Intravenous Heparin Research Articles

Dermatosurgery in the age of novel oral anticoagulants/direct oral anticoagulants

Current guidelines generally recommend continuation of blood thinning drugs in dermatologic surgery and the previously used "bridging" with subcutaneous or intravenous heparin is obsolete. While the guidelines are increasingly implemented in daily practice, there is still uncertainty concerning the use of the novel direct oral anticoagulants (NOAC = DOAC). In this review, we analyze current developments and formulate concise recommendations for continuation during skin surgery under consideration of individual risk.

Thrombolysis with reteplase in acute pulmonary embolism

ObjectiveReteplase (recombinant plasminogen activator) is a mutant of alteplase. It has a longer half-life than its parent molecule and has shown better vessel patency rates in acute myocardial infarction. In this study, we analyzed the efficacy and safety of reteplase in acute pulmonary embolism (PE). MethodsThis observational study included patients with high- and intermediate-risk acute PE, presenting within 14 days of symptom onset. The patients were treated with reteplase, which was given in two bolus doses of 10 U each, 30 min apart, along with intravenous heparin. Patients with hemodynamic compromise (high-risk or massive PE) and normotensive patients with evidence of right ventricular (RV) dysfunction (intermediate-risk or submassive PE) on echocardiography or computed tomography were included in the study. The efficacy outcomes assessed were in-hospital death and improvement of RV function by echocardiography. The safety outcomes were major bleeding, minor bleeding, and ischemic or hemorrhagic stroke during hospitalization. ResultsOf the 40 patients included, 25% were classified as high risk with hemodynamic compromise and 75% were classified as intermediate risk. RV dysfunction was present in all the patients (100%). Concomitant lower extremity deep vein thrombosis was present in 55% of the patients. The mortality rate was 5%. There was significant improvement in RV function and reduction in pulmonary artery systolic pressure and tricuspid regurgitation severity. There was no major bleeding event or stroke, and 7.5% patients had minor extracranial bleeding. ConclusionsDouble-bolus reteplase given with heparin is effective in the treatment of high- and intermediate-risk PE, with minimal risk of bleeding.

Left superior pulmonary vein stump thrombosis and right renal infarction after left upper lobectomy: case report and literature review

Left upper lobectomy (LUL) has been considered to have a higher risk of thrombus formation in the pulmonary vein stump (PVS) than other lobectomies. A case of thrombus formation in the PVS and right renal infarction detected by contrast-enhanced computed tomography (CECT) 12days after LUL is presented. The thrombus in the PVS was considered to be related to the renal infarction because of the lack of other potential explanations. After intravenous heparin treatment for 1week and continuous oral anticoagulation, the thrombus in the PVS became smaller 3months after the operation, and it basically disappeared after 1year. Scar formation was detected in the area of renal infarction 3months after the operation, and no specific change was detected from then on. One should consider performing postoperative chest and abdominal CECT routinely within 1week after LUL, and, if thrombosis is found, antithrombotic therapy might then be given.

Safety of Single-Site Laparoscopic Surgery Requiring Perioperative Heparinization in Colorectal Cancer: Propensity Score-Matched Analysis.

We assessed the feasibility and safety of single-site laparoscopic surgery for patients with colorectal cancer who required perioperative heparinization. This retrospective study reviewed the medical records of 390 patients who underwent single-site laparoscopic surgery for colorectal cancer from January 2010 to December 2016. Antithrombotic drugs were stopped preoperatively and heparin was administered according to the operative risk of each patient, based on consultation with the cardiologist physician or neurosurgeon. Propensity score modeling was utilized to adjust for baseline characteristics. Of 390 patients, 29 were treated with standard bridging intravenous heparin therapy. Propensity matching identified 119 patients: 22 patients in the heparinization group and 97 in the control group. The matched groups were not significantly different in operation times, bleeding volumes, or conversion rate. The mean postoperative hospital stay was 17.9days in the heparinization group and 9.5days in the control group (p = 0.034). Postoperative bleeding was observed in 4 patients (18.2%) in the heparinization group and 11 patients (11.4%) in the control group (p = 0.646), while other complications were similar in the two study groups (p = 0.502). Of these other complications, thromboembolic events were observed in two patients in the heparinization group and one patient in the control group. We found that single-site laparoscopic surgery for colorectal cancer with heparinization was feasible and safe. Heparinization did not increase the risk of postoperative bleeding complications, but postoperative hospital stay was prolonged.

Intravenous unfractionated heparin dosing in obese patients using anti-Xa levels.

There is limited guidance on intravenous dosing of unfractionated heparin in obese patients. The purpose of this study was to determine the efficacy and safety of a standard unfractionated heparin (UFH) protocol in obese patients based on total body weight (TBW) or adjusted body weight (ABW) to reach two consecutive therapeutic anti-Xa levels. This was a retrospective observational cohort study conducted in a large academic medical center. Adults received a standard UFH protocol between January 1, 2013 to December 31, 2015. Inclusion criteria included age ≥ 18 years of age, weight ≥ 100 kg with a BMI ≥ 30 kg/m2, andreceived intravenous UFH. Patients were excluded if they received an alternative UFH protocol, received < 24 h of the standard UFH protocol, or had inadequate compliance to protocol. Out of the 131 patients included, 109 patients reached two consecutive therapeutic UFH levels within 96 h. The average time to two consecutive therapeutic UFH levels was 29.4 h and 27.6 h in patients dosed by TBW and ABW, respectively (95% CI - 4.63 to 8.11; P = 0.93). Safety outcomes included major bleeding, overt bleeding, or death events between patients dosed by TBW compared to ABW, (p = 0.61, p = 1.0, p = 1.0, respectively). Dosing intravenous UFH based on TBW or ABW resulted in similar times to therapeutic anti-Xa levels and safety outcomes. The data provided suggests using either TBW or ABW in obese patients is as effective and safe to use.

The effect of heparin infusion intensity on outcomes for bridging hospitalized patients with atrial fibrillation.

BackgroundPerioperative bridging in atrial fibrillation (AF) is associated with low thromboembolic rates but high bleeding rates. Recent guidance cautions the practice of bridging except in high risk patients. However, the practice of bridging varies widely and little data exist regarding appropriate anticoagulation intensity when using intravenous unfractionated heparin (UFH).HypothesisTo determine if high intensity UFH infusion regimens are associated with increased bleeding rates compared to low intensity regimens for bridging patients with AF.MethodsWe conducted a single center retrospective cohort study of admitted patients with non‐valvular AF receiving UFH for ≥24 hours. UFH intensities were chosen at the providers' discretion. The primary endpoint was the rate of bleeding defined by the International Society on Thrombosis and Hemostasis during UFH infusion or within 24 hours of discontinuation. The secondary endpoint was a composite of cardiovascular events, arterial thromboembolism, venous thromboembolism, myocardial infarctions and death during UFH infusion.ResultsA total of 497 patients were included in this analysis. Warfarin was used in 82.1% and direct acting oral anticoagulants in 14.1% of patients. The rate of any bleed was higher among high intensity compared to low intensity UFH regimens (10.5% vs 4.9%, odds ratio = 2.29, 95% confidence interval = 1.07‐4.90). Major bleeding was significantly higher among high intensity compared to low intensity UFH regimens. There was no difference in composite thrombotic events or death.ConclusionsLow intensity UFH infusions, targeting lower anticoagulation targets, were associated with decreased bleeding rates without a signal of increased thromboembolic events in hospitalized AF patients.

45. Large vessel vasculitis associated with common iliac artery aneurysm and limb ischaemia

IntroductionAn 81-year-old gentleman with no prior medical history presented with a 5-month history of gradual onset malaise and reduced appetite. Weight loss of 2 stone was noted. Mild intermittent headache was present. After 3 months, he developed intermittent claudication of the right leg. A diagnosis of giant cell arteritis (GCA) was made. Disease was corticosteroid resistant, on the basis of clinical findings, biochemistry and imaging. Tocilizumab was commenced. Imaging also revealed dissection of the proximal right common iliac artery. The intermittent claudication progressed to acute limb ischaemia, which responded well to conservative treatment with heparin.Case descriptionHeadache was unilateral, intermittent and lasted a few minutes only, although it was described as severe. There were no visual symptoms, no scalp tenderness and no jaw or tongue claudication. His mobility was severely impacted by intermittent claudication. He was previously playing 3 rounds of golf per week but exercise tolerance reduced to fifty metres. There were no specific risk factors for atherosclerotic disease. He was a retired head teacher and had never smoked. Alcohol intake was 3 units per week. He was not taking any medication.The predominant features in the history were systemic upset and weight loss and the initial focus was on ruling out malignancy. Extensive investigations were performed by the general practitioner (GP). Erythrocyte sedimentation rate (ESR) was 80 and C-reactive protein (CRP) 74. A full blood count and serum biochemistry were otherwise unremarkable. Immunoglobulins were normal with no paraprotein detected. Thyroid stimulating hormone (TSH) was within the normal range. Prostate specific antigen (PSA) was raised at 17.8 but urology investigations revealed no evidence of malignancy.Computed tomography (CT) of the thorax, abdomen and pelvis showed non-specific inflammation of jejunum & mesenteric fat. Subsequent magnetic resonance imaging (MRI) of the small bowel showed resolution of these changes but noted a chronic focal area of dissection at the proximal right common iliac artery.The GP commenced prednisolone 40mg daily, increased after twelve days to 60mg daily due to partial response. Review in rheumatology clinic two weeks later noted ongoing intermittent claudication. Headache had resolved and weight stabilised. The right temporal artery was difficult to palpate and the right ulnar pulse was absent. Temporal artery ultrasound scan (TA USS) in clinic demonstrated bilateral ongoing active inflammation. Three pulses of 500mg intravenous methylprednisolone were arranged.DiscussionWhilst ESR had initially improved to 10 and CRP to < 3, they subsequently increased to 53 and 45 respectively. Subsequent positron emission tomography with computed tomography (PET-CT) showed diffuse metabolic activity in thoracic aorta, bilateral subclavian, axillary and femoral arteries.On the basis of bloods, ongoing claudicant symptoms and strongly positive TA-USS and PET-CT, the disease was felt to meet criteria for steroid non-responsiveness. As per NICE guidelines, permission was sought and granted from the local tertiary centre to commence tocilizumab. The patient was noted to have diverticulosis on the basis of imaging but had never been symptomatic. After appropriate patient counselling on the risks of gastrointestinal perforation, a decision was made to proceed with treatment.The finding of dissection at the proximal right common iliac artery prompted urgent referral to the vascular surgery team. However, whilst awaiting review, the patient developed acute limb ischaemia with pallor, weakness and pain of the right leg. He was admitted and managed conservatively with intravenous heparin, followed by subcutaneous heparin and clopidogrel. He responded well to medical therapy and remains under vascular follow up. Notably, the aneurysm was retrospectively noted on CT scan imaging, confirming that it predated corticosteroid treatment.Key learning pointsWhilst aneurysm formation is a recognised complication of giant cell arteritis, they are typically aortic and involvement of lower limb arteries is rareThere is no consensus opinion on optimal surveillance of extra-aortic aneurysms in GCA; decisions should be made on a case by case basisTocilizumab is an effective treatment for refractory GCA. The current NICE guideline on its usage is based on the GiACTA study findingsConflicts of interestThe authors have declared no conflicts of interest.

44. Buerger’s disease with severe eosinophilia and acute critical ischemia

IntroductionBuerger’s disease usually presents with normal blood tests. We present a case with significant eosinophilia, a phenomenon rarely reported. Eosinophilia with acute onset Raynaud’s and critical ischemia can be atypical early manifestation of Buerger’s disease (thromboangiitis obliterans).Case descriptionA case report of a 24-year-old male, smoker, with no other history, presented acutely, complaining of cool, painful hands with tricolour changes with worsening for 48 hours. On examination, apart from features of Raynaud’s and tender fingers, he had good perfusion, as shown by Doppler testing. Blood tests showed eosinophilia; 13x10*9 (Normal 0.04-0.40 x10*9) and mild raised C-reactive protein 24 (normal range <10.0 mg/L). Chest radiograph, ECG, and echocardiography showed no abnormalities. The results of initial screening including Immunoglobulins, complements, ANA, ANCA, RF, APLA and CCP were all negative. As there were no critical features of ischemia, we considered the patient for discharge from the hospital with a plan for close review. We strongly advised him not to smoke. He re-admitted within a week with worsening of Raynaud’s and features of critical ischemia with bluish nail and fingertip and some early features of mild digital necrosis. We began treatment with intravenous heparin, aspirin, and iloprost (prostacyclin) infusion for 10 days. The patient’s digital ischemia and intermittent claudication showed some improvement after 1 week, but eosinophilia persisted at 11x10*9 with ruminant pain in digits. The importance of smoking cessation was re-emphasised. Magnetic resonance angiography showed no occlusion of the distal arteries of the upper and lower extremities. Capillaroscopy showed micro haemorrhages (no connective tissue disease/scleroderma pattern abnormality). Investigations for parasitic infections and malignancy were negative. HIV / Hepatitis B/C CMV/EBV/Parvovirus IGM was all undetected. Schistosoma testing was negative. Haematology investigated him for the rare possibility of the genetic mutation for hypereosinophilic syndrome (PDGFRA and FIP1L1 genes) which was negative and underwent bone marrow biopsy which was also normal.We started him on oral prednisolone 1 mg/kg body weight with complete resolution of eosinophilia and ischemic symptoms plus Raynaud’s. Smoking stopped with help.DiscussionBuerger’s disease is a rare disease of exclusion and recognised as one form of vasculitis with a strong association with smoking and nicotine. There has been no consensus or any significant data for any specific therapies proven a benefit in this condition, more than in alone stopping smoking or even oral tobacco products. The main characteristic features of this form are present in young smokers with no systemic disease manifestation, normal inflammatory response, and negative immunology.Eosinophilia has only rarely been a feature of the presentation of Buerger’s disease. Its presence does not imply a systemic vasculitis or a related syndrome. Although there is limited evidence for the use of steroids in this condition, inflammatory features such as eosinophilia could strengthen the rationale for using steroids in certain cases by halting the ongoing immune driven inflammatory cascade. The presence of eosinophilia might suggest alternative pathogenic mechanisms in certain cases of Buerger’s.Key learning pointsTo recognise eosinophilia as a marker in atypical Buerger’s disease presentation. Being a disease of exclusion we have to rule out all other possibilities including some rare ones as was done in this case by seeking advice from infectious disease and haematology team.Conflicts of interestThe authors have declared no conflicts of interest.

The accuracy of a point of care measurement of activated partial thromboplastin time in intensive care patients

Point of care (POC) devices are increasingly being used in intensive care units to obtain faster results. Data are limited on the performance of these devices in critically ill patients, especially those on heparin infusion. The objective of this study was to assess the agreement between POC activated partial thromboplastin time (APTT) and laboratory APTT results in patients on heparin infusion and to determine its impact on the clinical decisions regarding heparin dosage. We screened all patients admitted to the intensive care unit (ICU) at St George Hospital, Sydney, over a 7-month period and enrolled those who were receiving intravenous heparin infusion. We measured APTT by two methods: bedside POC test (Hemochron Junior Signature Plus) and central laboratory method (STA analyser). We used the Bland-Altman method to test the statistical agreement between the two measurements and Cohen's kappa statistic to test the clinical agreement regarding heparin dosing decision. A total of 176 paired samples from 44 patients (mean age 63 years, 64% males, mean APACHE 18) were analysed. The mean turnaround time for the point of care APTT result was significantly shorter than the central laboratory result (5.0±0.2 min vs 64.6±2.7 min, p<0.0001). Despite the statistically significant correlation, the overall agreement tested by the Bland-Altman method was poor. The 95% limits of agreement were widest (-27.266 to 64.791) and mean percentage bias was highest (24%) for the comparison between POC APTT using citrated blood and laboratory APTT. When POC APTT results of less than 90 seconds using whole blood were compared to laboratory APTT results, the limits of the agreement became narrower (-23.243 to 28.419), and the mean percentage bias decreased to 5%. The agreement between clinical decisions regarding heparin dosage based on the two methods was poor for plain and citrated blood (kappa 0.35 and 0.11, respectively). The POC APTT results were not sufficiently accurate for use in patients on heparin infusion compared to laboratory APTT assay.

Acute Pulmonary Embolism: Presentation, Diagnosis, Management and Factors Impacting Clinical Outcome in a Tertiary Cardiac Centre in Pakistan.

To evaluate the presentation, diagnosis, management and outcome of acute pulmonary embolism for assessing the factors impacting mortality in such patients. Descriptive study. Rawalpindi Institute of Cardiology, Rawalpindi, Pakistan, from July 2015 to July 2018. Patients presenting with clinical suspicion of pulmonary embolism were subjected to a diagnostic algorithm consisting of Wells Rule, D-Dimer testing, echocardiography and CT pulmonary angiogram. Patients diagnosed with pulmonary embolism were subdivided into massive and submassive pulmonary embolism groups. Most patients diagnosed with massive pulmonary embolism were treated with streptokinase injection. For those diagnosed as submassive pulmonary embolism, the standard therapy remained anticoagulation with intravenous heparin, both the subsets of patients were further put on oral warfarin. Clinical outcome was defined as combined end-point including death during hospital stay, recurrence of PE and meed for repeat thrombolysis. A total of 174 patients diagnosed with pulmonary embolism were studied. The mean age was 49.1 +14.8 years (range 23-88 years) with 109 (62.6%) patients being male. The in-hospital clinical course was uneventful in 144 (83%) patients. Twenty-two patients (12.6%) patients died, of whom 3 died from major bleeding, one from cancer, and 18 from the pulmonary embolism process (14 patients from refractory shock and 4 patients from recurrent PE). A total of 8 (4.6%) had fatal or non-fatal recurrent PE. In patients who had echocardiography both pre- and post-thrombolysis, initial RV dysfunction was reversible in 136 (78%) within 48h following thrombolytic therapy. By univariate analysis, only shock (SBP) and delay in diagnosis for more than 6 hours were associated with adverse event. Early diagnosis by doing urgent CTPA in patients with suspected acute PE is the cornerstone in reducing mortality in acute PE patients.

Preoperative Bleeding and Blood Product Transfusion Association with the Preoperative Use of Aspirin and Heparin in Left Ventricular Assist Device Implantation

Introduction Perioperative bleeding in the setting of LVAD implantation adversely impact outcomes. Hypothesis This project aims to determine pre-operative and intraoperative risk factors for this complication. Methods A retrospective cohort study was conducted including 90 consecutive advanced heart failure patients who underwent LVAD implantation as a bridge to transplantation or destination therapy from 2008 to 2017. By protocol, all anti-platelet therapies other than aspirin were discontinued 7 days pre-implantation. Aspirin was continued if clinically indicated. Additionally, any patients on anti-coagulant therapy were transitioned to intravenous heparin. Heparin infusion was discontinued 6 hours pre-operatively. Perioperative hemodynamics, laboratory values, cardiopulmonary bypass parameters, and blood product utilization were collected. Results Observable bleeding within 7 days of implant occurred in 15 patients (16%). This was significantly associated with the pre-operative use of heparin (OR 6.4; 95% CI 1.8-23.2; p=0.005) and its incidence increased for each 1 mmHg increase in right atrial pressure during pre-operative right heart catheterization (OR 1.1; 95% CI 1.0-1.2; p=0.03). Aspirin use within 3 days of implant increased the need of packed RBC transfusion both intra-operatively (OR 3.2; 95% CI 1.3-8.2; p=0.01) and post-operatively (OR 3.0; 95% CI 1.1-8.4; p=0.04) as well as increased the risk of hemoglobin drop ≥3 gm/dl on post-operative day 1 or the need of more than 2 packed RBC units peri-operatively (OR 4.2; 95% CI 1.6-11.4; p=0.004). Cardiopulmonary bypass time > 60 minutes increased the need for packed RBC transfusion post-operatively (OR 3.07; 95% CI 1.05-9.01; p=0.04). Conclusions Pre-operative aspirin and heparin are reversible factors that may affect the need for peri-operative blood products transfusion. This may indicate that these agents may need to be withheld longer or alternative antithrombotic preoperative agents should be considered.

Discordance between aPTT and anti-factor Xa levels and implications in patients receiving intravenous unfractionated heparin therapy

Heparin, one of the world’s oldest anticoagulation medications, accelerates the rate ofinhibition of previously activated clotting factors. It is most often used in the prophylaxis andtreatment of thromboembolic disorders and complications associated with atrial fibrillation.The two most common ways to monitor plasma heparin levels and anticoagulation therapyare the activated partial thromboplastin time (aPTT) and anti-factor Xa assay (anti-Xa). Thisarticle assesses the performance of aPTT and anti-Xa monitoring protocols and analyzes thediscordance between aPTT and anti-Xa levels and its clinical implications in patients receivingintravenous heparin therapy.

Periprocedural Intravenous Heparin During Endovascular Treatment for Ischemic Stroke: Results From the MR CLEAN Registry.

Background and Purpose- Intravenous administration of heparin during endovascular treatment for ischemic stroke may improve outcomes. However, risks and benefits of this adjunctive therapy remain uncertain. We aimed to evaluate periprocedural intravenous heparin use in Dutch stroke intervention centers and to assess its efficacy and safety. Methods- Patients registered between March 2014 and June 2016 in the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke), including all patients treated with endovascular treatment in the Netherlands, were analyzed. The primary outcome was functional outcome (modified Rankin Scale) at 90 days. Secondary outcomes were successful recanalization (extended Thrombolysis in Cerebral Infarction ≥2B), symptomatic intracranial hemorrhage, and mortality at 90 days. We used multilevel regression analysis to evaluate the association of periprocedural intravenous heparin on outcomes, adjusted for center effects and prognostic factors. To account for possible unobserved confounding by indication, we analyzed the effect of center preference to administer intravenous heparin, defined as percentage of patients treated with intravenous heparin in a center, on functional outcome. Results- One thousand four hundred eighty-eight patients from 16 centers were analyzed, of whom 398 (27%) received intravenous heparin (median dose 5000 international units). There was substantial between-center variability in the proportion of patients treated with intravenous heparin (range, 0%-94%). There was no significant difference in functional outcome between patients treated with intravenous heparin and those without (adjusted common odds ratio, 1.17; 95% CI, 0.87-1.56), successful recanalization (adjusted odds ratio, 1.24; 95% CI, 0.89-1.71), symptomatic intracranial hemorrhage (adjusted odds ratio, 1.13; 95% CI, 0.65-1.99), or mortality (adjusted odds ratio, 0.95; 95% CI, 0.66-1.38). Analysis at center level showed that functional outcomes were better in centers with higher percentages of heparin administration (adjusted common odds ratio, 1.07 per 10% more heparin, 95% CI, 1.01-1.13). Conclusions- Substantial between-center variability exists in periprocedural intravenous heparin use during endovascular treatment, but the treatment is safe. Centers using heparin more often had better outcomes. A randomized trial is needed to further study these effects.

Cardiac Surgery Successfully Managed With Cangrelor in a Patient With Persistent Anti-PF4/Heparin Antibodies 8 Years After Heparin-Induced Thrombocytopenia

A 66-YEAR-OLD female requiring cardiac surgery had persisting anti-platelet factor 4 (PF4)/heparin antibodies (HIT-abs) 8 years after heparin-induced thrombocytopenia (HIT). In 2010, she developed thrombotic thrombocytopenic purpura (TTP) (ADAMTS-13 <5%, inhibitor at 1.0 BU/mL), which was treated successfully with corticotherapy, plasmapheresis, and intravenous heparin. While taking heparin, she developed HIT, as evidenced by a positive functional test. Her platelet count fully resolved without thrombotic complications with danaparoid treatment. In 2018, the preoperative titer of HIT-abs was still 0.38 U/mL by chemoluminescent immunoassay (CLIA), and positive by particle-gel agglutination immunoassay (PaGIA) with a titer of 2 and was strongly positive on an enzyme-linked immunosorbent assay (ELISA). The authors of the case report chose to use cangrelor combined with heparin during cardiopulmonary bypass (CPB). Cangrelor was used without increased postoperative bleeding or thrombotic complications. Postoperatively she exhibited a huge rise in HIT-abs (14.22 U/mL on postoperative day 11) with a positive functional assay. There was no recurrence of HIT, however. This case illustrates the importance of excluding the presence of persisting HIT-abs before CPB and ensuring close medical follow-up after even a single exposure to heparin.

Antithrombin plus alpha-1 protease inhibitor does not affect coagulation and inflammation in two murine models of acute lung injury

BackgroundIn acute respiratory distress syndrome (ARDS), uncontrolled production of activators of coagulation and proinflammatory mediators results in a shift from an adequate local innate immune response to hypercoagulability and inflammation. This study aimed to investigate whether the protease inhibitors antithrombin (AT) and alpha-1 protease inhibitor (A1PI) may attenuate an exaggerated pulmonary immune response.MethodsLung injury was induced either by single intranasal administration of lipopolysaccharide (LPS) (5 mg/kg) in BALB/c mice or by combination of an intravenous injection of LPS (10 mg/kg) with subsequent injurious ventilation using high tidal volumes (12–15 ml/kg) for 4 h in RccHan Wistar rats. Animals received either a single bolus of AT (250 IU/kg) or A1PI (60 mg/kg) alone or in combination, with or without intravenous low-dose heparin (100 U/kg). Control animals received saline. Additional controls received neither LPS, nor ventilation, nor treatment. Endpoints were local and systemic markers of coagulation, e.g., thrombin–antithrombin complexes (TATc), and inflammation, e.g., interleukin-6.ResultsBoth lung injury models resulted in a pronounced immune response within the pulmonary compartment shown by elevated levels of markers of coagulation and inflammation. The two-hit lung injury model also induced profound systemic coagulopathy and inflammation. Monotherapy with AT or A1PI did not reduce pulmonary coagulopathy or inflammation in any lung injury model. Nor did combination therapy with AT and A1PI result in a decrease of coagulation or inflammatory parameters. AT markedly reduced systemic levels of TATc in the two-hit lung injury model. Systemic inflammation was not affected by the different interventions. Additional administration of heparin did not lead to macroscopic bleeding incidences.ConclusionsIn two different murine models of acute lung injury, neither single therapy with AT or A1PI nor combination of both agents attenuates the pronounced pulmonary coagulation or inflammatory response.

Risk Factors for Intracardiac Thrombus During Liver Transplantation.

Intracardiac thrombus (ICT) is an intraoperative complication with high mortality that occurs during orthotopic liver transplantation (OLT). Patients with end-stage liver disease have compromised coagulation pathways, and when combined with stressors of surgery, thrombi can form. However, it is unknown which patients are most likely to develop ICT. We performed a retrospective cohort study of all OLT patients at our hospital from 2010 to 2017 to identify risk factors for ICT. An analysis was performed with conventional bivariate tests and logistic regression. The incidence of ICT during OLT was 4.2% (22/528) with a 45.5% (10/22) mortality. Patients who developed ICT had higher physiologic Model for End-Stage Liver Disease scores at the time of transplant (25.1 versus 32.4; P=0.004), received grafts from donors with a higher body mass index (28.1 versus 32.2kg/m2 ; P=0.007), and had longer intraoperative warm ischemia times (53.1 versus 67.5 minutes; P = 0.001). The odds of developing ICT were significantly lower after administration of intravenous (IV) heparin prior to inferior vena cava (IVC) clamping compared with no administration of heparin (odds ratio, 0.25; 95% confidence interval, 0.08-0.75; P = 0.01). In conclusion, the incidence of ICT at our institution is higher than previously reported, which may be explained by our routine use of transesophageal echocardiography. Although many factors associated with ICT in this study are nonmodifiable, administration of IV heparin prior to IVC cross-clamping is modifiable and was found to be protective. Further studies will be needed to confirm findings and ultimately aid in preventing these lethal events.

Role of Postoperative Anticoagulation in Predicting Digit Replantation and Revascularization Failure: A Propensity-matched Cohort Study.

The use of intravenous heparin after digit replantation or revascularization (DRR) varies greatly. The insufficient evidence presents a lack of clinical equipoise needed for a randomized trial; as such, a matched propensity score analysis was performed to evaluate the role of postoperative anticoagulation after DRR. The purpose of this study was to determine if the use of postoperative therapeutic anticoagulation reduced the risk of digit failure. A retrospective cohort of patients who underwent DRR from 2005 to 2016 was identified. A propensity score was calculated based on age, smoking, injury mechanism, procedure type, vein graft, and number of digits injured. Patients were matched 1:2 by propensity score to create 2 groups with similar risks of receiving anticoagulation postoperatively. Generalized estimating equation logistic model was used to determine differences in digit failure between groups. Digit replantation or revascularization was performed on 282 patients (92% male; median age, 43 years). Postoperative anticoagulation was administered in 69 (24%) patients, with continuous IV heparin in 34 patients and intravenous heparin with dextran in 35 patients. Digit failure occurred in 88 patients overall, representing 38% of patients receiving anticoagulation and 29% of those not. Major complications were higher among the anticoagulated patients (13% vs 3.3%). After propensity score matching, use of anticoagulation was not associated with digit failure (odds ratio, 0.79; 95% confidence interval, 0.47-1.32). Among DRR patients with similar predisposing characteristics for postoperative therapeutic heparin or dextran, the use of therapeutic anticoagulation does not have a protective effect against digit failure. Studies are needed to define the role of postoperative IV anticoagulation in DRR and to justify the risk of its administration.

Appropriate Use of Intravenous Unfractionated Heparin after Digital Replantation: A Randomized Controlled Trial Involving Three Groups.

The purpose of this study was to clarify the appropriate use of unfractionated heparin as an anticoagulation agent after digital replantation. This study was a prospective, randomized, single-blind, blinded-endpoint method, three-arm, parallel-group, controlled clinical trial conducted at a single institution. A total of 88 patients (101 fingers) following digital amputation and subsequent repair by anastomosis of both arteries and veins were randomly allocated into three groups: (1) control group (no heparin dose), (2) low-dose heparin group (10,000 IU/day), and (3) high-dose heparin group (start at 15,000 IU/day, then adjust the dose to achieve an activated partial thromboplastin time of 1.5 to 2.5 times the baseline). The outcomes were assessed regarding the proportion of success at 2 weeks after replantation of amputated digits, total or partial necrosis, and occurrence of complications. No significant differences were found among the three groups, except for complications of congestion. The odds ratio of the heparin group compared with the control group for a success proportion was 5.40 (95 percent CI, 0.85 to 34.20; p = 0.027) in subjects aged 50 years or older. Significant elevations of activated partial thromboplastin time, aspartate transaminase, and alanine aminotransferase occurred in high-dose heparin groups on day 7. Unfractionated heparin administration is considered effective for patients aged 50 years or older, although the routine use of unfractionated heparin is not necessary after digital replantation. Therapeutic, II.

Anti-Xa assays: What is their role today in antithrombotic therapy?

Although some suggest anti-Xa assays should be the preferred method for monitoring intravenous unfractionated heparin therapy, which method is best is unknown owing to the lack of large randomized controlled trials correlating different assays with clinical outcomes. This article provides an overview of heparin monitoring and the pros, cons, and clinical applications of anti-Xa assays.

Periprocedural Heparin During Endovascular Treatment of Tandem Lesions in Patients with Acute Ischemic Stroke: A Propensity Score Analysis from TITAN Registry.

Data on safety and efficacy of periprocedural use of heparin are limited during treatment of acute ischemic stroke patients with anterior circulation tandem occlusion. This study aimed to investigate the impact of heparin use during endovascular therapy of anterior circulation tandem occlusions on the functional and safety outcomes. A retrospective analysis of the multicenter observational TITAN registry was performed. Patients with anterior circulation tandem occlusion and treated with endovascular therapy (EVT) were included, with or without extracranial carotid intervention. We divided patients into two groups based on periprocedural heparin use (heparin vs. non-heparin). The dose of intravenous unfractionated heparin ranged from 1500 to 2500 I.U. Primary study endpoint was 90-day Modified Rankin Scale (mRS). Secondary study endpoint included angiographic and safety endpoints such as hemorrhagic complications. A propensity-score-matched analysis was performed. Among 369 patients, heparin was used in 68 patients (18.4%). In the propensity-score-matched cohort, favorable outcome (mRS 0-2) occurred in 51.3% in heparin group and 58.0% in non-heparin group (matched OR, 0.76; 95% CI, 0.32-1.78; P = 0.52). Similar result was found in propensity-score-adjusted cohort (adjusted OR, 0.72; 95%CI, 0.39-1.32; P = 0.28). Likewise, there was no difference in the rate of successful reperfusion (mTICI 2b-3) (propensity-score-adjusted OR, 1.03; 95%CI, 0.50-2.09; P = 0.93) neither in safety endpoints between the two groups. Periprocedural heparin use during EVT of anterior circulation tandem occlusions was not associated with better functional, angiographic or safety outcomes. These findings are applicable for low doses of heparin, and further studies are warranted.