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Symptom Management and Supportive Care

Management of Bleeding in Patients with Advanced Cancer
JOSE PEREIRA, TIEN PHAN
Department of Oncology, University of Calgary, Calgary, Alberta, Canada

Key Words. Bleeding · Hemorrhaging · Cancer · Palliative

L EARNING O BJECTIVES

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After completing this course, the reader will be able to:
1. List at least four local hemostatic agents and dressings for controlling localized bleeding in a patient with cancer.
2. List at least four systemic therapies for controlling bleeding in a patient with advanced cancer.
3. Describe a decision-making process related to managing bleeding in an end-of-life cancer patient.

CME Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com

A BSTRACT
Bleeding occurs in up to 10% of patients with advanced
cancer. It can present in many different ways. This article
provides a qualitative review of treatment options available
to manage visible bleeding. Local modalities, such as hemo-
static agents and dressings, radiotherapy, endoscopic lig-
ation and coagulation, and transcutaneous arterial
embolization, are reviewed in the context of advanced
cancer, as are systemic treatments such as vitamin K,
vasopressin/desmopressin, octreotide/somatostatin, antifi-
brinolytic agents (tranexamic acid and aminocaproic
acid), and blood products. Considerations at the end of life
are described. The Oncologist 2004;9:561-570

INTRODUCTION functioning and number. The underlying causes of these

Hemorrhaging occurs in approximately 6%-10% of
patients with advanced cancer [1]. When visible, it can be
particularly distressing to patients and their caregivers [2,
3]. In some patients, it may be the immediate cause of
death. This article focuses on hemorrhaging that is visible,
as opposed to occult bleeding. It reviews treatment options
in the context of advanced cancer.
Etiology and Clinical Presentation
Bleeding may result from local vessel damage and inva-
sion or from systemic processes such as disseminated
intravascular coagulopathy (DIC) or abnormalities in platelet
abnormalities are varied and include liver failure, medica-
tions such as anticoagulants, chemotherapy, radiotherapy,
surgery, and the cancer itself [4]. Occasionally, concurrent
diseases, such as idiopathic thrombocytopenia, may be
responsible. Hemorrhaging may manifest in a variety of ways,
including hematemesis, hematochezia, melena, hemoptysis,
hematuria, epistaxis, vaginal bleeding, or ulcerated skin
lesions [4]. It may also present as echymoses, petechiae, or
bruising. Hemorrhage may occur as an acute catastrophic
event, episodic major bleeds, or ongoing low-volume oozing.
These characteristics provide clues as to the underlying
cause and guide management.

Correspondence: Jose Pereira, MBChB, DA, CCFP, Palliative Care Office, Room 710, South Tower, Foothills Medical
Centre, 1403-29th Avenue NW, Calgary, Alberta, T2N 2T9, Canada. Telephone: 403-944-2307; Fax: 403-270-9652;
e-mail: pereiraj@ucalgary.ca Received November 19, 2003; accepted for publication March 22, 2004. ©AlphaMed Press
1083-7159/2004/$12.00/0

The Oncologist 2004;9:561-570 www.TheOncologist.com

Pereira, Phan
MANAGEMENT: GENERAL MEASURES
Treatment needs to be individualized and depends on
several factors, including the underlying cause(s), the like-
lihood of reversing or controlling the underlying etiology, and
the burden-to-benefit ratio of the treatment, all in the context
of the patient’s overall disease burden, life expectancy, and
goals of care. If the patient’s life expectancy and overall qual-
ity of life warrants it, then management of an acute bleeding
episode consists of general resuscitative measures, such as
volume and fluid replacement, and specific measures to
stop the bleeding. On the other hand, if the patient’s goals
of care are palliative, then management may include mea-
sures to stop the bleeding without full resuscitative mea-
sures. Comfort measures only may be most appropriate for
end-stage patients.
Management should focus on identifying the underlying
cause(s) and, where possible, controlling the bleeding. A
comprehensive history and examination is self-evident. A
review of concurrent medications and other illnesses may be
helpful in identifying the etiology or contributing factors,
such as the concurrent use of nonsteroidal anti-inflammatory
drugs, which may exacerbate or precipitate bleeding through
their actions on the gastrointestinal tract and platelet func-
tioning [5]. The burdens and risks of prophylactic anticoagu-
lation may outweigh the benefits in patients with very
advanced disease. Even when treated with appropriate thera-
peutic doses of anticoagulants, the incidence of bleeding
complications remains higher in patients with advanced can-
cer than in those with earlier-stage disease [6]. Investigations
may be helpful. Full blood counts and clotting profiles may
reveal systemic problems, while angiography or endoscopic
studies may identify the site of bleeding. Goals of care should
be explored. General measures may include applying pressure
over the wound, and protecting the bleeding area from trauma
and from the remaining infected granulation tissue [7].
Patients at high risk for bleeding should be identified,
and preventative measures should be taken before a crisis
occurs. Episodic, low-volume bleeding (e.g., hemoptysis)
may herald larger, catastrophic hemorrhages. Caregivers of
patients at risk for major bleeds ought to be informed and
prepared for such an event. However, this should be done
sensitively so as not to invoke too much fear.
MANAGEMENT: LOCAL INTERVENTIONS (TABLE 1)
Packing, Hemostatic Agents, and Dressings
Packing can be used with or without pressure to achieve
hemostasis when bleeding originates in the nose [8, 9],
vagina [10, 11], or rectum [12, 13]. Surgical swabs of vary-
ing sizes may be used. These can be coated with chemicals
that facilitate hemostasis; for example, acetone in vaginal
562
packing [10, 14] and cocaine in nasal packing. If possible,
the frequency of dressing changes should be reduced, and
nonadherent dressings should be used. Specially designed
catheters with inflatable balloons may be used to control
severe epistaxis. Foley catheters have also been used for this
purpose. Such measures are temporary, since prolonged
pressure may cause local ischemia.
A variety of agents and dressings, mostly designed for
surgical procedures, has been reported to be of benefit for
exterior, topical use in patients with advanced cancer [15].
The evidence to support this, however, is largely based on
case reports. The high costs of some of these products may
also be prohibitively expensive for regular usage. Thrombo-
plastin, a natural blood-clotting agent obtained from bovine
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plasma, is available as a powder for topical application [16].
Systemic injection or absorption can lead to serious clotting.
Absorbable gelatin is available as a sterile sponge-like dress-
ing or sterile powder [17-19]. It can be applied dry or satu-
rated with sterile sodium solution and is absorbed within 4-6
weeks. When applied, fibrin is deposited in the interstices of
the foam, resulting in swelling of the sponge, thereby forming
a large synthetic clot. When applied to nasal, rectal, or vagi-
nal mucosa, it liquifies within 2-5 days. Other bioabsorbable
topical hemostatic agents include fibrin sealants [20, 21] and
Table 1. Management of bleeding in patients with advanced cancer:
local measures
• Nonadherent dressings
• Hemostatic dressings
—Absorbable gelatin (sponge)
—Microfibrillar collagen
—Absorbable collagen sheet
—Absorbable collagen sponge
—Oxidized cellulose and regenerated cellulose
—Fibrin sealants
—Alginates
• Hemostatic agents
—Epinephrine
—Acetone
—Thrombin/thromboplastin
—Topical cocaine
—Prostaglandins E2 and F2
—Silver nitrate
—Formalin
—Aluminum astringents
—Sucralfate
• Radiotherapy
• Surgery
—Vessel ligation
—Tissue resection
• Endoscopy
• Interventional radiology
—Transcutaneous arterial embolization
—Transcutaneous arterial balloons
563
oxidized cellulose [13]. Fibrin sealants are derived from
human plasma and reproduce the final steps in the coagulation
pathway to form a clot. They are used in a broad range of sur-
gical procedures to assist hemostasis, including cardiovascu-
lar, hepatic, and splenic surgery. Some are impregnated with
clotting factor XIII and a solution of thrombin and calcium
chloride [9]. Collagen is another agent with inherent hemo-
static activity. When applied as a bovine-derived mesh it
comes into contact with blood, provokes the clotting cascade,
and forms a clot [11, 12]. Alternatively, oxidized cellulose
compounds and highly absorbent alginate dressings, derived
from seaweed, are available for topical use [12, 14].
Vasoconstricting or cauterizing agents provide an alter-
native modality to managing localized, capillary-based
bleeding. Epinephrine may be used, but its liberal use is dis-
couraged [12]. Prostaglandins E2 and F2 have been used to
control intractable hemorrhagic cystitis [22]. Bladder
spasms, however, may limit their utility. Silver nitrate, an
inorganic silver salt, induces a chemical cauterization and
has been used to control bladder hemorrhages and epistaxis
[12, 23]. Formalin, 2% or 4%, acts as a chemical cautery and
has been used to control intractable rectal [24-26] and blad-
der [22] hemorrhaging. In one case series, topical formalin
controlled bleeding in 49 of 55 patients (89%) with radiation-
induced rectal bleeding. Aluminum astringents, such as 1%
alum, can be delivered by continuous bladder irrigation [22].
Bladder spasms are controllable with antispasmodic medica-
tions. Sucralfate has shown some benefit in controlling can-
cer-related gastrointestinal bleeding and cutaneous oozing
[15]. In the latter, a gel is prepared by dispersing one 1-g
tablet of sucralfate in 5 ml of water soluble gel (e.g., K-Y®
Jelly; McNeil-PPC, Inc.; Skillman, NJ) and is applied once
or twice daily [15].
Radiotherapy
External-beam radiotherapy has been shown to
decrease hemoptysis caused by lung cancer, with control
occurring in up to 80% of patients [27-30]. The optimal
dose and fractionation remain controversial. Hypofrac-
tionation appears to be as effective as multiple fractions
(often 10 or more daily fractions) [31-33]. A single fraction
of 10 Gy has been shown to be as effective as multiple frac-
tions in patients with hemoptysis due to lung cancer [29].
Total doses of either 20 Gy (via multiple fractions) or 8 Gy
(via hypofractionation) are often suggested.
Radiotherapy should also be considered for bleeding from
cancerous lesions of the vagina [29, 34], skin [35], rectum, and
bladder [29, 36, 37]. External-beam radiotherapy may be suc-
cessful in controlling bleeding in up to 85% of cases of rectal
bleeding and 60% of cases of hematuria from bladder cancer
[29, 36]. One study found that a hypofractionated regimen
Bleeding Management in Advanced Cancer
(17 Gy in two fractions over 3 days) for patients with symp-
toms from advanced bladder cancer was as well tolerated as
and less distressing to patients than a regimen of 12 fractions
given over 26 days (45 Gy) [36].
Upper gastrointestinal hemorrhaging from malignant
processes is less amenable to radiotherapy. While radio-
therapy can be useful in controlling bleeding from head and
neck cancers, many of these patients have already received
maximal doses of radiotherapy when they present with
bleeding, thereby excluding further radiation [38]. Single
or reduced fraction regimens appear to be as effective as
multiple fractions in controlling bleeding [29].
Endoscopy
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Endoscopy-based treatments have, for a long time, been
used in managing bleeding from upper gastrointestinal
varices, particularly after systemic therapies such as vaso-
pressin or somatostatin analogues have failed. This treat-
ment method has been reported to be superior to balloon
tamponade [39]. It involves the injection of sclerosing
agents into the varices or ligation of the vessels.
Endoscopic interventions have also been proven to be
useful for managing cancer-related hemorrhaging of the
upper gastrointestinal tract [40, 41], lungs [42-44], and blad-
der [45]. Ethanol [46, 47], hyperosmotic saline epinephrine
[41], gelatin solutions [48], and sodium tetradecyl sulfate [41]
are injected into the site of bleeding. Alternatively, the vessels
may be cauterized by heat [47, 49], or by polar [47, 49] or
laser coagulation [50, 51].
Akhtar and colleagues reported on a series of 48 con-
secutive patients with esophagogastric cancer who under-
went endoscopic argon-beam plasma coagulation for
symptom and disease control [40]. Bleeding was well con-
trolled in three of the five patients treated for bleeding.
Hemostasis was achieved in approximately 70%-90% [41,
49] of cases treated for upper gastrointestinal bleeds.
Complications occurred in 5%-15% of cases and included
worsening of the bleeding and perforation of the tract. Cysto-
scopic-assisted cautery by either heat or laser probes has
been used in the treatment of hematuria in patients with blad-
der cancer [45]. Its role is mainly for patients in whom con-
tinuous bladder irrigation and lavage have failed. Under
direct vision, the urologist can inspect the bladder, identify
the source of bleeding, and fulgurate the bleeding vessel or
tumor [22, 29, 45]. In the case of hemoptysis, bronchoscopy
allows for ice-cold saline lavages [44] and/or the use of bal-
loon tamponade [44, 52], laser phototherapy [44], or topical
application of thrombin or fibrinogen at the site of bleeding
[44]. Endoscopic procedures have been used to control
bleeds from the lower gastrointestinal tract, although these
may be more challenging [53, 54]. Colonoscopic techniques
Pereira, Phan
vary and include bipolar electrocoagulation, heater probe,
argon [55], and Nd:YAG lasers [54].
Interventional Radiology
Transcutaneous arterial embolization (TAE) may be use-
ful in well-selected patients. The procedure is often performed
via a femoral or axillary approach under local anesthetic and
is generally well tolerated, requiring only mild sedation [56].
The blood vessel supplying the affected site is first identified
by arteriography. This is followed by the insertion of a hemo-
static agent, usually in the form of a coil. Limiting factors
include the presence of a bleeding disorder and the availabil-
ity of the appropriate expertise. Embolization is restricted to
areas where the blood vessels are accessible by the catheter
and where embolization of the blood vessel does not result in
ischemia of key organs. Benefits have been reported in
patients with cancers involving the head and neck [57-59],
pelvis [60-64], lung [43, 44, 61, 65], liver [66], and gastroin-
testinal tract [67]. As with other treatment options in this set-
ting, the majority of the evidence supporting this modality
relies on case reports.
Nabi and team evaluated the efficacy of bilateral inter-
nal iliac artery embolization with permanent coils to control
intractable hemorrhage from advanced pelvic urological
malignancies [60]. Bleeding was controlled in all but one of
six patients at the first attempt. The nonresponder was suc-
cessfully treated at a second attempt. Complications were
minor and included nausea, vomiting, and fever for a few
days. At 22-month follow-ups, no patient had experienced
bleeding recurrence.
TAE has been used to manage carotid artery rupture in
cancer patients. Bates and Shamsham reported on a patient
whose episodes of profuse (but self-limited) carotid hemor-
rhage were successfully controlled by an endovascular tech-
nique that combined placement of a flexible self-expanding
stent-graft to protect the common and internal carotid artery
with selective coil embolization of the affected external
carotid artery branches [57]. Sakakibara and colleagues used
an endoluminal balloon to control bleeding in three patients
prior to undergoing surgical ligation of the arteries [58].
Transhepatic arterioembolization was used to control
bleeding in five patients with inoperable hepatocellular cancer
who presented with gastrointestinal bleeding from a variety
of sources (esophageal varices or direct invasion of the duo-
denum, transverse colon, or stomach) [67]. Recordare and
colleagues described four patients who underwent TAE to
control spontaneous rupture of hepatocellular carcinoma
[66]. Patients lived for 3-62 months following the proce-
dure. A quality-of-life analysis was not reported. Wu and
colleagues suggested that acute upper gastrointestinal bleed-
ing is a potential complication following TAE in patients with
564
hepatocellular cancer [68]. Thirty-one of 208 patients who
underwent TAE in their service experienced upper gas-
trointestinal bleeding after the procedure. However, given
that gastric or duodenal ulcers were found in 21 of these
cases, Mallory-Weiss syndrome was found in three cases,
and esophageal varices were found in two cases, the bleed-
ing was likely the result of comorbidities and complications
of the cancer rather than the treatment itself. Notwith-
standing, the importance of meticulous case selection needs
to be underscored.
Surgery
Surgery may be appropriate for a small group of well-
selected patients who have failed conservative measures
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and who are deemed fit for surgery. Surgery usually con-
sists of ligation of larger vessels [69] or the removal of
bleeding tissue [70]. Two surgical approaches have been
described for the management of carotid artery rupture:
resection with reconstruction and ligation of the artery. Witz
et al. reported on three patients with head and neck cancers
who presented with acute or imminent carotid artery rup-
ture [69]. Those patients successfully underwent ligation
of the artery with no neurological sequelae. Yegappan and
colleagues reported on prospectively collected data from
55 women who presented with bleeding from radiation
proctitis [26]. Bleeding in six patients who did not respond
to topical formalin application was controlled with surgery.
MANAGEMENT: SYSTEMIC INTERVENTIONS (TABLE 2)
Vitamin K (Phytonadione, Menadiol)
Vitamin K is necessary for the hepatic production of a
number of clotting factors, including factors II, VII, IX, and
X. Liver disease, insufficient intake of leafy green vegetables
(a source of vitamin K), small bowel disease or resection, as
well as intrahepatic and extrahepatic biliary obstruction can
Table 2. Management of bleeding in patients with advanced cancer:
systemic interventions
• Vitamin K (phytonadione)
• Vasopressin/desmopressin
• Somatostatin analogues (octreotide)
• Antifibrinolytic agents
—Tranexamic acid
—Aminocaproic acid
—Aprotinin
• Blood Products
—Platelets
—Fresh frozen plasma
—Coagulation factors
—Packed red blood cell
565
lead to deficiencies in the clotting factors. Coagulation
screening studies reveal a prolonged prothrombin time or
international normalized ratio (INR) and partial thrombo-
plastin time with normal thrombin time, fibrinogen, and
serum fibrin-fibrinogen degradation products.
Vitamin K treatment may be helpful if either a derange-
ment of these factors or excessive warfarin therapy is impli-
cated in bleeding in a patient with advanced cancer. Doses of
2.5-10 mg are recommended, depending on the severity of the
situation. The jury is not out on which route of administration
is best. Whitling et al. evaluated four different routes of vita-
min K administration for reversing excessive anticoagulation:
high-dose intravenous (1-10 mg), low-dose intravenous (≤0.5
mg), subcutaneous (1-10 mg), and oral (2.5-5 mg) [71].
Anticoagulation was achieved in all four groups. Although
the high-dose intravenous method was the most effective at
lowering INR levels to <5, overcorrection occurred more fre-
quently with that method. Byrd and colleagues reported the
effective and safe reversal of excess warfarin anticoagulation
using subcutaneous phytonadione at doses of 1 mg for INR
levels >8 but <14 (group 1) and 2 mg for levels >14 (group 2)
[72]. The mean INR reductions in group 1 and group 2 after
24 hours were 49% and 67%, respectively. By 48 hours,
INR levels were below 4.5 in both groups. No hemorrhagic
or thrombotic complications were reported. The subcuta-
neous administration of phytonadione did not correct the
INR as rapidly or as effectively as intravenous administra-
tion in a randomized trial [73]. Higher doses of subcuta-
neous phytonadione were recommended for cases where full
anticoagulation reversal is required. Nee et al. suggested that
subcutaneous administration along with modification of the
warfarin dosing is acceptable, since all patients in their study
achieved safe levels of anticoagulation within 72 hours of
subcutaneous administration [74]. A recent retrospective
study of 105 patients reported that only two (1.9%) patients
who received intravenous phytonadione experienced
adverse reactions [75]. These anaphylactoid reactions mani-
fest as dyspnea, chest tightness, facial flushing, nausea, and,
in severe cases, cyanosis, loss of consciousness, hypotension,
and possibly death. However, review of the literature reveals
that these are rare occurrences [76].
A randomized, double-blind, placebo-controlled study
comparing oral phytonadione (2.5 mg) plus the omission of
further warfarin therapy with omission alone for reversing
excessive warfarin anticoagulation in 30 asymptomatic
patients (INR levels of 6-10) found that the addition of oral
phytonadione reduced the time to achieve a normal INR by 1
day [77]. Adverse effects did not differ between the two
groups. Fondevila et al., on the other hand, reported no advan-
tage of adding oral phytonadione (1 mg) to a regimen of sim-
ply discontinuing the warfarin in patients with excessive oral
Bleeding Management in Advanced Cancer
anticoagulation [78]. Oral menadiol (20 mg daily for 3 days)
was found to be as effective as intravenous phytonadione
(1 mg daily) in normalizing INR levels in 26 patients with
cholestasis [79]. Therefore, when possible, vitamin K should
be given by the subcutaneous or oral routes. When intra-
venous administration is considered unavoidable, the drug
should be injected slowly, probably not exceeding 1 mg per
minute. If, in 6-8 hours after parenteral administration, the
INR is not satisfactorily lowered, the dose may be repeated.
The role of prophylactic vitamin K administration for
asymptomatic patients with elevated INR levels from liver
involvement is unclear.
Vasopressin/Desmopressin
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Vasopressin is a posterior pituitary hormone that causes
splanchnic arteriolar constriction and reduction in portal pres-
sure when injected intravenously or intra-arterially [80]. This
method has been extensively used in managing variceal
bleeding related to portal gastropathy [81, 82]. Its use has
also been reported in oncology. In a controlled trial, vaso-
pressin therapy stopped bleeding in about half the patients
with active upper-malignancy-related gastrointestinal
bleeding [83]. Doses range from 0.1-0.4 mg by continuous
infusion. Vasoconstrictor effects on the myocardial, mesen-
teric, and cerebral circulation are the most notable potential
side effects.
Somatostatin Analogues
Octreotide, an analogue of somatostatin, has been used
to manage upper gastrointestinal bleeds [84]. Somatostatin
reduces splanchnic flow and pressure via venous dilatation,
thereby reducing portal pressure and portal venous flow. A
starting dose of 50-100 µg twice daily is recommended
[85]. The dose may be titrated, as needed, up to 600 µg per
day. An alternative regime consists of a bolus of 50 µg
given intravenously or subcutaneously, followed by a con-
tinuous subcutaneous or intravenous infusion of 50 µg/hour
for 48 hours [86]. At low doses, very few side effects are
reported, but at doses greater than 100 µg/hour, nausea,
abdominal discomfort, and diarrhea may occur.
D’Amico et al., in a meta-analysis, concluded that emer-
gency sclerotherapy should be used only after vasoactive
drugs (octreotide, somatostatin, vasopressin, terlipressin),
which are effective in approximately 83% of cases, have
failed [82]. A more recent meta-analysis reported that ligation
appears to be the most effective treatment for bleeding varices
(effective in a mean of 91% of times, 95% confidence inter-
val [CI] = 82%-96%): more effective than vasoconstrictive
treatment (vasopressin/terlipressin, which were effective
69% of times, 95% CI = 62%-83%), vasoactive treatment
(somatostatin/octreotide, 76%; 95% CI = 68%-83%), and
Pereira, Phan
sclerotherapy (81%; 95% CI = 72%-88%) [81]. The differ-
ence between ligation and sclerotherapy was not significant.
Except for preventing perioperative bleeding in pancre-
atic cancer resections [87], there are no reports related to
the use of octreotide/somatostatin in controlling bleeding in
cancer patients.
Antifibrinolytic Agents
Tranexamic acid (TA) and aminocaproic acid (EACA)
are synthetic antifibrinolytic agents that block the binding
sites of plasminogen, thereby inhibiting the conversion of
plasminogen into plasmin by tissue plasminogen activator
[88]. The end result is a decreased lysis of fibrin clots [89,
90]. Tranexamic acid is approximately 10 times more potent
than EACA in vitro [91, 92]. Fibrinolytic inhibitors have
been used successfully in a variety of nononcologic settings.
These include the control of bleeding following dental
extractions [93], subarachnoid hemorrhages [94], and gas-
trointestinal bleeds [95]. Several case reports and a few stud-
ies have been published that suggest a role for these agents
in the oncology setting [88, 96-101].
TA and EACA have been administered orally and
intravenously. The suggested intravenous dose of TA is
10 mg/kg three to four times a day, infused over about
1 hour. The suggested intravenous dose of EACA is 4-5 g
in 250 ml over the first hour then 1 g/hour in 50 ml admin-
istered continuously for 8 hours, or until the bleeding is
controlled [92]. The most common adverse effects are
gastrointestinal in nature (nausea, vomiting, and diarrhea)
and occur in 25% of cases [91]. Adverse effects appear to
be dose dependent. Thromboembolism is uncommon
[101, 102]. These antifibriolytics can also be applied top-
ically, rectally, or by intrapleural instillation [88, 97, 103].
A systematic review of randomized trials found that
hemostatic medications (TA, EACA, desmopressin, and apro-
tinin) used for reducing surgery-related bleeding have limited
or contradictory evidence of efficacy [104]. Large controlled
studies of these drugs are lacking in the cancer setting.
Blood Products
The frequency and severity of hemorrhages increases as
platelet count declines below 20,000/µl [105]. The risk of
severe bleeding rises only when the count is below 5-
10,000/µl. Patients with chronic autoimmune thrombocy-
topenia can tolerate platelet counts in the 5-10,000/µl range
for long periods of time. Platelet transfusion in the setting
of advanced cancer should be on a case-by-case basis with
the aim of controlling symptoms [106]. A single unit of
platelets should increase the platelet count in an average
adult by approximately 6,000-10,000/µl, assuming normal
splenic pooling. Four to six units are usually required to
566
control bleeding. There is no scientific basis for the old
20,000/µl cutoff [107-110]. The short half-life of platelets,
which decreases further as their counts drop, limits their use-
fulness in severely thrombocytopenic patients with end-stage
disease. Lassauniere and colleagues have proposed criteria
for platelet transfusions in patients with advanced hemato-
logic malignancies [106]. These criteria include continuous
bleeding of the mouth or gums, epistaxis, extensive and
painful hematomas, severe headaches, or disturbed vision
of recent onset, as well as continuous bleeding through the
gastrointestinal, gynecological, or urinary systems.
The issue of whether or not to continue platelet transfu-
sions in thrombocytopenic patients with end-stage disease
poses an ethical dilemma. While ongoing transfusions may be
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futile, patients and families may perceive the cessation of
transfusions as withdrawal of life-sustaining therapy. Sensitive
and empathic discussions among patients, their families, and
the attending physician and health team are essential to explore
their expectations, fears, and concerns and to engage in
advanced end-of-life planning while ensuring ongoing support
and commitment to providing optimal comfort care.
Fresh frozen plasma is reserved for a very select group
of patients with life expectancies greater than days to
weeks. These include: A) patients with specific deficiencies
in certain coagulation factors; B) patients in whom the
effects of warfarin need to be reversed urgently; C) patients
who require urgent invasive interventions such as thoracen-
teses or surgery; and D) when appropriate, the treatment of
DIC. Similarly, packed red cell transfusions are indicated
when anemia resulting from blood loss causes or aggravates
symptoms such as fatigue and dyspnea. Guidelines for red
blood transfusions in palliative patients have been published
elsewhere [111, 112].
END-OF-LIFE CONSIDERATIONS
The goals of care in a patient in the terminal phases of
cancer should be comfort. Invasive treatments may present
more burden than benefit in these patients, and comfort
without invasive procedures takes precedence. In some
cases, it is unclear as to whether or not a local or systemic
measure will be of benefit. Time-limited or therapeutic tri-
als (e.g., whether or not a platelet transfusion or an antifib-
rinolytic agent will provide benefit) may be warranted in
select circumstances.
When a terminally ill patient is identified as being at risk
for a major hemorrhage, family members and caregivers
need to be sensitively informed and prepared, since these
events can be extremely distressing. Using dark towels to
absorb blood, applying pressure to the site of hemorrhaging,
and placing patients in the lateral position (in the event
of hematemesis or hemoptysis) are simple empowering
567
measures. A rapid-acting sedative should be available for
sedation. Midazolam, 2.5 mg or 5 mg intravenously or sub-
cutaneously, serves this purpose well [1, 2]. If necessary, it
can be repeated after 10-15 minutes. Orders for a sedative
in case of such an emergency should be entered.
Families/caregivers should be instructed on how to admin-
ister the medication subcutaneously. An indwelling subcu-
taneous butterfly facilitates administration. Families should
be informed about whom to call in case of such an emer-
gency. When patients have expressed a wish for comfort
measures only, it would be inappropriate to call 911.
Anticoagulants should be reviewed, and the benefits
versus burdens of continuing with these treatments should
be considered. Maintaining therapeutic INR levels in termi-
nally ill patients taking warfarin can be challenging and
may require a switch to a low-molecular-weight heparin if
the benefits of continuing anticoagulation outweigh the
risks and burdens [113, 114]. The pharmacokinetics of
these drugs are more predictable, their interactions with
other drugs are less, they are not affected by liver dysfunc-
tion, and they require much less monitoring, negating the
need for regular blood tests in these patients [113, 115].
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