Page 2234 - Williams Hematology ( PDFDrive )

2208 Part XII: Hemostasis and Thrombosis Chapter 129: Disseminated Intravascular Coagulation 2209

Several laboratory and clinical observations support the hypothe- In a series of 18 critically ill patients from Paris with heat stroke
sis that DIC accompanies hepatic disorders. They include a shortened during the 2003 heat wave in Western Europe that caused numerous
251
half-life of radiolabeled fibrinogen and prolongation of fibrinogen deaths in France alone, patients had very high levels of IL-6 and
half-life by administration of heparin 234,235 ; failure of replacement ther- IL-8. In addition, there was a striking activation of white blood cells,
apy to significantly increase the levels of hemostatic factors (suggest- as demonstrated by β -integrin upregulation and increased production
2
ing continuous consumption); and increased blood levels of D-dimer, of reactive oxygen species. All patients also had evidence of a signifi-
thrombin–AT (TAT) complexes, and fibrinopeptide A, all consistent cant systemic activation of coagulation and DIC was present in approx-
with ongoing thrombin generation. 236–238 imately 35 percent of patients. There was a marked correlation between
Other observations and considerations argue against the hypoth- the extent of inflammation and coagulation activation and the clinical
esis that DIC accompanies liver diseases. They include (1) a very low severity of the heat stroke.
incidence (2.2 percent) of microthrombosis in the tissues of patients The severity of the syndrome and the stage of its development affect
who die of liver disease and (2) causes other than, or inconsistent with, the type and magnitude of hemostatic alterations. Thus, in a study of 56
237
DIC for the deranged findings in liver disease. Examples of alterna- patients, three groups were discernible: nonbleeders, bleeders without
tive explanations include the following: (1) a prolonged thrombin time DIC but with slight consumption of hemostatic factors, and bleeders
may result from acquired dysfibrinogenemia ; (2) low levels of coag- with typical signs of DIC. Prompt cooling and support of vital func-
252
239
ulation factors and inhibitors may result from reduced synthesis ; tions have substantially reduced the high mortality that was commonly
240
(3) increased FDP levels may be a consequence of primary fibrinoge- observed in early studies.
nolysis induced by reduced synthesis of α -antiplasmin and PAI-1 and
2
by decreased clearance of t-PA; (4) factor VIII levels are commonly
241
increased rather than decreased ; (5) the kinetic data show that the SNAKE BITES
apparently excessive consumption of fibrinogen can be explained by Several species of snakes belonging to the Viperidae family produce
242
loss of fibrinogen into extravascular spaces ; and (6) fibrinogen and venoms that have a wide range of activities affecting hemostasis. Prom-
plasminogen do not appear to be removed rapidly when labeled endoge- inent among these species are the Vipera, Echis (E. carinatus or E. color-
75
nously by Se-selenomethionine. 243 atus), Aspis, Crotalus, Bothrops, and Agkistrodon. Venoms of these snakes
A third hypothesis maintains that patients with liver disease usu- contain enzymes or peptides that exert the following activities 253–255 :
ally do not present with DIC but are extremely sensitive to the various (1) thrombin-like activity, cleaving fibrinopeptide A from the Aα chain
triggers of DIC because of their impeded capacity to clear procoagu- of fibrinogen (Agkistrodon rhodostoma); (2) activation of prothrombin
lants and to synthesize essential components of the coagulation, inhib- even in the absence of calcium ions (E. carinatus); (3) activation of factors
itory, and fibrinolytic systems. Patients with primary or metastatic liver X and V (Russell viper venom); (4) fibrinogenolytic activity (Agkistro-
disease who undergo a peritoneovenous shunt operation for severe don acutus); (5) induction of thrombocytopenia by platelet aggregation;
ascites are more likely to develop DIC than are patients with ascites who (6) inhibition of platelet aggregation by the low-molecular-weight argin-
undergo the same procedure because of other causes. 244 ine-glycine-aspartic acid–containing peptides from a variety of snake
What, then, should be the approach to patients with liver disease species; (7) activation of protein C; and (8) activities causing damage to
and bleeding without an apparent local cause? First, possible underlying endothelial cells, leading to bleeding, tissue ischemia, and edema. Inter-
causes of DIC should be considered and identified, and then a hemo- estingly, victims of snake bites rarely experience excessive bleeding or
static profile should be examined at frequent intervals so as to detect thromboembolism, in spite of the serious derangements in hemostatic
any dynamic changes that may be helpful in recognizing DIC. The sen- tests and findings that are sometimes consistent with DIC. 256–258
sitive assays that reflect thrombin generation (TAT complex and proth- The major symptoms and signs related to envenomation are vomit-
rombin fragments 1.2) or concomitant thrombin and plasmin generation ing, diarrhea, apprehension, hypotension, local swelling, ischemia, and
(D-dimer), as well as finding a normal or decreased level of factor VIII necrosis. Consequently, treatment for victims of snake bites consists of
may help establish the diagnosis of DIC in a patient with liver disease. 245 immediate immobilization, administration of antivenom and fluids,
and other general measures to preserve vital functions. Local incisions,
HEAT STROKE cooling, and application of tourniquet should be avoided. 253
In 1841, James Wellstead published his book Travels to the City of the
Caliphs (currently known as Baghdad) and vividly described that on
an extremely hot day in the Persian Gulf the decks of the ship Liverpool HEMANGIOMAS
resembled a slaughterhouse, so numerous were the bleeding patients. In 1940, Kasabach and Merritt described the association between giant
246
This is probably one of the first written reports on the occurrence of hemangioma and a bleeding tendency occurring mainly in infants. The
DIC in humans who suffer from heatstroke. Heat stroke is a syndrome pathogenesis and management of this syndrome have been reviewed.
229
259
characterized by a rise in body temperature to higher than 42°C, which Studies using radiolabeled fibrinogen and platelets provided evidence
follows collapse of the thermoregulatory mechanism. The following that within the hemangioma, consumption of platelets and fibrino-
predisposing factors have been identified: high environmental tem- gen occurs because of localized intravascular clotting and excessive
perature, strenuous physical activity, infection, dehydration, and lack fibrinogenolysis. 260,261 Conceivably, concomitant local activation of the
of acclimatization. 247,248 Extensive hemorrhage, unclottable blood, and coagulation pathway and release of large amounts of t-PA by the abnor-
venous engorgement were found as early as 1838 in postmortem exami- mal endothelium lining the tumor vessels occur. Microangiopathic
nations of patients who died of heat stroke. Investigations confirm hemolytic anemia and laboratory signs of DIC and fibrinolysis have
246
that a severe hemorrhagic diathesis and multiple organ failure often been demonstrated in patients with giant hemangiomas. Accelerated
262
accompany heat stroke. 229,249–251 Diffuse fibrin deposition and hemor- growth of these hemangiomas in infants is associated with augmented
rhagic infarctions are found in fatal human cases. DIC associated with consumption of hemostatic factors, and can be effectively treated with
profound fibrin(ogen)olysis is evident in patients with heat stroke. The glucocorticoids. Radiotherapy and interferon-α are also effective, but
possible triggers of DIC in patients with heat stroke include endothelial should only be used in life-threatening circumstances after failure of
cell damage and TF released from heat-damaged tissues. 249 glucocorticoid therapy because of severe adverse events. Spontaneous
263

Kaushansky_chapter 129_p2199-2220.indd 2209 17/09/15 3:46 pm