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Dose adjustment of unfractionated heparin (UFH) anticoagulation is an important factor to reduce hemorrhagic events. High doses of heparin can be monitored by Activated Clotting Time (ACT). Because of limited information about the monitoring of low-dose heparin we assessed monitoring by ACT, aPTT and anti-Xa. Blood samples from healthy volunteers (n = 54) were treated ex vivo with increasing UFH doses (0-0.4 IU/ml). Samples from ICU-patients (n = 60), were drawn during continuous UFH infusion. Simultaneous ACT measurements were performed using iSTAT and Hemochron. In UFH treated blood, iSTAT and Hemochron showed a significant change of ACT at ≥0.075 IU/ml and ≥0.1 IU/ml UFH, respectively. In ICU-patients no relationship between ACT and either UFH dose, aPTT and anti-Xa was observed. Hemochron was affected by antithrombin and platelet count. iSTAT was sensitive to CRP and hematocrit. A moderate correlation was identified between UFH dose and aPTT (R2 = 0.196) or anti-Xa (R2 = 0.162). In heparin-spiked blood, ACT is sensitive to heparin at levels of ≥0.1 IU/ml heparin. In ICU-patients, ACT did not correlate with UFH dose or other established methods. Both systems were differently influenced by certain parameters.

Posttraumatic stress disorders were induced in Wistar rats by modeling predatory stress. Animals tested in elevated plus-maze demonstrated signs of high anxiety and difficulties in space orientation. Behavioral disorders were paralleled by degenerative changes in hepatocytes. A course of low-dose high-molecular heparin after stress exposure promoted effective adaptation and normalization of behavioral and morphofunctional disorders. Analysis of the results indicated good prospects of heparin as an effective drug under conditions of exposure to extreme factors of psychotraumatic type.

Introduction: Central venous catheters (CVC) are often required in critical care settings to provide life-sustaining care. Their usage has improved the quality of care in pediatric patients by providing a secure point of access which minimizes the number of peripheral needle sticks. However, CVC usage is not without risks. Children can experience acute CVC-related complications such as venous thromboembolisms (VTEs) and infections. Over the past 20 years, CVC utilization has increased and its associated complications (VTE, central line associated blood stream infection [CLABSI], catheter dysfunction) result in increased lengths of stay and hospital costs. Clinical studies identify CVCs as the single most important risk for DVT in children. Incidence rates in critically-ill children are widely divergent with historical rates of 2.7-18% and 24.7-32.5 per 1000 catheter days. In addition, other historical rates for another CVC-related complication, CLABSI, are limited but demonstrate a rate of 1.21-6.5% and 14.4 per 1000 catheter days. Prevention of catheter-related thrombosis with prophylactic anticoagulants, such as unfractionated heparin, low molecular weight heparin or warfarin, have been tested in several studies in specific subgroups of patients and the majority of studies in pediatric populations were not able to clearly demonstrate a benefit. Despite this, nearly 50% of surveyed Pediatric Intensive Care Unit (PICUs) utilize various forms and doses of heparin prophylaxis to prevent CVC-associated complications. The Penn State Health Children's Hospital PICU utilizes low dose unfractionated heparin infusions (LDUFHI) at 5-15 units/kg/hr for catheter patency and for the prevention of CVC associated complications. Methods: A retrospective chart review of all CVCs, which include non-tunneled CVC (NT-CVC), tunneled lines (TL) and peripherally inserted central catheters (PICC), utilized in the PICU at The Penn State Health Children's Hospital in 2015 was performed to determine if the usage of LDUFHI in critically ill children to maintain catheter patency results in a lower incidence of VTE and CLABSI without increasing bleeding complications in comparison to historically reported data (Beck et al.,J Pediatr. 1998;133(2):237-241; Faustino et al.,J Pediatr. 2013;162(2):387-391; Krishnaiah et al.,Pediatr Crit Care Med. 2012;13(3):e176-e180.). Results: We identified 178 subjects who had CVC which received LDUFHI in 2015. There were a total of 228 CVCs with the majority being non-tunneled CVCs (54%) followed by tunneled lines (34%) and PICCs (12%). Combined, these catheters resulted in 2086 days of use. There was a total of 5 VTEs events for an overall incidence rate of 2.19% and 2.39 per 1000 catheter days. NT-CVC had the lowest rate (1.63%) followed by TL (2.56%) and PICCs (3.7%). However, PICCs has a slightly lower rate when measuring by catheter days (NT-CVC = 2.2 per 1000 catheter days; TL = 4.01 per 1000 catheter days; PICC = 1.46 per 1000 catheter days). There were 3 CLABSI events for an incidence rate of 1.32% and 1.43 per 1000 catheter days (NT-CVC = 1.63% and 2.2 per 1000 catheter days; TL no events; PICC = 3.7% and 1.46 per 1000 catheter days). There were no episodes of heparin induced thrombocytopenia or major bleeding. Overall, the VTE and CLABSI incidence rates are dramatically lower than historical comparisons (VTE = 2.19% and 2.39 per 1000 catheter days versus 15.8-18% and 24.7-32.5 per 1000 catheter days; CLABSI = 1.32% and 1.43 per 1000 catheter days versus 6.5% and 14.4 per 1000 catheter days). In addition, this study can offer more accurate rates as incidence was also measured as a factor in catheter days. Conclusion: This study used a single tertiary pediatric intensive care site in a non-randomized fashion. These data suggest an overall lower incidence of catheter related VTE and CLABSI in critically-ill children who received LDUFHI when compared to published with comparable pediatric study populations. The incidence of complications such as CLABSI were also lower with LDUFHI usage when compared to published data involving critically ill children. The incidence rates were even lower than recently published data involving non-critically ill children. These findings suggest that a multicenter randomized study should be pursued. Disclosures No relevant conflicts of interest to declare.

Background It is controversial issue that heparin decreases thrombosis for microsurgical anastomosis, and its effective role is under discussion. This study is for proving whether low-dose heparin is preventing thrombosis in free flap reconstruction. Methods Through chart reviews of 134 patients, using low-dose heparin for free tissue transfer from 2011 to 2016, retrospective analysis was performed. 33 patients received low-dose heparin therapy after surgery. And 101 patients received no-heparin therapy. Complications included flap necrosis, hematoma formation, dehiscence and infection. Results In no-heparin therapy group, comparing the flap necrosis revealed 16 cases (15.84%). And, flap necrosis was 6 cases (18.18%) in low-dose heparin therapy group. The statistical analysis of flap necrosis rate showed no significant difference (p=0.75). The results showed that there was no significant difference of flap necrosis rate between two groups. Conclusion In this study, patients in the low-dose heparin group had no significantly lower rates of flap failure compared with no-heparin group. This suggests that low-dose heparin may not prevent thrombosis and subsequent flap failure to a significant extent.

Purpose Pipeline embolization devices (PEDs) are associated with inherent thrombotic complications as well as potentially catastrophic spontaneous intraparenchymal hemorrhage. Anti-platelet and anticoagulation therapy must be optimized to reduce thrombotic complications without increasing the incidence of hemorrhage. Post-procedural low dose heparin drip is a prophylactic measure to reduce ischemic stroke risk, with no published data to date reporting efficacy and complications. Here we report the thrombotic and hemorrhagic complication rates of patients receiving post-operative low dose heparin drip, and we compare our results to the published literature rates of patients not receiving such prophylaxis. Materials and methods We completed a retrospective review of patients who had intracranial aneurysms treated with the Pipeline Embolization Device at Westchester Medical Center. A total of 73 individuals received post-operative low dose heparin for an average of 18 hours. Thrombotic and hemorrhagic complications were identified and reported. These rates were compared to the published literature rates of individuals not receiving post-operative heparin. Additional variables included PTT range, type of heparin protocol used (weight based vs physician controlled), total time of heparinization, heparin dose, and number of PEDs deployed. Results 0% (0/73) patients developed thrombotic complications in the post-operative period. The reported literature rate of symptomatic thrombotic events is 6.6%. Post-operative heparin reduced symptomatic thrombotic complications following PED placement (p=0.0125). 2.7% (2/73) patients developed intraparenchymal hemorrhage resulting in neurological deficit, compared to a published rate of hemorrhagic complications approximating 3%. Conclusions Post-procedural low dose heparin prophylaxis reduces thrombotic complications in the post-operative period, without increasing hemorrhagic complications. Disclosures I. Rybkin: None. J. Cooper: None. G. Kaur: None. F. Al-Mufti: None. C. Gandhi: None. J. Santarelli: None.

Background Impella CP® is a percutaneous left ventricular assist device that requires a heparin–dextrose purge solution. The manufacturer recommends heparin 50 units/mL, but supratherapeutic anticoagulation has been observed with this concentration. Objective The purpose of this evaluation was to observe the efficacy and safety of a low-dose heparin-based purge solution (25 units/mL in dextrose 20%). The primary outcome evaluated percentage of activated clotting times (ACTs) below therapeutic range. Secondary objectives included evaluating the incidence of device thrombosis and rate of heparin-induced thrombocytopenia (HIT). Platelet trends were characterized. Methods A single-site retrospective review was conducted for all adults with the Impella CP from January 2015 to December 2017. Results A total of 18 patients were included. The percentage of ACT readings within goal of 160 to 200 seconds was 49%, and 38% of readings were subtherapeutic. Per BARC bleeding criteria, 22% (n = 4) patients experienced class IIIa bleeding and 39% (n = 7) experienced class II bleeding. Though 4 (22%) patients were tested for HIT, no patients were positive. Patients showed universal reductions in platelet counts. Conclusions The use of a low-dose anticoagulation protocol of heparin 25 units/mL in dextrose 20% as needed warrants further evaluation.

Objectives: To identify patient, hospital, and central venous catheter factors that may influence the use of low-dose heparin infusion for central venous catheter patency in critically ill children. Design: Secondary analysis of an international multicenter observational study. Setting: Fifty-nine PICUs over four study dates in 2012, involving seven countries. Patients: Children less than 18 years old with a central venous catheter who were admitted to a participating unit and enrolled in the completed Prophylaxis against Thrombosis Practice study were included. All overflow patients were excluded. Interventions: None. Measurements and Main Results: Of the 2,484 patients in the Prophylaxis against Thrombosis Practice study, 1,312 patients had a central venous catheter. Five hundred seven of those patients used low-dose heparin infusion. The frequency of low-dose heparin infusion was compared across various patient, hospital, and central venous catheter factors using chi-square, Mann-Whitney U, and Fisher exact tests. In the multivariate analysis, age was not a significant factor for low-dose heparin infusion use. Patients with pulmonary hypertension had decreased low-dose heparin infusion use, whereas those with active surgical or trauma diagnoses had increased low-dose heparin infusion use. All centrally inserted central venous catheters were more likely to use low-dose heparin infusion when compared with peripherally inserted central venous catheters. The Asia-Pacific region showed increased low-dose heparin infusion use, along with community hospitals and smaller ICUs ( Conclusions: Patient, central venous catheter, and hospital factors are associated with the use of low-dose heparin infusion in critically ill children. Further study is needed to evaluate the efficacy and persistence of low-dose heparin infusion use.

Objective: To evaluate the therapeutic benefit of low dose heparin in cerebral venous thrombosis, occurring during period ofperpeurum. Study design: Descriptive study. Setting: Department of Medicine DHQ Hospital Mirpur (Department of Obs/Gynae DHQ HospitalMirpur(AK). Period: January 2010 to November 2011. Method: This study was carried on 100 patients with history of postpartum cerebralvenous thrombosis. Out of which 48 on heparin and 52 formed the control group. The ages of all patients were between 20 to 30 years.Parameter recorded included history. Blood pressure.,the diagnosis was supported by cranial computed tomography. The secondary causeswere ruled out on the basis of history and physical examination. The data and results were analyzed in SPSS. Results: Out of 48 patients inheparin group 30 with non-heamorrhage lesion and 18 with haemorrhagic infarction). 52 in control group. 34 non-haemorriagic lesion and 18with haemorragic infarct .in non-haemorrhagic CVT, there is no death in heparin group as compared to 5 deaths in control group. In patients withhaemorriagic lesions, there were 5 deaths in heparin group as compared to 7 deaths in the control group. Heparin faed better than the controlgroup, both in patients with haemorrhagic as well as non-haemorrhagic lesions. Conclusions: Low molecular weight (LMWH) at low doses issafe and effective for both non-haemorrhage and haemorrhgic infarct of postpartum cvt with regard to recovery and outcome as compared tocontrol group.

Background: Transradial access (TRA), compared to femoral access, is preferred for coronary procedures due to reduced access-related bleeding and mortality. Radial artery occlusion (RAO) is a known complication of TRA, and precludes its use as a future access site, conduit for CABG or for

This study reports our preliminary experience of percutaneous coronary angioplasty with low dose heparin and immediate withdrawal of the femoral sheath. After selection, 120 patients underwent a procedure with a low dose of heparin (4,300 ± 700 IU). A total of 120 of 123 lesions (97.6%) were treated successfully by the femoral route. There were no major cardiac complications during the procedure and hospital stay. Patients were allowed to be ambulant 6 hours after the procedure. No significant bleeding occurred. There was no need for surgery relative to the approach route nor for blood transfusion. The use of low dose heparin and immediate withdrawal of the femoral sheath did not increase the risk of coronary angioplasty in these selected patients. The period of bed confinement was shortened and the patients were ambulant earlier, leading to a reduction in their hospital stay with no increase in costs.

Nonvalvular atrial fibrillation (NVAF) is emphasized as a cause of cardioembolic stroke. However little has been investigated about the role of early anticoagulation for preventing early recurrence in elderly cardioembolic stroke patients with NVAF. Here we present the results of early anticoagulation therapy using low-dose heparin in elderly patients with cardioembolic stroke and NVAF, and compare them retrospectively with the rates of recurrence and hemorrhagic accident in untreated patients. Forty-one elderly patients who were admitted to our hospital from July 1992 to May 1998 with NVAF were treated with low-dose heparin (5000 IU/day) immediately after cardioembolic stroke (H+ group, mean age; 84.9). Only one patient (2.4%) suffered recurrent embolism, and 11 patients (26.8%) showed hemorrhagic infarction on CT within 28 days after the initial stroke. Severe hemorrhagic complications were not observed. In a control group (H - group, mean age; 80. 1), who were admitted to our hospital from July 1986 to July 1992 and treated only with conservative therapy, recurrent embolic stroke occurred in 6 (16.2%) of 37 patients, and hemorrhagic infarction was found in 15 (40.5%). Significantly fewer patients suffered recurrent embolism in the H + group than in the H - group (p

We retrospectively studied the incidence of recurrent embolization and hemorrhagic complications during a 2-week period after the onset of cardioembolic stroke according to the form of anticoagulation

Background At many centers, various heparin doses have been administrated systemically during living donor partial hepatectomy in an effort to minimize the potential for graft vascular thrombosis, which could lead to delayed graft function. However, there is no consensus regarding the advisability of heparin administration during living donor hepatectomy for liver transplantation. Methods We prospectively enrolled 270 donors between 2005 and 2011 to investigate donor and recipient outcomes between a low dose (25 IU/kg) and a conventional dose of heparin (50 IU/kg). Results The low-dose heparin group did not show an increased incidence of vascular thrombosis: the rates of hepatic artery and portal vein thromboses were not significantly different between the two groups ( P = .935 and P = .158, respectively). In addition, injection of low-dose heparin reduced donor complications with significant differences in postoperative hospital stay ( P P P = .05/ P = .02) and hemorrhagic complications ( P = .004). Conclusions Administration of low-dose heparin during living donor hepatectomy can be used without worsening vascular thrombosis or donor complications.

The blood coagulation processes in ligated vasa ovarica after preoperative injection of low-dose standard heparin were examined in 30 women during abdominal hysterectomy and adnexectomy. We resected the stumps after 30 min. Histological examination revealed that in 20% of the arteries and in 30% of the veins there were blood coagulation processes of different extent near the ligation only. The final vascular occlusion is mainly achieved via locally limited damage of vessels and endothelial cells which leads to a direct and quick obliteration of the lumen by proliferation of tissue fibroblasts.

The effect was studied of adding heparin to 10 per cent dextrose and to total parenteral nutrition (TPN) solutions infused into peripheral veins of premature babies. The median survival times of sites receiving 10 per cent dextrose and TPN solutions without heparin were 37 and 22 hours, respectively. Addition of 0. liu/ml heparin had little effect whereas adding 0.25iu/ml increased survival times to 48 and 32 hours, respectively. Adding 0.5iu/ml heparin increased survival times to 67 and 68 hours, and with liu/ml they rose further still, to 69 and 83 hours, respectively. These data suggest that 0.5iu/ml may be sufficient to prolong the survival of peripheral intravenous sites in premature babies.

The purpose of this study was to validate a device designed to measure activated clotting time in low-range heparin plasma concentrations (ACT-LR) prospectively during the post-operative period of vascular surgery. Measurement of ACT-LR and activated partial thromboplastin time (APTT) were performed before heparinisation (T0) and at the end of surgery (T1). ACT-LR(T1) and DeltaACT-LR (defined as ACT-LR(T1) - ACT-LR(T0)) were evaluated as diagnostic tests for excessive anticoagulation, defined by APTT more than twice the laboratory's normal, by Bland-Altman method and receiver operating characteristic (ROC) curves. In 103 patients, mean (SD) ACT-LR was 137 (33) s at T0 and 176 (39) s at T1. Bland-Altman graph did not show a good agreement between APTT and ACT-LR. Areas under ROC curves were 0.82 (95% CI: 0.75-0.89) and 0.87 (95% CI: 0.80-0.93) for ACT-LR(T1) and DeltaACT-LR, respectively. Using a threshold of 32 s for DeltaACT-LR, test sensitivity was 87% (95% CI: 81-93%), specificity was 85% (95% CI: 78-92%), positive predictive value was 90% (95% CI: 84-96%) and negative predictive value was 81% (95% CI: 73-86%). While DeltaACT-LR may have some potential in evaluating excessive anticoagulation in vascular surgery, the poor correlation between ACT-LR and APTT does not support its routine use.

Prevention of venous thromboembolism after acute spinal cord injury with low-dose heparin or low-molecular-weight heparin

This review examines the role of graduated elastic compression stockings in the prevention of postoperative deep vein thrombosis. Used alone compression stockings reduce the incidence of postoperative deep vein thrombosis by approximately 60 per cent and when used in combination with other preventive methods, such as low dose heparin or intermittent calf compression, they further reduce the incidence by up to 85 per cent.

The safety and feasibility of early ambulation was evaluated prospectively in 907 patients undergoing elective coronary angioplasty and stenting with the use of 6Fr guiding catheters, low-dose heparin (5,000 IU), and immediate postprocedural sheath removal by comparing ambulation after 4 hours with immobilization for at least 12 hours. Because no excess in puncture site complications (2.3% vs 2.2%) could be demonstrated after 4-hour ambulation, it is concluded that early ambulation after 6Fr guiding catheter angioplasty by the femoral route with low-dose heparin is feasible, safe, and may facilitate a shorter hospital stay.

Prophylaxis with standard low dose subcutaneous heparin has been shown to significantly decrease the risk of deep vein thrombosis and pulmonary embolism, without major bleeding complications. The present report describes a case of unexpected hematoma formation, possibly secondary to subcutaneous low dose heparin injection that was administered in the anterior abdominal wall in a patient who had previously undergone a transverse rectus abdominis musculocutaneous flap reconstruction.

In their article on low-dose heparin thromboembolism prophylaxis, Owings and Blaisdell 1 cited decreased levels of antithrombin III in severely injured patients as a reason for the failure of therapy with low-dose heparin. If this hypothesis holds true, then increasing the dose of unfractionated heparin, which would counteract the reduced bioavailability, or administering a product with predictable bioavailability such as low-molecular-weight heparin (LMWH) should be equally efficacious. The authors mention that the primary problem with the use of LMWH is the inability to document the effect of a given dose except through measurement of ex vivo antifactor Xa activity. Clinical evidence is mounting that LMWH is an option for thromboembolism prophylaxis in high-risk patients without routine laboratory study monitoring. 2 The antifactor IIa and Xa response differs with LMWH preparations. Therefore, these preparations should be evaluated individually for clinical efficacy. The conclusions drawn in this literature review are not consistent

Very low subcutaneous doses of standard and low molecular weight heparin inhibited the traffic of sensitized lymphocytes to a graft site, reduced in situ mononuclear cell infiltration and prolonged skin allograft survival in mice. Similar effects were caused by low doses of oral heparin, while higher oral doses prolonged graft survival. Our results suggest that oral heparin may have immunosuppressive properties applicable in clinical transplantation.

To the Editor: In their report on the efficacy of activated protein C in reducing mortality from sepsis at 28 days (March 8, 2001, issue),1 Bernard et al. presented the results of a retrospective s...