Factors Influencing Unfractionated Heparin Pharmacokinetics and Pharmacodynamics During a Cardiopulmonary Bypass.

BACKGROUND: Unfractionated heparin (UFH) is commonly used during cardiac surgery with a cardiopulmonary bypass to prevent blood clotting. However, empirical administration of UFH leads to variable responses. Pharmacokinetic and pharmacodynamic modeling can be used to optimize UFH dosing and perform real-time individualization. In previous studies, many factors that could influence UFH pharmacokinetics/pharmacodynamics had not been taken into account such as hemodilution or the type of UFH. Few covariates were identified probably owing to a lack of statistical power. This study aims to address these limitations through a meta-analysis of individual data from two studies. METHODS: An individual patient data meta-analysis was conducted using data from two single-center prospective observational studies, where different UFH types were used for anticoagulation. A pharmacodynamic/pharmacodynamic model of UFH was developed using a non-linear mixed-effects approach. Time-varying covariates such as hemodilution and fluid infusions during a cardiopulmonary bypass were considered. RESULTS: Activities of UFH's anti-activated factor/anti-thrombin were best described by a two-compartment model. Unfractionated heparin clearance was influenced by body weight and the specific UFH type. Volume of distribution was influenced by body weight and pre-operative fibrinogen levels. Pharmacodynamic data followed a log-linear model, accounting for the effect of hemodilution and the pre-operative fibrinogen level. Equations were derived from the model to personalize UFH dosing based on the targeted activated clotting time level and patient covariates. CONCLUSIONS: The population model effectively characterized UFH's pharmacokinetics/pharmacodynamics in cardiopulmonary bypass patients. This meta-analysis incorporated new covariates related to UFH's pharmacokinetics/pharmacodynamics, enabling personalized dosing regimens. The proposed model holds potential for individualization using a Bayesian estimation.

The missing slope: paradoxical shortening of activated partial thromboplastin time in a patient on unfractionated heparin therapy.

This case report describes false shortening of activated partial thromboplastin time (aPTT) due to erroneous optical reading of the clotting point in the presence of unfractionated heparin (UFH), and a biphasic waveform. Activated partial thromboplastin time performed on a coagulometer with photo-optical detection yielded an ambiguous clotting curve characterized by an early and steady decrease in light transmittance throughout the whole measuring range, with the clotting point read at 65 seconds. Further investigations included measurement of aPTT by means of a mechanical clot detection method as well as determination of another heparin-sensitive coagulation assay, that is thrombin time (TT), both being unmeasurably prolonged (> 150 seconds). Communication with clinicians revealed that the patient was on continuous UFH therapy and had an underlying sepsis, with highly elevated C-reactive protein (289 mg/L). The aPTT measurements requested at three timepoints later during the same day revealed gradual aPTT shortening and unveiled a peculiar biphasic waveform pattern. In this case, unmeasurably prolonged aPTT due to UFH therapy was masked by a biphasic aPTT curve pattern making only the first slope of the biphasic waveform visible within the measuring range. The early decrease in plasma light transmittance mimicked optical changes related to clot formation, thus causing erroneous optical reading and yielding a falsely shortened aPTT. This case emphasizes that such a pattern should be carefully inspected, especially when a combination of a critically ill condition and UFH therapy is present, in order to prevent erroneous reporting of aPTT and potential adverse effects on patient care.

Safety and Functional Pharmacokinetic Profile of APAC, a Novel Intravascular Antiplatelet and Anticoagulant.

ABSTRACT: Vascular intervention-induced platelet and coagulation activation is often managed with a combination of antiplatelets and anticoagulants, with evident benefits, but with a risk of systemic bleeding. Antiplatelet and anticoagulant (APAC) is a dual antiplatelet and anticoagulant heparin bioconjugate, which targets vascular injury sites to act as a local antithrombotic. We assessed the nonclinical safety and exposure of intravenously infused APAC in rats and cynomolgus monkeys by using single-day and 14-day repeat dose toxicology and pharmacodynamic markers. Activated partial thromboplastin time (APTT) was used as a functional surrogate of anticoagulant exposure of APAC. Routine clinical in-life observations were followed by clinical pathology and necropsy. The no-observed-adverse-effect level (NOAEL) in rats for the single APAC dose was 20 mg/kg and for the repeated administration was 10 mg/kg/d. Monkeys tolerated a single APAC dose of 10 mg/kg, although the red blood cell count reduced 16%-19% correlating with tissue hemorrhage at vein puncture and affected muscle sites during handling of the animals. However, after 2-week recovery, all clinical signs were normal. The single dose NOAEL exceeded 3 mg/kg. The repeat administration of 3-6 mg/kg/d of APAC was tolerated, but some clinical signs were observed. The NOAEL for repeated dosing was 0.5 mg/kg/d. APAC prolonged APTT dose-dependently in both species, returning to baseline after 1.5 (<10 mg/kg) or essentially by 6 hours also under repetitive dosing. The toxicology profile supports the safety of an intravenous APAC dose of 0.5 mg/kg/d for possible clinical applications. APTT is an acceptable indicator of the immediate systemic anticoagulation effect of APAC.

Routine fixed-dose heparin vs. ACT-guided heparin administration for elective PCI and its influence on patient in-hospital outcome: a retrospective study.

OBJECTIVE: Activated clotting time (ACT)-based heparin dosing during percutaneous intervention (PCI) is recommended by Society guidelines. However, the relationship between ACT and outcome in the setting of elective PCI has not been sufficiently studied. We sought to evaluate the in-hospital outcome of patients undergoing elective PCI while receiving fixed-dose heparin without ACT measurement versus those with ACT-guided management. METHODS: This retrospective study included consecutive patients undergoing elective PCI in a single-center between 11/2015 and 12/2018. Patients were divided into two groups, depending on whether ACT was measured. Heparin-only anticoagulation and non-femoral procedures were allowed. Patient demographics, procedural data and in-hospital outcomes were collected. The primary outcome was in-hospital major adverse cardiovascular events (MACE), secondary (safety) outcomes were in-hospital definite stent thrombosis, Bleeding Academic Research Consortium bleeding, access-related complications (any) as well as peri-procedural complications. RESULTS: In total, 500 procedures were included in the study, 151 ACT and 349 fixed-dose. Patient demographics and medical history in both groups were well balanced, but those having ACTs were younger (63.2 ± 10.9 vs. 66.5 ± 11.3; P = 0.003) and less likely to have a history of coronary artery disease (74 vs. 82%; P = 0.032) or kidney failure. Procedural data were similar; however, total heparin dose and procedure length were higher in the ACT group (6232 ± 1388 vs.5032 ± 417 units; P < 0.001; 40.1 ± 14.0 vs. 30.3 ± 12.7 min; P < 0.001). Primary and secondary outcome events were rare and similar (MACE 1.1 vs. 1.3%; P = 0.86). CONCLUSIONS: A fixed-dose heparin injection (5000 IU) approach for elective PCI while omitting ACT offers slightly shortened procedural time and similar in-hospital safety profile.

Prediction of heparin binding of mutated short sequences of rat thyroglobulin.

BACKGROUND: Binding of thyroglobulin (Tg) to heparin is involved in Tg transcytosis via megalin. Rat Tg (rTg) binds to heparin through an exposed carboxyl terminal region (RELPSRRLKRPLPVK, Arg2489-Lys2503) rich in positively charged residues. This region is not entirely conserved in human Tg (hTg) (Arg2489-Glu2503, REPPARALKRSLWVE), resulting in lower affinity binding. Here, we developed a score to predict to what extent secondary structure modifications affect the heparin-binding ability of rTg. METHODS: We designed eight synthetic peptides, including one with the Arg2489-Lys2503 sequence of rTg (rTgP), one with the corresponding sequence of hTg (hTgP), and six "mutant" peptides, each carrying a point mutation obtained by replacing one amino acid residue of rTgP with the corresponding residue of hTgP. Heparin binding was assessed in solid-phase assays. The Bmax and the constants of dissociation (Kd) were calculated. RESULTS: Using a no-fee online service, we obtained predictions of peptide secondary structures and developed a scoring system to estimate to what extent mutations are expected to modify rTg secondary structure. The score was designated as Probability of Secondary Structure Change (PSSC) and it significantly correlated with the BMax (R = 0.942, P < 0.001) and the Kds (R = - 0.744, P < 0.01) of heparin binding of hTgP and of the "mutant" peptides. CONCLUSIONS: The PSSC score allows predicting to what extent point mutations are likely to affect the heparin-binding ability of short sequences of proteins: in this case rTg, regardless of whether mutations affect charge of the sequence. The secondary structure of Tg is likely to play a role in heparin binding.

The heparin-von Willebrand factor interaction and conventional tests of haemostasis - the challenges in predicting bleeding in cardiopulmonary bypass.

Bleeding is a significant complication of cardiopulmonary bypass (CPB), despite routine anticoagulation monitoring. This is likely to be multifactorial. In this prospective, single-centre cohort study of 30 patients undergoing CPB surgery, our aim was to characterise the changes in von Willebrand factor (VWF) function, platelet interaction and the global coagulation changes during and after CPB surgery and to determine whether bleeding can be predicted. Samples were taken at six time points before, during and after CPB surgery. We observed a significant rise in VWF antigen (VWF:Ag) throughout surgery, which continued postoperatively. The absolute VWF collagen-binding assays (VWF:CB) and VWF ristocetin cofactor (VWF:RCo) rose significantly but the VWF:CB/VWF:Ag and VWF:Ag/VWF:RCo fell significantly (P = 0·0015 and P = 0·0143), suggesting loss of large multimers. We detected a non-significant trend to loss of VWF:RCo after heparinisation and a significant recovery after protamine reversal which could reflect a direct heparin effect. There was a significant increase in the R and K times with a fall in alpha angle and maximum amplitude after heparin administration, using heparinase-thromboelastography (TEG). The parameters both significantly improved following protamine (P = 0·007 and P = 0·0054). The activated clotting time (ACT) and heparin anti-Xa level correlated poorly; neither predicted clinically significant bleeding. None of these parameters had a relationship with intraoperative blood loss or requirement for blood product replacement.

The Relationship between the Initial Anti-factor Xa Measurement and the Duration of Direct Oral Anticoagulant Influence in Patients Transitioning to Heparin.

BACKGROUND: Anticoagulation monitoring during transition from direct oral anticoagulants (DOAC) to heparin infusions is a significant challenge. Factor Xa inhibitors influence the heparin calibrated antifactor Xa assay. The University of Virginia (UVA) Medical Center utilized a corrected antifactor Xa assay (c-AXA) during this transition period, which removes DOAC-mediated antifactor Xa activity (d-AXA) and reflects heparin-specific activity. Currently, the duration of this influence is not well described. STUDY OBJECTIVE: This study had two aims: to determine if the initial d-AXA is predictive of the duration of DOAC influence and to further characterize this influence among different patient populations. METHODS: This retrospective study included adult patients admitted to UVA Medical Center between September 2016 and March 2017, with c-AXA measurements, who received apixaban or rivaroxaban within 48 hours before heparin initiation. A Pearson correlation test, Kaplan-Meier Survival Analysis, and multivariate linear regression were used to assess the relationship between initial d-AXA and duration of influence. RESULTS: Sixty-eight patients met inclusion criteria and were maintained on either apixaban (85%) or rivaroxaban (15%) before heparin initiation. The initial d-AXA ranged from 0.11 to 3.27 IU/ml. The mean duration of influence was 69.3 ± 46.2 hours, with a median duration of 62.7 hours. No strong correlation was identified between initial d-AXA and duration of influence (R2 = 0.124). Presence of interacting medications significantly increased duration of influence (p=0.012). No significant difference in duration of influence existed between patients with normal renal function and those with dynamic renal function (p=0.84), or with body mass index (BMI) greater than 40 kg/m2 (p=0.16). CONCLUSIONS: The initial d-AXA was not predictive of duration of influence in patients transitioning from DOACs to heparin infusion; however, the median duration of influence suggests influence may be present for longer than currently stated in the literature, especially in those taking interacting medications.

Hot topics in coagulation testing: Important considerations for testing children for bleeding/thrombotic disorders.

The accurate use and interpretation of diagnostic investigations are essential for safe and effective patient care. Appropriate application and interpretation of coagulation testing can be challenging, and many controversies exist relating to the standardization of testing procedures, the application of relevant tests to different patient populations and the interpretation of test results. We present a list of the most prominent controversies in coagulation testing and have selected three specific examples (age-appropriate reference ranges, therapeutic anticoagulation monitoring and tests of thrombin generation) for closer discussion, highlighting examples with a paediatric framework. We discuss the limitations of discrete age-partitioned reference intervals, given the established principle of developmental haemostasis; the difficulties in establishing normative data across different laboratories; important pre-analytical variables affecting coagulation testing; the challenges in interpreting APTT and anti-Xa assays for monitoring unfractionated heparin therapy in different clinical situations; and the limitations in interpreting tests of thrombin generation due to current available thrombin-specific substrates and the complicating factor of variable alpha2-macroglobulin levels. These controversies are demonstrated using paediatric examples, but raise important implications for coagulation testing in patients of all ages and highlight the pressing need for further research in these areas.

A transport system based on a quantum dot-modified nanotracer is genetically and developmentally stable in pregnant mice.

The use of nanoscale materials (NMs) could cause problems such as cytotoxicity, genomic aberration, and effects on human health, but the impacts of NM exposure during pregnancy remain uncharacterized in the context of clinical applications. It was sought to determine whether nanomaterials pass through the maternal-fetal junction at any stage of pregnancy. Quantum dots (QDs) coated with heparinized Pluronic 127 nanogels and polyethyleneimine (PEI) were administered to pregnant mice. The biodistribution of QDs, as well as their biological impacts on maternal and fetal health, was evaluated. Encapsulation of QDs with a nanogel coating produces a petal-like nanotracer (PNt), which could serve as a nano-carrier of genes or drugs. PNts were injected through the tail vein and accumulated in the liver, kidneys, and lungs. QD accumulation in reproductive organs (uterus, placenta, and fetus) differed among phases of pregnancy. In phase I (7 days of pregnancy), the QDs did not accumulate in the placenta or fetus, but by phase III (19 days) they had accumulated at high levels in both tissues. Karyotype analysis revealed that the PNt-treated pups did not have genetic abnormalities when dams were treated at any phase of pregnancy. PNts have the potential to serve as carriers of therapeutic agents for the treatment of the mother or fetus and these results have a significant impact on the development and application of QD-based NPs in pregnancy.

Repairing peripheral nerve defects with revascularized tissue-engineered nerve based on a vascular endothelial growth factor-heparin sustained release system.

To enhance the angiogenic capacity of tissue-engineered peripheral nerves, we have constructed revascularized tissue-engineered nerves based on a vascular endothelial growth factor (VEGF)-heparin sustained release system. However, the effects of the repair of large peripheral nerve defects are not known. In this study, we used the above revascularized tissue-engineered nerve to repair large nerve defects in rats. The repair effects were observed through general observation, functional evaluation of nerve regeneration, ultrasound examination, neural electrophysiology, wet weight ratio of bilateral gastrocnemius muscle, histological evaluation, and quantitative real-time polymerase chain reaction (PCR) analysis. The results showed that the tissue-engineered peripheral nerve based on a VEGF-heparin sustained release system can achieve early vascularization and restore blood supply in the nerve graft area. The realization of early vascularization in the area of the nerve defect greatly promotes the speed of nerve regeneration and reconstruction in the area of the nerve defect, which greatly advances the process of nerve repair and reconstruction and accelerates the restoration of the normal morphological structure and function of peripheral nerves.

Unfractionated heparin dosing in obese patients.

Background The effect of obesity on the pharmacokinetics and pharmacodynamics of unfractionated heparin is not clearly understood, therefore to reduce the risk of bleeding, maximal dose (capped) nomograms are often used. This can lead to inadequate anticoagulation and increased mortality and morbidity. In Queensland, Australia, statewide nomograms recommend total-body-weight-based dosing, with capped initial bolus and maintenance doses. Objective To determine if current practices for unfractionated heparin dosing leads to inadequate anticoagulation in obese patients. Setting Princess Alexandra Hospital, Queensland, Australia. Method A retrospective audit of unfractionated heparin dosing in 200 patients divided into cohorts of; < 100 kg (defined as non-obese), 100-124.9 kg, 125-150 kg and > 150 kg, Main outcomes measured Mean maintenance doses in U/h and U/kg/h required to achieve two consecutive therapeutic activated partial thromboplastin times' and the corresponding time to achieve this endpoint. Results The mean ± standard deviation maintenance doses required to achieve two consecutive therapeutic activated partial thromboplastin times' in U/h were 1229 ± 316, 1673 ± 523, 2031 ± 596 and 2146 ± 846, and in U/kg/h were 16 ± 4.1, 15.1 ± 4.8, 14.9 ± 4.2 and 11.6 ± 4.2 for the weight cohorts respectively. The median time (inter-quartile range) to therapeutic activated partial thromboplastin times' for obese patients was 39 (21.5-56) h. Conclusions Our results suggest inadequate dosing in obese patients. We recommend the use of larger absolute doses (U/h) of nfractionated heparin but reduced uncapped total body weight-based doses-(U/kg/h) as patient weight increases.

Comprehensive Glycomic Analysis Reveals That Human Serum Albumin Glycation Specifically Affects the Pharmacokinetics and Efficacy of Different Anticoagulant Drugs in Diabetes.

Long-term hyperglycemia in patients with diabetes leads to human serum albumin (HSA) glycation, which may impair HSA function as a transport protein and affect the therapeutic efficacy of anticoagulants in patients with diabetes. In this study, a novel mass spectrometry approach was developed to reveal the differences in the profiles of HSA glycation sites between patients with diabetes and healthy subjects. K199 was the glycation site most significantly changed in patients with diabetes, contributing to different interactions of glycated HSA and normal HSA with two types of anticoagulant drugs, heparin and warfarin. An in vitro experiment showed that the binding affinity to warfarin became stronger when HSA was glycated, while HSA binding to heparin was not significantly influenced by glycation. A pharmacokinetic study showed a decreased level of free warfarin in the plasma of diabetic rats. A preliminary retrospective clinical study also revealed that there was a statistically significant difference in the anticoagulant efficacy between patients with diabetes and patients without diabetes who had been treated with warfarin. Our work suggests that larger studies are needed to provide additional specific guidance for patients with diabetes when they are administered anticoagulant drugs or drugs for treating other chronic diseases.

Structure-Based Site-Specific PEGylation of Fibroblast Growth Factor 2 Facilitates Rational Selection of Conjugate Sites.

Polyethylene glycol modification (PEGylation) can enhance the pharmacokinetic properties of therapeutic proteins by the attachment of polyethylene glycol (PEG) to the surface of a protein to shield the protein surface from proteolytic degradation and limit aggregation. However, current PEGylation strategies often reduce biological activity, potentially as a result of steric hindrance of PEG. Overall, there are no structure-based guidelines for selection of conjugate sites that retain optimal biological activity with improved pharmacokinetic properties. In this study, site-specific PEGylation based on the FGF2-FGFR1-heparin complex structure is performed. The effects of the conjugate sites on protein function are investigated by measuring the receptor/heparin binding affinities of the modified proteins and performing assays to measure cell-based bio-activity and in vivo stability. Comprehensive analysis of these data demonstrates that PEGylation of FGF2 that avoids the binding sites for fibroblast growth factor receptor 1 (FGFR1) and heparin provides optimal pharmacokinetic enhancement with minimal losses to biological activity. Animal experiments demonstrate that PEGylated FGF2 exhibits greater efficacy in protecting against traumatic brain injury-induced brain damage and neurological functions than the non-modified FGF2. This rational structure-based PEGylation strategy for protein modification is expected to have a major impact in the area of protein-based therapeutics.

Identifying optimal heparin management during cardiopulmonary bypass in Chinese people: a retrospective observational comparative study.

Traditionally heparin is adapted according to total body weight (TBW) to providing anticoagulation during cardiopulmonary bypass (CPB), but it may be inaccurate in some patients. The medical records of 100 adult patients who received CPB in Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology over a 10-month period in 2017 were included in the retrospective study. An unfractionated heparin (UFH) bolus of 300 IU/kg TBW was injected before initiation of CPB followed by additional doses (50 to 100 IU/kg) to maintain a target activated coagulation time (ACT) of at least 480 s. We used TBW, ideal body weight (IBW), lean body weight (LBW), or body mass index (BMI) to establish and evaluate a linear model of ACT and the amount of heparin respectively. The linear fit effect of the model based on BMI on the original data is better than the others. As the instruments to measure heparin concentration is unavailable in most medical institutions in China. The new linear model based on BMI is helpful to estimate a more individualized heparin dosage in the heparinized phase and to provide useful reference to the amount of remaining heparin in the neutralization phase.

Evaluation of the Activity of Heparin Injected into the Fully Implantable Catheter for Chemotherapy (Portocath) between Two Moments of Use.

BACKGROUND: The aim of this study is to analyze whether heparin, used as a lock in fully implantable catheter for chemotherapy (portocath), maintains its activity even if it remains in the catheter for a long period of time. METHODS: According to the institutional protocol, all catheters routinely use the lock solution with 3 mL of heparinized solution after chemotherapy and the time interval between each change as lock in the catheters studied ranged from 7 to 30 days. A total of 25 blood samples from 22 patients with 6 types of neoplasia on chemotherapy or not were collected according to routine, and the 10 mL of liquid contained in the first aspirated reservoir/catheter (corresponding to the lock of the last section), were sent for laboratory analysis for prospectively studied with the following tests: anti-Xa, partially activated thromboplastin time (APTT), thrombin time (TT), reptilase, and thromboelastogram. RESULTS: Heparin activity was found in 96% of the anti-Xa and APTT tests. In relation to TT, 92% presented activity. The reptilase test was performed on 24 samples with significant time reduction in all of them. In the INTEM stage, the thromboelastometry test showed activity in 92% of samples and in the HEPTEM phase there was reduction in time in all samples. In all samples, the heparin activity was found to be independent of the time of use. CONCLUSIONS: We can conclude that lock of heparinized solution used in our service in fully implantable central venous catheters for chemotherapy was maintained with active heparin even after a long period of time (up to 30 days), demonstrating that the half-life of the substance within the catheter is greater than its plasma half-life.

Evaluation of a simple off-the-shelf bi-layered vascular scaffold based on poly(L-lactide-co-ε-caprolactone)/silk fibroin in vitro and in vivo.

Purpose: In the field of small-caliber vascular scaffold research, excellent vascular remodeling is the key to ensuring anticoagulant function. We prepared an off-the-shelf bi-layered vascular scaffold with a dense inner layer and a loose outer layer and evaluated its remodeling capabilities by in vivo transplantation. Materials and Methods: Based on poly(L-lactide-co-ε-caprolactone) (PLCL), silk fibroin(SF), and heparin (Hep), PLCL/SF/Hep bi-layered scaffolds and PLCL/Hep bi-layered scaffolds were prepared by electrospinning. The inner layer was a PLCL/SF/Hep or PLCL/Hep nanofiber membrane, and the outer layer was PLCL/SF nano yarn. The in vitro tests included a hydrophilicity test, mechanical properties test, and blood and cell compatibility evaluation. The in vivo evaluation was conducted via single rabbit carotid artery replacement and subsequent examinations, including ultrasound imaging, immunoglobulin assays, and tissue section staining. Results: Compared to the PLCL/Hep nanofiber membrane, the hydrophilicity of the PLCL/SF/Hep nanofiber membrane was significantly improved. The mechanical strength met application requirements. Both the blood and cell compatibility were optimal. Most importantly, the PLCL/SF/Hep scaffolds maintained lumen patency for 3 months after carotid artery transplantation in live rabbits. At the same time, CD31 and α-SMA immunofluorescence staining confirmed bionic endothelial and smooth muscle layers remodeling. Conclusion: Using this hybrid strategy, PLCL and SF were combined to manufacture bi-layered small-caliber vascular scaffolds; these PLCL/SF/Hep scaffolds showed satisfactory vascular remodeling.

Heparin-induced thrombocytopenia complicating extracorporeal membrane oxygenation support: Review of the literature and alternative anticoagulants.

Heparin-induced thrombocytopenia (HIT) is a life-threatening prothrombotic, immune-mediated complication of unfractionated heparin and low molecular weight heparin therapy. HIT is characterized by moderate thrombocytopenia 5-10 days after initial heparin exposure, detection of platelet-activating anti-platelet factor 4/heparin antibodies and an increased risk of venous and arterial thrombosis. Extracorporeal membrane oxygenation (ECMO) is a form of mechanical circulatory support used in critically ill patients with respiratory or cardiac failure. Systemic anticoagulation is used to alleviate the thrombotic complications that may occur when blood is exposed to artificial surfaces within the ECMO circuit. Therefore, when HIT complicates patients on ECMO support, it is associated with a high thrombotic morbidity and mortality. The risk for HIT correlates with the accumulative dosage of heparin exposure. In ECMO patients receiving continuous infusion of heparin for circuit patency, the risk for HIT is not neglected and must be thought of in the differential diagnosis of the appropriate clinical and laboratory circumstances. The following article reviews the current knowledge in HIT complicating ECMO patients and the alternative anticoagulation options in the presence of HIT.

Clinical outcomes with unfractionated heparin monitored by anti-factor Xa vs. activated partial Thromboplastin time.

Anti-factor Xa (anti-Xa) monitoring of unfractionated heparin (UFH) is associated with less time to achieve therapeutic anticoagulation compared to the activated partial thromboplastin time (aPTT). However, it is unknown whether clinical outcomes differ between these methods of monitoring. The aim of this research was to compare the rate of venous thrombosis and bleeding events in patients that received UFH monitored by anti-Xa compared to the aPTT. A retrospective review of electronic health records identified adult patients that received UFH given intravenously (IV) for ≥2 days, with either anti-Xa or aPTT monitoring at an academic tertiary care hospital. This was a pre/post study design conducted between January 1 to December 30, 2014 (aPTT), and January 1 to December 30, 2016 (anti-Xa). All UFH adjustments were based on institutional nomograms. The primary outcome was venous thrombosis and the secondary outcome was bleeding, both of which occurred between UFH administration and discharge from the index hospitalization. A total of 2500 patients were in the anti-Xa group and 2847 patients aPTT group. Venous thrombosis occurred in 10.2% vs 10.8% of patients in the anti-Xa and aPTT groups, respectively (P = .49). Bleeding occurred in 33.7% vs 33.6% of patients in the anti-Xa and aPTT groups, respectively (P = .94). Anti-Xa monitoring was not an independent predictor of either outcome in multivariate logistic regression analyses. Our study found no difference in clinical outcomes between anti-Xa and aPTT-based monitoring of UFH IV.