Major operations, hemostatic parameters and venous thrombosis

Vol.

THROMBOSIS RESEARCH Printed in the United

MAJOR

HEMOSTATIC

OPERATIONS,

4, pp. 147-154, Pergamon Press,

States

PARAMETERS

AN3

1974 Inc.

VENOUS

THROMBOSIS U. Abildgaard

E. Korvald, From

Surgical

Hospital;

Department

and

haematology,

The

Blood

Ullevdl

(Received

and

and Medical

Bank

and

Hospital,

28.9.1973; Accepted by

M,K.

Fagerhol

Department

Department

Oslo,

A,Aker

of Immuno-

Norway.

in revised form 27.ll.1973. Editor B. BlombLck)

ABSTRACT Of 61 patients who underwent elective surgery, 14 (2396) developed deep leg vein thrombosis as diagnozed by the 125 J-fibrinogen test. None of them showed local symptoms suggesting thrombosis. Comparison between the thrombosis and the no thrombosis group failed to show significant differences between the mean levels of FDP, serum and plasma antithrombin III, plasminogen and The fibrinogen concentration was signifihematocrit. cantly lower in the thrombosis group preoperatively. At later control examinations the thrombosis group had a significantly lower mean a2-macroglobulin level, but the fibrinolytic capacity was similar in the two groups. One cancer patient, who antithrombin III level, cava.

showed a very marked died with thrombosis

decrease of vena

INTRODUCTION

sed

In the

postoperative

period,

the

levels

of fibrinogen

(1,2),

factor

platelet gen

count

(3).

concentrations

fibrin probably assumed

degradation reflecting that

thrombosis.

these

Antithrombin (5,6)

are

products

It is not

usually (FDP)

increased changes

III

147

shows

activity

(4) and

decreased.

The

in

serum

plasmino-

amount

increases

of fibrinogen.

to postoperative whether

the

increa-

(3) and

(At-III)

consumption

however,

usually

VIII

found

contribute

known,

blood

of (7),

It is venous

changes

are

in

148

THROMBOSIS

different

in the

those

do

who

nozing has

patients

not.

One

thrombosis.

been

shown

thrombosis

(8).

With

has

recently

this

Flute

et al

studied None

dextran.

those

patients

We

have

who

had

studied

develop

dextran

were

repeated

after

tive

activation

of

19 patients

test been

for

in

of diag-

125 J-fibrinogen

test

venous

shown

that

of the

Whole volume

blood

of 0.1

let-poor

about

one

nogen,

M sodium

At-III was

and

about calf

after

operation.

After

At-III

assay

contained

The

after Patient

the

contributed

performed

was

blood for

at -25°C

l/10

the of

plate-

fibri-

performed.

in glass

tubes.

2-4 hours

for

on

containing

immunoassay

M)

temperature

with

At-III

was

antisera

assay

to avoid

1 g/1000 capacity

occlusion

the Mancini obtained

and

of FDP,

were

ml

technique

from

obtained

Antifibrinogen

Germany.

In order

Fibrinolytic venous

tubes

until (a2-

stored

have

was

tests

if a defec-

centrifugation,

whole

performed

other

EDTA-K2,

dardized

was

against

of FDP.

at -25OC

at room

Marburg/Lahn,

werke,

After

collecting

were

antiserum Norway.

plastic

surgery.

plasminogen.

Immunoassays Rabbit

by

serum and

into

citrate.

stored

incubation

centrifugation,

METHODS

(10).

blood

to see

(11)

AND

not

The

might

test

the

between

did

drugs.

system

treated

elective

In order

a2-macroglobulin

obtained

who

occlusion

collected

was

those

year.

being

discriminated

underwent

fibrinolytic

2 years

was

plasma

and

or anticoagulant

the

about

74 of these

who

MATERIALS

Nyegaard

from serum

coagulation,

the

(12): & Co.,

Behringwas

gel

used

for

buffer

(13).

on fibrin of arms

plates

as

(11) was

studied

measured

by

Stan-

about

2 years

operations.

studies.

Blood and

and

difficulty

thrombosis

tests

thrombus,

the venous

to thrombosis,

blood

61 patients

received

Oslo,

the

it has

92 patients,

of the

None

serum

been

thrombosis,

reliable

method

patients

venous

available

and

Vol.4,No.l

(9).

veins

Serum

OPERATIONS

develop

a simple

3096 of postoperative

with

who

obstacle

The

to be

AFTER

on day

samples

were

3, 7 and

drawn

24-O

hours

10 postoperatively.

preoperatively A sample

was

(day also

0) drawn

THROMBOSIS

Vo1.4,Nc.l

about

one

The Flanc

year

later

(designated

125 J-fibrinogen

et al

AFTER

test

OPERATIONS

"control"

was

149

in the

performed

figures).

as described

by

(8).

RESULTS Of

the

bosis did

61 patients

of calf

the

veins

thrombosis

studied,

as

judged

extend

patients

showed

swelling

appeared

on the

operative

patients

(78%).

surgery

is

compared

shown

for

thrombosis

the

group

The

14 (23%) by

the

to the of

the

None

affected

leg.

and

incidence

of

I.

The

thrombosis

group

first

In no

of

these

The

operative

day

related

results

the

(14 patients)

of Thrombosis

Surgery

in

blood and

for

According

to Type

Percent with thrombosis

5

15

Abdominal,

malignant

1

8

Abdominal,

total

46

6

13

Prostatect.,

benign

7

3

43

Prostatect.,

malignant

2

2

100

Prostatect.,

total

9

5

56

6

3

50

malignant)

Malignancy,total

20

6

30

Without

41

8

19

61

14

23

malignancy,total material

General At by

changes the

about

third

14%

the

No with thrombosis

12

Total

tests

of were no

of Surgery.

34

(all

11

to type

benign

Thoracic

14

I

No of patients

Abdominal,

instance

thrombosis

thrombosis of

throm-

(47 patients). TABLE

Incidence

deep

125 J-test.

thigh.

day

in Table

developed

in the

hemostatic

postoperative

(Fig.

l), plasma

parameters.

day, At-III

mean

hematocrit

by about

16%

was (Fi#.

reduced 2),

and

150

THROMBOSIS

serum

At-III

by about

slowly

increased,

at the

tenth

plasma

At-III

vitro

but

(Fig.

they

had

2),

At

the all

not

day.

and

serum

were

about

values levels

about

decreased

by

year

to the

of

in

increased

by

about

Fibrinogen

about

one

2/3

during

consumption

(Fig.4).

FDP

similar

was

consumption

a2-M

20%

these

preoperative

At-III

the

2).

examination

values

reached

the At-III

by about

Vol.4,No.l

Thereafter,

Serum

(Fig.

(Fig.5)

control mean

2).

Apparently,

60%

OPERATIONS

reflecting

plasminogen

sed by about

(Fig.

(Fig.

postoperatively

(Fig.3),and

tions,

20%

postoperative

coagulation.

somewhat

AFTER

250%

20%

increa-

(Fig.6).

after

the

preoperative

operavalues

2,3,4,5,6).

Comparison

between

the

thrombosis

group

and

the

no

thrombosis

group. The

hematological The

groups.

mean

was

significantly

but

in the

The

mean

bosis

concentrations At-111

and

(Fig.

1 and

died

on

within had

the

the

the

levels

were

(O.O25)p)

were

was

difference

differences

very

lower

is not

between

statistically

almost

identical

0.020),

similar.

in the

throm-

statistically

mean

not

an extreme

plasminogen

significant, in the

after

found and

low was

between

as

day,

two

and

subgroups

it cannot

increased

At-III

found

the

only

the

thrombosis

mean

and

was The

legs,

and

be

deviate

excluded

consumption

that

showed

the no

patient died test

vena

cava

a bron-

Although

significantly

that

patient.

this

on

the

one who

from

material.

in

and

only

at autopsy

in viva

parameter

This

by metastases

not

for

66%

125 J-fibrinogen

thrombotic did

the

At-III. and

values

respectively.

infiltrated with

plasma

preoperatively

operation.

parameters

changes,

as well

137$,

in both

filled

hemostatic

extreme

and

the

to be

142%

in the

In contrast,

day. 156%

reduction

being

observed,

thrombosis

the mean

rence

mean

concentration

postoperative

month

was

a2-M

the

were

was

12th

carcinoma

duction

but

small

was

revealed

from

FDP

patient

group

other

the

two

(Fig.3)

2).

the

inferior

in

tests

postoperative

one

chial

group

(Fig.4)

concentration

thrombosis

in these

thrombosis

hematocrit

In one

3rd

similar

lower

(Fig.6), The

very

concentration

preoperative

group

were

fibrinogen

subsequent

significant.

the

changes

preoperative

decreased

pro-

contributed

to

a persistent

thrombosis

group

diffe(Fig.3).

THROMBOSIS

Vol.4,No.l

The

thrombosis

group

preoperatively, (Fig.3), the

but

control The

gave

difference

examination

mean

thrombosis

and

operation,

as

who for

and

was

capacity

results

for were

151

concentrations

of a2-M

at

examination

the

control

significant

(O.Ol<

the

as

tested

both

pyO.02)

available who one

group,

by venous

10 patients,

9 patients,

In each

OPERATIONS

at

only.

fibrinolytic

II).

lower

postoperatively the

similar

(Table

had

AFTER

who

had

for

examination

had

not

patient

occlusion sustained 2 years

developed

had

after

thrombosis

an activity

below

normal. TABLE Fibrinolytic methods),

Capacity studied

II

of Venous

on

Blood

19 Patients

(expressed

about

2 Years

see

in mm2, after

the

Operation. Prior to venous occlusion Mean S.D.

After venous occlusion Mean S.D.

9

104.0

54.8

493.3

144.0

10

100.9

77.9

443.0

199.1

No Thrombosis No

thrombosis

DISCUSSION The this

frequency

study

is in good

125 J-fibrinogen and

ciated

The for

the

(5,8).

carry

surgery.

with

agreement

test

prostatectomy

abdominal

of postoperative

As

a greater

mean

for

Neither

did

the mean

changes

hematocrit

differ

groups. dance

The

with

explained decrease

similar

the

very

decrease

the

in hematocrit,

no

obtained

both

also

on

in the

surgery than

do

to be asso-

to induce

in a2 -M paralleled

production the

decrease

At-III

decrease was

almost

by Flute plasma between groups

decrease

because

because

is known

in plasma

The

was

group,

in both

(5).

decrease The

FDP

significantly

alone,

increased

thoracic

seemed

in plasminogen,

of Ygge

and

based

thrombosis

thrombosis

to those

by hemodilution

for

and

in plasminogen

findings

that

observed

to thrombosis.

in fibrinogen

are

and

risk

(23%)

reports

malignancy

tendency

and

other

It appears

a greater

results

At-III

with

expected,

increase

thrombosis

thrombosis

the

identical

and

the

et al or the

(5).

serum two

is in accorcould

it exceeded operative

not the

trauma

of plasminogen

(5).

in plasminogen. only

slightly

be

greater

The

152

THROMBOSIS

than

the

decrease

vivo

consumption

patients.

that

of At-III

with

orthopaedic

of At-III.

The

in plasma

decrease

fractura

group

at a control

gical

of our nogen

of

"hypercoagulabilityt'

have

subnormal

should

the no

but

might

this

thrombosis.

in the

patient

who

thrombotic massive

in patients

test

for

risk

died

gives

the

the

small

thrombosis

massive

method

small

that

for

drop

about

pulmonary

leg vein

can

ruled our

in plasma calls The

the

seems

sugges-

for

thrombosis.

that

none

thrombosis.

thrombosis

thrombosis

of either

hematolo-

relevant

information

a simple and

cava

almost

125 J-fibri-

findings

pronounced

vena

performed

apparently

The

leg vein

development

syndrome,

The

acti-

that

dyspnoe was

with

develops

the

be very

with

little

who

by

of

group. single

not

with

was were

suggesting

scintigrams.

rate

however,

judged

condition

therefore

no

patient

postoperative

massive

studies

that

in mind, as

thrombosis

patients

test

thrombosis

the

symptoms

had

pulmonary

group"

be born

local

patient

a small

than

fibrinolytic

however,

conclusion for

many

this

(14),

thrombosis

other

Since

At-III

in the

that

findings,

and

the

with

a thrombus.

consumption

a different

shown

The

support

level

been

occlusion

embolism,

125 J-fibrknogen

needed.

it had

a2-M

reflect

with

further

between

it might

thrombosis

one

by negative

At-III

mean

thrombosis

It

only

out

post

but

showed

pulmonary

patients

lower

is characteristic

ted

for

of the

examination.

"thrombosis

an

in vivo

period.

14 patients

Further,

it is possible

indicator

is probably

(6).

test

in

serum

results

thrombosis

and

found

in

by venous

finding

(4),

was

decrease

in the

Our

femoris

At-III

in these

greater

leg vein

identical

colli

Because

as tested

in plasma

in

somewhat

is uncertain,

vity

accelerated

that

a greater

meaning

recurring

much

indicate

induces

At-III

fibrinolysis.

not

might

surgery

in the postoperative The

This

was

Vol.4,No.l

OPERATIONS

in hematocrit.

A greater

patients

AFTER

size

to carry

embolism discriminate

thrombosis

of

is

or

THROMBOSIS

Vol.4,No.l

AFTER

OPERATIONS

153

Antithrombin

-

III ~.OI rtndd

rmm)

PI,,,,

Hemrtocrit

.

0

3

7

lodm

PO

0

3

$

Plesminogen

10

c,r.

%

-_

Fibrinogen

F.D.P.

Mean changes in hemata lgical parameters at 0, 3, 7, FIG. 1 - 6. after surgery. FDP (Fig.6) 10 days and about one year (control the other proteins in per cent of stanis expressed in pg/ml, No thrombosis group. Whole lines: dards (cf. methods). Vertical lines indicate Broken lines: Thrombosis group. Standard Deviation.

154

THROMBOSIS

AFTER

OPERATIONS

Vol.4,No.

1

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2.

Quantitative and GODAL, H. C. nogen following major surgical 171, 687, 1962.

3-

Changes in the coagulation EGEBERG, 0. Acta med. stand. 2, major operations.

4.

M. K. and KORVALD, E. ABILDGAARD, U., GODAL, H. C., FAGERHOL, Antithrombin III in patients with acute changes of the hemoThe International Society on static mechanism. II Congress. Thrombosis and Hemostasis. Oslo 1971. pp. 142.

5.

Changes in blood coagulation and fibrinolysis YGGE, J. during the postoperative period. Am. J. Surg. 9, 225,

6.

Fibrinolysis FLUTE, P. T. Hot. Coll. Surn. Eng. 36,

qualitative operations.

in relation

changes in fibriActa med. stand.

system following 679, 1962.

to thrombosis.

197Q

Ann.

225, 1965.

7.

CASH, J. embolus.

8.

FLANC, C., KAKKAH, V. V. and CLARKE, venous thrombosis of the legs using Brit. J. Sura;. z, 742, 1968.

9.

KAKKAR, V. V., HOWE, C. T., NICOLAIDES, Deep vein thrombosis and CLARKE, M. B. , 527, 1970.

Diagnosis of suspected or occult 0. Brit. Med. J. 2, 576, 1969.

pulmonary

M. B. The detection of 125 J-labelled fibrinogen. A. N., RENNEY, J. T. of the leg. Am. J.

10.

FLUTE, P. T., KAKKAR, V. V., RENNEY, J. T. and NICOLAIDES, The blood and venous thrombo-embolism, p. 2 in A. N. Diagnosis and treatment. Churchill LivingThromboembolism: stone, London 1972.

11.

ROBERTSON, B. R., PANDOLFI, M. and NILSSON, I. M. "Fibrinoin healthy volunteers at different ages as lytic capacity" studied by standardized venous occlusion of arms and legs. Acta med. stand. 191, 199, 1972.

12.

A. 0. and HEREMANS, J. F. MANCINI, G., CARBONARA, chemical quantitation of antigens by single radial Int. J. Immunochem. diffusion. 1, 235, 1965.

13.

FAGERHOL, M. K. and ABILDGAARD, U. Immunological antithrombin III. Stand. J. Haemat. 2, 10, 1970.

14.

ISACSON, S. and NILSSON, I. M. Defective fibrinolysis blood and vein walls in recurrent "idiopathic" venous Acta chr. stand. B, 313, 1972. bosis.

Immunoimmunostudies

on

in throm-