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The Cochrane Database of Systematic... Apr 2018Outcome after spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is influenced by haematoma volume; up to one-third of ICHs enlarge within 24 hours of onset.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Outcome after spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is influenced by haematoma volume; up to one-third of ICHs enlarge within 24 hours of onset. Early haemostatic therapy might improve outcome by limiting haematoma growth. This is an update of a Cochrane Review first published in 2006, and last updated in 2009.
OBJECTIVES
To examine 1) the effectiveness and safety of individual classes of haemostatic therapies, compared against placebo or open control, in adults with acute spontaneous intracerebral haemorrhage, and 2) the effects of each class of haemostatic therapy according to the type of antithrombotic drug taken immediately before ICH onset (i.e. anticoagulant, antiplatelet, or none).
SEARCH METHODS
We searched the Cochrane Stroke Trials Register, CENTRAL; 2017, Issue 11, MEDLINE Ovid, and Embase Ovid on 27 November 2017. In an effort to identify further published, ongoing, and unpublished randomised controlled trials (RCT), we scanned bibliographies of relevant articles and searched international registers of RCTs in November 2017.
SELECTION CRITERIA
We sought randomised controlled trials (RCTs) of any haemostatic intervention (i.e. pro-coagulant treatments such as coagulation factors, antifibrinolytic drugs, or platelet transfusion) for acute spontaneous ICH, compared with placebo, open control, or an active comparator, reporting relevant clinical outcome measures.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data, assessed risk of bias, and contacted corresponding authors of eligible RCTs for specific data if they were not provided in the published report of an RCT.
MAIN RESULTS
We included 12 RCTs involving 1732 participants. There were seven RCTs of blood clotting factors versus placebo or open control involving 1480 participants, three RCTs of antifibrinolytic drugs versus placebo or open control involving 57 participants, one RCT of platelet transfusion versus open control involving 190 participants, and one RCT of blood clotting factors versus fresh frozen plasma involving five participants. We were unable to include two eligible RCTs because they presented aggregate data for adults with ICH and other types of intracranial haemorrhage. We identified 10 ongoing RCTs. Across all seven criteria in the 12 included RCTs, the risk of bias was unclear in 37 (44%), high in 16 (19%), and low in 31 (37%). Only one RCT was at low risk of bias in all criteria.In one RCT of platelet transfusion versus open control for acute spontaneous ICH associated with antiplatelet drug use, there was a significant increase in death or dependence (modified Rankin Scale score 4 to 6) at day 90 (70/97 versus 52/93; risk ratio (RR) 1.29, 95% confidence interval (CI) 1.04 to 1.61, one trial, 190 participants, moderate-quality evidence). All findings were non-significant for blood clotting factors versus placebo or open control for acute spontaneous ICH with or without surgery (moderate-quality evidence), for antifibrinolytic drugs versus placebo (moderate-quality evidence) or open control for acute spontaneous ICH (moderate-quality evidence), and for clotting factors versus fresh frozen plasma for acute spontaneous ICH associated with anticoagulant drug use (no evidence).
AUTHORS' CONCLUSIONS
Based on moderate-quality evidence from one trial, platelet transfusion seems hazardous in comparison to standard care for adults with antiplatelet-associated ICH.We were unable to draw firm conclusions about the efficacy and safety of blood clotting factors for acute spontaneous ICH with or without surgery, antifibrinolytic drugs for acute spontaneous ICH, and clotting factors versus fresh frozen plasma for acute spontaneous ICH associated with anticoagulant drug use.Further RCTs are warranted, and we await the results of the 10 ongoing RCTs with interest.
Topics: Acute Disease; Adult; Aminocaproic Acid; Antifibrinolytic Agents; Cerebral Hemorrhage; Disease Progression; Factor VIIa; Hemostasis; Hemostatics; Humans; Plasma; Platelet Transfusion; Randomized Controlled Trials as Topic; Recombinant Proteins
PubMed: 29664991
DOI: 10.1002/14651858.CD005951.pub4 -
Vox Sanguinis May 2017Prolonged storage improves availability of platelet products but could also influence safety and efficacy. This systematic review and meta-analyses summarize and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prolonged storage improves availability of platelet products but could also influence safety and efficacy. This systematic review and meta-analyses summarize and quantify the evidence of the effect of storage time of transfused platelets on clinical outcomes.
METHODS
A systematic search in seven databases was performed up to February 2016. All studies reporting storage time of platelet products and clinical outcomes were included. To quantify heterogeneity, I² was calculated, and to assess publication bias, funnel plots were constructed.
RESULTS
Twenty-three studies reported safety outcomes and fifteen efficacy outcomes. The relative risk of a transfusion reaction after old platelets compared to fresh platelets was 1·53 (95% confidence interval (CI): 1·04-2·25) (12 studies). This was 2·05 (CI:1·47-2·85) before and 1·05 (CI: 0·60-1·84) after implementation of universal leucoreduction. The relative risk of bleeding was 1·13 (CI: 0·97-1·32) for old platelets compared to fresh (five studies). The transfusion interval was 0·25 days (CI: 0·13; 0·38) shorter after transfusion of old platelets (four studies). Three studies reported use of platelet products: two for haematological patients and one for trauma patients. Selecting only studies in haematological patients, the difference was 4·51 units (CI: 1·92; 7·11).
CONCLUSION
Old platelets increase the risk of transfusion reactions in the setting of non-leucoreduction, shorten platelet transfusion intervals, thereby increase the numbers of platelet transfusions in haematological patients, and may increase the risk of bleeding.
Topics: Hemorrhage; Humans; Platelet Transfusion; Thrombocytopenia; Treatment Outcome
PubMed: 28271517
DOI: 10.1111/vox.12494 -
International Journal of Gynaecology... Sep 2021Hermansky-Pudlak syndrome (HPS) is a rare autosomal-recessive disorder with clinical manifestations of bleeding diathesis, multi-organ disease and variable... (Review)
Review
BACKGROUND
Hermansky-Pudlak syndrome (HPS) is a rare autosomal-recessive disorder with clinical manifestations of bleeding diathesis, multi-organ disease and variable oculocutaneous albinism (OCA). In women, it can cause life-threatening obstetric and gynecological (OB/GYN) bleeding.
OBJECTIVE
To summarize OB/GYN presentations, outcomes, and management strategies in women with HPS.
SEARCH STRATEGY
Main databases (MEDLINE, EMBASE, Cochrane, PubMed, Web of Science Core Collection and Google Scholar) were searched from inception until June 30, 2020.
SELECTION CRITERIA
Case reports/series of women with confirmed HPS.
DATA COLLECTION AND ANALYSIS
A systematic review using PRISMA guidelines. Methodological quality assessment performed using adapted Newcastle Ottawa scale.
MAIN RESULTS
A total 29 pregnancies in 15 women and 2 gynecological patients were identified. Heavy menstrual bleeding (HMB), the most common bleeding symptom, was reported in 8/15 (53%) of women. HMB and post-partum hemorrhage (PPH) led to diagnosis of HPS in 5/17 (29%) women. Primary PPH was reported in 12/27 (44%) of viable pregnancies; half were major PPH. In 17 pregnancies with known HPS diagnosis, 9 had hemostatic cover with desmopressin and 8 with platelet transfusion. Major PPH occurred in 3/9 (33%) pregnancies covered with desmopressin compared with none in the platelet group.
CONCLUSION
Diagnosis of HPS should be considered in women with OCA presenting with HMB or PPH. Hemostatic management options include desmopressin and platelet transfusion. Management should be multidisciplinary with close collaboration between OB/GYN and hematology teams.
Topics: Female; Hemorrhage; Hemorrhagic Disorders; Hemostatics; Hermanski-Pudlak Syndrome; Humans; Obstetrics; Pregnancy
PubMed: 33521972
DOI: 10.1002/ijgo.13632 -
Critical Reviews in Oncology/hematology Sep 2020Autologous platelet sequestration pattern is associated with post-splenectomy platelet response in patients with immune thrombocytopenia (ITP). However, published... (Meta-Analysis)
Meta-Analysis Review
Autologous platelet sequestration pattern is associated with post-splenectomy platelet response in patients with immune thrombocytopenia (ITP). However, published results are contradictory, and have not been systematically reviewed. Our aim is to systematically review and meta-analyse the association between sequestration pattern and post-splenectomy platelet response. Articles were selected from MEDLINE when they a) included ITP patients, b) performed scintigraphy, and c) included post-splenectomy platelet response. The 23 included studies (published between 1969-2018) represented 2966 ITP-patients. Response to splenectomy occurred most frequently in patients with a splenic pattern (87.1 % in splenic versus 47.1 % in mixed and 25.5 % in hepatic patterns). A pooled analysis of 8 studies showed an odds ratio of 14.21 (95 % CI: 3.65-55.37) for platelet response in the splenic versus the hepatic group. Our findings indicate that a splenic sequestration pattern is associated with better response after splenectomy. Platelet sequestration patterns may be useful in the clinical decision-making regarding splenectomy.
Topics: Blood Platelets; Humans; Purpura, Thrombocytopenic, Idiopathic; Radionuclide Imaging; Spleen; Splenectomy
PubMed: 32712518
DOI: 10.1016/j.critrevonc.2020.103040 -
The Journal of Emergency Medicine Oct 2015Patients taking antiplatelet agents (APAs) with intracranial hemorrhage (ICH) may be treated with platelet transfusion. (Review)
Review
BACKGROUND
Patients taking antiplatelet agents (APAs) with intracranial hemorrhage (ICH) may be treated with platelet transfusion.
OBJECTIVES
We conducted a systematic review of the use of platelet transfusion in the management of APA-related ICH.
METHODS
We searched the Cochrane, Medline, Embase, and CINAHL databases. Included studies were randomized, case-controlled, or cohort studies comparing outcomes in adult patients with APA-related ICH who received or did not receive platelet transfusion. Study quality was measured using appropriate scores. The primary outcome of interest was in-hospital mortality rate. Secondary outcomes included rates of craniotomy, neurological, medical, or radiological deterioration; mean length of hospital stay, delayed mortality, and functional status at discharge. We reported proportions, medians with interquartile ranges, and pooled odds ratios with their 95% confidence intervals. p values < 0.05 were considered statistically significant.
RESULTS
There were no randomized controlled trials. Seven retrospective cohort studies (four traumatic, three primary ICH) were included. For APA-related traumatic ICH, the pooled odds ratio (OR) for in-hospital mortality with platelet transfusion was 1.77 (95% confidence interval [CI] 1.00-3.13). There were no statistically significant differences for secondary outcomes except for proportion with medical decline (6/44 vs. 2/64; p = 0.006). For APA-related primary ICH, the pooled OR for in-hospital mortality with platelet transfusion was 0.49 (95% CI 0.24-0.98). There were no statistically significant differences for most secondary outcomes between the two groups. These studies had important methodological limitations.
CONCLUSIONS
The evidence for platelet transfusion in APA-related ICH was inconclusive due to methodological limitations.
Topics: Blood Transfusion, Autologous; Craniocerebral Trauma; Hospital Mortality; Humans; Intracranial Hemorrhages; Length of Stay; Platelet Aggregation Inhibitors; Platelet Transfusion
PubMed: 25843922
DOI: 10.1016/j.jemermed.2015.02.023 -
The Cochrane Database of Systematic... Jul 2017Platelet transfusions are used to prevent and treat bleeding in people who are thrombocytopenic. Despite improvements in donor screening and laboratory testing, a small... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Platelet transfusions are used to prevent and treat bleeding in people who are thrombocytopenic. Despite improvements in donor screening and laboratory testing, a small risk of viral, bacterial, or protozoal contamination of platelets remains. There is also an ongoing risk from newly emerging blood transfusion-transmitted infections for which laboratory tests may not be available at the time of initial outbreak.One solution to reduce the risk of blood transfusion-transmitted infections from platelet transfusion is photochemical pathogen reduction, in which pathogens are either inactivated or significantly depleted in number, thereby reducing the chance of transmission. This process might offer additional benefits, including platelet shelf-life extension, and negate the requirement for gamma-irradiation of platelets. Although current pathogen-reduction technologies have been proven to reduce pathogen load in platelet concentrates, a number of published clinical studies have raised concerns about the effectiveness of pathogen-reduced platelets for post-transfusion platelet count recovery and the prevention of bleeding when compared with standard platelets.This is an update of a Cochrane review first published in 2013.
OBJECTIVES
To assess the effectiveness of pathogen-reduced platelets for the prevention of bleeding in people of any age requiring platelet transfusions.
SEARCH METHODS
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 9), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 24 October 2016.
SELECTION CRITERIA
We included RCTs comparing the transfusion of pathogen-reduced platelets with standard platelets, or comparing different types of pathogen-reduced platelets.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane.
MAIN RESULTS
We identified five new trials in this update of the review. A total of 15 trials were eligible for inclusion in this review, 12 completed trials (2075 participants) and three ongoing trials. Ten of the 12 completed trials were included in the original review. We did not identify any RCTs comparing the transfusion of one type of pathogen-reduced platelets with another.Nine trials compared Intercept® pathogen-reduced platelets to standard platelets, two trials compared Mirasol® pathogen-reduced platelets to standard platelets; and one trial compared both pathogen-reduced platelets types to standard platelets. Three RCTs were randomised cross-over trials, and nine were parallel-group trials. Of the 2075 participants enrolled in the trials, 1981 participants received at least one platelet transfusion (1662 participants in Intercept® platelet trials and 319 in Mirasol® platelet trials).One trial included children requiring cardiac surgery (16 participants) or adults requiring a liver transplant (28 participants). All of the other participants were thrombocytopenic individuals who had a haematological or oncological diagnosis. Eight trials included only adults.Four of the included studies were at low risk of bias in every domain, while the remaining eight included studies had some threats to validity.Overall, the quality of the evidence was low to high across different outcomes according to GRADE methodology.We are very uncertain as to whether pathogen-reduced platelets increase the risk of any bleeding (World Health Organization (WHO) Grade 1 to 4) (5 trials, 1085 participants; fixed-effect risk ratio (RR) 1.09, 95% confidence interval (CI) 1.02 to 1.15; I = 59%, random-effect RR 1.14, 95% CI 0.93 to 1.38; I = 59%; low-quality evidence).There was no evidence of a difference between pathogen-reduced platelets and standard platelets in the incidence of clinically significant bleeding complications (WHO Grade 2 or higher) (5 trials, 1392 participants; RR 1.10, 95% CI 0.97 to 1.25; I = 0%; moderate-quality evidence), and there is probably no difference in the risk of developing severe bleeding (WHO Grade 3 or higher) (6 trials, 1495 participants; RR 1.24, 95% CI 0.76 to 2.02; I = 32%; moderate-quality evidence).There is probably no difference between pathogen-reduced platelets and standard platelets in the incidence of all-cause mortality at 4 to 12 weeks (6 trials, 1509 participants; RR 0.81, 95% CI 0.50 to 1.29; I = 26%; moderate-quality evidence).There is probably no difference between pathogen-reduced platelets and standard platelets in the incidence of serious adverse events (7 trials, 1340 participants; RR 1.09, 95% CI 0.88 to 1.35; I = 0%; moderate-quality evidence). However, no bacterial transfusion-transmitted infections occurred in the six trials that reported this outcome.Participants who received pathogen-reduced platelet transfusions had an increased risk of developing platelet refractoriness (7 trials, 1525 participants; RR 2.94, 95% CI 2.08 to 4.16; I = 0%; high-quality evidence), though the definition of platelet refractoriness differed between trials.Participants who received pathogen-reduced platelet transfusions required more platelet transfusions (6 trials, 1509 participants; mean difference (MD) 1.23, 95% CI 0.86 to 1.61; I = 27%; high-quality evidence), and there was probably a shorter time interval between transfusions (6 trials, 1489 participants; MD -0.42, 95% CI -0.53 to -0.32; I = 29%; moderate-quality evidence). Participants who received pathogen-reduced platelet transfusions had a lower 24-hour corrected-count increment (7 trials, 1681 participants; MD -3.02, 95% CI -3.57 to -2.48; I = 15%; high-quality evidence).None of the studies reported quality of life.We did not evaluate any economic outcomes.There was evidence of subgroup differences in multiple transfusion trials between the two pathogen-reduced platelet technologies assessed in this review (Intercept® and Mirasol®) for all-cause mortality and the interval between platelet transfusions (favouring Intercept®).
AUTHORS' CONCLUSIONS
Findings from this review were based on 12 trials, and of the 1981 participants who received a platelet transfusion only 44 did not have a haematological or oncological diagnosis.In people with haematological or oncological disorders who are thrombocytopenic due to their disease or its treatment, we found high-quality evidence that pathogen-reduced platelet transfusions increase the risk of platelet refractoriness and the platelet transfusion requirement. We found moderate-quality evidence that pathogen-reduced platelet transfusions do not affect all-cause mortality, the risk of clinically significant or severe bleeding, or the risk of a serious adverse event. There was insufficient evidence for people with other diagnoses.All three ongoing trials are in adults (planned recruitment 1375 participants) with a haematological or oncological diagnosis.
Topics: Adult; Antisepsis; Blood Platelets; Child; Disease Transmission, Infectious; Furocoumarins; Hemorrhage; Humans; Photosensitizing Agents; Platelet Transfusion; Randomized Controlled Trials as Topic; Riboflavin; Thrombocytopenia; Ultraviolet Rays
PubMed: 28756627
DOI: 10.1002/14651858.CD009072.pub3 -
Blood Transfusion = Trasfusione Del... Sep 2022Acquired platelet function disorders (PFD) are rare bleeding diseases that should be suspected in all patients with unexplained mucocutaneous bleedings of recent onset,... (Review)
Review
Acquired platelet function disorders (PFD) are rare bleeding diseases that should be suspected in all patients with unexplained mucocutaneous bleedings of recent onset, with no previous history of haemorrhages, and with normal coagulation test and platelet count. Drug-induced platelet function bleeding disorders are the most frequent PFDs and can easily be identified on the basis of recent administration of platelet-inhibiting drugs. Apart from these, the most challenging acquired PFDs are those caused by autoimmune mechanisms. In fact, demonstration of autoantibodies inhibiting platelet function may be difficult in most non-specialised centres. Among autoimmune PFDs (aPFDs), acquired Glanzmann thrombasthenia (aGT), which is caused by autoantibodies that bind to platelet αIIbβ3 integrin, inhibiting its function, is the most frequent. aGT can be associated with underlying haematological malignancies or autoimmune diseases but can also be idiopathic. More rarely, other immune-mediated PFDs can occur, such as acquired delta storage pool disease (aδSPD). Treatment of aPFDs must rely on the control of acute and chronic bleedings, treatment of the underlying disease in secondary forms, and immunosuppressive treatment for autoantibody reduction or eradication. aPFDs may completely resolve upon treatment of any underlying disease that may be present. In primary aPFDs, and in the majority of secondary forms, treatment relies on immunosuppressive therapies.Here we present a systematic review of previously described immune-mediated aGT and aδSPD cases. Clinical and laboratory characteristics, treatments for the control of bleedings and for the eradication of autoantibodies, and responses to treatments are also discussed. Although no guidelines are available for the management of these very rare conditions, presentation of all cases reported so far can help clinicians in the diagnosis and treatment of these life-threatening diseases.
Topics: Albinism; Autoantibodies; Autoimmune Diseases; Hemorrhagic Disorders; Hermanski-Pudlak Syndrome; Humans; Platelet Glycoprotein GPIIb-IIIa Complex; Thrombasthenia
PubMed: 34369869
DOI: 10.2450/2021.0119-21 -
Transfusion Medicine Reviews Jul 2017Lysine analogues are effective agents used for the reduction of blood loss and transfusion. However, the safety of lysine analogues in cancer patients remains in... (Meta-Analysis)
Meta-Analysis Review
Lysine analogues are effective agents used for the reduction of blood loss and transfusion. However, the safety of lysine analogues in cancer patients remains in question due to a potential risk of venous thromboembolism (VTE). The objective of our review is to investigate safety and efficacy of lysine analogue administration in the patients with cancer. Medline, Embase, and The Cochrane Library were searched from inception to June, 2016. Reference lists of retrieved studies were searched to identify additional publications. We included randomized clinical trials in adult cancer patients for which a lysine analogue was administered for the purpose of blood loss reduction. Abstract and full-text selection as well as data extraction and risk of bias assessment was done by 2 independent reviewers. The primary outcome was venous thromboembolic events. Secondary outcomes were other adverse events, blood transfusion, and blood loss. Overall, 11studies involving 1177 patients evaluated at least one of the primary or secondary outcomes. Nine studies evaluated the effects of tranexamic acid, one study evaluated the effects of aminocaproic acid and one study examined both agents. No increased risk of venous thromboembolism was observed for patients who received lysine analogues compared to control (Peto OR 0.58; 95% CI 0.26-1.28). The administration of a lysine analogue significantly decreased both transfusion risk (pooled RR 0.52, 95% CI 0.34-0.80) and blood loss (SMD -1.57, 95% CI -2.21 to -0.92). Among 3 eligible studies, no increased risk was observed for mortality (Peto OR 1.01; 95% CI 0.14-7.18) or infection (OR 0.58; 95% CI 0.27-1.27). The safety of lysine analogues in cancer patients has not been extensively studied. Based on the available literature, lysine analogue use has not been associated with increased risk of venous thromboembolism or other adverse events, while being effective in reducing blood loss and subsequent transfusion.
Topics: Adult; Aminocaproic Acid; Blood Loss, Surgical; Blood Transfusion; Erythrocyte Transfusion; Humans; Lysine; Neoplasms; Patient Safety; Platelet Transfusion; Randomized Controlled Trials as Topic; Tranexamic Acid; Treatment Outcome; Venous Thrombosis
PubMed: 28366637
DOI: 10.1016/j.tmrv.2017.03.002 -
Scottish Medical Journal Aug 2023This review aimed to examine if the platelet-lymphocyte ratio and lymphocyte-monocyte ratio can be useful in determining disease activity in patients with inflammatory... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This review aimed to examine if the platelet-lymphocyte ratio and lymphocyte-monocyte ratio can be useful in determining disease activity in patients with inflammatory bowel disease.
METHODS
PubMed, CENTRAL, Scopus, Embase, and Web of Science were searched for studies published up to 9 January 2023. Platelet-lymphocyte ratio and lymphocyte-monocyte ratio values from active and remission inflammatory bowel disease cases were compared to generate a mean difference (MD).
RESULTS
Nine studies were included. Meta-analysis showed that inflammatory bowel disease patients with active disease had significantly higher values of platelet-lymphocyte ratio as compared to those in remission (MD: 63.46 95% CI: 35.74, 91.17, = 89%). The values of platelet-lymphocyte ratio were significantly higher in both active ulcerative colitis and Crohn's disease patients. Meta-analysis also showed that lymphocyte-monocyte ratio values were significantly lower in active inflammatory bowel disease patients as compared to those under remission (MD: -1.28 95% CI: -1.42, -1.14, = 4%). Lymphocyte-monocyte ratio values were significantly lower in both ulcerative colitis and Crohn's disease patients with active disease.
CONCLUSION
Platelet-lymphocyte ratio and lymphocyte-monocyte ratio can be useful blood-based markers in differentiating active disease in inflammatory bowel disease patients. Active cases of ulcerative colitis and Crohn's disease have high platelet-lymphocyte ratio and low lymphocyte-monocyte ratio as compared to those in remission. Further studies with a larger sample size are needed to strengthen conclusions.
Topics: Humans; Colitis, Ulcerative; Crohn Disease; Monocytes; Inflammatory Bowel Diseases; Lymphocytes
PubMed: 37489108
DOI: 10.1177/00369330231188962 -
The Cochrane Database of Systematic... Aug 2016Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people with thrombocytopenia. Although considerable advances have been made... (Meta-Analysis)
Meta-Analysis Review
Alternatives, and adjuncts, to prophylactic platelet transfusion for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation.
BACKGROUND
Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people with thrombocytopenia. Although considerable advances have been made in platelet transfusion therapy since the mid-1970s, some areas continue to provoke debate especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding.
OBJECTIVES
To determine whether agents that can be used as alternatives, or adjuncts, to platelet transfusions for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation are safe and effective at preventing bleeding.
SEARCH METHODS
We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 4), MEDLINE (OvidSP, 1946 to 19 May 2016), Embase (OvidSP, 1974 to 19 May 2016), PubMed (e-publications only: searched 19 May 2016), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 19 May 2016).
SELECTION CRITERIA
We included randomised controlled trials in people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII, desmopressin (DDAVP), or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard care or platelet transfusion). We excluded studies of antifibrinolytic drugs, as they were the focus of another review.
DATA COLLECTION AND ANALYSIS
Two review authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two review authors assessed risk of bias in the included studies and extracted data independently.
MAIN RESULTS
We identified 16 eligible trials. Four trials are ongoing and two have been completed but the results have not yet been published (trial completion dates: April 2012 to February 2017). Therefore, the review included 10 trials in eight references with 554 participants. Six trials (336 participants) only included participants with acute myeloid leukaemia undergoing intensive chemotherapy, two trials (38 participants) included participants with lymphoma undergoing intensive chemotherapy and two trials (180 participants) reported participants undergoing allogeneic stem cell transplantation. Men and women were equally well represented in the trials. The age range of participants included in the trials was from 16 years to 81 years. All trials took place in high-income countries. The manufacturers of the agent sponsored eight trials that were under investigation, and two trials did not report their source of funding.No trials assessed artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin.Nine trials compared a TPO mimetic to placebo or standard care; seven of these used pegylated recombinant human megakaryocyte growth and differentiation factor (PEG-rHuMGDF) and two used recombinant human thrombopoietin (rhTPO).One trial compared platelet-poor plasma to platelet transfusion.We considered that all the trials included in this review were at high risk of bias and meta-analysis was not possible in seven trials due to problems with the way data were reported.We are very uncertain whether TPO mimetics reduce the number of participants with any bleeding episode (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.10 to 1.62, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce the risk of a life-threatening bleed after 30 days (OR 1.46, 95% CI 0.06 to 33.14, three trials, 209 participants, very low quality evidence); or after 90 days (OR 1.00, 95% CI 0.06 to 16.37, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce platelet transfusion requirements after 30 days (mean difference -3.00 units, 95% CI -5.39 to -0.61, one trial, 120 participants, very low quality evidence). No deaths occurred in either group after 30 days (one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce all-cause mortality at 90 days (OR 1.00, 95% CI 0.24 to 4.20, one trial, 120 participants, very low quality evidence). No thromboembolic events occurred for participants treated with TPO mimetics or control at 30 days (two trials, 209 participants, very low quality evidence). We found no trials that looked at: number of days on which bleeding occurred, time from randomisation to first bleed or quality of life.One trial with 18 participants compared platelet-poor plasma transfusion with platelet transfusion. We are very uncertain whether platelet-poor plasma reduces the number of participants with any bleeding episode (OR 16.00, 95% CI 1.32 to 194.62, one trial, 18 participants, very low quality evidence). We are very uncertain whether platelet-poor plasma reduces the number of participants with severe or life-threatening bleeding (OR 4.00, 95% CI 0.56 to 28.40, one trial, 18 participants, very low quality evidence). We found no trials that looked at: number of days on which bleeding occurred, time from randomisation to first bleed, number of platelet transfusions, all-cause mortality, thromboembolic events or quality of life.
AUTHORS' CONCLUSIONS
There is insufficient evidence to determine if platelet-poor plasma or TPO mimetics reduce bleeding for participants with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation. To detect a decrease in the proportion of participants with clinically significant bleeding from 12 in 100 to 6 in 100 would require a trial containing at least 708 participants (80% power, 5% significance). The six ongoing trials will provide additional information about the TPO mimetic comparison (424 participants) but this will still be underpowered to demonstrate this level of reduction in bleeding. None of the included or ongoing trials include children. There are no completed or ongoing trials assessing artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin in people undergoing intensive chemotherapy or stem cell transplantation for haematological malignancies.
Topics: Cause of Death; Female; Hematologic Neoplasms; Hemorrhage; Humans; Leukemia, Myeloid, Acute; Lymphoma; Male; Plasma; Platelet Transfusion; Polyethylene Glycols; Recombinant Proteins; Remission Induction; Stem Cell Transplantation; Thrombocytopenia; Thrombopoietin
PubMed: 27548292
DOI: 10.1002/14651858.CD010982.pub2