Thrombocytopenia in Critically Ill Patients

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.

KEYWORDS

Platelets - coagulation - intensive care - sepsis - thrombotic microangiopathy - immune thrombocytopenia

REFERENCES

• 1 Levi M. Platelets.  Crit Care Med. 2005;  33 S523-S525
• 2 Levi M, Opal S M. Coagulation abnormalities in critically ill patients.  Crit Care. 2006;  10 222-228
• 3 Vanderschueren S, De Weerdt A, Malbrain M et al.. Thrombocytopenia and prognosis in intensive care.  Crit Care Med. 2000;  28 1871-1876
• 4 Baughman R P, Lower E E, Flessa H C, Tollerud D J. Thrombocytopenia in the intensive care unit.  Chest. 1993;  104 1243-1247
• 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
• 6 Stephan F, Hollande J, Richard O, Cheffi A, Maier-Redelsperger M, Flahault A. Thrombocytopenia in a surgical ICU.  Chest. 1999;  115 1363-1370
• 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
• 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
• 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
• 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
• 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
• 12 Woodside D G, Liu S, Ginsberg M H. Integrin activation.  Thromb Haemost. 2001;  86 316-323
• 13 Ruoslahti E. Integrins.  J Clin Invest. 1991;  87 1-5
• 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
• 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
• 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
• 17 Shebuski R J, Kilgore K S. Role of inflammatory mediators in thrombogenesis.  J Pharmacol Exp Ther. 2002;  300 729-735
• 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
• 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
• 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
• 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
• 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
• 23 Ruggeri Z M. Platelets in atherothrombosis.  Nat Med. 2002;  8 1227-1234
• 24 Ruggeri Z M. Von Willebrand factor, platelets and endothelial cell interactions.  J Thromb Haemost. 2003;  1 1335-1342
• 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
• 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
• 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
• 28 Clemetson K J, Clemetson J M. Platelet collagen receptors.  Thromb Haemost. 2001;  86 189-197
• 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
• 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
• 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
• 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
• 33 Thiagarajan P, Kelly K L. Exposure of binding sites for vitronectin on platelets following stimulation.  J Biol Chem. 1988;  263 3035-3038
• 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
• 35 Levi M. Platelets in sepsis.  Hematology. 2005;  10(Suppl 1) 129-131
• 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
• 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
• 38 Levi M. Disseminated intravascular coagulation.  Crit Care Med. 2007;  35 2191-2195
• 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
• 40 Levi M, ten Cate H. Disseminated intravascular coagulation.  N Engl J Med. 1999;  341 586-592
• 41 Levi M, van Der P T, ten Cate H. Tissue factor in infection and severe inflammation.  Semin Thromb Hemost. 2006;  32 33-39
• 42 Gando S. Tissue factor in trauma and organ dysfunction.  Semin Thromb Hemost. 2006;  32 48-53
• 43 Osterud B, Bjorklid E. Sources of tissue factor.  Semin Thromb Hemost. 2006;  32 11-23
• 44 Tilley R, Mackman N. Tissue factor in hemostasis and thrombosis.  Semin Thromb Hemost. 2006;  32 5-10
• 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
• 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
• 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
• 48 Moake J L. Thrombotic microangiopathies.  N Engl J Med. 2002;  347 589-600
• 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
• 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
• 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
• 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
• 53 Warkentin T E. Heparin-induced thrombocytopenia: pathogenesis and management.  Br J Haematol. 2003;  121 535-555
• 54 Sheridan D, Carter C, Kelton J G. A diagnostic test for heparin-induced thrombocytopenia.  Blood. 1986;  67 27-30
• 55 Makoni S N. Acute profound thrombocytopenia following angioplasty: the dilemma in the management and a review of the literature.  Heart. 2001;  86 E18
• 56 Mannucci P M, Levi M. Prevention and treatment of major blood loss.  N Engl J Med. 2007;  356 2301-2311
• 57 Hirsh J, Heddle N, Kelton J G. Treatment of heparin-induced thrombocytopenia: a critical review.  Arch Intern Med. 2004;  164 361-369