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The Medical Letter on Drugs and... Jul 2022
Topics: Anticoagulants; Humans; Neoplasms; Venous Thromboembolism
PubMed: 35867417
DOI: No ID Found -
The Medical Letter on Drugs and... Jul 2022
Topics: Anticoagulants; Dabigatran; Humans; Pyridones; Rivaroxaban; Venous Thromboembolism
PubMed: 35867416
DOI: No ID Found -
Journal of Diabetes and Metabolic... Dec 2022Coronavirus Disease 2019 (COVID-19) is a recent public health issue worldwide. Also, diabetes is a frequent condition with high mortality. There is a strong relationship... (Review)
Review
Coronavirus Disease 2019 (COVID-19) is a recent public health issue worldwide. Also, diabetes is a frequent condition with high mortality. There is a strong relationship between COVID-19 and diabetes. This article analyses the intricate relationship between COVID-19 and hepcidin. Hepcidin increases in aged non-insulin diabetic patients. Hepcidin is the last target treatment of several medications commonly used. Viral diseases, especially SARS-CoV19, can activate the hepcidin pathway leading to an elevation in the iron load. This increased iron is released into the bloodstream and results in cell death through ferroptosis, like free iron. Excess iron has pro-coagulative and toxic effects. Hepcidin overexpression and iron overload are associated with COVID-19 infection and can be considered potential targets for treatment. Several studies have shown dalteparin (anti-Hepcidin) could improve the symptoms of COVID-19 in diabetics by appropriately modulating and decreasing oxidative stress and inflammation. This finding can be leading to enhancing the existing knowledge about Therapeutic measures for reducing Covid-19 impairments in diabetics and is suggested as a possible therapeutic agent in diabetes.
PubMed: 35812243
DOI: 10.1007/s40200-022-01053-9 -
The Journal of Allergy and Clinical... Nov 2022Heparin allergy most frequently manifests as delayed-type hypersensitivity (DTH) causing an itchy inflammatory skin reaction at the site of subcutaneous injection. An...
BACKGROUND
Heparin allergy most frequently manifests as delayed-type hypersensitivity (DTH) causing an itchy inflammatory skin reaction at the site of subcutaneous injection. An important differential diagnosis is circumscribed skin necrosis due to heparin-induced thrombocytopenia.
OBJECTIVES
An inflammatory skin reaction to subcutaneously injected heparin generally entails the quest for alternative anticoagulation; concerns may particularly arise in an emergency situation requiring intravenous heparin administration.
METHODS
All heparin DTH cases seen in our department over the last 17 years underwent standardized allergy diagnostics including challenge testing, that is, subcutaneous injection of fondaparinux and intravenous administration of unfractionated heparin (UFH).
RESULTS
Of a total of 50 patients with confirmed heparin allergy, DTH was found in 48 (96.0%), and immediate-type, presumably IgE-mediated hypersensitivity was diagnosed in only 2 (4.0%). In the 48 DTH cases, intradermal testing revealed broad cross-reactivity between UFH and low-molecular-weight heparins (LMWH) including nadroparin, dalteparin, and enoxaparin. Cross-reactivity with (or concomitant sensitization to) fondaparinux was seen in only 3 (6.3%) cases. Intravenous administration of UFH was tolerated by all 45 patients challenged, despite DTH to UFH and LMWH as demonstrated by intradermal testing.
CONCLUSIONS
If an inflammatory skin reaction at the site of subcutaneously injected heparin is observed or reported without any evidence of skin necrosis or thrombocytopenia, intravenous administration of UFH seems to be sufficiently safe and may be considered without allergy testing if urgently indicated in an emergency situation. Fondaparinux is the most suitable alternative for subcutaneous application.
Topics: Humans; Heparin; Fondaparinux; Heparin, Low-Molecular-Weight; Anticoagulants; Skin Tests; Drug Hypersensitivity; Injections, Subcutaneous; Administration, Intravenous; Necrosis
PubMed: 35788063
DOI: 10.1016/j.jaip.2022.06.030 -
Carbohydrate Polymers Sep 2022Catheter-related bloodstream infections (CRBSI) are the major concern of patients undergoing hemodialysis. The current study formulates bifunctional low molecular weight...
Catheter-related bloodstream infections (CRBSI) are the major concern of patients undergoing hemodialysis. The current study formulates bifunctional low molecular weight heparin (LMWH) coated nanosilver as an effective anticoagulant and antimicrobial/anti-biofilm agent. Nanosilver formulations were prepared using a microwave-assisted green synthesis approach and stabilized with pharmaceutically approved LMWH such as dalteparin (DL) and enoxaparin (EX) along with unfractionated heparin (HP) as a control. The obtained heparinized (HP/DL/EX) nanosilver was monodisperse, and the size ranged between 15 and 25 nm. DL/EX predominantly stabilized the nanosilver by primarily engaging their negatively charged sulfate groups. The obtained DL/EX coated nanosilver are hemocompatible, showed two times increase in their anticoagulation activity, and are highly potent in inhibiting/eradicating both mono- and polymicrobial biofilms. Henceforth, the observed biocompatible and enhanced bifunctional characteristics of DL/EX coated nanosilver can be used to replace the systemic antibiotics and can be an alternative catheter lock solution to prevent CRBSI in hemodialysis therapy.
Topics: Anticoagulants; Dalteparin; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Humans; Renal Dialysis; Sepsis
PubMed: 35698376
DOI: 10.1016/j.carbpol.2022.119546 -
Vector Borne and Zoonotic Diseases... Jul 2022The American Heartworm Society (AHS) recommends the three-dose alternate melarsomine therapeutic regimen, together with a macrocyclic lactone (ML) to reduce new...
The American Heartworm Society (AHS) recommends the three-dose alternate melarsomine therapeutic regimen, together with a macrocyclic lactone (ML) to reduce new infections and eliminate susceptible larvae and doxycycline against bacteria. Till now, only reports on ivermectin as an ML exist in the frame of this protocol. Between 2014 and 2020, the AHS protocol was used in 44 heartworm-positive dogs. Microfilaremic dogs were pretreated with prednisolone and clopidogrel for 1 week before the first moxidectin application. Moxidectin was applied on the 1st, 30th, 60th, and 90th therapeutic days. On the first day, dexamethasone and chloropyramine were used to avoid potential adverse effects caused by the destroyed microfilariae. During the 1st-28th days, doxycycline 10 mg/kg BID was given with probiotics. Adult heartworms were destroyed with melarsomine on the 60th, 90, and 91st days. Butorphanol and dexamethasone were given just before melarsomine injections. The depth of the intramuscular injection site was determined by ultrasound examination of the lumbar muscles. From the 60th day, dalteparin was applied for 10 days to decrease the chance of pulmonary thromboembolism. Moxidectin did not cause adverse reactions, even in microfilaremic dogs. Gastrointestinal side effects of doxycycline were observed in three (6%) dogs, they recovered after symptomatic therapy and by lowering the initial dose to 5 mg/kg BID. Transient anorexia and diarrhea were found in one (2%), and coughing and mild dyspnea in one (2%) animal as systemic post-therapeutic complications of melarsomine. No local side effects were observed in 13 (30%) dogs, mild local side effects occurred in 29 (66%) patients, and severe local swelling in 2 (4%) cases. All dogs recovered clinically by the 120th day and no microfilaremia was seen that time. An antigen test performed in 37/44 animals on the 271st day was also negative in all cases.
Topics: Animals; Arsenicals; Clinical Protocols; Dexamethasone; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Doxycycline; Filaricides; Macrolides; Triazines
PubMed: 35687421
DOI: 10.1089/vbz.2021.0108 -
Ophthalmology Oct 2022Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD.
DESIGN
Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis.
PARTICIPANTS
Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry.
METHODS
Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy.
MAIN OUTCOME MEASURES
Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon.
RESULTS
A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified.
CONCLUSIONS
Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.
Topics: Dalteparin; Double-Blind Method; Fluorouracil; Heparin; Heparin, Low-Molecular-Weight; Humans; Retinal Detachment; Vitrectomy; Vitreoretinopathy, Proliferative
PubMed: 35680097
DOI: 10.1016/j.ophtha.2022.05.024 -
Pediatric Blood & Cancer Aug 2022Data from registrational trials of pediatric venous thromboembolism (VTE) treatment are sparse, especially among cancer patients. We conducted a prospective,...
Data from registrational trials of pediatric venous thromboembolism (VTE) treatment are sparse, especially among cancer patients. We conducted a prospective, multicenter, open-label trial (NCT00952380) on dose-finding, safety, and efficacy (measured by 90-day risks of clinically relevant bleeding [CRB] and symptomatic recurrent VTE [srVTE]) of twice-daily subcutaneous dalteparin for acute VTE treatment in patients ≤18 years old. Among 38 patients (cancer, n = 26; noncancer, n = 12), median dalteparin dose requirements per kilogram varied with age but not cancer status. Risks of CRB and srVTE were <4% in cancer and noncancer subgroups. Dalteparin is an important FDA-approved treatment for pediatric VTE, particularly with cancer.
Topics: Adolescent; Anticoagulants; Child; Dalteparin; Hemorrhage; Humans; Neoplasms; Prospective Studies; Venous Thromboembolism
PubMed: 35678616
DOI: 10.1002/pbc.29764 -
Research and Practice in Thrombosis and... May 2022Venous thromboembolism (VTE) is a frequent complication in patients with cancer and a leading cause of morbidity and death.
BACKGROUND
Venous thromboembolism (VTE) is a frequent complication in patients with cancer and a leading cause of morbidity and death.
OBJECTIVES
The objective of the RIETECAT study was to compare the long-term effectiveness and safety of enoxaparin versus dalteparin or tinzaparin for the secondary prevention of VTE in adults with active cancer.
METHODS
We used the data from the multicenter, multinational RIETE registry to compare the rates of VTE recurrences, major bleeding, or death over 6 months in patients with active cancer and acute VTE using full doses of enoxaparin versus dalteparin or tinzaparin, and a multivariable Cox proportional hazard model was used to analyze the primary end point.
RESULTS
From January 2009 to June 2018, 4451 patients with active cancer received full doses of the study drugs: enoxaparin, 3526 patients; and dalteparin or tinzaparin, 925 (754 + 171) patients. There was limited difference in VTE recurrences (2.0% vs 2.5%) and mortality rate (19% vs 17%) between the enoxaparin and dalteparin or tinzaparin subgroups. However, there was a slight numerical increase in major bleeding (3.1% vs 1.9%). Propensity score matching confirmed that there were no differences in the risk for VTE recurrences (adjusted hazard ratio [aHR], 0.81; 95% confidence interval [CI], 0.48-1.38), major bleeding (aHR, 1.40; 95% CI, 0.80-2.46), or death (aHR, 1.07; 95% CI, 0.88-1.30) between subgroups.
CONCLUSIONS
In RIETECAT, in patients with cancer and VTE receiving full-dose enoxaparin or dalteparin or tinzaparin, no statistically significant differences were observed regarding effectiveness and safety outcomes over a 6-month period.
PubMed: 35664535
DOI: 10.1002/rth2.12736 -
Journal of Medical Cases May 2022Homozygous factor V Leiden (FVL) is a rare condition, occurring in 0.2% of the white population. This disease's rarity and aggressive pathophysiology can represent a...
Homozygous factor V Leiden (FVL) is a rare condition, occurring in 0.2% of the white population. This disease's rarity and aggressive pathophysiology can represent a challenge even to the most experienced clinicians. We report a case of a 35-year-old white man, who presented to the emergency department with a 1-week history of bilateral thigh swelling and pain. His past medical history included homozygous FVL mutation complicated by multiple venous thromboembolic events in the last decade, recent inferior vena cava (IVC) filter placement, diabetes mellitus type 2, and hypertension. Despite being trialed for different anticoagulation therapies over 10 years, including warfarin (international normalized ratio (INR) goal 2 - 3), rivaroxaban, and dalteparin, he continued to thrombose. On admission, while on a therapeutic dose of dalteparin, he was diagnosed with extensive acute deep vein thrombosis involving the bilateral femoral and iliac veins, extending proximally to his IVC filter to the renal veins, and pulmonary embolisms in the bilateral lower lobes and right middle lobe. A heparin drip was initiated, and he developed progressive thrombocytopenia over 96 h. Heparin was discontinued, and he was switched to argatroban. He was diagnosed with heparin-induced thrombocytopenia (HIT) with positive anti-platelet factor 4 (PF4)/heparin antibodies and a serotonin release assay. His platelets trended up to normal levels 5 days after heparin discontinuation. He underwent multiple thrombectomies, thrombolysis, and angioplasty of the abdominal and lower extremity veins. The IVC filter was removed. Secondary thrombophilia workup was remarkable for a positive lupus anticoagulant, which had been negative in the past. The patient was bridged to warfarin, discharged with a higher INR goal of 3 - 3.5, and continuously monitored factor II activity (goal 15-30%). This case illustrates a patient with recurrent episodes of thromboembolic events because of homozygous FVL. This condition's pathophysiology and therapeutic approach has been well studied in heterozygous carriers; however, homozygous individuals represent <1% of cases. Given the rareness of the disease, there are no well-established therapeutic guidelines, and long-term anticoagulation remains the therapeutic cornerstone. This case emphasizes the challenges in managing patients with homozygous FVL and complications that can occur due to this gap in the literature. We suggest further case reports and research studies to shed light on this serious condition and its lifetime complications.
PubMed: 35655628
DOI: 10.14740/jmc3914