SEARCH

SEARCH BY CITATION

Summary

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Competing interests
  7. References

Venous air embolism activates platelets in vitro and can evoke platelet dysfunction in swine. We tested the hypothesis that venous air embolism during semi-sitting craniotomy induces thrombocytopenia in humans. We analysed the charts of 799 patients who had an elective craniotomy in the semi-sitting position between 1990 and June 2009. Venous air embolism occurred in 52 patients (6.5%) and was associated with a decrease in mean (SD) in platelet count from 270 (75) × 109 l−1 to 194 (62) × 109 l−1 (p < 0.001). In age-matched controls without venous air embolism mean (SD) platelet count did not change (254 (82) × 109 l−1 vs. 250 (97) × 109 l−1 (NS). While mean (SD) haematocrit fell slightly in both groups (venous air embolism: 0.40 (0.05) to 0.32 (0.04), p < 0.001; no venous air embolism: 0.41 (0.04) to 0.35 (0.05), p < 0.001), normalising platelet count to haematocrit did not alter the results.

Venous air embolism [1–3] is a frequent and potentially lethal complication during neurosurgical operations in the semi-sitting position, and may occur whenever venous pressure at the site of surgery is below atmospheric pressure [1, 2, 4]. Intrapulmonary air following venous air embolism causes endothelial damage and induces gaps between endothelial cells, thus facilitating pulmonary oedema [5–7]. Furthermore, in vitro, direct air-blood contact leads to complement and platelet activation [8]. Adjacent, activated platelets can coat air bubbles, thus forming a stabilised platelet-air conglomerate [8–12].

However, little is known about effects of clinical venous air embolism on platelet count in vivo. Recent data from our group addressed the effects of high dose, lethal venous air embolism on platelets in swine and revealed that venous air embolism impaired platelet function, as assessed by impedance aggregometry [13]. However the mean (SD) cumulative amount of air injected was high (4.6 (1.6) ml.kg−1) eventually causing cardiocirculatory collapse in all animals studied [13]. Furthermore, extrapolating these data to intra-operative venous air embolism in humans is difficult, as blood coagulation in swine and humans differs and the amount of air entrained during surgery varies [3, 14]. Thus, it remains unclear whether intra-operative venous air embolism impacts on platelet count. We therefore tested the hypothesis that intra-operative venous air embolism during semi-sitting craniotomies in humans induces thrombocytopenia.

Methods

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Competing interests
  7. References

From 1990 in our institution, with informed consent, data have been prospectively collected and entered into a database on all neurosurgical patients operated on in the semi-sitting position. Information recorded includes the patient’s name, identification number, date of birth, day of surgery, classification of the operation (elective, unscheduled, emergency), intra-operative monitoring used (e.g. central venous catheter, arterial line, precordial Doppler etc), intra-operative transfusion, peri-operative complications and operation performed. The department of anaesthesiology and intensive care medicine delivers approximately 26 000 anaesthetics per year of which more than 2000 are for neurosurgical procedures.

To identify patients who underwent semi-sitting craniotomy at our institution the following steps were performed. First, a database analysis was run, results were reviewed and all 799 patients who were tagged as ‘semi-sitting-position’ and ‘elective operation’ between 1990 and June 2009 were analysed. Second, these patients’ charts (which included a copy of the anaesthetic record) were retrieved from the archive. Third, patients' charts were reviewed and all information regarding patients' characteristics, blood tests, operation performed, positioning, monitoring used or the occurrence of venous air embolism were documented. When there were inconsistencies between the database and a patient’s chart, the information in the chart and anaesthetic record was used for analysis. Fourth, all patients with an annotation in the anaesthetic report mentioning venous air embolism or positive air aspiration were assigned to the venous air embolism group. Values for invasive arterial blood pressure, end-tidal expiratory carbon dioxide tension, mean pulmonary artery pressure, catecholamines infused, positive Doppler signal and air aspiration at the time of venous air embolism were documented. To assess the severity of venous air embolism, haemodynamic variables documented immediately before venous air embolism and the first values following venous air embolism were noted. If documentation was unclear or if important values were missing, patients were not studied for analysis.

All patients accepted for analysis were treated according to the standard operating procedures (SOPs) of our department, which are handed out to every member of the anaesthetic staff and provided online on the department’s intranet. Thus, patients were administered propofol/fentanyl anaesthesia, no nitrous oxide, had their trachea intubated and their lungs were mechanically ventilated. For continuous arterial pressure monitoring, an arterial catheter (20-18 G; Vygon GmbH, Aachen, Germany) was inserted into a radial or femoral artery. A 7.5-F multi-orifice single lumen central venous catheter (Arrow International Inc., Reading, PA, USA) was placed using the internal jugular vein to enable intra-operative air aspiration in case of venous air embolism. A 5.5-F central venous catheter was used in children if the standard catheter diameter was considered too large. The central venous catheter was always positioned into the right atrium using intracardiac ECG recordings, as described previously [15, 16]. Furthermore, end-tidal carbon dioxide tension and a precordial Doppler signal (Model 915-AL; Parks Medical Electronics, Aloha, OR, USA) were recorded continuously for venous air embolism detection, as described [17]. In addition, in all adult patients, a 7.5-F pulmonary artery catheter (CritiCath. SP5507 TD Catheter; Becton Dickinson Inc., Sandy, UT, USA) was inserted via an 8.5-F sheath introducer (Arrow International Inc) using the right internal jugular or subclavian vein, and mean pulmonary artery pressure was documented. Whenever, documentation or adherence to SOPs was unclear, the patient was not studied for analysis.

Patients were either assigned to the venous air embolism group (patients with an annotation in the anaesthetic record mentioning intra-operative venous air embolism or positive air aspiration) or no venous air embolism group (patients without documented intra-operative venous air embolism).

Age, sex, pathology and duration of surgery were recorded. Furthermore, co-morbidities such as diabetes, congestive heart failure, bleeding disorders, smoking status, asthma or chronic obstructive pulmonary disease were documented. Results of blood tests drawn at pre-operative evaluation (baseline), and immediately after surgery on admission to the intensive care unit, were analysed and included whole blood count, haematocrit, fibrinogen concentration and coagulation variables such as partial thromboplastin time (PTT), thrombin time (TT) and international normalised ratio (INR). Intra-operative transfusion requirements were also documented.

Data analysis was performed using a matched pairs design, and age, sex and pathology were considered confounding variables. One control patient was assigned to every patient with intra-operative venous air embolism. Matching was performed in a stepwise order using greedy heuristics, while the investigator was blind to the outcome, as described previously [18]. Patients were first matched for age, then for sex and finally for pathology. The best match found was used to create pairs. Whenever suitable multiple matches were identified, one was randomly selected [18]. Furthermore, whenever documentation was unclear or missing, the patient was not studied for further analysis.

The authors determined the severity of venous air embolism at the time of data analysis, using the scale previously proposed by Girard et al. [4]. Grade 1 was defined as the occurrence of a positive precordial Doppler signal without haemodynamic alterations. Grade 2 was a positive precordial Doppler signal and an increase in systolic pulmonary artery pressure of more than 5 mmHg and/or a decrease in end-tidal carbon dioxide tension of more than 3 mmHg (0.4 kPa). Grade 3 required an arterial blood pressure decrease of at least 20% or a 20% increase in heart rate in the presence of at least one positive grade-2 criterion. Grade 4 was defined as a sudden arterial blood pressure decrease of at least 40% or a 40% increase in heart rate in the presence of at least one positive grade-2 criterion. Grade 5 venous air embolism was defined as cardiocirculatory collapse in the presence of at least one positive grade-2 criterion.

Statistical analyses were performed using spss 17.0 (SPSS Inc, Chicago, IL, USA), Graph Pad Prism 5 (Graph Pad Software, La Jolla, CA, USA) and G-Power 3.1.2 (Department of Psychology, University Düsseldorf, Germany) software. Age, sex, co-morbidities, pathology, duration of surgery and intra-operative transfusion requirements were compared between groups using Student’s t-test for paired samples. Correlation of changes in platelet count and venous air embolism grade was assessed using Spearman correlation. Platelet count, haematocrit, fibrinogen concentration and coagulation variables were compared at baseline and after surgery, and between groups using two-way ANOVA with post hoc Student’s t-test and Bonferroni correction (p < 0.05/n).

Results

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Competing interests
  7. References

Incidence of venous air embolism

A total of 799 patients underwent semi-sitting craniotomy at our institution between 1990 and June 2009. Sixty-two patients were not studied for analysis due to missing medical records or incomplete documentation, especially when it was unclear whether departmental SOPs were followed.

Venous air embolism occurred in 52 patients (6.5%), of whom 18 (34.6%) had a grade-1, 20 (38.4%) a grade-2, 11 (21.2%) a grade-3 and 3 (5.7%) a grade-4 venous air embolism. No patient had a grade-5 embolism. To reduce effects of possible confounders, one control patient, matched for age, sex and pathology, was assigned to every venous air embolism patient. Matched pairs were used for further analysis with a power (1−β) of 0.97 (α = 0.05; sample size 104) for detecting differences in platelet count between groups, as assessed by post hoc power analysis.

Influence of venous air embolism on platelet count

The occurrence of a venous air embolism was associated with a fall in mean (SD) platelet count from 270 (75) × 109 l−1 to 194 (62) × 109 l−1 (p < 0.001), whereas no decrease in platelet count was seen in matched controls without venous air embolism (254 (82) × 109 l−1 to 250 (97) × 109 l−1, p = NS). Mean (SD) haematocrit values fell in both groups (venous air embolism: 0.4 (0.05) to 0.32 (0.04), p < 0.001; no venous air embolism: 0.41 (0.04) to 0.35 (0.05), p < 0.001), as shown in Fig. 1. However, normalising platelet count to haematocrit did not alter the results.

image

Figure 1.  Venous air embolism induced thrombocytopenia. Platelet count (upper graphs) decreased following venous air embolism (inline image), whereas platelet count did not change in matched controls without venous air embolism (inline image). Haematocrit (lower graphs) decreased in both groups (venous air embolism: inline image; no venous air embolism:inline image), *p < 0.0001 no venous air embolism vs venous air embolism. #p < 0.0001 baseline vs after surgery.

Download figure to PowerPoint

Influence of venous air embolism grade on platelet count

We observed a strong correlation (r = −0.602, p < 0.0001) between venous air embolism grade and the severity of thrombocytopenia. Mean platelet count fell by 66 × 109 l−1 in patients with grade-1 venous air embolism, and further decreased when associated with higher venous air embolism grades (grade-2 venous air embolism: −72 × 109 l−1; grade-3 venous air embolism: −85 × 109 l−1; grade-4 venous air embolism: −129 × 109 l−1), as depicted in Fig. 2.

image

Figure 2.  Influence of venous air embolism grade on the change in platelet count. Fifty-two patients without venous air embolism were assigned to grade 0 and compared to matched patients with grade-1 to -4 venous air embolism. Platelet count decreased following venous air embolism, from 66 × 10l−1 in grade-1 venous air embolism to up to 129 × 10l−1 in grade-4 venous air embolism. Changes in platelet count and venous air embolism grade showed a strong inverse correlation (r = −0.602, p < 0.0001).

Download figure to PowerPoint

Transfusion requirements and influence of venous air embolism on coagulation variables

Eight patients in the venous air embolism group and six matched controls without venous air embolism required intra-operative transfusion of packed red cells. A total of 21 units of red packed cells were transfused in the venous air embolism group, compared to 14 units in the matched no venous air embolism group. Transfusion requirements did not differ significantly between the groups.

The PTT, TT, INR and fibrinogen plasma concentration did not differ between groups, and were not altered following venous air embolism The only exception was a prolonged PTT in the venous air embolism group when comparing baseline values with those after surgery (Table 1).

Table 1.   Coagulation tests in patients with and without venous air embolism. Values are mean (SD).
 Venous air embolismNo venous air embolism
BaselineAfter surgeryBaselineAfter surgery
  1. PTT, partial thromboplastin time; TT, thrombin time; INR, international normalised ratio.

  2. *p = 0.044 partial thromboplastin time in the venous air embolism group comparing baseline and after surgery values.

PTT; s29.8 (4.6)35.5* (9.9)29.6 (7.8)34.5 (4.9)
TT; s19.5 (4.4)17.2 (3.9)17.6 (2.8)16.6 (2.6)
INR1.0 (0.1)1.2 (0.3)1.0 (0.1)1.0 (0.1)

Patient characteristics

Patients, used for matched pairs analysis, were from 2 to 77 years old, with a mean (SD) age of 46 (19) years. Seventeen (16%) were children with a mean (SD) age of 9.5 (5.2) years. Fifty-nine (57%) were women, and the percentage of female patients did not differ between groups. Patients’ characteristics and incidence of comorbidities are in Table 2, and showed no differences between groups. Indications for semi-sitting craniotomies included meningioma (15%), tumours of childhood (14%), metastatic cancers (14%), neurinomas (13%), vascular diseases (13%), other benign tumours (13%), other malignancies (12%) and neuralgias (7%). Neither the incidence of intracranial pathology nor the mean (SD) procedure time (venous air embolism: 200 (83) min; no venous air embolism: 186 (76) min) differed significantly between groups.

Table 2.   Characteristics of patients with and without venous air embolism. Values are mean (SD) or number (proportion).
 Venous air embolismNo venous air embolismp value
  1. COPD, chronic obstructive pulmonary disease; RPC, red packed cells.

Age; years44 (19)44 (22)0.98
Female32 (62%)27 (52%)0.45
Pathology
 Meningiomas7 (14%)9 (17%)0.59
 Tumours of childhood6 (12%)9 (17%)0.41
 Metastatic cancers9 (17%)5 (10%)0.28
 Neurinomas9 (17%)5 (10%)0.25
 Vascular diseases5 (10%)8 (15%)0.41
 Other benign tumours8 (15%)5 (10%)0.32
 Other malignancies6 (12%)6 (12%)1
 Neuralgias2 (4%)5 (10%)0.18
Comorbidity
 Diabetes2 (4%)2 (4%)1
 Congestive heart failure4 (8%)3 (6%)0.70
 Bleeding disorders4 (8%)1 (2%)0.18
 Smokers11 (21%)10 (19%)0.79
 Asthma/COPD6 (12%)2 (4%)0.16
Procedure time; min200 (83)186 (76)0.30
RPC transfusion8 (15%)6 (12%)0.53

Discussion

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Competing interests
  7. References

Our data in a large patient cohort undergoing semi-sitting craniotomy show that venous air embolism is associated with a decrease in platelet count. Comparing venous air embolism patients to age-matched controls revealed that non-lethal venous air embolism induces an almost one-third decrease in platelet count, and that even grade-1 venous air embolism evokes marked thrombocytopenia. Former studies have shown that air bubbles can affect blood coagulation in vitro by activating the complement system, or by inducing platelet aggregation [8, 11]. However, to our knowledge, there are no studies analysing whether intra-operative venous air embolism has any effect on platelet count in humans. To test the hypothesis, we used a retrospective approach allowing us to identify almost 800 patients undergoing semi-sitting craniotomy, of whom 52 had a venous air embolism. The large sample size provided high statistical power which otherwise would be hard to achieve. All procedures were performed according to the SOPs, adding to consistency in management.

Our data show a 6.5% incidence of venous air embolism, which is in accordance with some of the recent literature [1, 19]. However, the reported incidence of venous air embolism varies widely, from 2 to 80%, [1, 3, 19–22]. The incidence will vary depending on the method of monitoring and definition of venous air embolism. Minor events are likely to remain unnoticed in routine clinical practice [19]. In our study, patients were assigned to the no venous air embolism group if venous air embolism was undocumented or undetected. This is a conservative analysis, emphasising the relevance of the observed decrease in platelet count following venous air embolism.

Our study revealed a significant fall in platelet count in non-lethal venous air embolism, with a strong correlation between venous air embolism grade and the fall in platelet count. This effect agrees with our data obtained in anaesthetised swine, showing a 47% decrease in platelet count following lethal, high dose venous air embolism, with an average of 4.6 ml.kg−1 of air infused [13].

The observed decrease in platelet count was surprisingly large considering that platelets are stored in various vascular compartments, ready to be released from megakaryocytes into the circulation whenever necessary [23, 24]. While we cannot pinpoint the mechanisms responsible for the marked decrease in platelet count following venous air embolism, the decrease in platelet count could be attributable to several pathophysiological effects. Firstly, intravascular air induces direct binding of platelets to air bubbles, forming air-platelet conglomerates [11, 12]. Secondly, pulmonary air embolism causes gaps between endothelial cells and consequential mediator release, which in turn can lead to platelet or complement activation [5–7, 25]. In vitro, direct air-blood contact leads to platelet activation and subsequent platelet aggregation [8, 11]. In turn, activated platelets adhere to and coat air bubbles, thus stabilising them [8, 12]. The formation of platelet-air-clots affects air reabsorption, and thus is likely to contribute to a sustained increase in right ventricular afterload, and prolonged occlusion of pulmonary arterioles or capillaries might aggravate cardiopulmonary complications of venous air embolism [11, 26].

Haematocrit fell in both groups when comparing baseline to postoperative values. This is due to peri-operative haemodilution, since, in addition to a crystalloid infusion, 500 ml colloid was administered before positioning the patient into the semi-sitting position. However, normalising the platelet count to haematocrit did not alter the results.

Coagulation variables did not differ between or within groups, apart from the average PTT measured after surgery, which was slightly prolonged following venous air embolism. However, even in lethal venous air embolism in swine, coagulation variables were poor at identifying venous air embolism induced coagulation abnormalities [13]. In contrast, rotational thrombelastometry and impedance aggregometry showed a high sensitivity for detecting venous air embolism induced platelet dysfunction in swine [13].

Patients with a major venous air embolism who already have bleeding disorders or pre-existing thrombocytopenia may be particularly at risk for peri-operative bleeding, as there is a relationship between the grade of venous air embolism and the severity of thrombocytopenia, with a greater fall in platelet count with a higher grade of venous air embolism. Further studies could evaluate whether venous air embolism is associated with an increase in intracerebral bleeding or worsened neurological outcome. Based on our data, it might be rational to reassess blood coagulation and platelet count intra-operatively, following venous air embolism. Near-patient tests such as rotational thrombelastometry and impedance aggregometry will allow immediate and sophisticated analysis of platelet function and whole blood coagulation [27–29].

Competing interests

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Competing interests
  7. References

No external funding and no competing interests declared.

References

  1. Top of page
  2. Summary
  3. Methods
  4. Results
  5. Discussion
  6. Competing interests
  7. References
  • 1
    Jadik S, Wissing H, Friedrich K, Beck J, Seifert V, Raabe A. A standardized protocol for the prevention of clinically relevant venous air embolism during neurosurgical interventions in the semisitting position. Neurosurgery 2009; 64: 5338.
  • 2
    Mammoto T, Hayashi Y, Ohnishi Y, Kuro M. Incidence of venous and paradoxical air embolism in neurosurgical patients in the sitting position: detection by transesophageal echocardiography. Acta Anaesthesiologica Scandinavica 1998; 42: 6437.
  • 3
    Souders JE. Pulmonary air embolism. Journal of Clinical Monitoring and Computing 2000; 16: 37583.
  • 4
    Girard F, Ruel M, McKenty S, et al. Incidences of venous air embolism and patent foramen ovale among patients undergoing selective peripheral denervation in the sitting position. Neurosurgery 2003; 53: 3169.
  • 5
    Townsley MI, Barman SA, Taylor AE. Pulmonary embolism: emboli and fibrinolysis inhibition in isolated canine lungs. American Journal of Physiology 1990; 258: H7548.
  • 6
    Albertine KH, Wiener-Kronish JP, Koike K, Staub NC. Quantification of damage by air emboli to lung microvessels in anesthetized sheep. Journal of Applied Physiology 1984; 57: 13608.
  • 7
    Moosavi H, Utell MJ, Hyde RW, et al. Lung ultrastructure in noncardiogenic pulmonary edema induced by air embolization in dogs. Laboratory Investigation 1981; 45: 45664.
  • 8
    Thorsen T, Klausen H, Lie RT, Holmsen H. Bubble-induced aggregation of platelets: effects of gas species, proteins, and decompression. Undersea and Hyperbaric Medicine 1993; 20: 10119.
  • 9
    Nossum V, Hjelde A, Bergh K, Ustad AL, Brubakk AO. Anti-C5a monoclonal antibodies and pulmonary polymorphonuclear leukocyte infiltration – endothelial dysfunction by venous gas embolism. European Journal of Applied Physiology 2003; 89: 2438.
  • 10
    Nossum V, Koteng S, Brubakk AO. Endothelial damage by bubbles in the pulmonary artery of the pig. Undersea and Hyperbaric Medicine 1999; 26: 18.
  • 11
    Barak M, Katz Y. Microbubbles: pathophysiology and clinical implications. Chest 2005; 128: 291832.
  • 12
    Eckmann DM, Armstead SC, Mardini F. Surfactants reduce platelet-bubble and platelet-platelet binding induced by in vitro air embolism. Anesthesiology 2005; 103: 120410.
  • 13
    Schafer ST, Neumann A, Lindemann J, Gorlinger K, Peters J. Venous air embolism induces both platelet dysfunction and thrombocytopenia. Acta Anaesthesiologica Scandinavica 2009; 53: 73641.
  • 14
    Velik-Salchner C, Schnurer C, Fries D, et al. Normal values for thrombelastography (ROTEM) and selected coagulation parameters in porcine blood. Thrombosis Research 2006; 117: 597602.
  • 15
    Gebhard RE, Szmuk P, Pivalizza EG, Melnikov V, Vogt C, Warters RD. The accuracy of electrocardiogram-controlled central line placement. Anesthesia and Analgesia 2007; 104: 6570.
  • 16
    McGee WT, Ackerman BL, Rouben LR, Prasad VM, Bandi V, Mallory DL. Accurate placement of central venous catheters: a prospective, randomized, multicenter trial. Critical Care Medicine 1993; 21: 111823.
  • 17
    Chang JL, Albin MS, Bunegin L, Hung TK. Analysis and comparison of venous air embolism detection methods. Neurosurgery 1980; 7: 13541.
  • 18
    Stuart EA. Comparison of multivariate matching methods: structures, distances, and algorithms. In: OsborneJ, ed. Best Practices in Quantitative Social Science. Thousand Oaks: Sage Publishing, 2007; 15575.
  • 19
    Shaikh N, Ummunisa F. Acute management of vascular air embolism. Journal of Emergencies, Trauma and Shock 2009; 2: 1805.
  • 20
    Papadopoulos G, Kuhly P, Brock M, Rudolph KH, Link J, Eyrich K. Venous and paradoxical air embolism in the sitting position. A prospective study with transoesophageal echocardiography. Acta Neurochirurgica (Wien) 1994; 126: 1403.
  • 21
    Stendel R, Gramm HJ, Schroder K, Lober C, Brock M. Transcranial Doppler ultrasonography as a screening technique for detection of a patent foramen ovale before surgery in the sitting position. Anesthesiology 2000; 93: 9715.
  • 22
    Tobias JD, Johnson JO, Jimenez DF, Barone CM, McBride DS Jr. Venous air embolism during endoscopic strip craniectomy for repair of craniosynostosis in infants. Anesthesiology 2001; 95: 3402.
  • 23
    Takizawa H, Eto K, Yoshikawa A, Nakauchi H, Takatsu K, Takaki S. Growth and maturation of megakaryocytes is regulated by Lnk/Sh2b3 adaptor protein through crosstalk between cytokine- and integrin-mediated signals. Experimental Hematology 2008; 36: 897906.
  • 24
    Bluteau D, Lordier L, Di Stefano A, et al. Regulation of megakaryocyte maturation and platelet formation. Journal of Thrombosis and Haemostasis 2009; 7(Suppl. 1): 22734.
  • 25
    Liu YC, Kao SJ, Chuang IC, Chen HI. Nitric oxide modulates air embolism-induced lung injury in rats with normotension and hypertension. Clinical and Experimental Pharmacology and Physiology 2007; 34: 117380.
  • 26
    Fitchet A, Fitzpatrick AP. Central venous air embolism causing pulmonary oedema mimicking left ventricular failure. British Medical Journal 1998; 316: 6046.
  • 27
    Calatzis A, Wittwer M, Krueger B. A new approach to platelet function analysis in whole blood – the multiplate analyzer. Platelets 2004, 15: 4856.
  • 28
    von Pape KW, Dzijan-Horn M, Bohner J, Spannagl M, Weisser H, Calatzis A. Control of aspirin effect in chronic cardiovascular patients using two whole blood platelet function assays. PFA-100 and multiplate. Hamostaseologie 2007; 27: 15560.
  • 29
    Flisberg P, Rundgren M, Engstrom M. The effects of platelet transfusions evaluated using rotational thromboelastometry. Anesthesia and Analgesia 2009; 108: 14302.