1982. Purpura Fulminants

8/11/2019 1982. Purpura Fulminants.

1/7

Purpura Fulminans

David 2. J. Chu, MD, Houston, Texas

F. William Blalsdell, MD, Sacramento, California

Purpura fulminans presents as a catastrophic febrile

illness, with initial hemorrhagic skin lesions that

progress to gangrene. The confluent purpura usually

occur in distal extremities in a symmetrical distri-

bution. The basic clinical picture is septicemia, shock

and disseminated intravascular coagulation. Pul-

monary, renal and hepatic failure, as well as gas-

trointestinal hemorrhage, are frequent complica-

tions. If these patients survive the initial critical

period, the management of skin necrosis and ex-

tremity gangrene, which characterize the disease,

challenges the surgical judgment.

Findings

A review of the records at the University of Cali-

fornia, Davis Medical Center from 1966 to 1979 re-

vealed 10 patients with purpura fulminans. This

constitutes the largest individual clinical experience

reported in the English literature. It is summarized

in Table I.

The patients in this series illustrate that purpura

fulminans appears as a complication of certain life-

threatening infections. The purpura occurs in two

forms: acute, which is immediately superimposed on

bacterial infections, and chronic, which follows viral

infections or idiopathic causes.

In nine of our cases the purpura fulminans mani-

fested acutely. Sepsis was evident, and the patients

blood cultures grew a variety of organisms. Menin-

gococci, groups B and XYZ, were the most common.

The exceptions were two patients cases 5 and 9)

whose blood cultures failed to grow any bacteria.

Shock developed within

48

hours of diagnosis of the

systemic infection. The progression of the disease was

then rapid, accompanied by disseminated intravas-

cular coagulation, confluent skin purpura, mottling

and distal cyanosis. Leukocytosis, prolongation of

clotting and decreased fibrinogen levels were com-

From the Department of Surgery, School of Medicine, Universityof California,

Davis Medical Center, Sacramento, California.

Requests for reprints should be addressed to David 2. J. Chu. MD, De-

partment of Surgery, M.D. Anderson Hospital and Tumor Institute, 6723

Bertner Avenue, Houston, Texas 77030.

mon; however, the most constant laboratory finding

was a decreased platelet count to below 50,000/mm3.

In patients 3 and 9 consumption coagulopathy was

manifested by bleeding from mucous membranes and

puncture sites. All of these patients required vigorous

fluid replacement amounting to 20 to 35 percent of

the total body water content in the first 48 hours.

Patient 3 died in the resuscitative phase from

overwhelming sepsis. Two patients died several

weeks later, one from multiple organ failure on the

16th hospital day, and the other after 4 weeks from

recurrent sepsis.

If the patient survives the first few days, organ

failure is the primary problem. Five patients devel-

oped multiple organ failure as evidenced by the res-

piratory distress syndrome, renal failure and elevated

liver enzymes. Two of these, as already noted, died.

Two patients had gastrointestinal bleeding which

required surgical intervention; one of them died. All

nine patients who survived the initial resuscitative

period had, in addition to skin necrosis, digital or

extremity gangrene. Two patients required ampu-

tation of digits. Another required excision of necrotic

skin and grafting over the foot and leg in an extended

area around the snake bite. Four patients required

amputation of limbs. One underwent above-elbow

amputation even though initially necrosis had in-

volved only the hand. This ascending necrosis may

have been a result of progressive arterial or venous

thrombosis. The patient who died from recurrent

sepsis had required bilateral below-knee amputation

and skin grafting. Another patient with skin necrosis

did not require skin grafting, and the wounds healed

by eschar formation and contracture.

Illustrative Cases

Patient

1:

Pediatric infection:

A 1 month old female

infant with a 3 day history of cold and diarrhea presented

in coma. One pound below birth weight, she was hypo-

thermic at 92.6F, pulse 156 beats/min and blood pressure

unobtainable. Dusky extremities were present. Laboratory

examination showed an hematocrit of 28 percent, a platelet

count of 23,000/mm3 and a prothrombin time greater than

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Purpura Fulminans

TABLE

I

Patients With Purpura fulmlnans at the University of Callfornfa, Davis Medical Center

Case

Age

Etiology

Outcome

1 1 month

E. coli

Amputation of toes

2

2 months

N. meningitis

Necrosis of hand with above-elbow amputation ultimately required

3 8 months N. meningitis Pregangrene of hands, legs and purpura of truncal skin; died 48 hours

after admission*

4

5 years

Varicella

Necrosis of skin over thighs and penis; healed by contracture

5

7 years

Snake bite

Multiple debridement and grafting of leg and foot extension from

site of bite), flexion contractures; renal and pulmonary failure

6 22 years

D. pneumonia

Postsplenectomy amputation of fingers and toes, with renal and

pulmonary failure and jaundice

7 33 years

N. meningitis

Forearm and above-knee amputations

8 36 years

N. meningitis

Below-knee amputations, debridement of skin of lower back, pulmonary

failure, gastrointestinal bleeding and adrenal hemorrhage*

9

58 years Undetermined

Two weeks postinguinal herniorrhaphy, bilateral below-knee and finger

amputations, renal and pulmonary failure, gastrointestinal bleeding

10

60 years P. mirabilis

Gangrene of toes, renal and pulmonary failure*

Deaths.

90 seconds.

Blood cultures grew E. cob. She was treated

with intravenous fluids, gentamicin, ampicillin and hepa-

rin. Her condition improved and amputations were limited

to four toes. She was discharged 1 month after admis-

sion.

Patient 4: Skin necrosis after a viral illness: A 5 year

old boy recovering from varicella developed painful, large,

purplish ecchymosis covering both calves. Temperature

and blood pressure were normal, although he was tachy-

cardic and pale. Hemoglobin was 12.3 mg/lOO ml, platelet

count was 64,OOO/mm,and prothrombin time was elevated

at 35 seconds. The skin lesions progressed to necrosis, and

in addition, the sacral skin and glans penis became in-

volved. Prednisone and heparin were given. The patient

was discharged after

35

days of hospitalization, and the

skin wounds healed by contracture without grafting.

Patient 7: Four extremity gangrene with large

vessel thrombosis:

A 33

year old woman with a 3 day

history of progressive malaise and headaches became co-

matose and developed generalized purpura and dusky

extremities. Blood pressure was 85/O mm Hg, pulse 110

beats/min and temperature 104F. The platelet count,

initially 165,000, decreased to 23,OOO/mms. Prothrombin

time and partial thromboplastin time were 16 seconds

control 11) and 53 seconds control 33), respectively.

Fundoscopic examination showed papilledema. Cerebro-

spinal fluid contained 1,250 leukocytes/mm and had

sheets of gram-negative cocci on smear. Cultures of the

blood, cerebrospinal fluid and nasopharynx grew Neisseria

meningitidis, group B. She was treated with penicillin and

steroids. Gangrene involved all four extremities and parts

of the face and trunk Figures 1 to 3). Above-knee ampu-

tations, forearm amputation and skin grafting of 50 percent

of the body surface area were performed. The patient was

discharged 2 months after admission.

Patient 1 : Multiple system failure:

A 60 year old man

with previous cardiac disease developed shortness of breath

and sweating. Initially treated for pulmonary edema, he

became hypotensive and

his feet became cyanotic. He-

matocrit was 38 percent, white blood cell count 17,000/mm3

and platelet count 33,000/mm3. Prothrombin time was 35

seconds and partial thromboplastin time was 105 seconds.

He was treated with gentamicin, cefazolin, dopamine and

Volume 143 March 1982

heparin. Blood cultures grew Proteus mirabilis. His con-

dition deteriorated. Respiratory distress syndrome and

renal failure developed. Death occurred 16 days after ad-

mission. The toes were gangrenous at the time of death.

Clinical Manifestations

The literature was reviewed to examine the

manifestations of purpura fulminans. Reports of

purpura fulminans and gangrene published after

1960 were collected and 58 cases studied [l-36].

There are two review articles, one by Hjort [I] and

the other by Spicer [2]. A collective analysis of 68

cases, 10 cases reported here and 58 cases reviewed

in the literature, revealed the following characteris-

tics Tables II and III).

The sex distribution is equal. The age distribution

has two peaks: infancy and old age. There are two

distinct clinical presentations. The first, the acute

state, is associated with acute infection and septice-

mia. The second, the chronic state, presents several

days after a febrile illness, usually a throat infection

or a viral exanthem. The latter condition has only

been reported in pediatric patients, and some in-

vestigators restrict the definition of purpura fulmi-

nans to this chronic state type [I].

In the collective series of 68 patients, 38 patients

presented in the acute state and 30 in the chronic

state. In the acute state, all 38 patients were septic

and in shock. In the chronic state, there was no bac-

teremia, and 11 patients developed shock as purpura

fulminans progressed. All 68 patients in both groups

had evidence of disseminated intravascular coagu-

lation. Patient 5 Table I), who developed purpura

fulminans on the second day after a rattlesnake bite

in the lower leg, is included in the acute group. The

snake venom contains toxic peptides capable of de-

grading complement and initiating disseminated

intravascular coagulation, and the bite site in this

patient demonstrated signs of spreading infection.

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Chu and Blaisdell

F@ee 1. Patlent 7. Necmtlc areas on he face, which ater healed

by contrature and eplthelfallzatlon.

The purpura varies from light brown, due to su-

perficial involvement of the epidermis Figure 4), to

dark red and blue, which indicates a deeper vascular

thrombosis and progression into the subcutaneous

tissue with perivascular hemorrhage Figures 3 and

5). The distal extremities are more severely affected,

and the distribution is usually symmetrical. The

trunk and face can also be affected Figures 1 and 3).

There is little edema because of thrombosis of all

small vessels. When edema develops it actually

carries a better prognosis, since it signifies the pres-

ence of open collateral vasculature.

Organ involvement is common, as shown in Table

II. There were 12 cases of pulmonary involvement,

most commonly respiratory distress syndrome.

Gastrointestinal bleeding occurred in eight patients,

perforated ulcers in four. In one patient intestinal

necrosis was demonstrated at operation. Eleven pa-

tients had renal complications: 8 had renal failure 5

deaths) and 3 had gross hematuria as an initial

manifestation.

The mortality rate was 40 percent for the group in

the acute state and 17 percent for the group in the

Ffgure 3. Patlent 7. Eztenslve gangrene of the

lower half of the body is evldent. Sequential

amputat ions were per form& thtwgh-knee and

then above-knee. 7%~ skln required mo it iple

dekMements

andgrafthg. The ugterskln areas

were spared.

FllBwe2.Patlent7.GarrgreneIspn ientk,the~hand.F4veam,

amputat ion was per formed; the stump required fur ther skin

gr

t lng.

chronic state, for a combined mortality of 30 percent.

This is a significant improvement from the pre-1960

mortality rates for patients with sepsis and dissem-

inated intravascular coagulation [37].

Etiology

Several microorganisms have been reported as

causal agents Table III). Meningococcus leads

among the various bacteria in the acute state group.

Varicella was found to be the most common viral

agent in the chronic state. In the latter group, un-

determined agents are found in purpura fulminans,

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Purpura Fulminans

TABLE II Extracutaneous Manifestations in the Total

Series (68 Patlents)

Acute State (n = 38)

Chronic State (n = 30)

Symptom Patients

Symptom

Patients

Pulmonary failure

Renal failure

Gastrointestinal

bleeding

Pulmonary embolus

Hematuria

Adrenal hemorrhage

Mycotic cerebral

aneurysm

Gastrointestinal

bleeding

Pulmonary failure

Bronchopneumonia

Renal failure

Hematuria

Renal vein thrombosis

Splenomegaly

Hepatomegaly

preceded by upper respiratory tract infections.

Streptococcal species are often implicated. Several

patients showed rising convalescent antistreptococcal

titers. In the acute state, the bacteria listed in Table

III were isolated from blood cultures. In four patients

blood cultures drawn after the institution of antibi-

otic therapy failed to grow any bacteria. Three of

these patients are listed under the category unde-

termined; the fourth had had a dog bite followed by

wound infection and purpura fulminans [22].

Pathophysiology

The generalized Shwartzman phenomenon pro-

duced by endotoxemia in experimental animals

provides the model for purpura fulminans. Initially,

the Sanarelli-Shwartzman phenomenon was de-

scribed as acute cortical necrosis from hemorrhagic

glomerulonephritis and occlusion of small vessels

after two intravenous injections of endotoxin in

rabbits

12

to

24

hours apart. Shock follows if suffi-

cient endotoxin is used. Since that first description,

microthrombi have been found in other organ sys-

tems. Other agents such as steroids or thorotrast can

be substituted for the first dose of endotoxin.

Endotoxin damages endothelial cells and activates

the Hagernan factor [38,39]. Platelets and leukocytes

are also involved in the initial steps of the reaction

TABLE Ill Etiologic Agents in the Total Series (68 Patients)

Flgm,

4.

Patlent 7. Skln biopsy o f /lght brow n

area

of he thtgh.

Superflclal epldemal necrosis

and vascuHtisare

present. The

capll lar les In the subc utaneous tissue are open. ( Magnlf lcatlon

X 450, r educ ed 24 percen t. )

[40,41].

Hemorrhage and intravascular thrombosis

occur in the venous capillaries and progress to the full

picture of disseminated intravascular coagulation.

In the chronic state, there is a deposition of anti-

gen-antibody complexes in tissues, particularly the

Agent

Acute State (n = 38)

Patients Deaths Agent

Chronic State (n =

30)

Patients Deaths

Meningococcus 12 2

Pneumococcus 6 2

Staphylococcus 6 4

Streptococcus 2 2

E. coli 2 2

Klebsiella 1 1

Proteus 1 1

Snake, dog bites 2 . .

Undetermined 3 1

Miscellaneous 3 .

One vibrio parahemolyticus, one Rickettsia and one leptospira.

t Mostly streptococcal pharyngitis, upper respiratory infection.

Varicella 7

Measles 4 1

Streptococcus 2

Undetermined7 17 4

Volume 143, March 1992

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Chu and Blaisdell

Figure 5. Patlent 7. Skln b&ps y o f dark blue area of thigh.

Full- thickness skin necrosis Is present and a small bl ood vessel

Is occlu ded. ( Magnlf lcatlon X 450, reduced 24 percent. )

skin, resembling the Arthus reaction [42]. The Arthus

reaction is produced locally in the skin by intrader-

ma1 injection of antigen, such as bovine albumin, in

a presensitized host. Intravascular clotting occurs,

followed by skin necrosis. In cases of large, skin sur-

face involvement, frank disseminated intravascular

coagulation occurs with results indistinguishable

from those of the Shwartzman phenomenon, Clini-

cally the chronic state of purpura fuhninans may well

be a severe form of the Henoch-Schiinlein pur-

pura.

The shock from sepsis, where the vascular volume

loss is due to increased vascular permeability, per-

petuates disseminated intravascular coagulation.

Hypovolemia worsens the peripheral vasoconstric-

tion and produces peripheral circulatory stasis, fa-

cilitating intravascular coagulation and vascular

thrombosis in the distal extremities and skin.

Gangrene and skin necrosis have been reported in

patients in whom circulatory stasis and hemolysis

occurred after cardiopulmonary bypass surgery

[43]

and in patients with cardiogenic shock [44]. In all of

Figure 6. The thign Is shown after heallng of grafted skln. ?& Is s

lntermlxed wlth regenerated skln after superfkial epldermalne-

crosls.

these patients disseminated intravascular coagula-

tion was present. Experimentally, a higher mortality

was found in animals subjected to shock and he-

molysis rather than to shock alone [45].

Treatment

The specific treatment of the infection and sec-

ondary shock has to be started promptly if the pa-

tient is to survive. Complete correction of hypovo-

lemia and specific antibiotics are the first priorities.

Both vascular and interstitial fluid deficits will re-

quire expansion. The key to volume replacement is

in establishing and maintaining urinary output. As

a general rule, urinary output below 0.5 ml/kg/hour

means inadequate renal perfusion. The cause is most

commonly inadequate fluid therapy but rarely may

be myocardial failure. If there is any question about

the adequacy of fluid therapy, pulmonary artery

catheterization is indicated. Left atria1 filling pres-

sure, cardiac output and mixed venous oxygen sat-

uration are ultimate guidelines. If pulmonary artery

wedge pressure is less than 10 to 15 mm Hg, more

fluid is indicated; if pressure is higher than 20 mm

Hg, cardiotonic agents are indicated to improve

cardiac output. Cardiac inotropic agents should be

used early in the treatment [46]. On the other hand,

drugs with peripheral and splanchnic alpha-adren-

ergic effects are discouraged, even in patients with

hypotension after correction of hypovolemia, since

they aggravate peripheral vasoconstriction and lower

perfusion in vascular beds with active thrombosis.

Heparin is recommended for all cases of purpura

fulminans. It has been shown to abort the Shwartz-

man reaction if given before the second challenge of

endotoxin. Heparin reverses ongoing intravascular

coagulation and diminishes the release of kinins from

clotting. Clotting protects the host in a localized in

fection. In purpura fulminans, however, coagulation

becomes counterproductive in poorly perfused skin

and viscera.

The use of steroids in septic shock is controversial.

Its beneficial effects are thought to be due to im-

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Purpura Fulminans

proved cardiovascular function and to a decrease in

the inflammatory reaction [47,48]. However, steroids

can also paralyze the immunologic mechanisms and

lead to greater vulnerability to infection [49]. If the

patient remains in refractory shock, a response to

physiologic doses of steroids 100 mg of hydrocorti-

sone) indicates the presence of an acute adrenal in-

sufficiency which is caused by the Waterhouse-

Friderichsen syndrome, the hemorrhagic adrenal

necrosis in septic shock [50]. Physiologic doses of

steroids must then be continued.

Surgical intervention is rarely indicated in the

initial management of purpura fulminans. The only

exception is when intestinal necrosis is suspected, as

in one of the reported cases. When there is asym-

metrical distal gangrene and the question of major

arterial thrombosis arises, heparinization and close

observation is appropriate. Arteriography is rarely

indicated as thrombectomy is invariably unsuccessful

[35]. The catheterization of vessels and operative

procedures may worsen the disease process by

damaging vascular endothelium, with resultant ex-

tension of the thrombotic process patient 2, Table

I). Fasciotomy is rarely indicated since edema is not

a feature of this disease.

cemia, shock, and disseminated intravascular coag-

ulation. The Shwartzman and Arthus reactions are

thought to be responsible for the pathogenesis of

purpura fulminans. The exact mechanisms of these

reactions are not completely understood. Immediate

resuscitation is the treatment for shock and sepsis.

Heparin is recommended to reverse the disseminated

intravascular coagulation component of this disease.

Surviving patients require treatment of skin necrosis

and digital and extremity gangrene. The former are

managed in a fashion similar to the management of

burns. Amputation should be delayed until maximal

collateral circulation has developed. A series of 10

patients is presented and 58 cases from the literature

are analyzed.

References

1.

2.

3.

4.

5.

Hjort PF. Purpura fulminans. Stand J Haematol 1964;l:

169-92.

Spicer TE. Purpura fulminans. Am J Med 1976;61:566-71.

Allen DM. Heparin therapy of purpura fulminans. Pediatrics

1966;38:21 l-3.

Amputation should await recovery of the patient

and the development of maximal collateral vessels.

This usually requires several weeks for optimal de-

marcation between viable and nonviable tissue. Ex-

tensive gangrene of limbs can be the foci of secondary

septicemia and may require earlier amputation.

When the poor condition of the patient so dictates,

transarticular amputation may be desirable. This

procedure is technically quicker to carry out and

avoids blood loss. Revisions of the stump can be done

at a more favorable time.

Becker FT. Purpura fulminans associated with varicella. Arch

Dermatol 1966;94:613-8.

Bernard PG. A civilian case of fatal meningococcemia due to

Neisseria meningitidis, group Y. Am J Clin Pathol 1977;

68:296-8.

6.

7.

Bettigole RE. Symmetric peripheral gangrene in pneumococcal

sepsis. Ann Intern Med 1962;54:335-42.

Bogumill GP. Bilateral above-the-knee amputation: a compli-

cation of chickenpox. J Bone Joint Surg 1965;47-A:371-

4.

a.

9.

10.

11.

12.

13.

14.

15.

16.

17.

Bouhasin JD. Purpura fulminans. Pediatrics 1964;34:264-

70.

Chaudhuri AKR. Peripheral gangrene afler measles. Br Med J

1970;4:679.

Dingman RO. Post-infectious intravascular thrombosis with

gangrene. Plast Reconstr Surg 1963;31:58-64.

Dudgeon DL. Purpura fulminans. Arch Surg 1971;103:351-

8.

Once the patient survives the resuscitative phase

of the treatment, the care of skin necrosis can be

approached as with burns, and burn team care is

recommended. The depth of the skin involvement

may not be clear initially. In some areas, indicated

by a lighter discoloration, only a second degree loss

of skin occurs Figures 4 and 6). Most wounds will

ultimately require excision to muscle fascia. Wound

dressings and medication, as used in burns, are ap-

plied. These dressings Silvadenem, Sulfamylon@ or

organic iodide) are changed meticulously to minimize

wound colonization by bacteria and evaporative

losses and to promote healing. The skin is debrided

and grafted when the wounds have demarcated and

when the patients condition permits. An adequate

nutritional state is most important. Intravenous

supplements to oral caloric intake are usually nec-

essary.

Gaze NR. Skin loss in meningococcal septicemia. Br J Plast

Surg 1976;29:257-6 1.

Goodwin JN. Symmetrical peripheral gangrene. Arch Surg

1974;108:780-4.

Gyde OHB. Gangrene of digits after chicken pox. Br Med J

1970;4:284.

Griffith GL. Massive skin necrosis in Rocky Mountain Spotted

Fever. South Med J 1978;71:1337-40.

Hall WH. Purpura fulminans with group B B-Hemolytic strep-

tococcal endocarditis. Arch Intern Med 1965;116:594-7.

Hampton TRW. The Waterhouse-Friderichsen syndrome and

its orthopedic consequences. Royal Naval Med Service J

1972;58:95-103.

18.

19.

Hattersley PG. Purpura fulminans. Am J Dis Child 1970;120:

467-71.

Leave11UW. Cutaneous changes in a case of purpura fulminans

following pneumococcal pneumonia. J Ky Med Assoc

1972;70:853-6.

Lloyd A. Peripheral gangrene in infancy and childhood. Br Med

J 1967;1:468-70.

Meade RH. A catastrophic infection. Hosp Pratt 1979;14:

50-4.

Summary

Purpura fulminans presents as a catastrophic ill-

ness with gangrene of the distal extremities and ne-

crosis of skin. The clinical picture consists of septi-

20.

21.

22.

23.

24.

Meyers BR. Generalized Shwartzman reaction in man after a

dog bite. Ann Intern Med 1970;73:433-8.

Morse TS. Purpura fulminans. Arch Surg 1970;93:368-70.

Murray HW. Staphylococcal septicemia and disseminated in-

travascular coagulation. Arch Intern Med 1977;137:844-

7.

Volume 143 March 1982

361


7/7

Chu and Blaisdell

25.

26.

27.

28.

29.

30.

31.

32.

33.

34.

35.

36.

37.

38.

Ddugbemi TO. Symmetrical gangrene of the extremities caused

by Neisseria meninaitldls tvpe C. East Afr Med J 197653:

143-8.

-.

Pfaller M. Leptospirosls and limb gangrene. MO Med 1979;

76:156-7.

Rahal JJ. Thrombocytopenia and symmetrical peripheral

gangrene associated with staphylococcal and streptococcal

bacteremla. Ann Intern Med 1968;69:35-43.

Robboy SJ. The skin In disseminated intravascular coagulation.

Br J Dermatol 1973;88:221-9.

Roland FR. Leg gangrene and endotoxin shock due to Vibrio

parahemolyt icus. N Engl J Med 1970;282:1306.

Stossel TP. Intravascular coagulation associated with pneu-

mococcal bacteremia and symmetrical peripheral gangrene.

Arch Intern Med 1970;125:876-8.

Turpie AG. Idiopathic gangrene in African children. Br Med J

1967;3:646-8.

Urbaniak JR. Purpura fulminans. J Bone Joint Surg 1973;55-

A:69-77.

Van Creveld S. Purpura fulminans: a case with recovery. Clin

Pediatr 1965;4:23-7.

Van der Horst RL. Purpura fulminans in a newborn baby. Arch

Dis Child 1962;37:436-41.

Wynne JM. Gangrene of the extremities in measles. South Afr

Med J 1977:52:117-21.

Zimmerman RR. Idiopathic gangrene. East Afr Med J 1977;

54:1-5.

Yoshikawa T. Infection and disseminated intravascular coag-

ulation. Medicine 1971;50:237-57.

Latour JG. Activation of the Hageman factor-pre Kallikrein

system in the pathogenesis of the generalized Shwartzman

reaction and of the hepatic vein thrombosis phenomenon

39.

40.

41.

42.

43.

44.

45.

46.

47.

48.

49.

50.

in the rat. Lab Invest 1979;41:237-45.

Rodriguez-Erdmann F. Studies on pathogenesis of generalized

Shwartzman reaction. Throm Diath Haemorrh 1964;12:

471-83.

Horn RG. Evidence for the participation of granulocytes in the

pathogenesis of the Shwartzman reaction. J Infect Dis

1973;128:2134-43.

Muller-Berghaus G. The role of platelets, leukocytes, and

complement in the activation of intravascular coagulation

of endotoxin. In: de Gaetano, ed. Platelets: a multidisciplinary

approach. New York: Raven Press, 1978.

McLean AJ. Type Ill Arthus) allergic reactions and endotoxin

toxicity in guinea-pigs. Experientia 1978;34:236-7.

Bick RL. Fatal purpura fulminans following total cardiopulmo-

nary bypass. J Cardiovasc Surg 1973;14:589-71.

McGouran RCM. Symmetrical peripheral gangrene. Br Heart

J 1977;39:569-72.

Hardaway RM. The danger of hemolysis in shock. Ann Surg

1979; 189:373-6.

Hinshaw LB. Myocardial functian in endotoxin shock. Circ Shock

1979 Suppl 1):43-51.

Schurner W. Steroids in the treatment of clinical septic shock.

Ann Surg 1976;184:333-41.

Weil M. Current understanding of mechanisms and treatment

of circulatory shock caused by bacterial infections. Ann Clin

Res 1977;9:181-91.

Zurier RB. Anti-immunologic and anti-inflammatory effects of

steroid therapy. In: Azarnoff DL. Steroid therapy. Philadel-

phia: WB Saunders, 1975:223-37.

Fox B. Dlsseminated intravascular coagulation and the Wa-

terhouse-Friderichsen syndrome. Arch Dis Child 1971;48:

680-5.

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The American Journal of Surgery

Documents

1982. Purpura Fulminants