By Betty Tran, MD, MSc
Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago
SYNOPSIS: In this multicenter, randomized, controlled, noninferiority trial of patients with severe thrombocytopenia, prophylactic platelet transfusion prior to central venous catheter (CVC) placement resulted in less CVC-related bleeding.
SOURCE: van Baarle FLF, van de Weerdt EK, van der Velden WJFM, et al. Platelet transfusion before CVC placement in patients with thrombocytopenia. N Engl J Med 2023;388:1956-1965.
Both central venous catheter (CVC) placement and blood transfusions are common events in the intensive care unit (ICU), and both are associated with potential risks. There is a paucity of good-quality evidence to inform the platelet-transfusion threshold for safe placement of a CVC. On the other hand, blood transfusions can have adverse consequences, including circulatory overload, acute lung injury, and alloimmunization, in addition to being both a limited and expensive resource, especially as platelet concentrates have a shorter life span compared to other blood products (five days compared to 42 days for packed red blood cells, for example).1 The Randomized, Controlled Trial on Prophylactic Platelet Transfusion Prior to Central Venous Catheter Placement in Patients with Thrombocytopenia (PACER) trial hypothesized that withholding prophylactic platelet transfusion in patients with platelets between 10,000 to 50,000/mm3 would not increase the risk of CVC-related bleeding.
This randomized, controlled, noninferiority trial was conducted at multiple hematology wards and ICUs across the Netherlands and included 393 CVC placements in 358 patients with platelets between 10,000 to 50,000/mm3 within 24 hours of CVC placement. Exclusion criteria included other factors that increased bleeding risk, such as therapeutic anticoagulation, coagulation factor deficiencies, and international normalized ratio (INR) > 3.0. Patients randomized to the transfusion group received one unit of platelet concentrate prior to CVC placement. CVC placement was done under ultrasound guidance by operators who had performed at least 50 CVC placements; operators were unaware of the trial assignment if possible, and catheters were placed approximately one hour after randomization. All types of CVCs (including tunneled catheters) and placement sites were included.
The primary outcome was catheter-related bleeding of grade 2 to 4 within 24 hours of placement and was assessed at hour 1 and hour 24. Grading was as follows: 0 (no bleeding), 1 (oozing, hematoma, < 20 minutes of manual compression to stop), 2 (bleeding requiring minor interventions to stop, such as > 20 minutes manual compression), 3 (bleeding requiring radiologic or elective operative intervention or red cell transfusion), or 4 (bleeding associated with hemodynamic instability, tachycardia, increased red cell transfusion, or fatal bleeding). Secondary outcomes, which were not adjusted for multiplicity, included major (grade 3 or 4) bleeding, grade 1 bleeding, need for transfusion within 24 hours of CVC placement, hemoglobin and platelet levels at one and 24 hours, allergic transfusion reactions, onset of acute lung injury within 48 hours, length of ICU and hospital stays, in-hospital mortality, and financial costs.
Among 393 CVC placements, catheter-related bleeding of grade 2 to 4 occurred in 4.8% of patients in the transfusion group and 11.9% of patients in the no-transfusion group (relative risk, or RR, of 2.45; 90% confidence interval [CI], 1.27 to 4.70). The risk of grade 3 bleeding was lower in the transfusion group vs. the no-transfusion group (2.1% vs. 4.9%; RR, 2.43; 95% CI, 0.75 to 7.93), and there were no grade 4 bleeding events. In terms of other secondary outcomes, platelet levels were higher at one and 24 hours in the transfusion group, the no-transfusion group received more platelet transfusions in the 24 hours after CVC placement, three allergic transfusion reactions occurred (one in the no-transfusion group) with one case of acute lung injury, length of ICU stay was slightly shorter in the no-transfusion group, and mortality was similar in the two groups. The total cost difference per catheter was higher in the transfusion group by $410, driven mainly by a cost of $682 for prophylactic platelet transfusion. However, transfusion costs in the 24 hours after CVC placement were higher in the no-transfusion group due to higher platelet transfusions related to bleeding in this group.
COMMENTARY
Perhaps surprisingly, in contrast to their hypothesis, the investigators found that noninferiority was not shown in withholding prophylactic platelet transfusion in patients with platelets between 10,000 to 50,000/mm3 in terms of grade 2 to 4 CVC-related bleeding. Although no grade 4 bleeding events occurred, the cost savings of foregoing prophylactic platelet transfusion was nullified when considering the need for post-CVC platelet transfusions in patients in the no-transfusion group, especially among those with a platelet count of 10,000 to 30,000/mm3 and were more commonly on the hematology wards.
These findings emphasize that adequate platelet counts are important in preventing CVC-related bleeding and are mirrored in guidelines from several organizations, including the Association for the Advancement of Blood and Biotherapies (AABB) and Society of Interventional Radiology, who endorse prophylactic platelet transfusion before CVC placement in patients with platelets below 20,000/mm3.2,3
Despite the findings noted earlier, I agree with the authors in their conclusion that a more personalized assessment should be made regarding platelet transfusion strategy in these patients with thrombocytopenia. First, to some degree, a platelet count of 20,000/mm3 as a safety threshold is arbitrary, since platelet function should be considered as well. Second, in terms of the study population, patients with hematologic malignancies who likely require ongoing platelet transfusions longer term are likely a different population than ICU patients who may have a temporary decrease in platelet counts and are under more intense monitoring; the former may derive more benefit from prophylactic platelet transfusion pre-CVC placement than the latter. On the other hand, the hematologic patient is at higher risk for transfusion-related adverse events given the sheer number of transfusions they receive overall. In summary, as with many medical issues, the risk/benefit ratio for intervention, in this case platelet transfusion, is best assessed at the individual patient level.
REFERENCES
- American Red Cross: Blood Components. How can one donation help multiple people? https://www.redcrossblood.org/donate-blood/how-to-donate/types-of-blood-donations/blood-components.html
- Kaufman RM, Djulbegovic B, Gernsheimer T, et al. Platelet transfusion: A clinical practice guideline from the AABB. Ann Intern Med 2015;162:205-213.
- Patel IJ, Rahim S, Davidson JC, et al. Society of Interventional Radiology consensus guidelines for the periprocedural management of thrombotic and bleeding risk in patients undergoing percutaneous image-guided interventions—Part II: Recommendations: Endorsed by the Canadian Association for Interventional Radiology and the Cardiovascular and Interventional Radiological Society of Europe. J Vasc Interv Radiol 2019;30:1168-1184.
