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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 -
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 -
Hematology Reports Mar 2022Patients with haemophilia present a significant challenge when admitted into the intensive care unit. To prevent haemorrhagic complications related to the infection or...
Patients with haemophilia present a significant challenge when admitted into the intensive care unit. To prevent haemorrhagic complications related to the infection or due to invasive procedures factor (F) VIII/IX must be substituted. As thromboembolic complications are frequent among critically ill COVID-19 patients, thromboprophylaxis is also applied to patients with haemophilia. This requires careful monitoring of FVIII/IX activity as well as other haemostatic parameters, such as D-dimer and antiXa. We describe a 44-year old patient with mild haemophilia A (FVIII activity of 6%), who required a prolonged intensive care unit stay due to a severe SARS-CoV-2 infection. FVIII was substituted via boluses, and dalteparin was given according to recommendations. The patient successfully recovered from the disease.
PubMed: 35466179
DOI: 10.3390/hematolrep14020015 -
Clinical and Applied... 2022Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. On the basis of results from randomized controlled trials, direct... (Review)
Review
Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. On the basis of results from randomized controlled trials, direct oral anticoagulants (DOACs) are now recommended for the treatment of cancer-associated VTE. The decision to use a DOAC requires consideration of bleeding risk, particularly in patients with gastrointestinal (GI) malignancies, the cost-benefit and convenience of oral therapy, and patient preference. While efficacy with apixaban, edoxaban, and rivaroxaban versus dalteparin has been consistent in the treatment of cancer-associated VTE, heterogeneity is evident with respect to major GI bleeding, with an increased risk with edoxaban and rivaroxaban but not apixaban. Although cost and accessibility vary in different countries of Latin America, DOACs should be considered for the long-term treatment of cancer-associated VTE in all patients who are likely to benefit. Apixaban may be the preferred DOAC in patients with GI malignancies and LMWH may be preferred for patients with upper or unresected lower GI tumors. Vitamin K antagonists should only be used for anticoagulation when DOACs and low molecular weight heparin are inaccessible or unsuitable.
Topics: Administration, Oral; Anticoagulants; Blood Coagulation; Humans; Incidence; Latin America; Neoplasms; Venous Thromboembolism
PubMed: 35261295
DOI: 10.1177/10760296221082988 -
IJU Case Reports Mar 2022We present a case of novel coronavirus disease-2019 that underwent combination therapy with nivolumab and ipilimumab for metastatic renal cell carcinoma.
INTRODUCTION
We present a case of novel coronavirus disease-2019 that underwent combination therapy with nivolumab and ipilimumab for metastatic renal cell carcinoma.
CASE PRESENTATION
A 50-year-old man complained of anorexia and weight loss. Contrast-enhanced computed tomography revealed a solid mass of 57 mm in diameter with cysts in the right kidney, along with liver, lung, and multiple bone metastases. Computed tomography-guided biopsy of the right kidney was performed, and a diagnosis of clear cell renal cell carcinoma was made. Three weeks after nivolumab and ipilimumab administration, the patient contracted coronavirus disease-2019. Anticoagulation therapy (dalteparin) was administered for 4 days once infection was confirmed, after which dexamethasone was administered for 10 days. The patient survived without experiencing worsened respiratory symptoms.
CONCLUSION
We administered nivolumab and ipilimumab combination therapy as treatment for metastatic renal cell carcinoma. No side effects or immune-related adverse events were observed for a short time.
PubMed: 35252798
DOI: 10.1002/iju5.12412 -
Cancers Jan 2022We evaluated the safety and efficacy of direct oral anticoagulants (DOACs) versus subcutaneous dalteparin for cancer-associated venous thromboembolism (CA-VTE) in...
A Phase II Study to Compare the Safety and Efficacy of Direct Oral Anticoagulants versus Subcutaneous Dalteparin for Cancer-Associated Venous Thromboembolism in Patients with Advanced Upper Gastrointestinal, Hepatobiliary and Pancreatic Cancer: PRIORITY.
BACKGROUND
We evaluated the safety and efficacy of direct oral anticoagulants (DOACs) versus subcutaneous dalteparin for cancer-associated venous thromboembolism (CA-VTE) in patients with advanced upper gastrointestinal (GI) tract, hepatobiliary, or pancreatic cancer.
METHODS
This was a multicenter, randomized, open-label, phase II trial in five centers. Patients randomly received rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily)/apixaban (10 mg twice daily for the first 7 days, then 5 mg twice daily) or dalteparin (200 IU/kg once daily for the first month, then 150 IU/kg once daily). Randomization was stratified by the Eastern Cooperative Oncology Group Performance Status, primary cancer type, active chemotherapy, and participating centers. The primary endpoint was the rates of clinically relevant bleeding (CRB) in the full analysis set (FAS).
RESULTS
A total of 90 patients were randomly assigned to the DOAC ( = 44) and dalteparin groups ( = 46) in FAS. CRB and major bleeding (MB) rates were 34.1% and 13.0% ( = 0.018) and 18.2% and 4.3% ( = 0.047) for the DOAC and dalteparin groups, respectively. Time to CRB and MB was higher in the DOAC group than in the dalteparin group (hazard ratio [HR] 2.83; = 0.031 and HR 4.32; = 0.064). Cancer involvement at the GI mucosa was also a significant risk factor for CRB. Recurrent CA-VTE occurred in 2.3% and 2.2% of patients given DOAC and dalteparin, respectively ( = 1.000).
CONCLUSION
DOAC therapy further increased the risk of bleeding compared with dalteparin in patients with active advanced upper GI tract, hepatobiliary, or pancreatic cancer, suggesting that extra caution should be taken when selecting anticoagulants for CA-VTE.
PubMed: 35158827
DOI: 10.3390/cancers14030559 -
CMAJ : Canadian Medical Association... Jan 2022
Topics: Administration, Intravenous; Adult; Anterior Compartment Syndrome; Anticoagulants; Dalteparin; Drug Overdose; Fasciotomy; Hemorrhage; Heparin Antagonists; Humans; Male; Protamines; Suicide, Attempted
PubMed: 35101871
DOI: 10.1503/cmaj.211083 -
Effects of dalteparin on anti-Xa activities cannot be predicted in critically ill COVID-19 patients.British Journal of Clinical Pharmacology Jun 2022Critically ill COVID-19 patients are at high risk of thromboembolic events despite routine-dosed low-molecular-weight heparin thromboprophylaxis. However, in recent...
Critically ill COVID-19 patients are at high risk of thromboembolic events despite routine-dosed low-molecular-weight heparin thromboprophylaxis. However, in recent randomized trials increased-intensity thromboprophylaxis seemed futile and possibly even harmful. In this explorative pharmacokinetic (PK) study we measured anti-Xa activities on frequent timepoints in 15 critically ill COVID-19 patients receiving dalteparin and performed PK analysis by nonlinear mixed-effect modelling. A linear one-compartment model with first-order kinetics provided a good fit. However, wide interindividual variation in dalteparin absorption (variance 78%) and clearance (variance 34%) was observed, unexplained by routine clinical covariates. Using the final PK model for Monte Carlo simulations, we predicted increased-intensity dalteparin to result in anti-Xa activities well over prophylactic targets (0.2-0.4 IU/mL) in the majority of patients. Therapeutic-intensity dalteparin results in supratherapeutic anti-Xa levels (target 0.6-1.0 IU/mL) in 19% of patients and subtherapeutic levels in 22%. Therefore, anti-Xa measurements should guide high-intensity dalteparin in critically ill COVID-19 patients.
Topics: Anticoagulants; Critical Illness; Dalteparin; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Venous Thromboembolism; COVID-19 Drug Treatment
PubMed: 34965610
DOI: 10.1111/bcp.15208 -
Cureus Nov 2021Venous stroke is an infrequent complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Coronavirus disease 2019 (COVID-19) acts as a...
Venous stroke is an infrequent complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Coronavirus disease 2019 (COVID-19) acts as a causative factor for thromboembolic events such as pulmonary embolism (PE), deep vein thrombosis (DVT), stroke (ischemic or hemorrhagic), and myocardial infarction. We report a case of cerebral venous thrombosis (CVT) following severe COVID-19 infection, with co-incidence of pulmonary thromboembolism. A 39-year-old English lady presented with fever and cough; subsequently, she was diagnosed with COVID-19 and was managed in the high dependency unit (HDU) due to the severity of symptoms; she received dexamethasone and tocilizumab. Her condition improved and she was discharged, but presented again after 15 days due to headache and left-sided weakness. Her neurological examination confirmed nystagmus, past pointing, and dysdiadochokinesia positive on the left side. Initial blood investigations showed D-dimer being raised at 1875 ng/ml. Head CT venogram reported evidence of thrombus in the superior sagittal sinus, left transverse sinus, and inferior sagittal sinus consistent with venous sinus thrombosis. She also underwent CT pulmonary angiogram (CTPA) which revealed lingular acute segmental PE and patchy ground-glass shadowing throughout both lung fields, confirming recent infective COVID-19 changes. She was started on a therapeutic dose of dalteparin (low-molecular-weight heparin). Luckily she made a good recovery from her neurological symptoms. Like this case and many other reported cases, COVID-19 acts as an independent risk factor for increased coagulopathy. Clinicians should maintain a high index of suspicion for CVT to aid in timely diagnosis and prompt treatment to save lives.
PubMed: 34926071
DOI: 10.7759/cureus.19602