Stereocontrolled synthesis of the aconitine D ring from D-glucose.

The synthesis of a fully oxygenated aconitine D ring precursor from (D)-(+)-glucose is described. The route features a highly diastereoselective alkynyl Grignard ketone addition and a base-mediated enelactone to 1,3-diketone rearrangement.

Hereditary thrombocytopenia with platelet sialic acid deficiency and mutations in the GNE genes.

BACKGROUND: The inherited macrothrombocytopenias are rare disorders and the underlying cause can be identified in many cases but in some, this can remain enigmatic. Platelet transfusions are often administered during hemorrhagic events. METHODS: A patient with previously unexplained inherited macrothrombocytopenia with a platelet count between 3-20 × 109 /L is described in which studies were performed using exome sequencing (ES) and platelet flow cytometry. RESULTS: Both the hemoglobin and white cell counts were normal. ES revealed two suspicious variants, one likely pathogenic and one a variant of uncertain significance, in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, and flow cytometry showed diminished expression of surface platelet sialic acid (about 5%) but normal red cell sialic acid. The Thrombopoietin (TPO) level was low, and the patient responded to TPO-mimetic treatment with an increase in the platelet count. CONCLUSION: Two variants in the GNE gene were able to be upgraded to pathogenic with apparently restricted expression to the megakaryocyte lineage. Platelet transfusion may be avoided in these patients with TPO-mimetic treatment.

In vitro comparison of CPD whole blood with conventional blood components.

INTRODUCTION: Resuscitation of severely injured trauma patients is commonly performed using red blood cells in additive solution supplemented with plasma and platelet concentrates. There is an increasing interest in the use of low anti-A titer Group O whole blood (LTOWB) in the early management of the resuscitation. It is unclear whether clinical outcome is improved using this approach. METHODS: Expired units of CPD-LTOWB were studied on Day 22 and expired units of thawed plasma on Day 6 and Day 7. LTOWB was assessed for hemoglobin content, clotting factor levels and platelet numbers and function using thromboelastography (TEG) and impedance aggregation. Assays of fibrinogen and FV, FVIII, FVII and FX were performed on the expired plasma. The LTOWB hemoglobin was compared to red cells in additive solution (AS-RBCs) and the clotting factor levels to those of expired thawed plasma. Platelet function was compared to fresh whole blood samples from healthy subjects. RESULTS: LTOWB contained slightly more hemoglobin than the AS-RBCs (Medians, 66 v 59 G), and the plasma content of fibrinogen was similar. Other clotting factors were reduced by approximately 15% except for FVIII which was 30% less. Both TEG and impedance aggregometry showed evidence of residual platelet function despite the prolonged period of refrigerator storage. CONCLUSION: LTOWB contains higher hemoglobin and adequate clotting factors, and residual platelet function is demonstrated indicating that this product would be expected to be at least equivalent to a single unit of each of the conventional components commonly used in trauma resuscitation.

Interaction Between Platelet and Fibrinogen on Clot Strength in Healthy Patients.

OBJECTIVE: The purpose of this study was to explore the relationship between platelet concentration (PLT) (× 109/L) and clot strength measured by thromboelastography maximum amplitude (TEG-MA) in healthy volunteers without a history of coagulation abnormalities. Secondarily, the relationship between fibrinogen (mg/dL) and TEG-MA was analyzed. DESIGN: A prospective study. SETTING: At a university's tertiary-care center. MEASUREMENTS AND MAIN RESULTS: Using whole blood, PLT was reduced in the first part, and hematocrit was reduced in the second part of the study by hemodilution with platelet-rich and -poor plasma. Thromboelastography (TEG 5000 Haemonetics) was performed to measure clot formation and strength. Spearman correlation coefficients regression analyses and receiver-operating characteristics (ROC) were obtained to analyze the relationships among PLT, fibrinogen, and TEG-MA. Strong correlations were found in univariate analysis between PLT and TEG-MA (r = 0.88; p < 0.0001) and between Fibrinogen and TEG-MA (r = 0.70; p = 0.003). A biphasic relationship between PLT and TEG-MA was linear below a PLT 90 × 109/L, followed by a plateau above 100 × 109/L (p = 0.001). A linear relationship between fibrinogen (190-474 mg/dL) and TEG-MA (53-76 mm) was found (p = 0.0007). The ROC analysis found that PLT = 60 × 109/L was associated with a TEG-MA of 53.0 mm. The product of PLT and fibrinogen concentrations was more strongly correlated (r = 0.91) to TEG-MA than either PLT (r = 0.86) or fibrinogen (r = 0.71) alone. A ROC analysis revealed that a TEG-MA of 55 mm was associated with a PLT × fibrinogen of 16,720. CONCLUSION: In healthy patients, a PLT of 60 × 109/L was associated with normal clot strength (TEG-MA ≥53 mm), and there was little change in clot strength with PLT >90 × 109/L. Although prior analyses described the contributions of platelets and fibrinogen toward clot strength, they are presented and discussed independently. The data above described clot strength as an interaction among them. Future analyses and clinical care should evaluate and recognize the interplay.

Influenza-associated thrombotic thrombocytopenic purpura: A report of two cases and a brief review of the literature.

BACKGROUND AND OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is often preceded by a recent history of an acute infection and influenza is the most implicated virus. MATERIALS AND METHODS: We identified two cases of TTP, which were preceded by influenza between 2010 and 2021. In one patient, we epitope mapped the binding specificity of antibodies using an overlapping peptide approach of the stalk protein of Influenza B and the cysteine-rich spacer domain (CRSD) of ADAMTS13. A literature search was performed for reports of influenza-associated TTP over the period 1980-2021. RESULTS: Two patients were identified in which TTP was preceded by influenza, one Influenza A and the other Influenza B. Epitope mapping of the latter's plasma identified target epitopes in both the stalk protein of Influenza B and CRSD of ADAMTS13. The literature review revealed only seven case reports, all but one from Europe or Asia and associated with Influenza A. Severe ADAMTS13 deficiency was demonstrated in only four cases. CONCLUSION: We report the first small case series of influenza-associated TTP. Moreover, it is the first case implicating Influenza B and a mechanism favouring polyclonal B-cell proliferation rather than molecular mimicry as the stimulus to form anti-ADAMTS13 auto-antibodies is suggested.

A Pilot Study to Assess the Clinical Onset of IV Heparin in Interventional Cardiology and Cardiac Surgery.

OBJECTIVES: To determine the onset of heparin anticoagulation, using 2 different measures of activated clotting times (ACT), thromboelastography (TEG; R-time), and anti-Xa levels, after administering low- (100 U/kg) and high- (300 U/kg) dose intravenous (IV) heparin to patients undergoing transcatheter aortic valve replacement (TAVR) and cardiac surgery, respectively. DESIGN: Prospective study. SETTING: Single academic institution. PARTICIPANTS: Patients with normal baseline coagulation presenting for TAVR or cardiac valve surgery. INTERVENTIONS: Coagulation studies were performed at baseline, 30 seconds, 90 seconds, and 180 seconds after IV heparin administration. The tests included iSTAT (iACT) and Hemochron ACT (hACT), TEG R-Time, and anti-Xa levels. At the authors' institution, anti-Xa is the preferred measure of heparin anticoagulation when time permits. ACT, a rapid point- of-care test, is used to assess intraprocedural anticoagulation. MEASUREMENTS AND MAIN RESULTS: After both low- and high-dose heparin, there are peak increases in ACT and anti-Xa at 30 seconds, followed by a decline at 90 seconds and plateau at 180 seconds. The TEG R-time remained elevated (>80 minutes) throughout. For TAVR cases, all anti-Xa was >1.5 IU/mL, and was associated with an iACT >180 seconds and an hACT >200 seconds. For cardiac valve surgery cases, all anti-Xa was >2.4 and associated with an iACT >420 seconds and and hACT >340 seconds. Compared with hACT, iACTs were significantly lower at all time points after low-dose heparin, but not after high-dose heparin. CONCLUSIONS: In this pilot study, heparin anticoagulation was detected as early as 30 seconds after IV administration, based on ACT, anti-Xa levels, and TEG R-time.

Acute ischemic stroke on anti-Xa inhibitors: Pharmacokinetics and outcomes.

BACKGROUND AND PURPOSE: Direct oral anticoagulant (DOAC) ingestion within 48 h is an exclusion for thrombolysis in acute ischemic stroke (AIS) patients. We aim to shed light on pharmacokinetic correlates and outcomes in patients with AIS excluded from thrombolysis due to DOAC use. METHODS: This is a single center retrospective study of consecutive patients with AIS within 4.5 h from last known normal and excluded from thrombolytic therapy due to confirmed Xa inhibitor DOAC (DOACXa) intake within the prior 48 h. We used linear regression to test the correlation between time from last DOACXa ingestion and anti-Xa level. RESULTS: Over a period of 2.5 years, we identified 44 patients who did not receive thrombolysis because of presumed DOAC intake within 48 h. In adjusted linear regression, there was an association between time from last DOAC ingestion and Xa level (beta = -0.69, p < 0.001). Among the 37 patients with known atrial fibrillation not receiving alteplase due to DOAC use, the 90-day mortality was 35.1% (13/37) and 77% (10/13) of deaths were stroke related. CONCLUSIONS: Patients with AIS on DOAC therapy face a heightened risk of mortality. Studies are needed to investigate the safety and efficacy of thrombolysis in such patients based on time of last DOAC ingestion and/or anti-Xa/drug level.

Convalescent Plasma for Patients With Severe Coronavirus Disease 2019 (COVID-19): A Matched Cohort Study.

BACKGROUND: The efficacy of convalescent plasma (CP) for the treatment of coronavirus disease 2019 (COVID-19) remains unclear. METHODS: In a matched cohort analysis of hospitalized patients with severe COVID-19, the impact of CP treatment on in-hospital mortality was evaluated using univariate and multivariate Cox proportional-hazards models, and the impact of CP treatment on time to hospital discharge was assessed using a stratified log-rank analysis. RESULTS: In total, 64 patients who received CP a median of 7 days after symptom onset were compared to a matched control group of 177 patients. The incidence of in-hospital mortality was 12.5% and 15.8% in the CP and control groups, respectively (P = .52). There was no significant difference in the risk of in-hospital mortality between the 2 groups (adjusted hazard ratio [aHR] 0.93, 95% confidence interval [CI] .39-2.20). The overall rate of hospital discharge was not significantly different between the 2 groups (rate ratio [RR] 1.28, 95% CI .91-1.81), although there was a significantly increased rate of hospital discharge among patients 65-years-old or greater who received CP (RR 1.86, 95% CI 1.03-3.36). There was a greater than expected frequency of transfusion reactions in the CP group (2.8% reaction rate observed per unit transfused). CONCLUSIONS: We did not demonstrate a significant difference in risk of mortality or rate of hospital discharge between the CP and control groups. There was a signal for improved outcomes among the elderly, and further adequately powered randomized studies should target this subgroup when assessing the efficacy of CP treatment.

Causes of an elevated international normalized ratio in the intensive care unit and the implications for plasma transfusion.

BACKGROUND: The presence of an elevated international normalized ratio (INR) is common in patients in the intensive care unit (ICU), but the cause rarely determined. These patients are at risk to receive prophylactic plasma prior to invasive procedures. STUDY DESIGN AND METHODS: Samples from patients with an INR of 1.5 or greater were frozen and subsequently thawed and assayed for procoagulant and anticoagulant clotting factors and anti-Xa to determine the likely cause of the INR. Samples showing a low FVII, FX, PC, and PS were categorized as a vitamin K deficiency pattern. Samples showing a low FV, low or normal fibrinogen, and high FVIII were categorized as a liver disease pattern. Samples showing an anti-Xa >0.01 IU/ml were assayed for anti-Xa DOACs. Samples which could not be categorized were grouped as equivocal. RESULTS: A total of 48 samples were obtained over a 6-month period. Nineteen showed a Vitamin K deficiency pattern, 17 a liver disease pattern, 7 showed an anti-Xa DOAC and 5 were equivocal. High FVIII and D-dimers and reduced levels of the anticoagulant proteins were present in the majority of the samples. FVII levels correlated inversely with the INR (r = -0. 81), as did FX (r = -0.67) but not FV (r = -0.04) nor fibrinogen (r = -0.15). CONCLUSION: Transfusion of plasma to reverse an elevated INR in the ICU should be discouraged since such a practice is either avoidable by the use of vitamin K or inappropriate in the case of liver disease or an anti-Xa DOAC.

Successful recovery from COVID-19 in three kidney transplant recipients who received convalescent plasma therapy.

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease that typically presents with greater severity in patients with underlying medical conditions or those who are immunosuppressed. We present a novel case series of three kidney transplant recipients with COVID-19 who recovered after receiving COVID-19 convalescent plasma (CCP) therapy. Physicians should be aware of this potentially useful treatment option. Larger clinical registries and randomized clinical trials should be conducted to further explore the clinical and allograft outcomes associated with CCP use in this population.

Aortic root replacement with Medtronic Freestyle bioprosthesis: 25-year experience.

BACKGROUND: Stentless porcine bioprothesis is a surgical strategy to treat aortic root disease. Use has been limited due to the concern for long-term valve degeneration. This study evaluated the perioperative and late outcomes of patients with aortic root disease requiring root replacement. METHODS: A total of 409 patients underwent aortic root replacement by a single surgeon using a stentless porcine bioroot between February 1996 and May 2020. The cohort was divided into two groups (age ≤65 and >65 years). Descriptive statistics were used to analyze the data and Kaplan-Meier curves used to evaluate long-term outcomes. RESULTS: Patients age >65 years were more likely to be female (p = .01), have hypertension (p = .01), require circulatory arrest (p = .01), and have concomitant coronary artery bypass grafting (CABG) (p = .04). Baseline creatinine >1.8 (p = .20), diabetes (p = .06), and ejection fraction (p = .20) were similar between groups. The 1-, 5-, and 10-year survival for patients age ≤65 years were 92%, 87%, and 69%, respectively, significantly better than patients age >65 (88%, 73%, and 43%, respectively) (p < .01, Figure 1). The 1-, 5-, and 10-year freedom from reoperation for patients ≤65 years were 99%, 97%, and 93% versus 99%, 98%, and 96% in patients age >65 years, respectively (p = .24). CONCLUSION: Patients with aortic root disease can be treated with acceptable perioperative outcomes, long-term survival, and low reoperation rates using a stentless porcine bioprothesis. It should be considered irrespective of age due to its excellent durability and freedom from anti-coagulation requirement.

Effect of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy on Quality of Life in Patients with Peritoneal Mesothelioma.

INTRODUCTION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is an accepted treatment for peritoneal mesothelioma. In this study, we evaluated QOL after HIPEC for peritoneal mesothelioma. METHODS: This was a prospective study performed after HIPEC for peritoneal mesothelioma between 2002 and 2015. Patients completed QOL surveys, including the Short Form-36 (SF-36), Functional Assessment of Cancer Therapy + Colon (FACT-C), Brief Pain Inventory (BPI), and Center for Epidemiologic Studies Depression Scale (CES-D) preoperatively and at 3, 6, 12, and 24 months postoperatively. RESULTS: Overall, 46 patients underwent HIPEC for peritoneal mesothelioma and completed QOL surveys. Mean age was 52.8 ± 13.8 years and 52% were male. Good preoperative functional status was 70%. Median survival was 3.4 years, and 1, 3, and 5-year survivals were 77.4, 55.2, and 36.5%, respectively. CES-D score decreased at 3 months postoperatively, but increased at 24 months (p = 0.014); SF-36 physical functioning scale decreased at 3 months but returned to baseline at 12 months (p = 0.0045); and the general health scale decreased at 3 months, then improved by 6 months (p = 0.0034). Emotional well-being (p = 0.0051), role limitations due to emotional problems (p = 0.0006), social functioning (p = 0.0022), BPI (p = 0.025), least pain (p = 0.045), and worst pain (p < 0.0001) improved. FACT-C physical well-being decreased at 3 months but returned to baseline at 6 months (p = 0.020), and total FACT-C score improved at 6 months (p = 0.052). CONCLUSION: QOL returned to baseline or improved from baseline between 3 months and 1 year following surgery. Despite the risks associated with this operation, patients may tolerate HIPEC well and have good overall QOL postoperatively.

Identification of Fatty Acid Binding Protein 5 Inhibitors Through Similarity-Based Screening.

Fatty acid binding protein 5 (FABP5) is a promising target for development of inhibitors to help control pain and inflammation. In this work, computer-based docking (DOCK6 program) was employed to screen ∼2 M commercially available compounds to FABP5 based on an X-ray structure complexed with the small molecule inhibitor SBFI-26 previously identified by our group (also through virtual screening). The goal was discovery of additional chemotypes. The screen resulted in the purchase of 78 candidates, which led to the identification of a new inhibitor scaffold (STK-0) with micromolar affinity and apparent selectivity for FABP5 over FABP3. A second similarity-based screen resulted in three additional hits (STK-15, STK-21, STK-22) from which preliminary SAR could be derived. Notably, STK-15 showed comparable activity to the SBFI-26 reference under the same assay conditions (1.40 vs 0.86 µM). Additional molecular dynamics simulations, free energy calculations, and structural analysis (starting from DOCK-generated poses) revealed that R enantiomers (dihydropyrrole scaffold) of STK-15 and STK-22 have a more optimal composition of functional groups to facilitate additional H-bonds with Arg109 of FABP5. This observation suggests enantiomerically pure compounds could show enhanced activity. Overall, our study highlights the utility of using similarity-based screening methods to discover new inhibitor chemotypes, and the identified FABP5 hits provide a strong starting point for future efforts geared to improve activity.

Adjunctive treatment of clinically severe babesiosis with red blood cell exchange: a case series of nineteen patients.

BACKGROUND: Infection with the protozoan parasite Babesia, the causative agent of babesiosis, can result in asymptomatic to life-threatening illness. Severe cases of babesiosis are characterized by high levels of parasitemia (>4%-10%) and commonly treated with adjunctive red blood cell exchange (RCE) in addition to antimicrobial therapy. The efficacy of RCE in this context is unknown. STUDY DESIGN AND METHODS: Blood bank records were examined for requests for RCE during a 10-year period from 2007 to 2017. Relevant clinical and laboratory variables were extracted from medical records from presentation to 35 days after RCE and analyzed in univariate and multivariate models. RESULTS: Nineteen cases of babesiosis were identified in which RCE was performed. The median age of patients was 77 years, 74% of whom were male. A total of 37% of patients were asplenic. RCE was performed on average 1.3 days after presentation, with procedural urgency driven mainly by the level of parasitemia. Mean pre- and post-RCE levels of parasitemia were 12.9 and 3.4%, respectively, resulting in a mean percent reduction in parasitemia of 75%. Preprocedural parasitemia (p = 0.047) and age (p = 0.028) were both significant predictors of postprocedural hospital length of stay (post-RCE LOS). Neither postprocedural parasitemia (p = 0.12) nor percent reduction in parasitemia (p = 0.72) correlated with post-RCE LOS. Four patients died, none of whom were asplenic. Mortality was not correlated with hematologic, parasitologic, or clinical variables analyzed. CONCLUSIONS: Reduction in the level of parasitemia is the only known benefit of RCE in severe babesiosis.

Heavy parasitemia in babesiosis treated without adjunctive red cell exchange.

Babesiosis is a tick-borne infectious disease caused by the protozoa Babesia but transplacental, and transfusion transmission may occur. While most infections are asymptomatic, rarely, it can present with a severe, life-threatening illness. Treatment is primarily with antibiotics, but red cell exchange (RCE) has been used in more severe cases which are characterized by high-grade parasitemia, evidence of severe hemolysis and or multi-organ failure. A threshold parasite level of 10% has arbitrarily been applied as an indication for RCE; however, this threshold is not evidence-based. We report on three cases of severe babesiosis in which we considered the use of RCE on the basis of a parasite level greater than 10%, but the procedure was not performed. We deferred RCE on account of the good clinical state of the patient and the absence of end-organ failure. All patients were followed daily until discharge. Two of these patients had been splenectomized, and each received a single unit of red blood cells during the hospitalization. The third patient had a long history of refractory lymphoma and was pancytopenic requiring multiple transfusions during the years before the diagnosis of babesiosis. She had transfusion-transmitted babesiosis from a red blood cell transfused 46 days prior to diagnosis. All three patients responded well to antibiotics, and none expired. This small case series suggests that requests for RCE solely on the basis of an arbitrary level of parasitemia should be questioned and the clinical state and evidence of end-organ failure considered in the decision to perform RCE.

Catalytic C-C Bond Formation Using a Simple Nickel Precatalyst System: Base- and Activator-Free Direct C-Allylation by Alcohols and Amines.

A "totally catalytic" nickel(0)-mediated method for base-free direct alkylation of allyl alcohols and allyl amines is reported. The reaction is selective for monoallylation, uses an inexpensive NiII precatalyst system, and requires no activating reagents to be present.

False-negative compatible antiglobulin crossmatches in samples with alloantibodies to cognate red blood cell antigens.

BACKGROUND: Patient samples showing a positive indirect antiglobulin test are further tested to identify alloantibody specificity using a panel of phenotypically characterized group O reagent red blood cells (RBCs). Donor RBCs phenotypically negative for the antibody specificity are then serologically crossmatched using an antiglobulin reagent. This latter test is performed to identify any incompatibility due to the presence of undetected minor blood group antibodies and considered an important step in patient safety. STUDY DESIGN AND METHODS: Samples with well-characterized alloantibodies were intentionally crossmatched against donor RBCs expressing the cognate antigen. In a separate set of specimens, the alloantibody was titered and crossmatched against both heterozygous and homozygous cells. RESULTS: Thirty-five samples containing 10 common alloantibodies crossmatched against 240 ABO-compatible donor cells phenotypically positive for the cognate antigen showed compatible crossmatches in 89 of 240 (37%). Antibody titering of 12 alloantibodies showed that a titer of 2 or more was required for incompatibility of all homozygous cells and a titer of 8 or more for incompatibility of all heterozygous cells. CONCLUSION: The antiglobulin crossmatch has a high failure rate (false-negatives) related to antibody titer and donor cell zygosity and is not reliable in interdicting incompatibility due to minor blood group antibodies.

Refractoriness to red blood cell transfusion therapy due to hypersplenism.

BACKGROUND: A 55-year-old male presented with myelodysplastic/myeloproliferative neoplasm and severe splenomegaly. The patient is blood group O, D+ with a negative indirect antiglobulin test. Transfusion of 5 units of red blood cells (RBCs) increased the hemoglobin (Hb) level from 6.7 to 7.2 g/dL. No active bleeding or hemolysis was evident. The patient was readmitted 1 week later with a Hb level of 3.3 g/dL. An additional 6 units of RBCs showed only an increase from 3.3 to 3.5 g/dL. Partial splenic embolization was performed, which resulted in a stabilization of the Hb level at approximately 7 g/dL. Because of this, total splenectomy was performed, which resulted in a gradual increase in Hb level to approximately 13 g/dL. The patient remains transfusion independent 160 days postsplenectomy. RESULTS: RBC transfusion increases Hb concentration by 1 g/dL per unit in a typical adult. This increase is attenuated in the presence of ongoing hemolysis or active blood loss. Occasionally, a low-RBC-volume unit transfused to a recipient with a large intravascular blood volume may show an unexpectedly small increase. In rare situations, however, the etiology of a greatly attenuated response is more perplexing. The pattern of Hb concentration posttransfusion was suggestive of splenic sequestration in our patient. CONCLUSION: Severe refractoriness to RBC transfusion attributable to severe hypersplenism is a rare event. Our case suggests that splenic artery embolization may be a useful initial approach in individual cases and a potential predictor of the utility of a subsequent surgical splenectomy.

Assessment of Heparin Anticoagulation Measured Using i-STAT and Hemochron Activated Clotting Time.

OBJECTIVE: Adequate anticoagulation, measured using activated clotting time (ACT), is important during vascular and cardiac surgeries. Unfractionated heparin is the most common anticoagulant used. The purpose of this analysis was to compare the i-STAT ACT (iACT) to the Hemochron ACT (hACT), both of which were then compared to anti-factor Xa (anti-Xa) assay, a representation of heparin level and activity. DESIGN: Prospective study. SETTING: Tertiary care cardiovascular center. PARTICIPANTS: Eleven consecutive elective adult cardiac surgical patients. INTERVENTIONS: Prior to cardiopulmonary bypass, ACTs were measured using i-STAT and Hemochron technologies and compared to each other and to anti-Xa assay prior to and during a cumulative administration of heparin. Data were compared using bias analyses. MEASUREMENTS AND MAIN RESULTS: Heparin (300 U/kg) was administered in quarterly doses. Coagulation labs were collected prior to and 3 minutes after each quarterly dose of heparin. The baseline ACTs for i-STAT and Hemochron were 147 and 142 seconds, respectively. A significant association was found between iACT and hACT (p = 0.002). The iACT measurements underestimated hACT at ACT levels >180 seconds or anti-Xa levels >0.75 U/mL. No significant difference was found between ACT data at anti-Xa levels <0.5 U/mL. CONCLUSION: There was a good association between the iACT and hACT; however, the 2 tests are not equivalent. Overall, the iACT underestimated the hACT. Agreement between the ACT technologies was good at lower ACTs and anti-Xa levels, but declined with an anti-Xa >0.75 U/mL.