Disseminated intravascular concentrate

Several phase I trials have been performed with LPS from Salmonella abortus equi administered i.v. in patients who suffered from disseminated cancer. White blood cell number decreased after each injection and returned to basal level by 24 hours. There were no changes in coagulation parameters, and no disseminated intravascular coagulation was observed. After the first injection of LPS, increases in TNF-a concentration and IL-6 activity in serum were detected. However LPS tolerance which is accompanied by a decrease in TNF-a and IL-6 production depended on the intervals between repeated injections, but it was not determined whether it was a benefit or a draw-back. Injections of IFN-y prevented this decrease in TNF-a and IL-6, and ibuprofen attenuated LPS toxicity [183,186],... 

Several inhibitors of plasma origin have been identified as important inhibitors of the coagulation process including antithrombin III (ATIII), protein C, TFPI and heparin cofiictor n. Of these inhibitors, ATIII is fee only agent which has been developed for commercial purposes. Patients wife hereditary thrombophilia due to a classic deficiency of ATin can be treated wife ATTII concentrate. In addition patients wife disseminated intravascular coagulation (DIG), renal insufficiency, post-surgical thrombosis, thermal injury and trauma which are associated with a decrease of ATTII in proportion to the degree of illness/injury, can also be treated (51). 

This may explain the effectiveness of treating patients with hemophilia who have inhibitors with high doses of factor VIII. Another approach involves the use of prothrombin complex concentrate to treat bleeding episodes in patients with factor VIII inhibitors (38) however, thromboembolic complications related to higher doses of prothrombin complex concentrate have been described, although these are relatively rare (39,40). Thrombotic events are extremely rare when highly purified factor IX is used. Activated prothrombin complex concentrate is also effective in patients with factor VIII inhibitors (41). Serious complications are rare, but disseminated intravascular coagulation has been reported (42). 

The administration of prothrombin complex concentrate to reverse anticoagulant treatment has been associated with thrombotic complications, such as disseminated intravascular coagulation (8). However, such complications have typically occurred in patients with liver failure or after repeated treatment, such as in patients with hemophilia B treated with prothrombin complex concentrate (9). 

Relative contraindications for prothrombin complex concentrate are liver disease, coronary heart disease, and factors that predispose to thrombosis (11). It is contraindicated in disseminated intravascular coagulopathy and hyperfibrinolysis. 

Rodie PH, Stirling C, Mayne EE, Ludlam CA. Thrombosis and disseminated intravascular coagulation following treatment with the prothrombin complex concentrate, DEFIX. Thromb Haemost 1999 81(4) 667. 

The hematological effects of tumor necrosis factor alfa mostly consist of dose-related thrombocytopenia and granulocytopenia, and decreased monocyte or lymphocyte counts (SED-13, 1111) (11,12). Septic episodes are sometimes associated with leukopenia. Coagulopathy with laboratory evidence of disseminated intravascular coagulopathy was found in 30% of patients and was sometimes associated with thromboembolic events (13). Other coagulation disorders include transient alterations in prothrombin time, and a rise in the plasma concentrations of von Willebrand factor was found in healthy volunteers (14). 

Hypoglycemia can be seen. Rhabdomyolysis, acute renal failure, disseminated intravascular coagulation, liver necrosis, and traumatic injury are reported complications. The anesthetic dose of phencyclidine is 0.25 mg kg intravenously. Doses of 1-5 mg are purported to cause euphoria and numbness, 5-10 mg cause excitation and hallucinations, and 20 mg or more cause coma and serious toxicity or death. Plasma concentrations of phencyclidine vary widely after overdose. Phencyclidine crosses the placenta resulting in hyperirritability, tremors and hypertonia, depressed reflexes, and nystagmus in neonates. 

Fresh frozen plasma contains the components of the coagulation system and is indicated for the replacement of deficient coagulation factors II, V, VII, X, XI, and XIII. Factor VIII and IX deficiencies are treated with specific factor concentrates. Fresh frozen plasma is also used for the rapid reversal of warfarin anticoagulation and in the treatment of disseminated intravascular coagulation. Thrombotic thrombocytopenic purpura is treated by means of therapeutic plasma exchange with fresh frozen plasma as the replacement fluid. Cryo-precipitate, which contains factor VIII, von Willebrand s factor, and fibrinogen, is indicated for the treatment of von Willebrand s disease that does not respond to desmopressin acetate, and for fibrinogen replacement (see Chap. 100). 

Cardiovascular The main adverse effect of prothrombin complex concentrates is a risk of thrombosis, as patients taking oral anticoagulants have prothrombotic susceptibility factors [31, 33 ]. Reported thromboembolic complications include ischemic stroke, venous thromboembolism (venous thrombosis or pulmonary embolism), myocardial infarction, and disseminated intravascular coagulation [32 ]. 

Hematologic Historically, there was concern that prothrombin complex concentrates were associated with thrombotic events such as stroke, myocardial infarction, pulmonary embolism, deep venous thrombosis, and disseminated intravascular coagulation. These events resulted mainly from the use of prothrombin complex concentrates as source of factor IX in patients with hemophilia B, and in particular after surgery, but the reported incidence is low and there is considerable evidence that the risk of thrombosis has been minimized with current prothrombin complex concentrates by reduced use of activated factors and the... 

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