Stephen

Thrombosis

is a multifactorial

probably

maintain

ofclotting

cesses relevant

process. a balance

Although

between

and clot lysis, it has been

thrombosis

requires

Administration

effects

in Rockville,

and

efficacy

dose

and

safety.

For

for study

and

pelvic

identify

a study

Outcomes whether

such

embolus.

and

Drug

angina,

their

selecting

infarction,

tection

use patients

transient

isch-

posed

stroke, are

risk for thrombotic

with

heart

failure,

paralysis,

polycythemia

have conditions with these patients

vera

to

events.

that make them the hematologic

the subject

trial. The instances

use ofa decreased hematocrit or platelet is a surrogate endpoint, which depends

pretation

on the index there

but is followed

link

as one

established

between

endpoint

indicate a thrombotic

tendency;

need to be identified

as distinguishable

relationship between

changes

and

count in such for its interin a hema-

the

norm,

in an index and meaningful

of venous

tein C-deficient which thrombotic dividuals

81 4S

thrombosis

60-80%

approached

to and

a

for

protein

C deficiency.

in pro-

Subsequently,

Am

iC/in

an

risk

patients

oral

coagulation trials. foods

and

their

experiments,

role.

clinical

risk an-

is significant

therapeutic

events

actual natural

in prospective that a demonstrated

use

ofdrug evaluation, effect on coagulation

nutritive

The

C or other

cascade

Although

of some

trials

studies. ab-

until

it is

food

sub-

we are concerned or some vascular hypotheses

may be generated are needed

or preventive

and

in asymppossible pro-

anticoagulation

ofbleeding.

must be investigated against assuming

increased

about

by in vitro to define

measures

ben-

as well

as

13

1 . Joist IH. Hypercoagulability: introduction Thromb Hemost 1990; 16:151-7. 2. Comp PC. Overview of the hypercoagulable Hemost 1990:16:158-61.

and perspective. states.

Semin

Semin Thromb

clinical

members (2). Other kindreds were identified in complications appear to be restricted to in-

homozygous

of the

with

counseling

of protein

at risk ofthrombotic

animal

knowledge

that

prophylactic

the increased

that high

References

effect would have to be established. For example, case-finding studies identified kindreds in which the incidence

than

for

donors

at a relatively

mdi-

normal are thought

such laboratory findings would from

is useful

efits and risks of treatments to establish their utility.

in a clinical

a change

and a clinical benefit. In apparently may be laboratory findings that

rather

people

show

of a kindred

concentrations

normality in the proven in clinical

factor

throm-

data

by long-term

by low

of blood

occurs

for thromboembolic complications, there is no evidence that the

outweighs

If we consider

prone to thrombotic finding not only

identifies

of thrombosis

stances from the viewpoint with their pharmacological

or pulmonary

or essential

present

of members

ticoagulant proteins This example warns

or deepchosen

population

C deficiency

Although C status

afforded

therapy

a population

characteristics

in a large protein

monitoring them tomatic individuals

relevant

to define

we often

when

at greater

as death,

Patients

bocytosis events;

tologic viduals

protein

or endpoints would be the development of thrombosis, coronary, cerebral, or venous, with or without clinical

sequelae

demonstrated

frequency.

injury,

clinically

agents

of having

clinical

population

Food

we evaluate

of myocardial

These

it was

asymptomatic

incidence

of the

neoplasms

of prevention

thrombosis.

vascular

of new drugs,

criteria

inpro-

that clinically

suggested

to therapeutic trials

who fulfill the entrance attacks,

Md.,

response

normal

the ongoing

hypercoagulability,

and stasis (for review, see Joist [1]). At the Center for Drug Evaluation

vein

for assessing

Fredd

dividuals

emic

are valid

Nuir

1992;56:8

‘From the Division of Gastrointestinal and Coagulation Drug ucts, Food and Drug Administration, Rockville, MD. 2 Address reprint requests to S Fredd, Division of Gastrointestinal

Prod-

Coagulation Administration,

Drug

l4S.

Printed

Drug Products, 5600 Fishers

in USA.

HFD-l80, Room 1092, Food Lane, Rockville, MD 20857.

© 1992 American

Society

for Clinical

and

and

Nutrition

Downloaded from https://academic.oup.com/ajcn/article-abstract/56/4/814S/4715639 by Boston University user on 14 January 2019

Which surrogate endpoints thrombotic tendency?1’2