Bleeding assessment following central venous catheter placement, a direct comparison of prospective and retrospective analyses.

BACKGROUND: Reported bleeding incidences following central venous catheter (CVC) placement highly depend on methods of bleeding assessment. To determine the direction and magnitude of the bias associated with retrospective data collection, we used data from the PACER randomized controlled trial and a previous retrospective cohort study. STUDY DESIGN AND METHODS: A patient-level comparison of CVC-related bleeding severity was made among (1) the prospectively collected clinical bleeding assessment of the PACER trial, (2) centralized assessment of CVC insertion site photographs, and (3) retrospective chart review. Interrater reliability for photographic bleeding assessment and retrospective chart review was assessed using Cohen's κ. The magnitude of underreporting of both methods compared to prospective clinical bleeding assessment at different cutoff points of clinically relevant bleeding was assessed using McNemar's test. RESULTS: Interrater reliability was acceptable for both methods (κ = 0.583 and κ = 0.481 for photographic assessment and retrospective chart review, respectively). Photographic bleeding assessment led to significant underreporting of bleeding complications at all cutoff points. Retrospective chart review led to significant underreporting of minor bleeding complications, with an odds ratio (95% CI) of 0.17 (0.044-0.51) for the cutoff point grade 1 (i.e., self-limiting or requiring at most 20 min of manual compression) or higher. There was no significant underreporting of major bleeding complications with retrospective chart review. DISCUSSION: Centralized photographic bleeding assessment and retrospective chart review lead to biased bleeding assessment compared to prospective clinical bleeding assessment.

Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia.

BACKGROUND: Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications. METHODS: In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement. The primary outcome was catheter-related bleeding of grade 2 to 4; a key secondary outcome was grade 3 or 4 bleeding. The noninferiority margin was an upper boundary of the 90% confidence interval of 3.5 for the relative risk. RESULTS: We included 373 episodes of CVC placement involving 338 patients in the per-protocol primary analysis. Catheter-related bleeding of grade 2 to 4 occurred in 9 of 188 patients (4.8%) in the transfusion group and in 22 of 185 patients (11.9%) in the no-transfusion group (relative risk, 2.45; 90% confidence interval [CI], 1.27 to 4.70). Catheter-related bleeding of grade 3 or 4 occurred in 4 of 188 patients (2.1%) in the transfusion group and in 9 of 185 patients (4.9%) in the no-transfusion group (relative risk, 2.43; 95% CI, 0.75 to 7.93). A total of 15 adverse events were observed; of these events, 13 (all grade 3 catheter-related bleeding [4 in the transfusion group and 9 in the no-transfusion group]) were categorized as serious. The net savings of withholding prophylactic platelet transfusion before CVC placement was $410 per catheter placement. CONCLUSIONS: The withholding of prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter did not meet the predefined margin for noninferiority and resulted in more CVC-related bleeding events than prophylactic platelet transfusion. (Funded by ZonMw; PACER Dutch Trial Register number, NL5534.).

Biotinylation of platelets for transfusion purposes a novel method to label platelets in a closed system.

BACKGROUND: Labeling of platelets (PLTs) is required to measure the recovery and survival of transfused PLTs in vivo. Currently a radioactive method is used to label PLTs. However, application of those radiolabeling methods is limited by both safety issues and the inability to isolate transfused PLTs from the circulation. Biotin-labeled PLTs are an attractive nonradioactive option. However, no validated protocol to biotinylate PLTs is currently available for human studies. STUDY DESIGN AND METHODS: Six PLT concentrates (PCs) were subaliquoted and biotinylated on Days 1 and 7 of storage. To distinguish the effect of the processing steps from the effects of biotin incubation, two control groups were used: 1) "sham" samples were processed without the biotinylation reagent and 2) control samples were assessed without any processing other than the PC isolation. For the biotinylation procedure, 50 mL of PCs was washed twice and incubated with 5 mg/L biotin for 30 minutes in a closed system. As measures of PLT activation, phosphatidylserine exposure and CD62p expression were assessed. RESULTS: After biotinylation, 98.4% ± 0.9% of PLTs were labeled. PLT counts, pH, and "swirling" were within the range accepted by the Dutch blood bank for standard PLT products. Biotinylated PLTs were more activated compared than controles but not more than sham samples, but were more activated than the controls. CONCLUSION: We developed a standardized and reproducible protocol according to Good Practice Guidelines standards, for biotin labeling of PLTs for clinical purposes. This method can be applied as nonradioactive alternative assess survival and recovery of transfused PLTs in vivo.

Prophylactic platelet transfusion prior to central venous catheter placement in patients with thrombocytopenia: study protocol for a randomised controlled trial.

BACKGROUND: Severe thrombocytopenia should be corrected by prophylactic platelet transfusion prior to central venous catheter (CVC) insertion, according to national and international guidelines. Even though correction is thought to prevent bleeding complications, evidence supporting the routine administration of prophylactic platelets is absent. Furthermore, platelet transfusion bears inherent risk. Since the introduction of ultrasound-guided CVC placement, bleeding complication rates have decreased. The objective of the current trial is, therefore, to demonstrate that omitting prophylactic platelet transfusion prior to CVC placement in severely thrombocytopenic patients is non-inferior compared to prophylactic platelet transfusion. METHODS/DESIGN: The PACER trial is an investigator-initiated, national, multicentre, single-blinded, randomised controlled, non-inferior, two-arm trial in haematologic and/or intensive care patients with a platelet count of between 10 and 50 × 109/L and an indication for CVC placement. Consecutive patients are randomly assigned to either receive 1 unit of platelet concentrate, or receive no prophylactic platelet transfusion prior to CVC insertion. The primary endpoint is WHO grades 2-4 bleeding. Secondary endpoints are any bleeding complication, costs, length of intensive care and hospital stay and transfusion requirements. DISCUSSION: This is the first prospective, randomised controlled trial powered to test the hypothesis of whether omitting forgoing platelet transfusion prior to central venous cannulation leads to an equal occurrence of clinical relevant bleeding complications in critically ill and haematologic patients with thrombocytopenia. TRIAL REGISTRATION: Nederlands Trial Registry, ID: NTR5653 ( http://www.trialregister.nl/trialreg/index.asp ). Registered on 27 January 2016. Currently recruiting. Randomisation commenced on 23 February 2016.

Reporting transfusion-related acute lung injury by clinical and preclinical disciplines.

BACKGROUND: Disciplines involved in diagnosing transfusion-related acute lung injury (TRALI) report according to a "one-hit" theory. However, studies showed that patients with an underlying condition are at increased risk of the development of TRALI. We investigated whether accumulating evidence on the "two-hit" theory has changed the practice of reporting TRALI. MATERIALS AND METHODS: Departments of haematology, haemovigilance, transfusion medicine, intensive care and anaesthesiology from all Dutch hospitals with at least five beds equipped for mechanical ventilation were invited to participate in an online survey. Using clinical vignettes with conjoint analysis we investigated the effect of patients' age, admission diagnosis, type and number of transfusions and presence of risk factors for acute lung injury on TRALI reporting. A positive ß-coefficient indicated a higher likelihood of reporting TRALI. RESULTS: We received 129 questionnaires (response rate 74%). Respondents were more likely to report TRALI in younger patients, if symptoms developed within 2 hours of transfusion and if patients had received multiple transfusions. Sepsis and the presence of a risk factor for acute lung injury reduced the inclination to report. Transfusion medicine physicians and haemovigilance staff no longer took the age of transfusion products into account in their diagnostic considerations on TRALI. DISCUSSION: We conclude that the multidisciplinary team involved in TRALI reporting, still considers TRALI a "one-hit" event, despite accumulating evidence that supports the "two-hit" theory. These results suggest that the patients most at risk of developing TRALI are not reported to the blood bank.

Central venous catheter placement in coagulopathic patients: risk factors and incidence of bleeding complications.

BACKGROUND: Central venous catheters are frequently inserted into patients with coagulation disorders. It is unclear whether preprocedural correction of hemostasis is beneficial. We determined the incidence of bleeding complications after central venous catheter placement in patients who had severe coagulopathy and identified potential risk factors for bleeding. STUDY DESIGN AND METHODS: The MEDLINE and Cochrane Library databases were systematically searched through November 2015. To be included, articles must have reported on hemorrhagic complications with specification of abnormal coagulation testing results. Severe coagulopathy was defined as a reduced platelet count of 50 × 109 /L or less, and/or an elevated international normalized ratio of 1.5 or greater, and/or a partial thromboplastin time of 45 seconds or greater. RESULTS: We included one randomized controlled trial and 21 observational studies. In total, there were 13,256 catheter insertions, including 4213 in patients with severe coagulopathy. Before 3150 central venous catheter placements, coagulopathy was not corrected. The bleeding incidence varied from 0 to 32%. The severity of coagulopathy did not predict the risk of bleeding. No study demonstrated a beneficial effect from the prophylactic administration of platelets or fresh-frozen plasma to prevent bleeding complications. Retrospective observational studies suggested that no preprocedural correction is required up to a platelet count of 20 × 109 /L and an international normalized ratio of 3.0. CONCLUSION: The incidence of major bleeding complications after central venous catheter placement is low, even in coagulopathic patients. Based on a systematic research of the literature, strong evidence supporting the correction of hemostatic defects before central venous catheter insertion is lacking. However, well-powered randomized controlled trials will be necessary to determine the minimal platelet count, the maximal international normalized ratio, and an activated partial thromboplastin time that is safe before central venous catheter insertion.

Level of agreement between laboratory and point-of-care prothrombin time before and after cardiopulmonary bypass in cardiac surgery.

BACKGROUND: Hemostasis monitoring in cardiac surgery could benefit from an easy to use and fast point-of-care coagulation monitor, since routine laboratory tests have a delay of 30-45minutes. This study investigated the level of agreement between the point-of-care prothrombin time (PT) with central laboratory PT before and after cardiopulmonary bypass. METHODS: Bland Altman and error grid analysis were used to analyze the agreement between the point-of-care Coaguchek XS Pro device (POC-PT) and the central laboratory prothrombin time (LAB-PT) before cardiopulmonary bypass (CPB) and 3minutes after protamine administration. Prothrombin times were expressed in international normalized ratios (INR). RESULTS: The average POC-PT and LAB-PT values of 73 patients were 1.06±0.14 and 1.09±0.13 (P=0.10) before CPB. POC-PT measurements before CPB showed a good agreement with the LAB-PT, with a bias of -0.02±0.07 INR and 94% of the values being represented in the clinical acceptable zone of error grid analysis. The mean POC-PT 3minutes after protamine administration was significantly lower than the LAB-PT (1.35±0.12 vs. 1.70±0.18; P<0.001). The PT at 3minutes after protamine administration showed a bias of 0.36±0.14, and 82% of the values were located outside of the clinical acceptable zone in the error grid analysis. CONCLUSIONS: Point-of-care prothrombin time testing was in concordance with conventional laboratory PT prior to cardiopulmonary bypass. At 3minutes following protamine administration, PT values of the point-of-care device were structurally lower than the laboratory PT values, leading to a disagreement between both tests at that time point.