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Platelet Transfusion:A Clinical PracticeGuideline Fromthe AABBRichard M. Kaufman, MD; Benjamin Djulbegovic, MD, PhD; Terry Gernsheimer, MD; Steven Kleinman, MD;

Alan T. Tinmouth, MD; Kelley E. Capocelli, MD; Mark D. Cipolle, MD, PhD; Claudia S. Cohn, MD, PhD; Mark K. Fung, MD, PhD;

Brenda J. Grossman, MD, MPH; Paul D. Mintz, MD; Barbara A. O’Malley, MD; Deborah A. Sesok-Pizzini, MD; Aryeh Shander, MD;

Gary E. Stack, MD, PhD; Kathryn E. Webert, MD, MSc; Robert Weinstein, MD; Babu G. Welch, MD; Glenn J. Whitman, MD;

Edward C. Wong, MD; and Aaron A.R. Tobian, MD, PhD

Background: The AABB (formerly, the American Association of Blood Banks) developed this guideline on appropriate use of platelet transfusion in adult patients.

Methods: These guidelines are based on a systematic review of randomized, clinical trials and observational studies (1900 toSeptember 2014) that reported clinical outcomes on patients re-ceiving prophylactic or therapeutic platelet transfusions. An ex-pert panel reviewed the data and developed recommendationsusing the Grading of Recommendations Assessment, Develop-ment and Evaluation (GRADE) framework.

Recommendation 1: The AABB recommends that plateletsshould be transfused prophylactically to reduce the risk for spon-

taneous bleeding in hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recom-mends transfusing hospitalized adult patients with a plateletcount of 10 × 109 cells/L or less to reduce the risk for spontane-ous bleeding. The AABB recommends transfusing up to a singleapheresis unit or equivalent. Greater doses are not more effec-tive, and lower doses equal to one half of a standard apheresisunit are equally effective. (Grade: strong recommendation;moderate-quality evidence)

Recommendation 2: The AABB suggests prophylactic platelettransfusion for patients having elective central venous catheterplacement with a platelet count less than 20 × 109 cells/L.(Grade: weak recommendation; low-quality evidence)

Recommendation 3: The AABB suggests prophylactic platelettransfusion for patients having elective diagnostic lumbar punc-ture with a platelet count less than 50 × 109 cells/L. (Grade: weakrecommendation; very-low-quality evidence)

Recommendation 4: The AABB suggests prophylactic platelettransfusion for patients having major elective nonneuraxial sur-gery with a platelet count less than 50 × 109 cells/L. (Grade:weak recommendation; very-low-quality evidence)

Recommendation 5: The AABB recommends against routineprophylactic platelet transfusion for patients who are nonthrom-bocytopenic and have cardiac surgery with cardiopulmonary by-pass. The AABB suggests platelet transfusion for patients having

bypass who exhibit perioperative bleeding with thrombocytope-nia and/or evidence of platelet dysfunction. (Grade: weak rec-ommendation; very-low-quality evidence)

Recommendation 6: The AABB cannot recommend for oragainst platelet transfusion for patients receiving antiplatelettherapy who have intracranial hemorrhage (traumatic or sponta-neous). (Grade: uncertain recommendation; very-low-qualityevidence)

Ann Intern Med. 2015;162:205-213. doi:10.7326/M14-1589 www.annals.org

For author affiliations, see end of text.

* This article was published online first at www.annals.org on 11 November

2014.

A pproximately 2.2 million platelet doses are trans-fused annually in the United States (1). A high pro-portion of these platelet units are transfused prophylac-tically to reduce the risk for spontaneous bleeding inpatients who are thrombocytopenic after chemother-apy or hematopoietic progenitor cell transplantation(HPCT) (1–3). Unlike other blood components, plateletsmust be stored at room temperature, limiting the shelf life of platelet units to only 5 days because of the riskfor bacterial growth during storage. Therefore, main-taining hospital platelet inventories is logistically diffi-

cult and highly resource-intensive (4, 5). Platelet trans-fusion is associated with several risks to the recipient(Table 1), including allergic reactions and febrile non-hemolytic reactions. Sepsis from a bacterially contami-nated platelet unit represents the most frequent infec-tious complication from any blood product today (8). Inany situation where platelet transfusion is being consid-ered, these risks must be balanced against the poten-tial clinical benefits.

GUIDELINE FOCUSThese guidelines were designed to provide prag-

matic recommendations, based on the best available

published evidence, about when platelet transfusionmay be appropriate in adult patients. For several com-mon clinical situations, we attempted to identify aplatelet count threshold below which platelet transfu-sion may improve hemostasis and above which platelettransfusion is unlikely to benefit the patient. We did notattempt to address all clinical situations in which plate-lets may be transfused, and these guidelines are notintended to serve as standards. Clinical judgment, andnot a specific platelet count threshold, is paramount indeciding whether to transfuse platelets.

T ARGET POPULATIONThese guidelines provide advice for adult patients

who are candidates for platelet transfusion.

GUIDELINEDEVELOPMENT PROCESSThe AABB commissioned and funded the develop-

ment of these guidelines.

Panel CompositionA panel of 21 experts was convened. Fifteen par-

ticipants were members of the Clinical TransfusionMedicine Committee of the AABB, all of whom were

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hematologists or pathologists with expertise in transfu-sion medicine. Five additional panel members includeda neurosurgeon, a cardiac surgeon, a critical care spe-cialist, an anesthesiologist, and a hematologist, repre-

senting the American Association of Neurological Sur-geons, the Society of Thoracic Surgeons, the Society of Critical Care Medicine, the American Society of Anes-thesiologists, and the American Society of Hematology,respectively. The final panel member was a Gradingof Recommendations Assessment, Development andEvaluation (GRADE) methodologist. Committee mem-bers had no substantial conflicts of interest as definedby the AABB conflict of interest policy. Pursuant to thepolicy, individual members were required to discloseactual and apparent financial, professional, or personalconflicts (Appendix Table 1, available at www.annals.org).

Systematic Review of theEvidenceThe guidelines were developed on the basis of a

recent systematic review of the literature on platelettransfusions, published separately (11). The searchstrategy is provided in Appendix Table 2 (available atwww.annals.org). We searched PubMed from 1946 tothe first week of April 2013, and the Cochrane CentralRegister of Controlled Trials and Web of Science from1900 to the first week of April 2013 (1024 studies iden-tified). An updated search of these databases was donefrom the first week of April 2013 to the first week of September 2014. Randomized, controlled trials (RCTs)and observational studies (prospective or retrospective

cohort studies, case–control studies, and those with nocontrol group) were eligible for inclusion. Outcomes of interest included all-cause mortality, bleeding-relatedmortality, bleeding, and number of platelet units trans-fused. Although all observational studies meeting theinclusion criteria were reviewed, data from observa-tional studies were not used when more than 2 RCTsaddressed a particular question. There were no lan-guage restrictions. After exclusions, 17 RCTs and 53observational studies were included in the final system-atic review. Only 1 relevant observational study (12)from the updated search was identified, and evidencefrom this study did not change our GRADE judgmentsof evidence quality or recommendation strength.

Grading of EvidenceThe GRADE method was used to assess the quality

of the evidence and determine the strength of recom-mendations (13, 14). The recommendations were de-veloped by consensus at an in-person panel meeting.Panel member judgments on 4 GRADE factors (qualityof evidence, balance between the intervention's bene-

fits and harms, resource use, and patient values andpreferences) and ratings of the strength of recommen-dations were validated using an online survey tool 1week after the meeting.

DefinitionsIn this guideline, a platelet unit refers to 1 aphere-

sis platelet unit or a pool of 4 to 6 whole blood–derivedplatelet concentrates, typically containing 3 to 4 × 1011

platelets. Thrombocytopenia refers to a platelet countbelow the lower limit of the normal range used by thelaboratory performing the count. Seven platelet trialsincluded in the systematic review (15–21) used a varia-tion of the World Health Organization scale (22) to as-

sess patient bleeding outcomes (23). A summary of themodified World Health Organization scale is providedin Table 2.

CLINICAL R ECOMMENDATIONSClinical Setting 1: Hospitalized Adult Patients With Therapy-InducedHypoproliferativeThrombocytopenia Recommendations

Recommendation 1: The AABB recommends thatplatelets should be transfused prophylactically to re-duce the risk for spontaneous bleeding in adult

patients with therapy-induced hypoproliferativethrombocytopenia.The AABB recommends transfusing hospitalized

adult patients with a platelet count of 10 × 109 cells/Lor less to reduce the risk for spontaneous bleeding.

The AABB recommends transfusing up to a singleapheresis unit or equivalent. Greater doses are notmore effective, and lower doses equal to one half of astandard apheresis unit are equally effective.

Quality of evidence: moderate; strength of recom-mendation: strong.

Evidence Summary

Three RCTs (n

= 1047) compared bleeding out-comes in hospitalized patients with radiation and/orchemotherapy-induced hypoproliferative thrombocyto-penia assigned to receive or not receive prophylacticplatelet transfusions (Appendix Table 3, available atwww.annals.org) (19, 21, 24, 25). All patients had he-matologic malignancy treated with chemotherapy orHPCT. Prophylactic platelet transfusions were found tosignificantly reduce the risk for spontaneous grade 2 orgreater bleeding (odds ratio [OR], 0.53 [95% CI, 0.32 to0.87]). Most bleeding events were classified as grade 2.In the 2 largest trials (19, 21), grade 2 or greater bleed-ing in patients assigned to the group that did not re-ceive prophylaxis occurred more frequently among pa-

Table 1. Approximate Per-Unit Risks for Platelet

Transfusion in the United States

Adverse Event Approximate Risk perPlatelet Transfusion

Reference

Febrile reaction 1/14 6

Allergicreaction

1/50 7

Bacterial sepsis 1/75 000 8

TRALI* 1/138 000 9

HBV i nfection 1/2 652 580 Personal communication†

HCV infecti on 1/3 315 729 Personal communication†

HIV infection 0 (95% CI, 0 to 1/1 461 888) Personal communication†

HBV = hepatitis B virus; HCV = hepatitis C virus; TRALI = transfusion-related acute lung injury.* The overall risk for TRALI from all plasma-containing blood productsis currently estimated to be approximately 1/10 000 (10).† Notari E, Dodd R, Stramer S.

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tients receiving chemotherapy for acute leukemiacompared with autologous HPCT recipients (58% vs.47% [19, 25]; 51% vs. 28% [21]).

The threshold platelet count at which plateletsshould be transfused prophylactically to reduce thebleeding risk in hospitalized patients with therapy-induced hypoproliferative thrombocytopenia was ex-

amined in 4 RCTs (n = 658) (Appendix Table 4, avail-able at www.annals.org). Patients were assigned toreceive prophylactic platelet transfusion for a morningplatelet count less than 10 × 109 versus 20 × 109 cells/L(26–28) or 30 × 109 cells/L (15). A greater platelet countthreshold (20 × 109 or 30 × 109 cells/L) was not associ-ated with a significantly lower incidence of grade 2 orgreater bleeding (OR, 0.74 [CI, 0.41 to 1.35]) orbleeding-related mortality (OR, 0.37 [CI, 0.02 to 9.22]).The total number of days with bleeding was greater inthe 10 × 109– cells/L threshold group. The 10 × 109–cells/L threshold was associated with lower platelet us-age and fewer transfusion reactions.

Four RCTs (n = 1132) (Appendix Table 5, availableat www.annals.org) examined whether prophylactictransfusion of low-dose platelets (defined as approxi-mately one half of the standard dose of 3 to 4 × 1011

platelets) would provide hemostasis equal to thatof standard-dose platelets in patients with therapy-induced hypoproliferative thrombocytopenia (16, 18,20, 29). There was no difference in grade 2 or greaterbleeding in recipients of standard-dose versus low-dose platelets (OR, 0.91 [CI, 0.70 to 1.19]). High-doseplatelets (approximately double the standard dose)were compared with standard-dose platelets in 2 RCTs(n = 951) (Appendix Table 6, available at www.annals.org) (17, 18). Prophylactic transfusion of high-dose

platelets did not reduce the risk for bleeding comparedwith standard-dose platelets (OR, 1.05 [CI, 0.79 to1.40]).

Rationale for Recommendations

Before routine platelet prophylaxis was introduced,severe hemorrhage was a common cause of deathamong patients receiving high-dose chemotherapy(30, 31). Today, severe hemorrhage is rarely encoun-tered in this setting. The original studies of platelet pro-phylaxis were done decades ago, and both chemother-apy and supportive care for patients with cancer have

changed dramatically over time. Therefore, the ran-domized trials reported by Wandt (21) and Stanworth(19) and their colleagues were designed to answer thequestion of whether a prophylactic as compared with atherapeutic platelet transfusion strategy provides ben-efit in contemporary cancer care. In the study by Wandtand colleagues (21), grade 2 or greater bleeding wasseen in 42% of patients assigned to receive therapeuticplatelet transfusions only, compared with 19% of pa-tients assigned to receive prophylactic platelet transfu-sion for a platelet count of 10 × 109 cells/L or less(P < 0.001). In the subset of patients with acute myelog-enous leukemia, intracerebral bleeding (grade 4) oc-curred significantly more often in the therapeutic plate-

let group compared with the prophylactic plateletgroup (7% vs. 2%; P = 0.010). In 11 of 13 cases, intra-cerebral bleeding was detectable on CT scan, but therewere no apparent clinical sequelae. Computed tomog-

raphy scans to investigate new headache or other ce-rebral symptoms were required only for patients in thetherapeutic platelet group, so subclinical intracerebralhemorrhage in the prophylactic platelet group mayhave been underdiagnosed. In the Trial of ProphylacticPlatelets (19), subtler differences in bleeding outcomeswere seen between the study groups. Grade 2 orgreater bleeding occurred in 50% of patients assignedto the group that did not receive prophylaxis, com-pared with 43% of patients receiving prophylacticplatelet transfusions (P = 0.06 for noninferiority). In pa-tients receiving chemotherapy (not HPCT), there was asignificant increase in grade 2 or greater bleeding in

the group that did not receive prophylaxis (risk differ-ence, 20% [90% CI, 7.9% to 32.2%]). There was also anonsignificant trend toward increased grade 3 and 4bleeding for all patients in the group that did not re-ceive prophylaxis. Thus, both the Wandt trial and theTrial of Prophylactic Platelets support the continueduse of prophylactic platelet transfusions in patients withtherapy-induced hypoproliferative thrombocytopenia.In this population, we recommend prophylactic platelettransfusion for a morning platelet count of 10 × 109

cells/L or less. Some data suggest that the risk for spon-taneous bleeding does not increase until the plateletcount decreases to less than approximately 6 × 109

cells/L (18, 32), but the 10 × 109–cells/L platelet count

Table 2. Summary of the Modified WHO Bleeding Scale*

WHO Bleeding Grade Examples

1 Oropharyngeal bleeding ≤30 min in 24 hEpistaxis ≤30 min in previous 24 hPetechiae of oral mucosa or skinPurpura ≤1 inch in diameterSpontaneous hematoma in soft tissue or

musclePositive stool occult blood testMicroscopic hematuria or hemoglobinuriaAbnormal vaginal bleeding (spotting)

2 Epistaxis >30 min in 24 hPurpura >1 inch in diameterJoint bleedingMelanotic stoolHematemesisGross/visible hematuriaAbnormal vaginal bleeding (more than

spotting)HemoptysisVisible blood in body cavity fluidRetinal bleeding without visual impairmentBleeding at invasive sites

3 Bleeding requiring red blood cell transfusion

over routine transfusion needsBleeding associated with moderatehemodynamic instability

4 Bleeding associated with severehemodynamic instability

Fatal bleedingCNS bleeding on imaging study with or

without dysfunction

CNS = central nervous system; WHO = World Health Organization.* From references 18 and 22.

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threshold seems to provide a good balance of safetyand practicality, and the accuracy of extremely lowplatelet count measurements is questionable (33, 34).The recommendation for prophylactic platelet transfu-sion based on a 10 × 109–cells/L platelet count thresh-old applies to hospitalized patients only. Prophylacticplatelet transfusion based on a more liberal (greater)

platelet count threshold may be appropriate whentreating outpatients, for reasons of practicality (fewerclinic visits).

The Platelet Dose study (18) established that pa-tients receiving low-dose prophylactic platelet transfu-sions for a morning platelet count of 10 × 109 cells/L orless had the same bleeding risk as patients receivingstandard- or high-dose platelets. However, low-doseplatelets did need to be transfused more often becausethey provided a lower increment. It is safe to providelow-dose platelet prophylaxis to patients with therapy-induced hypoproliferative thrombocytopenia, eitherroutinely or as a temporary maneuver in times of plate-let shortage. High-dose prophylactic platelet transfu-sions have not been shown to provide additional ben-efit, so they are not recommended as routine therapyfor inpatients.

Clinical Setting 2: Adult PatientsHavingMinorInvasive Procedures Recommendations

Recommendation 2: The AABB suggests prophy-lactic platelet transfusion for patients having electivecentral venous catheter placement with a platelet countless than 20 × 109 cells/L.

Quality of evidence: low; strength of recommenda-tion: weak.

Recommendation 3: The AABB suggests prophy-lactic platelet transfusion for patients having electivediagnostic lumbar puncture with a platelet count lessthan 50 × 109 cells/L.

Quality of evidence: very low; strength of recom-mendation: weak.

Evidence Summary

Eight observational studies of central venous cath-eter (CVC) placement in the setting of thrombocytope-nia were identified (n = 1311 cannulations) (AppendixTable 7, available at www.annals.org) (12, 35–41). Manypatients had acute leukemia or were having HPCT;

however, patients with renal failure, critically ill patients,and others were included. Overall bleeding complica-tion rates were low, ranging from 0% to 9% of catheterplacements. The largest series of nontunneled CVCplacements included 604 cannulations in 193 consecu-tive patients (41). In multivariate analysis, only patientswith preprocedure platelet counts less than 20 × 109

cells/L (n = 93) were at increased risk for bleeding com-pared with patients with platelet counts greater than100 × 109 cells/L. Ninety-six percent of bleeding eventswere grade 1, and the remaining 4% of bleedingevents were grade 2, requiring only local compression.In another single-center study, bleeding outcomeswere reported on 3170 tunneled CVCs placed under

ultrasonography guidance in 2512 patients (38). Nobleeding complications occurred in the 344 CVC place-ments performed with a preprocedure platelet countless than 50 × 109 cells/L, including 42 cases with aplatelet count less than 25 × 109 cells/L.

Data from 7 observational studies of children oradults who were thrombocytopenic and had diagnostic

or therapeutic lumbar puncture (LP) were evaluated(Appendix Table 8, available at www.annals.org) (42–49). The largest was a single-center observational studyof 5223 LPs in 956 pediatric patients with acute lym-phoblastic leukemia (45). A total of 199 LPs were per-formed with platelet counts of 20 × 109 cells/L or less,and 742 LPs were performed with platelet counts be-tween 21 × 109 cells/L and 50 × 109 cells/L. No bleed-ing complications were seen, regardless of plateletcount. The upper 95% CI for serious complications was1.75% for patients with platelet counts of 20 × 109

cells/L or less and 0.37% for patients with plateletcounts of 50 × 109 cells/L or less. Traumatic LP (>500red blood cells per high-power field) occurred in 10.5%of procedures but was not associated with adverse clin-ical outcomes. The largest reported series in adults in-cluded 195 diagnostic or therapeutic LPs in 66 adultpatients with acute leukemia and thrombocytopenia(49). Patients were prophylactically transfused withplatelets for a preprocedure platelet count less than20 × 109 cells/L. Thirty-five LPs were performed in pa-tients with platelet counts of 20 × 109 to 30 × 109

cells/L, and 40 were done with platelet counts of 31 × 109 to 50 × 109 cells/L. No bleeding complicationswere seen.

Rationale for RecommendationsSerious bleeding complications after CVC place-

ment are rare, and when they occur, they are often un-related to the platelet count (such as accidental arterialpuncture). In aggregate, the existing data support theuse of a 20 × 109–cells/L platelet count threshold forCVC placement. The reported studies included pa-tients with a wide range of primary diagnoses; this rec-ommendation is intended to be broadly applicable toadult patients with hypoproliferative thrombocytopenia.

Bleeding complications are rare with LPs, but hem-orrhage anywhere in the central nervous system has thepotential to cause devastating neurologic sequelae. In

the absence of better published data supporting thesafety of a lower threshold in adult patients, a fairly lib-eral platelet count threshold for LPs (that is, 50 × 109

cells/L) seems prudent. The 50 × 109–cells/L thresholdis intended for simple diagnostic or therapeutic LPsonly. Despite a lack of supportive data, a greater plate-let count is often recommended for other procedures,such as epidural anesthesia (50, 51).

Clinical Setting 3: Adult Patients Having MajorElectiveNonneuraxial Surgery Recommendations

Recommendation 4: The AABB suggests prophy-lactic platelet transfusion for patients having major




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elective nonneuraxial surgery with a platelet count lessthan 50 × 109 cells/L.


Recommendation 5: The AABB recommendsagainst routine prophylactic platelet transfusion for pa-tients who are nonthrombocytopenic and have cardiac

surgery with cardiopulmonary bypass (CPB). The AABBsuggests platelet transfusion for patients having CPBwho exhibit perioperative bleeding with thrombocyto-penia and/or with evidence of platelet dysfunction.


Evidence Summary

In 1 series (Appendix Table 9, available at www.annals.org) (52), 95 patients with acute leukemia andthrombocytopenia had 167 invasive procedures, in-cluding 29 major surgeries (such as thoracotomy) and

24 moderately invasive procedures (such as arterio-venous fistula construction). Platelet prophylaxis wasgiven before the 130 procedures in which the preoper-ative platelet count was less than 50 × 109 cells/L. Themedian postoperative platelet count in these cases was56 × 109 cells/L. Intraoperative blood loss greater than500 mL occurred in only 7% of all operations, and therewere no deaths due to bleeding. Preoperative plateletcount was not significantly associated with intraopera-tive or postoperative bleeding.

In a meta-analysis of 6 RCTs and a single pilot studyconducted during the licensure of aprotinin, adverseoutcome data were compared between cardiac surgi-cal patients who received (n = 284) or did not receive

(n = 1436) perioperative platelet transfusions (Appen-dix Table 10, available at www.annals.org) (53). Platelettransfusion was identified as an independent predictorof adverse outcomes, including mortality (OR, 4.76 [CI,1.65 to 13.73]). It is possible that platelet transfusionserved at least in part as a surrogate marker of sickerpatients in this analysis, rather than as a direct cause of adverse outcomes (that is, confounding by indication).


The consensus opinion of the panel is that plateletcounts of 50 × 109 cells/L and greater are safe for major

nonneuraxial surgery. There is no evidence of in-creased perioperative bleeding risk in thrombocytope-nic patients with platelet counts greater than 50 × 109

cells/L. We recommend that platelet transfusion bewithheld in nonbleeding surgical patients when theplatelet count is greater than 50 × 109 cells/L and thereis no evidence of coagulopathy. In contrast, we suggestthat platelet transfusion should be considered in car-diac surgical patients with perioperative bleeding andthrombocytopenia (see the Definitions section) and/orsuspected qualitative platelet abnormalities, which of-ten result from exposure of platelets to the CPB circuit(54). Platelet transfusions are often administered tononbleeding cardiac surgical patients (55). There are

no data supporting this practice, and it should bediscouraged.

Clinical Setting 4: Adult Patients Receiving Antiplatelet TherapyWhoHave IntracranialHemorrhage (Traumatic or Spontaneous) Recommendations

Recommendation 6: The AABB cannot recommendfor or against platelet transfusion for patients receivingantiplatelet therapy who have intracranial hemorrhage(traumatic or spontaneous).

Quality of evidence: very low; strength of recom-mendation: uncertain.

Evidence Summary

Five observational studies (n = 635) examined clin-ical outcomes among patients receiving antiplateletagents who present with traumatic brain injury (Appen-dix Table 11, available at www.annals.org) (56). Onestudy reported a greater mortality rate for patients who

received transfusions with platelets (relative risk, 2.4[CI, 1.2 to 4.9]) (57), and a second study reported alower mortality rate for patients receiving platelets (rel-ative risk, 0.21 [CI, 0.05 to 0.95]) (58). Three studiesshowed no significant effect on mortality rates whenpatients received transfusions with platelets (59– 61).One additional observational study (n = 88) reportedthat patients with traumatic brain injury and moderatethrombocytopenia (50 × 109 to 107 × 109 cells/L) whowere transfused with platelets had poorer survival thanthose who were not transfused with platelets (62). In allof these studies, it was not possible to establish acausal relationship between platelet transfusion andclinical outcomes, and confounding by indication waspossible.


In patients with intracerebral hemorrhage who arereceiving antiplatelet agents, the decision to transfuseplatelets requires an individual clinical decision basedon various clinical factors, including the size of thebleeding and the patient's level of consciousness. Forsurgeries involving the central nervous system, plate-lets are conventionally transfused prophylactically for apreprocedure platelet count less than 80 × 109 to100 × 109 cells/L, although only low-quality data sup-

porting this threshold are available.

DISCUSSIONA large proportion of platelet transfusions are ad-

ministered prophylactically to reduce the risk for spon-taneous hemorrhage in patients receiving chemother-apy or HPCT (1–3). With data available from severalRCTs (15–21, 24–29, 63), there is now a solid under-standing of the role of platelet transfusions in this spe-cific setting. Platelet prophylaxis, as compared with atherapeutic platelet transfusion strategy, reduces butdoes not eliminate the risk for bleeding in hospitalizedpatients with therapy-induced hypoproliferative throm-






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From Brigham and Women's Hospital, Boston, Massachusetts;University of South Florida, Tampa, Florida; University of Washington, Seattle, Washington; University of British Colum-bia, Vancouver, British Columbia, Canada; Ottawa HospitalResearch Institute, Ottawa, Ontario, Canada; Children's Hos-pital Colorado, Aurora, Colorado; Christiana Care HealthSystem, Wilmington, Delaware; University of Minnesota, Min-

neapolis, Minnesota; University of Vermont, Burlington, Ver-mont; Washington University School of Medicine, St. Louis,Missouri; U.S. Food and Drug Administration, Silver Spring,Maryland; Wayne State University, Detroit, Michigan; The Chil-dren's Hospital of Philadelphia, Philadelphia, Pennsylvania;Englewood Hospital and Medical Center, Englewood, NewJersey; Yale School of Medicine, New Haven, Connecticut;McMaster University, Hamilton, Ontario, Canada; University of Massachusetts School of Medicine, Worcester, Massachusetts;University of Texas Southwestern Medical Center, Dallas, Tex-as; Johns Hopkins University, Baltimore, Maryland; and Chil-dren's National Medical Center, Washington, DC.

Acknowledgment: The authors thank Theresa Wiegmann for

her outstanding skill and dedication in guiding this projectand Jacqlyn Riposo for her superb logistic support.

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1589.

Requests for Single Reprints: Richard M. Kaufman, MD, De-partment of Pathology, Brigham and Women's Hospital,Blood Bank, Amory 260, 75 Francis Street, Boston, MA 02115;e-mail, [email protected].

Current author addresses and author contributions are avail-able at www.annals.org.

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Rev. 2012;5:CD004269. [PMID: 22592695] doi:10.1002/14651858.CD004269.pub34. Fuller AK, Uglik KM, Braine HG, King KE. A comprehensive pro-gram to minimize platelet outdating. Transfusion. 2011;51:1469-76.[PMID: 21303370] doi:10.1111/j.1537-2995.2010.03039.x5. Riley W, Smalley B, Pulkrabek S, Clay ME, McCullough J. Usinglean techniques to define the platelet (PLT) transfusion process andcost-effectiveness to evaluate PLT dose transfusion strategies. Trans-fusion. 2012;52:1957-67. [PMID: 22320153] doi:10.1111/j.1537-2995.2011.03539.x6. Heddle NM, Blajchman MA, Meyer RM, Lipton JH, Walker IR, SherGD, et al. A randomized controlled trial comparing the frequency of acute reactions to plasma-removed platelets and prestorage WBC-reduced platelets. Transfusion. 2002;42:556-66. [PMID: 12084163]7. Heddle NM, Klama L, Meyer R, Walker I, Boshkov L, Roberts R,et al. A randomized controlled trial comparing plasma removal with

white cell reduction to prevent reactions to platelets. Transfusion.1999;39:231-8. [PMID: 10204584]8. Stramer SL. Current risks of transfusion-transmitted agents: a re-view. Arch Pathol Lab Med. 2007;131:702-7. [PMID: 17488155]9. Eder AF, Dy BA, Perez JM, Rambaud M, Benjamin RJ. The residualrisk of transfusion-related acute lung injury at the American RedCross (2008-2011): limitations of a predominantly male-donorplasma mitigation strategy. Transfusion. 2013;53:1442-9. [PMID:

23113676] doi:10.1111/j.1537-2995.2012.03935.x10. Toy P, Gajic O, Bacchetti P, Looney MR, Gropper MA, HubmayrR, et al; TRALI Study Group. Transfusion-related acute lung injury:incidence and risk factors. Blood. 2012;119:1757-67. [PMID:22117051] doi:10.1182/blood-2011-08-37093211. Kumar A, Mhaskar R, Grossman BJ, Kaufman RM, Tobian AA,Kleinman S, et al. Platelet transfusion: a systematic review of the clin-ical evidence. Transfusion. 2014. [PMID: 25387589] doi: 10.1111/trf.12943 [Epub ahead of print]12. Duffy SM, Coyle TE. Platelet transfusions and bleeding complica-tions associated with plasma exchange catheter placement in pa-tients with presumed thrombotic thrombocytopenic purpura. J ClinApher. 2013;28:356-8. [PMID: 23720092] doi:10.1002/jca.2127913. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al; GRADE Working Group. GRADE: an emerging con-sensus on rating quality of evidence and strength of recommenda-tions. BMJ. 2008;336:924-6. [PMID: 18436948] doi:10.1136/bmj.39489.470347.AD14. Guyatt GH, Oxman AD, Kunz R, Falck-Ytter Y, Vist GE, Liberati A,et al; GRADE Working Group. Going from evidence to recommen-dations. BMJ. 2008;336:1049-51. [PMID: 18467413] doi:10.1136/bmj.39493.646875.AE15. Diedrich B, Remberger M, Shanwell A, Svahn BM, Ringdén O. Aprospective randomized trial of a prophylactic platelet transfusiontrigger of 10 × 10(9) per L versus 30 × 10(9) per L in allogeneichematopoietic progenitor cell transplant recipients. Transfusion.2005;45:1064-72. [PMID: 15987349]16. Heddle NM, Cook RJ, Tinmouth A, Kouroukis CT, Hervig T, Klap-per E, et al; SToP Study Investigators of the BEST Collaborative. Arandomized controlled trial comparing standard- and low-dose strat-egies for transfusion of platelets (SToP) to patients with thrombocy-

topenia. Blood. 2009;113:1564-73. [PMID: 19109560] doi:10.1182/blood-2008-09-17823617. Sensebé L, Giraudeau B, Bardiaux L, Deconinck E, Schmidt A,Bidet ML, et al. The efficiency of transfusing high doses of platelets inhematologic patients with thrombocytopenia: results of a prospec-tive, randomized, open, blinded end point (PROBE) study. Blood.2005;105:862-4. [PMID: 15367427]18. Slichter SJ, Kaufman RM, Assmann SF, McCullough J, Triulzi DJ,Strauss RG, et al. Dose of prophylactic platelet transfusions and pre-vention of hemorrhage. N Engl J Med. 2010;362:600-13. [PMID:20164484] doi:10.1056/NEJMoa090408419. Stanworth SJ, Estcourt LJ, Powter G, Kahan BC, Dyer C, Choo L,et al; TOPPS Investigators. A no-prophylaxis platelet-transfusionstrategy for hematologic cancers. N Engl J Med. 2013;368:1771-80.[PMID: 23656642] doi:10.1056/NEJMoa1212772

20. Tinmouth A, Tannock IF, Crump M, Tomlinson G, Brandwein J,Minden M, et al. Low-dose prophylactic platelet transfusions in re-cipients of an autologous peripheral blood progenitor cell transplantand patients with acute leukemia: a randomized controlled trial witha sequential Bayesian design. Transfusion. 2004;44:1711-9. [PMID:15584985]21. Wandt H, Schaefer-Eckart K, Wendelin K, Pilz B, Wilhelm M,Thalheimer M, et al; Study Alliance Leukemia. Therapeutic platelettransfusion versus routine prophylactic transfusion in patients withhaematological malignancies: an open-label, multicentre, ran-domised study. Lancet. 2012;380:1309-16. [PMID: 22877506] doi:10.1016/S0140-6736(12)60689-822. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting re-sults of cancer treatment. Cancer. 1981;47:207-14. [PMID: 7459811]23. Estcourt LJ, Heddle N, Kaufman R, McCullough J, Murphy MF,Slichter S, et al; Biomedical Excellence for Safer Transfusion Collab-




http://www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1589http://www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1589http://www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1589mailto:[email protected]://www.annals.org/http://www.hhs.gov/ash/bloodsafety/2011-nbcus.pdfhttp://www.hhs.gov/ash/bloodsafety/2011-nbcus.pdfhttp://www.hhs.gov/ash/bloodsafety/2011-nbcus.pdfhttp://www.hhs.gov/ash/bloodsafety/2011-nbcus.pdfhttp://www.annals.org/mailto:[email protected]://www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1589http://www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1589http://www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1589


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orative. The challenges of measuring bleeding outcomes in clinicaltrials of platelet transfusions. Transfusion. 2013;53:1531-43. [PMID:23305609] doi:10.1111/trf.1205824. Murphy S, Litwin S, Herring LM, Koch P, Remischovsky J, Don-aldson MH, et al. Indications for platelet transfusion in children withacute leukemia. Am J Hematol. 1982;12:347-56. [PMID: 6981349]25. Stanworth SJ, Estcourt LJ, Llewelyn CA, Murphy MF, Wood EM;TOPPS Study Investigators. Impact of prophylactic platelet transfu-

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in adults with acute myeloid leukemia. Gruppo Italiano Malattie Ema-tologiche Maligne dell’Adulto. N Engl J Med. 1997;337:1870-5.[PMID: 9407153]29. Roy AJ, Jaffe N, Djerassi I. Prophylactic platelet transfusions inchildren with acute leukemia: a dose response study. Transfusion.1973;13:283-90. [PMID: 4750180]30. Fritz RD, Forkner CE Jr, Freireich EJ, Frei E 3rd, Thomas LB. Theassociation of fatal intracranial hemorrhage and blastic crisis in pa-tients with acute leukemia. N Engl J Med. 1959;261:59-64. [PMID:13666978]31. Han T, Stutzman L, Cohen E, Kim U. Effect of platelet transfusionon hemorrhage in patients with acute leukemia. An autopsy study.Cancer. 1966;19:1937-42. [PMID: 5224775]32. Slichter SJ, Harker LA. Thrombocytopenia: mechanisms andmanagement of defects in platelet production. Clin Haematol. 1978;

7:523-39. [PMID: 363326]33. Lozano M, Mahon A, van der Meer PF, Stanworth S, Cid J,Devine D, et al; Biomedical Excellence for Safer Transfusion (BEST)Collaborative. Counting platelets at transfusion threshold levels: im-pact on the decision to transfuse. A BEST Collaborative - UKNEQAS(H) International Exercise. Vox Sang. 2014;106:330-6. [PMID:24330101] doi:10.1111/vox.1211034. Segal HC, Briggs C, Kunka S, Casbard A, Harrison P, Machin SJ,et al. Accuracy of platelet counting haematology analysers in severethrombocytopenia and potential impact on platelet transfusion. Br JHaematol. 2005;128:520-5. [PMID: 15686462]35. Barrera R, Mina B, Huang Y, Groeger JS. Acute complications of central line placement in profoundly thrombocytopenic cancer pa-tients. Cancer. 1996;78:2025-30. [PMID: 8964028]36. Doerfler ME, Kaufman B, Goldenberg AS. Central venous cath-eter placement in patients with disorders of hemostasis. Chest. 1996;110:185-8. [PMID: 8681626]37. Fisher NC, Mutimer DJ. Central venous cannulation in patientswith liver disease and coagulopathy—a prospective audit. IntensiveCare Med. 1999;25:481-5. [PMID: 10401942]38. Haas B, Chittams JL, Trerotola SO. Large-bore tunneled centralvenous catheter insertion in patients with coagulopathy. J Vasc IntervRadiol. 2010;21:212-7. [PMID: 20123206] doi:10.1016/j.jvir.2009.10.03239. Mumtaz H, Williams V, Hauer-Jensen M, Rowe M, Henry-TillmanRS, Heaton K, et al. Central venous catheter placement in patientswith disorders of hemostasis. Am J Surg. 2000;180:503-5. [PMID:11182407]40. Ray CE Jr, Shenoy SS. Patients with thrombocytopenia: outcomeof radiologic placement of central venous access devices. Radiology.1997;204:97-9. [PMID: 9205228]

41. Zeidler K, Arn K, Senn O, Schanz U, Stussi G. Optimal preproce-dural platelet transfusion threshold for central venous catheter inser-tions in patients with thrombocytopenia. Transfusion. 2011;51:2269-76. [PMID: 21517892] doi:10.1111/j.1537-2995.2011.03147.x42. Breuer AC, Tyler HR, Marzewski DJ, Rosenthal DS. Radicular ves-sels are the most probable source of needle-induced blood in lum-bar puncture: significance for the thrombocytopenic cancer patient.Cancer. 1982;49:2168-72. [PMID: 7074532]

43. Creutzfeldt CJ, Weinstein JR, Longstreth WT Jr, Becker KJ,McPharlin TO, Tirschwell DL. Prior antiplatelet therapy, platelet infu-sion therapy, and outcome after intracerebral hemorrhage. J StrokeCerebrovasc Dis. 2009;18:221-8. [PMID: 19426894] doi:10.1016/j.jstrokecerebrovasdis.2008.10.00744. Feusner J. Platelet transfusion “trigger” for lumbar puncture [Let-ter]. Pediatr Blood Cancer. 2004;43:793. [PMID: 15368544]45. Howard SC, Gajjar A, Ribeiro RC, Rivera GK, Rubnitz JE, Sand-lund JT, et al. Safety of lumbar puncture for children with acute lym-phoblastic leukemia and thrombocytopenia. JAMA. 2000;284:2222-4. [PMID: 11056594]46. Kitanovski L, Trampus-Bakija A, Benedik-Dolnicar M. Prophylac-tic platelet transfusions before lumbal puncture. Zdravniski Vestnik-Slovenian Medical Journal. 2008;77:I111-I5.47. Ruell J, Karuvattil R, Wynn R, Will A. Platelet count has no influ-ence on traumatic and bloody lumbar puncture in children undergo-ing intrathecal chemotherapy [Letter]. Br J Haematol. 2007;136:347-8. [PMID: 17156399]48. Veen JJ, Vora AJ, Welch JC. Lumbar puncture in thrombocyto-penic children [Letter]. Br J Haematol. 2004;127:233-4. [PMID:15461636]49. Vavricka SR, Walter RB, Irani S, Halter J, Schanz U. Safety of lumbar puncture for adults with acute leukemia and restrictive pro-phylactic platelet transfusion. Ann Hematol. 2003;82:570-3. [PMID:12904898]50. van Veen JJ, Nokes TJ, Makris M. The risk of spinal haematomafollowing neuraxial anaesthesia or lumbar puncture in thrombocyto-penic individuals. Br J Haematol. 2010;148:15-25. [PMID: 19775301]doi:10.1111/j.1365-2141.2009.07899.x51. Choi S, Brull R. Neuraxial techniques in obstetric and non-obstetric patients with common bleeding diatheses. Anesth

Analg. 2009;109:648-60. [PMID: 19608843] doi:10.1213/ane.0b013e3181ac13d152. Bishop JF, Schiffer CA, Aisner J, Matthews JP, Wiernik PH. Sur-gery in acute leukemia: a review of 167 operations in thrombocyto-penic patients. Am J Hematol. 1987;26:147-55. [PMID: 3661547]53. Spiess BD, Royston D, Levy JH, Fitch J, Dietrich W, Body S, et al.Platelet transfusions during coronary artery bypass graft surgery areassociated with serious adverse outcomes. Transfusion. 2004;44:1143-8. [PMID: 15265117]54. Whitlock R, Crowther MA, Ng HJ. Bleeding in cardiac surgery: itsprevention and treatment—an evidence-based review. Crit Care Clin.2005;21:589-610. [PMID: 15992674]55. Qureshi H, Lowe D, Dobson P, Grant-Casey J, Parris E, Dalton D,et al; National Blood Service/Royal College of Physicians NationalComparative Audit of Blood Transfusion programme. National com-

parative audit of the use of platelet transfusions in the U.K. TransfusClin Biol. 2007;14:509-13. [PMID: 18359658] doi:10.1016/j.tracli.2008.01.00256. Nishijima DK, Zehtabchi S, Berrong J, Legome E. Utility of plate-let transfusion in adult patients with traumatic intracranial hemor-rhage and preinjury antiplatelet use: a systematic review. J TraumaAcute Care Surg. 2012;72:1658-63. [PMID: 22695437] doi:10.1097/TA.0b013e318256dfc557. Ohm C, Mina A, Howells G, Bair H, Bendick P. Effects of anti-platelet agents on outcomes for elderly patients with traumatic intra-cranial hemorrhage. J Trauma. 2005;58:518-22. [PMID: 15761345]58. Wong DK, Lurie F, Wong LL. The effects of clopidogrel on elderlytraumatic brain injured patients. J Trauma. 2008;65:1303-8. [PMID:19077618] doi:10.1097/TA.0b013e318185e23459. Downey DM, Monson B, Butler KL, Fortuna GR Jr, Saxe JM,Dolan JP, et al. Does platelet administration affect mortality in elderly





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head-injured patients taking antiplatelet medications? Am Surg.2009;75:1100-3. [PMID: 19927514]60. Ivascu FA, Howells GA, Junn FS, Bair HA, Bendick PJ, Janczyk RJ.Predictors of mortality in trauma patients with intracranial hemor-rhage on preinjury aspirin or clopidogrel. J Trauma. 2008;65:785-8.[PMID: 18849791] doi:10.1097/TA.0b013e3181848caa61. Washington CW, Schuerer DJ, Grubb RL Jr. Platelet transfusion:an unnecessary risk for mild traumatic brain injury patients on anti-

platelet therapy. J Trauma. 2011;71:358-63. [PMID: 21825939] doi:10.1097/TA.0b013e318220ad7e62. Anglin CO, Spence JS, Warner MA, Paliotta C, Harper C, MooreC, et al. Effects of platelet and plasma transfusion on outcome intraumatic brain injury patients with moderate bleeding diatheses. JNeurosurg. 2013;118:676-86. [PMID: 23259827] doi:10.3171/2012.11.JNS1262263. Solomon J, Bofenkamp T, Fahey JL, Chillar RK, Beutel E. Plateletprophylaxis in acute non-lymphoblastic leukaemia [Letter]. Lancet.1978;1:267. [PMID: 74683]64. British Committee for Standards in Haematology, Blood Trans-fusion Task Force. Guidelines for the use of platelet transfusions. Br JHaematol. 2003;122:10-23. [PMID: 12823341]65. JPAC – Joint United Kingdom (UK) Blood Transfusion and TissueTransplantation Services Professional Advisory Committee. Transfu-sion Handbook: Transfusion in Surgery. 2013. Accessed at

www.transfusionguidelines.org.uk/transfusion-handbook/7-effective-transfusion-in-surgery-and-critical-care/7-1-transfusion-in-surgeryon 25 September 2014.66. Haas FLJM, van Rhenen DJ, de Vries RRP, Overbeeke MAM,Novotny VMJ, Henny CP. Blood Transfusion Guideline. Utrecht,Netherlands: Institute for Healthcare Improvement; 2011. Accessedat www.sanquin.nl/repository/documenten/en/prod-en-dienst/287294/blood-transfusion-guideline.pdf on 25 September 2014.67. Samama CM, Djoudi R, Lecompte T, Nathan N, Schved JF;French Health Products Safety Agency (AFSSAPS) Expert Group.Perioperative platelet transfusion. Recommendations of the FrenchHealth Products Safety Agency (AFSSAPS) 2003. Minerva Anestesiol.2006;72:447-52. [PMID: 16682914]

68. Samama CM, Djoudi R, Lecompte T, Nathan-Denizot N, SchvedJF; Agence Française de Sécurité Sanitaire des Produits de Santé expert group. Perioperative platelet transfusion: recommendationsof the Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSaPS) 2003. Can J Anaesth. 2005;52:30-7. [PMID: 15625253]69. Schiffer CA, Anderson KC, Bennett CL, Bernstein S, Elting LS,Goldsmith M, et al; American Society of Clinical Oncology. Platelettransfusion for patients with cancer: clinical practice guidelines of the

American Society of Clinical Oncology. J Clin Oncol. 2001;19:1519-38. [PMID: 11230498]70. Tosetto A, Balduini CL, Cattaneo M, De Candia E, Mariani G,Molinari AC, et al; Italian Society for Haemostasis and Thrombosis.Management of bleeding and of invasive procedures in patients withplatelet disorders and/or thrombocytopenia: Guidelines of the Ital-ian Society for Haemostasis and Thrombosis (SISET). Thromb Res.2009;124:e13-8. [PMID: 19631969] doi:10.1016/j.thromres.2009.06.00971. Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB,Saha SP, et al; Society of Thoracic Surgeons Blood ConservationGuideline Task Force. 2011 update to the Society of Thoracic Sur-geons and the Society of Cardiovascular Anesthesiologists bloodconservation clinical practice guidelines. Ann Thorac Surg. 2011;91:944-82. [PMID: 21353044] doi:10.1016/j.athoracsur.2010.11.07872. Malloy PC, Grassi CJ, Kundu S, Gervais DA, Miller DL, Osnis RB,

et al; Standards of Practice Committee with Cardiovascular and In-terventional Radiological Society of Europe (CIRSE) Endorsement.Consensus guidelines for periprocedural management of coagula-tion status and hemostasis risk in percutaneous image-guided inter-ventions. J Vasc Interv Radiol. 2009;20:S240-9. [PMID: 19394868]doi:10.1016/j.jvir.2008.11.02773. Patel IJ, Davidson JC, Nikolic B, Salazar GM, Schwartzberg MS,Walker TG, et al; Standards of Practice Committee, with Cardiovas-cular and Interventional Radiological Society of Europe (CIRSE) En-dorsement. Consensus guidelines for periprocedural managementof coagulation status and hemostasis risk in percutaneous image-guided interventions. J Vasc Interv Radiol. 2012;23:727-36. [PMID:22513394] doi:10.1016/j.jvir.2012.02.012




http://www.transfusionguidelines.org.uk/transfusion-handbook/7-effective-transfusion-in-surgery-and-critical-care/7-1-transfusion-in-surgeryhttp://www.transfusionguidelines.org.uk/transfusion-handbook/7-effective-transfusion-in-surgery-and-critical-care/7-1-transfusion-in-surgeryhttp://www.sanquin.nl/repository/documenten/en/prod-en-dienst/287294/blood-transfusion-guideline.pdfhttp://www.sanquin.nl/repository/documenten/en/prod-en-dienst/287294/blood-transfusion-guideline.pdfhttp://www.sanquin.nl/repository/documenten/en/prod-en-dienst/287294/blood-transfusion-guideline.pdfhttp://www.sanquin.nl/repository/documenten/en/prod-en-dienst/287294/blood-transfusion-guideline.pdfhttp://www.transfusionguidelines.org.uk/transfusion-handbook/7-effective-transfusion-in-surgery-and-critical-care/7-1-transfusion-in-surgeryhttp://www.transfusionguidelines.org.uk/transfusion-handbook/7-effective-transfusion-in-surgery-and-critical-care/7-1-transfusion-in-surgery


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Current Author Addresses: Dr. Kaufman: Department of Pa-thology, Brigham and Women's Hospital, Blood Bank, Amory260, 75 Francis Street, Boston, MA 02115.Dr. Djulbegovic: University of South Florida, 3515 EastFletcher Avenue, Health/Therapy 1201, Health/College of Medicine 27, Tampa, FL 33612.Dr. Gernsheimer: University of Washington, 1959 NE Pacific

Street, Box 356330, Seattle, WA 98195.Dr. Kleinman: University of British Columbia, 1281 RockcrestAvenue, Victoria, British Columbia V9A 4W4, Canada.Dr. Tinmouth: Clinical Epidemiology Research Unit, OttawaHospital Research Institute, General Campus, Box 201, Room1812-C, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada.Dr. Capocelli: Department of Pathology, Children's HospitalColorado, B120, Aurora, CO 80045.Dr. Cipolle: Christiana Care Health System, Surgical and Crit-ical Care Associates, 4755 Ogletown-Stanton Road, Suite1320, Newark, DE 19713.Dr. Cohn: Department of Laboratory Medicine and Pathology,University of Minnesota, Mayo D242, Mayo Mail Code 609,420 Delaware Street Southeast, Minneapolis, MN 55455.Dr. Fung: Department of Pathology, University of Vermontand Fletcher Allen Health Care, 111 Colchester Avenue, Bur-lington, VT 05401.Dr. Grossman: Department of Pathology and Immunology,Washington University School of Medicine, 660 South EuclidAvenue, Campus Box 8118, St. Louis, MO 63110.Dr. Mintz: Division of Hematology Clinical Review, Center forBiologics Evaluation and Research, U.S. Food and Drug Ad-ministration, 10903 New Hampshire Avenue, Silver Spring,MD 20993.Dr. O’Malley: Department of Pathology, Wayne State Univer-sity School of Medicine, 3990 John R. Road, Harper UniversityHospital, Detroit Medical Center, Detroit, MI 48202.Dr. Sesok-Pizzini: Children's Hospital of Philadelphia, 5136Main Hospital, 34th Street and Civic Center Boulevard, Phila-delphia, PA 19104-4399.Dr. Shander: Department of Anesthesiology and Critical CareMedicine, Englewood Hospital and Medical Center, 350Engle Street, Englewood, NJ 07631.Dr. Stack: Yale School of Medicine, Pathology and LaboratoryMedicine Service/113, 950 Campbell Avenue, West Haven,CT 06516-2770.Dr. Webert: Canadian Blood Services, 35 Stone Church Road,Suite 200, Ancaster, Ontario L9K 1S5, Canada.

Dr. Weinstein: University of Massachusetts Medical School, 55Lake Avenue North, LA-113, Worcester, MA 01655.Dr. Welch: University of Texas Southwestern Medical Center,5161 Harry Hines Boulevard, CS5.112, Dallas, TX 75390-8855.Dr. Whitman: Division of Cardiac Surgery, Johns Hopkins Uni-versity, Suite 7107/Zayed Tower, 1800 Orleans Street, Balti-more, MD 21287.

Dr. Wong: Division of Laboratory Medicine, Children's Na-tional Medical Center, 111 Michigan Avenue NW, Washing-ton, DC 20010.Dr. Tobian: Department of Pathology, Division of TransfusionMedicine, Johns Hopkins University, Carnegie 437, 600 NorthWolfe Street, Baltimore, MD 21287.

Author Contributions: Conception and design: R.M. Kaufman,B. Djulbegovic, T. Gernsheimer, S. Kleinman, A.T. Tinmouth,B.J. Grossman, P.D. Mintz, D.A. Sesok-Pizzini, G.E. Stack, K.E.Webert, R. Weinstein, A.A.R. Tobian.Analysis and interpretation of the data: R.M. Kaufman, B. Djul-begovic, T. Gernsheimer, S. Kleinman, A.T. Tinmouth, K.E. Ca-pocelli, C.S. Cohn, M.K. Fung, B.J. Grossman, P.D. Mintz, B.A.

O’Malley, D.A. Sesok-Pizzini, A. Shander, G.E. Stack, K.E. We-bert, R. Weinstein, B.G. Welch, G.J. Whitman, E.C. Wong,A.A.R. Tobian.Drafting of the article: R.M. Kaufman, B. Djulbegovic, T. Gern-sheimer, S. Kleinman, A.T. Tinmouth, K.E. Capocelli, M.D. Ci-polle, D.A. Sesok-Pizzini, A. Shander, B.G. Welch, A.A.R.Tobian.Critical revision of the article for important intellectual con-tent: R.M. Kaufman, B. Djulbegovic, T. Gernsheimer, S. Klein-man, A.T. Tinmouth, K.E. Capocelli, M.D. Cipolle, M.K. Fung,B.J. Grossman, P.D. Mintz, B.A. O’Malley, D.A. Sesok-Pizzini, A.Shander, K.E. Webert, R. Weinstein, G.J. Whitman, E.C. Wong,A.A.R. Tobian.Final approval of the article: R.M. Kaufman, B. Djulbegovic, T.Gernsheimer, S. Kleinman, A.T. Tinmouth, K.E. Capocelli, C.S.Cohn, M.K. Fung, B.J. Grossman, P.D. Mintz, B.A. O’Malley,D.A. Sesok-Pizzini, A. Shander, K.E. Webert, R. Weinstein, B.G.Welch, E.C. Wong, A.A.R. Tobian.Provision of study materials or patients: B. Djulbegovic.Statistical expertise: B. Djulbegovic.Administrative, technical, or logistic support: M.K. Fung,A.A.R. Tobian.Collection and assembly of data: B. Djulbegovic, G.E. Stack,A.A.R. Tobian.

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Appendix Table 1. Panel Members' Conflicts of Interest

Panel Member Conflicts of Interest

Kelley E. Capocelli, MD None

Mark D. Cipolle, MD, PhD None

Claudia S. Cohn, MD, PhD None

Benjamin Djulbegovic, MD, PhD None

Mark K. Fung, MD, PhD None

Terry Gernsheimer, MD NoneBrenda J. Grossman, MD, MPH None

Richard M. Kaufman, MD None

Steven Kleinman, MD None

Paul D. Mintz, MD None

Barbara A. O'Malley, MD None

Deborah A. Sesok-Pizzini, MD None

Aryeh Shander, MD None

Gary E. Stack, MD, PhD None

Alan T. Tinmouth, MD None

Aaron A.R. Tobian, MD, PhD None

Kathryn E. Webert, MD, MSc None

Robert Weinstein, MD None

Babu G. Welch, MD None

Glenn J. Whitman, MD None

Edward C. Wong, MD None

Annals of Internal Medicine • Vol. 162 No. 3 • 3 February 2015 www.annals.org



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Appendix Table 2. Search Strategy Used for Systematic Review of the Literature*

PubMed

1. Search strategy for prophylactic platelet transfusion studies(blood transfusion OR Blood Transfusion[Mesh] OR "Blood Cells/transplantation"[Mesh] OR transfus* [tiab])

AND

(Platelet Count[Mesh] OR platelet count [tiab]) OR Platelet [tiab] transfusion OR Platelet Transfusion[Mesh] OR platelet* [tiab]

AND

(Prophyla* [tiab] OR bleed* OR transfus*[tiab])AND

(threshold* OR trigger* OR count OR policy [tiab] OR adminis* OR guideline* OR dose [tiab] OR dosing [tiab] OR dosage [tiab] OR transfus*[tiab] ORpractice [tiab] OR transfus*)

2. Search strategy for therapeutic platelet transfusion studies

(blood transfusion OR Blood Transfusion[Mesh] OR "Blood Cells/transplantation"[Mesh] OR transfus* [tiab])

AND

(Platelet Count[Mesh] OR platelet count [tiab]) OR Platelet [tiab] transfusion OR Platelet Transfusion[Mesh] OR platelet* [tiab]

AND

(Therapeutic [tiab] OR therap*[tiab])

AND

(threshold* OR trigger* OR count OR policy [tiab] OR adminis* OR guideline* OR dose OR dosing OR dosage OR practice [tiab] OR transfus* [tiab])

Cochrane Central Register of Controlled Trials

3. Search strategy for prophylactic platelet transfusion studiesProphyla* platelet* transfuse*

4. Search strategy for therapeutic platelet transfusion studies

Therapeutic* platelet* transfuse*

Web of Science

No subject heading-all keywords

5. Search strategy for prophylactic platelet transfusion studies (blood transfusion OR Blood Cells transplantation OR transfus*)

AND

(platelet AND (count OR transfus*)) OR (Prophyla* OR bleed* OR transfus*) (whole phrase in title field)

AND

(threshold* OR trigger* OR count* OR policy OR adminis* OR guideline* OR dose OR dosing OR dosage OR practice OR transfus*)

6. Search strategy for therapeutic platelet transfusion studies (blood transfusion OR Blood Cells transplantation OR transfus*)

AND

(platelet AND (count OR transfus*)) OR (Therapeutic [tiab] OR therap*[tiab]) (whole phrase in title field)

AND

(threshold* OR trigger* OR count OR policy [tiab] OR adminis* OR guideline* OR dose OR dosing OR dosage OR practice [tiab] OR transfus* [tiab])

7. Additional search

The yield on the original search strategy was not optimum for all diseases. Therefore, we also searched the Pubmed clinical queries by using a combinationof 2 terms of “platelet transfusion” AND “disease category”.

7.1. Platelet transfusion AND idiopathic thrombocytopenic purpura. The resultant search strategy from PubMed Clinical Queries is shown below:

Therapy/Broad[filter] AND (("platelet transfusion"[MeSH Terms] OR ("platelet"[All Fields] AND "transfusion"[All Fields]) OR "platelet transfusion"[All Fields])AND ("purpura, thrombocytopenic, idiopathic"[MeSH Terms] OR ("purpura"[All Fields] AND "thrombocytopenic"[All Fields] AND "idiopathic"[All Fields])OR "idiopathic thrombocytopenic purpura"[All Fields] OR ("idiopathic"[All Fields] AND "thrombocytopenic"[All Fields] AND "purpura"[All Fields])))

7.2. Platelet transfusion AND Disseminated Intravascular Coagulation

Therapy/Broad[filter] AND (("platelet transfusion"[MeSH Terms] OR ("platelet"[All Fields] AND "transfusion"[All Fields]) OR "platelet transfusion"[All Fields])AND ("disseminated intravascular coagulation"[MeSH Terms] OR ("disseminated"[All Fields] AND "intravascular"[All Fields] AND "coagulation"[All Fields])OR "disseminated intravascular coagulation"[All Fields]))

7.3. Platelet transfusion AND Idiopathic Thrombocytopenic Purpura

Therapy/Broad[filter] AND (("platelet transfusion"[MeSH Terms] OR ("platelet"[All Fields] AND "transfusion"[All Fields]) OR "platelet transfusion"[All Fields])AND ("purpura, thrombocytopenic, idiopathic"[MeSH Terms] OR ("purpura"[All Fields] AND "thrombocytopenic"[All Fields] AND "idiopathic"[All Fields])OR "idiopathic thrombocytopenic purpura"[All Fields] OR ("idiopathic"[All Fields] AND "thrombocytopenic"[All Fields] AND "purpura"[All Fields])))

7.4. Platelet transfusion AND Thrombotic Thrombocytopenic Purpura - Hemolytic Uremic Syndrome

Therapy/Broad[filter] AND (("platelet transfusion"[MeSH Terms] OR ("platelet"[All Fields] AND "transfusion"[All Fields]) OR "platelet transfusion"[All Fields])AND (("purpura, thrombotic thrombocytopenic"[MeSH Terms] OR ("purpura"[All Fields] AND "thrombotic"[All Fields] AND "thrombocytopenic"[AllFields]) OR "thrombotic thrombocytopenic purpura"[All Fields] OR ("thrombotic"[All Fields] AND "thrombocytopenic"[All Fields] AND "purpura"[All

Fields])) AND ("haemolytic uraemic syndrome"[All Fields] OR "hemolytic-uremic syndrome"[MeSH Terms] OR ("hemolytic-uremic"[All Fields] AND"syndrome"[All Fields]) OR "hemolytic-uremic syndrome"[All Fields] OR ("hemolytic"[All Fields] AND "uremic"[All Fields] AND "syndrome"[All Fields]) OR"hemolytic uremic syndrome"[All Fields])))

8. Manual search

The search strategy was supplemented by a manual search of references of the obtained full-text articles and existing guidelines in the field. In addition, wealso contacted the members of the AABB Guidelines Panel to identify any unpublished articles or studies that were missed in the search.

All obtained citations were entered into an EndNote database. In the first step, all duplicate citations were removed using the remove duplicate feature inthe EndNote. Next, the abstract and title of all remaining citations were printed and manually reviewed for inclusion or exclusion by 2 reviewers accordingto the predetermined criteria. All the included studies were first sorted on the basis of study design and disease category. That is, in the first attempt, allreviewed studies were classified as randomized or observational; then, within the study design, all studies were collated according to the broad categoryof treatment vs. prophylactic followed by various disease categories (e.g., surgery, hematologic malignant tumors, and central venous catheter). Allincluded observational studies within a disease category were classified as prospective observational or retrospective observational. For prospectiveobservational cohort studies, we classified all studies as cohort studies either with comparison or without comparison. For retrospective observationalstudies, all studies were further classified as retrospective cohort with comparison or single-group or case series or case reports.

* From reference 11.

www.annals.org Annals of Internal Medicine • Vol. 162 No. 3 • 3 February 2015



13/17

A p p e n d i x T a b l e 3 .

P r o p h y l a c t i c P l a t e l e t T r a n s f u s i o n V e r s u s N o P r o p h y l a c t

i c P l a t e l e t T r a n s f u s i o n i n T h e r a p y - I n d u

c e d H y p o p r o l i f e r a t i v e T h r o m b o c y t o p e

n i a

S t u d i e s b y

S u b g r o u p , n

Q u a l i t y A s s e s s m e n t *

P a t i e n t s , n / N ( % )

E f f e c t

Q u a l i t y

I m p o r t a n c e

D e s i g n

R i s k o f B i a s

I n c o n s i s t e n c y

I n d i r e c t n e s s

I m p r e c i s i o n

O t h e r

C o n s i d e r a t i o n s

P r o p h y l a c t i c

P l a t e l e t

T r a n s f u s i o n

N o P r o p h y l a c t i c

P l a t e l e t


O d d s R a t i o

( 9 5 %

C I )

A b s o l u t e

G r a d e 2 o r g r e a t e r

b l e e d i n g :

3 ( 2 1

, 2 4

, 2 5 )

R a n d o m i z e d

t r i a l s

N o s e r i o u s

r i s k

N o s e r i o u s

i n c o n s i s t e n c y

N o s e r i o u s

i n d i r e c t n e s s

N o s e r i o u s

i m p r e c i s i o n

R e p o r t i n g

b i a s †

1 9 2 / 5 2 8 ( 3 6

. 4 )

2 5 8 / 5 1 9 ( 4 9

. 7 )

0 . 5

3 ( 0

. 3 2 – 0 . 8

7 )

1 5 3 f e w e r b l e e d i n g

e v e n t s p e r 1 0 0 0 ( f r o m

3 5 f e w e r t o 2 5 7 f e w e r

b l e e d i n g e v e n t s )

M o d e r a t e

C r i t i c a l


b l e e d i n g ,

c h e m o t h e r a p y

s u b g r o u p :

3 ( 2 1

, 2 4

, 2 5 )

R a n d o m i z e d

t r i a l s

N o s e r i o u s

r i s k

N o s e r i o u s


N o s e r i o u s


N o s e r i o u s


R e p o r t i n g

b i a s †

7 7 / 1 8 7 ( 4 1

. 2 )

1 1 5 / 1 6 9 ( 6 8

. 0 )

0 . 3

4 ( 0

. 2 2 – 0 . 5

2 )


e v e n t s p e r 1 0 0 0 ( f r o m

1 5 5 f e w e r t o 3 6 1 f e w e r


M o d e r a t e

C r i t i c a l


b l e e d i n g ,

a u t o l o g o u s

H P C T s u b g r o u p :

2 ( 2 1

, 2 5 )

R a n d o m i z e d

t r i a l s

S e r i o u s ‡

N o s e r i o u s


N o s e r i o u s


N o s e r i o u s


N o n e

1 0 3 / 3 0 8 ( 3 3

. 4 )

1 2 8 / 3 1 3 ( 4 0

. 9 )

0 . 4

8 ( 0

. 1 2 – 1 . 9

2 )


e v e n t s p e r 1 0 0 0 ( f r o m

3 3 2 f e w e r t o 1 6 2 m o r e


M o d e r a t e

C r i t i c a l

A l l - c a u s e m o r t a l i t y :

4 ( 2 1

, 2 4

, 2 5

, 6 3 )

R a n d o m i z e d

t r i a l s

N o s e r i o u s

r i s k

N o s e r i o u s


N o s e r i o u s


S e r i o u s §

R e p o r t i n g

b i a s ¶

1 3 / 5 4 5 ( 2

. 4 )

1 6 / 5 3 1 ( 3

. 0 )

0 . 7

2 ( 0

. 3 0 – 1 . 5

5 )

8 f e w e r d e a t h s p e r 1 0 0 0

( f r o m 2 1 f e w e r t o 1 6

m o r e d e a t h s )

L o w

C r i t i c a l

B l e e d i n g - r e l a t e d

m o r t a l i t y :

4 ( 2 1

, 2 4

, 2 5

, 6 3 )

R a n d o m i z e d

t r i a l s

N o s e r i o u s

r i s k

N o s e r i o u s


N o s e r i o u s


S e r i o u s

R e p o r t i n g

b i a s ¶

3 / 5 4 4 ( 0

. 6 )

4 / 5 3 0 ( 0

. 8 )

0 . 5

4 ( 0

. 0 9 – 3 . 1

0 )

3 f e w e r d e a t h s p e r 1 0 0 0

( f r o m 7 f e w e r t o 1 5

m o r e d e a t h s )

L o w

C r i t i c a l

H P C T = h e m a t o p o i e t i c p r o g e n i t o r c e l l t r a

n s p l a n t a t i o n .

* Q u a l i t y a s s e s s m e n t e v a l u a t e d r i s k o f b i a s , i n c o n s i s t e n c y ( b a s e d o n h e t e r o g e n e i t y a m

o n g t r i a l s ) , i n d i r e c t n e s s ( b a s e d o n a s s e s s m

e n t o f g e n e r a l i z a b i l i t y o f r e s u l t s ) ,

a n d i m p r e

c i s i o n ( b a s e d o n w i d t h

o f C I s ) .

† O n l y 3 / 6 r a n d o m i z e d

, c o n t r o l l e d t r i a l s r e p o r t e d t h i s o u t c o m e .

‡ I n W a n d t e t a l ( 2 1 ) , p r o t o c o l d e v i a t i o n s o c c u r r e d i n 3 0 % o f t r a n s f u s i o n s i n t h e t h e r a p e u t i c g r o u p v s .

1 4 % i n t h e p r o p h y l a c t i c g r o u p .

§ S t a n w o r t h e t a l ( 1 9 ) r e p o r t e d n o d e a t h s

d u e t o b l e e d i n g .

W e u s e d t h e c o n t i n u i t y c

o r r e c t i o n ( 0

. 5 a s e v e n t ) t o i n c l u d e t h i s s t u d

y i n p o o l i n g t h e d a t a

.

W i d e C I s

.

¶ O n l y 4 / 6 r a n d o m i z e d

, c o n t r o l l e d t r i a l s r e p o r t e d t h i s o u t c o m e .

Annals of Internal Medicine • Vol. 162 No. 3 • 3 February 2015 www.annals.org



14/17

A p p e n d i x T a b l e 4 .

H i g h e r V e r s u s L o

w e r P l a t e l e t C o u n t T h r e s h o l d s f o r P r o p h y l a c t i c P l a t e l e t T r a n s f u s i o n s i n T h e r a p y - I n d u c e d H y p o p r o l i f e r a t i v e T h r o m b

o c y t o p e n i a

S t u d i e s b y

S u b g r o u p , n

Q u a l i t y A s s e s s m e n t *

P a t i e n t s , n / N ( % )

E f f e c t

Q u a l i t y

I m p o r t a n c e

D e s i g n

R i s k o f

B i a s

I n c o n s i s t e n c y

I n d i r e c t n e s s

I m p r e c i s i o n

O t h e r

C o n s i d e r a t i o n s


T h r e s h o l d

< 2 0

1 0 9

c e l l s / L o r

< 3 0

1 0 9

c e l l s / L

T r a n s f u s i o

n

T h r e s h o l d

< 1 0

1 0 9

c e l l s / L

O d d s R a t i o

( 9 5 %

C I )

A b s o l u t e

G r a d e 2 o r

g r e a t e r

b l e e d i n g :

4 ( 1 5

, 2 6 – 2

8 )

R a n d o m i z e d

t r i a l s

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