Disordered “fibrinolytic potential” in coronary heart disease

DISORDERED

“FIBRINOLYTIC

CORONARY I .D. Walker;

POTENTlAL”

IN

HEART DISEASE.

J .F. Davidson;

I. Hutton

and T .D .V.

Lawrie.

Department of Haematoiogy and University Department Glasgow Royal Infirmary. of Medical Cardiology, Scot la rut. Glasgow,

(Received 23.7.1976; in revi.sed form l.3.12.1976. Accepted by Editor A.S. Todd. Received by Executive Editorial Office 28.1.1977) ABSTRACT 25 male patients with and 14 male controls without, angiographic evidence of coromry heart disease were each subjected to a 5 minute venous occlusion test of “fibrinolytic potential”. 13 of the patients had evidence of disordered “fibrinolytic potential” whilst all of the controls were normal. It is concluded that disordered “fibrinolytic potential” may be associated with coronary heart disease and it is suggested that disordered fibrinolysis should be corrsidered as a possible “risk factor” in the development of coror~~ry heart disease.

INTRODUCTION. The aetiology of atherosclerotic coronary heart disease is imperfectly understood, but it would appear to be multifactorial and the identification and evaluation of possible “risk factors” which are associated with the development of vascular disease continues. Rokitansky (1) first associated atherosclerosis with excessive fibrin deposition in the arterial intima and recently this thrombogenic theory of atherosclerosis has been reIt is postulated that normally in vivo an equilibrium exists between examined (2, 3). coagulation and fibrinolysis so that there is a balance between the deposition and t&set of this balance, by, for example a defect in the dissolution of fibrin (4). fibrinolytic system could permit continuous vascular fibrin deposition and consequently a predisposition to thrombosis and eventua I ly to atherosclerosis. The fibrinalytic activity of plasrw is largely due to the presence in the plasma Resting levels of of a labile protein the so-called vascular plasminogen activator. this activator are often low so that their measurement may yield conflicting results which Release of this fibrinolytic do not readily permit inter-individual comparisons. activator is enhanced by a number of different stimuli including, pyrogens, adremline, 509

510

"FIBRINOLYTICPOTENTIAL"

nicotinic acid or other vasoactive agents and physical or emotioml

Vol.lO,No.3

stress. (5, 6, 7, 8,

9). Marked increases in local fibrinolytic activity also normally occur during venous occlusion of a limb. (TO, 11, 12). and this phenomenon has formed the basis of a number Providing the conditions are rigidly standardised, 20 minutes of clinically useful tests. venous occlusion can be used to assess “fibrinolytic capacity” (13) but 20 minutes venous occlusion is painful and appears to cause significant depletion of the endothelial stores A more convenient and acceptable test is the 5 minute venous of vascular aativator. cuff “fibrinolytic potential” which is less painful and can be repeated at short intervals (14). Recent studies have demonstrated an increased incidence of defective fibrinolytic response to venous occlusion in subjects with recurrent venous thrombosis (l5) and it is well documented that the South African Bantu, in whom coromry atherosclerosis is extremely tore, have much greater spontaneous fibrinolytic activity than their white counterparts in whom coromry artery disease is relatively common (l6, 17). In the study reported here, patients with coromry angiographic evidence of coronary heart disease have been studied, and the incidence of disordered “fibrimlytic potential” in a group of 25 such patients recorded.

PATIENTS

AND

METHODS.

Patients: 25 male patients (mean age 46 years) with angiogmphic evidence of occlusive coronary arterial disease and 14 male controls (mean age 45 years) with normal coronary All 25 patients had angina pectoris and 16 vessels on angiogmphy have been studied. of them had E .C .G. evidence of previous myocardial infarction. Nine of the 14 controls were men with a history of chest pain admitted to exclude commry heart disease. The remaining 5 controls had evidence of valvular disease of the heart and had diagnostic cardiac catheterisation with viswlisation of the coronary arteries by aortogmphy. Patients with peripheml vascular disease or a history of venous thrombosis were excluded and no one with diabetes mellitus or known or suspected neoplastic disease was examined. Special care was taken to exclude subjects who had been taking 13 adrenergic receptor blocking agents during the preceding 6 months and no one who had had any kind of invasive procedure in the month before admission was studied. Details of each subjects past (within 5 years) and present smoking habit were recorded. Patients and controls were admitted to the ward 24 -48 hours before entering the study and angiogmphy was not performed until after the last venous occlusion test had been aarried out. All 25 patients and the 9 controls with chest pain had Commry Artery Visualisation: coronary angiogmphy carried out using either the Judkin’s (l8) cr the Sane’s (l9) Left ventriculogmphy was performed and views of the right coromry artery technique. were obtained in the left anterior oblique, the left lateml and the right anterior oblique positions. Views of the left coronary artery were obtained in these positions and in’the posterior anterior position. The 6 controls with valvular disease of the heart had left heart catheterisations performed using a percutaneous technique with the femoml artery as the site of entry. Biplane cineangiogmphic views were obtained in the right anterior oblique and the left Jateml positions at aortogmphy thus allowing viswlisation

Vol.lO,No.3

"FIBRINOLYTICPOTENTIAL"

of both right and left coromry arteries. 5 minute venous occlusion “fibrinolytic potential”: A standardbed 5 minute venous occlusion test has been developed to assess “fibrinolytic potential”. Resting spontaneous fibrinolytic activity is measured in blood collected from the right antecubital fossa and compared with the activity in blood collected from the left antecubital fossa after precisely 5 minutes venous occlusion of the left upper arm. Fibrinolytic activity is measured in euglobulin precipitates prepared from the plasma samples using a meticulous cold technique and adjusting the pH of the plasm0 dilutions to 5.9 (20). The assays were performed in triplicate on unheated plasminogen rich bovine fibrin plates and the product of two perpendicular diameters of the lysed areas arbitmrily expressed as the “area of lysis - in rnd#I. The methodology for this has been described in detail in a previous publication (14). On all subjects a total of three 5 minute venous occlusion testsweredone-atOhours(9am-Doyl),at5hounQpm-Dayl)andat72hours (9 am - Day 4). The subjects were resting supine during the tests and for at least 20 minutes prior to each test. They had been fasting for 12 hours before the tests at 0 hours and 72 hours but had had a light lunch 2 hours before the 5 hour test. Fasting Lipoprotein Status: Samples for measuring the fasting lipoprotein status were taken from the subjects immediately before the 0 hour venous occlusion test and after the subjects had been fasting for 12 hours. Total plasma cholesterol was measured using the method described by Annon (21) and a fluorometric assay of the triglycerides @2) was also done on each subjects plasma. In addition many of the subjects fasting plasmas underwent full lipoprotein fmctiomtion (23) by ultmcentrifugation and precipitation. The mnges used in assessing the results were the age related upper limits of normality described by Fredrickson 04).

RESULTS . Spontaneous Resting Fibrinolytic Activity: The mnges of fibrinolytic activity in samples taken from the resting subjects’ right (unoccluded)arms at 0 hours, 5 hours and 72 hours along with the means of these values are recorded in Table 1 . These mnges were very wide, especially in the patient group. There were no significant differences at the P (0.01 level between the patient and control means at any test time, but at 5 hours the control mean was significantly greater than the patient mean at the P 4 0.025 level. This significant difference is probably due to a reduction of fibrinolytic diurnal variation in the patient group. Two of the patients had no spontaneous fibrinolytic activity on any of the three occasions on which they were tested. One patient had no activity at 0 hours, and very low levels at 5 hours and 72 hours. All of the controls had evidence of spontaneous fibrinolytic activity every time they were tested but again the range of activity noted at each time was wide. The ranges of fibrinolytic activity in the samples Post Occlusion Fibrinolytic Activity: taken from the subjects’ left arms after 5 minutes venous occlusion along with the means of these values are recorded in Table 2. At 0 hours and at 72 hours, that is in the two tesk carried out at 9 am, no significant differences were observed in the mean post-occlusion activities in the patient group

Vol.lO,No.3

"FIBRINOLYTICPOTENTIAL"

512

TABLE

0 hours Patients

tNumber Range (mm2) Mean (mm2) S.D. (mn$) S.E. (mm )

t value P value

I

1.

5 hours

I

Controls

Patienk

Controls

13 81-323 147 70 19

24 O-406 185 94 19

13 156-325 238 51 14

25 G355 116 77 15 1.277 LO.15

,

<

72 hours

I

23 &433 127 93 19

8 65L178 102 41 16

1.019 4 0.1

2.221 0.025

The ranges of fibrinolytic activity expressed as mm2 in samples taken from the resting subieck’ right (unoccluded) arms at 0 hours, 5 houn and 72 hours along with the mean activities, standard deviations, and standard errors and P values of an analysis by the student’s t test comparing patient and control means. At 5 hours - the 2 pm test - the mean post compared with the control (P(O. 1). occlusion fibrinolytic activity in the patients’ plasma samples was significantly less he of the two patients who consistently had (PLO.0025) than in the control samples. no spontaneous fibrinolytic activity, also had no post occlusion fibrinolytic activity ot 0 hours or 72 hours, although he did “respond” at the 5 hour test.

TABLE

0 hours

t value P value

2.

5 hours

72 hours

Patien k

Cciltrols

Patien k

Controls

Patients

Contn3lr

25 O-616 227 157 31

13 132- 850 307 183 51

24 96-625 354 156 32

13 272- 900 533 168 47

23 &498 151 124 26

8 96612 224 168 59

1.336 c 0.1

3.168 4 0.0025

(

1.128 0.15

The ranges of fibrinolytic activity expressed as mm2 in samples taken from the resting subieck’ left arms after 5 minutes venous occlusion at 0 houn, 5 hours and 72 hours along with the mean activities, standard deviations and standard errors and P values of an analysis by the student’s t test comparing patient and control means.

Vol.lO,No.3

5 minute

venous cuff

"FIBRINOLYTICPOTENTIAL"

“Fibrinolytic

The difference

between

subiect’s

(unoccluded)

right

the fibrinolytic

minutes venous occlusion represented

graphically

to a positive occlusion

“response”

1, 2,

found in samples taken

study,

-

with

to define

Increased

test.

the corresponding

any increase as an indication

whatsoever

left arms after

(14).

5

These are

or less than in the corresponding to demonstrate

disordered

fibrinolytic

fibrinolysis

activity

resting sample

If the activity

uncuffed

a response to the 5 minute

in the

has been designated

in the area of lysis produced

of “response”.

said to have potential”

potential”

it WGS decided

sample was the same, “failed”

from the resting

in samples from their

and 3.

venous occlusion

samples compared

being accepted

activity

gives a measure of “fibrinolytic in Figure

in terms of the 5 minute

‘I:

arms and the activity

For the purposes of this particular post occlusion

Potential

513

sample,

post

in the cuffed the subject

venous cuff

was

“fibrinolytic

test.

CONTROLS - 0 HOURS

PATIENTS

-

0

HOURS

?

600

04 Un4f.d

6ff.d

Uncufhd

Fig.

Cuffed

1.

Fibrinolytic activity in specimens and controls at 0 hours comparing with levels taken after 5 minutes deviation). mean z one standard

of plasma taken from patients spontaneous resting levels venous occlusion (T represents I

"FIBRINOLYTICPOTENTIAL"

514

CONTROLS - 5 HOURS

Vol.lO,No.3

MTIENIS-5

/

HOUR5

Roe

, 600 0

5 -5 .I

400

z B

f

200

i

0 UlKUffWi

Unwffad

Cuffad

Fig.

Cdfd

2.

Fibrinolytic activity in specimens of plasma taken from patients and controls at 5 hours comparing spontaneous restin levels with levels taken after 5 minutes venous occlusion. f represents f. mean 2 one standard deviation). CONTROLS

Uncuffed

- 72

PATIENTS - 72 tiOURS

HOUR5

Cuffed

Uncufhd

Fig.

3.

Fibrinolytic activity in specimens and controls at 72 hours comparing with levels taken after 5 minutes deviation). mean *one standard

of plasma taken from patients spontaneous resting levels venous occlusion (2 represents _L

"FIBRINOLYTICPOTENTIAL"

Vol.lO,No.3

Each of the 14 controls

had a positive

response to venous occlusion

5 hours and 72 hours) - but of the 25 patients, failed

to respond twice Thirteen

tested.

to the 5 minute

and one failed

If these failures

to respond are related

failed

to respond on their Lipid

and Type

a disorder

to the time of testing

it is noted

on which in their

4 he was

response

that 4 patients

72 hours,

Fig.

1, 2 and 3).

of h perlipoproteinaemia

and on full

k lipoprotein were identified.

was found in a number of

quan titation,

a number of Type Ila

No Type

IV hyperlipoprotein-

found in the groups studied.

Smoking:

20 of the 25 patients

There was little

difference

had smoked twenty

and 6 of the 14 controls or more cigarettes

in the smoking

or more cigarettes

had been similarly

At the time of testing

years.

test (0 hours,

to respond at 5 hours and 11 of the 25 patients

Ilb hyperlipoproteinaemias

Cigarette

three occasions

demonstmted

test (at

Evidence

and controls

aemias were

twenty

4 failed

thjrd

Status:

patients

therefore

at every

to respond on one occasion,

to respond on all

out of 25 patients

to respond at 0 hours,

Fasting

8 failed

venous cuff test,

failed

both

515

modemtely

5 of the patients

habits of the two groups.

daily

heavy

within

the past 5 years.

smokers within

and 4 of the controls

the post 5

were still

smoking

daily. DISCUSSION.

In this study 13 out of 25 patients disease were fibrinolytic Fourteen

found to have

“disordered

response to the challenge male

controls

with

with angiogmphically

fibrinolytic of three serial

angiogrophically

proven

potential” 5 minute

normal

coronary

heart

as assessed using the venous occlusion

coronary

arteries

tests.

responded

normolly

to venous occlusion. Because levels inter

variation, conflicting patient

results. (Table

the control

fibrinolytic

l),

ranges.

enough

here,

to completely

than one standard

deviation

consistently

less than one standard

above

the control

levels

the mean level

deviotion

and lower,

activity

in the control

had spontaneous below

found in the

group range at each

both higher

fibrinolytic

personal

levels produce

than

consistently group

fibrinolytic

(at 0 hours,

activity

the means in the control

group

(Fig.

and 3). Out of the 25 patients,

on at

with

had spontaneous

5 hours and 72 hours) and four of the patients 1, 2,

have a wide

the mnges of activity

contain

so that there were patients Two patients

activity

based on studies of resting

In the groups reported

group were wide

test time greater

of spontaneous

individual comparisons

least one occasion,

of zero spontaneous

fibrinolytic

Because of the wide ranges of resting

activity,

three had no spotaneous

a phenomenon activity

not observed must therefore

mnges and the overlap

it was considered

fibrinolytic be regarded

between

necessary

activity

omong the controls.

The finding

as abnormal.

patient

to develop

at all

ond control

o more dynamic

method of assessing fibrinolysis. For clinical convenient,

use the 5 minute

safe and well

tolemted

venous cuff

test which

“fibrinolytic

can be repeated

potential”

is o

at short intervals.

In

516

“FIBRINOLYTIC

POTENTIAL”

Vol.lO,No.3

this test the spontaneous resting fibrinolytic activity of blood taken from the uncuffed right arm is compared with the activity in blood from the left (cuffed) arm after 5 minutes venous occlusion. because the fibrinolytic activity is measured in resuspended euglobulin precipitates obviously a number of componenk of the fibrinolytic system both activators and inhibitors, influence the result and minor variations in technique from laboratory to laboratory will cause considerable variations in the areas of lysis produced on the fibrin After careful consideration, therefore, it was decided that the most practical plates. method of assessing the resulk of the 5 minute venous occlusion test was on a “response” or “failure” basis. Any increase at all in fibrinolytic activity following venous occlusion was recorded as a positive “response” and no increase in the cuffed sample was recorded as a “failure”. In doing this, almost certainly the number of patients with defective or bordefc line fibrinolytic responsiveness has been slightly underestimated,

13 out of the 25 patienk failed to respond to venous occlusion on at least one occasion. AS is shown in Figure 1, 2, and 3, most of the failures occurred in patients whose spontaneous resting level was close to the mean patient level at that test time, or below it. he of the two patients with consistently high spontaneous activity failed to produce an increase in activity following venous occlusion in the 5 hour test, and one of the failures recorded at 72 hours occurred in a patient who, on that test, had a high spontaneous activity. Obviously failures to respond to venous occlusion occurring in subieck with high resting activity are, in clinical temsss, likely to be less important than failures occurring when the resting activity is low. The rapid rate of increase in plasma plasminogen activator levels in response to physiological stimuli suggests that this so-called vascular activator is released from a store Fibrin autography studies have demomstrated that this store is, at least in part, (9). located in the endothelial cells of the small veins (25) and it is probable that activator It is assumed that the local increase in vascular synthesis also occurs in these cells (26). activator which occurs in response to venous occlusion is due to increased release of this Failure to respond to venous occlusion therefore type of activator from the endothelium. may be due to a defect in the activator release mechanism but could also occur if there was either a defective activator store or a reduced activator synthesis rate resulting, on repeated testing, in an effectively depleted store. A defective release mechanism might be expected to be evident at every venous 0-11~ one patient batient number 25) failed to respond completely at occlusion test. every test - Table 3. Store defects or synthesis rate defects may not be evident on a stngle 5 minute cuff test since 5 minutes venous occlusion is unlikely to cause total depletion of the endothelial activator store, hence the importance of repeating the test after a short In the study reported here, most of the “failures” occurred not on the first interval. test, but on repeat testing (Table 3) perhaps indicating, that in these patients at least, * the disorder is more likely to be in the activator store or synthesis mte, than in activator release.

"FIBRINOLYTICPOTENTIAL"

Vol.lO,No.3

TABLE

517

3.

Patienk 0 hours.

Number.

5 hours.

13

+

+

14

+

+

0

15

+

+

0

0

17

+

+

0

18

+

+

0

19

+

+

0

22

+

0

0

23

+

0

0

25

0

0

21

0

0 +

24

0

+

20

0 +

No specimen

0 +

0

+

16

5 minute resulk

venous cuff

on patienk

Disorders identify

.

.~.

correlation

group studied (Type

potential”

activator

incidence

may not be evident

of previous However,

there was no obvious

In all subjects, anterior

branches

“fibrinolytic

artery

arteries).

previously

“fibrinolytic

arteries.

It seems,

therefore,

in the

abnormalities

response. and and left

these are referred of

to respond to 5 minutes

- 9 had atheromatous

of disordered

lipid

who had evidence lesions in all

4 had lesions in two of these vessels.

three maior vessels and the other 8 had less extensive

or currently

Similarly

.were visualised

(by convention

Of the 13 patients

and the other

who had no evidence

to

in the patient

clad in the circumflex

- in other words who failed

on at least one occasion

two of the major coronary

smoking

fibrinolytic

arteries

of the left coronary

potential”

tesk are

is essential

group there was no

the observed

and defective

artery

coronary

12 patients

cigarette

smoked either

coronary

venous occlusion arteries

if only single

short intervals

the patient

between

both right and left coronary

to as the three maior coronary disordered

heavy

within

relationship

lesions sought in the right

descending

was

to respond to 5 minutes venous occlusion.

Ila or Type Ilb hyperlipoproteinaemias)

atheromatous

being

an increase

tesk at predetermined

the number of cigarettes

of failure

increased

store or synthesis defeck.

the controls. between

and the incidence

to produce

as a +.

of repeat

test

venous occlusion

produced

There was a higher obvious

they failed

as an 0, and those in which

with

group than amongst

potential”

recorded

of “fibrinolytic

individuals

0

to respond normally.

in the left arm after

A progmmme

performed.

“fibrinolytic

who failed

Those tests on which activity

all

72 hours.

potential”, disease

three major

Of the remaining 4 had lesions in

involving

that disordered

only one or “fibrinolytic

Vol.lO,No.3

"FIBRINOLYTICPOTENTIAL"

518

potential ” is more likely to be associated with extensive coronary atheromatous disease. However, no correlation with previous myocardial infarction was demonstrated since of the 16 patients with histories of previous infarct, 8 had evidence of defective fibrinolytic response and 8 were normal. Special care was taken to exclude subjeck who had been taking long term oralp adrenergic blocking agents because these agenk appear to interfere with the fibrinolyttc response to venous occlusion in a not entirely predictable fashion (27). The exact relationship between coronary artery disease and disordered fibrinolytic potential is not clear, but if a defective fibrinolytic mechanism does upset an equilibrium in favour of intmvascular fibrin deposition and if this in turn contributes to the development of atherosclerosis, then perhaps a normal fibrinolytic system is an essential pre-requisite for protection agoinst degenerative vascular disease. Disordered “fibrinolytic potential” has been demonstrated in patienk with coronary heart disease but not in a control group with normal coronary vessels. Defective fibrinolysis would appear to be another “risk factor” worthy of consideration in the pathogenesis of atherosclerosis.

REFERENCES:

1.

ROKITANSKY, K. Sydenhom Society,

2.

DUGUID, J.B., atherosclerosis.

3.

DUGUID,

4.

ASTRUP, T., 1958.

5.

BIGGS, R., MacFARLANE, R.G., Experimental activity fibrinolysis. Lancet, 1, 402, 1947.

6.

FLETCHER, A.P. and ALKJAERSIG, LINDEMAYER, R. I., SHERRY, S., Studies on enhanced fibrinolytic activity in man. J. Clin. Invest. 38, 810, 1959.

7.

MOXLEY, R.T., BRAKMAN, P., and ASTRUP, T. fibrinolysis in blood in inactive and exercising men. 28, 549, 1970.

Resting levels of J.Appl. Physiol.

8.

NILSSON, I.M., and PANDOLFI, R. Fibrinolytic Thromb. Diath. Haemorrh. Suppl. 40, 231, wall.

response of the vascular 1970.

A Manual of pathological London 1852.

anatomy.

4, 261

Thrombosis as a factor in the pathogenesis of coronary J. Path. Bact. 58, 207, 1946.

J.B.,

Mum1 thrombosis in arteries.

The haemostatic balance.

Thromb.

Brit. Med. Bull. 11, 36, 1955. Diath.

Haemorr.

2, 347,

and PILLING, J. Observations on produced by exercise or adrenaline.

N.,

"FIBRINOLYTICPOTENTIAL"

vol.lO,No.3

519

9.

CASH, J.D., and ALLEN, A.G.E. The fibrinolytic response to modemte exercise and intravenous adrenaline in the same subieck. Brit. J. Haemat. 13, 376, 1967.

10.

CLARKE, R.L., ORANDI, A., fibrinolysis by venous occlusion.

11.

HOLEMANS, R. J.Appl . Physiol.

12.

AMERY, A., VERMYiEN, J., MAES, H. and VERSTRAETE, M. Enhancing the fibrinolytic activity in human blood by occlusion of blood vessels. Thromb. Diath. Haemorr. 7, 70, 1962.

13.

ROBERTSON, B. On thrombosis, thrombolysis and fibrinolysis. Acta, Chir. Stand. Suppl. 421, 42, 1971.

14.

WALKER, I.D., DAVIDSON, J.F., and HUTTON, I. “Fibrinolytic Potential”. The response to a 5 minute venous occlusion test. Thromb. Res. 8, 629, 1976.

15.

NILSSON, I.M., Phenformin and Ethyloestrenol in recurrent venous thrombosis. In-Progress in chemical fibrinolysis and thrombolysis. Vol. 1. (Edit. Davidson, J.F., Samama, M. M., Desnoyers, P.C). Raven Press, New York, 1975, p.1.

16.

MERSKEY, C., GORDON, H., LACKNER, H. withcollaboration of SCHRIRE, V KAPLAN, B.J., SOUGIN-MIBASHAN, R., NOSSELL, H.L. and MOODIE A:’ Blood coagulation and fibrinolysis in relation to coronary heort disease; a comparative study of normal white men, white men with overt coronary heart disease and normal Bantu men. Brit. Med. J. 1, 219, 1960.

17.

and HATHORN, M. GILLMAN, T., NARDOO, S.S., and atherosclerosis in Africans. Lancet. 2, 696, 1957.

18.

JUDKINS,

19.

SONE, R.M. Jr. and SHIRLEY, E.K. Cine coronary arteriography. concepts of cardiovascular disease. 31, 735, 1962.

20.

A standardised fibrin plate method and a BRAKMAN, P. Fibrinolysis. Scheltema and Holkema. Amsterdam, 1967. fibrinolytic assay of plasminogen.

21.

ISHERWOOD, D. M. ANNAN, I.W., determination of total serum cholesterol.

22.

In “Automation in analytical KESSLER, S., and LEDERER, H. New York, 1965, p. 341. (edit. Skeggs, L.T).

23.

CARLSON, K. 5, 32, 1973.

M.P.,

and CLIFFTON, E.E. Induction of Angiology, 11, 367, 1960.

Increase in fibrinolytic 18, 1123, 1963.

activity

by venous occlusion.

Selective coronary orteriogmphy.

Lipoprotein fractionation.

Fat, fibrinolysis,

Rodiology, 89, 815, 1967. Modem

An automated method for the direct J. Med. Lab. Technol. 24, 202, 1967.

J. Clin.

chemistry”

Path. 26, Suppl. (A.C.P).

520

"FIBRINOLYTICPOTENTIAL"

Vol.lO,No.3

24.

LEVY, R. I. and LEES, R. S. Fat tmnsport in FREDRICKSON, D .S., lipoproteins as an integrated approach to mechanisms and disorders. New Eng. J. Med. 276, 34, 1967.

25.

Histological TODD, A.S. Bact. 78, 281, 1959.

26.

PANDOLFI, M. Persistence of fibrinolytic activity in fragments of human veins Thromb. Diath. Haemorrh. 24, 43, 1970. cultured in vitro.

27.

DAVIDSON, J.F. HUTTON, I., LAWRIE, T.D.V. WALKER, I.D., Disordered fibrinolytic response in coronary heart disease: A coronary Proc. 7th. European Cardiology Congress (Amsterdam) angiogmphic study. p.342, 1976. (Abstmct).

localization

of fibrinolysin activator.

J. Path.