Biomarkers of disseminated intravascular coagulation in pediatric intensive care unit in Thailand
Wiralpat PadungmaneesubSanit ReungrongratSuphara ManowongKanda FanhchaksaiNoppamas PanyasitRungrote Natesirinilkul
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Disseminated intravascular coagulation (DIC) is a systemic activation of hemostatic system caused by several causes. Biomarkers including antithrombin (AT), protein C (PC), and thrombomodulin (TM) were reported as the additional markers for DIC in adults. This study aimed to determine the association between biomarkers among patients with overt DIC (ODIC) and nonovert DIC (NDIC) in children in PICU.We enrolled 103 subjects, aged 1 month-18 years, who were admitted to PICU at Chiang Mai University (CMU) Hospital >24 hours with underlying conditions predisposing to DIC were enrolled. Biomarkers were tested after 24 hours of admission. Subject who had NDIC on the 1st investigations would have other tests on days 3-5 of admission.The incidence of ODIC by the International Society on Thrombosis and Hemostasis (ISTH) DIC score was found 24%. The bleeding, thrombosis, and death were significantly higher in ODIC group (P < 0.05). Mean levels of AT and PC in ODIC group were significantly different from NDIC one (66.9% vs 79.9%, P < 0.001 and 46.1% vs 59.2%, P = 0.004, respectively) while mean level of TM was not different between two groups. Adding AT to DIC score was better than the original score for predict mortality [area under curve (AUC) = 0.662 vs AUC = 0.65] and bleeding (AUC = 0.751 vs AUC = 0.732).ODIC is prevalent among critically ill children. Adverse outcomes were more commonly found in children with ODIC. AT and PC levels after 24 hours of PICU admission seem to be the useful biomarkers for ODIC in PICU.Keywords:
Thrombomodulin
【目的】外科的介入を行った敗血症性disseminated intravascular coagulation（DIC）における遺伝子組み換え型ヒト可溶性トロンボモジュリン（recombinant human soluble thrombomodulin, rTM）併用投与の効果を検討した。【方法】重症敗血症で集中治療管理を要したもののうち，外科的処置で感染巣をコントロールした症例を対象とした。従来のアンチトロンビン（antithrombin, AT）のみで治療したAT群と，rTMを併用投与したAT＋rTM群に分け，治療開始7日目までの臓器障害，凝血学的指標などの継時変化および治療転帰を後ろ向きに比較検討した。【結果】AT群で第1日目にAT活性値が低かったが，第3・5・7病日のDIC score，Sequential Organ Failure Assessment（SOFA）score・P/F比，血小板数・FDP値・AT活性値に有意差がなかった。両群の60日生存率は100％であり，集中治療管理・人工呼吸器・透析管理日数も差がなかった。【結語】敗血症性DICの治療の原則は感染巣の治療である。外科的介入で感染巣をコントロールが可能な場合，ATとrTMの併用療法に明らかな必要性は認めなかった。
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We examined the changes in plasma levels of soluble thrombomodulin in 66 cases of disseminated intravascular coagulation (DIC), to investigate the damage to vascular endothelial cells and its relationship to multiple organ failure. A significant elevation of plasma levels of soluble thrombomodulin was observed in most cases of DIC, especially in patients with sepsis. However, no such significant elevation was observed in patients with acute promyelocytic leukemia. Plasma levels of both soluble thrombomodulin and active plasminogen activator inhibitor were higher in the cases of DIC with multiple organ failure than in those without multiple organ failure. The levels of soluble thrombomodulin were decreased with the clinical improvement in most cases of DIC but were further increased or remained at high levels in patients who showed no improvement of DIC. It was suggested that an increase in soluble thrombomodulin indicates the damage to the vascular endothelial cells in cases of DIC and that the damage to vascular endothelial cells plays some role in further progression of multiple organ failure.
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The paper presents provisional data on the use of antithrombin III concentrate in the therapy of disseminated intravascular coagulation. Correction of insufficient antithrombin III activity in the complex therapy of thrombinemia and multiple organ dysfunctions is pathogenetically substantiated.
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A study was conducted to test the hypotheses that antithrombin III (antithrombin) improves disseminated intravascular coagulation (DIC) when applied to DIC patients diagnosed by sensitive criteria and that the administration of high-dose antithrombin is a beneficial treatment for DIC. Twenty-three DIC patients diagnosed based on the Japanese Association for Acute Medicine (JAAM) DIC diagnostic criteria were treated with either high-dose (60 IU/kg/day) or low-dose (30 IU/kg/day) antithrombin concentrates for 3 days. The clinical conditions that cause DIC were restricted to systemic inflammatory response syndrome (SIRS) and sepsis. Data of antithrombin activity, platelet counts, coagulation and fibrinolytic markers, and DIC scores before antithrombin administration (day 0), on days 1 to 3, and on day 7 were retrospectively collected from computer-based records. Patients who met the JAAM DIC criteria were administered either high-dose (12 patients) or low-dose (11 patients) antithrombin. The patients’ backgrounds and antithrombin activity (high dose, 51.5 ± 14.5%; low dose, 62.6 ± 19.3%; P = .153) on day 0 were identical in the 2 groups. The JAAM DIC score and prothrombin time ratio on day 7 significantly improved when compared with those on day 0. However, mortality at 28 days as well as interaction within the antithrombin doses administered showed no difference. There were also no differences in the time course of the platelet counts, coagulation and fibrinolytic markers, and DIC scores in the 2 groups. The authors conclude that the effects of antithrombin on prognosis and coagulation and fibrinolytic parameters are independent of the doses administered in patients with SIRS/sepsis-associated DIC.
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Disseminated intra-vascular coagulation (DIC) is associated with severe bleeding tendency and organ failure, the extent of which is thought to be related to the prognosis of DIC patients. Thrombomodulin (TM) is a high-affinity thrombin receptor on vascular endothelial cells. Clinical importance of soluble TM is still controversy as a diagnostic and prognostic indicator in patients with disseminated intravascular coagulation (DIC). We compared plasma levels of TM with fibrin degradation product (FDP) in patients with DIC through the clinical course. The significant elevation of circulating TM in nonsurvivors with DIC compared with survived patients with DIC(TM 3.1+/-1.52 vs 8.1+/-3.89 FU/ml), as well as FDP (12.9+/-12.12 vs 49.8+/-55.42 microg/ml) but the levels of FDP were not different between the two groups. The measurement of circulating TM was a relatively good prognostic marker of patients with DIC.
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In several animal experiments, high doses of antithrombin III concentrates have shown beneficial effects on mortality and reversal of coagulation abnormalities which had resulted from disseminated intravascular coagulation. Other experiments have suggested that antithrombin III infusion without heparin is effective in the treatment of organ failure. We clinically treated children suffering disseminated intravascular coagulation only with antithrombin concentrate. Four patients suffering disseminated intravascular coagulation with organ failure were selected. We started antithrombin III concentrate infusion as soon as the diagnosis was established. The dosage of antithrombin III was 120–250 units/kg/day for 2 or 3 days. Heparin was not used. All 4 patients recovered completely and quickly without any complications within 14 days. We suggest that the high-dose antithrombin III infusion without heparin is an effective and safe therapy for disseminated intravascular coagulation with organ failure. © 1996 Wiley-Liss, Inc.
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Purpose: Few reports have been made on the therapeutic effects as well as pathological features of an antithrombin preparation in patients diagnosed with septic disseminated intravascular coagulation (DIC) by the diagnostic criteria for acute DIC.Materials and Methods: A total of 88 sepsis patients who had received inpatient hospital care during the period from January 2000 through December 2008 were divided into two groups, an antithrombin group and a non-antithrombin group, to study the outcomes.Furthermore, the relationship between sepsis-related factors and DIC in 44 patients was studied.Results: The antithrombin group contained 34 patients, and the non-antithrombin group contained 54 patients.The outcomes were significantly better in the antithrombin group.The levels of protein C were low in DIC patients.Conclusion: Our results suggest that early administration of antithrombin might improve outcomes of septic DIC patients in the diagnostic criteria for Japanese Association for Acute Medicine acute DIC.
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Abstract This study demonstrated that intravenous infusion of recombinant human soluble thrombomodulin (rhs‐TM) could Inhibit disseminated Intravascuiar coagulation (DIC) caused by 4 hr infusion of tissue factor (TF) in rats. Extended infusion of TF reduced fibrinogen and platelet counts and elevated serum FDP level. Pretreatment and coinfusion of rhs‐TM could block changes of these DIC‐parameters without prolongation of APTT. Heparin, which is a potent anti‐DIC drug, could also inhibit these changes with extra prolongation of APTT and PT. Thus, these results suggest thrombomodulin prevent DIC less bleeding tendency than heparin. © 1994 Wiley‐Liss, Inc.
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