Thrombocytopenia in Critically Ill Patients

 

 Buy Article Permissions and Reprints

ABSTRACT

Critically ill patients often have a low platelet count. A proper identification of the underlying cause of this abnormality is required, because various underlying disorders may necessitate different diagnostic and therapeutic management strategies. Platelets are part of the first line of defense of the body against bleeding, hence, thrombocytopenia may increase the risk of hemorrhage. In case of systemic inflammatory syndromes, such as the response to sepsis, disseminated intravascular platelet activation may occur, which will contribute to microvascular failure and thereby play a role in the development of organ dysfunction. A low platelet count is a strong and independent predictor of an adverse outcome in critically ill patients, thereby facilitating a simple and practical risk assessment in these patients and potentially guiding the use of complex or expensive treatment strategies.

REFERENCES

• 1 Levi M. Platelets.  Crit Care Med. 2005;  33 S523-S525
  CrossrefPubMedGoogle Scholar
• 2 Levi M, Opal S M. Coagulation abnormalities in critically ill patients.  Crit Care. 2006;  10 222-228
  CrossrefPubMedGoogle Scholar
• 3 Vanderschueren S, De Weerdt A, Malbrain M et al.. Thrombocytopenia and prognosis in intensive care.  Crit Care Med. 2000;  28 1871-1876
  CrossrefPubMedGoogle Scholar
• 4 Baughman R P, Lower E E, Flessa H C, Tollerud D J. Thrombocytopenia in the intensive care unit.  Chest. 1993;  104 1243-1247
  CrossrefPubMedGoogle Scholar
• 5 Strauss R, Wehler M, Mehler K, Kreutzer D, Koebnick C, Hahn E G. Thrombocytopenia in patients in the medical intensive care unit: bleeding prevalence, transfusion requirements, and outcome.  Crit Care Med. 2002;  30 1765-1771
  CrossrefPubMedGoogle Scholar
• 6 Stephan F, Hollande J, Richard O, Cheffi A, Maier-Redelsperger M, Flahault A. Thrombocytopenia in a surgical ICU.  Chest. 1999;  115 1363-1370
  CrossrefPubMedGoogle Scholar
• 7 Hanes S D, Quarles D A, Boucher B A. Incidence and risk factors of thrombocytopenia in critically ill trauma patients.  Ann Pharmacother. 1997;  31 285-289
  PubMedGoogle Scholar
• 8 Akca S, Haji Michael P, de Medonca A, Suter P M, Levi M, Vincent J L. The time course of platelet counts in critically ill patients.  Crit Care Med. 2002;  30 753-756
  CrossrefPubMedGoogle Scholar
• 9 Oppenheim-Eden A, Glantz L, Eidelman L A, Sprung C L. Spontaneous intracerebral hemorrhage in critically ill patients: incidence over six years and associated factors.  Intensive Care Med. 1999;  25 63-67
  CrossrefPubMedGoogle Scholar
• 10 Hawiger J J. Adhesive interactions of blood cells and the vascular wall in hemostasis and thrombosis. In: Colman RW, Hirsh J, Marder V, Salzman E Hemostasis and Thrombosis. Basic Principles and Clinical Practice, 3rd ed. Philadelphia, PA; J.B.Lippincott 1994: 639-653
  Google Scholar
• 11 Ware J A, Heistad D D. Seminars in medicine of the Beth Israel Hospital, Boston. Platelet-endothelium interactions.  N Engl J Med. 1993;  328 628-635
  CrossrefPubMedGoogle Scholar
• 12 Woodside D G, Liu S, Ginsberg M H. Integrin activation.  Thromb Haemost. 2001;  86 316-323
  PubMedGoogle Scholar
• 13 Ruoslahti E. Integrins.  J Clin Invest. 1991;  87 1-5
  CrossrefPubMedGoogle Scholar
• 14 Phillips D R, Prasad K S, Manganello J, Bao M, Nannizzi-Alaimo L. Integrin tyrosine phosphorylation in platelet signaling.  Curr Opin Cell Biol. 2001;  13 546-554
  CrossrefPubMedGoogle Scholar
• 15 Clemens R, Pramoolsinsap C, Lorenz R, Pukrittayakamee S, Bock H L, White N J. Activation of the coagulation cascade in severe falciparum malaria through the intrinsic pathway.  Br J Haematol. 1994;  87 100-105
  CrossrefPubMedGoogle Scholar
• 16 Furie B, Furie B C, Flaumenhaft R. A journey with platelet P-selectin: the molecular basis of granule secretion, signalling and cell adhesion.  Thromb Haemost. 2001;  86 214-221
  Article in Thieme ConnectPubMedGoogle Scholar
• 17 Shebuski R J, Kilgore K S. Role of inflammatory mediators in thrombogenesis.  J Pharmacol Exp Ther. 2002;  300 729-735
  CrossrefPubMedGoogle Scholar
• 18 Romo G M, Dong J F, Schade A J et al.. The glycoprotein Ib-IX-V complex is a platelet counterreceptor for P-selectin.  J Exp Med. 1999;  190 803-814
  CrossrefPubMedGoogle Scholar
• 19 Simon D I, Chen Z, Xu H et al.. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18).  J Exp Med. 2000;  192 193-204
  CrossrefPubMedGoogle Scholar
• 20 Clemetson J M, Polgar J, Magnenat E, Wells T N, Clemetson K J. The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to FcalphaR and the natural killer receptors.  J Biol Chem. 1999;  274 29019-29024
  CrossrefPubMedGoogle Scholar
• 21 Jung S M, Takemura Y, Imamura Y et al.. Collagen-type specificity of glycoprotein VI as a determinant of platelet adhesion.  Platelets. 2008;  19(1) 32-42
  CrossrefPubMedGoogle Scholar
• 22 Silverstein R L, Asch A S, Nachman R L. Glycoprotein IV mediates thrombospondin-dependent platelet-monocyte and platelet-U937 cell adhesion.  J Clin Invest. 1989;  84 546-552
  CrossrefPubMedGoogle Scholar
• 23 Ruggeri Z M. Platelets in atherothrombosis.  Nat Med. 2002;  8 1227-1234
  CrossrefPubMedGoogle Scholar
• 24 Ruggeri Z M. Von Willebrand factor, platelets and endothelial cell interactions.  J Thromb Haemost. 2003;  1 1335-1342
  CrossrefPubMedGoogle Scholar
• 25 Arya M, Anvari B, Romo G M et al.. Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers.  Blood. 2002;  99 3971-3977
  CrossrefPubMedGoogle Scholar
• 26 Jung S M, Moroi M. Activation of the platelet collagen receptor integrin alpha(2)beta(1): its mechanism and participation in the physiological functions of platelets.  Trends Cardiovasc Med. 2000;  10 285-292
  CrossrefPubMedGoogle Scholar
• 27 Massberg S, Konrad I, Bultmann A et al.. Soluble glycoprotein VI dimer inhibits platelet adhesion and aggregation to the injured vessel wall in vivo.  FASEB J. 2004;  18 397-399
  PubMedGoogle Scholar
• 28 Clemetson K J, Clemetson J M. Platelet collagen receptors.  Thromb Haemost. 2001;  86 189-197
  Article in Thieme ConnectPubMedGoogle Scholar
• 29 Jurk K, Clemetson K J, De Groot P G et al.. Thrombospondin-1 mediates platelet adhesion at high shear via glycoprotein Ib (GPIb): an alternative/backup mechanism to von Willebrand factor.  FASEB J. 2003;  17 1490-1492
  PubMedGoogle Scholar
• 30 Roberts D D, Sherwood J A, Spitalnik S L et al.. Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence.  Nature. 1985;  318 64-66
  CrossrefPubMedGoogle Scholar
• 31 Brittain J E, Mlinar K J, Anderson C S, Orringer E P, Parise L V. Activation of sickle red blood cell adhesion via integrin-associated protein/CD47-induced signal transduction.  J Clin Invest. 2001;  107 1555-1562
  CrossrefPubMedGoogle Scholar
• 32 Ill C R, Engvall E, Ruoslahti E. Adhesion of platelets to laminin in the absence of activation.  J Cell Biol. 1984;  99 2140-2145
  CrossrefPubMedGoogle Scholar
• 33 Thiagarajan P, Kelly K L. Exposure of binding sites for vitronectin on platelets following stimulation.  J Biol Chem. 1988;  263 3035-3038
  PubMedGoogle Scholar
• 34 Mavrommatis A C, Theodoridis T, Orfanidou A, Roussos C, Christopoulou-Kokkinou V, Zakynthinos S. Coagulation system and platelets are fully activated in uncomplicated sepsis.  Crit Care Med. 2000;  28 451-457
  CrossrefPubMedGoogle Scholar
• 35 Levi M. Platelets in sepsis.  Hematology. 2005;  10(Suppl 1) 129-131
  CrossrefPubMedGoogle Scholar
• 36 Folman C C, Linthorst G E, van Mourik J et al.. Platelets release thrombopoietin (Tpo) upon activation: another regulatory loop in thrombocytopoiesis?.  Thromb Haemost. 2000;  83 923-930
  PubMedGoogle Scholar
• 37 Francois B, Trimoreau F, Vignon P, Fixe P, Praloran V, Gastinne H. Thrombocytopenia in the sepsis syndrome: role of hemophagocytosis and macrophage colony-stimulating factor.  Am J Med. 1997;  103 114-120
  CrossrefPubMedGoogle Scholar
• 38 Levi M. Disseminated intravascular coagulation.  Crit Care Med. 2007;  35 2191-2195
  CrossrefPubMedGoogle Scholar
• 39 Warkentin T E, Aird W C, Rand J H. Platelet-endothelial interactions: sepsis, HIT, and antiphospholipid syndrome.  Hematology Am Soc Hematol Educ Program. 2003;  497-519
  PubMedGoogle Scholar
• 40 Levi M, ten Cate H. Disseminated intravascular coagulation.  N Engl J Med. 1999;  341 586-592
  CrossrefPubMedGoogle Scholar
• 41 Levi M, van Der P T, ten Cate H. Tissue factor in infection and severe inflammation.  Semin Thromb Hemost. 2006;  32 33-39
  Article in Thieme ConnectPubMedGoogle Scholar
• 42 Gando S. Tissue factor in trauma and organ dysfunction.  Semin Thromb Hemost. 2006;  32 48-53
  Article in Thieme ConnectPubMedGoogle Scholar
• 43 Osterud B, Bjorklid E. Sources of tissue factor.  Semin Thromb Hemost. 2006;  32 11-23
  Article in Thieme ConnectPubMedGoogle Scholar
• 44 Tilley R, Mackman N. Tissue factor in hemostasis and thrombosis.  Semin Thromb Hemost. 2006;  32 5-10
  Article in Thieme ConnectPubMedGoogle Scholar
• 45 Taylor F BJ, Toh C H, Hoots W K, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation.  Thromb Haemost. 2001;  86 1327-1330
  Article in Thieme ConnectPubMedGoogle Scholar
• 46 Bakhtiari K, Meijers J C, de Jonge E, Levi M. Prospective validation of the international society of thrombosis and maemostasis scoring system for disseminated intravascular coagulation.  Crit Care Med. 2004;  32 2416-2421
  CrossrefPubMedGoogle Scholar
• 47 Dhainaut J F, Yan S B, Joyce D E et al.. Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation.  J Thromb Haemost. 2004;  2 1924-1933
  CrossrefPubMedGoogle Scholar
• 48 Moake J L. Thrombotic microangiopathies.  N Engl J Med. 2002;  347 589-600
  CrossrefPubMedGoogle Scholar
• 49 Tsai H M. Platelet activation and the formation of the platelet plug: deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura.  Arterioscler Thromb Vasc Biol. 2003;  23 388-396
  CrossrefPubMedGoogle Scholar
• 50 van den Born B J, van der Hoeven N V, Groot E et al.. Association between thrombotic microangiopathy and reduced ADAMTS13 activity in malignant hypertension.  Hypertension. 2008;  51 862-866
  CrossrefPubMedGoogle Scholar
• 51 Verma A K, Levine M, Shalansky S J, Carter C J, Kelton J G. Frequency of heparin-induced thrombocytopenia in critical care patients.  Pharmacotherapy. 2003;  23 745-753
  CrossrefPubMedGoogle Scholar
• 52 Warkentin T E, Levine M N, Hirsh J et al.. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin.  N Engl J Med. 1995;  332 1330-1335
  CrossrefPubMedGoogle Scholar
• 53 Warkentin T E. Heparin-induced thrombocytopenia: pathogenesis and management.  Br J Haematol. 2003;  121 535-555
  CrossrefPubMedGoogle Scholar
• 54 Sheridan D, Carter C, Kelton J G. A diagnostic test for heparin-induced thrombocytopenia.  Blood. 1986;  67 27-30
  CrossrefPubMedGoogle Scholar
• 55 Makoni S N. Acute profound thrombocytopenia following angioplasty: the dilemma in the management and a review of the literature.  Heart. 2001;  86 E18
  CrossrefPubMedGoogle Scholar
• 56 Mannucci P M, Levi M. Prevention and treatment of major blood loss.  N Engl J Med. 2007;  356 2301-2311
  CrossrefPubMedGoogle Scholar
• 57 Hirsh J, Heddle N, Kelton J G. Treatment of heparin-induced thrombocytopenia: a critical review.  Arch Intern Med. 2004;  164 361-369
  CrossrefPubMedGoogle Scholar

Marcel LeviM.D. Ph.D. F.R.C.P. 

Department Internal Medicine, Academic Medical Centre F-4, Meibergdreef 9

1105 AZ Amsterdam, The Netherlands

Email: m.m.levi@amc.uva.nl