Therapeutic Dose Low-molecular Weight Research Articles

664 Superior Mesenteric Vein and Portal Vein Thrombosis in a Patient With COVID-19: A Rare Case

Abstract A 68-year-old man was referred to the general surgeons on account of his abdominal pain of unknown cause. He had contracted COVID-19, 9 days prior. CT chest abdomen and pelvis revealed an extensive thrombus extending from the portal vein to the superior mesenteric vein. Further investigation ruled out haematological causes, and COVID-19 was determined to be the cause. He was treated with an extended course of therapeutic dose low molecular weight heparin under the guidance of the haematology team. He was discharged once he was clinically stable and pain-free, with a plan to be followed up by both the surgeons and haematologists. This case highlights the different ways in which COVID-19 presents, and the need for clearer guidance on the treatment and prevention of thromboembolism in COVID-19.

Acute myocardial infarction and arterial embolism in a patient with newly diagnosed renal mass: management dilemmas! A case report

BackgroundCancer is often associated with a hypercoagulable state and new thrombosis is often the first clinical manifestation of cancer. Surgical treatment of the primary tumor is crucial since it provides the only curative approach in most cases, but management of patients is highly complex, especially in the presence of new antiplatelet drugs and/or anticoagulants. Paraneoplastic syndromes (PNS) represent a frequent complication of renal cell carcinomas (RCC) and include different hematological symptoms in patients, whilst occlusion of arterial blood vessels displays a rare form of PNS accompanying renal tumors.Case presentationWe report the case of a 62-year old man who was initially hospitalized due to acute coronary syndrome. He subsequently underwent coronary angioplasty treatment including multiple stenting and treatment with ticagrelor and aspirin. Post-interventional, acute arterial thrombotic emboli of several limb arteries required thrombectomy. By computer tomography we identified a renal lesion suspicious for an RCC and suspected a PNS as underlying cause of the thrombotic complications. Triple anticoagulant therapy was maintained with therapeutic dose low molecular weight heparin (LMWH), aspirin, and clopidogrel, by which we replaced ticagrelor. Surgery was postponed for 4 weeks. We paused LMWH, aspirin and clopidogrel only at the day of surgery and perioperatively restored hemostasis by transfusion of two platelet concentrates. Laparoscopic nephrectomy was uneventful. Pathology confirmed a clear cell RCC. The patient fully recovered whilst slowly reducing anticoagulation dose.ConclusionsA multidisciplinary team approach of experts in urology, cardiology and hemostasis was key in managing this patient since a personalized thrombosis consult was needed to minimize the risk of reinfarction due to in-stent thrombosis. We report a therapeutic protocol that may be helpful for the management of similar cases. Furthermore, the finding of thrombotic arterial occlusions in larger blood vessels represents a novel complication of PNS in RCC and adds to the varied possible manifestations of this clinical chameleon.

Human-Centered Design of a Low Molecular Weight Heparin Order Set to Reduce Medication Errors.

Inpatient anticoagulation medication errors for venous thromboembolism (VTE) therapy are common. Our VTE Team identified frequent dosing and duplicate order errors for therapeutic-dose low molecular weight heparin, which (lacking computerized physician order entry) was ordered using blank forms. To decrease such errors, a nonmandatory order form with weight-based dosing and prechecked orders discontinuing existing injectable anticoagulation was developed using human-centered design innovation principles/processes emphasizing end-user engagement in all phases: observation, exploring solutions, and rapid prototyping/feedback. Three physicians independently reviewed ordering errors the year before versus after implementation. Before implementation, 11% of orders contained any error versus 10.5% after implementation (p = .82); 6.2% had a dosing or duplicate therapy error versus 4.2% after implementation (all made when the form was not used; p = .19). No dosing or duplicate therapy errors were made when the form was used. Were the form mandatory, all such ordering errors would likely have been eliminated, leaving 11% before versus 6.3% after implementation orders with any error (p = .015), and 6.2% before versus 0% after implementation orders with duplicate or dosing therapy errors (p < .001). Human-centered design of an anticoagulation order form can reduce anticoagulation order errors; such principles can be applied to other health care innovations, including electronic order sets.

Outcomes Following Placement of Venous Stents for Treatment of Thrombotic Venous Disease

BackgroundEndovenous stenting is a method to overcome venous outflow obstruction in the treatment of patients with acute iliofemoral deep vein thrombosis (DVT) or in those with symptomatic post-thrombotic syndrome (PTS). These treatments allow maximal luminal expansion of the caval and/or iliac venous segment leading to a reduction in venous hypertension. While there is growing enthusiasm for their use, particularly as conventional treatments usually with anticoagulation are not always effective there is however little clinical data regarding efficacy in improving clinical outcome.ObjectivesTo determine the outcomes in patients following placement of venous stents for treatment of obstruction in acute venous thrombotic and post-thrombotic syndrome.MethodsConsecutive patients with a history of DVT in whom a venous stent was inserted at two UK specialist tertiary referral centres between 2012-2015 were included. ‘Acute’ patients consisted of those with a fresh symptomatic iliofemoral DVT; chronic patients were those with recalcitrant PTS unresponsive to conventional therapy. Patients planned for intervention were discussed by a multidisciplinary team made up from Haematology, Interventional Radiology and Vascular Surgery.Stents were placed under general anaesthesia. Venous access was obtained using ultrasound guidance. Intravascular ultrasound (IVUS) was used to size the stent and to ensure it was fully expanded. Endophlebectomy with arterio-venous fistula formation was carried out in selected patients. All patients were given therapeutic dose low molecular weight heparin (LMWH) post procedure before transition to oral anticoagulation.Ultrasound surveillance commenced the day after the procedure and at 2 weeks, 6 weeks, 3 months, 6 months, 1 year and annually thereafter. Clinical follow-up was at 6 weeks, 6 monthly thereafter. Primary patency was defined as a patent stent with <50% diameter reduction. Primary-assisted patency was defined as a stent that had not occluded, but had required a re-intervention to maintain patency, based on imaging findings and/or symptoms. Secondary patency included stents that had blocked and were successfully re-opened. Ulcer healing or changes in Villalta Score were used as measures of clinical outcome following intervention.Results379 venous stents were placed in 148 patients. The median age of patients was 42yrs (range: 18-81yrs), and 86 (58%) patients were female. Symptoms in the left leg were most common (116 patients, 78%).There were 60 (41%) patients who had a venous stent placed to treat an underlying stenosis following catheter directed thrombolysis of an acute iliofemoral DVT. 88 (58%) patients had stent placement to treat a post-thrombotic obstruction considered pathological for PTS.Primary, primary-assisted and secondary patency was 67%, 85% and 88% respectively at one-year in the acute DVT group (figure 1) and 64%, 86% and 86% respectively for the PTS group (figure 2). The median Villata score was 0 (range 0-14), 12 months after stenting, though new ulceration was noted in three patients in the acute DVT group. Median Villalta scores in patients without ulceration decreased from 15 (range 6-23) to 5 (range 1-22) one-year following the procedure (P<0.0001) in the PTS group with the greatest improvement in Villalta score in patients with a patent stent (P<0.0001). Ulcer healing occurred in 6 of 13 patients during follow-up. Four patients with severe pre-operative PTS developed an ulcer six-months following intervention.There was one death from cancer during follow-up, but no stent related mortality or major bleeding complications.ConclusionsThis is the largest reported series of outcomes of venous stents placed in patients with acute iliofemoral venous thrombosis or severe post-thrombotic syndrome. Patients had a minimum follow-up of one year Venous stenting offer potential for the treatment of patients with obstruction related to thrombotic venous disease with good clinical outcomes at one year. Further study on patient selection, outcomes and optimal anticoagulation is required. [Display omitted] DisclosuresBreen:Veniti: Speakers Bureau. Cohen:Bayer Healthcare: Employment, Speakers Bureau. Uprichard:Bayer Healthcare: Speakers Bureau. Black:Veniti: Speakers Bureau.

Recording inpatient weight: implications for medicines administration.

To identify the proportions of hospital inpatients with recorded weights: among all patients, and among those receiving weight-dosed drug therapy. Survey of clinical notes of hospital inpatients across a convenience sample of 11 secondary and tertiary referral hospitals in England and Wales in November 2011. 1068 patients were included, and 1061 patient clinical notes were available (99.3%). Nearly all paediatric patients had recorded weights (77/78; 98.7%). Half of adult inpatients had recorded weights (503/983, 51.2%). The proportion of adult inpatients with recorded weights varied by hospital, ranging from 13.5% to 92.5% (p<0.0001). In those receiving gentamicin or therapeutic-dose low molecular weight heparin (t-LMWH), only 64.5% (71/110) had a recorded weight. Half of adult inpatients, and two-thirds of those receiving gentamicin or t-LMWH, had recorded weights. There was significant variation in rates of weighing adult inpatients across hospitals. This may put patients at increased risk of side effects and problems resulting from malnutrition.

Antipsychotic Drug Use and the Risk of Venous Thromboembolism in Elderly Patients

Our aim was to investigate the relationship between exposure to antipsychotic drugs and the risk of venous thromboembolism (VTE) in elderly patients. A time-matched case-control analysis nested within a cohort of 111,818 patients with at least 1 antipsychotic drug prescription during 1998 to 2008. Data were used from the PHARMO institute's database, which contains drug dispensing data from community pharmacies and hospital admission data. The index date was for the cases defined as the date of hospital admission for VTE (deep venous thrombosis [DVT] or pulmonary embolism) or, for outpatient cases, the start of therapeutic dose low-molecular weight heparin therapy. For each case, 4 controls matched by age and sex were randomly sampled from the cohort. Two measures were used to evaluate the temporal relationship between antipsychotic drug use and the occurrence of VTE: being a current, recent, or past user and the duration of use up to the index date. The strength of the association was expressed as odds ratios with 95% confidence intervals, taking into account potential confounders. We identified 367 cases of hospital admission for DVT, 342 cases of hospital admission for PE, and 323 cases of outpatient treatment of DVT. Current exposure to antipsychotic drugs was not associated with an increased risk of VTE, compared with nonusers (odds ratio, 0.9; 95% confidence interval, 0.7-1.1). We found no association between dosage, the duration of use, or the type of antipsychotic drug and the risk of VTE. We found no evidence of an increased risk of VTE in elderly patients using antipsychotic drugs.

Use of therapeutic dose low molecular weight heparin during pregnancy in women with mechanical heart valves

Management of anticoagulation in women with mechanical heart valves (MHV) is one of the most challenging issues faced by obstetric physicians who manage pregnant women with cardiac problems. The already high risk of valve thrombosis is increased further during pregnancy because of the prothrombotic changes of pregnancy. The safest option for the mother, to reduce the risk of valve thrombosis leading to valve failure or systemic thromboembolism, is to remain on oral anticoagulants such as warfarin. However, warfarin crosses the placenta with a 5–6% risk of warfarin embryopathy if taken between six and nine weeks gestation.1 In addition, warfarin anticoagulates the fetus and there is a high rate of late fetal loss, up to 40% in some studies,2 which further increases women's reluctance to continue taking this form of anticoagulation. Heparin, which does not cross the placenta, is an effective alternative to warfarin for treatment and prevention of venous thrombosis during pregnancy, but there are concerns relating to its efficacy as an anticoagulant in women with MHV. Subcutaneous unfractionated heparin, even when given in high and monitored doses, is associated with an unacceptably high rate of maternal thrombosis. The more predicable anticoagulant effect of low molecular weight heparin (LMWH) makes it is an attractive agent for use in this clinical situation but there are limited data relating to its safety and efficacy. In 2004, Oran and co-workers3 reviewed published case reports and case series of LMWH use in pregnant women with MHV. The overall rate of thromboembolic complications in 81 pregnancies was 11.1% but four of these events were reported in single case studies. Monitoring of anti-Xa levels was not carried out in all centres and women received LMWH for variable periods during pregnancy. Such discrepancies make it difficult to extrapolate these data to other situations.

4 Efficacy and safety of once-daily therapeutic dose low molecular weight heparin (tinzaparin sodium) in high-risk pregnancy

4 Efficacy and safety of once-daily therapeutic dose low molecular weight heparin (tinzaparin sodium) in high-risk pregnancy

Use of Therapeutic Dose Low Molecular Weight Heparin in Patients with Renal Insufficiency: Analysis of Anti-Xa Levels and Creatinine Clearance.

Low molecular weight heparin (LMWH) is predominantly eliminated by the kidneys. In patients with severe renal impairment, use of therapeutic dose LMWH may be associated with accumulation and a resultant bleeding risk. Tinzaparin may be less dependent on renal clearance due to its higher molecular mass and greater negative charge compared to other LMWHs. The objective of this prospective cohort study was to serially measure the anti-Xa anticoagulant effect of therapeutic dose tinzaparin over 5–7 days, used for the initial treatment of venous thromboembolism (VTE) in patients with varying degrees of renal insufficiency. We present the anti-Xa results from the first 78 patients enrolled in the study, correlated with renal function. In this study, consecutive in- and outpatients with objectively confirmed VTE requiring anticoagulation were enrolled and stratified into 4 groups based on the calculated Cockcroft-Gault creatinine clearance (CrCl): > 60 mL/min, 30–60 mL/min, ≤ 30 mL/min and hemodialysis-dependent. Tinzaparin 175 IU/kg was administered subcutaneously once daily for 5–7 days or until the INR ≥ 2.0 with warfarin therapy. Trough anti-Xa levels were measured prior to the 3rd, 5th and/or 7th tinzaparin doses. Patients with anti-Xa level > 0.5 IU/mL received tinzaparin dose adjustment using a standardized nomogram. Bleeding and recurrent VTE events were recorded. The relationship between anti-Xa levels and CrCl is shown in Figure 1. Based on our predefined anti-Xa threshold of 0.5 IU/mL, 5 of 78 patients (6.4%) required dose adjustment; 1 hemodialysis dependent patient, 2 patients with CrCl < 30 mL/min, 1 patient each with CrCl 30–60 and > 60 mL/min, respectively. None of these patients developed bleeding or recurrent VTE. Among all 78 patients, 1 hemodialysis-dependent patient developed a hematoma following a traumatic line insertion, and no patients developed recurrent VTE. In conclusion, in a cohort of 78 patients with differing degrees of renal function including patients requiring hemodialysis, use of therapeutic-dose tinzaparin for the initial treatment of VTE resulted in accumulation (defined by trough anti-Xa > 0.5 IU/mL) in 6% of patients. There appears to be a weak inverse relationship between renal function and trough anti-Xa levels, but does not result in clinically significant accumulation when tinzaparin is used for up to 7 days. Further evaluation of tinzaparin in patients with severe renal insufficiency is required. [Display omitted]