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Cheng Hock Toh

Publications and source records attributed to Cheng Hock Toh.

10 recordsLinked to original sources
PubMed2005

Performance and prognostic importance of a new clinical and laboratory scoring system for identifying non-overt disseminated intravascular coagulation.

A template for diagnosing the non-overt phase of disseminated intravascular coagulation (DIC) has recently been proposed. However, validation of its performance and the proposal of a defining score are required. The aim was to assess feasibility of the non-overt DIC scoring template and its potential prognostic significance. Consecutive patients admitted to a university hospital intensive care unit were initially assessed over 2 months. Following this, a 12-month study examined the prognostic performance of the derived scores prospectively. Outcome parameters were overt DIC and 28-day mortality. The 2-month study, involving 66 patients and 919 time points, demonstrated practical feasibility and prognostic associations for mortality with scores of 5 and greater. The 12-month study involving 450 patients showed that the mortality rate was 29% (105 of 360) and 78% (70 of 90) for scores below 5 and scores of 5 or above, respectively. The mortality rate for overt DIC was also 78% (38 of 49). The non-overt DIC scoring template is workable and has prognostic relevance. A score of 5 and greater is recommended as diagnostic of non-overt DIC.

Disseminated Intravascular Coagulation↗
PubMed2004

Activated protein C induces the release of microparticle-associated endothelial protein C receptor.

Activated protein C (APC) treatment is now used for patients with severe sepsis. We investigated its effect in vitro on primary, physiologically relevant cells and demonstrate a novel mechanism of endothelial protein C receptor (EPCR) release that is not inhibited by metalloproteinase inhibitors. Exposure of human umbilical vein endothelial cells or monocytes to APC (6.25-100 nM) results in the release of EPCR-containing microparticles, as demonstrated by confocal microscopy and characterized through flow cytometry, enzyme-linked immunosorbent assay quantitation of isolated microparticles, and Western blotting. The phenomenon is time- and concentration-dependent and requires the APC active site, EPCR, and protease activated receptor 1 (PAR1) on endothelial cells. Neither protein C nor boiled or D-Phe-Pro-Arg-chloromethylketone-blocked APC can induce microparticle formation and antibody blockade of EPCR or PAR1 cleavage and activation abrogates this APC action. Coincubation with hirudin does not alter the APC effect. The released microparticle bound is full-length EPCR (49 kDa) and APC retains factor V-inactivating activity. Although tumor necrosis factor-alpha (10 ng/mL) can also induce microparticle-associated EPCR release to a similar extent as APC (100 nM), it is only APC-induced microparticles that contain bound APC. This novel observation could provide new insights into the consequences of APC therapy in the septic patient.

Anticoagulants↗
PubMed2004

Prothrombinase enhancement through quantitative and qualitative changes affecting very low density lipoprotein in complex with C-reactive protein.

The biphasic waveform that can predict for disseminated intravascular coagulation (DIC) is due to the formation of a calcium-dependent complex between C reactive protein (CRP) and very low density lipoprotein (VLDL). As thrombin generation is pivotal to DIC, this aspect has been specifically investigated and the VLDL component has been found to increase prothrombinase activity via both quantitative and qualitative changes. The specific prothrombinase activity of VLDL from patients manifesting the biphasic waveform was 2.5 times that of normal individuals or critically ill patients without the biphasic waveform. This activity was due to an increase in anionic phospholipid surfaces that could be inhibited with excess annexin V and which was dependent on structurally intact apolipoprotein B. The qualitative change appeared to be due to a deficiency of phosphatidylethanolamine in VLDL from patients with the biphasic waveform. The functional consequence of this enhanced prothrombinase activity was an increased procoagulant effect in plasma. Using a modified activated partial thromboplastin time assay, the mean normal clot time decreased significantly when VLDL from patients with biphasic waveforms was substituted. These results indicate that VLDL derived from patients with the biphasic waveform can enhance thrombin procoagulant activity. As the CRP-VLDL complex exists in vivo, it could have a pathogenic role in disseminating the process of intravascular coagulation.

Adsorption↗
PubMed2003

Current clinical practice. DIC 2002: a review of disseminated intravascular coagulation.

The turn of the millennium has seen clear advances in the understanding and management of Disseminated Intravascular Coagulation (DIC). The recognition that its pathogenesis stems from sustained thrombin generation in fuelling the cycle between inflammation and coagulation has seen the first successful treatment in severe sepsis through targeting this activity. An advance in treatment brings heightened relevance to laboratory testing, which now emphasises earlier detection and better monitoring to facilitate improved risk-identification and assessment of therapeutic efficacy. This review article also provides insights into future strategies that might build on the foundation of improving prognosis for the patient with DIC.

Anticoagulants↗
PubMed2003

Characterization of thrombin activatable fibrinolysis inhibitor in normal and acquired haemostatic dysfunction.

Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme, which is synthesized in the liver and circulates in the blood at a concentration of about 275 nmol/l. Once activated, by thrombin or plasmin, TAFI down regulates fibrinolysis, slowing clot lysis by cleaving the C-terminal lysine and arginine residues from partially degraded fibrin. Thrombomodulin enhances thrombin activation of TAFI by more than 1000-fold, suggesting that the thrombin-thrombomodulin complex is the physiological activator of TAFI. Activated protein C can up-regulate fibrinolysis by limiting the activation of TAFI via the attenuation of thrombin production. While impairment of fibrinolysis may predispose to thrombosis, excessive fibrinolysis may result in a bleeding tendency. In acquired coagulopathies, TAFI antigen levels are reduced in patients with disseminated intravascular coagulation. In focusing on women with major post-partum haemorrhage requiring blood transfusion, a significant reduction in TAFI levels is observed. The precise degree of TAFI activation is currently being characterized using new and more specific assays. The resulting data may provide insight into therapeutic options to treat post-partum haemorrhage, which is associated with significant morbidity.

Adult↗
PubMed2002

Early identification of sepsis and mortality risks through simple, rapid clot-waveform analysis. Implications of lipoprotein-complexed C reactive protein formation.

OBJECTIVE: To determine if the rapid waveform profile of the activated partial thromboplastin time (aPTT) assay, which detects lipoprotein-complexed C reactive protein (LCCRP) formation, predicts sepsis and mortality in critically ill patients. DESIGN: Observational, cohort study. SETTING: General intensive therapy unit (ITU) of a tertiary care hospital. PATIENTS AND PARTICIPANTS: A total of 1187 consecutive patients admitted to the ITU. INTERVENTION: Activated partial thromboplastin time transmittance waveform analysis was performed within the first hour of admission to the ITU. The degree of change causing a biphasic waveform was quantified through the drop in light transmittance level. MEASUREMENTS AND RESULTS: Three hundred forty-six patients had a biphasic waveform on admission to the ITU with a mortality rate of 44% compared with 26% for those with normal waveforms. Logistic regression models showed direct correlation between the likelihood for sepsis and in-patient mortality with increasing waveform abnormalities. The mortality fraction was 0.3 with normal waveforms versus 0.6 when the light transmittance decreased by 30%. The odds ratio (OR) for mortality and sepsis were 4.5 and 11, respectively, from the most abnormal to normal aPTT waveforms. These were comparable with APACHE II scores and superior to those estimated by CRP for mortality (OR 2.3) / sepsis (OR 6.4) prediction. CONCLUSION: Waveform analysis within the first hour of ITU admission is a single, simple and rapid method of identifying the risks of mortality and sepsis. Its measure of LCCRP formation shows superior prediction over CRP alone and it warrants further assessment as a tool to triage and target prompt, appropriate treatment in the ITU.

C-Reactive Protein↗
PubMed2002

Biphasic transmittance waveform in the APTT coagulation assay is due to the formation of a Ca(++)-dependent complex of C-reactive protein with very-low-density lipoprotein and is a novel marker of impending disseminated intravascular coagulation.

A decrease in light transmittance before clot formation, manifesting as a biphasic waveform (BPW) pattern in coagulation assays, was previously correlated with the onset of disseminated intravascular coagulation (DIC). In this study of 1187 consecutive admissions to the intensive care unit, the degree of this change on admission predicts DIC better than D-dimer measurements. Additionally, the BPW preceded the time of DIC diagnosis by 18 hours, on average, in 56% (203 of 362) of DIC patients. The BPW is due to the rapid formation of a precipitate and coincident turbidity change on recalcification of plasma. The isolated precipitate contains very-low-density lipoprotein (VLDL) and C-reactive protein (CRP). The addition of CRP and Ca(++) to normal plasma also causes the precipitation of VLDL and IDL, but not LDL or HDL. The K(d) of the CRP/VLDL interaction is 340 nM, and the IC(50) for Ca(++) is 5.0 mM. In 15 plasmas with the BPW, CRP was highly elevated (77-398 microg/mL), and the concentration of isolated VLDL ranged from 0.082 to 1.32 mM (cholesterol). The turbidity change on recalcification correlates well with the calculated level of the CRP-VLDL complex. Clinically, the BPW better predicts for DIC than either CRP or triglyceride alone. The complex may have pathophysiological implications because CRP can be detected in the VLDL fraction from sera of patients with the BPW, and the VLDL fraction has enhanced prothrombinase surface activity. The complex has been designated lipoprotein complexed C-reactive protein.

Biomarkers↗
PubMed2002

Transmittance waveform of routine coagulation tests is a sensitive and specific method for diagnosing non-overt disseminated intravascular coagulation.

The transmittance waveform profile on the routine coagulation test of the activated partial thromboplastin time can be characteristically biphasic in patients with disseminated intravascular coagulation (DIC). We have previously shown that there is increasing positive predictive value for DIC with increasing abnormality in this profile, and that waveform changes often preceded those in the more conventional parameters used for diagnosing DIC. We now show that a single analysis of the activated partial thromboplastin time waveform within the first hour of intensive care admission can assign risk of DIC development, and that this is superior to that of D-dimer measurements. Additionally, the analysis can also rapidly monitor progression from non-overt to overt DIC. This offers the potential of improved diagnostic means for targeting therapeutic intervention early in the DIC progress, as can be particularly useful in sepsis.

Blood Coagulation Tests↗
PubMed2002

Lipoprotein-complexed C-reactive protein and the biphasic transmittance waveform in critically ill patients.

The 'biphasic transmittance waveform' (BTW) refers to a decrease in light transmittance that often occurs prior to clotting in coagulation assays of critically ill patient plasmas. It correlates with disseminated intravascular coagulation and mortality. The present work shows that the BTW is due to the rapid formation of a precipitate and a coincident change in turbidity in re-calcified plasma. The precipitate was isolated from patient plasma and contained lipids typical of very low density lipoprotein (VLDL), plus the proteins apolipoprotein B-100 and C-reactive protein (CRP). Precipitation also occurred in normal plasma supplemented with CRP. In addition, CRP precipitated with VLDL and intermediate density lipoprotein, but not low density lipoprotein or high density lipoprotein. The Kd value for the CRP/VLDL interaction is 340 nM. The IC50 value of Ca2+ for complex formation is 5.0 mM, and epsilon-aminocaproic acid inhibits the process. In 15 plasmas with the BTW from critically ill patients, CRP was highly elevated (77-398 microg/mL) and VLDL cholesterol ranged from 0.082 to 1.32 mM. The magnitude of the turbidity change on re-calcification correlated well with the calculated level of the CRP/VLDL complex. Thus, the Ca2+-dependent formation of a complex between CRP and VLDL accounts for the BTW.

C-Reactive Protein↗