Lack of Increased Bleeding after Liver Biopsy in Patients
with Mild Hemostatic Abnormalities
PATRICIA A. MCVAY, M.D. AND PEARL T. C. Y. TOY, M.D.
Prophylactic transfusions of fresh frozen plasma and platelets
are sometimes given to patients with mild elevations in prothrombin time (PT) and partial thromboplastin time (PTT) and
mild thrombocytopenia before percutaneous liver biopsy. To determine whether PTs and PTTs 1.1-1.5 times midrange normal
levels and platelet counts 50-99 X 10 9 /L are associated with
increased bleeding complications, hospital records of all patients
who underwent percutaneous liver biopsy during 56 consecutive
months (n = 291) were reviewed. Complete information was
available for 177 inpatient procedures (155 standard, 22 fine
needle). Overall, the frequency of bleeding complications in patients with platelet counts 2:50 X lO'/L was 3.4% (6 of 175),
with no significant difference between patients with mild hemostatic abnormalities and patients with normal parameters.
These data suggest that prophylactic transfusions may not be
necessary. One factor was highly associated with bleeding complications: a patient diagnosis of malignancy, 14% (7 of 50) compared with 0.8% (1 of 127) among other patients (P < 0.001).
These patients should be monitored closely after biopsy. (Key
words: Liver biopsy; Bleeding complications; Thrombocytopenia;
Coagulopathy) Am J Clin Pathol 1990;94:747-753
ALTHOUGH PERCUTANEOUS LIVER biopsies are
not recommended in patients with prothrombin time (PT)
greater than 3 or 4 seconds prolonged 1025 or when the
platelet count (Pit) is less than 50'° or 80 X 109/L,25 the
safety of biopsy in patients with less severe hemostatic
abnormalities has not been established. In many hospitals,
if there is any abnormality in PT or partial thromboplastin
time (PTT), or if the Pit count is < 100 X 109/L, the patient
is either treated prophylactically with blood component
transfusions or the patient has a liver biopsy with a laparoscopic approach or transvenous approach, or by percutaneous plugged liver biopsy, all of which are more difficult.512'27 Prophylactic transfusions or alternate biopsy
methods are often chosen because bleeding cannot be immediately visualized and treated. The purpose of this study
was to determine whether mild hemostatic abnormalities
increase the risk of bleeding associated with standard percutaneous liver biopsy. These are defined as PTs or PTTs
1.1-1.5 times midrange of normal (PTs up to 4.2 seconds
Received January 26, 1990; received revised manuscript and accepted
for publication March 23, 1990.
Supported in part by Public Health Service Transfusion Academic
Award (K.07HL01270) from the National Heart, Lung and Blood Institute, National Institutes of Health.
Address reprint requests to Dr. Toy: Blood Bank, 2M6, San Francisco
General Hospital, 1001 Potrero Avenue, San Francisco, California 94110.
Blood Bank, San Francisco General Hospital Medical Center,
and Department of Laboratory Medicine, University of
California San Francisco, San Francisco, California
and PTTs up to 9.5 seconds prolonged) and Pit counts of
50-99 X 109/L.
Materials and Methods
Patient Selection and Exclusion
Retrospectively, records of all patients who underwent
percutaneous liver biopsy between January 1, 1983, and
August 31, 1987, were reviewed. Patients were eligible for
the study if they met all of the following criteria: age 16
years or older; inpatient; postbiopsy notes, both immediate
and follow-up, written by a physician; hemoglobin concentration (Hb) results within 48 hours prebiopsy and 5 48 hours postbiopsy; and PT, PTT, and Pit count within
10 days before or after biopsy. When multiple values of
Hb were available postbiopsy, the value closest to 48 hours
was chosen, and, when multiple values of PTs, PTTs, and
Pit counts were available, the closest values to the procedure were used. Patients were excluded if they received
prophylactic fresh frozen plasma (FFP) or had active
bleeding unrelated to the procedure, such as gastrointestinal hemorrhage, during the study interval.
Diagnoses
In Table 1 (Primary Patient Discharge Diagnoses) each
patient was placed into the first diagnostic group as arbitrarily listed. For example, if a patient had the diagnoses
of acquired immune deficiency syndrome (AIDS) and
lymphoma, that patient was listed under the diagnosis of
AIDS. Similarly, in Table 2 (Liver Biopsy Diagnoses), for
each procedure the first appropriate biopsy diagnostic
group was chosen. For example, if a biopsy showed both
hepatoma and cirrhosis, that biopsy was listed under hepatoma.
Coagulation Tests
The determination method and normal ranges for PTs
and PTTs did not change during the study period. PT
747
MCVAY A N D T O Y
748
Clinical Procedure
Table 1. Primary Patient Discharge Diagnoses
Procedures
Fine
Needle
Total
24
2
26
9
3
22
10
—
6
19
3
28
15
15
11
—
—
—
15
15
11
28
11
5
12
155
—
—
28
11
9
12
177
Standard
Needle
AIDS
Malignancy
Hepatoma
Lymphoma*
Otherf
Hepatitis
Alcoholic
Viral
Other/unknown
Cirrhosis
Alcoholic
Other
Infection*
Other
Total
4
—
22
A.J.C.P.. December 1990
* AIDS patients and viral hepatitis patients excluded,
t Predominantly metastatic adenocarcinoma.
was performed as a one-stage test with the use of a rabbit
brain and lung thromboplastin reagent (General Diagnostic Simplastin® Automated Reagent, Organon Teknika Corp., Durham, NC) (normal PT = 9.5-11.5 seconds). The PTT was performed with the use of micronized
silica to activate the intrinsic clotting factors in the plasma
and the mixture was clotted with CaCl2 (General Diagnostics Automated PTT Reagent®) (normal PTT = 2434 seconds).
Measurement of Blood Loss
To find bleeding complications, the Hb difference was
calculated for each event by subtraction of the postbiopsy
Hb from the prebiopsy Hb and adding 10 g/L (1.0 g/dL)
for every unit of packed red blood cells (RBCs) transfused
between the Hb measurements, the expected increase in
an adult.28 A major bleeding complication after biopsy
was defined as a Hb decrease of 20 g/L or greater (>2.0
g/dL) because the average prebiopsy Hb was 116 ± 22 g/
L (11.6 ± 2.2 g/dL) for all study patients, and a 20 g/L
(2.0 g/dL) decrease represents a 17% loss in blood volume.
An acute loss of at least 15% of the blood volume is considered the minimal bleed for which transfusion of RBCs
should be considered.9 This value was also chosen to help
eliminate overestimation of bleeding caused by minor
fluid shifts. In all patients, regardless of Hb difference,
additional suggestive evidence of bleeding was sought from
changes in blood pressure and pulse, new onset of abdominal or shoulder pain, or transfusion of RBCs after
biopsy. A probable bleeding complication was defined as
an Hb decrease less than 20 g/L (<2.0 g/dL), but the patient was given a transfusion of RBCs for symptoms of
hypovolemia after biopsy.
Standard Menghini-style KJatskin needles were used
for most standard needle biopsies, and Tru-Cut® needles
were used occasionally. Most fine-needle biopsies were
performed with the use of 22-gauge needles. Most standard
needle biopsies were done by gastroenterology fellows and
fine-needle biopsies by radiology residents. All were under
the supervision of attending physicians. A few biopsies
were done by attending physicians.
Routine orders after biopsies with standard needles were
as follows: vital signs were checked every 15 minutes for
two hours, 30 minutes for two hours, 60 minutes for two
hours; the patient had strict bed rest for six hours; oral
liquids were given after four hours if the patient was stable;
and the house officer was called if the systolic blood pressure was less than 100 mmHg or the pulse rate was more
than 110 beats per minute. Also, Hb was routinely checked
approximately five hours after biopsy and often again the
next day. Orders after fine-needle biopsies included the
same parameters for notifying the house officer but had
variable times for vital signs to be recorded.
Statistics
A two-tailed Fisher-Irwin exact test was used to compare proportions, and a two-tailed Student's Mest was
used to compare means. Power (beta) calculations for the
comparisons of proportions were done with the use of
equations 3.19 and 3.20 from Fleiss.8
Results
During 56 consecutive months, 291 percutaneous liver
biopsy procedures (events) were reviewed, 223 by standard
needle and 68 by fine needle. All study criteria were fulfilled in 177 procedures (61%), 155 standard needle (70%)
and 22fine-needle(32%) biopsies in 169 patients (8 paTable 2. Liver Biopsy Diagnoses
Procedures
Standard
Needle
Malignancy
Hepatoma
Lymphoma
Other
Cirrhosis and hepatitis
Hepatitis
Cirrhosis
Granuloma
Infection
Normal
Other
Total
7
3
12
20
44
33
18
2
5
11
155
Fine
Needle
Total
Vol. 94 • No. 6
749
LIVER BIOPSY IN MILD COAGULOPATHY
tients had two procedures at different times during the
study). The percentage of male patients was 73% (130 of
177), and the average age was 45 ± 14 years.
One hundred fourteen procedures (112 patients) were
excluded primarily because laboratory data were incomplete: 46 fine-needle (68%) and 68 standard needle (30%)
procedures. Ten of the excluded patients (eight who had
standard needle and two who hadfine-needleprocedures)
were given FFP for bleeding prophylaxis without record
of active clinical bleeding. None of these ten patients had
bleeding complications, and all had abnormal PT values
with a mean of 13.9 ± 1.3 seconds. Seven had abnormal
PTT values with a mean of 40.2 ± 9.4 seconds. Also excluded were six patients with active gastrointestinal
bleeding. The remaining 96 patients, all with incomplete
laboratory data, included only 3 requiring RBC transfusion within 48 hours after biopsy. Two received transfusions for chronic anemia and one for a possible biopsyinduced hemorrhage. (His chart, including laboratory
data, was unobtainable, but his standard needle biopsy
diagnosis was hepatoma; he received a two-unit RBC
transfusion the evening after biopsy.) This gives at most
a 1% bleeding rate in these 96 patients (98 procedures).
Table 1 shows the primary patient discharge diagnoses
with hepatitis (26%, 41 of 155), the most common diagnosis for standard needle biopsy patients, and malignancy
(73%, 16 of 22), the most common diagnosis for fineneedle biopsy patients. Table 2 presents the liver biopsy
diagnoses in study patients, determined by pathologic examination of biopsy tissue.
The overall frequency of major and probable bleeding
complications was 4.5% (8 of 177), with only 3.4% (6 of
177) of these patients requiring RBC transfusions. Four
of these six patients had prebiopsy Hb values of less than
100 g/L (< 10 g/dL) and may not have required transfusion
if they were not anemic before biopsy. Table 3 shows the
six patients who had major bleeding complications and
the two patients who had probable bleeding complications.
One patient died, the first patient, who had a rapid 49
g/L (4.9 g/dL) decrease in Hb and adult respiratory distress
syndrome; the patient died four days after biopsy. No
autopsy was permitted.
No difference in the proportion of patients with bleeding
complications and in the average Hb difference was observed in patients with normal or mildly abnormal PTs
and PTTs (Tables 4 and 5) (all P > 0.10). No bleeding
was observed in one patient with a PT more than 1.5
times normal (16.3 seconds). The rate of bleeding complications in all 76 patients with mildly abnormal PTs
was 5.3% (4 of 76) and only 2.6% (2 of 76) had major
bleeding complications. Among the 60 patients with
mildly abnormal PTTs, the rate of bleeding complications
was 1.7% (1 of 60). There were no patients with the diagnosis of AIDS who had PTTs prolonged 38 seconds or
more who did not also have abnormal PTs. Although
patients with moderately prolonged PTTs had a higher
rate of bleeding complications, 14% (2 of 14) compared
with 4.9% (5 of 103) among patients with normal PTTs,
this was not statistically significant (P = 0.20), and both
bleeding complications were probable.
Table 3. Patients with Clinical or Laboratory Evidence of Bleeding Complications*
Patient
Age/Sex
32 F
23 F
45 M
Needle
(passes)
Standard
(2)
Standard
(2)
Standard
(1)
65 M
Standard
(3)
56 M
48 M
Fine (5)
Fine
(several)
Standard
(4)
Standard
(2)
46 M
62 M
Patient Diagnosis
Biopsy
Diagnosis
Pit
(X109/L)
PT
(s)
PTT
(s)
Hb Change
(g/Dt
Hepatoma
Hepatoma
114
13.0
38.8
-49
Hodgkins disease
Normal
571
9.6
33.8
-35
OWRJ
ITP
Hepatitis
48
10.1
29.2
-34
Multiple
myeloma,
Sickle cell
disease
Hepatoma
Bile duct
carcinoma
Hepatoma
Hemosiderosis
16
11.2
30.9
-32
Hepatoma
Normal
176
227
12.0
10.2
31.8
30.4
-23
-21
Hepatoma
470
13.2
43.6
Lymphoma, renal
failure"
Lymphoma
63
12.5
71.5
* Normal ranges: PT = 9.5-11.5 sec: PTT = 24-34 sec; RBC = red blood cells.
t H b g / L = 10 X g/dL (e.g. - 4 9 g/L = -4.9 g/L).
X OWR (Osier-Weber-Rendu syndrome) Technetium scan of liver showed no vascular malformations; ITP (idiopathic thrombocytopenic purpura); computerized tomography used for biopsy.
Signs and
Symptoms
Blood
Products
Received
Pain, hypotension,
tachycardia
Pain, hypotension
4 RBC, 4 FFP
Pain, tachycardia,
hypotension,
fever
Pain, hypotension,
tachycardia
1 RBC
None
6 RBC
20 pits
20 cryo
None
2 RBC
-13
None
Hypotension,
fever§
Hypotension
-12
Tachycardia
1 RBC
2 RBC
§ Blood cultures grew Pscudomonas aeruginosa.
11
Creatinine 740 timo\/L (8.4 mg/dL); patient was given DDAVP and 10 units Pit before
biopsy.
750
MCVAY AND
TOY
A.J.C.P.. December 1990
Table 4. Patients with Bleeding Complications and Average Hemoglobin Difference by Prothrombin Time
PT Range
(seconds)
Normal
<;11.5
Mildly prolonged
11.6-13.5
13.6-15.7
Total
Total
Events (%)
No. of Bleeding
Complications
(% of events)
Average Hb
Difference ± SD
(g/L)*
Standard
100 (57)
4 (4.0)
-2.7 ± 8.9
89
65 (37)
11(6)
176(100)
4 (6.2)
0
8 (4.5)
2.6 ± 9.8
2.2 ± 6.2
54
11
154
Needle Type
Fine
11
0
22
* Hb g/L = 10 X g/dL (e.g. -2.7 g/L = -0.27 g/dL).
No difference in bleeding rate between patients with
normal Pit counts and those with mild thrombocytopenia
was observed (Table 6) (P = 0.48). The distribution of
the 18 patients with mild thrombocytopenia was 50-59
in one patient; 60-69 in four patients; 70-79 in six patients; 80-89 in two patients; and 90-99 in five patients.
The one patient with a bleeding complication with mild
thrombocytopenia (63 X 109/L Pit count) is described in
Table 3 and that was a probable bleeding complication.
Both patients with Pit counts <50 X 109/L had major
bleeding complications also described in Table 3.
Two factors were found to be significantly associated
with bleeding. The most important was the patient diagnosis of malignancy, with 14% (7 of 50) of patients with
that diagnosis having bleeding complications compared
with 0.8% (1 of 127) among other patients (P < 0.001).
These patients also had a 4.5-fold increase in average Hb
loss (-5.8 ± 1.1 g/L [-0.58 ±0.11 g/dL] vs. -1.3 ± 7.7
g/L [-0.13 ± 0.77 g/dL], P = 0.002). Of these 50 patients,
only 35 actually had the diagnosis of malignant cells made
at that specific procedure. (Three of the 38 patients in
Table 2 with the biopsy diagnosis of malignancy had a
primary patient diagnosis of AIDS and had lymphoma
on biopsy.) Of the remaining 35 patients with a biopsy
diagnosis of malignant cells, 4(11%) had bleeding complications (Table 3). This was significant compared with
2.8% (4 of 142) of patients whose biopsy diagnosis was
not malignancy (P = 0.05). The average Hb loss in these
35 patients compared with the 142 patients was 2.7-fold
greater (-5.4 ± 10.8 g/L [-0.54 ± 1 . 1 g/dL] vs. - 2 . 0
± 8.5 g/L [-0.20 ± 0.85 g/dL], P = 0.05).
The second factor associated with increased bleeding
complications could only be detected after biopsy: the
patient's complaint of pain after biopsy. Thirteen percent
(4 of 31) of patients with this complaint had bleeding
complications compared with 2.7% (4 of 146) in other
patients (P = 0.03). Also, their average Hb loss was 3.2fold greater (-5.8 ± 1.4 g/L [-0.58 ± 0.14 g/dL] vs. -1.8
± 7.6 g/L [-0.18 ± 0.76 g/dL], P = 0.03). Of the four
patients who did not complain of pain but had bleeding
complications, two had fine-needle biopsies and two had
probable bleeding complications.
Discussion
Bleeding Complication Rate
In this patient population the major bleeding complication rate after percutaneous liver biopsy was low: 3.4%
(6 of 177) for all patients and 2.3% (4 of 175) for patients
with Pit counts >50 X 109/L. Overall 4.5% of patients (8
of 177) had either major or probable bleeding compli-
Table 5. Patients with Bleeding Complications and Average Hemoglobin Difference
by Partial Thromboplastin Time
PTT Range (seconds)
Normal
^34.0
Mildly prolonged
34.1-37.9
38.0-43.5
Moderately prolonged
^43.6
Total
Total
Events (%)
No. of Bleeding
Complications
(% of events)
103 (58)
5 (4.9)
-3.0
37(21)
23(13)
14(8)
177(100)
* Hb g/L = 10 X g/dL (e.g.. -3.0 g/L = -0.30 g/dL).
Average Hb
Difference ± SD
Needle Type
Standard
Fine
±9.1
89
14
0
1 (4.3)
-0.56 ± 7.3
-2.5 ± 1.2
34
20
3
3
2(14.3)
8 (4.5)
-4.7
12
155
2
22
(g/D*
±6.1
vol.94.No.6
LIVER BIOPSY IN MILD COAGULOPATHY
751
Table 6. Patients with Bleeding Complications and Average Hemoglobin Difference by Platelet Count
Pit Range
(X 109/L)
Normal
£100
Mild thrombocytopenia
50-99
Moderate/marked thrombocytopenia
16,48
Total
Total
Events (%)
No. of Bleeding
Complications
(% of events)
Average Hb
Difference ± SD
(g/L)*
Standard
Fine
157(89)
5(3.2)
- 2 . 3 ± 8.8
137
20
18(10)
1(5.6)
-1.1 ± 6 . 2
16
2
2(1)
177(100)
2(100)
8(4.5)
-3.3 ±0.1
2
155
0
22
Needle Type
* Hb g/L = 10 X g/dL (e.g.. - 2 . 3 g/L = -0.23 g/dL).
cations, including the two patients with Pit counts
<50 X 109/L. Only one patient, who had hepatoma,
died (0.6%).
Frequency of bleeding in our population was higher
than previously reported. Significant bleeding after the 1second Menghini technique using the Menghini-style
needle has been reported to be 0.5-0.7%. 1U4 By not routinely measuring the prebiopsy and postbiopsy Hb, these
studies may have underestimated bleeding.2 We may have
underestimated minor bleeding complications because
subcapsular hematomas have been reported in as many
as 23% of patients,16 although in that study no patients
required transfusion. We may have overestimated bleeding complications by selecting only inpatients, who were
closely monitored, and selecting those who had PTs, PTTs,
Pit counts, and Hb values before and after biopsy. Patients
in whom a postbiopsy Hb or a PT, PTT, or Pit count was
not ordered probably showed no signs or symptoms
suggestive of bleeding. This is supported by our finding a
possible bleeding complication in only 1 of 96 patients
excluded for incomplete laboratory data. Because the chart
was not available for this patient, it is not known whether
he received a transfusion for a gastrointestinal hemorrhage
resulting from portal hypertension caused by his hepatoma, for preexisting anemia, or for a complication of
liver biopsy.
It is of interest that 9.1% (2 of 22) of fine-needle biopsies
were associated with bleeding, whereas only 3.9% (6 of
155) of standard needle biopsies were associated with
bleeding. This probably reflects a selection bias because
68% of fine needle and only 30% of standard needle procedures were excluded. The overall complication rate, including all excluded patients, would be nearly identical,
2.9% (2 of 68) for fine needle and 2.7% (6 of 223) for
standard needle procedures.
Causes of Increased Bleeding Complications
It has been suggested that bleeding after liver biopsy is
a random event and cannot be predicted by currently
available methods.15 Local intrahepatic clotting and elastic
factors may prevent bleeding.6 Also, increased capillary
fragility in hepatic disease may predispose a patient to
bleeding.29 Laceration of major vessels cannot be predicted, and especially among patients with cirrhosis, that
risk is increased because large subcapsular venous collaterals can develop that may be biopsied inadvertently.
Although we do not know the precise cause of bleeding
in the eight patients who had bleeding complications in
our study, all had suspected risk factors. The one factor
most significantly associated with bleeding complications
was the primary patient diagnosis of malignancy, 14% of
these patients having bleeding complications (seven of the
eight patients with bleeding complications) compared with
0.8% of patients without this diagnosis. This has been
reported previously by Fisher and Faloon,7 who suggested
that the presence of tumor is a contraindication for biopsy;
12% of the 33 patients who had tumors died after liver
biopsy. In their study, the Vim-Silverman needle was used.
In other studies that reported use of the same needle, malignancy was not a contraindication.19'30 Many studies using the smaller Menghini-style needles, as were used primarily in this study, have also not found malignancy
to be a contraindication,3-20'21 except in myeloid metaplasia.18
Other risk factors in these patients include the following:
(1) Multiple passes are a risk factor, with seven patients
requiring more than one pass and three requiring four or
more passes. Perrault and associates21 have shown that
more passes increase complications in transthoracic standard liver biopsies from 4% for one pass to 10% for two
or three passes and 14% for more than four passes. (2)
Biliary tract obstruction, present in the patient with bile
duct carcinoma, has been suggested as a risk factor because
of possible biliary peritonitis and bacteremia (the latter
occurred in this patient), leading to high morbidity and
mortality,26 although this has been refuted in other studies
using the smaller Menghini-style needle. 317 (3) Osier-Weber-Rendu syndrome sometimes includes vascular malformations of the liver. Although a technetium scan was
752
McVAY AND TOY
performed on our patient, angiography was not, and a
small lesion could have been missed. (4) Moderate to
marked thrombocytopenia is a risk factor that is discussed
below.
Hemostatic Factors
Mild abnormalities in PT and PTT were not associated
with increased bleeding complications in this patient
population. Because the study sample sizes were small,
we calculated the proportion of bleeding complications
that could be detected at a level of significance of P = 0.05
(Type I error 5%) with a power of 80% (Type II error
20%). If a 5% baseline of bleeding complications in patients with normal PTs or PTTs is assumed, an approximately fourfold increase in bleeding complications (an
increase of 15%) could have been detected, with 76 patients with mildly increased PT and 60 patients with
mildly increased PTT. No trend was seen toward an increase and in fact a trend toward a decrease was seen for
mildly abnormal PTTs. If only the six patients with Hb
decreases of 20 g/L or greater (>2.0 g/dL) are considered,
there is a trend toward a decrease with mildly abnormal
PTs (the mildly abnormal PT complication rate becomes
2 of 76, 2.6%). To detect a doubling in bleeding complication rate from 5 to 10%, a total of 950 patients (assuming
equal numbers of patients with normal and mildly abnormal hemostatic parameters) would be necessary, which
would require 25 study years. Therefore, detection of a
twofold increase in bleeding rate is not possible at a single
institution, especially with the increasing use of transvenous liver biopsy and plugged liver biopsy for patients
with abnormal hemostatic parameters.
The ten excluded patients given FFP could have been
perceived as having a higher risk of bleeding by their clinicians and may have had evidence of active clinical
bleeding not noted in their charts. One patient did have
a history of an upper gastrointestinal hemorrhage, no
longer active at the time of biopsy. These patients did
have larger abnormalities in PTs and PTTs than patients
included in the study, with one patient having both moderately prolonged PT and PTT and two other patients
having moderately abnormal PTTs. Also, seven patients
had both mildly prolonged PTs and PTTs. Only in the
unlikely event that all nine patients with mildly abnormal
PTs bled without having received FFP would the bleeding
rate have increased from 5.3% (4 of 76) to 15% (13 of 85)
in the group with mildly elevated PTs, and then the bleeding rate would be significantly higher (P = 0.01, compared
with the 4% complication rate in patients with normal PTs).
The conclusion of no increase in bleeding complications
with mild PT or PTT abnormalities is supported in the
A.J.C.P. • December 1990
literature. Ewe showed in patients who had undergone
liver biopsy at laparoscopic examination that there was
no correlation of the liver bleeding time with PT, whole
blood clotting time, and Pit count. 6 Other studies also
have shown that a PT or PTT prolonged less than 1.5
times the control value is not associated with increased
bleeding in open surgical procedures13,23 or in patients
receiving massive transfusions after trauma. 14
Mild thrombocytopenia also was not associated with
increased bleeding complications because only one patient
(5.6%, 1 of 18) with a Pit count of 63 X 109/L had a
bleeding complication. This patient, whose bleeding
complication was probable, had significant uremia and
may have had dysfunctional platelets.22 Both patients with
Pit counts <50 X 109/L (48 and 16 X 109/L) had major
bleeding complications. These data support those of
Sharma and associates,24 who had no bleeding in 16 patients with Pit counts of 61-90 X 109/L, but found that
3 of 13 patients with Pit counts of 30-60 X 109/L (45,
53, and 56 X 109/L) bled. Also, in Ewe's study of laparoscopic liver bleeding times,6 from his graph there appear
to be approximately 35 patients with Pit counts of 50100 X 109/L and only 2 patients had bleeding for which
compression was required. Because our study sample size
is small, if we combine our 18 patients with the 16 and
35 patients discussed above (total, 69) and use this number
to calculate the proportion of bleeding complications that
could be detected at a level of significance of P = 0.05
with a power of 80%, assuming a 5% baseline of bleeding
complications, approximately a fourfold increase in
bleeding complications (an increase of 15%) could have
been detected.
Conclusions
Ishak and associates suggested that liver biopsies should
not be performed if the PT is prolonged greater than 4
seconds and if the platelet count is <50 X 109/L,10 and
Sherlock suggested that a PT greater than 3 seconds prolonged and a platelet count of <80 X 109/L (or possibly
60 X 109/L in patients with hypersplenism) are contraindications to biopsy.25 However, the safety of percutaneous
liver biopsy in patients with mild elevations in PTs and
PTTs and mild thrombocytopenia is not established. Our
data suggest that a PT prolonged less than 1.5 times midrange normal (4 seconds) and a PTT prolonged less than
1.5 times midrange normal (9 seconds) are not associated
with increased bleeding complications after percutaneous
liver biopsy. Although the number of patients with platelets 50-99 X 109/L was low, when considered in addition
to published data discussed above, we conclude that mild
thrombocytopenia, without risk factors for dysfunctional
platelets, does not significantly increase the risk of bleeding
Vol. 94 • No. 6
LIVER BIOPSY IN MILD COAGULOPATHY
after biopsy. These data suggest that prophylactic transfusions of FFP and platelets may not be necessary before
percutaneous liver biopsy in patients with mild hemostatic
abnormalities. A large multicenter prospective randomized controlled trial with half of the patients treated with
prophylactic transfusion would be necessary to provide a
definitive answer.
One factor was highly associated with bleeding complications in this study, a primary patient diagnosis of
malignancy. These patients should be monitored closely.
Another factor, pain, which cannot be predicted before
liver biopsy, is associated with increased bleeding complications and has been previously reported.14'21 Patients
complaining of pain after biopsy should also be closely
monitored.
Acknowledgment. The authors thank Frederick J. Roll, M.D., Rice
Liver Center, San Francisco General Hospital, Department of Medicine,
University of California, San Francisco, for his critical review of this
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