Course Of Disseminated Intravascular Coagulation Research Articles

Disseminated Intravascular Coagulation in Cancer: An Update.

Cancer often leads to the activation of coagulation, manifesting as disseminated intravascular coagulation (DIC) in its most extreme form. DIC is characterized by systemic intravascular coagulation activation (leading to deposition of intravascular platelets and fibrin) and simultaneous consumption of coagulation proteins and thrombocytes (which may cause bleeding complications). The clinical course of DIC in patients with malignancies is typically less intense compared with DIC complicating alternative clinical settings, including systemic inflammatory responses following infection or traumatic injury. A more slowly proceeding, less fulminant, and widespread hemostatic derangement can remain asymptomatic. Eventually, the ongoing consumption may result in low levels of platelets and coagulation factors, and bleeding complications (frequently localized at the site of the tumor or distant metastases) may be the first clinical manifestation of DIC. An alternative clinical scenario is dominated by thrombotic complications, ranging from clinically manifest vascular thrombosis to microvascular platelet plugs. The main principle of DIC management is adequate treatment of the precipitating disorder; however, there are clinical presentations that may require additional supportive strategies specifically aimed at the amelioration of the coagulopathy.

Limited Superiority Of Recombinant Thrombomodulin For Disseminated Intravascular Coagulation; A Comparative Analysis In 41 Children

Background and ObjectivesRecombinant thrombomodulin (rTM), a new type of natural anticoagulant, has been available in Japan since 2008 for the treatment of disseminated intravascular coagulation (DIC). Since limited information is available on its efficacy in children, we compared the efficacy of rTM to that of conventional treatment. Patients and MethodsOf 41 children with DIC, 21 were treated with rTM as a first-line therapy (rTM group) and 20 weere treated with conventional treatment (control group). The day on which anti-DIC treatment was first given was defined as day 1. We used the DIC criteria of the Japan Welfare and Health Ministry. We evaluated the overall survival at day 28 after anti-DIC treatment, the cumulative incidence of DIC resolution, and the total fresh frozen plasma (FFP) and platelet transfusion volumes during the course of DIC. ResultsClinical outcomes are summarized in the Table. Both groups showed comparable overall survival (95.2% in the rTM group and 95.0% in the control group). In addition, the cumulative incidence of DIC resolution in the rTM group (90.5%) was not different from that in the control group (70.0%) (p=0.210) (Figure). However, the median FFP and platelet transfusion volumes in the rTM group (0 U/kg and 0.28 U/kg) were lower those in the control group (0.14 U/kg and 0.76 U/kg) (p=0.041 and 0.063, respectively). [Display omitted] ConclusionThe use of rTM in children with DIC should reduce the social and ethical problems as well as the biological risks associated with human-derived blood products. Although the limited advantages of rTM were shown, the present study was limited by the small and heterogeneous patient population. Therefore, larger prospective studies are warranted to fully evaluate the efficacy of rTM. Disclosures:No relevant conflicts of interest to declare.

Presence of Antiheparin/Platelet Factor 4 Immunoglobulin G Is Associated With Poor Prognosis in Patients With Suspected Disseminated Intravascular Coagulation

The underlying inflammatory or infectious condition in disseminated intravascular coagulation (DIC) may stimulate the formation of antiheparin/platelet factor 4 (PF4) antibody, and the resulting antibody may affect the clinical course of DIC. We investigated the prognosis of antiheparin/PF4 antibodies in patients with suspected DIC. We measured heparin/PF4 immunoglobulin G (IgG) and total antibody levels using an automated chemiluminescence system in 118 patients with DIC. Of the 118 patients, 13 (11.0%) patients were positive for total antiheparin/PF4, and 6 (5.1%) patients were positive for antiheparin/PF4 IgG. These 13 patients were negative for platelet-activating antibody and had low-heparin-induced thrombocytopenia probability scores. Patients with antiheparin/PF4 IgG were older and had lower antithrombin levels than patients without antiheparin/PF4 IgG. Patients with antiheparin/PF4 IgG had a higher risk of mortality than those without antiheparin/PF4 IgG. The presence of antiheparin/PF4 IgG in old age or low antithrombin level patients with DIC with old age or low antithrombin level suggests a poor prognosis.

The relation of aquaporinl gene expression and kidney injury in rats with disseminated intravascular coagulation

Objective To characterize the effects of AQP1 expression on kidney damage in rat disseminated intravascular coagulation(DIC) caused by lipopolysaccharide(LPS) dosing. Method Fifty male Wistar rats (clean grade) were randomly assigned into 5 groups of 10 rats. The 10 control rats were dosed with 10 ml of 0.9%NaCl solution by a drip via the vena caudalis within 4 h, and blood and tissues were obtained after treatment completion. In the DIC groups, the rats were dosed with LPS (30 mg/kg body weight in 10 ml of 0.9% NaCl solution) by a drip via the vena caudalis within 4 h, and blood and tissues were obtained at 4, 6, 8 and 10 h. The blood platelet(PLT) count, prothrombin time(PT) , activated partial thromboplastin time(APTT), fibrin(FIB) and D-dimer(D-D) were detected. Hematoxylin and eosin(HE) staining was used to examine the pathologic changes in the lung and kidney tissues of each group (both hematologic parameters and tissue pathologic changes were used to judge the course of DIC). The AQP1 gene expression levels in the kidney tissues from the groups were evaluated by the mRNA levels using RT-PCR. Statistical analyses were performed by the SNK- q method. Results The PLT count, PT, APTT, FIB and D-D examinations revealed remarkable changes in all DIC groups compared with the control group (P < 0.01). The AQP1 mRNA level was significantly decreased in the DIC group at 4 h compared with the control group (P < 0.01) , and further decreased to the minimum level in the DIC group at 6 h. Moreover, cloudy swelling of renal tubular cells was observed at 6 h and cell degeneration and necrosis were observed at 8 h among the DIC groups. Conclusions Downregulation of AQP1 mRNA expression occurred before damage to the renal tubular cells in DIC, indicating that AQP1 expression may be involved in the kidney damage observed in rat DIC. Key words: Lipopolysaccharide; Disseminated intravascular coagulation; Kidney damage; Aquaporinl

Correction of Antithrombin III Deficiency in Disseminated Intravascular Coagulation

Although antithrombin (AT) III concentrate therapy is attended by an increased risk of hemorrhage, the data available in the literature suggest that the agent may have a positive effect on outcome in disseminated intravascular coagulation (DIC). Administration of fresh frozen plasma (FFP) is associated with a less risk of hemorrhage; however, there is no evidence for its impact on prognosis in DIC. Objective: to compare the effects of AT concentrate and FFP on the activity of AT and on the clinical course of DIC. Subjects and methods. Forty-three patients diagnosed as having as DIC (according to the JAAM scale) and &lt;70% AT deficiency were included into a randomized clinical study. The inclusion criteria were as follows: age less than 16 years and more than 75 years; malignancy; hemorrhage; hemostatic therapy; a thrombocytopenia of &lt;50X109/l. The patients were randomized into 3 groups: A) AT concentrate 500— 1000 IU/day; B) FFP 10 ml/kg/day; C) combined therapy. The agents were daily administered for 4 days in a persistent AT deficiency of 70%. Nadroparin, 95 IU AXa/kg/day, was used as concurrent therapy. Results. The activity of AT substantially increased in Group A and great differences between Groups A and B preserved during therapy: 69±16 and 51±14% (p=0.007); 72±18 and 56±13% (p=0.02); 73±14 and 57±16% (p=0.03), respectively. No significant differences were found in the severity of respiratory disorders, dysfunction of other organs, DIC scale scores, the incidence of hemorrhages (2 cases in Group A), allergic reactions (2 cases of urticaria in Group C) and in 30-day mortality — 40, 53.3, and 30.8% in Groups A, B, and C, respectively. Conclusion. As compared with FFP and combined therapy, AT concentrate therapy for DIC provides a more effective correction of AT deficiency. Further studies are needed to compare the impact of three therapy modalities on the outcome and incidence of complications in DIC. Key words: disseminated intravascular coagulation (DIC), diagnostic criteria for DIC, antithrombin III deficiency, antithrombin III concentrate, fresh frozen plasma.

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.

Good or poor responses of hemostatic molecular markers in patients with hematopoietic disorders after treatment of disseminated intravascular coagulation.

Changes of hemostatic markers in 226 patients with disseminated intravascular coagulation (DIC) and hematopoietic disorders were examined after treatment of DIC. The changes in prothrombin time (PT) ratio, fibrinogen, fibrin and fibrinogen degradation products (FDP), antithrombin, and protein C, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), and soluble fibrin monomer complex (SFMC) in all patients with DIC were significant during the clinical course of DIC, but those of D-dimer, thrombomodulin (TM), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) were not. Activated partial thromboplastin time (aPTT) and PT were significantly longer in the poor response group than in good response group. Plasma levels of FDP, TAT, PPIC, SFMC, TM, and DIC score were significantly higher in poor response group than in good response. Protein C and antithrombin levels were significantly lower in poor response group than in good response group. The changes of PT ratio, fibrinogen, FDP, DIC score, antithrombin, plasmin inhibitor, and protein C were significant in the good response group, but these levels were not significant in the poor response group. The changes in plasma TAT and SFMC levels were significant in the good response group but were not in poor response group. The changes in D-dimer, TM, TF, or TFPI were not significant in both groups. These findings suggest that anticoagulant agents should be administered at levels below TAT 40 ng/mL or SFMC 300 microgram/mL in patients with DIC and hematopoietic disorders.

The association of disseminated intravascular coagulation with specific diseases

Disseminated intravascular coagulation (DIC) is a syndrome that occurs in the course of a diversity of severe diseases and which is associated with an increased rate of morbidity and mortality. Although still an enigmatic syndrome, a recent consensus definition and criteria for clinical diagnosis have been proposed. The diseases responsible for 2/3 of cases of DIC are associated with infections (sepsis and disseminated viral infections) and malignancies (solid tumors as well as haematological malignancies). The presentation of DIC may be variable, ranging from acute thrombo-hemorrhagic symptoms in meningococcal sepsis, to chronic low grade DIC in certain malignancies. Other important groups of disorders are trauma (grade of DIC depending on the extent and origin of trauma), emergencies of pregnancy (abruptio placentae, amniotic fluid embolism, pre-eclampsia), snake bites, and major vascular disorders (aneurysm). The present availability of diagnostic tools to assess the presence and course of DIC should allow for the timely confirmation of this syndrome and may help to decide on the use of anticoagulant or other treatment, preferably after determining the efficacy in clinical trials.

Changes in plasma tissue factor pathway inhibitor levels during the clinical course of disseminated intravascular coagulation.

In healthy volunteers, the plasma total tissue factor pathway inhibitor (TFPI) level was 68.7+/-14.1 ng/ml; the plasma free TFPI level, 17.7+/-5.4 ng/ml; the lipoprotein-associated TFPI (LP-TFPI), 51.1+/-12.0 ng/ml; the free TFPI/total TFPI ratio 0.26+/-0.07; and the plasma tissue factor levels were 149+/-46 pg/ml. Plasma tissue factor levels in patients with disseminated intravascular coagulation (DIC) were significantly higher than those in pre-DIC patients or in non-DIC patients. Plasma total-TFPI, free-TFPI and LP-TFPI levels were significantly higher in DIC patients than those in pre-DIC patients or in non-DIC patients. Before the onset of DIC, the plasma levels of tissue factor gradually increased, and 3 days before the onset of DIC they were significantly higher than those in non-DIC patients. The plasma levels of tissue factor reached their highest level 1 day before the onset of DIC and gradually decreased after the onset of DIC. Plasma levels of total-TFPI, free-TFPI, and LP-TFPI gradually increased before the onset of DIC, and the total-TFPI and LP-TFPI reached their highest levels at the onset of DIC. Plasma free-TFPI reached highest level one day after the onset of DIC. During the clinical course of DIC, the plasma level of tissue factor was the first to increase, then that of LP-TFPI and finally the free-TFPI plasma levels. These differences in the peak plasma levels of tissue factor, free-TFPI, and LP-TFPI might be related to the clinical course of DIC.

Plasma tissue factor and tissue factor pathway inhibitor levels in patients with disseminated intravascular coagulation.

We measured the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with disseminated intravascular coagulation (DIC) to examine the relationship between TFPI and vascular endothelial cell injury. Plasma TF (273 +/- 90 pg/ml) and TFPI (252 +/- 125 ng/ml) levels were significantly increased in patients with DIC compared with non-DIC patients. Plasma TF antigen level was significantly increased in pre-DIC patients (285 +/- 85 pg/ml), while the plasma TFPI level (152 +/- 54 ng/ml) was not markedly increased in such a state. The plasma TF/TFPI ratio was high in the pre-DIC patients (2.10 +/- 0.90), and low in the DIC patients (1.40 +/- 0.87) and healthy volunteers (0.84 +/- 0.26). There was no significant difference between the DIC patients with a good outcome and those with a poor outcome in terms of plasma TF levels, although the plasma TFPI level in the DIC patients with a good outcome (289 +/- 133 ng/ml) was significantly higher than those with a poor outcome (187 +/- 75 ng/ml). During the clinical course of DIC, plasma TF antigen was increased first, and an increase of the plasma TFPI level followed the increase in plasma TF level. These findings suggest that plasma TFPI is released from vascular endothelial cells and it may reflect vascular endothelial cell injury. It is conceivable that TF and TFPI may play an important role in the onset of DIC.

Plasma tissue factor and tissue factor pathway inhibitor levels in patients with disseminated intravascular coagulation.

We measured the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with disseminated intravascular coagulation (DIC) to examine the relationship between TFPI and vascular endothelial cell injury. Plasma TF (273 +/- 90 pg/ml) and TFPI (252 +/- 125 ng/ml) levels were significantly increased in patients with DIC compared with non-DIC patients. Plasma TF antigen level was significantly increased in pre-DIC patients (285 +/- 85 pg/ml), while the plasma TFPI level (152 +/- 54 ng/ml) was not markedly increased in such a state. The plasma TF/TFPI ratio was high in the pre-DIC patients (2.10 +/- 0.90), and low in the DIC patients (1.40 +/- 0.87) and healthy volunteers (0.84 +/- 0.26). There was no significant difference between the DIC patients with a good outcome and those with a poor outcome in terms of plasma TF levels, although the plasma TFPI level in the DIC patients with a good outcome (289 +/- 133 ng/ml) was significantly higher than that in those with a poor outcome (187 +/- 75 ng/ml). During the clinical course of DIC, plasma TF antigen was increased first, and an increase of the plasma TFPI level followed the increase in plasma TF level. These findings suggest that plasma TFPI is released from vascular endothelial cells and it may reflect vascular endothelial cell injury. It is conceivable that TF and TFPI may play an important role in the onset of DIC.

Tissue factor in plasma of patients with disseminated intravascular coagulation.

Recently it has been shown that tissue factor (TF), an important trigger for initiating blood coagulation, is present in the circulating plasma. In order to assess the clinical implications of TF in plasma, plasma concentration of TF was quantitated in 65 patients with disseminated intravascular coagulation (DIC). The mean concentration of plasma TF was elevated in patients with DIC at presentation as compared with healthy subjects (446 +/- SD 536 pg/ml vs. 138 +/- 51 pg/ml, P < 0.001). Abnormally high levels were found only in 46.2% of the patients, predominantly in patients with non-hematological solid tumors and acute leukemia. Plasma TF did not correlate with hemostatic markers of DIC such as thrombin-antithrombin III complex, prothrombin fragment 1 + 2, plasma-alpha 2-plasmin inhibitor complex, FDP, D-dimer, or fibrinogen. Serial determinations of plasma TF demonstrated that plasma TF changes roughly in parallel with the course of DIC in most patients with elevated TF at presentation of DIC. These findings suggest that plasma TF is potentially valuable for monitoring the progress of DIC in a limited population of patients.

The effect of a long-acting recombinant hirudin (PEG-hirudin) on experimental disseminated intravascular coagulation (DIC) in rabbits

Reproducible disseminated intravascular coagulation in rabbits was provoked by two intravenous injections 24 hours apart of endotoxin from Salmonella enteritidis.There were mild symptoms of DIC before the second injection which considerably increased thereafter. In detail there was a sharp drop of the platelet count and a considerable diminution of Antithrombin III,of Protein C,Plasminogen and Antiplasmin as well as an appearance of fibrin monomer complexes and an increase of the aPTT. When PEG-hirudin in a single dose of 1 mg/kg BW was given simultaneously with the second injection of endotoxin the following alterations were observed: The drop of the platelet count and of the activities of Antithrombin III, Protein C, Plasminogen and Antiplasmin was significantly less pronounced. The fibrin monomer complexes were lower and the aPTT was less prolonged. The thrombin time,however,as a sign of a direct action of hirudin on thrombin was considerably more prolonged than in the controls. The combined effect of these alterations strongly points in the direction of a favourable influence of PEG-hirudin on the course of DIC. It is of special interest that 6 h after the intravenous injection of PEG-hirudin its full effect on the thrombin time was still detectable. This is apparently due to a longer half-life in circulation of PEG-hirudin than of natural hirudin.

Evaluation of Clinical Usefulness of a Rapid Measurement of Plasmin-α2-Plasmin Inhibitor Complex by Latex Agglutination Immunoassay

Plasma levels of plasmin-α2-plasmin inhibitor complex (PPI) were measured by a rapid semi-quantitative method based on the latex agglutination immunoassay in patients with a variety of diseases such as hematological malignancies, infection, thrombotic disease and disseminated intravascular coagulation (DIC). As compared with healthy subjects, plasma levels of PPI were markedly elevated in the patients with DIC. In addition, some patients with thrombotic disease and hematological malignancies had high PPI levels. Serial determinations of PPI demonstrated a dynamic fluctuation of PPI during the course of DIC and during fibrinolytic therapy. On the whole, PPI values obtained by this assay were correlated well with those measured by an enzyme-linked immunosorbent assay. In addition, the plasma PPI level was correlated positively with concurrently assayed FDP and D-dimer levels, and negatively with plasma levels of fibrinogen, α2-plasmin inhibitor and plasminogen. No correlation was found between the PPI level and antithrombin III, protein C or thrombin-antithrombin III complex values. These findings indicate that a rapid measurement of the plasma PPI level with this method would be useful for the assessment of activation of fibrinolysis in these disease states.

Disseminated intravascular coagulation and decrease in fibrinogen levels induced by vincristine/prednisolone therapy of lymphoid blast crisis of chronic myeloid leukemia

Therapy with vincristine (2 mg i.v. weekly) and prednisolone (100 mg p.o. daily) caused a decrease in fibrinogen levels in nine patients treated for lymphoid blast crisis LBC) of chronic myeloid leukemia (CML). During the first days of treatment disseminated intravascular coagulation (DIC), evidence by a positive ethanol gelation test, markedly increased thrombin-antithrombin III complex and fibrin-split product D-dimer levels, and a rapid fall in fibrinogen levels was observed in two patients. The induction of DIC in these two patients caused profuse bleeding in one and necessitated substitution therapy with fibrinogen and platelet concentrates. The remaining seven patients revealed no signs of DIC; nevertheless, four of them showed a moderate increase in D-dimer levels after initiation of therapy. In these patients a well-known side effect of long-term steroid therapy, namely a decrease of fibrinogen levels, was observed within the first week of treatment. Fibrinogen levels did not fall below 150 mg/dl and increased after dose reduction from 100 mg/day to 50 mg/day. We conclude from our results that two types of disturbances in fibrinogen metabolism can be observed during vincristine/prednisolone therapy of LBC of CML: (a) a decrease of fibrinogen levels due to a steroid-mediated impairment of liver synthesis, and (b) a rapid fall in fibrinogen levels in the course of DIC, most likely induced by the release of procoagulants from deteriorating blast cells, leading to severe bleeding in selected cases.

Clinical Valuableness of the Measurement of Thrombin/Antithrombin III Complex

We measured Thrombin/Antithrombin III Complex (TAT) in the plasma from normal subjects and the patients with various diseases by a two-step sandwich enzyme immunoassay. The measurements were performed periodically for the patients with acute promyelocytic leukemia with disseminated intravascular coagulation (DIC). During the course of DIC, the levels of TAT varied according to the activity of DIC. TAT level was so sensitive that it could detect latent activation of the clotting pathway. Besides DIC, marked elevation of TAT level was found in some patients with advanced cancer, collagen diseases with vasculitis and infectious diseases. We conclude that the measurement of TAT is valuable for the assessment of activation of clotting pathway.

新しいＤダイマー測定試薬を用いた各種血栓性疾患における安定化フィブリン分解産物の測定

In patients with various thromboembolic diseases and normal subjects, plasma levels of crosslinked fibrin derivatives (XDP) were measured by a latex agglutination procedure using a new monoclonal antibody. Plasma XDP was undetectable (<1μg/ml) in all normal subjects, and in all patients with chronic arterial or venous thromboembolic diseases. It was elevated in 2 of 6 patients with acute venous thromboembolism, in 3 of 13 patients with acute arterial thromboembolism, and in all 18 patients with disseminated intravascular coagulation (DIC). In patients with DIC, XDP values correlated well with currently used FDP, and changed in parallel with the clnical course of DIC. Following the fibrinolytic therapy, plasma XDP level increased in 4 of 12 patients studied. It was suggested that this new reagent for the quantitation of XDP is useful for the assessment of secondary fibrinolysis, although it is not sensitive to mild elevation of XDP.

Plasmin‐α2‐plasmin inhibitor complex in plasma of patients with disseminated intravascular coagulation

Plasmin-alpha 2-plasmin inhibitor (alpha 2PI) complex, an indicator of in vivo plasmin generation, was measured in the plasma of 48 patients with disseminated intravascular coagulation (DIC), by enzyme-linked immunosorbent assay (ELISA). Plasmin-alpha 2PI complex was markedly elevated to 7.9 +/- 4.26 mg/liter (mean +/- SD) in DIC at presentation, with normal values at less than 0.8 mg/liter. The concentration of plasmin-alpha 2PI complex changed in parallel with the course of DIC and decreased to 1.9 +/- 1.49 mg/liter (n = 28) in remission. Among various underlying disorders, DIC, in patients with acute promyelocytic leukemia, had the highest complex levels (mean 10.8 mg/liter), and septic patients had the lowest levels (mean 3.4 mg/liter). No significant correlation was found between FDP and plasmin-alpha 2PI complex. These results indicate that the quantitative assay of plasmin-alpha 2PI complex in plasma would be valuable in the assessment of hyperfibrinolysis in DIC.

The influence of drugs on disseminated intravascular coagulation (DIC) III. Effects of busulfan-induced thrombocytopenia and inhibition of platelet function by acetylsalicylic acid

Abstract The role of platelets in thrombin-induced disseminated intravascular coagulation (DIC) was studied in rats. Thrombin was infused in an amount causing a pronounced decrease in fibrinogen concentration, increase in plasma hemoglobin concentration, reduction of total oxygen consumption of the animals, and microthrombus formation. During thrombin infusion, platelet counts decreased and the platelets remaining in the circulating blood showed a reduced aggregability and a disturbed serotonin uptake. Busulfan-induced thrombocytopenia or administration of acetylsalicylic acid (ASA) did not prevent microthrombosis but reduced the increase in plasma hemoglobin. The oxygen consumption did neither drop in thrombocytopenic nor in ASA-treated animals. Thus, platelets do not seem to be involved in thrombin-induced microthrombosis, but they are considered to be mediators of secondary reactions in the course of DIC.