Clinical bleeding and thrombin generation in admissions to critical care with prolonged prothrombin time: an exploratory study

Background: Dengue is one of the important causes of acute febrile illnesses in India. Dengue can be a fatal disease, however there are no reliable markers which can predict mortality among these patients.Methods: A prospective cross sectional study was done in patients who were admitted to a tertiary care hospital with features of dengue fever. A total of 364 patients with IgM dengue serology positive were included in the study. Relevant clinical and laboratory parameters were collected from all patients. Association between clinico-laboratory parameters with mortality was studied using appropriate statistical methods.Results: Among the 364 patients recruited in this study, 14 (3.85%) patients died. Mortality among patients with age group 18-40 years was 2.04%, in patients aged above 40 years was 7.56%. Mortality among patients with hypotension was 42.42% (14 out of 33), bleeding manifestations was 15.38% (8/52), platelets <20,000/mm3 was 10.41% (10/96), ALT >200 was 13.04% (6/46), AST>200 was 12.34% (10/81), prolonged prothrombin time was 60%(12/20), renal failure was 28%(14/50), encephalopathy was 31.57% (6/19), multi organ dysfunction syndrome(MODS) was 43.33% (13/30), acute respiratory distress syndrome (ARDS) was 45.45% (5/11), pleural effusion was 7.5% (6/80).Conclusions: The overall mortality in the present study was 3.85%. Following variables were associated with increased risk of death among the dengue patients: Age >40 years, presence of hypotension, platelets <20000 cells/mm3, ALT>200U/L, AST>200U/L, prolonged prothrombin time, presence of renal failure, encephalopathy, MODS, ARDS and bleeding tendency (p value <0.05). Early identification of factors associated with mortality can help to make appropriate decision on care required.

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Thrombin Generation and Antithrombin Activity in Infants Undergoing Cardiopulmonary Bypass—An Exploratory Study

Journal of Cardiothoracic and Vascular Anesthesia ◽

10.1053/j.jvca.2019.12.008 ◽

2020 ◽

Vol 34 (8) ◽

pp. 2083-2090

Author(s):

Elena Ashikhmina ◽

Pamela M. Johnson ◽

Devon O. Aganga ◽

Gregory A. Nuttall ◽

Brian D. Lahr ◽

...

Keyword(s):

Cardiopulmonary Bypass ◽

Exploratory Study ◽

Thrombin Generation ◽

Antithrombin Activity

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An automated approach to characterize, in simple kinetic terms, the generation and inactivation of thrombin and the interaction of fibrinogen with thrombin.

Clinical Chemistry ◽

10.1093/clinchem/34.10.1971 ◽

1988 ◽

Vol 34 (10) ◽

pp. 1971-1975 ◽

Cited By ~ 2

Author(s):

D R Hoak ◽

S K Banerjee ◽

G Kaldor

Keyword(s):

Prothrombin Time ◽

Rate Constant ◽

Thrombin Generation ◽

Order Rate Constant ◽

Clinical Use ◽

First Order ◽

Pathological Conditions ◽

Pseudo First Order ◽

Instantaneous Concentration

Abstract Here, we used a fully automated, computer-directed centrifugal analyzer (which permitted simultaneous turbidimetry and calculation of results) and purified thrombin, fibrinogen, and various inhibitors to study clot formation. The Km and Vm for these reactions were useful in detecting and partly characterizing anticoagulants. We also explored the generation and inactivation of thrombin, using the two-stage prothrombin time and antithrombin activity tests. The amount of thrombin instantaneously generated and inactivated was monitored under artificially created pathological conditions. The pseudo-first-order rate constant for thrombin generation and inactivation and the instantaneous concentration of enzymatically active and inactive thrombin were used in the characterization of these conditions. We believe this approach is suitable for routine clinical use.

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Prolonged prothrombin time after a five months efficient vitamin E supplementation in cystic fibrosis patients

Clinical Nutrition ◽

10.1016/0261-5614(92)90255-o ◽

1992 ◽

Vol 11 ◽

pp. 67

Author(s):

B.M. Winklhofer-Roob ◽

D.H. Shmerling

Keyword(s):

Cystic Fibrosis ◽

Vitamin E ◽

Prothrombin Time ◽

Prolonged Prothrombin Time ◽

Vitamin E Supplementation

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Exploratory study of staff perceptions of shift safety in the critical care unit and routinely available data on workforce, patient and organisational factors

BMJ Open ◽

10.1136/bmjopen-2019-034101 ◽

2020 ◽

Vol 10 (6) ◽

pp. e034101

Author(s):

Clare Leon-Villapalos ◽

Mary Wells ◽

Stephen Brett

Keyword(s):

Critical Care ◽

Work Environment ◽

Exploratory Study ◽

Routine Data ◽

Care Staff ◽

Staff Perceptions ◽

Large Teaching Hospital ◽

Level 3 ◽

Perceptions Of Safety ◽

Organisational Factors

ObjectivesTo explore bedside professional reported (BPR) perceptions of safety in intensive care staff and the relationships between BPR safety, staffing, patient and work environment characteristics.DesignAn exploratory study of self-recorded staff perceptions of shift safety and routinely collected data.SettingA large teaching hospital comprising 70 critical care beds.ParticipantsAll clinical staff working in adult critical care.InterventionsStaff recorded whether their shift felt ‘safe, unsafe or very unsafe’ for 29 consecutive days. We explored these perceptions and relationships between them and routine data on staffing, patient and environmental characteristics.Outcome measuresRelationships between BPR safety and staffing, patient and work environment characteristics.Results2836 BPR scores were recorded over 29 consecutive days (response rate 57.7%). Perceptions of safety varied between staff, including within the same shift. There was no correlation between perceptions of safety and two measures of staffing: care hours per patient day (r=0.13 p=0.108) and Safecare Allocate (r=−0.19 p=0.013). We found a significant, positive relationship between perceptions of safety and the percentage of level 3 (most severely ill) patients (r=0.32, p=0.0001). There was a significant inverse relationship between perceptions of safety and the percentage of level 1 patients on a shift (r=−0.42, p<0.0001). Perceptions of safety correlated negatively with increased numbers of patients (r=−0.44, p=0.0006) and higher percentage of patients located side rooms (r=0.63, p<0.0001). We found a significant relationship between perceptions of safety and the percentage of staff with a specialist critical care course (r=0.42. p=0.0001).ConclusionExisting staffing models, which are primarily influenced by staff-to-patient ratios, may not be sensitive to patient need. Other factors may be important drivers of staff perceptions of safety and should be explored further.

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A Risk Model for Early Intracranial Hemorrhage in Acute Leukemia.

Blood ◽

10.1182/blood.v104.11.4473.4473 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4473-4473

Author(s):

Hawk Kim ◽

Seong-Jun Choi ◽

Je-Hwan Lee ◽

Jung-Shin Lee ◽

Kyoo Hyung Lee

Keyword(s):

Acute Leukemia ◽

Prothrombin Time ◽

Acute Promyelocytic Leukemia ◽

Induction Chemotherapy ◽

Intracranial Hemorrhage ◽

Risk Model ◽

Female Gender ◽

Promyelocytic Leukemia ◽

Free Survival ◽

Prolonged Prothrombin Time

Abstract Early intracranial hemorrhage (EICH), which is defined by noticeable ICH within 10 days of diagnosis, is a life-threatening hemorrhagic complication in patients with acute leukemia. To ascertain risk factors associated with EICH, we retrospectively analyzed 792 newly-diagnosed acute leukemia patients treated between July 1988 and March 2003. Thirty-one patients (3.9 %) had analyzable EICH. Multivariate analysis showed that female gender (OR = 3.064, P < 0.001), acute promyelocytic leukemia (OR = 8.797, P = 0.003), leukocytosis (OR = 6.056, P = 0.004), and prolonged prothrombin time (OR = 10.026, P = 0.016) were factors significantly associated with occurrence of EICH. Risk scores (RS) were calculated by a product of odds ratio and each risk factor (RF) and taking their sum, generating an RS ranging 0 to 27.943. The cutoff of RS 9 was of statistical significance to predict probability of EICH. Receiver-operating characteristics curve shows the sensitivity and 1 - specificity relative to risk score (AUC = 0.917; S.E. = 0.021; 95% CI, 0.876–0.958; Figure 1). In this regards, RF for EICH was classified as major (prolonged prothrombin time) and minor (female gender, acute promyelocytic leukemia, leukocytosis). Risk model demonstrated that EICH was low probable when no major RF and less than two minor RFs were present. Risk model for ICH in acute leukemia classified acute leukemia patients into two risk groups; low probable EICH group (LPG) and probable EICH group (PG). When applied to our patients, PG was positively correlated with more incidence of FICH than LPG (n = 27/173 vs. 4/619, P < 0.001). Induction chemotherapy could be undertook more frequently in LPG than in PG (p = 0.002, Table 1). Kaplan-Meier curves show the probability of EICH-free survival relative to probability of EICH. ICH-free survival was significantly longer in LPG than in PG (p < 0.0001, Figure 2). Our findings suggest that our risk model may predict the occurrence of EICH in patients with acute leukemia. Table 1. The relationship of risk model and frequency of early intracranial hemorrhage (EICH) or performance of induction chemotherapy. Figure Figure Figure Figure Low probable EICH group, n (%) Probable EICH group, n (%) P EICH (−) 615 (77.7 %) 146 (18.4 %) < 0.001 EICH (+) 4 (0.5 %) 27 (3.4 %) Induction chemotherapy (+) 563 (71.1 %) 143 (18.1 %) 0.002 Induction chemotherapy (−) 56 (7.1 %) 30 (3.8 %)

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Rebalanced Thrombin Generation in Liver Cirrhosis Calls for Tailored Transfusion Protocols

Blood ◽

10.1182/blood.v126.23.3523.3523 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3523-3523 ◽

Cited By ~ 1

Author(s):

Romy Kremers ◽

Marie-Claire Kleinegris ◽

Hugo ten Cate ◽

Bas De Laat ◽

Rob Wagenvoord ◽

...

Keyword(s):

Liver Cirrhosis ◽

Prothrombin Time ◽

In Silico ◽

Healthy Subjects ◽

Thrombin Generation ◽

Prothrombin Complex Concentrate ◽

Bleeding Risk ◽

Coagulation Factors ◽

Blood Product Transfusion ◽

Cirrhosis Patient

Abstract Introduction Most coagulation factors are produced by the liver, and therefore in liver cirrhosis both pro- and anticoagulant factor levels are reduced. Cirrhosis patients show no clear systemic bleeding or thrombotic phenotype and thrombin generation (TG) is (almost) unaffected, therefore it has previously been proposed that coagulation is rebalanced in cirrhosis because both pro- and anticoagulant processes are affected to a similar extent. Nevertheless, clinical parameters such as the prothrombin time indicate a bleeding risk in cirrhosis patients, and based on these tests patients often receive blood product transfusion during surgery. In this study we investigated thrombin generation and its main underlying pro- and anticoagulant processes (prothrombin conversion and thrombin inactivation) to provide empirical evidence for the hypothesis of rebalanced thrombin generation in liver cirrhosis. In addition, we used in silico experimentation to study the consequences of rebalanced TG for current transfusion practices. Methods 25 cirrhosis patients and 25 healthy subjects were enrolled in our study. The group of cirrhosis patients consisted of 22 Child-Pugh A and 3 Child-Pugh B patients. Prothrombin, antithrombin (AT) and α2Macroglobulin (α2M) levels were determined and TG was measured at 5 pM tissue factor by calibrated automated thrombinography. Prothrombin conversion and thrombin inactivation were quantified from each TG curve, and thrombin-antithrombin and thrombin-α2Macroglobulin complex formation was determined. The effect of transfusion of prothrombin complex concentrate (PCC) was simulated by an in silico increase of prothrombin conversion. The increase of prothrombin conversion was simulated by substituting the prothrombin conversion curve of a cirrhosis patient by the average healthy subject prothrombin conversion curve, to normalize prothrombin conversion in patients. Thrombin generation curves were calculated based on this normalized prothrombin conversion curve and the original thrombin inactivation parameters of each cirrhosis patient. Results Prothrombin and antithrombin are significantly decreased in cirrhosis patients (74 % and 70 %, p<0.001), whereas the α2M level is significantly increased (p<0.001). Thrombin generation in healthy subjects and patients is similar (figure), although prothrombin conversion (65 %, p<0.001) and thrombin inactivation (73 % p<0.001) are markedly reduced in cirrhosis patients. Acquired AT deficiency results in a reduction of thrombin inactivation by AT (64 %, p<0.001), but the substitution of AT by α2M leads to increased thrombin inactivation by α2M (220 %, p<0.001). The effect of prothrombin complex concentrate transfusion on thrombin generation in cirrhosis patients was determined by computational modeling (figure). In silico normalization of prothrombin conversion, as would be achieved by PCC transfusion, causes TG to rise to levels that have been shown to be highly prothrombotic (ETP 2878 ± 1323 nM∙min, p<0.001). Conclusions Despite large differences in prothrombin conversion and thrombin inactivation, TG in liver cirrhosis patients remains within the normal range (rebalanced), in contrast to the prothrombin time that predicts a bleeding risk in these patients. The transfusion of PCC based on a prolonged prothrombin time would result in a substantial elevation of thrombin generation. This indicates that standard transfusion protocols need to be tailored to the specific needs of cirrhosis patients. Figure 1. Thrombin generation in healthy subjects (■), cirrhosis patients (●), and cirrhosis patients transfused with PCC (in silico; ○). ***p<0.001 Figure 1. Thrombin generation in healthy subjects (■), cirrhosis patients (●), and cirrhosis patients transfused with PCC (in silico; ○). ***p<0.001 Disclosures Kremers: Synapse bv: Employment. De Laat:Synapse bv: Employment. Wagenvoord:Synapse bv: Employment. Hemker:Synapse bv: Employment.

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