Are the Point-of-Care Diagnostics MULTIPLATE and ROTEM Valid in the Setting of High Concentrations of Heparin and Its Reversal With Protamine?

doi:10.1053/j.jvca.2010.11.020

Journal of Cardiothoracic and Vascular Anesthesia

Volume 25, Issue 6, December 2011, Pages 981-986

https://doi.org/10.1053/j.jvca.2010.11.020 Get rights and content

Objectives

To evaluate the in vitro effects of high concentrations of heparin and its reversal with protamine on routine laboratory parameters as well as on modified thromboelastogram (ROTEM; TEM International, Munich, Germany) and impedance aggregometry (MULTIPLATE; Dynabyte, Munich, Germany).

Design

An observational, nonrandomized in vitro study.

Setting

A single-center, university hospital.

Participants

Ten healthy volunteers.

Interventions

Heparinization of whole blood to levels of 2, 4, 6, and 8 IU/mL of heparin and reversal with protamine. For MULTIPLATE measurements, heparin levels up to 20 IU/mL were tested.

Measurements and Main Results

The present results show that the prothrombin time (PT) and fibrinogen measurements are altered significantly by heparin concentrations above 2 IU/mL. Protamine reversal also affected coagulation tests except for the fibrinogen. The INTEM test using the ROTEM system was influenced significantly by heparin concentrations of 2 IU/mL or higher, whereas EXTEM measurements remained stable up to 4 IU/mL. The findings for the FIBTEM test were stable up to 6 IU/mL but then declined to values less than 50% of baseline at 8 IU/mL. HEPTEM results remained valid under all concentrations of heparin tested. The effect of protamine on ROTEM was seen mainly in the INTEM and HEPTEM measurements. Heparin concentrations up to a level of 20 U/mL had no effect on MULTIPLATE measurements. Effects of protamine on MULTIPLATE became significant at heparin-to-protamine ratios below 1:1 and were more pronounced for adenosine diphosphate than for thrombin receptor-activated protein testing.

Conclusions

Neither fibrinogen (Clauss) nor derived fibrinogen or FIBTEM testing is valid in the setting of high concentrations of heparin unless antagonized by heparinase. Reversal of heparin with protamine worsens platelet function at all ratios as detected by aggregometry (MULTIPLATE) and thromboelastography (ROTEM), starting at a 1:1 ratio. Therefore, appropriate coagulation testing under cardiopulmonary bypass conditions should be selected carefully according to heparin levels. In particular, fibrinogen values are falsely low at heparin levels of 2 IU/mL and above. Therefore, newer algorithms promoting the correction of fibrinogen levels on cardiopulmonary bypass should be based on appropriate testing.

Section snippets

Methods

Ten healthy volunteers were recruited from the authors' department, and informed consent was obtained. All refrained from taking any medication that could possibly interfere with coagulation or platelet function for more than a week. Institutional review board approval was waived because of the in vitro nature of the study.

Blood was drawn from a venipuncture site with a 21-G butterfly needle into 3.8-mL tubes containing 0.38 mL (0.129 mol/L) buffered (pH 5.5) sodium citrate (Sarstedt,

Results

Of the 10 test subjects, 2 were female. None of the test subjects suffered from subclinical cell counts or coagulation abnormalities that could interfere with testing.9, 10 Baseline values for complete blood counts were a hemoglobin of 14.0 ± 0.8 mg/dL and a platelet count of 218,000 ± 31,000/μL. Baseline coagulation values are presented in Table 1 and Figure 1.

PT, PTT, and fibrinogen Clauss and derived fibrinogen measurements were influenced significantly by heparin concentrations starting at

Discussion

The authors were able to show that heparin plasma levels higher than 2 IU/mL can alter regular laboratory results as well as certain tests of the ROTEM monitoring system.

This in vitro study showed that unmodified PT, PTT, and fibrinogen tests are not applicable to blood samples with high heparin concentrations. INTEM testing started to change at 2 IU/mL, whereas EXTEM and FIBTEM results were only altered significantly at heparin levels above 4 IU/mL. HEPTEM testing using heparinase I

Acknowledgment

The authors acknowledge the exceptional assistance of the medical technicians in the blood bank and the hospital laboratory as well as Doris Kienmoser for her assistance creating the graphs.

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Original articleAre the Point-of-Care Diagnostics MULTIPLATE and ROTEM Valid in the Setting of High Concentrations of Heparin and Its Reversal With Protamine?

Objectives

Design

Setting

Participants

Interventions

Measurements and Main Results

Conclusions

Section snippets

Methods

Results

Discussion

Acknowledgment

J Cardiothorac Vasc Anesth

Br J Anaesth

Br J Anaesth

Thromb Res

Blood

J Cardiothorac Vasc Anesth

Br J Anaesth

Br J Anaesth

Thromb Res

Ann Thorac Surg

Biochim Biophys Acta

Blood

Ann Thorac Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Rapid evaluation of coagulopathies after cardiopulmonary bypass in children using modified thromboelastography

Anesth Analg

Perioperative coagulation management and control of platelet transfusion by point-of-care platelet function analysis

Transfus Med Hemother

Lack of correlation between activated clotting time and plasma heparin during cardiopulmonary bypass

Ann Surg

Thrombelastography/thromboelastometry

Clin Lab Haematol

Original article
Are the Point-of-Care Diagnostics MULTIPLATE and ROTEM Valid in the Setting of High Concentrations of Heparin and Its Reversal With Protamine?