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Table 1.  Demographic Characteristics and Outcomes of Patients With Platelet Counts of 50 × 103/μL or Above vs Below 50 × 103/μL
Demographic Characteristics and Outcomes of Patients With Platelet Counts of 50 × 103/μL or Above vs Below 50 × 103/μL
Table 2.  Risk Factors for Perioperative Bleeding on Multivariable Regression
Risk Factors for Perioperative Bleeding on Multivariable Regression
1.
Estcourt  LJ, Desborough  M, Hopewell  S, Doree  C, Stanworth  SJ.  Comparison of different platelet transfusion thresholds prior to insertion of central lines in patients with thrombocytopenia.   Cochrane Database Syst Rev. 2015;(12):CD011771. doi:10.1002/14651858.CD011771 PubMedGoogle Scholar
2.
Patel  RM, Josephson  C.  Neonatal and pediatric platelet transfusions: current concepts and controversies.   Curr Opin Hematol. 2019;26(6):466-472. doi:10.1097/MOH.0000000000000542PubMedGoogle ScholarCrossref
3.
Zeidler  K, Arn  K, Senn  O, Schanz  U, Stussi  G.  Optimal preprocedural platelet transfusion threshold for central venous catheter insertions in patients with thrombocytopenia.   Transfusion. 2011;51(11):2269-2276. doi:10.1111/j.1537-2995.2011.03147.x PubMedGoogle ScholarCrossref
4.
Josephson  CD, Granger  S, Assmann  SF,  et al.  Bleeding risks are higher in children versus adults given prophylactic platelet transfusions for treatment-induced hypoproliferative thrombocytopenia.   Blood. 2012;120(4):748-760. doi:10.1182/blood-2011-11-389569 PubMedGoogle ScholarCrossref
5.
Oakley  FD, Woods  M, Arnold  S, Young  PP.  Transfusion reactions in pediatric compared with adult patients: a look at rate, reaction type, and associated products.   Transfusion. 2015;55(3):563-570. doi:10.1111/trf.12827 PubMedGoogle ScholarCrossref
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    Research Letter
    Pacific Coast Surgical Association
    June 30, 2021

    Association of Thrombocytopenia With Bleeding Risk During Central Venous Catheter Placement in Pediatric Patients With Cancer

    Author Affiliations
    • 1Department of Surgery, University of California, Davis, Sacramento
    • 2Division of Pediatric Surgery, Shriners Hospital for Children Northern California, Sacramento
    JAMA Surg. 2021;156(9):887-889. doi:10.1001/jamasurg.2021.2080

    Tunneled central venous catheters (CVCs) are frequently required in pediatric patients with cancer, but data on platelet transfusion thresholds in this population are limited. The commonly used threshold of 50 × 103/μL (to convert platelet count to ×109/L, multiply by 1) is based on expert opinion.1,2 This study compared bleeding complications in pediatric patients with a platelet count of 50 × 103/μL or above vs below 50 × 103/μL.

    Methods

    We performed a retrospective cohort study of patients younger than 18 years who had cancer and underwent CVC placement at a tertiary pediatric hospital between January 1, 2014, and December 31, 2019. The primary outcome was perioperative bleeding. Bleeding was classified as minor if there was documentation of a hematoma or oozing requiring pressure or a topical hemostatic agent. Bleeding was classified as major if the patient required red blood cell transfusion, return to the operating room, or any invasive procedure for bleeding. This study was approved by the institutional review board at the University of California, Davis and conducted by medical record review with no patient contact or intervention; therefore, informed consent was waived. We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. Statistical analysis was performed using the Kruskall-Wallis test, χ2 test, and multivariable logistic regression were used. Covariates for logistic regression were selected according to plausibility and/or demonstrated association and included age, weight, preoperative hemoglobin level, solid tumor vs hematologic malignant neoplasm, and use of a Broviac catheter vs a port-a-cath. Two-sided P values were significant at P < .05. Statistical analysis was performed in Minitab (Minitab, LLC).

    Results

    Among the 235 patients included in the study, the median age was 6 years (interquartile range [IQR], 3-12 years), the median weight was 21 kg (IQR, 15-43 kg), 139 (59.1%) were boys, and 96 (40.9%) were girls. From this cohort, a total of 279 CVC placements were included. At the time of CVC insertion, 22 patients (7.8%) had platelet counts below 50 × 103/μL (Table 1). Patients with platelet counts below 50 × 103/μL had higher rates of hematologic malignant neoplams (19 of 22 patients [86.4%] vs 145 of 257 [56.4%]; P = .01) and lower absolute neutrophil counts (median [IQR], 400/μL [205-1150/μL] vs 3000 [1159-3000/μL]; P < .001) (to convert to ×109/L, multiply by 0.001). Of patients with a platelet count below 50 × 103/μL, 13 (59.1%) received a planned intraoperative platelet transfusion. These patients had preoperative platelet counts similar to those who were not transfused (34 vs 41 × 103/μL, P = .23).

    The overall incidence of perioperative bleeding was 3.2% (n = 9). Bleeding was more frequent in patients with a preoperative platelet count below 50 × 103/μL (3 patients [13.6%] vs 6 [2.3%]; P = .03). Minor bleeding occurred at higher rates in patients with platelet counts below 50 × 103/μL (3 patients [13.6%] vs 3 [1.2%]; P = .01). Major bleeding occurred in 3 patients (1.1%), and all of these episodes occurred in patients with platelet counts of 50 × 103/μL or above (Table 1). Two patients had oozing postoperatively with an associated hemoglobin level decrease greater than 1 g/dL (to convert to g/L, multiply by 10) and received a 15-mL/kg transfusion of red blood cells. One patient developed a hematoma with an associated hemoglobin level decrease of 3 g/dL and received a 10-mL/kg transfusion of red blood cells. On multivariate analysis, only a preoperative platelet count below 50 × 103/μL was significant risk factor for perioperative bleeding complications (adjusted odds ratio, 6.3; 95% CI, 1.3-30.0; P = .02) (Table 2).

    Discussion

    To our knowledge, this was the largest study evaluating the association of preoperative thrombocytopenia with bleeding risk during CVC placement in pediatric patients with cancer. This study found that a platelet count below 50 × 103/μL was associated with an increased risk of perioperative bleeding. However, this pertained only to minor bleeding complications.

    Central venous catheters placement can be performed in adults at platelet counts of 20 × 103/μL to 50 × 103/μL without increased bleeding episodes.3 However, the applicability of adult data to pediatric patients is limited. Children have both a higher bleeding risk4 and higher rates of transfusion reactions to platelets.5 While these data suggest that children with a platelet count below 50 × 103/μL may experience higher rates of minor bleeding complications, we also found that major bleeding complications were exceedingly rare and may not be associated with a threshold of 50 × 103/μL. Of note, many patients with platelet counts below 50 × 103/μL received intraoperative transfusions, which may have protected against bleeding complications.

    This study was limited by its single-center, retrospective nature and the relatively low number of patients with a platelet count below 50 × 103/μL. We were unable to perform an analysis to assess an optimal platelet threshold owing to the rarity of bleeding complications. Furthermore, patients with lower platelet counts had predominantly hematologic malignant neoplasms; however, the type of malignant neoplasm was not a significant risk factor for bleeding complications on multivariate analysis.

    Conclusions

    The findings of this cohort study suggest that a platelet count below 50 × 103/μL may be associated with increased rates of minor bleeding complications in pediatric patients with cancer; however, major bleeding complications are rare and may not be associated with this threshold. For patients with thrombocytopenia, the risk of minor bleeding complications must be weighed against the risk of receiving platelet transfusions.

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    Article Information

    Accepted for Publication: April 4, 2021.

    Published Online: June 30, 2021. doi:10.1001/jamasurg.2021.2080

    Corresponding Author: Sarah C. Stokes, MD, Department of Surgery, University of California, Davis, 2335 Stockton Blvd, Room 5107, Sacramento, CA 95817 (scstokes@ucdavis.edu).

    Author Contributions: Dr Stokes had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Stokes, Brown.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Stokes.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Stokes, Brown.

    Supervision: Brown.

    Conflict of Interest Disclosures: None reported.

    Funding/Support: The study was supported by grant UL1 TR001860 from the National Center for Advancing Translational Sciences, which is funded by the National Institutes of Health (Dr Brown).

    Role of the Funder/Sponsor: The National Institutes of Health had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Disclaimer: The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

    Meeting Presentation: This paper was presented at the virtual American College of Surgeons Clinical Congress; October 4, 2020, and was accepted for presentation at the 92nd Annual Meeting of the Pacific Coast Surgical Association Meeting; February 18-20, 2021; Monterey, California. However, that meeting was canceled.

    References
    1.
    Estcourt  LJ, Desborough  M, Hopewell  S, Doree  C, Stanworth  SJ.  Comparison of different platelet transfusion thresholds prior to insertion of central lines in patients with thrombocytopenia.   Cochrane Database Syst Rev. 2015;(12):CD011771. doi:10.1002/14651858.CD011771 PubMedGoogle Scholar
    2.
    Patel  RM, Josephson  C.  Neonatal and pediatric platelet transfusions: current concepts and controversies.   Curr Opin Hematol. 2019;26(6):466-472. doi:10.1097/MOH.0000000000000542PubMedGoogle ScholarCrossref
    3.
    Zeidler  K, Arn  K, Senn  O, Schanz  U, Stussi  G.  Optimal preprocedural platelet transfusion threshold for central venous catheter insertions in patients with thrombocytopenia.   Transfusion. 2011;51(11):2269-2276. doi:10.1111/j.1537-2995.2011.03147.x PubMedGoogle ScholarCrossref
    4.
    Josephson  CD, Granger  S, Assmann  SF,  et al.  Bleeding risks are higher in children versus adults given prophylactic platelet transfusions for treatment-induced hypoproliferative thrombocytopenia.   Blood. 2012;120(4):748-760. doi:10.1182/blood-2011-11-389569 PubMedGoogle ScholarCrossref
    5.
    Oakley  FD, Woods  M, Arnold  S, Young  PP.  Transfusion reactions in pediatric compared with adult patients: a look at rate, reaction type, and associated products.   Transfusion. 2015;55(3):563-570. doi:10.1111/trf.12827 PubMedGoogle ScholarCrossref
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