Severity Of Disseminated Intravascular Coagulation Research Articles

Prognostic value of immature platelet fraction and plasma thrombopoietin in disseminated intravascular coagulation

Although platelet count is a good parameter for the diagnosis of disseminated intravascular coagulation (DIC), a single measurement of platelet is not enough to reflect the ongoing platelet consumption because of compensatory synthesis of circulating platelet number. Increased thrombopoiesis owing to peripheral destruction is expected in patients with DIC. Reticulated platelet, measured as immature platelet fraction (IPF), and plasma thrombopoietin (TPO) are markers of platelet production. We investigated the potential usefulness of circulating IPF and TPO in 222 patients suspected of having DIC. Both IPF and TPO levels were significantly increased in overt DIC patients and well correlated with DIC score. IPF also correlated with fibrin-related marker such as fibrinogen degradation product and D-dimer. Both IPF and TPO showed better mortality prediction than platelet count with the multivariate logistic regression and Kaplan-Meier survival analysis. These results suggest that IPF and TPO are new potential candidates to detect the severity of DIC and to predict DIC mortality.

Relationship between Procalcitonin Levels and Severity of DIC Induced by Bacterial Infection.

<Background and Methods> In the past few years, structural and functional studies have demonstrated an increasingly tight interplay between the coagulation and inflammatory systems. These studies support an important role of systemic inflammatory response syndrome (SIRS) in the development of disseminated intravascular coagulation (DIC) in these critically ill patients. Although PCT is important clinical marker, it role in the DIC process is unkown. We measured serum levels of PCT in septic patients with DIC (n=15) and acute promyelocytic leukemia (APL)-induced DIC (n=5). Serum levels of PCT were determined by the EIA (BIOMERIEMX, France).<Results> The thrombin antithrombin complexes (TAT) levels were higher in both DIC patients as reported by others. ?Levels of PCT elevated in all patients with bacterial infection. In the septic patients with DIC, we found significant elevations of serum PCT levels (97.3±72.3 ng/ml) as compared with septic patients with non overt DIC (30.5±42.4 ng/ml). All the patients that levels of PCT increased than 100 ng/ml died. However, we did not find any difference serum levels of PCT in the APL and EB virus infected patients with DIC.<Conclusion> These results suggest that assess of thrombin generation capacity may be helpful in the making the diagnosis in septic patients with DIC. It appears that serum levels of PCT may contribute to the severity of DIC induced bacterial infection.

Significance of decreased plasma D-dimer levels following lipopolysaccharide-induced disseminated intravascular coagulation in rats.

Plasma D-dimer (DD) is considered to be one of the most useful markers in the diagnosis and assessment of disseminated intravascular coagulation (DIC). The present study was performed to clarify the role of DD in a rat model of lipopolysaccharide (LPS)-induced DIC in which low-molecular-weight heparin (LMWH) and tranexamic acid (TA) were used. We investigated whether a relationship exists between plasma DD levels and severity of DIC. Experimental DIC was induced in rats by a sustained 4-hour infusion of 30 mg/kg LPS administered via the tail vein (LPS group). Rats received either LPS alone (LPS group) or LPS combined with 200 U/kg LMWH (LPS+LMWH group) or 50 mg/kg TA (LPS+TA group) from -30 minutes to 4 hours. Blood was drawn from each rat at 4, 8, and 12 hours. Plasma levels of thrombin-antithrombin complex (TAT) and creatinine were suppressed in the LPS+LMWH group, and less glomerular fibrin deposition was observed compared with the LPS group. On the other hand, an increased level of creatinine and increased glomerular fibrin deposition were observed in the LPS+TA group compared with the LPS group. LMWH demonstrated a protective effect against LPS-induced DIC, resulting in increased survival at 12 hours, whereas TA had the opposite effect. From these results, it appears that LMWH protects against LPS-induced DIC, but TA exacerbates LPS-induced DIC. It was interesting that plasma levels of DD were almost completely suppressed by concurrent administration of either TA or LMWH in this LPS-induced DIC model. This finding suggested that plasma levels of DD were suppressed by inhibition of coagulation (reduced deposition of fibrin) in the LPS+LMWH group and that DD levels were also suppressed by inhibition of fibrinolysis (reduced degradation of fibrin by plasmin) in the LPS+TA group. Thus care should be taken when evaluating the significance of plasma DD levels, because suppressed levels can occur with progressive fibrin deposition and worsening organ dysfunction or improvement in the course of DIC.

The place of plasmapheresis in septic patients complicated with disseminated intravascular coagulation

Sepsis, complicated with disseminated intravascular coagulation (DIC), is the most frequent cause of mortality in the ICU despite improvements in patient care [1]. Plasmapheresis is a tool to remove endotoxins and inflammatory mediators responsible for pathophysiology. We design a study in a small group of septic patients complicated with DIC to evaluate the changes on coagulation parameters, severity of sepsis and outcome of plasmapheresis. After ethical approval for the trial and written informed consent was obtained, patients were prepared for plasmapheresis. The criteria for entry to the trial were sepsis as described by Bone [2], and DIC [3] as described by Bick. The exclusion criteria were uncontrolled hemorrhagia, recent (< 48 hours) cardiac surgery, recent(< 48 hours) resuscitation, platelets < 20,000/mm3, positive human immunodeficiency virus serology, morbid obesity and pregnancy. After obtaining the laboratory data and scores first, plasmapheresis was performed using fresh frozen plasma as a 1:1 ratio for the calculated plasma volume for each patient. The second plasmapheresis was performed after 48 hours. The severity of illness and mortality rates was calculated using the APACHE II scale and the severity of DIC was calculated by the DIC score. The outcomes at 28 days were recorded. Statistical analysis was performed with SPSS version 11.0 for Windows (Chicago, IL, USA), values are expressed as mean ± SD and P < 0.05 considered statistically significant. Thirteen patients were treated in the ICU with plasmapheresis from 2002 to 2003. The difference between the calculated mortality rate based on initial APACHE II scores (59.6 ± 21.3), and 28-day mortality of all patients (20%), was significant (P < 0.05). The decrease in prothrombin time and activated partial thromboplastic time, based on initial results, were significant in 24, 48 and 72 hours (P < 0.05). The enhancement of the DIC score (from 6.2 ± 0.6 to 3.7 ± 0.9) between the baseline and the end of the procedure was statistically significant (P < 0.01). The level of D-dimer before the first plasmapheresis (1333 ± 972) was decreased (638.6 ± 252.9) significantly at the end of the procedure (P < 0.007). The increase in biological markers of sepsis (antithrombin, protein C and protein S activity) was statistically significant (P < 0.01). It was also found that the protein C activity was controversially correlated with 28-day survival (P < 0.02). We thought that repeated plasmapheresis in the early stages of sepsis may be considered a therapeutic method even during progressive sepsis that is complicated with DIC.

Successful Treatment for Multiple Cerebral Hemorrhage in a Newly Diagnosed Patient with Acute Promyelocytic Leukemia

Acute promyelocytic leukemia (APL) is characterized by severe bleeding associated with coagulation abnormalities. High incidence of disseminated intravascular coagulation (DIC) in APL often causes early hemorrhagic death. We report a case of APL with massive cerebral hemorrhage and respiratory failure in a 24-year old woman. A combination of all-trans retinoic acid (ATRA) differential therapy and blood component therapy was given to control DIC and stop bleeding. In order to minimize the severity of DIC during chemotherapy induced acute cytolysis, ATRA was started 8 days before the induction chemotherapy which consisted of idarubicin (IDA) and cytosine arabinoside (Ara-C). Complete clinical remission was achieved in this APL patient despite of the severity of the hemorrhage.

Disseminated intravascular coagulation: objective clinical and laboratory diagnosis, treatment, and assessment of therapeutic response.

Current concepts of the etiology, pathophysiology, clinical and laboratory diagnosis and management of fulminant and low-grade disseminated intravascular coagulation (DIC) have been presented. Considerable attention has been devoted to interrelationships within the hemostasis system. Only by clearly understanding the pathophysiological interrelationships can the clinician and laboratory scientist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. Objective clinical and laboratory criteria for diagnosis of DIC have been delineated, thus avoiding needless confusion and empirical decisions regarding the diagnosis. Many therapeutic decisions to be made are controversial and will remain so until more is published about specific therapeutic modalities and survival patterns. Also, therapy must be highly individualized depending on the nature of DIC, age, etiology of DIC, site and severity of hemorrhage or thrombosis, and hemodynamic and other clinical parameters. Also presented are clear criteria for severity of DIC and objective criteria for defining a response to therapy. Also, since it is often difficult for the individual physician to decide when to stop expensive therapy, objective criteria by which therapy may be stopped when continuation is likely fruitless are presented as a guideline.

Effects of DX-9065a, an Orally Active, Newly Synthesized and Specific Inhibitor of Factor Xa, against Experimental Disseminated Intravascular Coagulation in Rats

We investigated the protective effects of DX-9065a, an orally active, newly synthesized and specific inhibitor of factor Xa, against two kinds of experimental disseminated intravascular coagulation (DIC) in rats. Endotoxin-induced experimental DIC was induced by a 4-h sustained infusion of endotoxin at a dose of 100 mg/kg. Thromboplastin-induced experimental DIC was induced by a bolus injection of thromboplastin at a dose of 150 mg/kg. The rats were orally administered DX-9065a at 10, 30 or 100 mg/kg 30 min before endotoxin or thromboplastin injection. In both DIC models, DX-9065a showed a protective effect against DIC, at all doses and in all parameters, including fibrin/fibrinogen degradation products (FDP), fibrinogen level, prothrombin time, activated partial thromboplastin time, platelet count and the number of renal glomeruli with fibrin thrombi. When DX-9065a was orally administrated at 100 mg/kg without endotoxin or thromboplastin, no significant changes were seen in hemostatic parameters except PT and APTT, and no fibrin thrombi or abnormal bleeding were seen in renal specimens. These findings suggest that the new oral anti-Xa drug, DX-9065a, has an effect in reducing the severity of DIC. However, further dose-finding and safety studies of this drug have still to be assessed.

Improved or fatal acute disseminated intravascular coagulation in systemic lupus erythematosus.

To analyze the outcome of systemic lupus erythematosus (SLE) associated with acute disseminated intravascular coagulation (DIC) and also to clarify the clinical factor(s) contributing to the outcome, we retrospectively investigated 120 SLE patients treated between 1981 and 1991. Eight of these patients (6.7%) developed acute DIC; four recovered and the other four died within 2 weeks of onset. Infection preceded acute DIC in all these patients. Acute DIC associated with atypical pneumonia was always fatal, while the patients with pharyngitis or urinary tract infection survived when they were treated adequately. Comparison of the dead and surviving groups revealed that the activity of SLE before the onset of DIC, the severity of DIC, and the treatment given for DIC and the coexistent infection were not significantly related to a fatal outcome. However, severe infection such as atypical pneumonia in patients with secondary immunodeficiency was likely to be fatal irrespective of the presence of DIC.

Disseminated Intravascular Coagulation Associated with Staphylococcus aureus Septicemia Is Mediated by Peptidoglycan-Induced Platelet Aggregation

Disseminated intravascular coagulation (DIC) may complicate severe septicemia caused by Staphylococcus aureus. S. aureus can induce spontaneous platelet aggregation in vitro, the rapidity and degree of which correlates with the severity of DIC in patients with sepsis. Purified peptidoglycan from DIC isolates aggregated human platelets in the presence of staphylococcal protein A with significantly shorter aggregation times than did peptidoglycan from non-DIC isolates. Purified teichoic acid from DIC and non-DIC isolates failed to aggregate platelets in vitro, or in vivo in guinea pigs but inhibited the peptidoglycan-induced aggregation in a dose-response manner. These studies suggest that peptidoglycan may mediate S. aureus-induced spontaneous platelet aggregation in vitro and DIC in vivo. The variability among strains of S. aureus to induce DIC and platelet aggregation may depend on the unique composition of their peptidoglycan and perhaps also the extent of exposure or availability of cell wall teichoic acid.

Factor VIII (procoagulant activity VIII:C, and antigen VIII:CAg, related antigen VIIIR:Ag and ristocetin cofactor VIIIR:Cof) in intensive care patients with clinically suspected disseminated intravascular coagulation (DIC).

VIII:C, VIII:CAg, VIIIR:Ag and VIIIR:Cof were determined repeatedly in nine shock patients with suspected DIC and in five patients with uncomplicated acute myocardial infarction and compared with the clinical course and the severity of DIC as reflected by a score based on six routine coagulation and fibrinolysis parameters. All shock patients showed high levels of VIIIR:Ag, VIIIR:Cof, and VIII:CAg, averaging fivefold to sixfold the normal level, of VIII:C averaging threefold the normal level. VIIIR:Cof and VIIIR:Ag significantly correlated in both groups of patients. In shock patients, VIII:C values were lower than VIII:CAg and varied between 40-90% of VIII:CAg. There were significant negative correlations between the DIC score on the one hand and ratios of VIII:C/VIIIR:Ag, VIII:C/VIII:CAg, and VIII:CAg/VIIIR:Ag on the other. The two patients who died from irreversible shock had the highest DIC score and lowest ratios of VIII:C/VIIIR:Ag and VIII:CAg/VIIIR:Ag as well as VIII:C/VIIIR:Cof and VIII:CAg/VIIIR:Cof. Released VIIIR:Ag multimers possess the ristocetin cofactor activity. In DIC, VIII:CAg is partially proteolyzed, however, less than VIII:C. The quotient VIII:C/VIIIR:Cof or VIII:C/VIIIR:Ag is a good indicator of the severity of DIC and may have important prognostic value.

Experimental model of disseminated intravascular coagulation induced by sustained infusion of endotoxin.

Experimental disseminated intravascular coagulation (DIC) was induced by sustained infusion of endotoxin into the femoral vein in rats. The severity of DIC was determined with reference to various parameters, such as fibrinogen and fibrin degradation products (FDP), prothrombin time (PT), partial thromboplastin time (PTT), platelet count, and number of renal glomeruli having fibrin thrombi. Experimental DIC could be induced by a 4-h sustained infusion of endotoxin in a dose of 100 mg/kg. The DIC induced in rats showed a close resemblance to human DIC as judged from such changes as an elevation in FDP, prolongation of PT and PTT, depression in fibrinogen and platelet count, and increase in glomeruli having fibrin thrombi. This experimental model has an advantage in that severity of DIC can be determined by measuring various parameters. It will be of use in the studies aimed at the establishment of a therapy for DIC as well as in the studies on DIC in rats.