Disseminated intravascular coagulation (DIC) was first observed clinically in a case of sepsis following severe trauma. It was postulated that the observed clotting defect and bleeding were due to the using up of clotting factors in an episode of intravascular clotting. It was also postulated that the multiple organ failure observed was due to obstruction of the microcirculation of the organs by microclots. Evidence for this process was worked out in many animal studies. It was then postulated that if these microclots could be lysed before organ necrosis was produced, organ failure could be prevented. This prevention was shown to be possible in animals. It was then tried in humans using plasminogen activators, and the approach was found to be effective. Using a low dose of plasminogen activator over a 24-hour period caused no changes in the coagulation profile or bleeding.
Get full access to this article
View all access options for this article.
References
1.
HardawayRMMckayDGWilliamsJH.Lower nephron nephrosis. Am J Surg1954;87: 41–49.
2.
HardawayRMChunBRutherfordRB.Coagulation in shock in various species including man. Acta Chir Scand1965;130: 157–164.
3.
HardawayRMChunBRutherfordRB.Histologic evidence of disseminated intravascular coagulation in clinical shock. Report of a new finding. Vas Dis1965;2: 254–265.
4.
HardawayRM.Syndromes of disseminated intravascular coagulation with special reference to shock and hemorrhage. Springfield, Ill: Charles Thomas Pub., 1966.
5.
HardawayRMMckayDG.Production of lower nephron nephrosis in dogs by means of an episode of intravascular clotting. Surg Form1959;9: 134–137.
6.
HardawayRMMckayDG.Intravascular thrombi and the intestinal factor of irreversible shock. Ann Surg1959;150: 261–265.
7.
HardawayRMMckayDG.Pathologic study of intravascular coagulation following incompatible blood transfusion in dogs. Am J Surg1956;91: 24–40.
8.
HardawayRMMckayDG.Production of acute hemorrhagic pancreatitis in dogs by means of an episode of DIC. Surgery1959;45: 557–561.
9.
HardawayRM.Pulmonary microthrombi. Presented at the Symposium on Pulmonary Embolic Disease, Boston, MA, May 22–23, 1964.
HardawayRMJamesJMAndersonRWIntensive study and treatment of shock in man. JAMA1967;199: 779–790.
12.
HardawayRMHusniEAGeeverEFEndotoxin shock: a manifestation of intravascular coagulation. Ann Surg1961;154: 791–802.
13.
HardawayRMJohnsonDGElovitzMJInfluence of trauma and hemolysis on hemorrhagic shock in dogs. J Trauma1969;4: 624–641.
14.
HardawayRM.Mechanism of traumatic shock. Surg Gyn Obstet1980;151: 65–69.
15.
HardawayRMWilliamsCHMarvastiM.Prevention of adult respiratory distress syndrome with plasminogen activator. Crit Care Med1990;18: 1413–1418.
16.
HardawayRMWilliamsCH.Prevention of multiple organ failure with plasminogen activator. Curr Therap Res1991;49: 711–722.
17.
HardawayRM.Treatment of adult respiratory distress syndrome with plasminogen activator. Hematol Rev Commun1994;9: 3–19.
18.
The Medical Department of the United States Army in the World War.Surgery1927. Published by the Surgeon General, U.S. Army.
19.
HewsonW. In: GulliverG, ed. The works of William Hewson, FRS. The Sydenham Society, 1848:46.
20.
HardawayRMJohnsonDGElovitzMJInfluence of trauma and hemolysis on hemorrhagic shock in dogs. J Trauma1964;4: 624–641.
21.
MillerSETrunkeyDDMillerCL.The immunologic effects of trauma. In NinnemannJL, ed. Traumatic injury infection and other immunologic sequelae. Baltimore: University Park Press, 1983.
22.
HardawayRM.Tissue injury and activation of the coagulation system. In: JohnsonSAGuestM. Dynamics of thrombic formation and dissolution. Philadelphia: Lippincott, 1963.
23.
SperoJALewisJHHasibaV.Disseminated intravascular coagulation: findings in 346 patients. Thromb Haemost1980;43: 28–33.
24.
BlalockA.Experimental shock—the cause of the low blood pressure produced by muscle injury. Arch Surg1939;20:954.
25.
HardawayRM.Care of the wounded in the United States Army from 1775–1991. Surg Gyn Obstet1992;175: 74–88.
26.
TrunkeyDD.Hypovolemic and traumatic shock. In: HardawayRM, ed. Shock—the reversible stage of dying. Chicago: Year Book, 1988.
27.
HardawayRM.Shock—the reversible stage of dying. Chicago: Year Book, 1988.
28.
AmsellJSlepchukNKumarRHeparin induced thrombocytemia; a prospective study. Thromb Haemonst1980;43: 61–65.
29.
HardawayRMElovitzMJBrewsterWRClotting time of heparinized blood influence of acidosis. Arch Surg1964;89: 701–705.
30.
HardawayRM.When too much fluid is just enough. Emerg Med1982;14: 40–41.
31.
HardawayRM.Treatment of severe shock with phenoxybenzamine. Surg Gyn Obstet1980;151: 725–734.
32.
ArcherLT.Septic shock: pathological aspects. In: HardawayRM, ed. Shock—the reversible stage of dying. Chicago: Year Book, 1988.
33.
SchumerW.Septic shock: clinical aspects. In: HardawayRM, ed. Shock—the reversible stage of dying. Chicago: Year Book, 1988.
34.
SchumerW.Treatment of septic shock with steroids. In: HardawayRM, ed. Shock—the reversible stage of dying. Chicago: Year Book, 1988.
35.
HinshawLBBellerBK.Septic shock: physiological aspects. In: HardawayRM, ed. Shock—the reversible stage of dying. Chicago: Year Book, 1988.
36.
ShatneyCH.The role of corticosteriods in the treatment of shock. In: HardawayRM, ed. Shock—the reversible stage of dying. Chicago; Year Book, 1988.
37.
MacconnellKL.Vasoactive drugs in the treatment of shock. In: HardawayRM, ed. Shock—the reversible stage of dying. Chicago: Year Book, 1988.
38.
BowenJCReesM.Endogenous opiates in shock. In: HardawayRM, ed. Shock—the reversible stage of dying. Chicago: Year Book, 1988.
39.
GaffinSL.Antibody therapy in shock. In: HardawayRM, ed. Shock—the reversible stage of dying. Chicago: Year Book, 1988.
40.
DudleyMN.Interleukin-1 receptor antagonists significantly reduce death from sepsis. University of Rhode Island, Multi Center Study. Gen Surg News1993;28–29.
41.
Editor's Note.Gen Surg News1993;28.
42.
QuezadoZMNNatansonCAssingDWA controlled trial of HA-IA in a canine model of gram-negative septic shock. JAMA1993;269: 2221–2227.
43.
Statistical Abstract of the United States1992.
44.
SingerSNNicolsonGL.The fluid mosaic model of the structure of cell membrane. Science1972;175:720.
45.
SchwartzRSChiuDTYLubinB.Studies on the organization of plasma membrane phospholipids in human erythrocyte. In: KruchebergWEEatonJWAsterJ, eds. Erythrocyte membranes: 3 recent clinical and experimental advances. New York: Alan R. Liss, 1984;89–122.
46.
ChiuDLubinBShohetSB.Erythrocyte membrane lipid organization during the sickling process. Br J Hematol1974, 41: 223–234.
47.
FeolaMSimoniJConigaroPCToxicity of polymerized hemoglobin solution. Surg Gyn Obstet1988;166: 211–222.
48.
TuomanenE.Breaching the blood-brain barrier. Sci Am1993;268: 80–84.
49.
HardawayRMMckayDG.Disseminated intravascular coagulation. A cause of shock. Ann Surg1959;149: 462–470.
50.
HardawayRMHusniEGeevaEFEndotoxin shock—a manifestation of intravascular coagulation. Ann Surg1961;154: 791–802.
51.
HardawayRMJohnsonO.Clotting mechanism in endotoxin shock. Arch Intern Med1963;112: 775–782.
52.
HardawayRMWilliamsCHYangS.Treatment of endotoxemic shock with plasminogen activator. Crit Care Med1995 (in press).
53.
HardawayRMHarkeH.Plasminogen activator—a new approach to the treatment of adult respiratory distress syndrome. Compr Therapy1995 (in press).
