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Microvascular thrombosis in pediatric multiple organ failure: Is it a therapeutic target?

Nguyen T, Hall M, Han Y, Fiedor M, Hasset A, Lopez-Plaza I, et al.

Pediatr Crit Care Med, 2001 Jul;2(3):187-196.
PMID: 12793940

PURPOSE: To discuss the current rationale for the use of specific and nonspecific therapies for thrombotic microangiopathy in thrombocytopenia-associated pediatric multiple organ failure syndromes. Methods: Pertinent PubMed and MEDLINE citations and proceedings of recent critical care meeting presentations were reviewed. RESULTS: Critical care clinicians have reported using antithrombin III concentrate, protein C concentrate, activated protein C, prostacyclin and its analogues, heparin, tissue factor pathway inhibitor concentrate, plasma infusion, plasma exchange, whole blood exchange, pentoxifylline, tissue plasminogen activator, urokinase, and streptokinase with perceived therapeutic benefits in patients with thrombocytopenia-associated multiple organ failure, including those with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, disseminated intravascular coagulation syndrome, and secondary thrombotic microangiopathy syndrome without prolonged prothrombin time/activated partial thromboplastin time. CONCLUSION: Assuming that underlying disease is remediable, a consensus has developed that thrombotic microangiopathy is a therapeutic target in children with thrombocytopenia-associated multiple organ failure syndromes. Studies are warranted to delineate efficacious use of specific and nonspecific therapies to prevent and reverse thrombotic microangiopathy in these patients.

Matched MeSH terms: Prothrombin Time
Coagulopathy in acute head injury--a study of its role as a prognostic indicator

Selladurai BM, Vickneswaran M, Duraisamy S, Atan M

Br J Neurosurg, 1997 Oct;11(5):398-404.
PMID: 9474270

The aim of this investigation was to determine the prognostic value of coagulation abnormalities in a defined subset of patients with acute head injury. Prothrombin time, accelerated partial thromboplastin time (APTT), thrombin clotting time, fibrinogen assay, platelet count, fibrin degradation products (FDP) were assayed in 204 patients with acute closed head injury. Their values were graded on a score 0-3 and the sum score for each patient regarded as the disseminated intravascular coagulation (DIC) score. Moderate to severe DIC scores were evident in 38% of the cohort. At least one parameter was abnormal in 71% of patients. The DIC score correlated inversely with the Glasgow coma score (GCS) (p < 0.0001). In the GCS 13-15 subset, FDP scores were significant predictors of poor outcome (p < 0.001). In the GCS 6-12 subset, the APTT score (p < 0.001), and DIC score (p < 0.0001) predicted an adverse outcome. The DIC scores were significantly abnormal in most patients who had a poor outcome, without evidence of adverse predictors on CT. Logistic regression analysis confirmed the independent predictive capacity of APTT, FDP and DIC scores when values for GCS were fixed. Abnormal haemostatic parameters may enhance the predictive ability in subsets of patients with acute head injury defined by clinical or CT predictors.

Matched MeSH terms: Prothrombin Time
Macular haemorrhage in adult acute leukaemia patients at presentation and the risk of subsequent intracranial haemorrhage

Jackson N, Reddy SC, Harun MH, Quah SH, Low HC

Br J Haematol, 1997 Jul;98(1):204-9.
PMID: 9233585

Retinal changes are common in adult acute leukaemia patients at presentation, but whether they correlate with the risk of subsequent intracranial haemorrhage is unknown. A 4-year study has been carried out in 82 newly-diagnosed acute leukaemia patients, aged 12-77 years, who were studied prospectively for the presence of intra-retinal haemorrhages (IRH), white-centred haemorrhages (WCH), cotton-wool spots (CWS) and macular haemorrhages (MH). Groups with and without these features were compared for their risk of intra-cranial haemorrhage (ICH) within the first 30 d following diagnosis. There was no association between the incidence of ICH and the presence of IRH, WCH or CWS. However, 6/13 of those with MH developed ICH, compared to 6/69 of those without MH (relative risk 5.0, CI 95% [2.03-12.33], P=0.003). The only other identifiable risk factor for ICH was the M3 subtype of AML, but if the four cases of M3-AML were discounted from analysis, MH remained a highly significant risk factor for ICH. Patients with MH should be monitored intensively for the development of ICH, and receive priority in the allocation of platelets where these are in short supply.

Matched MeSH terms: Prothrombin Time
Fulltext Development and blood compatibility assessment of electrospun polyvinyl alcohol blended with metallocene polyethylene and plectranthus amboinicus (PVA/mPE/PA) for bone tissue engineering

Qi J, Zhang H, Wang Y, Mani MP, Jaganathan SK

Int J Nanomedicine, 2018;13:2777-2788.
PMID: 29785105 DOI: 10.2147/IJN.S151242

Introduction: Currently, the design of extracellular matrix (ECM) with nanoscale properties in bone tissue engineering is challenging. For bone tissue engineering, the ECM must have certain properties such as being nontoxic, highly porous, and should not cause foreign body reactions.
Materials and methods: In this study, the hybrid scaffold based on polyvinyl alcohol (PVA) blended with metallocene polyethylene (mPE) and plectranthus amboinicus (PA) was fabricated for bone tissue engineering via electrospinning. The fabricated hybrid nanocomposites were characterized by scanning electron microscopy (SEM), Fourier transform and infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), contact angle measurement, and atomic force microscopy (AFM). Furthermore, activated partial thromboplastin time (APTT), prothrombin time (PT), and hemolytic assays were used to investigate the blood compatibility of the prepared hybrid nanocomposites.
Results: The prepared hybrid nanocomposites showed reduced fiber diameter (238±45 nm) and also increased porosity (87%) with decreased pore diameter (340±86 nm) compared with pure PVA. The interactions between PVA, mPE, and PA were identified by the formation of the additional peaks as revealed in FTIR. Furthermore, the prepared hybrid nanocomposites showed a decreased contact angle of 51°±1.32° indicating a hydrophilic nature and exhibited lower thermal stability compared to pristine PVA. Moreover, the mechanical results revealed that the electrospun scaffold showed an improved tensile strength of 3.55±0.29 MPa compared with the pristine PVA (1.8±0.52 MPa). The prepared hybrid nanocomposites showed delayed blood clotting as noted in APTT and PT assays indicating better blood compatibility. Moreover, the hemolysis assay revealed that the hybrid nanocomposites exhibited a low hemolytic index of 0.6% compared with pure PVA, which was 1.6% suggesting the safety of the developed nanocomposite to red blood cells (RBCs).
Conclusion: The prepared nanocomposites exhibited better physico-chemical properties, sufficient porosity, mechanical strength, and blood compatibility, which favors it as a valuable candidate in bone tissue engineering for repairing the bone defects.

Matched MeSH terms: Prothrombin Time
Expression and characterization of anticoagulant activity of salivary protein alALP from Asian tiger mosquito Aedes albopictus

Li XP, Lin D, Zhang Y, Chen SQ, Bai HQ, Zhang SN, et al.

Trop Biomed, 2020 Mar 01;37(1):116-126.
PMID: 33612723

Several bioactive molecules isolated from the saliva of blood-sucking arthropods, such as mosquitoes, have been shown to exhibit potential anticoagulant function. We have previously identified a 30kDa allergen named Aegyptin-like protein (alALP), which is highly homologous to Aegyptin, from the salivary glands of female Aedes albopictus (Asian tiger mosquito). In this study, we identified the conserved functional domain of alALP by using bioinformatic tools, and expressed the His-tagged alALP recombinant protein in sf9 insect cells by generation and transfection of a baculoviral expression plasmid carrying the fulllength cDNA of alALP. We purified this recombinant protein and examined its function on the inhibition of blood coagulation. The results showed that the purified His-alALP prolonged the Activated Partial Thromboplastin Time (APTT), Prothrombin Time (PT) and Thrombin Time (TT) in vitro as well as the Bleeding Time (BT) in vivo, which suggest that alALP could be a novel anticoagulant.

Matched MeSH terms: Prothrombin Time
Fulltext Fulminant hepatitis in dengue infection

Lum LC, Lam SK, George R, Devi S

Southeast Asian J. Trop. Med. Public Health, 1993 Sep;24(3):467-71.
PMID: 8160054

Eight cases of liver failure and encephalopathy were observed among twenty cases of grade 3 and grade 4 dengue hemorrhagic fever/dengue shock syndrome admitted to the Department of Pediatrics, University Hospital, Kuala Lumpur from January 1990 to December 1991. All patients with deterioriation in mental status showed a marked increase in liver enzymes (aspartate and alanine aminotransaminases) and severe coagulopathy. Six patients needed cerebral protection, including ventilation, intravenous sedation and muscle relaxants. There was one death during the period of study and one case of residual hemiparesis in a boy who had, in addition, intracerebral hemorrhage. All other survivors had complete recovery of liver and neurological function.

Matched MeSH terms: Prothrombin Time
Prothrombotic markers in Thalassemia major patients: A paradigm shift

Sultan S, Irfan SM, Zaidi SM

Med J Malaysia, 2018 08;73(4):185-189.
PMID: 30121679

BACKGROUND: It is being increasingly recognised that thalassemia major patients, like intermedia, have increased propensity for thromboembolism. Deficiency of natural anticoagulants is more recently defined finding contributing to the hypercoagulable state. The aim this study is to determine natural anticoagulants levels and their correlation with maternal characteristics, haematological and biochemical markers.
METHODS: This is a prospective case-control study. We registered 80 patients and 60 healthy controls from Jan 2009 to Dec 2013. Complete blood counts, prothrombin time, activated partial thromboplastin time, protein C, protein S, antithrombin, serum ferritin, liver enzymes; HbsAg and Anti- HCV were evaluated.
RESULT: There were 42 males and 38 females with mean age of 12.30±5.50 years. The mean protein C, protein S and antithrombin in patients and control were 58.25±22.5 versus 110.67±22.60, 67.90±19.58 versus 98.70±21.54 and 89.73±18.09 versus 104.0±10.98 (p<0.001) respectively. Protein C was predominantly deficient in 65% followed by protein S and antithrombin in 35% and 20% respectively. Protein C deficiency divulged positive correlation with protein S deficiency (p = 0.035) and antithrombin deficiency with hemoglobin of ≤8gm% (p<0.0025). No significant correlation of prothrombotic markers was established with maternal characteristics, hepatic dysfunction, hepatitis and serum ferritin.
CONCLUSION: Substantial decrement in prothrombotic markers, primarily protein C, may be implicated in elevated thrombosis; however follow-up data is required to establish definitive thromboembolic events.

Matched MeSH terms: Prothrombin Time
Fulltext A comparison of enoxaparin with unfractionated heparins in patients with coronary heart disease in an emergency department in rural South Indian tertiary care teaching hospital

Ahmad A, Patel I, Asani H, Jagadeesan M, Parimalakrishnan S, Selvamuthukumaran S

Indian J Pharmacol, 2015 Jan-Feb;47(1):90-4.
PMID: 25821318 DOI: 10.4103/0253-7613.150360

Antithrombotic therapy with heparin plus antiplatelets reduces the rate of ischemic events in patients with coronary heart disease. Low molecular weight heparin has a more predictable anticoagulant effect than standard unfractionated heparin, is easier to administer, does not require monitoring and is associated with less ADRs. The purpose of the present study was to evaluate and compare the clinical and cost outcomes of Enoxaparin with a standard unfractionated heparin in patients with coronary heart disease.

Matched MeSH terms: Prothrombin Time
Fulltext Microwave-assisted fibrous decoration of mPE surface utilizing Aloe vera extract for tissue engineering applications

Balaji A, Jaganathan SK, Supriyanto E, Muhamad II, Khudzari AZ

Int J Nanomedicine, 2015;10:5909-23.
PMID: 26425089 DOI: 10.2147/IJN.S84307

Developing multifaceted, biocompatible, artificial implants for tissue engineering is a growing field of research. In recent times, several works have been reported about the utilization of biomolecules in combination with synthetic materials to achieve this process. Accordingly, in this study, the ability of an extract obtained from Aloe vera, a commonly used medicinal plant in influencing the biocompatibility of artificial material, is scrutinized using metallocene polyethylene (mPE). The process of coating dense fibrous Aloe vera extract on the surface of mPE was carried out using microwaves. Then, several physicochemical and blood compatibility characterization experiments were performed to disclose the effects of corresponding surface modification. The Fourier transform infrared spectrum showed characteristic vibrations of several active constituents available in Aloe vera and exhibited peak shifts at far infrared regions due to aloe-based mineral deposition. Meanwhile, the contact angle analysis demonstrated a drastic increase in wettability of coated samples, which confirmed the presence of active components on glazed mPE surface. Moreover, the bio-mimic structure of Aloe vera fibers and the influence of microwaves in enhancing the coating characteristics were also meticulously displayed through scanning electron microscopy micrographs and Hirox 3D images. The existence of nanoscale roughness was interpreted through high-resolution profiles obtained from atomic force microscopy. And the extent of variations in irregularities was delineated by measuring average roughness. Aloe vera-induced enrichment in the hemocompatible properties of mPE was established by carrying out in vitro tests such as activated partial thromboplastin time, prothrombin time, platelet adhesion, and hemolysis assay. In conclusion, the Aloe vera-glazed mPE substrate was inferred to attain desirable properties required for multifaceted biomedical implants.

Matched MeSH terms: Prothrombin Time
Association between gastrointestinal manifestations following acetaminophen poisoning and outcome in 291 acetaminophen poisoning patients

Zyoud SH, Awang R, Sulaiman SA, Al-Jabi SW

Pharmacoepidemiol Drug Saf, 2010 May;19(5):511-7.
PMID: 20333776 DOI: 10.1002/pds.1940

Acetaminophen poisoning is a common clinical problem, and early identification of patients with more severe poisoning is key to improving outcomes.

Matched MeSH terms: Prothrombin Time
Childhood autoimmune liver disease: indications and outcome of liver transplantation

Chai PF, Lee WS, Brown RM, McPartland JL, Foster K, McKiernan PJ, et al.

J Pediatr Gastroenterol Nutr, 2010 Mar;50(3):295-302.
PMID: 20118802 DOI: 10.1097/MPG.0b013e3181bf0ef7

Graft rejection and disease recurrence are well-recognized complications of liver transplantation (LT) for autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (AISC). We describe indications and outcome of LT for childhood AIH and AISC.

Matched MeSH terms: Prothrombin Time