Disseminated Intravascular

Coagulopathy
James J. Corrigari, Jr, MD

This excellent review of dissemi- (N 25-40 sec); prothrombin time

nated intravascular coagulopathy by (PT), 32.8 seconds (N 1 2-1 4 sec);
a recognized expert may seem at thrombin time, 1 8.4 seconds (N 12- EDUCATIONAL
first to be more than the practitioner 1 4 sec); and euglobulin clot lysis OBJECTIVE
wants to know about the complex time > 2 hours (N > 2 hr). Further
Recognize and evaluate the in-
subject. The author has highlighted coagulation studies revealed re-
the most important clinical issues in duced factors II (20%), V (1 7%), and fant or child at risk of dissemi-
the summary as well as addressing VIII (43%), and fibrinogen (70 mg/ nated intravascular coagula-
the underlying pathophysiology. dl) in plasma, and the presence of tion.
Many of us find that we can remem- fibrinolytic split products in his se-
ber the important clinical points of rum. Subsequently, Neisseria men-
the summary better if we understand ingitidis grew from the blood cul-
the pathophysiology of the condi- tures.
tion. It is in this spirit that this com- Comment: The coagulopathy
prehensive review of an important
present in this case of septic shock
clinical problem is presented in PE-
has the classical findings of dissem-
DIATRICS IN REVIEW.
mated intravascular coagulation:
R.J.H.
clinical evidence of bleeding, throm-
bocytopenia, hypofibrinogenemia,
reduced factors II, V, and VIII in
CASE HISTORY plasma, and the finding of fibrinolytic
A 6-month-old boy was noted by split products in the serum.
his mother to be fussy and have
temperatures ranging from 38.3 to
ACTIVATION OF COAGULATION-
41 .1 C one day prior to hospitaliza-
FIBRINOLYTIC MECHANISMS
tion. The morning of admission, he
was lethargic and the mother noted
Definition
blue spots on the legs, genital area,
buttocks, abdomen, and face. On The slow intravenous infusion of
admission, he was febrile (37.8 C); thromboplastin into animals pro-
the blood pressure was not obtain- duces incoagulable blood with
able; petechiae and purpuric lesions a very characteristic hematologic
were present on the face, trunk and change. The blood demonstrates
extremities, and the mucous mem- hypofibrinogenemia, thrombocyto-
branes, and there were large ecchy- penia, with severe reduction in co-
motic areas of the lower extremities agulation factors II, V, and VIII. De-
(Figs 1 (top) and 2 (bottom)). The pending upon the animal model em-
feet were cold and cyanotic. He was ployed, thrombi may also be present
unresponsive to painful stimuli. The in smaller blood vessels. These in
central venous pressure was 0 cm vivo coagulation results are exactly
H20. Laboratory data showed the as that seen in vitro when plasma or
following values: hemoglobin, 11 whole blood is allowed to clot in a
gm/100 ml; hematocrit, 33%; white test tube. When the coagulation
blood cell count (WBC), 6,400 characteristics of a patient’s plasma
mm3, with 37% segmented forms, (which contains all the coagulation
36% lymphocytes, 12% band forms, factors) resembles those of serum
8% metamyelocytes, 1 nucleated (lacking fibrinogen, factor II, factor
red blood cell (RBC) per 100 WBC, V, and factor VIII) then disseminated
Dr. corrigan is Professor of Pediatrics, chief,
and fragmented RBCs; platelet intravascular coagulation (DIG) is
Section of Pediatric Hematology-Oncology,
count, 77,000/mm3; partial throm- said to be occurring. DIG is due in University of Arizona, Health Sciences cen-
boplastin time (PTT), 120 seconds most cases to the presence of ter, Tucson, Arizona.

pediatrics in review #{149}

vol. 1 no. 2 august 1979 PIR 37
Downloaded from http://pedsinreview.aappublications.org/ by guest on October 28, 2018
Figs 1 (left)and 2 (right).

thrombin in the systemic circulation activation of the coagulation mech- levels of naturally occurring inhibi-
which leads to the formation of fibrin, anism. In addition, the coagulopathy tors are critical factors in determin-
consumption of specific procoagu- may be compensated or decompen- ing the rate, duration, and extent of
lants, thrombocytopenia, and sec- sated depending upon the degree of DIG. Regardless of the underlying
ondary activation of the fibrinolytic consumption of the various proco- primary disease state, the clinical
system. It is a pathophysiologic re- agulants and platelets. If the con- picture in patients with DIG can be:
action triggered by some underlying sumption of these procoagulants ex- (1) predominantly bleeding, (2)
disease state and, depending upon ceeds production, then the resultant thrombosis, (3) both, or (4) neither.
its severity, the patients will manifest levels may be reduced and many
varying degrees of thrombosis and/ cases may be reduced below normal
or bleeding. Because these changes hemostatic levels. In such cases,
Effect of Thrombin on Platelets,
are elicited by the in vivo consump- one would see a decompensated
Coagulation Factors, and
tion of blood clotting factors and form of DIG which, by and large, is Fibrinolysis
platelets, other terms have been the predominant variety present in
used to describe DIG and they pediatric patients. The diagnosis of disseminated in-
include: consumption coagulopa- travascular coagulation is made by
thy, defibrination syndrome, intra- laboratory testing. In order to under-
Mechanism of Activation
vascular coagulation-fibrinolysis stand the use of screening and spe-
syndrome, and generalized intravas- The conversion of fibrinogen to cific tests for this entity, a brief re-
cular coagulation. fibrin is the final pathway common to view of these laboratory tests is
Disseminated intravascular coag- all the entities with DIG. But the needed. Since disseminated intra-
ulation implies that the coagulation agent or material which is intro- vascular coagulation is due to the
mechanism has been activated by duced into the circulation that initi- presence of thrombin in the systemic
the introduction into the systemic ates intravascular clotting may be circulation in most, if not all cases,
circulation of clot-promoting mate- different. Table 1 shows known clot- the action of this enzyme in the
rials. However, a consumption co- promoting agents in animal models coagulation-fibrinolytic system is
agulopathy can also occur second- for intravascular coagulation and the shown on Figure 3. Thrombin is gen-
ary to large localized clotting events, proposed human equivalent. Just erated from prothrombin by activa-
such as in arterial aneurysms and how these can produce human dis- tion of either the intrinsic and/or
giant hemangiomas, in which ease is not known, but the animal extrinsic coagulation systems. The
enough clotting occurs locally so experiments suggest that factors coagulation mechanism is com-
that the circulating blood may exhibit such as the quantitative amount of posed of the intrinsic and the extrin-
the findings of DIG. Thus a consump- clot-promoting material, the func- sic or tissue systems. The intrinsic
tion coagulopathy can be produced tional capability of the reticuloendo- system is initiated by way of contact
by either generalized or localized thelial system, vascular flow, and the activation of factor XII and is the

PIR 38 pediatrics in review #{149} vol. 1 no. 2 august 1979

Downloaded from http://pedsinreview.aappublications.org/ by guest on October 28, 2018
system analyzed by the partial
thromboplastin time. The extrinsic TABLE 1. Disseminated Intravascular Coagulation and Consumption
system is initiated by tissue throm- Coagulopathy: Triggering Mechanisms
boplastin-activating factor VII, by-
Experimental Triggering Agent Possible Pediatric Equivalent
passing factors XII, XI, IX, and VIII,
Endotoxin Gram negative septicemia
as is analyzed by the prothrombin
?Necrotizing enterocolitis
time. Thrombin itself is very short-
Thromboplastic material Shock
lived and difficult to measure. Thus, (tissue juices) Endothelial damage (virus, bacterial, rickettsia,
the effects of thrombin on the circu- heat stroke)
lating blood are usually used to de- Trauma/burns
tect its presence. As can be seen Ascitic fluid (LaVeen shunt)
from the Figure, thrombin is a known Hypoxia-acidosis, severe (HMD)
activator of the fibrinolytic mecha- Malignancies (acute leukemia, neuroblastoma,
nism. Thrombin also acts on fibrino- rhabdomyosarcoma)
Dead fetal twin
gen in a very specific way to release Hemolytic transfusion reaction
two peptides (peptides A and B) pro- Small for gestational age and postmaturity (pla-
ducing a fibrinogen molecule that is cental infarction)
still soluble in plasma called fibrin Antigen-antibody complexes Immune disease (?purpura fulminans)
monomer. Fibrin monomer then Anaphylactic shock
polymerizes and is converted to the Blood stasis Generalized: shock
insoluble fibrin form by the action of Localized: giant hemangioma, chorangioma
Particulate matter Hemolytic transfusion reaction
activated factor XIII. Factor XIII is
similarly activated by thrombin.
Thrombin also acts on platelets to
induce aggregation and subsequent
thrombocytopenia occurs. During
the process of aggregation, the
INTRINSIC EXTRINSIC
platelets release a number of mate- COAGULATION COAGULATION
rials including platelet factor 4 and SYSTEM SYSTEM
fl-thromboglobulin. Thrombin in 4 I
small amounts acts on both the in- -J
trinsic and extrinsic coagulation sys- THROMBIN
tems by facilitating the reactions of
factors VIII and V in the intrinsic and
factor V in the extrinsic system; in
‘I, II,
PLASMINOGEN FIBRINOGEN FACTOR XIII PLATELETS
larger amounts, these factors are
(oth er / peptade A
consumed. The formation of plasmin
(fibrinolysin) is a very necessary part activators) 4, , / _______ Peptide B
“P
of the normal physiologic response AGGREGATION
to thrombin generation. Fibrin may S

‘I,
‘4
.4
now be lysed by this enzyme. It Release of
should be noticed, however, that PLASMIN ‘4
FIBRIN
FIBRIN MONOMER FACTOR XIIIa
%4
POLYMER ft TG
plasmin may also degrade fibrin others.
polymer, fibrin monomer, and fibrin-
ogen. All four of these reactions re-
sult in the formation of what are FIBRIN THROMBOCYTOPENIA
called fibrinolytic split or degrada-
tion products (FSP, FDP). A knowl-
edge of this reaction is important for “P
FIBRINOLYTIC
later understanding of the various SPLIT PRODUCTS
Fig 3.
tests employed in the DIG syn-
dromes.

pediatrics in review #{149} vol. 1 no. 2 august 1979 PIR 39

Downloaded from http://pedsinreview.aappublications.org/ by guest on October 28, 2018

CLINICAL APPLICATION velop this condition. However, chil- Ewing’s sarcoma, histiocytosis X,
dren with rickettsial diseases and a and erythrophagocytosis Iympho-
Pediatric Diseases with DIC variety of disseminated viral dis- histiocytosis.
eases may manifest a DIG state in Massive head injury such as oc-
Table 2 shows some of the pedi-
the absence of shock. Perhaps this curs in accidents and gunshot
atric diseases in which DIG has been
is related to the fact that these two wounds can release enormous
reported. The most common causes
conditions have severe dissemi- amounts of thromboplastic material
of the consumption coagulopathy in
nated endothelial disease, a condi- into the systemic circulation, result-
children appear to be bacterial sep-
tion similar to heat stroke. Infants ing in a consumption coagulopathy.
tic shock, severe respiratory dis-
with very severe respiratory distress Transfusion reactions can produce
tress syndrome in newborns, giant
syndrome regularly exhibit DIG. this; however, these are very rare in
hemangiomas, and certain malig-
Other newborns with less severe children. The entity of necrotizing
nancies. Absent from this list are the
RDS tend not to have a consumption enterocolitis in newborns may also,
hemolytic uremic syndrome, throm-
coagulopathy. Small for gestational in a select group of these patients,
botic thrombocytopenic purpura,
age and postmature infants also demonstrate DIG.
and other generalized vasculitic dis-
have been reported to have DIG
ease states which do not fulfill the Clinical Picture
which may be related to placental
criteria for generalized or dissemi-
injury and the subsequent release of The complex clinical picture of
nated intravascular coagulation as
thromboplastic material from that or- DIG is due, in part, to the various
defined above.
gan. Purpura fulminans (or postin- manifestations related to the primary
Children with bacterial septicemia
fectious gangrene) clearly has dis- or the underlying disease process
who are not in shock, rarely, if ever,
seminated intravascular coagulation and in part to the wide variability of
develop disseminated intravascular
associated with it. In this rare con- DIG itself. Since DIG is a secondary
coagulation. It appears that only
dition, both thrombosis and bleeding process, a careful search will invari-
those who have hypotension asso-
are the cardinal manifestations of ably reveal the underlying primary
ciated with their septicemic state de-
the clinical picture. The exact mci- disease state. Regardless of the un-
dence of a consumption coagu- denying primary disease, the clinical
lopathy in patients with giant heman- picture in patients with DIG can be
giomas is not known. However, predominantly bleeding as the major
TABLE 2. Pediatric Diseases with DIC there are a number of reports in the manifestation and/or thrombosis. In
Infections literature clearly demonstrating the the majority of children with DIG, the
Bacterial septic shock existence of the coagulopathy as- main clinical finding is the presence
Rickettsial sociated with this benign tumor. Cer- of bleeding. Thrombosis, except in
Viral, disseminated
tain snakebites are associated with rare instances, usually is not clini-
Protozoal
a coagulopathy that looks like dis- cally obvious. Retrospective data,
Malignancies
Giant hemangioma seminated intravascular coagula- usually from postmortem studies,
Purpura fulminans tion. In the United States, this is al- suggest that fibrin deposition does
Snake bites most always due to rattlesnake not always occur, and, even if pres-
Shock states bites. The venom of this snake con- ent, does not always cause irrevers-
Heat stroke
tains a thrombin-like material, but it ible tissue damage even in florid
Massive head injury
Transfusion reactions is not thrombin. The shock states, cases of DIG. This is probably due
Neonatal conditions severe trauma, and burns in general, to lysis of the fibrin by the fibrinolytic
Severe hypoxia-acidosis (asphyxia; have been associated with DIG. Cer- mechanism before it is deposited in
respiratory distress syndromes) tain malignancies in children have the blood vessel, or by the reticulo-
Infections been noted to have DIG. There is no endothelial system removing circu-
Obstetrical (abruptio placentae, dead
doubt that the coagulopathy occurs lating activated coagulation prod-
twin fetus, eclampsia-pre-eclampsia,
small for gestational age, and post- in acute progranulocytic leukemia, ucts and fibrin. The diagnosis is sus-
maturity) and all the leukemias have the po- pected by having a patient with a
Miscellaneous (severe EBF; necrotizing tential of developing the coagu- disease entity that is known to have
enterocolitis, shock) lopathy with treatment. There are DIG associated with it and by abnor-
scattered reports of DIG being seen malities in appropriately picked
in patients with rhabdomyosarcoma, screening tests.

PIR 40 pediatrics in review #{149} vol. 1 no. 2 august 1979

Downloaded from http://pedsinreview.aappublications.org/ by guest on October 28, 2018

 Patients with disseminated intra- penia, as defined as a platelet count
vascular coagulation usually present less than 1 50,000, has been present
TABLE 3. Expected Results of Screen-
with bleeding at multiple sites. The in 97% of our cases. The prothrom-
ing Tests in 200 Children with DIC
bleeding may be in the form of pe- bin time and partial thromboplastin
Expected
techiae of the skin and mucous time have been prolonged in 100%; Screening Tests
Findings
membranes, oozing from cut-down thus, there appears to be no benefit
Blood smear Fragmented
sites and venipuncture sites, or from doing both tests. Hypofibrino-
RBCs
rarely, heavy bleeding from the gas- genemia, defined as less than 150 Reduced
trointestinal or genitourinary tract. mg/dI, was helpful in 77% of the platelets
Clinically significant central nervous cases and FSPs (FDPs) were posi- Platelet count <150,000/
system bleeding is very rare. The tive in 92%. It should be noted that cu mm
reason for the hemorrhagic diathesis Partial thromboplas- Prolonged
these are only screening tests and
tin time (PTT)
is due to three mechanisms. One, do not provide enough evidence to
Prothrombin time Prolonged
when the level of the plasma proco- make a diagnosis of DIG. The (PT)
agulants (fibrinogen, factor II, factor screening tests are valuable, how- Fibrinogen concen- <150 mg/dI
V, and factor VIII) is below normal ever, in detecting that a coagu- tration
hemostatic levels, bleeding can oc- lopathy exists and the severity of the FSP Positive
cur. Two, thrombocytopenia simi- abnormalities. Although the pres-
Iarly can be severe enough to allow ence of fibrinolytic split products has
bleeding. And, three, the fragments been thought to be diagnostic of
produced by plasmin action on fibrin DIG, it should be noted that these
and/or fibrinogen have effects in the fragments can be present in other
TABLE 4. Specific Tests for DIC
coagulation mechanism. Thus the disease states without associated
bleeding diathesis that appears in DIG as defined in this article. Presence of soluble fibrin’ in plasma
these patients is due to the con- (fibrin monomer and its complexes)
Specific Tests. In order to diag-
Reduction in plasma levels of fibrinogen
sumption of varying clotting factors nose DIG specifically, other labora-
and factors II, V, and VIII
and platelets and to the secondary tory tests are necessary. The tests Elevation of fibrinolytic split/degrada-
activation of the fibrinolytic mecha- available are shown in Table 4. The tion products in serum
nism. tests that are most commonly em- Presence of fibrinopeptide A in plasma
ployed and available to the clinician Presence of platelet factor 4 and/or fi-
thromboglobin in plasma
are those that detect the presence
Laboratory Tests Short platelet and fibrinogen in vivo sur-
of soluble fibrin and coagulation fac- vival
Screening Tests. Accurate diag- tor assays for factors II, V, and VIII, Evidence for fibrin deposition by biopsy,
nosis is made by specific laboratory and fibrinogen. autopsy, or clinical evidence of throm-
testing since other acquired coagu- The presence of fibrin monomer boembolic events
lopathies can produce similar find- and its complexes (soluble fibrin)
ings. Table 3 lists the screening tests and/or fibrinopeptide A in plasma
that are commonly employed. In an provides strong evidence for intra-
analysis of 200 children with dis- vascular thrombin activity. Various
seminated intravascular coagulation tests are available for detecting sol- thrombotic diathesis, a specific co-
the most useful screening tests have uble fibrin; these include: the agulation test profile, in some pa-
been the platelet count, prothrombin ethanol gelation test, protamine sul- tients the presence of fibrin thrombi,
time, and the presence of fibrinolytic fate precipitation test, column chro- and the occasional patient’s re-
split products. The examination of matography, 14CgIycine ethyl ester sponse to specific therapy.
the blood smear looking for frag- incorporation into fibrin, fibrinogen Differential The differ-
Diagnosis.
mented red blood cells has not been immune precipitate test, and so ential diagnosis of the abnormal co-
as valuable a finding as was previ- forth. The use of platelet and fibrin- agulation screening tests include
ously expected. There are many ogen survival is generally not prac- liver disease, vitamin K deficiency,
other things that can produce frag- tical for acute DIG but is useful in dilutional changes secondary to
mented red blood cells and there chronic DIG. Thus, the diagnostic massive volume replacement, and
are cases of DIG that have normal manifestations of DIG include the septicemia without DIG. Table 5
red cell morphology. Thrombocyto- clinical findings of a hemorrhagic- shows the results of the various tests

pediatrics in review #{149} vol. 1 no. 2 august 1979 PIR 41

Downloaded from http://pedsinreview.aappublications.org/ by guest on October 28, 2018

 in patients with bacterial septicemia
as subdivided on the basis of the
TABLE 5. Screening Test Results in Bacterial Septicemia’
presence or absence of shock. As
Blood Pressure PU PT Platelets Fibrinogen FSPs can be seen, 25% of the patients
Normotensive(24) 6/24 7/24 9/19 0/24 0/20 with normal blood pressures dem-
25% 29% 47% = 460 onstrate prolonged prothrombin
Hypotensive(26) 26/26 26/26 23/26 20/26 16/22 times and partial thromboplastin
100% 100% 89% 77% 72% times and 48% had thrombocyto-
= 160
penia. However, as clearly different
4 Values for PTT and PT are for number prolonged/total patients; values for
from the hypotensive group, these
platelets and fibrinogen are for number reduced/total patients; values for FSPs are patients had normal to elevated fi-
for number present/total patients. Number of patients is shown in parentheses; y brinogen and the absence of fibri-
= mean value (mg/dl).
nolytic split products. In the hypo-
tensive group the prothrombin time
- and PU were prolonged in all cases
and thrombocytopenia was present
in 90% of the cases. Fibrinogen was
clearly lower in this group with 77%
TABLE 6. Comparison Between DIC and Liver Disease being below 1 50 mg/dI. Fibrinolytic
Platelets FSP split products were present in 72%.
PT (sec) Fibrinogen
(mg/dl) (x103/cu mm) (%+) Thus, in the child with bacterial sep-
DIC (40 cases) ticemia, the presence of a low fibrin-
Mean 29.3 131 60 ogen and positive FSPs indicates
Range 1 7.6-1 50 0-524 4-226 that DIG is present. Probably the
% abnormal 1 00 77 97 81
most difficult disease entity that can
%1OOmg/dl - 64 - -
be confused with DIC is severe hep-
%5O,O0O/cumm - - 50 -

Liver disease (20 cases) atocellular disease. Table 6 shows

Mean 28.4 117 116 a comparison between 40 cases of
Range 1 5.7-52.5 33-257 26-386 DIG and 20 cases with severe hep-
% abnormal 1 00 83 63 20 atocellular disease. As can be seen,
%1OOmg/dl - 50 -
the prothrombin
-
time was abnormal
%5O,0O0/cumm - - 18 -
in both groups. Also, in both groups
the fibrinogen was below normal,
77%ofthecasesin DIG and 83% of
the cases in liver disease. Those
patients with marked hypofibrinoge-
TABLE 7. Comparison of Screening and Specific Tests between DIC and nemia were more common in the DIG
Entities Confused with DIC’ cases, however. Thrombocytopenia
occurred in 97% of the DIC cases,
DIC Liver Vitamin K Dilutional Sepsis with- and also in 63% of the patients with
Disease Deficiency out Shock
#{149}1
liver disease. However, severe
Parbal thromboplastin time P P P P P
Prothrombin time P P P P P thrombocytopenia, as defined as
Fibrinogen R R N R E less than 50,000, was more com-
Factorll R R R R R mon in the DIG cases. Similarly the
FactorV R R N R E presence of fibrinolytic split prod-
Factor VIII R N-E N R E ucts was more common in those pa-
Platelets R N-R N R N-R
tients with DIG. The data show, how-
FSPs + ± 0 0 0
ever, the overlap and similarity in the
‘‘Soluble fibrin’ ‘ + 0 0 0 0
screening test between these two
S Abbreviations used are: P, prolonged; N, normal; R, reduced; + present;
, 0, disease entities. More definitive test-
absent; E, elevated. H ing such as the presence or absence
. of soluble fibrin complexes or a re-

PIR 42 pediatrics in review #{149} vol. 1 no. 2 august 1979

Downloaded from http://pedsinreview.aappublications.org/ by guest on October 28, 2018

duction in factor VIII would help to replace the depleted procoagulants, tress syndrome in newborns, and
differentiate between the two differ- and then depending on a need, various malignancies.
ent types of coagulopathies. either medically interrupt the proc- In some patients, however, the
Two other conditions that can give ess with anticoagulants, or anti- treatment of the underlying disease
abnormal screening tests, and are venom in the caseof snakebites. may be inadequate or too slow, or
commonly encountered in the pedi- It is clear thatmost important
the replacement therapy has not been
atric patient, are vitamin K defi- aspect of management is proper effective so that the management
ciency and dilutional changes. In vi- treatment for the underlying disease must now be aimed at medically in-
tamin K deficiency, factors II, VII, IX, such as appropriate measures for terrupting the DIG with anticoagula-
and X may be below hemostatic combating shock, chemotherapy-ra- tion. Heparin has been the drug of
levels and thus the prothrombin time diotherapy-operation for malignan- choice in view of its rapid onset of
and PTT will be abnormal. However, cies, operation or radiation therapy action, potent anticoagulating activ-
in these cases the fibrinogen and for giant hemangiomas, and so forth. ity, and ease of regulation and neu-
platelet count are normal, and FSPs There are now a number of reports tralization. Heparin can be given on
are not present. The child who has that strongly suggest that prompt either a continuous or intermittent
had massive volume replacement and adequate elimination of the pri- intravenous schedule. Studies in
with coagulation and/or platelet mary disease will abolish DIG and adults have shown that therapeutic
poor material can demonstrate the anticoagulation may not be neces- effectiveness is the same using
laboratory abnormalities seen in sary. either schedule. However, the con-
DIG. However, the difference is that The next aim of therapy, espe- tinuous schedule has been associ-
FSPs are not present nor is there cially in the patient who is bleeding, ated with less heparin-induced
evidence of circulating fibrin com- is replacement of the coagulation bleeding, suggesting that this may
plexes. As a rule of thumb, if the factors and/or platelets to hemo- be the safer means of treatment; but
patient has been replaced with co- static levels. Depending on the this has not been evaluated in chil-
agulation-platelet poor material in need, this may be by the use of dren. Since individual patients vary
the volume that is equal to his blood platelet concentrates (one concen- in their response, and the response
volume, then the coagulation factors trate per 5 kg of body weight), fresh in the same patient may vary during
and platelets will be reduced 50%. or fresh frozen plasma (1 0 to 1 5 mI/ the course of treatment, sequential
For example, if a child with a 2-liter kg), cryoprecipitates for fibrinogen coagulation evaluations must be
blood volume has a fibrinogen con- and factor VIII (3 to 4 bags/lO kg), done in order to judge the effective-
centration of 200 mg/dl and is given or other concentrates. Subsequent ness, or lack of effectiveness, of an-
replacement therapy of 2 liters of replacement is determined by the ticoagulant therapy. Although the
fluid or colloid which does not con- half-life of the factors and platelets. partial thromboplastin time can be
tain coagulation factors, then the fi- Antifibrinolytic therapy is not rec- used to evaluate the heparin dose,
brinogen will drop to 100 mg/dl. ommended and can be dangerous. in disseminated intravascular coag-
Table 7 shows the expected findings It has been suggested by some in- ulation specific coagulation factor
in these entities as compared to vestigators that replacement therapy assays are more desirable for judg-
those with disseminated intravascu- should not be given to patients with ing the duration and effectiveness of
lar coagulation. DIG unless they are heparinized. The therapy. In our patients, we use the
reason for this recommendation is fibrinogen concentration as the pre-
based on the presumption that the liminary guide to the effectiveness of
Management of DIC
addition of more procoagulants will the therapy. Bleeding is the most
The objectives of management are only allow more consumption to pro- common and most significant com-
to abolish the bleeding and to elimi- ceed. However, our experience and plication of heparin therapy. Al-
nate the threat of fibrin deposition. that of others suggest that this does though the frequency of heparin
Since DIG results from some under- not actually occur in the majority of bleeding in documented cases of
lying disease, it follows that removal patients treated with replacement DIG appears to be low, it does occur
of the cause will abolish the coagu- therapy without concomitant anti- even at a time when laboratory data
lopathy. However, this may not be coagulation. Replacement therapy suggest that DIG is being brought
completely possible in all situations, alone has been used quite success- under control. In some cases hepa-
in which case other approaches are fully in patients with DIG associated rin induces thrombocytopenia, in
necessary. The approach is to first with septic shock, respiratory dis- which case the bleeding can be due

pediatrics in review #{149}

vol. 1 no. 2 august 1979 PIR 43

Downloaded from http://pedsinreview.aappublications.org/ by guest on October 28, 2018

to this and not just anticoagulation. treatment of the infection and re- time). In the presence of liver dis-
Although controlled studies on the moval of the shock. In certain clinical ease, reduced factor VIII and/or the
use of heparin in DIG are few, the settings, heparin will be useless be- presence of circulating soluble fibrin
accumulated data suggest that hep- cause of the event that elicited the complexes would be needed to di-
arm has benefited most cases of coagulopathy. The best example of agnose DIG. Once the diagnosis is
acute promyelocytic leukemia, and this is snakebites. Some snakes, established and the underlying ill-
giant hemangioma, purpura fulmi- such as the rattlesnake, have a ness identified and treated, the ther-
nans, and the intravenous infusion thrombin-like material in the venom. apy of the DIG is generally suppor-
of ascitic fluid, and perhaps in dys- Thus, hypofibrinogenemia with or tive. Anticoagulation (heparin) man-
mature or SGA infants. In purpura without thrombocytopenia may be agement is rarely needed except in
fulminans, heparin is recommended seen. However, the material is not cases of purpura fulminans, where
and has been shown to reduce the thrombin and cannot be eliminated it can be lifesaving, and selected
morbidity and mortality associated with heparin. Antivenom is a treat- cases of giant hemangioma or malig-
with this disease. In acute promye- ment of choice in this hematologic nancy. In cases of septic shock and
locytic leukemia, adequate treat- disorder. in severe RDS, successful manage-
ment of this disease may not be pos- At the present time, the use of ment of the shock and the respira-
sible or the response to therapy may other agents in the treatment of DIG tory failure will cause the DIG to dis-
be delayed, thus heparin therapy is still investigational. Such things as appear without the use of anticoag-
may be necessary to control DIG and platelet inhibitors, fibrinolytic acti- ulation.
its consequences. Although DIG dis- vators, and dextran are presently
appears when there is removal or being studied, but no general rec-
SUGGESTED READING
reduction in size of the giant heman- ommendations can be made.
gioma, in some cases, anticoagula- 1. Antley RM, McMillan CW: Sequen-
tion may be necessary to abolish a tial coagulation studies in purpura
SUMMARY fulminans. N Engi J Med 276:1 287,
hemorrhagic diathesis. In all these
1967
cases, absolute control of DIG ne- Disseminated intravascular coag-
2. Champion LAA, Luddy RE,
cessitates the effective removal of ulation is most common in children Schwartz AD: Disseminated intra-
the underlying disease state. Anti- with bacterial septic shock, infants vascular coagulation in childhood
coagulation may result in only a tem- with severe respiratory distress syn- acute leukemia with poor prognos-
porary cessation of the coagu- drome, in giant hemangiomas, and tic features. Cancer4l :1 642, 1978
lopathy. in purpura fulminans. The diagnosis 3. Colman RW, Robboy SJ, Minna JD:
There are a great number of dis- is suspected when purpuric bleeding Disseminated intravascular coagu-
ease states in which DIG is pre- and/or thrombosis occurs in those lation (DIC): An approach. Am J
sumed to be operative, but the value clinical settings known to have DIG Med52:679, 1972
4. Corrigan JJ Jr, Bennett BB, Bueffel
of heparin in either correcting the associated with them. The coagu-
B: The value of factor VIII levels in
DIG or in influencing the total clinical lopathy is also suspected when the
acquired hypofibrinogenemia. Am J
course is not established. Such con- patient has thrombocytopenia and C/in Patho/ 60:897, 1973
ditions as bacterial infections, heat prolonged clotting times in coagula- 5. Corrigan JJ Jr: Heparin therapy in
stroke, a variety of neonatal dis- tion screening tests (prothrombin bacterial septicemia. J Pediatr 91:
eases, viral, rickettsial, and fungal time and partial thromboplastin 695, 1977
disease fall into this category. For time). Gonfirmation of the diagnosis 6. Hagerman U, Czapek EE, Donnel-
example, patients with bacterial sep- requires further laboratory data. Al- Ian WL, et al: Giant hemangioma
ticemia and shock do have DIG. though it would be ideal to have a with consumption coagulopathy. J
However, heparin therapy in this set- complete analysis of all the coagu- Pediatr 87:766, 1975
7. Hathaway WE: Care of the critically
ting has not improved mortality rates lation factors, this is generally not
ill child: The problem of dissemi-
and the hematologic data are incon- universally available nor always nec-
nated intravascular coagulation.
clusive with regard to its effect on essary in all cases. In the absence Pediatrics 46:767, 1970
the coagulopathy. There have been of liver disease, the minimal criteria 8. Kazmier FJ, Bowie EJW, Hagedorn
reports on patients with septic shock for diagnosis is the combination of AB: Treatment of intravascular co-
and DIG who have not received hep- thrombocytopenia, positive fibrino- agulation and fibrinolysis (OCF)
arm and survived. In these patients, lytic split products, and hypofibri- syndromes. Mayo C/in Proc 49:
the DIG was abolished by successful nogenemia (or prolonged thrombin 665, 1974

PIR 44 pediatrics in review #{149} vol. 1 no. 2 august 1979

Downloaded from http://pedsinreview.aappublications.org/ by guest on October 28, 2018

 9. Marder VJ, Matchett MO, Sherry 5: 11. M#{252}ller-Berghaus G: Pathophysiol- Pathology of disseminated intravas-
Detection of serum fibrinogen and ogy of generalized intravascular co- cular coagulation: Analysis of 26
fibrin degradation products: Com- agulation. Semin Thromb Hemostas cases. Hum Patho/ 3:327, 1972
parison of six techniques using pur- 3:209, 1977 15. Roberts HR, Cederbaum Al: The
ified products and application in 12. O’Donnell TF: Acute heat stroke: liver and blood coagulation: Physi-
clinical studies. Am J Med 51:71, Epidemiologic, biochemical, renal ology and pathology. Gastroenter-
1971 and coagulation studies. JAMA o/ogy63:297, 1972
10. McMilIan CW: Hemostasis: General 234:824, 1975 16. Yoshikawa T, Tanaka KR, Guze LB:
considerations, in Miller DR, Pear- 13. Owen CA Jr, Bowie EJW: Chronic Infection and disseminated intra-
son HA, Baehner RL, et al (eds): intravascular coagulation syn- vascular coagulation. Medicine 50:
Smith’s Blood Diseases of In fancy dromes: A summary. Mayo C/in 237, 1971
and Childhood, ed 4. St. Louis, CV Proc 49:673, 1974
Mosby Co, 1978, p 679 14. Robboy SJ, Colman RW, Minna JD:

Abstract
EDUCATIONAL Pregnancy Use of Diethylstilbestrol
OBJECTIVES
Health Effects of the Pregnancy Use of Diethylstilbestrol (DES). Rich-
Advise parents of adolescents mond JB. Department of Health, Education, and Welfare Physician Advi-
with a history of Intrauterine ex- sory, Oct 4, 1978.
posure to diethylstilbestrol. DES has been available since 1 938. There is a definite association of
intrauterine exposure to DES and clear cell adenocarcinoma in female
Counsel parents of the child
offspring (DES daughters). Other DES daughters have developed benign
whose mother has received dieth-
vaginal adenosis. Mothers taking DES during pregnancy (DES mothers)
ylstllbestrol during her pregnancy. have an increased incidence of breast and gynecologic cancers. Male
offspring (DES sons) have an excess of external genital anomalies including
cryptorchidism, hypoplastic testes, and decreased sperm.
The risk of adenocarcinoma in DES daughters is less than 2/1000.
Adenosis rarely, if ever, progresses to carcinoma and should be followed
rather than aggressively treated. DES daughters should have thorough
pelvic examinations with special tests (Papanicolaou smear and iodine
staining) yearly beginning at menarche with culposcopy for those with
abnormal findings.
DES mothers should have routine screening for breast and gynecologic
cancer. DES sons should have a routine genital examination to detect
abnormalities.
The use of DES for postcoital contraception incurs a risk of possible
existence of pregnancy and should be discouraged. DES use by DES
mothers and daughters incurs additional risks and should be used pru-
dently-perhaps avoided if suitable alternatives exist. (R.H.R.)

pediatrics in review #{149} vol. 1 no. 2 august 1979 PIR 45

Downloaded from http://pedsinreview.aappublications.org/ by guest on October 28, 2018

 Disseminated Intravascular Coagulopathy
James J. Corrigan, Jr
Pediatrics in Review 1979;1;37
DOI: 10.1542/pir.1-2-37

Updated Information & including high resolution figures, can be found at:
Services http://pedsinreview.aappublications.org/content/1/2/37
Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its
entirety can be found online at:
https://shop.aap.org/licensing-permissions/
Reprints Information about ordering reprints can be found online:
http://classic.pedsinreview.aappublications.org/content/reprints

Downloaded from http://pedsinreview.aappublications.org/ by guest on October 28, 2018

 Disseminated Intravascular Coagulopathy
James J. Corrigan, Jr
Pediatrics in Review 1979;1;37
DOI: 10.1542/pir.1-2-37

The online version of this article, along with updated information and services, is located on
the World Wide Web at:
http://pedsinreview.aappublications.org/content/1/2/37

Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1979. Pediatrics in Review is owned, published, and
trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143.
Copyright © 1979 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0191-9601.

Downloaded from http://pedsinreview.aappublications.org/ by guest on October 28, 2018