HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Guest Access | Sign In via User Name/Password

This Article Abstract Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (47) Citing Articles via Google Scholar Google Scholar Articles by Stéphan, F. Articles by Flahault, A. Search for Related Content PubMed PubMed Citation Articles by Stéphan, F. Articles by Flahault, A.

Thrombocytopenia in a Surgical ICU^*

^* From the Service d'Anesthésie-Réanimation chirurgicale (Drs. Stéphan, Hollande, Richard, and Cheffi), Laboratoire d'Hématologie (Dr. Maier-Redelsperger), and the Antenne de Biostatistiques et d'Informatique médicale (Dr. Flahault), Hôpital Tenon, Paris, France.

Correspondence to: François Stéphan, MD, PhD, Unité de Réanimation Chirurgicale et Traumatologique, Hôpital Henri Mondor, 55 S1 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil Cedex, France

	Abstract

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Study objectives: To assess the incidence of thrombocytopenia in surgical ICU patients, the factors associated with thrombocytopenia, the outcome of thrombocytopenic patients, and the possible mechanisms involved.

Design: Prospective study.

Setting: An 8-bed surgical ICU in an 885-bed teaching hospital.

Patients: 147 consecutive patients admitted to the surgical ICU during a 6-month period.

Main outcome measures: Incidence of thrombocytopenia (defined by a platelet count < 100,000/mm³), risk factors for thrombocytopenia, or death in thrombocytopenic patients identified by a stepwise logistic regression analysis, as well as the mechanisms involved.

Results: Thrombocytopenia occurred in 52 patients (35%) with a mortality rate of 38%, compared with a 20%mortality rate in nonthrombocytopenic patients (p = 0.02). Sepsis, episodes of bleeding or transfusions, and an acute physiology and chronic health evaluation (APACHE) II score of > 15 were the independent risk factors identified for thrombocytopenia. The correction of thrombocytopenia was a protective factor reducing the risk of mortality in thrombocytopenic patients. Disseminated intravascular coagulation was found in 40% of thrombocytopenic patients, elevated platelet-associated IgG in 33%, and hemophagocytic histiocytes in 67%. Combinations of two of these mechanisms were demonstrated in one quarter of thrombocytopenic patients.

Conclusions: Sepsis was the major independent risk factor identified. Thrombocytopenic patients had a higher ICU mortality due to the severity of overall clinical status. Bone marrow examination could be diagnostic when no obvious causes are demonstrated. Thrombocytopenia probably reflects the severity and course of an underlying pathologic condition, as its correction appears to be a good prognostic factor.

Key Words: disseminated intravascular coagulation • hemophagocytic histiocytes • ICU • platelet-associated IgG • sepsis • thrombocytopenia

	Introduction

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Thrombocytopenia is a common problem in the ICU and has been considered to play a role in worsening the prognosis of ICU patients.¹ A platelet count of < 100,000/mm³ has been previously reported in 23 to 27% of ICU patients.^{1 2} Several risk factors, particularly sepsis, have been identified^{1 2 3} and many studies have focused on the development and consequences of thrombocytopenia in patients with septicemia.^{4 5 6 7} The possible mechanisms leading to thrombocytopenia in ICU patients could involve the presence of disseminated intravascular coagulation (DIC) and immune mechanisms, such as elevated platelet-associated IgG (PAIgG).⁸ However, most of the previous studies are > 20 years old, and the definition of sepsis and scoring systems have changed dramatically since then. Moreover, no prospective study of ICU patients in general has analyzed the causes and consequences of thrombocytopenia. Therefore, this prospective study was conducted during a 6-month period to assess (1) the current incidence of thrombocytopenia in ICU patients; (2) the factors associated with the development of thrombocytopenia; (3) the outcome of thrombocytopenic patients; and (4) the possible mechanisms involved.

	Materials and Methods

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Study Population and Data Collection
During a 6-month period (from January 1 to June 30, 1996), all patients admitted to the surgical ICU were included in the study. One hundred and forty-seven patients were prospectively studied until discharge from the ICU or death. Patients with a history of platelet disorders, hematologic malignancies or chemotherapy, splenectomy, or mechanical heart valves, and those undergoing cardiopulmonary bypass surgery were excluded from the patient population. The following information was recorded: (1) age, sex, previous health status, admission category, severity of underlying medical conditions stratified according to the criteria of McCabe and Jackson⁹ ; (2) first-day acute physiology and chronic health evaluation (APACHE) II score¹⁰ ; (3) presence of preexisting organ failure, using definitions included in the APACHE II score; (4) presence of monitoring equipment, ie, arterial catheter, central venous catheter, pulmonary artery catheter; (5) treatment regimen during the ICU stay with special emphasis on ß-lactam antibiotics, furosemide, H₂-antagonists, unfractionated heparin and low-molecular-weight heparin; (6) RBC or platelet transfusion requirements; and (7) laboratory values including BUN, serum creatinine, liver function tests, and arterial blood gases. Full blood count and coagulation studies (factor V assay and D-dimer detection) were performed only when prothrombin time was abnormal. Episodes of bleeding, shock, and sepsis during the ICU stay were also recorded. For the thrombocytopenic patients, monitoring equipment, treatment regimen, episodes of bleeding, transfusion, or shock were taken into account only if they were present before or at the time of diagnosis of thrombocytopenia. Episodes of sepsis were taken into account if they took place before or within 24 to 48 h after the diagnosis of thrombocytopenia. A platelet antibody test was also performed in the presence of thrombocytopenia whenever possible. Bone marrow aspirates were performed within 24 h following the onset of thrombocytopenia in patients with no obvious cause of thrombocytopenia, or cytopenia involving another cell line. Particular attention was paid to the presence of histiocytes with hematophagocytic activity.¹¹ Bone marrow aspirates were graded on a scale of 0 to 4+, based on the number of marrow histiocytes and their hematophagocytic activity. Only patients graded 2+ or greater were considered to be suffering from hemophagocytosis.¹¹

The study protocol was approved by the institution's clinical investigation committee. No informed consent was mandatory, as this observational study did not modify current diagnostic or therapeutic strategies.

Definitions
Thrombocytopenia: Platelet count was performed daily for all patients. Thrombocytopenia was defined as a platelet count of < 100,000/mm³ occurring at least once during the ICU stay. Low platelet counts were confirmed by direct examination of the blood smear. Platelet transfusions were administered to actively bleeding patients and patients scheduled for emergency surgery if their platelet count fell below 50,000/mm³.¹² Likewise, platelet transfusions were administered to patients at risk for bleeding complications (eg, postoperative patients, or after GI bleeding) when their platelet count fell below 20,000/mm³. Correction of thrombocytopenia was assessed when the platelet count rose above 100,000/mm³.

Sepsis and Shock: The criteria for sepsis have been previously reported.¹³ Shock was defined as a decrease in systolic BP (< 90 mm Hg) despite adequate vascular filling or the need for vasoactive drugs (dopamine > 5 µg/kg/min, dobutamine, epinephrine, or norepinephrine).

Platelet Antibody Test: PAIgG was measured with a radio-immunoassay with I¹²⁵-labeled polyclonal antihuman IgG.¹³ Control patients had < 1,000 IgG/platelet.¹⁴ PAIgG was measured in 10 control ICU patients. Two of them were found positive: the first with a concomitant high level of immune circulating complexes, the second with a number of antibodies just above the normal value.

DIC: The definition of DIC required the following three criteria: (1) a decrease in prothrombin level activity to < 50%; (2) a decrease in the level of factor V to < 50%; and (3) the presence of fibrin degradation products (D-dimers).

Statistical Analysis
Data were computerized and analyzed using BMDP statistical packages (BMDP Statistical Software; Los Angeles, CA). Categorical variables were compared using the ² test or Fisher's exact test, and continuous variables were compared using the Mann-Whitney U test. The risk of thrombocytopenia or death in thrombocytopenic patients associated with selected factors was evaluated using stepwise logistic regression analysis to estimate odds ratios (ORs) and their 95% confidence intervals (CIs). Continuous variables were dichotomized by using the median as the cut-off value. A p value of 0.05 by univariate analysis was chosen as the criterion for submitting variables to the model. Goodness of fit was assessed by the Hosmer-Lemeshow ² test. Because of missing data, two patients were excluded from analysis of risk factors for thrombocytopenia, and two patients were excluded from analysis of risk factors for death. Because platelet antibody tests were available for only 36 patients, and despite a significant statistical association on univariate analysis, this variable was not taken into account in the multivariate analysis. Finally, to assess the role of several shared risk factors that confound the relationship between thrombocytopenia and ICU deaths, another stepwise logistic regression analysis was performed on the 147 patients. Selected factors known to be associated with mortality and/or highly predictive of the outcome of ICU patients were taken into account: age, APACHE II score, shock, and severity of underlying disease. Results are expressed as mean ± SEM for continuous variables and as a percentage for categorical variables.

	Results

TOP Abstract Introduction Materials and Methods Results Discussion References

 
In this series of 147 patients, 52 thrombocytopenic (THR+) patients (35%) had a platelet count of < 100,000/mm³ during their ICU stay. The mean platelet count of the nonthrombocytopenic (THR-) patients was 232,000 ± 10,000/mm³. Thrombocytopenia occurred 1.8 ± 0.5 days (range, 0 to 22) after ICU admission, with a mean platelet count at the time of diagnosis of 68,900 ± 3,000/mm³. The frequency of thrombocytopenia according to its severity is shown in Figure 1 . The mean nadir platelet count was 52,600 ± 3,800/mm³, and there was no association between underlying illness and the severity of thrombocytopenia.

View larger version (11K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Distribution of thrombocytopenia according to its severity, showing thrombocytopenia-related mortality. Open bars = survivors; solid bars = nonsurvivors

The platelet count rose to > 40,000 to 50,000/mm³ several hours after platelet transfusion, but never > 100,000/mm³. Platelet transfusion alone therefore did not allow complete correction of thrombocytopenia. Thrombocytopenia was corrected within 3.7 ± 0.5 days (range, 1 to 11) in 28 patients; reversal of thrombocytopenia did not differ according to the underlying disease.

Main reasons for ICU admission included 45 postoperative cases (orthopedic surgery, 16; thoracic and vascular surgery, 13; abdominal surgery, 8; other surgery, 8); 28 cases of shock (cardiogenic, septic, or undetermined); 20 cases of GI hemorrhage; 17 cases of trauma; 16 cases of acute respiratory failure; 15 cases of neurologic disorders; and 6 miscellaneous causes.

At the time of thrombocytopenia, main diagnoses included 21 cases of sepsis (8 cases of pneumonia, 5 cases of peritonitis, 2 cases of acute mesenteric ischemia, 2 intra-abdominal abscesses, 2 cases of biliary or urinary tract infection, 1 prosthetic joint infection, and 1 vascular prosthetic graft infection); 20 cases of postoperative bleeding or GI hemorrhage; and 11 miscellaneous causes.

When considering all isolates from all sources identified, Gram-negative bacilli were recovered in 16 of the 21 episodes (76%; 62% had Gram-negative infection only), Gram-positive or -negative cocci in 8 episodes (38%), and Candida spp in 3 episodes; 29% of the episodes were associated with polymicrobial infection. Bacteremia occurred in 43% of the 21 patients with sepsis. The most prevalent species were Escherichia coli, Klebsiella spp, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus spp, and Streptococcus pneumoniae.

Risk Factors for Thrombocytopenia During ICU Stay
Factors associated with the development of thrombocytopenia in univariate analysis are reported in Tables 1 and 2Table 2 . Factors not associated with the development of thrombocytopenia were age, preexisting liver failure (3 of 95 vs 5 of 52; p = 0.13), PaO₂/fraction of inspired oxygen (FIO₂) ratio, serum transaminases, BUN, serum creatinine, prescription of unfractionated or low-molecular-weight heparin, furosemide, H₂-antagonist and ß-lactam antibiotics during ICU stay.

Outcome in Thrombocytopenic Patients
The ICU mortality was much higher in THR+ patients than in THR- patients (38 vs 20%; p = 0.02). ICU mortality in THR+ patients, stratified by the lowest platelet count, is reported in Figure 1 . THR+ patients with a platelet count of < 50,000/mm³ had a higher mortality rate (54 vs 23%; p < 0.05). The development of thrombocytopenia was also associated with an increased ICU stay (10.4 ± 2.0 vs 5.8 ± 0.95 days; p = 0.02) and a longer hospital stay (27 ± 3.0 vs 16 ± 1.6 days; p = 0.0007).

The factors associated with increasing mortality in the thrombocytopenic population in univariate analysis are listed in Table 3 . The factors not associated with mortality in thrombocytopenic patients were admission category, severity of underlying disease, transfusion requirements (including platelet transfusion), leukocyte count, hemoglobin value, and liver function test results.

Risk factors identified for ICU death in the whole cohort after multivariate analysis were an APACHE II score at admission of > 19 (OR, 23.8; 95% CI, 8.2 to 69.2; p < 0.0001) and shock (OR, 3.22; 95% CI, 1.16 to 9.03; p < 0.02). However, thrombocytopenia was not identified as a variable independently associated with death (p = 0.2). The goodness-of-fit ² remained nonsignificant during the two steps (p = 0.86 at the last step).

Mechanisms Involved in Thrombocytopenia and Bone Marrow Findings
The contribution of DIC episodes, positive PAIgG tests, and the presence of hemophagocytic histiocytes to thrombocytopenia are reported in Table 4 for patients with medical conditions associated with thrombocytopenia. At least two complementary investigations (DIC, PAIgG test, or bone marrow aspirate) were performed in 39 episodes of thrombocytopenia. The mean level of PAIgG in patients with and without a positive PAIgG test was 3,800 ± 836 and 446 ± 41 IgG/platelet, respectively.

DIC was found in 40% of thrombocytopenic patients, elevated PAIgG levels in 33%, and hemophagocytic histiocytes in 67% when bone marrow aspiration was performed. Combinations of two of these mechanisms were demonstrated in one quarter of all thrombocytopenic patients.

	Discussion

TOP Abstract Introduction Materials and Methods Results Discussion References

 
In our patient population, the incidence rate of thrombocytopenia < 100,000/mm³ was 35%. Previous studies have reported an incidence of 23 to 27% in ICU patients,^{1 2} up to 41% in trauma patients,³ and 35 to 58% in patients with sepsis or septicemia.^{4 15} A large number of our patients presented with sepsis or trauma, which can explain the relatively high percentage of thrombocytopenic patients. Several issues regarding the correct management of patients with DIC remain controversial. If serious depletion of platelets and clotting factors occurs, replacement therapy should be considered. However, replacement should not be instituted on the basis of laboratory findings alone and is required only in patients who are actively bleeding, who require an invasive procedure, or who are at risk for bleeding complications (eg, postoperative patients).¹⁶ If the patient is hemorrhagic and the platelet count is < 50,000/mm³, then platelet transfusion (to keep the platelet count in the range of 50,000 to 70,000/mm³) seems quite reasonable.¹² In the postoperative period, when treatment of the underlying cause is achieved, severe thrombocytopenia could have a harmful effect by promoting or maintaining active bleeding. In this case, platelet transfusions in combination with other therapies are justified in an attempt to control hemostasis.

The presence of sepsis was the predominant risk factor identified. A close relationship between sepsis or septicemia and thrombocytopenia has been postulated for a long time^{1 4 5 7 15 17} , and thrombocytopenia has even been suggested to be indicative of acute infection.^{4 7} Bleeding and transfusion are the other identified risk factors. Blood loss with subsequent volume replacement using crystalloids or colloids, when sufficiently severe, can significantly decrease the platelet count.¹⁸ Likewise, a fall in platelet count has been noted following blood transfusions. The incidence of thrombocytopenia has been specifically reported to be directly proportional to the number of RBC transfusions.³ This posttransfusional fall can be attributed to dilution by stored blood containing low concentrations of viable platelets⁸ or splenic platelet sequestration following routine blood transfusion.¹⁹ Development of thrombocytopenia and a cause-and-effect relationship with these risk factors is also supported by the fact that the correction of thrombocytopenia appears to be related to successful treatment of the underlying disease. Finally, thrombocytopenia was associated with the most severely ill patients as reflected by a higher APACHE II score, an observation reported by other investigators.^{1 7}

A platelet count on admission of > 185,000/mm³ is the only identified protective factor. In fact, platelet count on admission probably reflects the importance of the surgical procedure or the intensity of the bleeding, since 56% of our patients had a primary admission diagnosis of postoperative management, GI hemorrhages, or trauma.

Several medical conditions or monitoring procedures are known to be associated with thrombocytopenia in the ICU setting,⁸ including ARDS, use of the pulmonary artery catheter, and drug therapies. In contrast to the present study, previous studies have noted that Swan-Ganz catheterization was associated with thrombocytopenia.^{1 20} In the first study, many confounding factors were present and no definitive conclusions can be drawn,¹ and in the second study the platelet count never fell below 150,000/mm³.²⁰ Similarly, none of the medications studied was associated with the development of thrombocytopenia in our study, confirming the fairly small relative contribution of drug-induced thrombocytopenia.^{2 3} However, heparin-induced thrombocytopenia is a rare but severe complication of treatment with heparin or low-molecular-weight heparin.²¹ An early, transient fall in platelet count occurred during the early postoperative period in one third of patients receiving heparin.²² This may actually resolve within 3 days despite continuation of heparin.^{8 22} Heparin-induced thrombocytopenia typically appears 5 or more days after starting heparin therapy.^{21 22} Heparin-induced thrombocytopenia has been recently reported to occur in 2.7% of heparin-treated patients and in no patients treated with low-molecular-weight heparin.²² Because heparin-induced thrombocytopenia is such a severe complication, any patient who becomes thrombocytopenic during heparin therapy should be considered at risk for thrombosis.²¹ Thrombocytopenia is common in patients with severe acute respiratory failure and ARDS.^{8 23 24} Despite a lower and severe PaO₂/FIO₂ ratio in THR+ patients who died, acute respiratory failure was not identified as a risk factor. The low incidence of ARDS in our ICU may explain this result.

Univariate analysis also showed that THR+patients had a higher ICU mortality rate, which has been reported previously^{1 7} and was recently confirmed in a multicenter prospective ICU study.¹⁵ As suggested by Baughman et al,¹ mortality appears to be inversely proportional to the nadir platelet count. However, we were unable to demonstrate that thrombocytopenia itself worsened the prognosis of ICU patients. Finally, the higher ICU mortality among THR+ patients could be simply due to the severity of the overall clinical status. Interestingly, correction of thrombocytopenia appears to be an independent protective factor of death, as previously mentioned by Oppenheimer et al⁵ and François et al,²⁵ and platelet transfusion did not seem to contribute to this correction. Thrombocytopenia therefore probably reflects the severity and progression of an underlying pathologic condition.

In our study, one third of THR+ patients had evidence of DIC or PAIgG; coexistence of such mechanisms was noted in 35% of our septic patients. Several mechanisms leading to thrombocytopenia in the ICU setting have been identified.^{8 17 25 26} These mechanisms have been particularly studied during bacterial infection.^{17 25 26} One mechanism is DIC, with an incidence of 11 to 92% in severe thrombocytopenia occurring during systemic infection^{6 17} ; DIC could contribute to an unfavorable outcome.⁷ However, some studies did not report such a frequency,^{4 5} and other causative mechanisms have therefore been suggested. The demonstration that platelet-bound IgG is elevated in many THR+ patients with septicemia suggests that immune mechanisms may generate thrombocytopenia.^{27 28} Although platelet autoantibody is one mechanism proposed to explain the increased PAIgG value,²⁸ circulating immune complexes could also be involved.^{17 29} Finally, PAIgG is a nonspecific finding and its significance therefore remains unclear. Unfortunately, measurements of specific antiplatelet glycoprotein antibodies or circulating immune complexes were not performed. Nevertheless, DIC and immune mechanisms cannot explain all cases of thrombocytopenia.

Results of bone marrow aspiration showed that suppression of thrombopoietic components is unusual,^{11 25 26} but three quarters of patients had evidence of hemophagocytic histiocytes. Hemophagocytic histiocytosis is characterized by systemic proliferation of nonneoplastic histiocytes that are actively engaged in phagocytosis of hematopoietic cells, resulting in cytopenia.³⁰ Several viral and bacterial infections, as well as some noninfectious conditions, have been recognized to be associated with reactive hemophagocytosis.^{25 26 30} A strong association between the development of hemophagocytic histiocytes and recent blood transfusion or sepsis was reported by Suster et al,¹¹ and hemophagocytic histiocytes constitute a probable mechanism of thrombocytopenia in ICU patients, as recently suggested.^{25 26}

Assessment of the respective role of hemophagocytic histiocytosis among several concomitant causes remains difficult. However, given the large volume of bone marrow in the body, it is conceivable that hemophagocytic histiocytes detected in the marrow smears could be involved in the mechanism of thrombocytopenia.²⁶ In the recent study by François et al,²⁵ the mortality rate was reported to be markedly higher in patients with hemophagocytic histiocytosis. However, hemophagocytic histiocytosis was identified in the most severely ill patients. Hemophagocytosis therefore appears to be an additional marker of severity of the underlying illness.

The management of the thrombocytopenic ICU patient is difficult because there are so many potential causes for the problem and because withdrawal of the supposed precipitating factors (eg, drugs) may be complicated and dangerous.⁸ Therefore, diagnosis of hemophagocytic histiocytosis as an additional cause of the platelet destruction process could be helpful. The presence of hemophagocytic histiocytes was the sole finding explaining the thrombocytopenia in three septic patients. Finally, contrary to the study by Baughman et al,¹ we think that bone marrow examination could be diagnostic when no obvious causes of severe thrombocytopenia are demonstrated, or when cytopenia involves another cell line.

In conclusion, thrombocytopenia occurs frequently in critically ill patients and probably reflects the severity and progression of an underlying disease. Physicians must be aware that the onset of thrombocytopenia may be indicative of acute infection, and thrombocytopenia seems to be a reliable monitoring parameter in patients with sepsis or during the postoperative period, as its correction appears to be a good prognostic factor of outcome.

	Acknowledgements

	Footnotes

 
Abbreviations: APACHE = acute physiology and chronic health evaluation; CI = confidence interval; DIC = disseminated intravascular coagulation; FIO₂ = fraction of inspired oxygen; OR = odds ratio; PAIgG = platelet-associated IgG; THR+ = thrombocytopenic; THR- = nonthrombocytopenic

Received for publication May 12, 1998. Accepted for publication October 16, 1998.

	References

TOP Abstract Introduction Materials and Methods Results Discussion References

 

1. Baughman, RP, Lower, EE, Flessa, HC, et al (1993) Thrombocytopenia in the intensive care unit. Chest 104,1243-1247[Abstract/Free Full Text]
2. Bonfiglio, MF, Traeger, SM, Kier, KL, et al (1995) Thrombocytopenia in intensive care patients: a comprehensive analysis of risk factors in 314 patients. Ann Pharmacother 29,835-841[Abstract]
3. Hanes, SD, Quarles, DA, Boucher, BA (1997) Incidence and risk factors of thrombocytopenia in critically ill trauma patients. Ann Pharmacother 31,285-289[Abstract]
4. Riedler, GF, Straub, PW, Frick, PG (1971) Thrombocytopenia in septicemia: a clinical study for the evaluation of its incidence and diagnostic value. Helv Med Acta 36,23-38[ISI][Medline]
5. Oppenheimer, L, Hryniuk, WM, Bishop, AJ (1976) Thrombocytopenia in severe bacterial infections. J Surg Res 20,211-214[CrossRef][ISI][Medline]
6. Neame, PB, Kelton, JG, Walker, IR, et al (1980) Thrombocytopenia in septicemia: the role of disseminated intravascular coagulation. Blood 56,88-92[Abstract/Free Full Text]
7. Svanbom, M (1980) A prospective study on septicemia: clinical manifestations and complications, results of antimicrobial treatment and report of a follow-up study. Scand J Infect Dis 12,189-206[ISI][Medline]
8. Bogdonoff, DL, Williams, ME, Stone, DJ (1990) Thrombocytopenia in the critically ill patient. J Crit Care 5,186-205[CrossRef]
9. McCabe, WR, Jackson, GG (1962) Gram-negative bacteria. I. Etiology and ecology. Arch Intern Med 110,847-855[ISI]
10. Knaus, WA, Draper, EA, Wagner, DP, et al (1985) APACHE II: a severity of disease classification system. Crit Care Med 18,818-829
11. Suster, S, Hilsenbeck, S, Rywlin, AM (1988) Reactive histiocytic hyperplasia with hemophagocytosis in hematopoietic organs: a reevaluation of the benign hemophagocytic proliferations. Hum Pathol 19,705-712[CrossRef][ISI][Medline]
12. Kitchens, CS (1995) Disseminated intravascular coagulation. Curr Opin Hematol 2,402-406[Medline]
13. . American College of Chest Physicians/Society of Critical Care Medicine Consensus Committee (1992) Definitions for sepsis and organ failures and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20,864-874[ISI][Medline]
14. Debré, M, Bonnet, M-C, Fridman, W-H, et al (1993) Infusion of Fc fragments for treatment of children with acute immune thrombocytopenic purpura. Lancet 342,945-949[CrossRef][ISI][Medline]
15. Brun-Buisson, C, Doyon, F, Carlet, J, et al (1995) Incidence, risk factors, and outcome of severe sepsis and septic shock in adults: a multicenter prospective study in intensive care units. JAMA 274,968-974[Abstract]
16. Baglin, T (1996) Disseminated intravascular coagulation: diagnosis and treatment. BMJ 312,683-687[Abstract/Free Full Text]
17. Wilson, JJ, Neame, PB, Kelton, JG (1982) Infection-induced thrombocytopenia. Semin Thromb Hemost 8,217-233[ISI][Medline]
18. Spiess, BD (1992) Hemorrhagic problems during the immediate postoperative period. Vender, JS Spiess, BD eds. Post anesthesia care ,131-140 WB Saunders Philadelphia, PA.
19. Bareford, D, Chandler, ST, Hawker, RJ, et al (1987) Splenic platelet sequestration following routine blood transfusion is reduced by filtered/washed product. Br J Haematol 67,177-180[ISI][Medline]
20. Kim, YL, Richman, KA, Marshall, BE (1980) Thrombocytopenia associated with Swan-Ganz catheterization in patients. Anesthesiology 53,261-262[CrossRef][ISI][Medline]
21. Slaughter, TF, Greenberg, CS (1997) Heparin-associated thrombocytopenia and thrombosis: implications for perioperative management. Anesthesiology 87,667-675[CrossRef][ISI][Medline]
22. Warkentin, TE, Levine, MN, Hirsh, J, et al (1995) Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 332,1330-1335[Abstract/Free Full Text]
23. Schneider, RC, Zapol, WM, Carvalho, A (1980) Platelet consumption and sequestration in severe acute respiratory failure. Am Rev Respir Dis 122,445-451[ISI][Medline]
24. Heffner, JE, Sahn, SA, Repine, JE (1987) The role of platelets in the adult respiratory distress syndrome: culprits or bystanders? Am Rev Respir Dis 135,482-492[ISI][Medline]
25. François, B, Trimoreau, F, Vignon, P, et al (1997) Thrombocytopenia in the sepsis syndrome: role of hemophagocytosis and macrophage colony-stimulating factor. Am J Med 103,114-120[CrossRef][ISI][Medline]
26. Stéphan, F, Thiolière, B, Verdy, E, et al (1997) Role of hemophagocytic histiocytosis in the etiology of thrombocytopenia in patients with sepsis syndrome or septic shock. Clin Infect Dis 25,1159-1164[ISI][Medline]
27. Kelton, JG, Neame, PB, Gauldie, J, et al (1979) Elevated platelet-associated IgG in the thrombocytopenia of septicemia. N Engl J Med 300,760-764[Abstract]
28. van der Lelie, J, van der Plas-Van Dalen, CM, von dem Borne, AE (1984) Platelet autoantibodies in septicaemia. Br J Haematol 58,755-760[ISI][Medline]
29. George, JN (1990) Platelet immunoglobulin G: its significance for the evaluation of thrombocytopenia and for understanding the origin of -granule proteins. Blood 76,859-870[Free Full Text]
30. Wong, KF, Chan, JKC (1991) Hemophagocytic disorders: a review. Hematol Rev 5,5-37

This article has been cited by other articles:

				D. Moreau, J.-F. Timsit, A. Vesin, M. Garrouste-Orgeas, A. de Lassence, J.-R. Zahar, C. Adrie, F. Vincent, Y. Cohen, B. Schlemmer, et al. Platelet Count Decline: An Early Prognostic Marker in Critically Ill Patients With Prolonged ICU Stays Chest, June 1, 2007; 131(6): 1735 - 1741. [Abstract] [Full Text] [PDF]

				D. Lasne, B. Jude, and S. Susen From normal to pathological hemostasis: [De l'hemostase normale a l'hemostase pathologique]. Can J Anesth, June 1, 2006; 53(6_suppl): S2 - S11. [Abstract] [Full Text] [PDF]

				E. de Maistre, Y. Gruel, and D. Lasne Diagnosis and management of heparin-induced thrombocytopenia: [Le diagnostic et le traitement de la thrombopenie induite par l'heparine]. Can J Anesth, June 1, 2006; 53(6_suppl): S123 - S134. [Abstract] [Full Text] [PDF]

				N. Valade, F. Decailliot, Y. Rebufat, Y. Heurtematte, P. Duvaldestin, and F. Stephan Thrombocytosis after trauma: incidence, aetiology, and clinical significance Br. J. Anaesth., January 1, 2005; 94(1): 18 - 23. [Abstract] [Full Text] [PDF]

				S. Kluge, A. Meyer, P. Kuhnelt, H. J. Baumann, and G. Kreymann Percutaneous Tracheostomy Is Safe in Patients With Severe Thrombocytopenia Chest, August 1, 2004; 126(2): 547 - 551. [Abstract] [Full Text] [PDF]

				T. G. DeLoughery Thrombocytopenia in Critical Care Patients J Intensive Care Med, November 1, 2002; 17(6): 267 - 282. [Abstract] [PDF]

				R. E. DREWS and S. E. WEINBERGER Thrombocytopenic Disorders in Critically Ill Patients Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 347 - 351. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (47) Citing Articles via Google Scholar Google Scholar Articles by Stéphan, F. Articles by Flahault, A. Search for Related Content PubMed PubMed Citation Articles by Stéphan, F. Articles by Flahault, A.