Denumirea procedurii terapeutice evaluate: Transfuzia de masa

trombocitara profilactic pentru reducerea riscului hemoragic

Transfuzia alogena de masa
trombocitara joacă un rol major în managementul pacienţilor trombocitopenici.
Transfuzia de trombocite nu este indicata ca răspuns la un număr redus de
trombocite din sângele periferic. Mecanismul de bază ce
cauzează trombocitopenia şi riscurile hemoragice trebuie să fie luate în
considerare.

Transfuzia de masă trombocitară poate fi administrata fie profilactic pentru a

reduce risculde sângerare, în absenţa semnelor
clinice de hemoragie (profilactic) sau pentru a controla sângerare activă atunci când
este prezenta (transfuzii terapeutice).

Scurta descriere si indicatii actuale: La începutul anilor 1970 transfuzia de

masa trombocitara a devenit parte din tratamentul standard al
pacienţilor trombocitopenici cu măduvă osoasă hipoproliferativa. (Slichter SJ.
Relationship between platelet count and bleeding risk in thrombocytopenic patients.
Tranfus Med Rev. 2004;18:153-167). La acea vreme, mai multe
studii observationale au fost efectuate pentru a determina rolul posibil al transfuziei
profilactice de masa trombocitara pentru a reduce riscul de sângerare. Pe baza unor
astfel de studii, a devenit o practică obisnuita transfuzia de masa trombocitara
profilactic la pacienţii cu numărul de trombocite sub 20 × 109 / L.
O serie de ghiduri clinice au fost publicate atât în Europa cat şi in America de
Nord, furnizand recomandări bazate pe dovezi pentru utilizarea profilactica a
9
transfuziei de masa trombocitara la un nr. de sub 10 × 10 /L si nu la mai
putin de 20 x 109 trombocite/ L, conform vechilor ghiduri. (Slichter SJ.
Evidence-based platelet transfusion guidelines. Hematology (Am Soc Hematol Educ
Program). 2007:172- 178); Schiffer CA, Anderson KC, Bennett CL, et al. Platelet
transfusions for patients with cancer: clinical practice guidelines of the American
Society of Clinical Oncology. J Clin Oncol. 2001;19:1510-1538; Stanworth SJ, Hyde
C, Heddle N, Rebulla P, Brunskill S, Murphy MF. Prophylactic platelet transfusion for
haemorrhage after chemotherapy and stem cell transplantation (Review). Cochrane
Database Syst Rev. 2004;4:CD004269; Stanworth SJ, Hyde C, Brunskill S, et al.
Platelet transfusion prophylaxis for patients with haematological malignancies: where
to now? Br J Haematol. 2005;131:588-595.)

Non indicatii actuale privind transfuzia profilactica de masa

trombocitara la nr. de trombocite sub 20 x 10 9/L: In 1997 Rebulla et al
publica un studiu randomizat multicentric care a evaluat frecventa si severitatea
evenimentelor hemoragice la pacientii nou diagnosticati cu leucemie acuta mieloida
la inductie si care au primit transfuzii de trombocite profilactic la mai putin de 10 x 10
9
trombocite / L versus 20 × 109 / L.(Rebulla P, Finazzi G, Marangoni F, et al. The
threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia.
N Engl J Med. 1997;337:1870-1875). Pacientii au fost impartiti in braţul de
control, în care subiecţii au primit masa trombocitara în cazul în care numărul
de trombocite dimineaţă a fost mai mic de 20 × 109 / L sau dacă exista hemoragia
clinic manifesta şi braţul experimental, care a inclus subiecţi care au
primit transfuzii de trombocite la nr. de trombocite dimineaţă mai puţin
de 10 × 109 /L. Dozele mai mari de trombocite au fost date în cazul în
care subiecţii studiului aveau sângerare activa sau au avut o temperatură mai mare
de 38 ° C. Rezultatele acestui studiu au aratat că nu a existat nici
o diferenţă semnificativă între cele două braţe în ceea ce priveste evenimentele
hemoragice severe sau mortalitatea.

De atunci au fost cel puţin 7 alte studii care au evaluat pragul optim pentru initierea
transfuziei de trombocite profilactic, la numărul de trombocite de sub 10
× 109 / L faţă de cel acceptat anterior de 20 × 109 / L. Aceste 7 studii au arătat ca
nu exista nici o creştere a riscului de sângerare sau un necesar transfuzional mai
mare atunci cand se initiaza transfuzia de masa trombocitara la mai putin de 10 x 10
9
trombocite /L comparativ cu limita minim acceptata anterior de 20 x 10 9 trombocite
/L.

3 surse bibliografice in sprijinul non – indicatiilor actuale:

1.
Hematology 2007

Evidence-Based Platelet Transfusion Guidelines

Sherrill J. Slichter

Sherrill J. Slichter, MD, Director, Platelet Transfusion Research, Puget Sound Blood
Center, 921 Terry Avenue, Seattle

„Previously, a plt count of 20,000/µL was considered to be an indication for

a prophylactic plt transfusion. However, four randomized prospective
transfusion trials comparing prophylactic plt transfusion triggers of 10,000
plts/µL versus 20,000 plts/µL showed no differences in hemorrhagic risks
(reviewed in Slichter SJ. Relationship between platelet count and bleeding
risk in thrombocytopenic patients. Trans Med Rev. 2004;18:153–167).
Because fewer plt transfusions were used in the lower trigger arm, a cost-
savings of 22% to 33% was achieved compared with patients in the higher
trigger arm.”

2.
Journal of Clinical Oncology, Vol 19, Issue 5 (March), 2001: 1519-1538
Platelet Transfusion for Patients With Cancer:
Clinical Practice Guidelines of the American Society
of Clinical Oncology*
By Charles A. Schiffer, Kenneth C. Anderson, Charles L. Bennett, Steven
Bernstein, Linda S. Elting, Miriam Goldsmith, Michael Goldstein, Heather
Hume, Jeffery J. McCullough, Rosemary E. McIntyre, Bayard L. Powell, John M.
Rainey, Scott D. Rowley, Paolo Rebulla, Michael B. Troner, Alton H. Wagnon,
for the American Society of Clinical Oncology

„Level of Evidence: I
Grade of Recommendation: A
The appropriateness of decreasing the threshold of prophylactic platelet transfusion
in patients with leukemia from the traditional level of 20,000 to 10,000 platelets/µL is
supported by one observational study and three comparative studies published
between 1991 and 1998. In 1991, Gmür et al57 reported their 10-year experience in
103 patients with leukemia who received transfusions at the following levels: 0 to
5,000 platelets/µL in every case; 6,000 to 10,000/µL in the presence of fresh minor
hemorrhage or body temperature greater than 38°C; 11,000/µL to 20,000/µL in the
presence of coagulopathy and/or heparin therapy and before bone marrow biopsy or
lumbar puncture; and greater than 20,000/µL in the presence of (and until control of)
major bleeding complications and before minor surgical procedures. Three fatal
hemorrhages occurred, similar to the 3.2% incidence reported from another study of
31 patients who received transfusion prophylaxis with a threshold at 15,000
platelets/µL.58 Of note is that the serious episodes of hemorrhage often occurred at
relatively high platelet counts, greater than 40,000/µL, emphasizing the importance of
clinical factors other than the platelet count in the cause of bleeding. Gmür and
Schaffner59 reported that their protocol could also be applied using random-donor
platelets rather than single-donor, apheresis platelets.
Two prospective randomized clinical trials comparing the 20,000/µL and the
10,000/µL thresholds were published in 1997. A single-center study of 72 patients
with acute leukemia performed in Iowa City by Heckman et al60 showed a reduction
from 11 to seven platelet transfusions per patient using thresholds of 20,000/µL and
10,000/µL, respectively. There were no statistically significant differences between
the groups with regard to red cell transfusion requirements, febrile days, days
hospitalized, days thrombocytopenic, need for HLA-matched platelets, remission
rate, or death during induction chemotherapy. Moreover, no patient in either group
died from hemorrhage or underwent major surgery for bleeding complications.
A large multicenter trial was performed by the Gruppo Italiano Malattie Ematologiche
dell’Adulto, which enrolled 255 assessable patients in 21 Italian centers.61 This study
focused on platelet support during the first remission induction in patients with adult
acute leukemia, excluding individuals with the French-American-British M3 subtype.
A total of 7,336 patient-days were evaluated. Patients were randomized to the
traditional 20,000/µL threshold (controls) or to a threshold of 10,000/µL when in
stable condition and less than 20,000/µL in the presence of fresh hemorrhage, fever
greater than 38°C, or invasive procedures. The 10,000/µL threshold was associated
with a 21.5% reduction in platelet requirements. There were no significant differences
in the number of red cell transfusions, patients with severe bleeding episodes, or
deaths during induction. Overall, clinically significant hemorrhages occurred in 3.1%
and 2% of the days in the 10,000/µL and 20,000/µL arms, respectively.
The most recently published evidence supporting the safety of the 10,000/µL
threshold was reported in 1998 by Wandt et al,62 who studied 105 leukemia patients
undergoing 216 remission-induction or consolidation treatment cycles in 17 centers in
Germany. Individual participating centers had previously chosen to adopt either a
20,000/µL or a 10,000/µL threshold level for their prophylactic transfusion policy. In
this study, there were 20 bleeding complications (18%) in 110 chemotherapy cycles
in the 10,000/µL group and 18 (17%) in 106 cycles in the 20,000/µL group.
Hemorrhagic deaths occurred in two patients at platelet counts of 36,000/µL and
50,000/µL treated in hospitals using the 20,000/µL threshold. Mean platelet
consumption per cycle was one third lower in the 10,000/µL group.
It should be reiterated that all of these studies had provisions for transfusion at
counts greater than 10,000/µL in patients with clinical conditions believed to be
associated with increased risks of bleeding. In addition, although contemporary blood
cell counters are quite accurate at low platelet counts, small variations in count can
result from limitations of the technology, and the decision to transfuse should
therefore be based on the clinical situation and the pattern of recent platelet counts
as well as the absolute platelet count at a given moment63
As emphasized earlier, it is important that clinicians are aware of the average number
of platelets provided in pooled PC and apheresis products in their community so as to
be able to order an appropriate number of units in specific clinical situations. A typical
interval between prophylactic transfusions in patients with acute leukemia is every 2
to 4 days depending on other clinical factors. This can usually be accomplished with
doses of 4 to 6 units of PC/transfusions in adults of average size. Larger doses may
be needed to achieve higher counts in patients who are bleeding or who require
invasive procedures (see below).”

3.
The Oncologist, Vol. 6, No. 5, 446-450, October 2001

New Strategies for Prophylactic Platelet Transfusion

in Patients with Hematologic Diseases
Hannes Wandta, Gerhard Ehningerb, Walter Michael Gallmeiera
a
5th Medical Department and Institute of Medical Oncology and Hamatology,
Nüremberg, Germany; b Medical Clinic I, Technical University, Dresden, Germany

Correspondence: Hannes Wandt, M.D., 5th Medical Department and

Institute of Medical Oncology and Hamatology, Prof.-Ernst-Nathan-Str. 1,
D-90340 Nürnberg, Germany.

„There has been a long-lasting debate over whether the traditional threshold for
prophylactic platelet transfusion of 20,000/µl is really necessary to prevent
hemorrhagic complications. During the last 10 years several studies with more
than 1,000 patients together have proven the safety of a platelet transfusion
trigger of 10,000/µl or even lower when patients are clinically stable without
active bleeding. This experience has been mostly gathered in patients with
acute leukemia. But this stringent platelet transfusion policy can be used also
after blood stem cell and bone marrow transplantation. In stable patients with
aplastic anemia and myelodysplasia, prophylactic transfusions should be
replaced in most patients by a therapeutic transfusion strategy. Such
restrictive platelet transfusion strategies decrease the risk of infectious
disease transmission, immunization, and febrile transfusion reactions. Besides
reduced hospital visits and a shorter hospital stay for the patients, the costs
for platelet transfusions are lowered by 20%-30% compared with traditional
transfusion strategies. The decision to administer platelet transfusions should
incorporate individual clinical characteristics of the patients and not simply be
a reflexive reaction to the platelet count. Further clinical studies are needed to
answer the still open question of whether patients with acute leukemia should
also be transfused therapeutically rather than prophylactically when they are
in stable condition without signs of active bleeding.”

Voi incheia cu ghidul Universitatii din Iowa privind transfuzia de masa

trombocitara:

The University of Iowa Hospitals and Clinics

HOSPITAL ADVISORY COMMITTEE
TRANSFUSION SUBCOMMITTEE

GUIDELINES FOR PLATELET TRANSFUSIONS

Platelet transfusions should not be given simply in response to a given blood

platelet count. The underlying mechanism causing thrombocytopenia and the
clinical risks of thrombocytopenia must be considered.
No Further Justification for PLATELET Transfusions is Required if One or More
of the Following can be found in the medical record:

1. Blood platelet count < 50,000/ul and either significant active bleeding as recorded
in physician notes or suggested by fall in hemoglobin of 2 g/dl (Hematocrit 6%)
within 24 hours prior to transfusion or a trauma patient or one in the perioperative
period (up to 3 days postop or patient in ICU) or a patient scheduled to undergo an
invasive procedure such as biopsy, thoracentesis, lumbar puncture, bronchoscopy,
etc.

Transfusion of platelets to bleeding or injured patients with blood platelet counts

> 50,000/ul can be justified only by continued bleeding thought due to
thrombocytopenia (i.e., other clotting studies normal); demonstration of qualitative
platelet defect (see item 3).

2. Blood platelet count < 10,000/ul and no evidence of significant bleeding PLUS
bone marrow failure by a diagnosis of progenitor cell transplant, or cancer such as
leukemia, lymphoma, carcinoma, sarcoma, or precancerous state or evidence of
severe bone marrow hypoplasia as by the diagnosis of aplastic/hypoplastic anemia or
myelodysplastic syndrome. Transfusion at a blood platelet count of 10,000 to
20,000/ul in this "prophylactic" setting is justified only by factors that increase
the risk of bleeding (e.g. active infection, liver disease with abnormal clotting
study results, renal failure).

3. Mention of active bleeding in physician, anesthesia or operative notes in patients

likely to have qualitative (functional) platelet defects — regardless of blood platelet
counts. Patients with qualitative platelet disorders should not receive platelet
transfusions unless they exhibit bleeding or are to undergo an invasive procedure.
Such patients may be identified by either the diagnosis of a "qualitative or functional"
platelet disorder (e.g., storage pool disease) mentioned in physician progress note or
by a diagnostic platelet function test reported to be abnormal. Abnormal results of
platelet function tests are poorly predictive of bleeding risk and should not, by
themselves, serve to justify a platelet transfusion.

4. Acute, massive bleeding in any patient regardless of clotting studies, except as

follows:
a. The first transfusion of platelet concentrates may be of an urgent nature and may
be given without further justification during treatment of massive blood transfusion in
which > 1 blood volume has been lost in < 24 hrs. The quantity of blood lost can be
estimated by one of several methods.
First, if the volume of blood lost has been recorded, measured or estimated in the
medical record, the volume lost can be related to the assumed normal blood volume
of 70 ml/kg (e.g., a 70 kg patient has an estimated blood volume of 4900 ml and
would be considered to require massive blood transfusion if the recorded volume of
blood lost in 24 hrs exceeded 4900 ml).

Second, when the volume of blood lost has not been recorded, it can be estimated by
noting the quantity of fluids infused intravenously to maintain acceptable vital signs
(e.g., the illustrative patient above would be considered to experience massive
transfusions if > 4900 ml of intravenous fluids had been administered in < 24 hrs).

Third, the physician's note may state that "massive" blood loss is occurring and
platelet transfusions need not await documentation of total blood lost or replaced.
Additional platelet transfusions might be necessary if bleeding continues, but the
blood platelet count must be documented to be < 50,000/ul. To justify additional
platelet transfusions (i.e., the second and all subsequent ones during the 24 hours
that follow the first platelet transfusion given for massive blood loss), clotting studies
(minimum of PT, PTT, fibrinogen and platelet count) must be done within 6 hours,
before or after the transfusion, and the blood platelet count should be documented to
be < 50,000/ul.

b. To justify platelet transfusions for smaller volumes of blood lost (< 70 ml/kg in < 24
hrs), the patient must exhibit both active hemorrhage (as described above) plus have
a blood platelet count documented to be < 50,000/ul.