurosurg. 1997;87:207–14.PubMedCrossRefGoogle Scholar
  15. 15.
    Juvela S, Siironen J. D-dimer as an independent predictor for poor outcome after aneurysmal subarachnoid hemorrhage. Stroke. 2006;37:1451–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Khorana AA, Francis CW, Blumberg N, Culakova E, Refaai MA, Lyman GH. Blood transfusions, thrombosis, and mortality in hospitalized patients with cancer. Arch Intern Med. 2008;168:2377–81.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Spinella PC, Carroll CL, Staff I, Gross R, Quay McJ, Keibel L, et al. Duration of red blood cell storage is associated with increased incidence of deep vein thrombosis and in hospital mortality in patients with traumatic injuries. Crit Care. 2009;13:R151.PubMedCrossRefGoogle Scholar
  18. 18.
    Geerts WH, Code KI, Jay RM, Chen E, Szalai JP. A prospective study of venous thromboembolism after major trauma. N Engl J Med. 1994;331:1601–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Quick AJ. The development and use of the prothrombin tests. Circulation. 1959;19:92–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Stein SC, Browne KD, Chen XH, Smith DH, Graham DI. Thromboembolism and delayed cerebral ischemia after subarachnoid hemorrhage: an autopsy study. Neurosurgery. 2006;59:781–7 (discussion 787–8).PubMedCrossRefGoogle Scholar
  21. 21.
    de Leeuw FE, de Kleine M, Frijns CJ, Fijnheer R, van Gijn J, Kappelle LJ. Endothelial cell activation is associated with cerebral white matter lesions in patients with cerebrovascular disease. Ann N Y Acad Sci. 2002;977:306–14.PubMedCrossRefGoogle Scholar
  22. 22.
    Antovic J, Bakic M, Zivkovic M, Ilic A, Blomback M. Blood coagulation and fibrinolysis in acute ischaemic and haemorrhagic (intracerebral and subarachnoid haemorrhage) stroke: does decreased plasmin inhibitor indicate increased fibrinolysis in subarachnoid haemorrhage compared to other types of stroke? Scand J Clin Lab Invest. 2002;62:195–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Denton IC, Robertson JT, Dugdale M. An assessment of early platelet activity in experimental subarachnoid hemorrhage and middle cerebral artery thrombosis in the cat. Stroke. 1971;2:268–72.PubMedCrossRefGoogle Scholar
  24. 24.
    Ilveskero S, Juvela S, Siironen J, Lassila R. D-dimer predicts outcome after aneurysmal subarachnoid hemorrhage: no effect of thromboprophylaxis on coagulation activity. Neurosurgery. 2005;57:16–24. –discussion 16–24.PubMedCrossRefGoogle Scholar
  25. 25.
    Tsai AG, Hofmann A, Cabrales P, Intaglietta M. Perfusion versus oxygen delivery in transfusion with “fresh” and “old” red blood cells: the experimental evidence. Transfus Apher Sci. 2010;43:69–78.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Toda N, Okamura T. The pharmacology of nitric oxide in the peripheral nervous system of blood vessels. Pharmacol Rev. 2003;55:271–324.PubMedCrossRefGoogle Scholar
  27. 27.
    Smith MJ, Le Roux PD, Elliott JP, Winn HR. Blood transfusion and increased risk for vasospasm and poor outcome after subarachnoid hemorrhage. J Neurosurg. 2004;101:1–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Toda N, Toda H. Coronary hemodynamic regulation by nitric oxide in experimental animals: recent advances. Eur J Pharmacol. 2011;667:41–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Jy W, Ricci M, Shariatmadar S, Gomez-Marin O, Horstman LH, Ahn YS. Microparticles in stored red blood cells as potential mediators of transfusion complications. Transfusion. 2011;51:886–93.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Bilgin YM, van de Watering LM, Versteegh MI, van Oers MH, Brand A. Effects of allogeneic leukocytes in blood transfusions during cardiac surgery on inflammatory mediators and postoperative complications. Crit Care Med. 2010;38:546–52.PubMedCrossRefGoogle Scholar
  31. 31.
    Hebert PC, Fergusson D, Blajchman MA, Wells GA, Kmetic A, Coyle D, et al. Clinical outcomes following institution of the canadian universal leukoreduction program for red blood cell transfusions. JAMA. 2003;289:1941–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Naidech AM, Shaibani A, Garg RK, Duran IM, Liebling SM, Bassin SL, et al. Prospective randomized trial of higher goal hemoglobin after subarachnoid hemorrhage. Neurocrit Care. 2010;13:313–20.PubMedCrossRefGoogle Scholar
  33. 33.
    Diringer MN, Bleck TP, Hemphill JC 3rd, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocrit Care. 2011;15:211–40.PubMedCrossRefGoogle Scholar
  34. 34.
    Wartenberg KE, Mayer SA. Medical complications after subarachnoid hemorrhage: new strategies for prevention and management. Curr Opin Crit Care. 2006;12:78–84.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Monisha A. Kumar
    • 1
    • 2
    • 3
  • Torrey A. Boland
    • 4
  • Mohamed Baiou
    • 5
  • Michael Moussouttas
    • 5
  • Jay H. Herman
    • 6
  • Rodney D. Bell
    • 5
  • Robert H. Rosenwasser
    • 7
  • Scott E. Kasner
    • 1
  • Valerie E. Dechant
    • 8
  1. 1.Department of NeurologyHospital of the University of Pennsylvania, University of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of NeurosurgeryUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of Anesthesiology and Critical CareUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of NeurologyMassachusetts General HospitalBostonUSA
  5. 5.Department of NeurologyThomas Jefferson University HospitalsPhiladelphiaUSA
  6. 6.Transfusion Medicine Service, Department of Pathology, Anatomy and Cell BiologyThomas Jefferson UniversityPhiladelphiaUSA
  7. 7.Department of NeurosurgeryJefferson Hospital for Neuroscience Thomas Jefferson University HospitalsPhiladelphiaUSA
  8. 8.Department of NeurologyChristiana Care Health SystemNewarkUSA

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