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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 -
Journal of Investigative Medicine : the... Mar 2022The evaluation criteria for dosage of low-molecular-weight heparin (LMWH) for pregnant women at high risk of venous thromboembolism (VTE) remain unclear. A retrospective...
The evaluation criteria for dosage of low-molecular-weight heparin (LMWH) for pregnant women at high risk of venous thromboembolism (VTE) remain unclear. A retrospective study was performed to investigate the relative appropriate LMWH administration strategy and dosage for pregnant women at risk of VTE. 219 pregnant women with perinatal and postpartum VTE were reviewed and divided into group A (fixed dose group: n=73, 5000 IU dalteparin daily for all women), group B (weight group: n=73, 2500 IU dalteparin daily for women less than 50 kg; 5000 IU dalteparin daily for women more than 50 kg), and group C (anti-factor Xa (FXa) + weight group: n=73, 5000 IU once daily for women less than 50 kg; 7500 IU once daily for women weighing 50-80 kg; 10,000 IU once daily for women weighing over 80 kg). Further dose administration was adjusted according to peak anti-FXa level, maintaining the peak at the 0.5-1.0 IU/mL range. Women in group C presented lower incidence of VTE and other pregnancy complications than group A and group B. Adjusting the dosage of LMWH according to both weight and anti-FXa level of pregnant women not only prevented VTE but also reduced the risk of postpartum hemorrhage induced by LMWH administration. In addition, adjusting the dose of LMWH according to anti-FXa level and body weight also affected the recurrence of VTE and the occurrence of postpartum hemorrhage in pregnant women.
Topics: Anticoagulants; Dalteparin; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Postpartum Hemorrhage; Pregnancy; Pregnant Women; Retrospective Studies; Venous Thromboembolism
PubMed: 34921124
DOI: 10.1136/jim-2021-002050 -
The Cochrane Database of Systematic... Dec 2021Compared with people without cancer, people with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE. (Review)
Review
BACKGROUND
Compared with people without cancer, people with cancer who receive anticoagulant treatment for venous thromboembolism (VTE) are more likely to develop recurrent VTE.
OBJECTIVES
To compare the efficacy and safety of three types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the initial treatment of VTE in people with cancer.
SEARCH METHODS
We performed a comprehensive search in the following major databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid) and Embase (via Ovid). We also handsearched conference proceedings, checked references of included studies, and searched for ongoing studies. This update of the systematic review is based on the findings of a literature search conducted on 14 August 2021.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing the benefits and harms of LMWH, UFH, and fondaparinux in people with cancer and objectively confirmed VTE.
DATA COLLECTION AND ANALYSIS
Using a standardised form, we extracted data - in duplicate - on study design, participants, interventions, outcomes of interest, and risk of bias. Outcomes of interest included all-cause mortality, symptomatic VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and thrombocytopenia. We assessed the certainty of evidence for each outcome using the GRADE approach.
MAIN RESULTS
Of 11,484 identified citations, 3073 were unique citations and 15 RCTs fulfilled the eligibility criteria, none of which were identified in the latest search. These trials enrolled 1615 participants with cancer and VTE: 13 compared LMWH with UFH; one compared fondaparinux with UFH and LMWH; and one compared dalteparin with tinzaparin, two different types of low molecular weight heparin. The meta-analyses showed that LMWH may reduce mortality at three months compared to UFH (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.40 to 1.10; risk difference (RD) 57 fewer per 1000, 95% CI 101 fewer to 17 more; low certainty evidence) and may reduce VTE recurrence slightly (RR 0.69, 95% CI 0.27 to 1.76; RD 30 fewer per 1000, 95% CI 70 fewer to 73 more; low certainty evidence). There were no data available for bleeding outcomes, postphlebitic syndrome, quality of life, or thrombocytopenia. The study comparing fondaparinux with heparin (UFH or LMWH) found that fondaparinux may increase mortality at three months (RR 1.25, 95% CI 0.86 to 1.81; RD 43 more per 1000, 95% CI 24 fewer to 139 more; low certainty evidence), may result in little to no difference in recurrent VTE (RR 0.93, 95% CI 0.56 to 1.54; RD 8 fewer per 1000, 95% CI 52 fewer to 63 more; low certainty evidence), may result in little to no difference in major bleeding (RR 0.82, 95% CI 0.40 to 1.66; RD 12 fewer per 1000, 95% CI 40 fewer to 44 more; low certainty evidence), and probably increases minor bleeding (RR 1.53, 95% CI 0.88 to 2.66; RD 42 more per 1000, 95% CI 10 fewer to 132 more; moderate certainty evidence). There were no data available for postphlebitic syndrome, quality of life, or thrombocytopenia. The study comparing dalteparin with tinzaparin found that dalteparin may reduce mortality slightly (RR 0.86, 95% CI 0.43 to 1.73; RD 33 fewer per 1000, 95% CI 135 fewer to 173 more; low certainty evidence), may reduce recurrent VTE (RR 0.44, 95% CI 0.09 to 2.16; RD 47 fewer per 1000, 95% CI 77 fewer to 98 more; low certainty evidence), may increase major bleeding slightly (RR 2.19, 95% CI 0.20 to 23.42; RD 20 more per 1000, 95% CI 14 fewer to 380 more; low certainty evidence), and may reduce minor bleeding slightly (RR 0.82, 95% CI 0.30 to 2.21; RD 24 fewer per 1000, 95% CI 95 fewer to 164 more; low certainty evidence). There were no data available for postphlebitic syndrome, quality of life, or thrombocytopenia.
AUTHORS' CONCLUSIONS
Low molecular weight heparin (LMWH) is probably superior to UFH in the initial treatment of VTE in people with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review. The decision for a person with cancer to start LMWH therapy should balance the benefits and harms and consider the person's values and preferences.
Topics: Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Venous Thromboembolism
PubMed: 34878173
DOI: 10.1002/14651858.CD006649.pub8 -
Journal of Pharmaceutical and... Feb 2022Low molecular weight heparins (LMWHs) are heterogeneous mixtures of glycosaminoglycan chains composed of mixture of different lengths and substitution patterns....
Low molecular weight heparins (LMWHs) are heterogeneous mixtures of glycosaminoglycan chains composed of mixture of different lengths and substitution patterns. Structural characterization and quality control of LMWHs have always been challenging. The Chinese drug regulatory authorities have been committed to improve the supervision standards of LMWHs to better regulate the quality and safety of LMWHs in current Chinese market. In the present paper, 80 batches of three types LMWHs (dalteparin, enoxaparin and naldroparin) marketed in China from different manufacturers were studied by H NMR experiments and chemometric analysis. The method can be used not only to monitor impurities and contaminants, but also to check the batch-to-batch consistency of each manufacture. Moreover, for the biosimilar LMWHs from different manufactures, they can be differentiated and clustered according to their slightly different structural compositions originated from production process. By using this method, the quality and safety of LMWHs marketed in China were initially assessed.
Topics: Anticoagulants; Chemometrics; Enoxaparin; Heparin, Low-Molecular-Weight; Magnetic Resonance Spectroscopy; Quality Control
PubMed: 34864594
DOI: 10.1016/j.jpba.2021.114472 -
Chest Mar 2022Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated VTE. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Direct oral anticoagulants (DOACs) are an alternative to low-molecular-weight heparin for treating cancer-associated VTE.
RESEARCH QUESTION
Is rivaroxaban as efficient and safe as dalteparin to treat patients with cancer-associated VTE?
STUDY DESIGN AND METHODS
In a randomized open-label noninferiority trial, patients with active cancer who had proximal DVT, pulmonary embolism (PE), or both were assigned randomly to therapeutic doses of rivaroxaban or dalteparin for 3 months. The primary outcome was the cumulative incidence of recurrent VTE, a composite of symptomatic or incidental DVT or PE, and worsening of pulmonary vascular or venous obstruction at 3 months.
RESULTS
Of 158 randomized patients, 74 and 84 patients were assigned to receive rivaroxaban and dalteparin, respectively. Mean age was 69.4 years, and 115 patients (76.2%) had metastatic disease. The primary outcome occurred in 4 and 6 patients in the rivaroxaban and dalteparin groups, respectively (both the intention-to-treat and per-protocol populations: cumulative incidence, 6.4% vs 10.1%; subdistribution hazard ratio [SHR], 0.75; 95% CI, 0.21-2.66). Major bleeding occurred in 1 and 3 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 1.4% vs 3.7%; SHR, 0.36; 95% CI, 0.04-3.43). Major or clinically relevant nonmajor bleeding occurred in 9 and 8 patients in the rivaroxaban and dalteparin groups, respectively (cumulative incidence, 12.2% vs 9.8%; SHR, 1.27; 95% CI, 0.49-3.26). Overall, 19 patients (25.7%) and 20 patients (23.8%) died in the rivaroxaban and dalteparin groups, respectively (hazard ratio, 1.05; 95% CI, 0.56-1.97).
INTERPRETATION
In this trial comparing rivaroxaban and dalteparin in the treatment of cancer-associated VTE, the number of patients was insufficient to reach the predefined criteria for noninferiority, but efficacy and safety results were consistent with those previously reported with DOACs. An updated meta-analysis of randomized trials comparing DOACs with low-molecular-weight heparin in patients with cancer-associated VTE is provided.
TRIAL REGISTRY
ClinicalTrials.gov; No.: NCT02746185; URL: www.
CLINICALTRIALS
gov.
Topics: Aged; Anticoagulants; Dalteparin; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism
PubMed: 34627853
DOI: 10.1016/j.chest.2021.09.037 -
BMC Pregnancy and Childbirth Oct 2021To compare three commonly used low-molecular-weight heparins (LWMHs) in the treatment of recurrent spontaneous abortion (RSA) by evaluating the anti-Xa peak levels and... (Comparative Study)
Comparative Study Observational Study
Effect of low-molecular-weight heparins on anti-Xa peak levels and adverse reactions in Chinese patients with recurrent spontaneous abortion: a single-center, observational study.
OBJECTIVE
To compare three commonly used low-molecular-weight heparins (LWMHs) in the treatment of recurrent spontaneous abortion (RSA) by evaluating the anti-Xa peak levels and adverse reactions.
METHODS
In this single-center, observational study, we enrolled 310 patients with RSA in whom anti-Xa levels were measured during pregnancy. Patients were divided into three groups according to the LMWH they used: the nadroparin group, enoxaparin group and dalteparin group. We compared the peak anti-Xa levels and the coagulation status of each group, and analyzed the incidence of adverse reactions, including local allergy, liver and renal dysfunction, and the impact on platelet.
RESULTS
Patients in the enoxaparin group had a higher anti-Xa peak level than those in the nadroparin group (0.80 ± 0.22 IU/ml vs. 0.61 ± 0.24 IU/ml; P < 0.0001), although most patients in the three groups reached the target concentration of anti-Xa. Furthermore, patients in the enoxaparin group had a more stable anti-Xa levels during pregnancy. In addition, patients in the nadroparin group had a higher rate of local allergy than those in the enoxaparin group (60.5% vs. 42.5%; P = 0.004) and those in the dalteparin group (60.5% vs. 33.3%; P = 0.002). Further examination by the type of local allergy indicated a dramatic difference in pruritus and induration between the nadroparin group and the other two groups. No difference was found in the incidence of liver and renal dysfunction and thrombocytopenia.
CONCLUSION
Compared with nadroparin and daltepatin, enoxaparin showed a better performance regarding anti-Xa levels and the incidence of adverse reactions in the treatment of RSA.
Topics: Abortion, Habitual; Adult; Anticoagulants; Asian People; Blood Coagulation; China; Dalteparin; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Enoxaparin; Factor Xa Inhibitors; Female; Heparin, Low-Molecular-Weight; Humans; Incidence; Nadroparin; Pregnancy
PubMed: 34620101
DOI: 10.1186/s12884-021-04161-1 -
BMC Veterinary Research Sep 2021Lobular dissecting hepatitis (LDH) is a rare form of canine liver cirrhosis that may be accompanied by portal hypertension in American Cocker Spaniels. In human patients...
BACKGROUND
Lobular dissecting hepatitis (LDH) is a rare form of canine liver cirrhosis that may be accompanied by portal hypertension in American Cocker Spaniels. In human patients with liver cirrhosis, portal vein thrombosis (PVT) is a common complication. However, PVT has not been reported in dogs with LDH. Herein, we describe the long-term follow-up of PVT in an American Cocker Spaniel with LDH.
CASE PRESENTATION
An 8-year-old neutered male American Cocker Spaniel presented with a 1-month history of severe abdominal effusion. The dog was histopathologically diagnosed with LDH and treated with low-dose prednisolone on day 14. On day 115, computed tomography angiography (CTA) confirmed the presence of a thrombus in the portal vein. Therefore, the dog was subcutaneously administered with the anticoagulant dalteparin, and low-dose prednisolone was continued. As a follow-up for PVT, CTA examinations were performed on days 207, 515, 886, and 1168, and the dog's antithrombin and D-dimer levels were measured. Following anticoagulant therapy, the dog was confirmed to have gradually increased antithrombin activity and decreased D-dimer concentrations. In addition, although the thrombus was confirmed to be in the same area of the portal vein system by CTA, atrophy and increased CT values due to organization were observed during the follow-up period. The dog's condition remained stable without clinical signs until day 1112 when it developed hepatic encephalopathy. The dog died on day 1208. On postmortem examination, histopathologically, the liver showed marked bile duct hyperplasia and fibrosis with chronic thrombus in the portal vein.
CONCLUSIONS
This case demonstrated that low-dose glucocorticoid combined with dalteparin allowed long-term follow-up of PVT in an American Cocker Spaniel with LDH.
Topics: Animals; Anticoagulants; Computed Tomography Angiography; Dalteparin; Dog Diseases; Dogs; Follow-Up Studies; Hepatitis; Liver Cirrhosis; Male; Portal Vein; Prednisolone; Venous Thrombosis
PubMed: 34592989
DOI: 10.1186/s12917-021-03017-2 -
The Bone & Joint Journal Oct 2021The aim of this study is to compare the effectiveness and safety of thromboprophylactic treatments in patients undergoing primary total knee arthroplasty (TKA). (Comparative Study)
Comparative Study Observational Study
AIMS
The aim of this study is to compare the effectiveness and safety of thromboprophylactic treatments in patients undergoing primary total knee arthroplasty (TKA).
METHODS
Using nationwide medical registries, we identified patients with a primary TKA performed in Denmark between 1 January 2013 and 31 December 2018 who received thromboprophylactic treatment. We examined the 90-day risk of venous thromboembolism (VTE), major bleeding, and all-cause mortality following surgery. We used a Cox regression model to compute hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome, pairwise comparing treatment with dalteparin or dabigatran with rivaroxaban as the reference. The HRs were both computed using a multivariable and a propensity score matched analysis.
RESULTS
We identified 27,736 primary TKA patients who received thromboprophylactic treatment (rivaroxaban (n = 18,846); dalteparin (n = 5,767); dabigatran (n = 1,443); tinzaparin (n = 1,372); and enoxaparin (n = 308)). In the adjusted multivariable analysis and compared with rivaroxaban, treatment with dalteparin (HR 0.68 (95% CI 0.49 to 0.92)) or dabigatran (HR 0.31 (95% CI 0.13 to 0.70)) was associated with a decreased risk of VTE. No statistically significant differences were observed for major bleeding or all-cause mortality. The propensity score matched analysis yielded similar results.
CONCLUSION
Treatment with dalteparin or dabigatran was associated with a decreased 90-day risk of VTE following primary TKA surgery compared with treatment with rivaroxaban. Cite this article: 2021;103-B(10):1571-1577.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithrombins; Arthroplasty, Replacement, Knee; Dabigatran; Dalteparin; Denmark; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Perioperative Care; Postoperative Complications; Postoperative Hemorrhage; Proportional Hazards Models; Registries; Rivaroxaban; Tinzaparin; Venous Thromboembolism; Young Adult
PubMed: 34587805
DOI: 10.1302/0301-620X.103B10.BJJ-2021-0023.R1 -
Thrombosis Research Nov 2021Heparin-induced thrombocytopenia in pregnancy is an uncommon phenomenon which rarely occurs in the first trimester. Therapeutic options and duration of therapeutic...
Heparin-induced thrombocytopenia in pregnancy is an uncommon phenomenon which rarely occurs in the first trimester. Therapeutic options and duration of therapeutic anticoagulation are varied amongst reported published cases. We report a 41-year-old female with confirmed HIT following anticoagulation with dalteparin for deep vein thrombosis (DVT). She was treated with therapeutic fondaparinux for 3 months followed by prophylaxis dosage until delivery and for 6 weeks thereafter. A review of reported cases of the development of HIT in the first trimester and subsequent clinical management is discussed.
PubMed: 34547613
DOI: 10.1016/j.thromres.2021.09.001 -
Thrombosis and Haemostasis May 2022Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients with CAT and are not recommended for practice.
OBJECTIVES
To compare methods of estimating clinically relevant (major and clinically relevant nonmajor) bleeding risk in patients with CAT: (1) existing risk scores for bleeding in venous thromboembolism, (2) pragmatic classification based on cancer type, and (3) new prediction model.
METHODS
In a posthoc analysis of the Hokusai VTE Cancer study, a randomized trial comparing edoxaban with dalteparin for treatment of CAT, seven bleeding risk scores were externally validated (ACCP-VTE, HAS-BLED, Hokusai, Kuijer, Martinez, RIETE, and VTE-BLEED). The predictive performance of these scores was compared with a pragmatic classification based on cancer type (gastrointestinal; genitourinary; other) and a newly derived competing risk-adjusted prediction model based on clinical predictors for clinically relevant bleeding within 6 months after CAT diagnosis with nonbleeding-related mortality as the competing event ("CAT-BLEED").
RESULTS
Data of 1,046 patients (149 events) were analyzed. Predictive performance of existing risk scores was poor to moderate (C-statistics: 0.50-0.57; poor calibration). Internal validation of the pragmatic classification and "CAT-BLEED" showed moderate performance (respective C-statistics: 0.61; 95% confidence interval [CI]: 0.56-0.66, and 0.63; 95% CI 0.58-0.68; good calibration).
CONCLUSION
Existing risk scores for bleeding perform poorly after CAT. Pragmatic classification based on cancer type provides marginally better estimates of clinically relevant bleeding risk. Further improvement may be achieved with "CAT-BLEED," but this requires external validation in practice-based settings and with other DOACs and its clinical usefulness is yet to be demonstrated.
Topics: Anticoagulants; Hemorrhage; Humans; Neoplasms; Risk Factors; Thrombosis; Venous Thromboembolism
PubMed: 34544170
DOI: 10.1055/s-0041-1735251