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Fulltext Adverse outcomes of anticoagulant use among hospitalized patients with chronic kidney disease: a comparison of the rates of major bleeding events between unfractionated heparin and enoxaparin

Saheb Sharif-Askari F, Syed Sulaiman SA, Saheb Sharif-Askari N, Al Sayed Hussain A, Railey MJ

PLoS One, 2014;9(9):e106517.
PMID: 25181525 DOI: 10.1371/journal.pone.0106517

Anticoagulation therapy is usually required in patients with chronic kidney disease (CKD) for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding.

Matched MeSH terms: Heparin/adverse effects*
Fulltext Extensive dural sinus thrombosis and bilateral lateral rectus palsy as an uncommon complication of chronic suppurative otitis media

Balasubramanian A, Mohamad I, Sidek D

BMJ Case Rep, 2013;2013.
PMID: 23355565 DOI: 10.1136/bcr-2012-007414

Dural venous sinus thrombosis, especially of the sigmoid sinus, is a known but uncommon intracranial extradural complication of chronic suppurative otitis media. Even rarer is the simultaneous occurrence of bilateral abducens palsy in the same patient. We report the case of an adolescent male who presented with signs of raised intracranial pressure, diplopia and bilateral lateral rectus palsy associated with a history of left ear discharge and neck swelling. Extensive dural sinus thrombosis extending right up to the left internal jugular vein was confirmed on CT imaging. The patient was successfully treated with thrombolytic agents and antibiotic therapy. The pathophysiology of the concurrent complications is discussed.

Matched MeSH terms: Heparin/therapeutic use
Fulltext Mefenamic Acid induced nephrotoxicity: an animal model

Somchit MN, Sanat F, Hui GE, Wahab SI, Ahmad Z

Adv Pharm Bull, 2014 Dec;4(4):401-4.
PMID: 25436198 DOI: 10.5681/apb.2014.059

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model.
METHODS: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil) or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day). Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN) and creatinine activities were measured.
RESULTS: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine.
CONCLUSION: RESULTS from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

Matched MeSH terms: Heparin
Fulltext Idiopathic hypereosinophilic syndrome with unusual presentation: two case reports and review of literature

Suria, A.A., Hafizah, H., Nurasyikin, Y., Azlin, I., Yousuf, R., Azma, R Z., et al.

Medicine & Health, 2018;13(2):208-216.
MyJurnal

Idiopathic hypereosinophilic syndrome (HES) is an uncommon disorder which usually presents with prolonged and significant primary eosinophilia with end-organ dysfunction. Damaging proteins released by the eosinophilic granules are responsible for the tissues and organ system damage. Here we report two cases of idiopathic HES. Both the patients were young lady presented with high grade fever and concomitant symptoms. Laboratory findings showed leucocytosis with predominant neutrophilia and marked eosinophilia. A diagnosis of idiopathic HES was made after excluding secondary causes of eosinophilia. However, the first patient was complicated with multiple venous thrombosis and intravenous heparin was started which was later changed to subcutaneous low molecular weight heparin (LMWH). The patient developed pleural effusion and consolidation. Intravenous Tazoscin, tablet Prednisolone and tablet Hydroxyurea was started and the patient responded well. Despite treatment, two weeks later, suddenly the patient collapsed and unfortunately succumbed. On the other hand, the second patient was complicated with fever, thrombocytopenia, haemolytic anaemia, acute renal failure and neurological deficit which were part and parcel of thrombotic thrombocytopenic purpura (TTP). Plasma exchange was commenced and patient’s condition had slowly improved. Nevertheless, the hypoxia which she sustained during the multiple episodes of fits had resulted in permanent brain injury and thus requiring a tracheostomy for prolonged ventilatory support. Currently, there is no cure for HES. The main aim of treatment is to minimise the tissue damage caused by the hypereosinophilia. Early diagnosis and intervention are therefore crucial in preventing the spread of the disease and the end-organ damage.

Matched MeSH terms: Heparin, Low-Molecular-Weight
Fulltext A case of urgent colonoscopic hemostasis of a cecal hemorrhagic ulceration in a patient receiving heparin for COVID-19 coagulopathy

Yoshida N, Hirose R, Watanabe M, Yamazaki M, Hashimoto S, Matsubara S, et al.

JGH Open, 2021 Jan;5(1):160-162.
PMID: 33490630 DOI: 10.1002/jgh3.12435

COVID-19 rarely causes lower gastrointestinal bleeding even though its RNA has been detected in patient's stool. Urgent colonoscopy in a COVID-19 patient with massive bloody stool requires various procedural and equipment considerations. Here, we present a case of colonoscopic hemostasis of a cecal hemorrhagic ulceration in a patient on heparin for COVID-19 coagulopathy. We also share various management methods for the prevention of COVID-19 contamination. A 71-year-old man was diagnosed with COVID-19 pneumonia and subsequently underwent hemodiafiltration. Heparin was initiated for COVID-19 coagulopathy. At day 42, the patient experienced 2000 mL of bloody stool. An operator performed urgent colonoscopy with three assistants in a negative-pressure room with full personal protective equipment. A hemorrhagic ulceration was detected at the cecum, and endoscopic hemostasis was performed. Immunohistochemistry was positive for cytomegalovirus. Postprocedure, the endoscopic systems were thoroughly cleaned, and specific measures for endoscope reprocessing and disinfection were performed to prevent contamination with COVID-19.

Matched MeSH terms: Heparin
Fulltext Blood Profiling of Captive and Semi-Wild False Gharial in Peninsular Malaysia

Latip MQA, Tengku Azizan TRP, Ahmad H, Abu Hassim H, Noor MHM, Mikail M

Animals (Basel), 2021 May 21;11(6).
PMID: 34063794 DOI: 10.3390/ani11061481

The involvement of veterinary medicine in wildlife research has played an important role in understanding the health status of various wildlife species. Health status is a very important aspect of species conservation. However, it requires a widely employed knowledge of veterinary clinical pathology, as a diagnostic tool in diagnosing the various disease conditions of wildlife species. Notwithstanding, a gap exists in the literature about the clinical pathology of the false gharial, due to the lack of normal reference values for hematological and serum biochemical analysis. The present study investigated the normal blood profile of 10 healthy false gharials, from two different zoos, and wildlife conservation centers located in three different states of Peninsular Malaysia. Blood samples were collected from the lateral caudal vein and divided into a vacutainer without anticoagulant for biochemical analysis, and a lithium heparin vacutainer (containing sodium heparin) for hematological studies. The results of the study indicated that the false gharial has a smaller erythrocyte dimension compared to other crocodilian species. At the same time the study revealed that the false gharial in a natural captive pond showed more leukocytes than false gharial kept in zoos, hence, habitat and environmental factors significantly affect hematological values. The biochemistry values also showed differences between the false gharial in different environmental conditions. Total protein, albumin (Alb), globulin (Glob), and Alb: Glob ratio were higher in false gharials kept in wildlife conservation centers than in false gharials kept in zoos. The values obtained in this study provide baseline data of hematological and serum biochemical values of the false gharial for future research and routine clinical diagnosis.

Matched MeSH terms: Heparin
Polysulfonate suramin inhibits Zika virus infection

Tan CW, Sam IC, Chong WL, Lee VS, Chan YF

Antiviral Res, 2017 07;143:186-194.
PMID: 28457855 DOI: 10.1016/j.antiviral.2017.04.017

Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log10 PFU viral reduction with IC50value of ∼2.5-5 μg/ml (1.93 μM-3.85 μM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor.

Matched MeSH terms: Heparin/analogs & derivatives; Heparin/pharmacology; Heparin/chemistry
Fulltext Safety and Effectiveness of Bivalirudin in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

Ahmad Hamdi AH, Dali AF, Mat Nuri TH, Saleh MS, Ajmi NN, Neoh CF, et al.

Front Pharmacol, 2017;8:410.
PMID: 28744215 DOI: 10.3389/fphar.2017.00410

Recent clinical trials have shown that while bivalirudin exhibits similar efficacy with heparin, it offers several advantages over heparin, such as a better safety profile. We aimed to evaluate the efficacy and safety of bivalirudin use during Percutaneous Coronary Intervention (PCI) in the treatment of angina and acute coronary syndrome (ACS). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, EMBASE, and Science Direct from January 1980 to January 2016. Randomized controlled trials (RCTs) comparing bivalirudin to heparin during the course of PCI in patients with angina or ACS were included. Outcome measures included all-cause mortality, myocardial infarction, revascularisation, stent thrombosis, stroke, and major bleeding. The selection, quality assessment, and data extraction of the included trials were done independently by four authors, and disagreements were resolved by consensus. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated. A total of 12 RCTs involving 44,088 subjects were included. Bivalirudin appeared to be non-superior compared to heparin in reducing all-cause mortality, myocardial infarction, revascularisation, and stroke. Bivalirudin appeared to be related to a higher risk of stent thrombosis when compared to heparin plus provisional use of a glycoprotein IIb/IIIa inhibitor (GPI) at day 30 (RR 1.94 [1.16, 3.24] p < 0.01). Overall, bivalirudin-based regimens present a lesser risk of major bleeding (RR 0.56 [0.44-0.71] p < 0.001), and Thrombolysis In Myocardial Infarction (TIMI) major bleeding (RR 0.56 [0.43-0.73]) compared with heparin-based regimens either with provisional or routine use of a GPI. However, the magnitude of TIMI major bleeding effect varied greatly (p < 0.001), depending on whether a GPI was provisionally used (RR 0.42 [0.34-0.52] p < 0.001) or routinely used (RR 0.60 [0.43 -0.83] p < 0.001), in the heparin arm. This meta-analysis demonstrated that bivalirudin is associated with a lower risk of major bleeding, but a higher risk of stent thrombosis compared to heparin.

Matched MeSH terms: Heparin
Fulltext Management of Takotsubo Syndrome: A Comprehensive Review

Sattar Y, Siew KSW, Connerney M, Ullah W, Alraies MC

Cureus, 2020 Jan 03;12(1):e6556.
PMID: 32042529 DOI: 10.7759/cureus.6556

Takotsubo syndrome (TTS), also known as Takotsubo cardiomyopathy, is a transient left ventricular wall dysfunction that is often triggered by physical or emotional stressors. Although TTS is a rare disease with a prevalence of only 0.5% to 0.9% in the general population, it is often misdiagnosed as acute coronary syndrome. A diagnosis of TTS can be made using Mayo diagnostic criteria. The initial management of TTS includes dual antiplatelet therapy, anticoagulants, beta-blockers, angiotensin-converting enzyme inhibitors or aldosterone receptor blockers, and statins. Treatment is usually provided for up to three months and has a good safety profile. For TTS with complications such as cardiogenic shock, management depends on left ventricular outflow tract obstruction (LVOTO). In patients without LVOTO, inotropic agents can be used to maintain pressure, while inotropic agents are contraindicated in patients with LVOTO. In TTS with thromboembolism, heparin should be started, and patients should be bridged to warfarin for up to three months to prevent systemic emboli. Our comprehensive review discussed the management in detail, derived from the most recent literature from observational studies, systematic review, and meta-analyses.

Matched MeSH terms: Heparin
Bilateral ophthalmic vein thrombosis secondary to nasal furunculosis

Rohana AR, Rosli MK, Nik Rizal NY, Shatriah I, Wan Hazabbah WH

Orbit, 2008;27(3):215-7.
PMID: 18569833 DOI: 10.1080/01676830802009754

We were presented with a teenage female who developed superior ophthalmic vein thrombosis and cavernous sinus thrombophlebitis after a 1-week history of a single acne-like lesion or furuncle at the anterior tip of the nose. She was managed aggressively with heparin and intravenous antibiotic. Signs and symptoms improved after 2 weeks of treatment, and she was discharged with an anticoagulant.

Matched MeSH terms: Heparin/therapeutic use
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: Heparin
Profile of Patients Diagnosed With Acute Venous Thromboembolism in Routine Clinical Practice: The RE-COVERY DVT/PE™ Study

Goldhaber SZ, Ageno W, Casella IB, Chee KH, Schellong S, Singer DE, et al.

Am J Med, 2020 08;133(8):936-945.
PMID: 32325043 DOI: 10.1016/j.amjmed.2020.03.036

BACKGROUND: The safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) for the treatment of venous thromboembolism (VTE) have been established in randomized controlled trials, but limited data are available on their use in clinical practice across geographical regions.
METHODS: In the international RE-COVERY DVT/PE observational study (enrollment January 2016 to May 2017), we sought to characterize the patient population and describe the prescribed anticoagulant. Patient characteristics and anticoagulants administered after objective diagnosis of VTE were recorded at the baseline visit and again at hospital discharge or at 14 days after the diagnosis, whichever was later.
RESULTS: A total of 6095 patients were included, 50.2% were male, and the mean age was 61.5 years. The most common comorbidities were hypertension (35%), diabetes mellitus (11%), cancer (11%), prior VTE(11%), and trauma/surgery (7%). Overall, 77% of patients received oral anticoagulants, with 54% on NOACs and 23% on vitamin K antagonists (VKAs); 20% received parenteral anticoagulation only. NOACs comprised about 60% of anticoagulant treatment in Europe and Asia but substantially less in Latin America (29%) and the Middle East (21%). For NOAC therapies, the distribution (as a percentage of the total cohort) was rivaroxaban 25.6%, dabigatran 15.5%, apixaban 11.3%, and edoxaban 1.7%. Treatment with NOACs was less frequent in patients who had cancer, chronic renal disease, heart failure, or stroke.
CONCLUSIONS: These findings enhance our understanding of baseline characteristics and the initial management of patients with VTE in routine practice.

Matched MeSH terms: Heparin/therapeutic use

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