Does the platelet function analyser (PFA-100®) predict blood loss after cardiopulmonary bypass?

M. Fattorutto, O. Pradier, D. Schmartz, B. Ickx and L. Barvais

Department of Anaesthesiology and Haematology, Hopital Erasme, 808 route de Lennik, B-1070 Brussels, Belgium

Corresponding author. E-mail: m.fattorutto@swing.be

Accepted for publication: January 13, 2003


    Abstract
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 Abstract
 Introduction
 Methods and results
 Comments
 References
 
Background. This study was designed to determine if a new point-of-care test (PFA-100® platelet function analyser) that assesses platelet function predicts blood loss after cardiac surgery.

Methods and results. Blood samples from 70 patients were drawn before and after cardiopulmonary bypass (CPB) for PFA-100® measurements. The system consists of a cartridge in which a membrane and an aperture are coated with either collagen/adenosine-5'-diphosphate or collagen/epinephrine. The instrument determines the time required for full occlusion of the aperture (closure time). We observed a weak correlation between pre-CPB collagen/epinephrine closure time and second-hour mediastinal blood loss (r=0.34, P=0.01). The sensitivity and positive predictive value of the PFA-100® measurements were comparable to platelet count for predicting excessive bleeding after CPB (75 and 27% vs 100 and 25%, respectively).

Conclusions. The PFA-100® is a logical test for detecting patients who could have excessive bleeding after CPB. However, the PFA-100® was not able to separate patients at low risk of subsequent bleeding from those who had substantial bleeding.

Br J Anaesth 2003; 90: 692–3

Keywords: heart, cardiopulmonary bypass; blood, platelets; complications, haemorrhage


    Introduction
 Top
 Abstract
 Introduction
 Methods and results
 Comments
 References
 
Platelet dysfunction is the most important reason for bleeding after cardiopulmonary bypass (CPB).1 A device designed to simulate platelet-dependent haemostasis in whole blood in vitro has recently been developed.2 We studied if the platelet function analyser (PFA-100®) could predict blood loss after CPB.


    Methods and results
 Top
 Abstract
 Introduction
 Methods and results
 Comments
 References
 
After institutional review board approval and written informed consent, patients undergoing elective heart surgery with CPB were enrolled. Seventy patients with normal coagulation function and platelet counts in whom antiplatelet drugs had been withdrawn for at least 5 days before surgery were studied. Aprotinin was given to all patients. Heparin was given to maintain an activated coagulation time (ACT) greater than 480 s and reversed with protamine sulfate to return ACT to baseline value. Blood samples were collected before CPB (T1) and after protamine-induced heparin neutralization (T2). The following variables were measured: haematocrit, platelet count and platelet aggregation. Following a randomization table, the aggregation studies were performed in 20 patients on platelet-rich plasma (Platelet Aggregation Profiler-4®, Hatboro, USA). The agonist solution included ADP 5 µmol litre–1. The PFA-100® creates an artificial vessel consisting of a bioactive membrane with a microscopic aperture.2 Anticoagulated whole blood is aspirated through a capillary under steady high shear rates (5000–6000 s–1). A controlled negative pressure aspirates blood across a microscopic aperture cut into the membrane, which is coated with equine type I 2 µg collagen and either epinephrine bitartrate 10 µg or adenosine-5'-diphosphate (ADP) 50 µg. The presence of the platelet agonist and the high shear rates result in a platelet plug that gradually occludes the aperture. The time required to obtain full occlusion of the aperture is defined as the collagen/ADP closure time (CACT) or collagen/epinephrine closure time (CECT). Any closure time greater than 300 s was reported as 300 s. Mediastinal blood loss (MBL) was recorded during the first, second, 12th and 24th hour. Excessive MBL was defined as >200 ml for two successive hours. Abnormal test results (a positive test value) were defined as CECT or CACT=300 s. All variables were assessed for normality of distribution using the Shapiro–Wilk test. Continuous data were compared using the paired Student’s t-test. Spearman’s rank correlation test was used to assess the relationship between MBL and closure time, platelet aggregation or platelet count. Comparison of categorical data was done with the {chi}2-test. All results are expressed as mean (SD). A P-value <0.05 was considered as statistically significant.

The mean total MBL was 495 (SD 301) ml and the mean CPB time was 105 (26) min. The incidence of excessive MBL was 6%. A significant increase in CECT and CACT values occurred between pre-CPB and time after protamine period (192 (71) vs 232 (65) s, P=0.005 and 119 (53) vs 143 (53) s, P=0.05). There was a significant decrease in ADP-induced platelet aggregation after CPB (72 (13) vs 40 (17)%, P=0.005). Similarly, there was a significant decrease in platelet count after CPB (214 (33) vs 140 (22)x109 litre–1, P=0.001) No correlation was found between pre-CPB ADP-induced platelet aggregation and CACT. However, a weak correlation was found between ADP-induced platelet aggregation and CACT after protamine (r=–0.40, P=0.05). The pre-CPB CECT measurement correlated weakly with first- and second-hour MBL (r=0.32, P=0.01 and r=0.34, P= 0.01, respectively). On the other hand, there was no correlation between platelet count and MBL. The pre-CPB CECT had a sensitivity and positive predictive value comparable to the platelet count after protamine for predicting excessive blood loss after CPB (sensitivity 75% and 100%; positive predictive value 27% and 25%, respectively) (Table 1).


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Table 1 PFA-100® and platelet count results in relation to mediastinal blood loss after cardiopulmonary bypass (CPB) (>200 ml h–1 for two successive hours)
 

    Comments
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 Abstract
 Introduction
 Methods and results
 Comments
 References
 
Measurement of closure time by PFA-100® depends on functional platelets GPIb and GPIIb/IIIa, von Willebrand factor, platelet count and haematocrit.2 All these variables are altered by contact of blood with extracorporeal circulation.1 As expected, closure times after CPB increased compared with pre-CPB value. This supports previous reports.3 4 However, to show that this platelet function test is accurate it should be related to standard tests of platelet function, including platelet aggregometry. We found a significant correlation between ADP-induced platelet aggregation and CACT, and previous reports have found a correlation between PFA-100® results and aggregometry.5 The positive predictive value presented in the current study corroborates recent observations suggesting that the PFA-100® failed to predict bleeding after CPB.6


    References
 Top
 Abstract
 Introduction
 Methods and results
 Comments
 References
 
1 Rinder CS, Mathew JP, Rinder HM, Bonan J, Ault KA, Smith BR. Modulation of platelet surface adhesion receptors during cardiopulmonary bypass. Anesthesiology 1991; 75: 563–70[ISI][Medline]

2 Kundu SK, Heilmann EJ, Sio R, Garcia C, Ostgaard RA. Characterisation of an in vitro platelet function analyser, PFA-100TM. Clin Appl Thromb Hemost 1996; 2: 241–9[ISI]

3 Lasne D, Fiemeyer A, Chatellier G, Chammas C, Baron JF, Aiach M. A study of platelet functions with a new analyser using high shear stress (PFA100TM) in patients undergoing coronary artery bypass graft. Thromb Haemost 2000; 84: 794–9[ISI][Medline]

4 Wahba A, Sander S, Birnbaum DE. Are in-vitro platelet function tests useful in predicting blood loss following open heart surgery? Thorac Cardiovasc Surg 1998; 46: 228–31[ISI][Medline]

5 Mammen EF, Comp PC, Gosselin R, et al. PFA-100TM system: A new method for assessment of platelet dysfunction. Semin Thromb Hemost 1998; 24: 195–202[ISI][Medline]

6 Slaughter TF, Sreeram G, Sharma AD, El-Moalem H, East CJ, Greenberg CS. Reversible shear-mediated platelet dysfunction during cardiac surgery as assessed by the PFA-100® platelet function analyser. Blood Coagul Fibrinolysis 2001; 12: 85–93[CrossRef][ISI][Medline]





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