A Pilot Study to Evaluate the Feasibility of Anti-Fibrinolytic Agents in Reducing Hemorrhagic Complications in Pediatric Patients with Thrombocytopenia

Background: The risk of bleeding remains high in thrombocytopenic pediatric hematology-oncology patients despite the use of prophylactic platelet transfusions. In one study, WHO grade 2 or higher bleeding occurred in >80% of pediatric subjects receiving hematopoietic stem cell transplantation or chemotherapy despite a platelet transfusion threshold of 10,000/µl. The risk of bleeding is not decreased with higher transfusion thresholds or increased platelet doses. Bleeding episodes are associated with increased mortality rates, greater utilization of resources and increased transfusion requirements. We examined the use of anti-fibrinolytic agents in decreasing bleeding events and platelet transfusions. Methods: We conducted a randomized double-blinded Phase 2 trial of tranexamic acid versus placebo in inpatient pediatric patients undergoing chemotherapy or HSCT expected to have prolonged thrombocytopenia. All patients admitted to the Oncology or HSCT services were screened for eligibility. Patients consenting for enrollment received either tranexamic acid 10m/kg/dose or normal saline every 8 hours while the platelet count as <30,000/ul until discharge or spontaneous platelet recovery (maximum 30 days). We conducted daily hemostatic assessments using the WHO bleeding scale and monitored adverse events and platelet transfusion requirements. Follow-up assessments took place at 7 and 30 days following completion of study medication. Primary aims were to assess safety and feasibility of tranexamic acid in children with hypoproliferative thrombocytopenia. Results: We screened 697 admissions over 11 months, 31 patients were eligible for enrollment. Enrollment was suspended in March 2020 for COVID reasons though screening continued through July 2020. An additional 10 eligible patients were identified in this period. The most common reasons for ineligibility included recent asparaginase administration, predicted inpatient stay <5 days and age ≤ 2 or ≥ 18 years. Eleven patients enrolled and completed all study procedures. There were no missed doses of medication, 88.4% of doses were administered within one hour of prescribed time. Patients remained on study for a mean of 11.1 days. Five patients each met criteria for spontaneous platelet count recovery or discharge, 1 patient received the study medication for 30 days. Bleeding (all grades) occurred on 29.5% of days. Grade 2 or higher bleeding occurred on 4.9% of days and was experienced by 27.3% of patients. The most common sites of bleeding were oral/nasal and cutaneous. Subjects received a median of 2 platelet transfusions per patient. There were no thromboembolic events or serious adverse events. Conclusion: Tranexamic acid is well tolerated can be safely administered to pediatric oncology patients as an adjunct to therapy. We are planning a multi-center randomized controlled trial to assess the efficacy of tranexamic acid in reducing bleeding complications in this population. Disclosures Triulzi: Fresenius Kabi: Consultancy; Cerus Corp: Research Funding. OffLabel Disclosure: Tranexamic Acid - This medication is being studied as an adjuvant to therapy to prevent bleeding complications and reduce platelet transfusions in pediatric patients with hypoproliferative thrombocytopenia.

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Assessing Bleeding Risk in Pediatric Patients Undergoing Major Spinal Surgery

Blood ◽

10.1182/blood.v126.23.3518.3518 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3518-3518

Author(s):

Jennifer Anadio ◽

Adam Lane ◽

Cristina Tarango ◽

Peter Sturm ◽

Joseph S. Palumbo

Keyword(s):

Platelet Count ◽

Platelet Transfusion ◽

Pediatric Patients ◽

Bleeding Risk ◽

Bleeding Disorder ◽

Bleeding Complications ◽

Type I ◽

Preoperative Screening ◽

History Of ◽

Clinically Significant

Abstract Preoperative screening for bleeding disorders in pediatric patients is problematic due to children's limited exposures to significant hemostatic challenges and the inherent difficulty in obtaining blood samples from young patients. Overcoming these challenges is of particular importance for surgical procedures that carry a significant bleeding risk, such as spinal surgeries. Many pediatric surgeons, including the Pediatric Orthopedic team at our Institution, rely on an unfocused history and measurement of general markers of hemostasis for preoperative screening. In order to improve preoperative screening of pediatric patients undergoing spinal procedures, we instituted the use of a detailed semi-quantitative questionnaire based on the ISTH Bleeding Assessment Tool (BAT), in combination with evaluation of PT, aPTT, platelet count, and PFA. The BAT gives positive points for a personal or family history of bleeding, and negative points for significant hemostatic challenges that did not result in bleeding complications. It was decided a priori that a BAT score of ≥3 would result in referral to Pediatric Hematology. A total of 212 patients presenting for major spinal surgeries (e.g., spinal fusion, growth rod placement) ranging in age from 3 to 25 years were prospectively evaluated in this fashion. A total of 41 patients (19.3%) had a prolongation of the PT and/or aPTT, none of which had a high BAT score. The majority of the abnormal PT/aPTT values were minimal prolongations that were not reproducible on repeat testing. Prolongation of the PT and/or aPTT revealed 3 patients with mild deficiencies of either factors VII, X, or XI, none of which were felt to be clinically significant. Prolonged PFAs were observed in 32 patients (16%), 1 of which was diagnosed with type I VWD (BAT score = 1), and the other with "possible VWD" based on a borderline VWF antigen level (BAT score = 0). Both were treated with Humate P. The remainder of the patients with a prolonged PFA were determined not to have a significant bleeding disorder after further testing. A total of 15 patients were referred to Hematology based on a high BAT score. Of these, 2 had a history of thrombocytopenia (1 with known DiGeorge syndrome and 1 with Depakote-related thrombocytopenia). Neither required platelet transfusion. One patient with a high BAT score was known to have type I VWD and was treated with Humate P, another was diagnosed with low expression of glycoprotein GP1b and was treated with Humate P and platelet transfusion. The remainder of the patients with high BAT scores were not felt to have a clinically significant bleeding disorder based on a Hematologist's assessment. None of the 212 patients evaluated were felt to have excessive intraoperative bleeding by the surgical team, suggesting that none of the patients had a significant undiagnosed hemostatic defect. Together, these results suggest that reliance on history or screening labs alone may not be sufficient for many pediatric surgery patients. While the PFA identified 2 patients with mild/possible VWD that would have been missed by the BAT, the PFA also had a significant number of apparent false positives. The combination of a BAT and a platelet count, as well as assessment of VWF activity for patients without previous hemostatic system challenges, may provide a more effective screening methodology for institutions with ready access to VWF activity measurement. Disclosures No relevant conflicts of interest to declare.

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Severe Thrombocytopenia Does Not Increase Bleeding Complications in Patients Undergoing Bronchoscopy

Blood ◽

10.1182/blood.v124.21.4293.4293 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4293-4293

Author(s):

Lakshminarayanan Nandagopal ◽

Muthu Veeraputhiran ◽

Tania Jain ◽

Ayman Soubani ◽

Charles A. Schiffer

Keyword(s):

Platelet Count ◽

Renal Dysfunction ◽

Platelet Transfusion ◽

Conflicts Of Interest ◽

Bleeding Complications ◽

British Thoracic Society ◽

Severe Thrombocytopenia ◽

Platelet Counts ◽

Number Of Patients ◽

Platelet Transfusions

Abstract Introduction Prophylactic platelet transfusions are often performed prior to bronchoscopy or broncho-alveolar lavage (BAL) to prevent bleeding in thrombocytopenic patients. There is a paucity of data to validate this approach, with a platelet transfusion threshold of <50,000/mm3 largely based on expert opinion. We conducted a retrospective study on the incidence of bleeding complications in thrombocytopenic patients undergoing bronchoscopy. Methods We identified 150 consecutive patients with platelet counts <100,000/mm3 who underwent bronchoscopy and/or BAL from January 2009 to May 2014 at our institution. Bronchoscopies performed in patients with frank hemoptysis and trans-bronchial lung biopsy procedures were excluded. Patient characteristics, underlying diagnosis, platelet count prior to bronchoscopy, administration of platelet transfusions and bronchoscopy details were recorded. Factors affecting bleeding risk including presence of renal dysfunction (defined as BUN >30 and/or Cr>2.0) and coagulation studies (PT, PTT, INR) were identified. The British Thoracic Society guidelines1 were used to categorize bleeding as a result of bronchoscopy. Data were analyzed using descriptive statistics. Results The median age was 59 years (range 27-90), with two-thirds of patients (63%) being male. One hundred and seventeen (78%) patients had underlying malignancy and 55 (37%) had thrombocytopenia related to malignancy. Fellows and residents under the supervision of a bronchoscopy certified attending performed all but 4 of the bronchoscopies. Infection (40%) was the primary indication for bronchoscopy with BAL performed in 127 (85%) patients. Fifty-eight of 89 (65%) patients with baseline platelet counts <50,000/mm3 received prophylactic transfusions compared to 8% of those with platelet counts >50,000/mm3. The platelet count did not rise to >50,000//mm3 in many transfused patients. Seventy patients (47%) had counts <50,000/mm3 and eighty patients (53%) had counts >50,000/mm3 at the time of bronchoscopy. 49% were receiving immunosuppressive medications, 45% had renal dysfunction and 8% had INR >1.5. Bloody lavage that resolved spontaneously without continuous suctioning (Grade 0) was observed in 9 (6%) patients. Bleeding that required continuous suctioning but then resolved spontaneously (Grade 1) was noted in 1 patient with a platelet count of 61,000/mm3. Of 10 total bleeding events, 7 occurred in patients who were intubated. Two additional patients with platelet counts of 30,000/mm3 and 53,000/mm3 had diffuse alveolar hemorrhage, which was present before bronchoscopy. “Old” blood and blood clots were observed in 6 patients. Discussion The low incidence of bleeding complications from bronchoscopy +/- BAL even in patients with platelet counts <30,000/mm3 (3 episodes in 31 patients, all grade 0) demonstrates that bronchoscopy can be safely done in severely thrombocytopenic patients. Adopting a lower threshold for prophylactic transfusions could save a considerable number of platelet units and translate into significant cost savings and decreased risk of transfusion-related complications. Table 1 Platelet count, transfusion history and bleeding complications during bronchoscopy Platelet count at the time of bronchoscopy Number (n) and percentage (%) of patients who underwent bronchoscopy Number of patients who received prior platelet transfusion Bleeding during bronchoscopy n % 0-15,000/mm3 9 6% (9/150) 5 Grade 0=1 pt 16-29 22 15% 16 Grade 0=2 pts 30-39 17 11% 9 Grade 0=1 pt 40-49 22 15% 9 Grade 0=3 pts 50-75 44 29% 14 Grade 1=1 pt 76-100 36 24% 10 Grade 0=2 pts Total 150 63 Grade 0=9 pts, Grade 1=1 pt. 1.Du Rand IA, Blaikley J, Booton R, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. Thorax. 2013:68 Suppl 1:i1-i44 Disclosures No relevant conflicts of interest to declare.

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Bleeding Complications and Transfusion Threshold in Thrombopenic Patients Receiving Antithrombotic Therapy.

Blood ◽

10.1182/blood.v108.11.962.962 ◽

2006 ◽

Vol 108 (11) ◽

pp. 962-962

Author(s):

Jean-Louis H. Kerkhoffs ◽

Rinie J. van Wordragen-Vlaswinkel ◽

Jeroen C.J. Eikenboom ◽

Anneke Brand

Keyword(s):

At Risk ◽

Platelet Count ◽

Anticoagulant Therapy ◽

Platelet Transfusion ◽

Diagnosis And Treatment ◽

Bleeding Complications ◽

Red Cell ◽

Transfusion Threshold ◽

Risk Of Bleeding ◽

The Mean

Abstract Introduction: Central venous catheters are frequently used in hematooncological patients for the administration of chemotherapy, antibiotics and parenteral feeding. Despite low platelet counts, observed in this category of patients, catheter related thrombosis (VTE), with the need for anticoagulant therapy, still occurs in 9.7% of the patients. Treatment of this complication in our institute consists of the removal of the catheter and anti-coagulant therapy, consisting of conventional heparin or low molecular weight heparin. Although solely based on expert opinion, the generally accepted platelet transfusion threshold of 10 x 109/l is raised to 20 – 40 x 109/l. In our institute a trigger of 30 x 109/l is used. We investigated whether this trigger policy is effective in the prevention of bleeding complications. Methods: We performed a case-control study to study bleeding complications and threshold policy. From 1 February 2000 to 1 May 2005 we reviewed medical records of patients, admitted at the hematology department of the Leiden University Medical Center. A total of 22 patients were identified having thrombosis confirmed by ultrasound or phlebography. The database of a recently performed clinical trial in our institution was used to select a control group. Thirty-one controls were selected, matched for age, gender, diagnosis and treatment. For each patient, we calculated the days at risk of bleeding, i.e. days of thrombocytopenia with or without anti-coagulant therapy and recorded bleeding complications, platelet and red cell transfusions from the medical charts. Statistical analysis was performed using SPSS. Results: There were no significant differences between patients with or without VTE in regard to age, gender, diagnosis and treatment. The number of days at risk of bleeding for patients without VTE was 511 days and for VTE group 239 days. The table shows the number of bleeding complications, the mean platelet count, the mean platelet transfusion threshold and the number of platelet and red cell transfusions. Both univariate as multivariate analysis (including age, gender, diagnosis, treatment and VTE-status) showed a significant effect of the existence of VTE on the occurrence of bleeding complications. The Odds’ ratio of bleeding in the VTE group compared to the non-VTE group was 2.9 (CI 95: 1.7 – 5.0; p = 0.0002). More then 95% of the bleeding complications consisted of WHO grades I and II. No lethal bleeding was observed. Discussion: Patients experiencing (catheter-related) venous thrombosis treated with anticoagulant therapy during a period of thrombocytopenia showed an increased risk of bleeding complications, despite a higher platelet transfusion threshold. Whether steering between Scylla and Charibdis can be facilitated by raising the platelet transfusion threshold remains to established. Study outcome No VTE VTE p value n = number Days at risk 511 239 n bleeding complications per day at risk 0.05 0.13 0.0002 mean platelet count (10E9/l) +/− SD 28 +/− 16 38 +/− 17 < 0.0001 mean platelet transfusion threshold (10E9/l) +/− SD 12 +/− 9 28 +/− 12 < 0.0001 n platelet transfusions per day at risk 0.35 0.49 0.0003 n red cell transfusions per day at risk 0.34 0.41 0.073

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Platelet Transfusions for Thrombocytopenic Preterm Neonates: The Monet Study

Blood ◽

10.1182/blood.v130.suppl_1.707.707 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 707-707

Author(s):

Suzanne F Fustolo-Gunnink ◽

K Fijnvandraat ◽

I M Ree ◽

C Caram-Deelder ◽

P Andriessen ◽

...

Keyword(s):

Sensitivity Analysis ◽

Platelet Count ◽

Platelet Transfusion ◽

Bleeding Risk ◽

Hazard Ratio ◽

Sensitivity Analyses ◽

P Value ◽

Risk Of Bleeding ◽

The Impact ◽

Platelet Transfusions

Abstract Introduction Limited evidence supports the widely used practice of administering platelet transfusions to prevent major bleeding in preterm thrombocytopenic neonates. Only 1 randomized controlled trial addressed this issue, but used thresholds higher than those currently used in clinical practice. In order to assess the impact of platelet transfusions on bleeding risk, the primary objective of this study was to develop a prediction model for bleeding. Platelet transfusion was included as variable in this model. In these secondary analyses, we further explored the impact of platelet transfusions on bleeding risk. Materials and methods In this multicenter cohort study, neonates with a gestational age (GA) <34 weeks at birth, admitted to a neonatal intensive care unit (NICU) who developed a platelet count <50x109/L were included. The main study endpoint was major bleeding, defined as intraventricular hemorrhage (IVH) grade 3, IVH with parenchymal involvement, other types of intracranial hemorrhage visible on ultrasound scans, pulmonary hemorrhage or any other type of bleeding requiring immediate interventions. The prediction model was developed using landmarking, in which multiple cox models at regular time-points were combined into 1 supermodel. To further explore the impact of platelet transfusions on bleeding risk, we performed 3 sensitivity analyses by selecting specific transfusions (instead of all transfusions). Sensitivity analysis 1 : transfusions according to protocol, defined as transfusions for platelet counts >20x109/L only allowed in case of GA<32 weeks and <1500 grams and presence of NEC, sepsis, or treatment with mechanical ventilation, or in case of invasive procedures. Sensitivity analysis 2: transfusions with fair increments, defined as platelet count ≥50x109/L within 24 hours. Sensitivity analysis 3: transfusion dose 11 ml/kg or higher. Results A total of 640 neonates were included with a median gestational age of 28 weeks. 70 neonates developed a major bleed. IUGR, postnatal age, platelet count and mechanical ventilation were independent predictors of bleeding. The model allowed calculation of two bleeding risks for individual neonates: one in case of platelet transfusion and one in case of no platelet transfusion. 1361 platelet transfusions were administered to 449 of 640 (70%) neonates, of which 87 were hyperconcentrates. The hazard ratio for transfusion in the original model was 1.0, indicating no predictive power. Sensitivity analysis 1: 704 (52%) transfusions were given according to protocol. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.5, but the p-value remained > 0.05.Sensitivity analysis 2: 764 (56%) of transfusions resulted in a count >50x109/L within 24 hours. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.25, but the p-value remained >0.05. 115 (8%) transfusions did not have a follow up platelet count within 24 hours. Sensitivity analysis 3: of the non-hyperconcentrated platelet transfusions, 517 of 1274 (41%) transfusions were ≥ 11 ml/kg. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.1, with a p-value of 0.05. Conclusion With this tool, absolute risk of bleeding in individual preterm thrombocytopenic neonates can be calculated. Additionally, risk of bleeding can be assessed for 2 scenarios: with and without platelet transfusion. This can help clinicians in deciding whether or not to transfuse a patient. In the primary model, platelet transfusion was not a predictor for bleeding risk. However, the findings of the sensitivity analyses suggest that transfusions with a dose > 11ml/kg may have a more profound effect on bleeding risk. Disclosures No relevant conflicts of interest to declare.

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Patients Receiving Palifermin in Conjunction with Melphalan 200 Required Fewer Platelet Transfusions: Analysis of a Retrospective Cohort Study.

Blood ◽

10.1182/blood.v108.11.5261.5261 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5261-5261

Author(s):

Donald A. Hutcherson ◽

Amelia Langston ◽

Cheryl H. Lin ◽

Christopher Flowers ◽

Mary Jo Lechowicz ◽

...

Keyword(s):

Platelet Count ◽

Platelet Transfusion ◽

Conditioning Regimen ◽

Control Group ◽

Indirect Measure ◽

Platelet Recovery ◽

Autologous Transplant ◽

Transfusion Requirements ◽

Severity Scores ◽

Platelet Transfusions

Abstract Background: Mucosal injury and concomitant associated side effects represents a major toxicity of autologous transplant for myeloma. The use of Palifermin has been demonstrated to reduce mucositis severity scores and duration in randomized trials. We sought to evaluate the effect of palifermin on overall platelet transfusion requirements as an indirect measure of reduced GI toxicity. Since palifermin has been shown to decrease mucosal damage caused by conditioning regimens for PBSCT, it was theorized that palifermin’s protective effects might lead to a reduction in the platelet transfusion requirements for these patients. Methods: Thirty six consecutive myeloma PBSCT patients conditioned with melphalan 200 mg/m2 plus palifermin (dosed per manufacturers recommendations) were retrospectively evaluated for platelet transfusion requirements following autologous transplant. As a historical control, data were retrospectively collected on thirty eight consecutive myeloma PBSCT patients conditioned with the same regimen prior to the routine use of palifermin. Platelet support consists of transfusion of leukoreduced irradiated single donor pheresis products. Platelet transfusions were dictated by standard clinical practice on the transplant service either for a routine platelet count <10K or 20k when patients had evidence for bleeding. Identical platelet transfusion criteria were used in the control and palifermin groups. The number of platelet transfusions required from the time of transplant until platelet recovery was analyzed for each patient. Patients who did not have adequate platelet recovery (Platelets <100,000) at the initiation of transplant conditioning were excluded from analysis in both groups. Results: The palifermin and control patients were of similar age and renal function. Baseline median platelet count was higher in the palifermin group (260 vs 213.5; p=.01), but both groups had mean platelet counts well above the normal range. Patients in the palifermin group required an average of 1.11 platelet transfusions compared with 2.42 transfusions for the control group (p=.055). In the palifermin group, 17 (46%) of the patients required no platelet transfusions compared to only 8 (21%) in the control group (p=.017). When analyzing only the patients who had normal platelet count (> 150,000) prior to start of the conditioning regimen, the palifermin patients (33) required an average of 1.1 transfusions compared to 1.7 transfusions in the control patients (33). The numbers of patients requiring only 1 transfusion were 11 (31%) in the palifermin group and 13 (34%) in the control group. The time to platelet engraftment was similar in both the 2 groups (14.5 days in the palifermin group and 15 days in the control group). Conclusion: The use of palifermin is associated with reduced platelet transfusion requirements among a group of patients who received melphalan 200 mg/m2 conditioning and autologous transplant for myeloma. Further cost analysis and quality of life analysis are needed to further justify this approach for all patients.

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Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000/microL versus 20,000/microL.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.3.1143 ◽

1997 ◽

Vol 15 (3) ◽

pp. 1143-1149 ◽

Cited By ~ 209

Author(s):

K D Heckman ◽

G J Weiner ◽

C S Davis ◽

R G Strauss ◽

M P Jones ◽

...

Keyword(s):

Acute Leukemia ◽

Induction Therapy ◽

Platelet Transfusion ◽

Remission Rate ◽

Randomized Study ◽

Bleeding Complications ◽

Major Surgery ◽

Transfusion Requirements ◽

Significant Difference ◽

Platelet Transfusions

PURPOSE We designed and conducted a randomized single-institution trial comparing two common prophylactic platelet transfusion thresholds in patients undergoing induction therapy for acute leukemia. PATIENTS AND METHODS Seventy-eight patients undergoing induction therapy for acute leukemia were randomized to receive prophylactic apheresis platelet concentrates when the platelet count was either < or = 10,000/microL or < or = 20,000/microL. RESULTS There was no significant difference in the total number of bleeding episodes per patient with a median of four in the < or = 10,000/microL arm and two in the < or = 20,000/microL arm (25th to 75th percentiles of 2, 7 and 1, 5, respectively; P = .12). Patients randomized to the < or = 10,000/microL arm received more platelet transfusions for bleeding [one (0, 2) v zero (0, 0); P = .0003]. In contrast, patients on the < or = 20,000/microL arm received more platelet transfusions for prophylactic indications [10 (5, 14) v six (3, 8); P = 0.001], as would be expected, but less for bleeding. Nevertheless, the total number of platelet transfusions given to patients on the < or = 20,000/microL arm was higher and nearly significant [11 (6, 15) v seven (5, 11); P = .07]. There were no statistically significant differences between the groups with regard to RBC transfusion requirements, febrile days, days hospitalized, days thrombocytopenic, need for HLA-matched platelets, remission rate, or death during induction chemotherapy. No patient in either group died from hemorrhage or underwent major surgery for bleeding complications. CONCLUSION Giving prophylactic platelets at a threshold of < or = 10,000/microL compared with < or = 20,000/microL can decrease the total utilization of platelets with only a small adverse effect on bleeding, and no statistically significant effect on morbidity.

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Influence of Prophylactic Platelet Transfusions on the Recovery of Bone Marrow Function After Intensive Chemotherapy for Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v116.21.1118.1118 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1118-1118

Author(s):

Roland MH Kivit ◽

Peter Joosten ◽

Mels Hoogendoorn ◽

Joost TM De Wolf

Keyword(s):

Bone Marrow ◽

Platelet Count ◽

Myeloid Leukemia ◽

Platelet Transfusion ◽

Bleeding Complications ◽

Intestinal Bleeding ◽

Intensive Chemotherapy ◽

Bone Marrow Function ◽

Acute Myeloid ◽

Platelet Transfusions

Abstract Abstract 1118 Introduction: Treatment of acute myeloid leukemia (AML) patients (< 65 years) consists of intensive chemotherapy. During the aplastic period after chemotherapy it is common to support the patient with prophylactic platelet transfusions (PT) in order to keep platelet count above 10 × 109/L. However, by some it is questioned if the prophylactic transfusion is necessary and whether a therapeutic platelet transfusion (TT) policy might be sufficient. We studied the effects of the two transfusion policies on number of platelet transfusions, bleeding complications, duration of thrombocytopenia and days of hospital stay in two departments of hematology: one in a large tertiary care hospital (MCL;TT) and the other in an university hospital (UMCG; PT). In both hospitals the same chemotherapy was used for the treatment of AML patients. The first chemotherapy course consists of Ara-C (200 mg/m2/ci, days 1–7) and Idarubicin (12 mg/m2/i.v., days 5,6,7); the second course consists of Ara-C (1000 mg/m2, 3 hrs inf, q 12 hrs × 12, days 1–6) and Amsa (120 mg/m2/i.v. days 3,5,7); some patients received a third course consisting of Mitoxantrone (10 mg/m2/i.v. × 5, days 1–5) and Etoposide (100 mg/m2/i.v. × 5, days 1–5). With PT platelets were transfused if the morning platelet count dropped below 10 × 109/L; in case of TT platelets were transfused when new petechiae developed, clinically relevant bleeding occurred or gastro-intestinal bleeding is suspected. Results: 26 patients were treated with 54 chemotherapy courses and received PT; 15 patients, 34 chemotherapy courses received TT. Age was similar in both groups: 50 ± 11 resp 50 ± 12 years. There was no significant difference in the number of different chemotherapy courses between the two groups. 48% of the chemotherapy courses in the PT group consisted of Ara-C/Idarubicin, 44% Ara-C/Amsa en 8% Mitoxantrone /Etoposide, compared to 41% (p=0.7), 38% (p=0.7) and 21% (p=0.1) in the TT group. In the PT group 8,5 ± 5,1 platelet transfusions were used per chemotherapy course compared to 4,2 ± 2,5 in the TT group (p < 0.0001). Bleeding complications occurred significantly more in the TT group. In the TT group 11 bleeding complications were observed in 34 chemotherapy courses: 6 gastro-intestinal bleedings, inconvenient vaginal bleeding in 2 chemotherapy courses, 1 hematuria,1 significant subcutaneous bleeding and 1 cerebral hemorrhage; in the PT group 7 bleeding complications occurred in 54 courses (p=0.03): 5 chemotherapy courses were complicated by vaginal bleedings, 1 retinal bleeding and 1 gastro-intestinal bleeding. Especially gastro-intestinal bleedings occurred significantly more in the TT group: 6/34 courses vs 1/54 courses (p=0.01) in the PT group. Recovery of bone marrow function (absolute neutrophil count > 0.5 × 109/L; platelet count > 20 × 109/L, without platelet transfusions) was reached earlier in the TT group. Absolute neutrophil count > 0.5 × 109/L was noticed 26 ± 12 days after start of chemotherapy in the TT group compared to 32 ± 7 days after start chemotherapy in the PT group (p=0.01). Platelet count > 20 × 109/L without platelet transfusions was seen 21 ± 11 days after start chemotherapy in the TT group compared to 32 ± 13 days in the PT group (p<0.0001). Days in hospital was significantly reduced in the TT group: 29 ± 8 days compared to 38 ± 15 in the PT group (p=0.002). In summary, these data demonstrate that a therapeutic platelet transfusion strategy might lead to a reduced number of platelet transfusions, faster recovery of bone marrow function after chemotherapy and reduced hospital stay. Although manageable, more gastro-intestinal bleedings occurred in this group of patients. Disclosures: No relevant conflicts of interest to declare.

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Thrombopoietic Agonists Show Efficacy in ITP Related to Allogeneic Stem Cell Transplantation,

Blood ◽

10.1182/blood.v118.21.3292.3292 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3292-3292 ◽

Cited By ~ 1

Author(s):

Emma M O'Donovan ◽

Katy Rezvani ◽

Jeremy Sargent ◽

Deborah Richardson ◽

Hannah Tharmalingam ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Platelet Count ◽

Platelet Transfusion ◽

Significant Rise ◽

Platelet Counts ◽

Transfusion Requirements ◽

Cell Transplants ◽

Clinically Significant ◽

Platelet Transfusions

Abstract Abstract 3292 Patients with refractory immune thrombocytopenia (ITP) have limited therapeutic options, with morbidity and mortality as often from infection as from bleeding. Thrombopoietin (TPO) mimetics allow an increase in the platelet count without causing immunosuppression. These agents may be especially useful in patients with secondary forms of ITP. We report three patients treated with TPO agonists for ITP post Allogeneic Stem Cell Transplants (SCT). Patient 1: MC, 37yrs, developed refractory ITP after a myeloablative allogeneic SCT for Accelerated Phase CML. He was unresponsive to standard treatments (figure 1a), requiring platelet transfusions 3x weekly for active bleeding. He started Eltrombopag 50mg/day in July 2009. He had a clinically significant increase in his platelet count (supported count increased to 40) so platelet transfusions were reduced to 2x weekly. Eltrombopag was increased to 75mg in November with a subsequent platelet increase to 90 and by December 2009 he was platelet independent, maintaining a platelet count 90–120 on Eltrombopag alone, 25mg/day, 5 days week. Patient 2: BT, 4yrs(12kg), underwent a myeloablative allogeneic PBSCT in September 2009 for JIA/HLH. She became thrombocytopenic in June 2010, presumed to be ITP. She had no response to prednisolone or rituximab and a only a minimal response to IVIG; requiring platelets 1x weekly. She started Eltrombopag 7mg OD in November 2010, escalated to 12mg by February 2011. This had a synergistic effect with IVIG and she became platelet independent after one month of Eltrombopag and IVIG, maintaining platelet counts 50–200 (figure1b). Patient 3: MG, 62yrs, underwent a reduced intensity allogeneic SCT in March 2010 for stage 3 Sezary syndrome. Post SCT he developed pancytopenia associated with EBV reactivation. He received daily GCSF, regular blood and weekly platelet transfusions. In July he developed GI bleeding from HSV colitis and his platelet transfusion requirements increased to alternate days. In October 2010 he was started on Romiplostim 250mcg, increased to 350mcg weekly, erythropoetin and GCSF. He had a clinically significant rise in his platelet counts and a reduction in his platelet requirements to 1x weekly within weeks of starting romiplostim. By December he was platelet independent, with counts persistently over 50, and romiplostim was stopped (figure1c). All three patients remain in remission at the time of submission of the abstract. Immune cytopenias are well-recognised post myeloablative allografts occurring in 5–37% of SCT recipients. The occurrence of ITP in SCT recipients has been reported, in which GVHD or the production of anti-platelet alloantibodies of recipient origin was considered to play major roles. Although small numbers, these case studies show efficacy of thrombopoietic agents (recently licensed for use in chronic ITP) in patients with thrombocytopenia post SCT refractory to standard therapies, with an early reduction and subsequent cessation in platelet transfusion requirements in all three patients. The lack of immune suppression with these agents may be particularly relevant in patients post SCT, in whom immune reconstitution is vital not only in preventing infections, but also in preventing rejection of the graft and in establishing a graft versus leukaemia effect. Given that TPO receptors are present on haematopoietic stem cells at all stages of development and that TPO provides a growth factor for stem cells, the use of these agents in patients treated for leukaemia requires caution. There was no evidence of progression of disease in these patients and TPO agents were only required for a period of time (patient 3 is off therapy and the others only receive minimal doses). Formal evaluation of these agents in allogeneic SCT is warranted. Disclosures: Cooper: GSK: Honoraria; Amgen: Honoraria.

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Effectiveness of platelet transfusion in acute leukemic pediatric patients: a prospective study

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20181407 ◽

2018 ◽

Vol 5 (3) ◽

pp. 824

Author(s):

S. Subash ◽

D. Umesh

Keyword(s):

Platelet Count ◽

Acute Leukemia ◽

Platelet Transfusion ◽

Pediatric Patients ◽

Tertiary Care ◽

Hematologic Malignancies ◽

Bleeding Complications ◽

Study Population ◽

One Year ◽

A Prospective Study

Background: In India, leukemia account for 25-35% of hematologic malignancies affecting children. Pediatric patients with acute leukemia have to undergo chemotherapy, which may cause protracted thrombocytopenia due to the cytotoxic effects of the drugs prescribed and due to the primary disease. The aim of the present study was to evaluate the need for platelet transfusion in leukemic children and to assess the effectiveness of platelet transfusion among them. Methods: A prospective observational study was conducted in the Department of transfusion medicine and hematology at a tertiary care teaching hospital for a period of one year. The study population included children diagnosed as acute leukemia in the age group 1-12 years. The transfusion was given depending upon the clinical sign of bleeding and the platelet count. The pre and post transfusion platelet count (24 hours after the transfusion) were estimated using hematology analyzer. Statistical analysis was performed using SPSS software. Results: 198 episodes of platelet transfusion were given to 30 children with acute leukemia. It was found for 95% CI of the mean between the pre and post-transfusion platelet count for single, double units and more than two units platelet transfusion, the rise in platelet count was significant (p<0.0001) and there was no refractoriness. All children were negative for transfusion transmissible infections at the end of the study.Conclusions: In the present study, the clinical management of children with acute leukemia has significantly improved with use of platelet transfusions and thereby, the mortality rate due to bleeding complications has dropped rapidly with remarkable clinical improvement in clinical outcomes.

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Insertion of central venous catheters in children undergoing bone marrow transplantation: is there a platelet level for a safe procedure?

Annals of Pediatric Surgery ◽

10.1186/s43159-020-00056-6 ◽

2020 ◽

Vol 16 (1) ◽

Author(s):

Ahmed Elgendy ◽

Ahmed M. Ismail ◽

Eslam Elhawary ◽

Ahmed Badran ◽

Mohammed Ramadan El-Shanshory

Keyword(s):

Bone Marrow ◽

Platelet Count ◽

Bone Marrow Transplantation ◽

Postoperative Complications ◽

Marrow Transplantation ◽

Central Venous Catheters ◽

Bleeding Complications ◽

Safe Procedure ◽

Central Venous ◽

Platelet Transfusions

Abstract Background Bone marrow transplantation (BMT) is a therapeutic procedure for the management of several hematological diseases and malignancies in pediatric population. Central venous catheters (CVCs) play a pivotal role during the process of BMT. The aim of this study was to compare the complications of CVCs placements in children undergoing BMT with platelet levels above and below 50,000/μL and also to detect if there is a platelet count for a safe insertion. This prospective study included all children who had placements of tunneled CVCs during BMT at our hospital between March 2017 and March 2020. Procedures were divided into two groups accordingly to preoperative platelet counts (above and below 50,000/μL). Data were compared between both groups regarding postoperative complications including bleeding or catheter-related blood stream infections (CRBSIs). Results Forty-six CVC insertions were performed in 40 patients. There were 20 procedures below 50,000/μL (median 27,500; range 5000–42,000) inserted with perioperative platelet transfusions, and their postoperative levels were median 59,500/μL, range 18,000–88,000. Allogeneic BMT was adopted in 39 patients (97.5%). Beta thalassemia major was the commonest indication (21/40, 52.5%), followed by acute lymphocytic leukemia in six patients (15%). There were nine postoperative complications (bleeding n = 2 and CRBSIs n = 7) encountered in all placements. Four of them occurred in insertions below 50,000/μL (two bleeding complications that managed conservatively, and two CRBSIs). Post-procedural morbidities regarding bleeding or CRBSIs did not differ significantly between both groups (p value = 0.099 and 0.695, respectively). Conclusions Postponement of CVC insertions in thrombocytopenic children due to the fear of potential complications seems unwarranted, as it has no significant impact on the morbidity. Placements of such catheters can be safe under cover of perioperative platelet transfusions irrespective of the preoperative platelet count.

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