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Fulltext The effect of higher-intensity dosing of anticoagulation on the clinical outcomes in hospitalized patients with COVID-19: A meta-analysis of randomized controlled trials

Kow CS, Ramachandram DS, Hasan SS

J Infect Chemother, 2022 Feb;28(2):257-265.
PMID: 34840039 DOI: 10.1016/j.jiac.2021.11.008

OBJECTIVE: We aimed to perform a meta-analysis to summarize the overall evidence from randomized controlled trials related to higher-intensity anticoagulation in hospitalized patients with COVID-19.
METHODS: A systematic literature search was performed in electronic databases to identify randomized controlled trials comparing the clinical outcomes between intermediate/ therapeutic anticoagulation and prophylactic anticoagulation. Meta-analyses with random-effects models were used to estimate the pooled odds ratio (OR) for outcomes of interest at a 95% confidence interval (CI).
RESULTS: Eight randomized controlled trials were included, with a total of 5405 hospitalized patients with COVID-19. The meta-analysis revealed no statistically significant difference in the odds of mortality (pooled OR = 0.92; 95% CI 0.71-1.19) but a statistically significant reduction in the odds of development of thrombotic events (pooled OR = 0.55; 95% CI 0.42-0.72), and significantly increased odds of development of major bleeding (pooled OR = 1.81; 95% CI 1.20-2.72) with the use of intermediate/therapeutic anticoagulation, relative to prophylactic anticoagulation. Subgroup analysis in patients with a severe course of COVID-19 observed a statistically significant reduction in the odds of development of thrombotic events (pooled OR = 0.66; 95% CI 0.45-0.98) but no significant difference in the odds of development of major bleeding events (pooled OR = 1.37; 95% CI 0.74-2.56), with the use of intermediate/therapeutic anticoagulation, relative to prophylactic anticoagulation.
CONCLUSION: There could be net clinical benefits with higher-intensity dosing of anticoagulation relative to prophylactic-dosing of anticoagulation among hospitalized patients with severe COVID-19.

Matched MeSH terms: Hemorrhage/chemically induced
Spontaneous Bilateral Basal Ganglia Haemorrhage Secondary to Methanol Poisoning

Sohor NJ, Loh WC, Pang RY, Khan AH, Chia PK, Sulaiman WAW, et al.

Neurol India, 2023;71(6):1260-1262.
PMID: 38174472 DOI: 10.4103/0028-3886.391392

Methanol toxicity remains as major problem in the medical field.[1],[2],[3] With its active metabolite, formic acid often leads to severe metabolic acidosis and to some extend brain damaged.[4],[5],[6] We are reporting a case of brain hemorrhage at the right external capsule and left basal ganglia with mass effect and obstructive hydrocephalus in a methanol poisoning patient. A confused 29-year-old gentleman was brought into hospital. Initial investigation showed severe metabolic acidosis with raised anion gap. Initial brain CT scan was normal. Subsequently, serum methanol was reported to be high (112 mg/dL). Intravenous (IV) ethanol 10% was given without any delayed. As there was no improvement in his consciousness level, a repeat brain CT was performed and it showed multiple cerebral hemorrhage with obstructive hydrocephalus. Hence, clinicians should have high index of suspicion for cerebral hemorrhage in a patient with methanol toxicity, who presented with altered mental status and severe metabolic acidosis.

Matched MeSH terms: Cerebral Hemorrhage/chemically induced
Fulltext "Chap Kaki Tiga" a possible cause of upper gastrointestinal haemorrhage

See IO

Med J Malaysia, 1996 Mar;51(1):159-60.
PMID: 10968003
Matched MeSH terms: Gastrointestinal Hemorrhage/chemically induced*
The biological properties of venoms of some American coral snakes (Genus micrurus)

Tan NH, Ponnudurai G

Comp. Biochem. Physiol., B, 1992 Mar;101(3):471-4.
PMID: 1582185

1. The biological properties of nine venom samples from six taxa of Micrurus were investigated. The venoms exhibited low protease, phosphodiesterase and 5'-nucleotidase activities, moderate to strong phospholipase A and hyaluronidase activities, variable L-amino acid oxidase activity and were devoid of arginine ester hydrolase and thrombin-like activities. Some venom samples exhibited strong acetylcholinesterase activity. Venoms of M. c. dumerili and M. frontalis exhibited exceptionally high alkaline phosphomonoesterase activity while two of the M. f. fulvius venom samples tested exhibited strong hemorrhagic activity in mice. 2. The polyacrylamide gel electrophoretic patterns of the venoms indicate that most of the Micrurus venom proteins are basic proteins. All Micrurus venoms tested exhibited similar SDS-polyacrylamide gel electrophoretic patterns, with an intense low mol. wt protein band. 3. The Micrurus venoms appear to exhibit biological properties similar to other elapid venoms found in Asia and Africa. There are, however, no common characteristics in the biological properties of the venoms examined at the generic level.

Matched MeSH terms: Hemorrhage/chemically induced
The effect of fibrinogen concentrate on postoperative blood loss: A systematic review and meta-analysis of randomized controlled trials

Ng KT, Yap JLL, Kwok PE

J Clin Anesth, 2020 Aug;63:109782.
PMID: 32193125 DOI: 10.1016/j.jclinane.2020.109782

BACKGROUND: Low level of fibrinogen is a risk factor of perioperative bleeding, which is a major complication in surgical patients. However, the safety and efficacy of fibrinogen supplementation with fibrinogen concentrate to minimize postoperative bleeding remains unclear.
OBJECTIVES: The primary aim of this review was to investigate the effect of fibrinogen concentrate in postoperative blood loss in adult surgical patients.
DESIGN: Systematic review and meta-analysis.
DATA SOURCES: Databases of MEDLINE, EMBASE and CENTRAL were searched from their start date until July 2019.
ELIGIBILITY CRITERIA: All randomized clinical trials comparing intravenous fibrinogen concentrate and placebo in adult surgical patients were included, regardless of type of surgery. Observational studies, case reports, case series and non-systematic reviews were excluded.
RESULTS: Thirteen trials (n = 900) were included in this review. In comparison to placebo, fibrinogen concentrate significantly reduced the first 12-hour postoperative blood loss, with a mean difference of -134.6 ml (95% CI -181.9 to -87.4). It also significantly increased clot firmness in thromboelastometry (FIBTEM) with a mean difference of 2.5 mm (95%CI 1.1 to 3.8). No significant differences were demonstrated in the adverse events associated with fibrinogen concentrate use, namely incidence of thromboembolism, myocardial infarction and acute kidney injury.
CONCLUSIONS: In this meta-analysis of 13 randomized trials, low level of evidence and substantial heterogeneity with small sample size limit strong recommendation on the use of fibrinogen concentrate in adult surgical patients. However, its use is tolerable without any notable adverse events.
TRIAL REGISTRATION: CRD42019149164.

Matched MeSH terms: Postoperative Hemorrhage/chemically induced
Fulltext Factor VIII activity and bleeding risk during prophylaxis for severe hemophilia A: a population pharmacokinetic model

Tiede A, Abdul Karim F, Jiménez-Yuste V, Klamroth R, Lejniece S, Suzuki T, et al.

Haematologica, 2021 07 01;106(7):1902-1909.
PMID: 32327501 DOI: 10.3324/haematol.2019.241554

During factor VIII prophylaxis for severe hemophilia A, bleeding risk increases with time when factor VIII activity is below 1%. Maintaining trough activity above 1% does not protect all patients from bleeding. The relationship between factor VIII activity during prophylaxis and bleeding risk has not been thoroughly studied. We investigated factor VIII activity and annualized bleeding rate for spontaneous bleeds during prophylaxis. A population pharmacokinetic model derived from three clinical trials was combined with dosing data and bleed information from patient diaries. Each patients' time on prophylaxis was divided into five categories of predicted activity (0-1%, >1-5%, >5-15%, >15-50%, and >50%). Exposure time, mean factor VIII activity, and bleed number (from patient diaries) were calculated for each activity category, and annualized bleeding rates estimated using negative binomial regression and a parametric model. Relationships between these bleeding rates and factor VIII activity were evaluated by trial phase (pivotal vs. extension) and age (adults/adolescents [≥12 years] vs. children [0-<12 years]). In total (N=187; 815 patient-years' exposure), factor VIII activity was predicted to reach >1% for 85.64% of the time. Annualized bleeding rate decreased as factor VIII activity increased in each trial phase and age group. However, for a given activity level, bleeding rate differed substantially by trial phase, and age. This suggests that bleeding risk can change over time and is influenced by factors independent of factor VIII pharmacokinetics and trough levels. Target trough and prophylactic regimen should consider patient age, joint disease activity, and other bleeding risk determinants.

Matched MeSH terms: Hemorrhage/chemically induced
Biological properties of Trimeresurus purpureomaculatus (shore pit viper) venom and its fractions

Nget Hong Tan, Chon Seng Tan

Toxicon, 1988;26(11):989-96.
PMID: 3245058

The toxic and biological activities of four samples of Trimeresurus purpureomaculatus venom were examined. The lethality, protein composition and biological activities of the four venom samples were similar. Three of the venom samples had LD50 (i.v.) values of 0.9 micrograms/g while the fourth had a lower LD50 (i.v.) of 0.45 micrograms/g. All four venom samples exhibited hemorrhagic, edema-inducing, anticoagulant and thrombin-like activities as well as the usual enzymes found in crotalid venoms. DEAE-Sephacel ion exchange chromatographic fractionation of the venom yielded 10 protein fractions. Only two fractions (fractions A and F) were lethal to mice; the major lethal fraction being fraction F. This fraction had an LD50 (i.v.) of 0.2 micrograms/g and exhibited hemorrhagic, edema-inducing and thrombin-like activity. It also exhibited phospholipase A, arginine ester hydrolase, arginine amidase, protease, 5'-nucleotidase, acetylcholinesterase and alkaline phosphomonoesterase activities. The lethal potency of fraction F is potentiated by fraction G, which exhibited anticoagulant activity as well as hemorrhagic, edema-inducing and enzymatic activities. Fractions F plus G account for almost 100% of the lethal potency of the venom.

Matched MeSH terms: Hemorrhage/chemically induced
Fulltext Diffuse alveolar haemorrhage and myocardial infarction: life-threatening effects from self-injected hyaluronic acid dermal filler

Che Ani AA, Mohd Akhir S, Chiang Li-Xue W, Shahidan NZ, Abd Hamid A

Monaldi Arch Chest Dis, 2021 Jul 22;91(4).
PMID: 34296835 DOI: 10.4081/monaldi.2021.1845

Hyaluronic acid (HA) is a widely used dermal filler for soft tissue augmentation. We described a case of a 38-year-old transwoman who presented with sudden onset of severe respiratory distress following self-injection of HA dermal filler. She developed multiple episodes of pulmonary haemorrhage, and her chest X-ray showed diffuse ground-glass opacities consistent with diffuse alveolar haemorrhage (DAH). There were no relevant drugs or past medical histories. Anti-nuclear antibodies and rheumatoid factor were negative. Initially, the pulmonary haemorrhage episodes and ventilation requirement improved with systemic steroid, however she subsequently developed acute myocardial infarction with progressive clinical deterioration leading to death. To the best of our knowledge, this is the first HA-related DAH with myocardial infarction reported with a fatal outcome. This case highlights the importance of awareness and the necessity of having a high suspicion of DAH in patients with history of illicit HA dermal filler use.

Matched MeSH terms: Hemorrhage/chemically induced
Clopidogrel Vs Aspirin Monotherapy Following Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis

Tan BE, Wong PY, Baibhav B, Thakkar S, Azhar AZ, Rao M, et al.

Curr Probl Cardiol, 2023 Aug;48(8):101174.
PMID: 35341798 DOI: 10.1016/j.cpcardiol.2022.101174

Current guidelines recommend 6-12 months of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) followed by aspirin monotherapy indefinitely. We aimed to assess the efficacy and safety of clopidogrel vs aspirin in the post-PCI population after completing DAPT. We systematically searched 5 electronic databases to identify studies comparing clopidogrel with aspirin following completion of DAPT after PCI. We pooled outcomes for major adverse cardiac events (MACE), cardiac death, all-cause death, major bleeding, myocardial infarction (MI), and stroke. We included 5 studies with 13,850 patients, of whom 5601 (40.4%) received clopidogrel. Mean follow-up was 12-36 months. All patients received drug-eluting stents. Duration of DAPT before antiplatelet monotherapy was 1-18 months. Clopidogrel was associated with reductions in MACE (Risk ratio [RR] 0.77, 95% confidence interval [CI] 0.65-0.91), any stroke (RR 0.51; 95% confidence interval [CI] 0.35-0.76), ischemic stroke (RR 0.55; 95% CI 0.32-0.94), and hemorrhagic stroke (RR 0.24; 95% CI 0.09-0.68) when compared with aspirin. Cardiac death (RR 0.87; 95% CI 0.53-1.41), all-cause death (RR 1.06; 95% CI 0.81-1.39), major bleeding (RR 0.74; 95% CI 0.43-1.29), MI (RR 1.01; 95% CI 0.64-1.60), repeat revascularization (RR 0.88; 95% CI 0.71-1.09), target vessel revascularization (RR 0.76; 95% CI 0.52-1.13), and stent thrombosis (RR 0.96; 95% CI 0.35-2.59) were not significantly different among groups. Compared with aspirin, clopidogrel was associated with reductions in MACE and stroke (ischemic and hemorrhagic) following DAPT completion after PCI. There were no significant differences in mortality, major bleeding, MI, and repeat revascularization between groups.

Matched MeSH terms: Hemorrhage/chemically induced
Evaluation of the predictive performance of bleeding risk scores in patients with non-valvular atrial fibrillation on oral anticoagulants

Beshir SA, Aziz Z, Yap LB, Chee KH, Lo YL

J Clin Pharm Ther, 2018 Apr;43(2):209-219.
PMID: 29030869 DOI: 10.1111/jcpt.12634

WHAT IS KNOWN AND OBJECTIVE: Bleeding risk scores (BRSs) aid in the assessment of oral anticoagulant-related bleeding risk in patients with atrial fibrillation. Ideally, the applicability of a BRS needs to be assessed, prior to its routine use in a population other than the original derivation cohort. Therefore, we evaluated the performance of 6 established BRSs to predict major or clinically relevant bleeding (CRB) events associated with the use of oral anticoagulant (OAC) among Malaysian patients.
METHODS: The pharmacy supply database and the medical records of patients with non-valvular atrial fibrillation (NVAF) receiving warfarin, dabigatran or rivaroxaban at two tertiary hospitals were reviewed. Patients who experienced an OAC-associated major or CRB event within 12 months of follow-up, or who have received OAC therapy for at least 1 year, were identified. The BRSs were fitted separately into patient data. The discrimination and the calibration of these BRSs as well as the factors associated with bleeding events were then assessed.
RESULTS: A total of 1017 patients with at least 1-year follow-up period, or those who developed a bleeding event within 1 year of OAC use, were recruited. Of which, 23 patients experienced a first major bleeding event, whereas 76 patients, a first CRB event. Multivariate logistic regression results show that age of 75 or older, prior bleeding and male gender are associated with major bleeding events. On the other hand, prior gastrointestinal bleeding, a haematocrit value of less than 30% and renal impairment are independent predictors of CRB events. All the BRSs show a satisfactory calibration for major and CRB events. Among these BRSs, only HEMORR2 HAGES (C-statistic = 0.71, 95% CI 0.60-0.82, P

Matched MeSH terms: Hemorrhage/chemically induced*; Gastrointestinal Hemorrhage/chemically induced
Irreversible blindness following intravenous streptokinase

Peyman M, Subrayan V

JAMA Ophthalmol, 2013 Oct;131(10):1368-9.
PMID: 23929315 DOI: 10.1001/jamaophthalmol.2013.4489
Matched MeSH terms: Eye Hemorrhage/chemically induced*
A comparative study of the biological properties of venoms of some old world vipers (subfamily viperinae)

Tan NH, Ponnudurai G

Int. J. Biochem., 1992 Feb;24(2):331-6.
PMID: 1733799

1. The hemorrhagic, procoagulant, anticoagulant, phosphodiesterase, hyaluronidase, alkaline phosphomonoesterase, 5'-nucleotidase, arginine ester hydrolase, phospholipase A, L-amino acid oxidase and protease activities of 30 samples of venoms from nine species (12 taxa) of the old world vipers (Subfamily Viperinae) including snakes from the genera Bitis, Causus, Cerastes, Echis, Eristicophis and Pseudocerastes, were determined and the Sephadex G-75 gel filtration patterns for some of the venoms were also examined. 2. Examination of the biological properties of the venoms of the Viperinae tested indicates the presence of common venom biological characteristics at the various phylogenic levels. 3. Venoms of most species of the Viperinae examined exhibited characteristic biological properties at the species level, and this allows the differentiation of the Viperinae species by differences in their biological properties. 4. Particularly useful for this purpose, are the effects of venom on kaolin-cephalin clotting time of platelet poor rabbit plasma and the Sephadex G-75 gel filtration pattern and arginine ester hydrolase activity of the venom.

Matched MeSH terms: Hemorrhage/chemically induced
Haemolytic, oedema and haemorrhage inducing activities of tentacular extract of the blubber jellyfish (Catostylus mosaicus)

Azila N, Siao FK, Othman I

Comp Biochem Physiol C Comp Pharmacol Toxicol, 1991;99(1-2):153-6.
PMID: 1675964

1. An extract prepared from the tentacle of the jellyfish (CE), Catostylus mosaicus exhibited haemolytic, oedema and haemorrhage-inducing activities. 2. Acetone treatment of the tentacle extract produced an acetone soluble extract (AE) which showed an increase in specific haemolytic and haemorrhagic activities by 25- and 120-fold respectively; the minimum oedema dose was reduced by 30-fold. 3. The AE caused a rapid onset of oedema in the mouse foot pad. The effect was long-lasting, reaching a maximum in about 30 min after injection and sustained up to 4 hr. 4. Fractionation of the AE on Q-Sepharose gave 4 bound fractions which induced oedema and haemorrhage; however only 3 of the fractions exhibited haemolytic activity.

Matched MeSH terms: Hemorrhage/chemically induced*
Isolation and characterization of a hemorrhagin from the venom of Ophiophagus hannah (king cobra)

Tan NH, Saifuddin MN

Toxicon, 1990;28(4):385-92.
PMID: 2190359

The major hemorrhagin (termed hannahtoxin) of the venom of Ophiophagus hannah (king cobra) was purified to electrophoretic homogeneity by DEAE-Sephacel ion exchange chromatography, Sephadex G-200 gel filtration followed by a second DEAE-Sephacel chromatography. Proteolytic activity was associated with the hemorrhagic activity throughout the purification procedures. Hannahtoxin constituted approximately 2% of the crude venom. It had an isoelectric point of 5.3, a carbohydrate content of 12%, a mol. wt of 66,000 as determined by SDS-polyacrylamide gel electrophoresis and 63,000 as determined by gel filtration. It contains 1 mole of Zn per mole of protein. The minimum hemorrhage doses for hannahtoxin are 0.7 microgram and 75 micrograms, respectively, in rabbits and in mice. Hannahtoxin was not lethal to mice at a dose of 2 mg/kg (i.v.) but killed rabbits at doses above 0.18 mg/kg (i.v.). It liberated protein from rabbit glomerular basement membrane but not rat glomerular basement membrane. Treatment of the hemorrhagin with EDTA and 1,10-phenanthroline eliminated both the proteolytic and hemorrhagic activities completely.

Matched MeSH terms: Hemorrhage/chemically induced
Proteolytic specificity of rhodostoxin, the major hemorrhagin of Calloselasma rhodostoma (Malayan pit viper) venom

Tan NH, Ponnudurai G, Chung MC

Toxicon, 1997 Jun;35(6):979-84.
PMID: 9241791

The proteolytic specificity of rhodostoxin, the major hemorrhagin from Calloselasma rhodostoma (Malayan pit viper) venom was investigated using oxidized B-chain of bovine insulin as substrate. Six peptide bonds were cleaved: Ser9-Hist10, His10-Leu11, Ala14-Leu15, Tyr16-Leu17, Gly20-Glu21 and Phe24-Phe25. Deglycosylated rhodostoxin, however, cleaved primarily at Arg22-Gly23.

Matched MeSH terms: Hemorrhage/chemically induced*
Fulltext Development of an adverse drug reaction risk assessment score among hospitalized patients with chronic kidney disease

Sharif-Askari FS, Syed Sulaiman SA, Saheb Sharif-Askari N, Al Sayed Hussain A

PLoS One, 2014;9(4):e95991.
PMID: 24755778 DOI: 10.1371/journal.pone.0095991

Adverse drug reactions (ADRs) represent a major burden on the healthcare system. Chronic kidney disease (CKD) patients are particularly vulnerable to ADRs because they are usually on multiple drug regimens, have multiple comorbidities, and because of alteration in their pharmacokinetics and pharmacodynamic parameters. Therefore, one step towards reducing this burden is to identify patients who are at increased risk of an ADR.

Matched MeSH terms: Hemorrhage/chemically induced
Statements of the Malaysian Society of Gastroenterology & Hepatology and the National Heart Association of Malaysia task force 2012 working party on the use of antiplatelet therapy and proton pump inhibitors in the prevention of gastrointestinal bleeding

Tan HJ, Mahadeva S, Menon J, Ng WK, Zainal Abidin I, Chan FK, et al.

J Dig Dis, 2013 Jan;14(1):1-10.
PMID: 23134105 DOI: 10.1111/1751-2980.12000

The working party statements aim to provide evidence and guidelines to practising doctors on the use of antiplatelet therapy and proton pump inhibitors (PPIs) in patients with cardiovascular risk as well as those at risk of gastrointestinal (GI) bleeding. Balancing the GI and cardiovascular risk and benefits of antiplatelet therapy and PPIs may sometimes pose a significant challenge to doctors. Concomitant use of anti-secretory medications has been shown to reduce the risk of GI bleeding but concerns have been raised on the potential interaction of PPIs and clopidogrel. Many new data have emerged on this topic but some can be confusing and at times controversial. These statements examined the supporting evidence in four main areas: rationale for antiplatelet therapy, risk factors of GI bleeding, PPI-clopidogrel interactions and timing for recommencing antiplatelet therapy after GI bleeding, and made appropriate recommendations.

Matched MeSH terms: Gastrointestinal Hemorrhage/chemically induced
Minor oral surgery in anticoagulated patients: local measures alone are sufficient for haemostasis

Ramli R, Abdul Rahman R

Singapore Dent J, 2005 Dec;27(1):13-6.
PMID: 16438263

Minor oral surgery in warfarinized patients can be performed without stopping or altering the dose of the drug. Thirty patients underwent various types of oral surgical procedures without interruption of their anticoagulant therapy and their therapeutic international normalized ratio maintained. Local measures such as pressure, packing the sockets with oxidized regenerated cellulose, and suturing were applied. In some patients, tranexamic acid mouthwashes were prescribed to further enhance haemostasis. Four patients had minimal postoperative bleeding in the form of bloodstained saliva, which lasted for 24 hours. This study highlights the importance of local measures in controlling postoperative bleeding in warfarinized patients undergoing minor oral surgical procedures.

Matched MeSH terms: Hemorrhage/chemically induced
Fulltext Massive bleeding from colonic diverticular disease with NSAID use

Muthu A, Qureshi A, Ismail MA

Med J Malaysia, 1999 Sep;54(3):374-6.
PMID: 11045068

Non-steriodal anti-inflammatory drugs (NSAID) are not only associated with bleeding in the stomach and duodenum, but can also complicate pre-existing diverticular disease of the colon. Here, a 58 year-old male with severe per rectal bleeding is presented and the role of NSAID as a causative factor of his problem is discussed.

Matched MeSH terms: Gastrointestinal Hemorrhage/chemically induced*
The biological properties of venoms from juvenile and adult taipan (Oxyuranus scutellatus) snakes

Tan NH, Armugam A, Mirtschin PJ

Comp. Biochem. Physiol., B, 1992 Nov;103(3):585-8.
PMID: 1458834

1. The biological properties of four venom pooled samples from adult taipan (Oxyuranus scutellatus) snakes and one pooled venom sample from six juvenile taipan snakes (11 months old) were compared. 2. The intravenous LD50 (median lethal dose), procoagulant activity and enzymatic activities of the juvenile venom were not significantly different from those of the adult venoms. 3. The juvenile and adult venoms exhibited similar polyacrylamide gel electrophoretic (PAGE) and SDS-PAGE patterns, indicating that they possessed a similar protein composition. 4. The results suggest that there is no significant age-dependency in the biological properties of taipan venom.

Matched MeSH terms: Hemorrhage/chemically induced

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