OTT-68469-the-use-of-allogenic-platelet-gel-in-the-management-of-chemo


© 2015 Di Costanzo et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0)  
License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further 

permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on 
how to request permission may be found at: http://www.dovepress.com/permissions.php

OncoTargets and Therapy 2015:8 401–404

OncoTargets and Therapy Dovepress

submit your manuscript | www.dovepress.com

Dovepress 
401

C a s e  r e p O r T

open access to scientific and medical research

Open access Full Text article

http://dx.doi.org/10.2147/OTT.S68469

Use of allogeneic platelet gel in the management 
of chemotherapy extravasation injuries: a case 
report

Gaetano Di Costanzo1

Giovanna Loquercio1

Gianpaolo Marcacci2

Vincenzo Iervolino1

stefano Mori3

arnolfo petruzziello1

pasquale Barra1

Carmela Cacciapuoti1

1Transfusion service, Department of 
Haematology, National Cancer Institute 
“G pascale” Foundation, IrCCs, 
Naples, Italy; 2Hematology-Oncology 
and stem Cell Transplantation 
Unit, National Cancer Institute 
“G pascale” Foundation, IrCCs, 
Naples, Italy; 3Department of surgery, 
Melanoma – soft Tissues – Head 
and Neck – skin Cancers, National 
Cancer Institute “G pascale” 
Foundation, IrCCs, Naples, Italy

Abstract: The allogeneic platelet (PLT) gel offers to be a valid supportive measure in the 
management of chemotherapy extravasation injuries. We report a case of a 58-year-old patient 

with multiple myeloma enrolled for high-dose chemotherapy and autologous stem cell trans-

plantation. As pretransplant therapy, the patient received induction therapy with bortezomib, 

adriblastina, and desametazone. A port was inserted in the vein on the back of the hand. After 

three cycles, the patient reported rapid development of redness, pain, and necrotic tissue in the 

left hand, and a diagnosis of extravasation was addressed. The patient presented a raw area on 

the back of the hand caused by cytotoxic/chemotherapeutic drug leakage because of the mal-

position of venous access devices. Skin ulcer was debrided, and the wound was reconstructed 

with a combination of local random rotational flap and abdomen skin graft. Two weeks later, a 

20% skin flap necrosis was observed. In the context of wound healing, topical plasma-rich PLT 

gel is able to accelerate the regeneration and repair of tissue, so it was set out to assess PLT 

gel efficacy in this case. The PLT gel was applied topically once every 5 days, for a duration 

of 60 days on average. There were no adverse reactions observed during the topical therapy. 

Complete wound healing was observed after 12 PLT-rich plasma applications. No ulcer recur-

rence was noted in the patient during the follow-up period of 2–19 months.

Keywords: growth factors, platelet gel, chemotherapy, management, extravasation

Introduction
Extravasation is an important complication in cancer patients under chemotherapy.1–4 

Currently, chemotherapy extravasation management remains controversial,3 and there 

is no definitive standard procedure to solve the problem. We report the management of 

a patient with massive skin necrosis after extravasation of bortezomib, adriblastina, and 

desametazone. In addition to surgical debridement of necrotic tissue and skin grafting, 

we used platelet (PLT) gel, rich in growth factors (PDGF, EGF, VEGF, and TGB-α 
and -β) to stimulate healing of skin ulceration and wound closure.5

Case report
A 58-year-old man with multiple myeloma,6 Durie–Salmon stage III,7 was enrolled 

for high-dose chemotherapy and autologous stem cell transplantation. As pretrans-

plant therapy, the patient received induction therapy with bortezomib, adriblastina, 

and desametazone. A port was inserted on the back of the hand. The patient reported 

rapid development of redness and pain in the left hand, 2 weeks after the completion 

of the third cycle. The patient presented a raw area on the back of the hand because 

of leakage of cytotoxic/chemotherapeutic drugs from the malposition of venous 

access devices. Skin ulcer was debrided, and the wound was reconstructed with local 

Correspondence: Giovanna Loquercio
Department of Haematology, National 
Cancer Institute “G pascale” Foundation, 
IrCCs, via Mariano semmola, 80131, 
Napoli, Italy
Tel +39 81 590 3433
Fax +39 81 545 3560
email giovyloquercio@libero.it 

Journal name: OncoTargets and Therapy
Article Designation: Case report
Year: 2015
Volume: 8
Running head verso: Di Costanzo et al
Running head recto: Allogeneic PLT in the management of chemotherapy extravasation
DOI: http://dx.doi.org/10.2147/OTT.S68469

 
O

n
co

T
a

rg
e

ts
 a

n
d

 T
h

e
ra

p
y 

d
o

w
n

lo
a

d
e

d
 f

ro
m

 h
tt

p
s:

//
w

w
w

.d
o

ve
p

re
ss

.c
o

m
/ 

b
y 

1
2

8
.1

8
2

.8
1

.3
4

 o
n

 0
6

-A
p

r-
2

0
2

1
F

o
r 

p
e

rs
o

n
a

l u
se

 o
n

ly
.

Powered by TCPDF (www.tcpdf.org)

                               1 / 1

http://www.dovepress.com/permissions.php
http://creativecommons.org/licenses/by-nc/3.0/
www.dovepress.com
www.dovepress.com
www.dovepress.com
http://dx.doi.org/10.2147/OTT.S68469
mailto:giovyloquercio@libero.it


OncoTargets and Therapy 2015:8submit your manuscript | www.dovepress.com
Dovepress 

Dovepress

402

Di Costanzo et al

random rotational flap and abdomen skin graft. Two weeks 

later, a 20% skin flap necrosis was observed. In the contest 

of wound healing, numerous studies and clinical findings 

have demonstrated that topical, nontransfusional plasma-rich 

PLT gel is able to accelerate the regeneration and repair of 

the tissue, through the action of the various growth factors 

within the alpha granules of the PLTs.8–12 The PLT gel treat-

ment has been used based on biological and clinical results 

reported in literature. According to the standard current 

approach,13 the lesion management included the surgical 

removal of necrotic material and cleansing of margins 

of the wound bed before PLT gel application (Figure 1). 

After moist saline dressing, the wound was covered with 

allogeneic platelet-rich plasma (PRP) and fatty gauze. In 

our case, a blood component (thrombin) was produced 

from allogeneic whole blood using a “homemade” system. 

The PLT gel was prepared the day of the treatment. Samples 

of whole blood (total 40 mL) were collected in 10-mL acid-

citrate-dextrose vacutainers (Becton Dickinson Labware, 

Franklin Lakes, NJ, USA) from periodic donors. The whole 

blood was centrifuged at 180 g for 10 minutes to obtain 

concentrated erythrocytes and PRP. PRP were centrifuged 

again at 1,800 g for 10 minutes to separate PLT concentrate 

from PLT-poor plasma.

To activate the PRP homologous and to accelerate the 

gelling process, thrombin autologous was prepared by adding 

calcium gluconate to the PLT-poor plasma (ratio 0.2:1 mL). 

After 15–40 minutes of incubation at 37°C, the product was 
centrifuged at 1,800 g for 10–15 minutes. One milliliter 

of thrombin-containing supernatant and 0.50 mL of ion-

ized Ca++ were added to the previously separated PRP, in a 

Petri dish (Falcon, Becton Dickinson Labware), and mixed 

until a gelatinous mixture was obtained (from 2 minutes to 

5 minutes). All the procedure has been performed under a 

laminar-flow hood (Faster Bio48).

The nonhealing ulcer measured 3×4 cm (Figure 1). 
Three days after adjusting debridement, the wound 

was covered with allogeneic PRP (Figure 2A). The PLT 

gel was applied topically once every 5 days. The healing 

time was 60 days on average. The wound healed completely 

after 12 applications (Figure 3). The presence of granulation 

tissue was observed and recorded by digital photography in 

the patient after the second application of PLT gel. Figure 1 

illustrates the ulcer before the treatment; Figures 2B and 3  

show the same lesion, respectively, after 20 days and 

60 days. No adverse reactions were observed during the topic 

therapy. No ulcer recurrence during the follow-up period of 

2–19 months in the patient was noted.

Figure 1 skin lesion after surgical debridement of necrotic tissue.

Figure 2 (A) First application of platelet gel. (B) skin photograph 20 days after the start of therapy.

 
O

n
co

T
a

rg
e

ts
 a

n
d

 T
h

e
ra

p
y 

d
o

w
n

lo
a

d
e

d
 f

ro
m

 h
tt

p
s:

//
w

w
w

.d
o

ve
p

re
ss

.c
o

m
/ 

b
y 

1
2

8
.1

8
2

.8
1

.3
4

 o
n

 0
6

-A
p

r-
2

0
2

1
F

o
r 

p
e

rs
o

n
a

l u
se

 o
n

ly
.

Powered by TCPDF (www.tcpdf.org)

                               1 / 1

www.dovepress.com
www.dovepress.com
www.dovepress.com


OncoTargets and Therapy 2015:8 submit your manuscript | www.dovepress.com
Dovepress 

Dovepress

403

allogeneic pLT in the management of chemotherapy extravasation

Discussion
Accidental extravasation of chemotherapy into surround-

ing tissue is a frequent event. Indeed, the phenomenon is 

estimated at a rate of between 0.1% and 6%.14–16 Treatment 

of extravasations depends on the quantity extravasated, the 

delay until therapy is started, and the size of the resulting 

necrotic injury. Historically, a number of local treatments 

have been used, such as dimethyl sulfoxide17,18 cooling and 

intralesional injection of corticosteroids19 with either no 

proven benefit or even detrimental effect. However, if the 

condition is missed, the consequences may be dramatic, with 

massive necrosis and ensuing tissue destruction. Here we 

have described the case of a patient with multiple myeloma 

and severe skin necrosis induced by chemotherapy, who was 

treated with PLT gel. PLT gel rapidly repaired the ulceration 

damage, blocked the progression of lesion, reduced the 

intensity of pain, and restored the patient’s ability to move 

the hand. Greppi et al demonstrated the efficacy of PLT 

gel to treat recalcitrant ulcers in geriatric and hypomobile 

patients with chronic skin ulcers unresponsive to previous 

treatment with advanced medications.13 A meta-analysis 

review had revealed PRP as an advanced wound therapy in 

hard-heal acute and chronic wounds, favored significantly 

for complete healing.20,21 This process was regulated by 

PLTs, not only for their hemostatic function but also for their 

ability to repair and regenerate damaged tissues.22–27 These 

mechanisms are regulated by cytokines and growth factors 

released by activated PLTs. The cytokines and growth fac-

tors contained within PLT-α granules act via an endocrine, 
paracrine, and autocrine mechanism, binding to the tyrosine 

kinase-activated membrane receptors found on the various 

tissue effectors, thereby regulating chemotaxis, cell prolif-

eration, angiogenesis, and the synthesis and degradation of 

extracellular matrix proteins.28–30 Although in several clinical 

studies, topical therapy seems to exhibit no clear adjuvant 

effect on wound healing,31,32 based on our experience we 

suggest that the use of PLT gel, together with conventional 

therapies, could be considered as an effective treatment for 

the management of chemotherapy-induced damage and tissue 

necrosis in oncologic patients.

Acknowledgment
We acknowledge the medical assistance of technical and 

nursing staff: Antonio Mattiello, Vincenza Passante, and 

Assunta Coppola.

Patient consent
Patient consent was obtained for this study.

Disclosure
The authors declare no conflicts of interest in this work.

References
 1. Ener RA, Meglathery SB, Styler M. Exstravasation of systemic hemato-

oncological therapies. Annals Oncol. 2004;15:858–862.
 2. Sauerland C, Engelking C, Wickham R, Corbi D. Vesicant extravasa-

tion part I: mechanisms, pathogenesis, and nursing care to reduce risk. 
Oncol Nurs Forum. 2006;33(6):1134–1141.

 3. Schulmeister L. Extravasation management: clinical update. Semin 
Oncol Nurs. 2011;27(1):82–90.

 4. Schrijvers DL. Extravasation: a dreaded complication of chemotherapy. 
Ann Oncol. 2003;14(suppl 3):iii26–iii30.

 5. Iervolino V, Di Costanzo G, Azzaro R, et al. Platelet gel in cutaneous 
radiation dermatitis. Support Care Cancer. 2013;21(1):287–293.

 6. Greipp PR, San Miguel J, Durie BG, et al. International staging system 
for multiple myeloma. J Clin Oncol. 2005;23:3412–3420.

 7. Durie BG, Salmon SE. A clinical staging system for multiple myeloma. 
Correlation of measured myeloma cell mass with presenting clinical fea-
tures, response to treatment, and survival. Cancer. 1975;36:842–854.

 8. Balbo R, Avonto I, Marenchino D, Maddalena L, Menardi G, Peano G. 
Platelet gel for the treatment of traumatic loss of finger substance. Blood 
Transfus. 2010;8(4):255–259.

 9. Chen TM, Tsai JC, Burnouf T. A novel technique combining platelet 
gel, skin graft, and fibrin glue for healing recalcitrant lower extremity 
ulcers. Dermatol Surg. 2010;36(4):453–460.

 10. Picardi A, Lanti A, Cudillo L, et al. Rome transplant network. Platelet 
gel for treatment of mucocutaneous lesions related to graft-versus-host 
disease after allogeneic hematopoietic stem cell transplant. Transfusion. 
2010;50(2):501–506.

 11. Sclafani AP, Romo T 3rd, Ukrainsky G, et al. Modulation of wound 
response and soft tissue ingrowth in synthetic and allogeneic implants 
with platelet concentrate. Arch Facial Plast Surg. 2005;7(3):163–169.

 12. Smrke D, Gubina B, Domanoviç D, Rozman P. Allogeneic platelet gel 
with autologous cancellous bone graft for the treatment of a large bone 
defect. Eur Surg Res. 2007;39(3):170–174.

 13. Greppi N, Mazzucco L, Galetti G, et al. Treatment of recalcitrant ulcers 
with allogeneic platelet gel from pooled platelets in aged hypomobile 
patients. Biologicals. 2011;39:73–80.

 14. Schulmeister L, Camp Sorrell D. Chemotherapy extravasation from 
implanted ports. Oncol Nurs Forum. 2000;27(3):531–538.

 15. Schulmeister L. Management vesicant extravasations. Oncologist. 2008; 
13:284–288.

Figure 3 The previous ulceration photograph 60 days posttreatment showing 
complete closure of the lesion and re-epithelialization tissue with no inflammation.

 
O

n
co

T
a

rg
e

ts
 a

n
d

 T
h

e
ra

p
y 

d
o

w
n

lo
a

d
e

d
 f

ro
m

 h
tt

p
s:

//
w

w
w

.d
o

ve
p

re
ss

.c
o

m
/ 

b
y 

1
2

8
.1

8
2

.8
1

.3
4

 o
n

 0
6

-A
p

r-
2

0
2

1
F

o
r 

p
e

rs
o

n
a

l u
se

 o
n

ly
.

Powered by TCPDF (www.tcpdf.org)

                               1 / 1

www.dovepress.com
www.dovepress.com
www.dovepress.com


OncoTargets and Therapy

Publish your work in this journal

Submit your manuscript here: http://www.dovepress.com/oncotargets-and-therapy-journal

OncoTargets and Therapy is an international, peer-reviewed, open 
access journal focusing on the pathological basis of all cancers, potential 
targets for therapy and treatment protocols employed to improve the 
management of cancer patients. The journal also focuses on the impact 
of management programs and new therapeutic agents and protocols on 

patient perspectives such as quality of life, adherence and satisfaction. 
The manuscript management system is completely online and includes 
a very quick and fair peer-review system, which is all easy to use. Visit 
http://www.dovepress.com/testimonials.php to read real quotes from 
published authors.

OncoTargets and Therapy 2015:8submit your manuscript | www.dovepress.com
Dovepress 

Dovepress

Dovepress

404

Di Costanzo et al

 16. Yildizeli B, Laçin T, Batirel HF, Yüksel M. Complication and manage-
ment of long-term central venous access catheters and ports. J Vasc 
Access. 2004;5(4):174–178.

 17. Bertelli G, Gozza A, Forno GB, et al. Topical dimethylsulfoxide for 
the prevention of soft tissue injury after extravasation of vesicant 
cytotoxic drugs: a prospective clinical study. J Clin Oncol. 1995;13: 
2851–2855.

 18. Dorr RT, Alberts DS. Failure of DMSO and vitamin E to prevent 
doxorubicin skin ulceration in the mouse. Cancer Treat Rep. 1983;67: 
499–501.

 19. Dorr RT, Alberts DS, Chen HS. The limited role of corticosteroids 
in ameliorating experimental doxorubicin skin toxicity in the mouse. 
Cancer Chemother Pharmacol. 1980;5:17–20.

 20. Carter MJ, Fylling CP, Parnell LK. Use of platelet rich plasma gel on 
wound healing: a systematic review and meta-analysis. Eplasty. 2011; 
11:e38.

 21. de Leon JM, Driver VR, Fylling CP, et al. The clinical relevance of 
treating chronic wounds with an enhanced near-physiological concen-
tration of platelet-rich plasma gel. Adv Skin Wound Care. 2011;24(8): 
357–368.

 22. Cooper DM, Yu EZ, Hennessey P, Ko F, Robson MC. Determination 
of endogenous cytokines in chronic wounds. Ann Surg. 1994;219: 
688–691.

 23. Everts PA, Brown MC, Hoffmann JJ, et al. Platelet-rich plasma 
preparation using three devices: implications for platelet activation and 
platelet growth factor release. Growth Factors. 2006;24:165–171.

 24. Frechette JP, Martineau I, Gagnon G. Platelet-rich plasmas: growth factor 
content and roles in wound healing. J Dent Res. 2005;84:434–439.

 25. Mazzucco L, Medici D, Serra M, et al. The use of autologous platelet 
gel to treat difficult-to-heal wounds: a pilot study. Transfusion. 2004;44: 
1013–1018.

 26. Okuda K, Kawase T, Momose M, et al. Platelet-rich plasma contains 
high levels of platelet-derived growth factor and transforming growth 
factor-beta and modulates the proliferation of periodontally related cells 
in vitro. J Periodontol. 2003;74:849–857.

 27. Tarroni G, Tessarin C, De SL, et al. [Local therapy with platelet-derived 
growth factors for chronic diabetic ulcers in haemodialysis patients]. 
G Ital Nefrol. 2002;19:630–633. Italian.

 28. Anitua E, Sanchez M, Nurden AT, Nurden P, Orive G, Andia I. New 
insights into and novel applications for platelet-rich fibrin therapies. 
Trends Biotechnol. 2006;24:227–234.

29. Borzini P, Mazzucco L. Platelet gels and releasates. Curr Opin Hematol. 
2005;12:473–479.

 30. Verheul HM, Jorna AS, Hoekman K, Broxterman HJ, Gebbink MF, 
Pinedo HM. Vascular endothelial growth factor-stimulated endothelial 
cells promote adhesion and activation of platelets. Blood. 2000;96: 
4216–4221.

 31. Senet P, Bon FX, Benbunan M, et al. Randomized trial and local 
biological effect of autologous platelets used as adjuvant therapy for 
chronic venous leg ulcers. J Vasc Surg. 2003;38(6):1342–1348.

 32. Stacey MC, Mata SD, Trengove NJ, Mather CA. Randomised 
double-blind placebo controlled trial of topical autologous platelet 
lysate in venous ulcer healing. Eur J Vasc Endovasc Surg. 2000;20(3): 
296–301.

 
O

n
co

T
a

rg
e

ts
 a

n
d

 T
h

e
ra

p
y 

d
o

w
n

lo
a

d
e

d
 f

ro
m

 h
tt

p
s:

//
w

w
w

.d
o

ve
p

re
ss

.c
o

m
/ 

b
y 

1
2

8
.1

8
2

.8
1

.3
4

 o
n

 0
6

-A
p

r-
2

0
2

1
F

o
r 

p
e

rs
o

n
a

l u
se

 o
n

ly
.

Powered by TCPDF (www.tcpdf.org)

                               1 / 1

http://www.dovepress.com/oncotargets-and-therapy-journal
http://www.dovepress.com/testimonials.php
www.dovepress.com
www.dovepress.com
www.dovepress.com
www.dovepress.com

	Publication Info 2: 
	Nimber of times reviewed: