Management of platelet disorders and platelet transfusions in ICU patients Neil Blumberg, Jill M. Cholette, Amy E. Schmidt, Richard P. Phipps, Sherry L. Spinelli, Joanna M. Heal, Anthony P. Pietropaoli, Majed A. Refaai, Patricia J. Sime PII: DOI: Reference:
S0887-7963(17)30048-2 doi: 10.1016/j.tmrv.2017.04.002 YTMRV 50505
To appear in:
Transfusion Medicine Reviews
Received date: Revised date: Accepted date:
9 March 2017 19 April 2017 22 April 2017
Please cite this article as: Blumberg Neil, Cholette Jill M., Schmidt Amy E., Phipps Richard P., Spinelli Sherry L., Heal Joanna M., Pietropaoli Anthony P., Refaai Majed A., Sime Patricia J., Management of platelet disorders and platelet transfusions in ICU patients, Transfusion Medicine Reviews (2017), doi: 10.1016/j.tmrv.2017.04.002
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
T
Management of platelet disorders and platelet transfusions in ICU patients
RI P
Neil Blumberg,1 Jill M. Cholette,2 Amy E. Schmidt,1 Richard P. Phipps,1,3,4 Sherry L. Spinelli,1 Joanna M. Heal,1 Anthony P. Pietropaoli,5 Majed A. Refaai1 and
NU
SC
Patricia J. Sime5
1
Transfusion Medicine, Department of Pathology and Laboratory, 2Critical Care
MA
and Cardiology, Department of Pediatrics, 3,4Departments of Environmental Medicine; Microbiology and Immunology, 5Pulmonary and Critical Care,
ED
Department of Medicine; all at Strong Memorial Hospital and Golisano Children’s
PT
Hospital, University of Rochester Medical Center, Rochester NY (USA) Corresponding Author:
AC
Box 608
CE
Neil Blumberg MD
601 Elmwood Avenue Rochester, NY 14642 (USA) Telephone 585 275 9656 Email:
[email protected] The authors declare they have no relevant conflicts of interest. Keywords: Platelet transfusion, intensive care, thrombocytopenia
1
ACCEPTED MANUSCRIPT Abstract Thrombocytopenia or receipt of anti-platelet drugs, with or without
T
bleeding, are common indications for platelet transfusions in the ICU. However
RI P
there is almost no evidence base for these practices other than expert opinion. Also common is use of platelet transfusions prior to invasive procedures or
SC
surgery in patients with thrombocytopenia. Likewise there is no high quality
NU
evidence that such practices are efficacious or safe. Recently, it has become clear that, whether causal or not, patients receiving prophylactic platelet
MA
transfusions experience high rates of nosocomial infection, thrombosis, organ failure and mortality, which increases the urgency and need for randomized trials
ED
to assess these practices. Investigational methods of improving the safety and
PT
efficacy of platelet transfusions include use of alternate strategies such as antifibrinolytics, use of ABO identical, leukoreduced and washed platelet
AC
CE
transfusions, and improved storage solutions.
2
ACCEPTED MANUSCRIPT Introduction Platelet disorders are common in critically ill adult and pediatric patients.
T
The most frequently encountered issue is thrombocytopenia. Suspected or
RI P
actual platelet dysfunction, due to disease, or, in adult and some pediatric patients, use of anti-platelet drugs and/or heparin, is also a commonly seen
SC
clinical issue. Severe congenital qualitative or quantitative disorders of platelet
NU
function or number, for example, Glanzmann’s thrombasthenia or neonatal alloimmune thrombocytopenia, are uncommon, but can be life threatening.
MA
Acquired platelet disorders, for example, autoimmune thrombocytopenia (ITP) or thrombotic thrombocytopenic purpura (TTP) are also relatively uncommon. All of
ED
these conditions have been recently reviewed by multiple authors. 1-3 We will
PT
focus on the treatment rationale for platelet transfusion in critically ill patients. By far the most common challenge in both pediatric and adult ICU settings
CE
is thrombocytopenia due to infection, sepsis, severe liver disease, multi-organ
AC
failure or massive blood loss. Frequent causes of platelet dysfunction in adult patients are use of anti-platelet agents in patients who have experienced or are at high risk of arterial thrombosis. These include such drugs as aspirin, clopidogrel and antibodies to platelet glycoproteins. This paper will touch upon the recent data suggesting that platelet transfusion may be less effective and safe than previously thought in the setting of bleeding while receiving anti-platelet drugs. There are no specific treatments for most of the above mentioned clinical problems (with the exception of ITP and TTP) except for platelet transfusions.
3
ACCEPTED MANUSCRIPT Platelet transfusions traditionally have been liberally employed to treat hemorrhage in thrombocytopenic patients and in those receiving anti-platelet
T
drugs. Platelet transfusions are routinely and frequently administered with the
RI P
expectation of preventing hemorrhage in thrombocytopenic patients who are not bleeding, but are about to undergo invasive procedures such as vascular
SC
catheter insertion, organ biopsy, and surgery.
NU
Although guidelines exist, almost no high quality clinical evidence is available concerning the efficacy and safety of platelet transfusions in the setting
MA
of critical care. This is particularly true of prophylactic platelet transfusion in non-
procedure or surgery.
ED
bleeding patients, and, in particular, in those about to undergo an invasive
PT
In patients with hematologic malignancies and severe thrombocytopenia, prophylactic platelet transfusions reduce rare, serious bleeding in acute myeloid
CE
leukemia (AML) patients during induction therapy, yet provide minimal benefit to
AC
similar but more stable patients undergoing autologous stem cell transplant. 4 How this information can be extrapolated to ICU patients is not entirely clear. Recent reports, discussed in detail later in this review, question whether prophylactic platelet transfusions to non-bleeding ICU patients, invariably at much higher platelet count thresholds than in AML, provide benefit, and with what risks.
4
ACCEPTED MANUSCRIPT
Observational data concerning the necessity/utility of prophylactic platelet
RI P
T
transfusions and therapeutic platelet transfusions in bleeding patients
In general, there are no randomized controlled trial data supporting use of
SC
transfusion of platelets to ICU patients with disorders of platelet number or
NU
function, bleeding or not. All guidelines are based upon expert opinion, and generally have been contradicted by most observational studies. Patients with
MA
disorders of platelet destruction, such as ITP and TTP usually, in our experience, do not receive platelet transfusions unless actively bleeding. There are reports
ED
that platelet transfusions to patients with TTP and heparin induced
PT
thrombocytopenia (but not ITP) are associated with increases in arterial thrombosis.5 Prophylactic platelet transfusions prior to invasive procedures or
CE
surgery have recently been associated, without proof of causation, with a high
AC
thrombosis rate (5%), and mortality rate (17%) in the ensuing weeks. 6, 7 However, importantly, the mortality rates without platelet transfusion are not well characterized. The degree to which platelet transfusions, which contain highly activated rather than resting state platelets, promote thrombosis8 is an important knowledge gap in our use of platelet transfusions in general. This is particularly true for ICU patients given these patients’ higher baseline risk for both arterial and venous thromboses. These recent reports raise questions of platelet transfusion efficacy and safety not heretofore investigated.
5
ACCEPTED MANUSCRIPT Platelet transfusion efficacy in bleeding patients Patients with disorders of platelet production, such as patients with acute
T
leukemia who have received myelotoxic chemotherapy, may benefit from
RI P
prophylactic transfusions, but this is the only setting where there are favorable randomized trial data.4 There are no data at all, other than anecdotal personal
SC
experience, whether platelet transfusions effectively treat bleeding in actively
NU
hemorrhaging patients with disorders of platelet number or function, regardless of the mechanism of thrombocytopenia. It may be that alternative approaches, such
MA
as anti-fibrinolytics, would be equally or more effective. Assessment of the effectiveness of platelet transfusions in actively hemorrhaging patients, and the
ED
efficacy when given prophylactically prior to invasive procedures and surgery, are
PT
long-standing knowledge gaps in for the management of ICU patients, and patients in general. That said, it is almost impossible to withhold platelet
AC
x109/L.
CE
transfusions from severely bleeding patients when the platelet count is
