Low Molecular Weight Heparin Therapy Research Articles

Treatment of cancer-associated thrombosis: The evolution of anticoagulant choice and clinical insights into practical management.

Low-molecular-weight heparin (LMWH) therapy is recommended over vitamin K antagonists (VKAs) for the treatment of cancer-associated thrombosis (CAT) and extended therapy is recommended in those with active cancer to prevent recurrent thrombosis. However, the inconvenience of daily subcutaneous injections and the cost of LMWH therapy hinder long-term use. Observational data demonstrate that persistence with LMWH therapy is low in clinical practice and that many patients are switched to oral alternatives - namely VKAs and direct oral anticoagulants (DOACs). Recently, the efficacy and safety of apixaban, edoxaban, and rivaroxaban versus LMWH therapy for the treatment of CAT have been demonstrated in randomized trials. This review provides a critical evaluation of studies with DOACs in this setting and an update on the guidance regarding anticoagulant use for the treatment of CAT. In recognition of the heterogeneity of patients with cancer and the challenges of CAT, patient cases with expert clinical perspectives are presented.

Spontaneous abdominal bleeding associated with SARS-CoV-2 infection: causality or coincidence?

Authors present 6 cases of abdominal bleeding associated with COVID-19, representing 1.35% of all hospitalized COVID-19 patients and hypothesize that there could be, although not very frequently, a relationship between SARS-CoV2 and bleeding. They excluded a side effect of the low molecular weight heparin therapy that all patients underwent during the course of the disease or other possible causes. Alterations of the coagulation state or a weakness of the vascular wall due toa presumed endotheliitis SARS-CoV-2 infection induced, are hypothesized by the authors. Investigation and follow-up for possible hemorrhagic problems in patients with COVID-19 is recommended. In particular, clinicians should be vigilant about retroperitoneal hemorrhage in COVID-19 patients. In addition to the fact that these patients are being treated with anticoagulants, anemia and abdominal pain are the signs that should lead us to suspect this type of haemorrhage. More studies are needed to understand if COVID-19 can be directly associated with bleeding. (www.actabiomedica.it)

Clinical study of anticoagulant therapy in patients with severe coronavirus disease: A single-center retrospective analysis

OBJECTIVE: The prognosis of COVID-19 is related to thrombotic events. This study investigated prognostic risk factors, anticoagulant therapy effects, and potential instruction of treatment or prognostic with D-dimer in patients with severe COVID-19 receiving anticoagulant therapy. MATERIALS AND METHODS: We undertook a retrospective study of 87 severe COVID-19 patients who had prophylactic low-molecular-weight heparin (LMWH) therapy. Patients were divided into two groups according to whether high-flow oxygen therapy was required during hospitalization: Better and poor prognoses. RESULTS: Multivariate logistic regression using risk factors measured before LMWH therapy revealed that older age (P 4 μg/ml fibrin equivalent unit (FEU), 33 (70.6%) and 18 (45%) had better prognosis (P = 0.012), respectively. CONCLUSION: Anticoagulant therapy reduced inflammation in patients with better prognosis; conversely, minimal effect was observed in those with poor prognosis. During LMWH therapy patients with D-dimer levels, patients receiving anticoagulant therapy at D-dimer levels ≤4 μg/ml FEU had a better prognosis than those at >4 μg/ml FEU.

Impact of proactive low-molecular weight heparin therapy on outcomes in COVID-1.

Low molecular weight heparin (LMWH) may provide beneficial effects on outcomes of COVID-19. We aimed to examine the impact of LMWH treatment on clinical outcomes (duration of hospitalization, admission to intensive care unit, the requirement for mechanical ventilation, and death) of COVID-19 patients with normal D-dimer levels at admission. Coronavirus disease-2019 (COVID-19) predisposes patients to arterial and venous thrombosis. In this retrospective, multicentre and observational study we analysed the data of 308 confirmed COVID-19 patients with normal D-dimer levels at initial admission. After propensity score matching (PSM) patients were grouped; Group 1; patients who received LMWH with D-dimer ≤0.5 mg/L, Group 2; patients who received LMWH after D-dimer levels exceeded 0.5 mg/L, and Group 3; patients who did not receive LMWH. After PSM, each group comprised 40 patients. The patients in Group1 had the best clinical outcomes compared to the other groups. Group 3 had the worst clinical outcomes (p<0.005). The benefit of LMWH increased with early prophylactic therapy especially when started while the D-dimer levels were ≤0.5 mg/L. Our results strongly suggest that proactive LMWH therapy improves clinical outcomes in hospitalized COVID-19 patients even with normal D-dimer levels (≤ 0.5 mg/L) (Tab. 3, Fig. 2, Ref. 34).

Effect of combined WeChat video and comprehensive medical therapy on severe COVID‐19 with moderate Alzheimer's disease: A case report

ObjectiveWe present a case report of recovery from severe COVID ‐ 19 (novel coronavirus 2019) in a patient with cognitive decline (84‐year old, female), behavioral and psychiatric symptoms, hip arthroplasty, sacroiliac decubital necrosis, cachexia, after comprehensive therapy.BackgroundBecause of cognitive and behavioral disorders, patients with Alzheimer’s disease have poor coordination of treatment especially in an unfamiliar environment. Communicating with close family members through WeChat video can relieve patients' anxiety and other mental symptoms, leading to better cooperating with drug treatment and nasal feeding diet.MethodsPatient received 1 hour daily WeChat video communication with her son at isolation ward, including psychological comfort, care and positive words. The WeChat video communication were last for 4 weeks, during this time, the elderly patient was also treated with methylprednisolone (for 5 days), immunoglobulin (for 5 days), ulinastatin, thymus methoxide (for twice a week), acetylcysteine, antibiotics, low molecular weight heparin, probiotics, nutrition and other symptomatic support therapy.ResultsBefore WeChat video communication about 4 weeks, the patient refused medical treatment, consisting of extraction of infusion set and removal of gastric tube, which greatly affects the treatment of drugs and the nutritional intake of patients; and the state of the patient’s condition became even worse. However, after 4 weeks WeChat video communication, the patient showed a significant improvement in the Mini‐mental state examination scores from 8 to 12 (Education: illiterate) and in the Neuropsychiatric questionnaire scores from 35 to 10. Besides, after 4 weeks WeChat video communication and comprehensive therapy, the patient’s pneumonia improved significantly and the nucleic acid test turned negative.ConclusionsWeChat video communication may be a promising noninvasive approach for patients with Alzheimer’s Disease, which may help alleviate neuropsychiatric behavioral symptoms and can be more cooperative with medical workers.

First three months of anticoagulation for venous thromboembolism in non-cancer patients: LMWH VS. VKAs. Findings from the RIETE registry

BackgroundThe use of low-molecular-weight heparin (LMWH) for long-term therapy of venous thromboembolism (VTE) in patients without cancer has not been consistently evaluated. MethodsWe used the data in the RIETE registry to compare the 3-month outcomes (VTE recurrences, major bleeding or death) in non-cancer patients with VTE, according to long-term therapy with LMWH or vitamin K antagonists (VKAs). ResultsAs of March 2018, 14,582 non-cancer patients with VTE had received initial therapy with LMWH and then switched to VKAs, while 9151 were prescribed LMWH for initial and long-term therapy. Overall, 11,494 had initially presented with pulmonary embolism (PE) and 12,239 with isolated deep vein thrombosis (DVT). Among 11,494 patients initially presenting with PE, 84 had VTE recurrences, 204 major bleeding and 406 died. Among 12,239 patients with isolated DVT, 133 developed VTE recurrences, 137 bled and 289 died. On propensity score analysis, PE patients on long-term LMWH therapy were at increased risk for PE recurrences (OR: 3.30; 95%CI: 1.67–6.48), major bleeding (OR: 1.68; 95%CI: 1.21–2.32) or death (OR: 3.16; 95%CI: 2.43–4.09) compared with those receiving VKAs. In patients with DVT, those on long-term LMWH also were at increased risk for PE recurrences (OR: 2.31; 95%CI: 1.13–4.73), major bleeding (OR 2.28; 95%CI: 1.51–3.44) or death (OR: 2.32; 95%CI: 1.54–3.51). ConclusionsIn the RIETE non-cancer patients with VTE, long-term therapy with VKAs was associated with a lower risk for recurrences, major bleeding or death.

A case report of arterial and venous thromboembolism in a patient with severe COVID-19 pneumonia.

BackgroundCoronavirus disease 2019 (COVID-19) has spread rapidly worldwide since the outbreak originated in Wuhan, China in December 2019. Cardiovascular complications in patients with severe COVID-19 have been reported and are associated with a worse outcome. Coagulopathy is one of the most common life-threatening complication increasing mortality; however, little evidence is available regarding prevention strategies or its treatment in COVID-19 patients.Case summaryWe report a case of a 70-year-old woman admitted to hospital with severe COVID-19 bilateral pneumonia who developed severe coagulopathy with multiple both, venous and arterial, embolisms in major vessels such as bilateral pulmonary embolism, acute thrombus in abdominal aorta, and acute thrombotic occlusion of the right iliac common artery. The patient underwent emergent surgical thrombectomy of the right lower limb; in spite of anticoagulant treatment at therapeutic doses, patient presented poor clinical evolution and an infracondylar amputation of right lower limb was made finally. Subsequently, the patient received low molecular weight heparin (LMWH), antibiotics and antiviral therapy improving her renal function and her pneumonia, so she could be discharged safely.DiscussionProthrombotic coagulopathy due to enhanced acute inflammatory response and diffuse intravascular coagulation has been described in severe critical COVID-19 patients. This state of hypercoagulability is associated with organ dysfunction and mortality and may predispose to both, venous and arterial, thromboembolism. Little data are available regarding the best therapeutic and prevention strategies in this scenario, although thrombosis prophylaxis with LMWH has been associated with a better outcome.

Combined hereditary thrombophilias are responsible for poor placental vascularization development and low molecular weight heparins (LMWH) prevent adverse pregnancy outcomes in these patients

Background Even though thrombophilias are associated with negative pregnancy outcomes (PO), there is not a consensus of when thrombophilias should be screened for, or how they affect placental vascularization during pregnancy. Therefore, the main aim of this study was to discover inherited thrombophilias (IHT) in the first trimester in women with otherwise no indications for thrombophilia screening, based on their vascularization parameters. LMWH treatment in improvement of placental vascularization and PO was also assessed. Finally, the classification of thrombophilias based on observed obstetric risks was proposed. Methods Women were included in study based on their poor gestational sac and later utero-placental juncture vascularization signal and screening for inherited thrombophilias. LMWH were then initiated and Resistance index of Uterine artery (RIAU) was followed alongside PO (preterm birth, preeclampsia, placental abruption, intrauterine growth reduction). Study group consisted of women with combined inherited thrombophilias. Control group consisted of patients with inherited thrombophilias who have received LMWH therapy since pregnancy beginning. Findings Out of 219 women, 93 had IHT, and 43 had combined IHT. All pregnancies both in both groups ended up with live births. Vaginal birth was more present in the control group (p < .001), and all women in study group delivered by CS. Premature birth was present in 8.4% of patients in control group, and in 32.55% of the patients in the study (p < .001). PE wasn’t noted, and only 1 case of PA in control group. In the control group, 6.5% patients had IUGR, and 32.55% in the study group (p < .05). Based on RIAU and PO, thrombophilia categories were established: S (severe), MO (moderate), MI (mild) and L (low). Higher risk thrombophilias had higher RIAU later in the pregnancy, earlier pregnancy termination and Intrauterine Growth Reduction (IUGR). Conclusions Thrombophilias should be considered and screened when poor vascularization is noted early in the pregnancy with Doppler sonography. Intervention with LMWH prevents adverse PO in these patients.

Intensive care for seriously ill patients affected by novel coronavirus sars - CoV - 2: Experience of the Crema Hospital, Italy.

Intensive care for seriously ill patients affected by novel coronavirus sars - CoV - 2: Experience of the Crema Hospital, Italy.

Comparing low-molecular-weight heparin dosing for treatment of venous thromboembolism in patients with obesity (RIETE registry)

AbstractBecause of the absence of comparative evidence, current guidelines and product monographs diverge in the dosing of low-molecular-weight heparin (LMWH) for obese patients with venous thromboembolism (VTE). We used the RIETE registry to compare the primary composite outcomes (VTE recurrence, major bleeding, or death) in patients with VTE who weighed >100 kg during LMWH therapy with capped doses of LMWH (18 000 IU/d) vs uncapped doses (>18 000 IU/d). Multivariable logistic regression analysis was used to account for possible confounders. A total of 2846 patients who weighed >100 kg were included: 454 (16%) received capped doses of LMWH, and the remaining 2392 received uncapped doses. Mean (standard deviation) LMWH treatment duration was 14.8 (20.6) and 14.3 (32.3) days, respectively. Thirty-one patients (1.9%) had VTE recurrences, 38 (1.3%) had bleeding episodes, 65 (2.3%) died, and 122 (4.3%) had at least 1 of the composite outcomes. Unadjusted outcome rates revealed that capped dosing was associated with a decrease in the composite outcome (rate ratio, 0.22; 95% confidence interval [CI], 0.04-0.75). Multivariable analysis confirmed that patients who received capped doses had significantly lower rates of the composite outcome (odds ratio, 0.16; 95% CI, 0.04-0.68) while receiving LMWH. These retrospective observational data suggest that capped dosing of LMWH is an acceptable alternative to uncapped dosing based on body weight, given the significantly lower composite event rate of VTE recurrence, major bleeding, and all-cause death.

The effect of anti-Xa monitoring on the safety and efficacy of low-molecular-weight heparin anticoagulation therapy: A systematic review and meta-analysis.

Low-molecular-weight heparin (LMWH) is widely used in the prevention and treatment of venous thromboembolism (VTE), and anti-Xaassay is the gold standard for monitoring LMWH. However, it is still controversial whether monitoring is necessary for patients receiving LMWH therapy. Therefore, we conducted a meta-analysis to explore the effect of anti-Xa monitoring on the safety and efficacy of LMWH anticoagulant therapy. PubMed, EMBASE, Web of Science and The Cochrane Library were searched on 27 May 2019 for eligible studies published in English. Odds ratio (OR) and 95% confidence intervals (CI) were estimated (Mantel-Haenszel method) using Review Manager version 5.3 software. The systematic review and meta-analysis was performed according to the recommendations of the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) statement. Six studies involving 1617 patients were eligible for our meta-analysis, with 724 patients in the anti-Xa monitoring group and 893 patients in the control group. There was no significant difference in the incidence of bleeding events between the two groups, while the anti-Xa monitoring group had a lower incidence of venous thromboembolism events (OR 0.44, 95% CI 0.29-0.68, P=.0002). Subgroup analysis showed that the incidence of venous thromboembolism events in the anti-Xa monitoring group was lower than that in the control group when the trough level was monitored (OR 0.40, 95% CI 0.25-0.63, P<.0001), while there was no significant difference between the two groups when the peak level was monitored. Patients receiving LMWH anticoagulant therapy to prevent VTE can benefit from anti-Xa monitoring, for which the trough level may be the more appropriate time status to monitor.

Do Anti-Factor Xa Levels have any Impact on Pregnancy Outcome in Women with Previous Adverse Outcomes?

Low-molecular-weight heparin (LMWH) is used during pregnancy in women diagnosed with thrombophilia for prevention of thromboembolic events and prevention of recurrent pregnancy loss. Prophylactic dosing does not always achieve target anti-FXa levels of 0.2-0.6 IU/ml. We aimed to determine if anti-FXa levels, measured in the first trimester, have an influence on pregnancy outcome. Eighty-one first-trimester women with a history of adverse pregnancy outcomes under LMWH therapy during pregnancy were enrolled in this study. Anti-FXa levels were measured in the first trimester, and fetal and maternal outcomes were recorded. The mean age of women was 28±4 (19-40) and mean anti-FXa level 0.44±0.93 IU/ml. No bleeding or clotting complications were associated with LMWH administration. Anti-FXa levels did not have a relationship with gestational age at birth, fetal weight, type of delivery, cesarean indications, postpartum bleeding, APGAR scores, or admission to the neonatal intensive care unit (p>0.005). Anti-FXa levels were not correlated with live birth rates. Anti-FXa levels did not have an influence on pregnancy and fetal outcomes. The effect of LMWH on pregnancy outcomes may not be due to anticoagulant activity but other mechanisms.

How we manage Philadelphia-negative myeloproliferative neoplasms in pregnancy.

The combined incidence of classical Philadelphia-negative myeloproliferative neoplasm (MPN) is 6-9/100000 with a peak frequency between 50 and 70years. MPN is less frequent in women of reproductive age. However, for essential thrombocythaemia (ET) in particular there is a second peak in women of reproductive age and 15% of polycythaemia vera (PV) patients are less than 40years of age at the time of diagnosis. Thus these diseases are encountered in women of reproductive potential and may be diagnosed in pregnancy or in women being investigated for recurrent pregnancy loss. The incidence of MPN pregnancies is 3·2/100000 maternities per year in the UK. The majority of data regarding Philadelphia-negative MPNs relates to patients with ET, for which the literature suggests significant maternal morbidity and poor fetal outcome; specifically maternal thrombosis and haemorrhage, miscarriage, pre-eclampsia, intrauterine growth restriction (IUGR), stillbirth and premature delivery as summarised in the recent systematic review and meta-analysis in Blood, 2018, 132, 3046. The literature for PV is more sparse but increasing and is concordant with ET pregnancy outcomes. The literature regarding primary myelofibrosis (PMF) is even more scarce. Treatment options include aspirin, venesection, low molecular weight heparin (LMWH) and cytoreductive therapy. Data and management recommendations are often extrapolated from other pro-thrombotic conditions or from ET to PV and PMF. Women of reproductive age with a diagnosis of MPN should receive information and assurance regarding management and outcome of future pregnancies. From pre-conceptual planning to the post-partum period, women should have access to joint care from an obstetrician with experience of high-risk pregnancies and a haematologist in a multidisciplinary setting. This paper provides an update with regards to Philadelphia-negative MPN in pregnancy, details local practise in an internationally recognised centre for patients with MPN and outlines a future research strategy.

Deep venous thrombosis induced by intravenous thrombogenic drugs

Background: Deep vein thrombosis (DVT) is a major preventable cause of morbidity and mortality worldwide with the potential to cause a dreaded pulmonary embolism (PE). Disease and patient-specific considerations are preferably incorporated into therapeutic options for effective management. Materials and methods: Sixty-eight cases of acute deep vein thrombosis were treated within a period of 3 years from January 2016. All the cases were subjected to routine investigations with the Doppler study of the affected limb. Low molecular weight heparin (dalteparin) was administered in all the cases for a period of 15 days and the Doppler study was repeated at the end of the drug therapy. After the course of low molecular weight heparin, the patients were given acenocoumarol 2mg daily. Estimation of partial thromboplastin time and prothrombin time were performed before starting and during the treatment of the low molecular weight heparin and acenocoumarol regularly. A venogram was done only when the repeated Doppler study revealed unsatisfactory response to low molecular weight heparin therapy. Eight cases underwent thrombectomy and the postoperative period was uneventful. Results: Age group of 21-30 years was most affected (80.8%) with right lower limb being the commonest affected site of injection and associated lesions. Conclusion: DVT in the young population remains a challenge to the evaluating clinician. A variety of disease states can alter the anticoagulant factors. Urgent diagnosis and appropriate intervention carry paramount importance.

D-Dimer Assay May Guide LMWH Treatment in Repeated Biochemical Pregnancy Losses in Women with Positive Antiphospholipid Antibody.

Do D-dimer levels influence the pregnancy outcomes after treatment with low molecular weight heparin (LMWH) in women of recurrent miscarriage (RM), repeated biochemical pregnancy losses (BPL), and a positive test for antiphospholipid antibodies (aPLs)? This study was a retrospective chart review of 569 RM patients who were identified as having a history of BPL and a positive aPL. These patients were grouped into three groups according to their treatment plan including those who received low dose aspirin (LDA) alone (group A), LDA plus LMWH after ovulation therapy (group B), and LDA plus LMWH after pregnancy confirmation (group C). We hypothesized that the administration of LMWH after ovulation increased the rates of live birth. D-dimer may predict the pregnancy outcome after treatment. The live birth rate of group B and group C is significantly higher than group A (86.96% and 66.80% vs. 52.89%, p < 0.0001, respectively). The live birth rate in group A, B, and C with elevated D-dimer is 36.92%, 90.52%, and 61.60% respectively. However, there is no significant difference in live birth rate among those who had normal baseline D-dimer. These results suggest that LMWH therapy is more effective in improving the live birth rate when given after ovulation than after pregnancy confirmation. The plasma D-dimer assay can possibly guide LMWH treatment appropriately.

Paraneoplastički sindrom kao mogući uzrok plućne tromboembolije kod pacijentkinje sa nefrotskim sindromom

A 59-year-old female patient was admitted to the hospital due to suffocation, lower leg swelling, and general weakness. She had been treated previously with immunosuppressive therapy for several years because of focal segmental glomerulosclerosis with nephrotic syndrome. The expected therapeutic response was not accomplished. Upon admission, the following were determined in the laboratory: hypoalbuminemia, hyperlipidemia and nephrotic range proteinuria. X-ray of the lungs showed bilateral pleural effusion, because of which a pleural puncture was performed and which drained 800 mL of fluid. Tumor markers test, breast echosonography and mammography were performed, along with bone scintigraphy, which was done upon the recommendation of an oncologist. Mammography described microcalcifications bilaterally while bone scintigraphy showed pathological accumulation of radiopharmaceuticals in the V thoracic vertebra and sternum corpus, and III and IV ribs on the left. On the fifth day of hospitalization, there was a deterioration of patient's general condition with hypotension, tachycardia and angina, as well as an increase in D-dimer. On the ECG sinus rhythm, f 80 / min, low voltage in standard and unipolar leads. Upon the recommendation of a cardiologist, CT was performed according to the program for pulmonary thromboembolism (PTE), which showed submassive PTE. Low molecular weight heparin therapy was used, along with oxygen therapy with dopaminergics, bronchodilators, human albumin and plasma infusions, statins and transient treatment of hypervolemia by means of hemodialysis. The patient was hospitalized for 61 days due to multiorgan dysfunction. Breast magnetic resonance imaging was not performed due to the poor general condition of the patient. Most likely it was breast cancer with secondary deposits, which was recognized late. PTE, as a probable consequence of paraneoplastic nephrotic syndrome, was diagnosed and treated in a timely manner.

Positive Heparin/PF4 Antibodies and High Mortality Rate: a Retrospective Case-Series Analysis.

IntroductionHeparin-induced thrombocytopenia (HIT) is a potentially lethal complication of unfractionated or low-molecular weight heparin therapy. We aimed to determine the incidence and mortality rate of patients with positive heparin/platelet factor 4 (PF4) antibodies, which is a rapid detection test of HIT.MethodsCoronary artery bypass grafting and mitral and aortic valve surgeries were evaluated. Cardiopulmonary bypass was employed in all patients. The diagnosis of HIT was based on immunological assays. Postoperative complications, mortality rates, and the causes of death were specified in patients with positive heparin/PF4 antibodies.ResultsPostoperative thrombocytopenia was detected in 257 patients. Twenty of these patients undergoing open heart surgery were included in the final analysis. Antibodies against heparin/PF4 complex were positive in 20 patients. The mean body mass index was 28.8±2.3 kg/m2, mean value of left ventricular ejection fraction was 48.3±6.7%, cardiopulmonary bypass time was 113.0±35.0 min, aortic cross-clamping time was 88.0±32.7 min, mean intensive care unit length of stay was 10.9±4.9 days, mean preoperative platelet count was 307.250±88528 platelets/microliter, and mean postoperative platelet count was 243.050±89.354 platelets/microliter. The mean duration of heparin exposure was 6.9±2.9 days. The mortality rate was 45% (nine patients) and 1.2% (three patients) in heparin/PF4 complex positive and negative patients, respectively.ConclusionAlthough the incidence of HIT was low in patients undergoing open heart surgery, an increased rate of early mortality was observed in patients with positive heparin/PF4 antibodies.

Post-pulmonary embolism syndrome phenotyping with systematic multiparametric evaluation: A Prospective Study on 153 patients

Persistence of symptoms and discomfort after pulmonary embolism (PE) is frequent and poorly understood. To identify patients who remained symptomatic 6 months after an acute PE, and to determine factors associated with a 6-months functional impairment. One hundred and fifty-three patients with acute symptomatic PE were prospectively included from February 2015 to January 2017 at the University hospital of Toulouse, France. Clinical and paraclinical data were evaluated at inclusion and after 6 months of follow-up. Six-month follow-up included clinical evaluation, psychiatric survey, echocardiography and functional cardiopulmonary test. Symptomatic patients (i.e. patients with dyspnea and/or chest discomfort) underwent a ventilation-perfusion scintigraphy scan. Sixty (39%) patients remained symptomatic 6 months after the acute PE. After multivariate analysis, only an initial history of deep vein thrombosis (DVT) was predictive of 6-months symptoms (OR 3.35, 95% CI [1.19–9.39], P = 0.022), while initial use of low molecular weight heparin (LMWH) was protective (OR 0.36, 95% CI [0.13–0.96], P = 0.041). The six-month functional test appears to be related to symptoms. There was no difference in clinical, laboratory or echocardiographic parameters between symptomatic and asymptomatic patients. No pathological defect was found on ventilation-perfusion scintigraphy for 27 (52%) of symptomatic patients. Persistence of symptoms at six months of PE is frequent and is associated with a history of DVT and less frequent with initial LMWH therapy. Pathophysiology of post-pulmonary embolism syndrome is complex and not related to the initial PE severity nor the parameters of echocardiography.

Could high levels of cell-free DNA in maternal blood be associated with maternal health and perinatal outcomes?

The aim of this study was to evaluate the maternal and foetal factors affect higher cell-free DNA (cfDNA) levels and to investigate a possible relationship between high cfDNA levels and adverse perinatal outcomes. From a total of 4594 women who underwent non-invasive prenatal testing from January 2016 to March 2018 in our hospital, 112 women had high levels of cfDNA, which was not appropriate for testing. Maternal characteristics and perinatal outcomes were compared between patients with high levels of cfDNA and normal levels of cfDNA. Patients with high levels of cfDNA had greater risks than patients with normal cfDNA levels of pregnancy complications but no statistically significant difference was found. Patients with high cfDNA levels had higher foetal death rates with a statistically significant difference (9.8% versus 1.8%, p = .024). An increase in foetal death could be expected in patients with increased cfDNA levels; therefore, these patients should be carefully followed up during pregnancy.IMPACT STATEMENTWhat's already known about this topic? Most studies about cfDNA levels are focussed on the foetal fraction. There are new arguments about maternal health and cfDNA. It is known that autoimmune diseases as systemic lupus erythematosus (SLE) and maternal obesity increase cell turnover. There are also clinical studies suggesting a relationship between low molecular weight heparin therapy and the amount of cfDNA.What do the results of this study add? This is the first study evaluating the maternal and foetal biological factors affecting cfDNA concentrations and investigating the possible relationship between high cfDNA levels and adverse perinatal outcomes in patients with high levels of cfDNA compared to patients with normal levels of cfDNA. In the present study, it was found that an increase in foetal death could be expected in patients with higher cfDNA levels.What are the implications of these findings for clinical practice and/or further research? If potential effects and underlying causes of increased cfDNA could be explained, cfDNA might be used as a biomarker for adverse perinatal outcomes.

Rivaroxaban treatment for cancer-associated venous thromboembolism in a patient with heparin-induced thrombocytopenia: a case report

Low molecular weight heparin (LMWH) is the first-line therapy in acute cancer-associated venous thromboembolism (CAT). However, heparin-induced thrombocytopenia (HIT) is a life-threatening adverse drug reaction that occurs in anticoagulation therapy with LMWH. This article reports the case of a 66-year-old Chinese male who received nadroparin 4100IU twice daily for treating CAT. Unfortunately, the epistaxis persisted and the blood count examination revealed serious thrombocytopenia on postoperative day 5. The patient was diagnosed with HIT and thereafter LMWH therapy was replaced with rivaroxaban. During three months follow-up, the patient had a good recovery without recurrent CAT or bleeding.