Changes in heparin dose response slope during cardiac surgery: possible result in inaccuracy in predicting heparin bolus dose requirement to achieve target ACT

Perfusion ◽  
2017 ◽  
Vol 32 (6) ◽  
pp. 474-480 ◽  
Author(s):  
Junko Ichikawa ◽  
Tetsu Mori ◽  
Mitsuharu Kodaka ◽  
Keiko Nishiyama ◽  
Makoto Ozaki ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Platelet Count ◽  
Dose Response ◽  
Complete Blood Count ◽  
Activity Level ◽  
Heparin Dose ◽  
Dose Requirement ◽  
Heparin Concentration ◽  
Heparin Administration

Introduction: The substantial interpatient variability in heparin requirement has led to the use of a heparin dose response (HDR) technique. The accuracy of Hepcon-based heparin administration in achieving a target activated clotting time (ACT) using an HDR slope remains controversial. Methods: We prospectively studied 86 adult patients scheduled for cardiac surgery requiring cardiopulmonary bypass. The total dose of calculated heparin required for patient and pump priming was administered simultaneously to achieve a target ACT of 450 s for HDR on the Hepcon HMS system. Blood samples were obtained after the induction of anesthesia, at 3 min after heparin administration and after the initiation of CPB to measure kaolin ACT, HDR slope, whole-blood heparin concentration based on the HDR slope and anti-Xa heparin concentration, antithrombin and complete blood count. Results: The target ACT of 450 s was not achieved in 68.6% of patients. Compared with patients who achieved the target ACT, those who failed to achieve their target ACT had a significantly higher platelet count at baseline. Correlation between the HDR slope and heparin sensitivity was poor. Projected heparin concentration and anti-Xa heparin concentration are not interchangeable based on the Bland–Altman analysis. Conclusion: It can be hypothesized that the wide discrepancy in HDR slope versus heparin sensitivity may be explained by an inaccurate prediction of the plasma heparin level and/or the change in HDR of individual patients, depending on in vivo factors such as extravascular sequestration of heparin, decreased intrinsic antithrombin activity level and platelet count and/or activity.

Factors associated with errors in the heparin dose response test: recommendations to improve individualized heparin management in cardiopulmonary bypass

Perfusion ◽  
2020 ◽  
pp. 026765912095297
Author(s):  
Min-Ho Lee ◽  
William Riley
Keyword(s):  
Cardiopulmonary Bypass ◽  
Dose Response ◽  
Clotting Time ◽  
Critical Aspect ◽  
Heparin Dose ◽  
Factors Associated ◽  
Heparin Concentration ◽  
Activated Clotting Time

Background: A critical aspect of cardiopulmonary bypass (CPB) is to achieve full anticoagulation to prevent thrombosis and consumptive coagulation without using excessive amount of heparin. This can be achieved with heparin dose response (HDR) test in vitro to calculate an individualized heparin bolus to reach a target activated clotting time (ACT) and heparin concentration. However, we often observe that the measured ACT (mACT) with the calculated heparin bolus gives significant errors, both positive (mACT is higher than expected) and negative (mACT is lower), from expected ACT (eACT). Methods: We performed a retrospective study of 250 patients who underwent cardiac surgery to attain an error distribution of the mACT from eACT with calculated heparin bolus. In addition, it is aimed to identify possible patterns of baseline ACT (bACT), calculated heparin concentration (CHC) and HDR slope that are associated with the significant positive and negative errors. Results: We found that individualized heparin bolus by HDR test is consistently underestimated while it gave a significant number of positive and negative errors. Further analysis indicates that significant negative errors correlate with high bACT and slope and low CHC while significant positive errors with low bACT and slope and high CHC. Conclusion: The mACT can be substantially different from eACT. The accuracy of the HDR test appears to be dependent upon bACT, slope, and CHC. Based on our analysis, we provide several recommendations and a flow chart to improve the quality of individualized heparin management on CPB.

Controlling Anticoagulation in Extracorporeal Blood Circuits (hemoperfusion)

1984 ◽  
Vol 7 (1) ◽  
pp. 11-21
Author(s):  
L. Mor ◽  
S. Sideman ◽  
M. Mihich ◽  
A. Tzipiniuk ◽  
S. Lupovich ◽  
...  
Keyword(s):  
Elimination Rate ◽  
Blood System ◽  
Heparin Infusion ◽  
Heparin Concentration ◽  
Extracorporeal Blood ◽  
Heparin Administration ◽  
Pre Treatment ◽  
Second Procedure

The study demonstrates that different individuals (monkeys) need different heparin doses so as to avoid either clotting or bleeding when an extracorporeal blood system is involved. The linear correlation between PT and WBPTT values enables to utilize the latter for monitoring the heparin level in the blood. One procedure is based on the application of the Gotch and Keen intravenous heparinization model in its steady state limit by utilizing the pre-treatment evaluation of k/S, the ratio of the elimination rate constant to the individual's sensitivity to heparin. A second procedure involves the direct heparinization of the extracorporeal system. The heparin infusion rate is monitored through the arterial WBPTT values after relating the individual's PT or WBPTT values to the in vitro heparin concentration in the blood. In vitro and in vivo study of the effect of hemoperfusion through a column containing anion exchange particles on the amount and rate of heparin administration indicates that only the in vivo results are meaningful. The sharp response of WBPTT to relatively small changes of citrate concentration in the blood precludes individual monitoring by WBPTT. Work on the advantage of utilizing heparin together with citrate is required.

In vitro and in vivo effects of hemodilution on kaolin-based activated clotting time predicted heparin requirement using a heparin dose–response technique

2016 ◽  
Vol 30 (6) ◽  
pp. 923-928 ◽  
Author(s):  
Junko Ichikawa ◽  
Satoshi Hagihira ◽  
Testu Mori ◽  
Mitsuharu Kodaka ◽  
Keiko Nishiyama ◽  
...  
Keyword(s):  
Dose Response ◽  
Clotting Time ◽  
Heparin Dose ◽  
Activated Clotting Time ◽  
In Vivo Effects

scholarly journals Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double blind dose response study in Lagos

2021 ◽  
Author(s):  
OE Babalola ◽  
CO Bode ◽  
AA Ajayi ◽  
FM Alakaloko ◽  
IE Akase ◽  
...  
Keyword(s):  
Platelet Count ◽  
Dose Response ◽  
Repeated Measures ◽  
Standard Of Care ◽  
Double Blind ◽  
Parallel Group ◽  
Clinical Benefits ◽  
Randomised Controlled

ABSTRACTIntroductionIn vitro studies have shown the efficacy of Ivermectin (IV) to inhibit the SARS - CoV-2 viral replication, but questions remained as to In-vivo applications. We set out to explore the efficacy and safety of Ivermectin in persons infected with COVID19.MethodsWe conducted a translational proof of concept (PoC) randomized, double blind placebo controlled, dose response, parallel group study of IV efficacy in RT - PCR proven COVID 19 positive patients. 62 patients were randomized to 3 treatment groups. (A) IV 6mg regime, (B)IV 12 mg regime (given Q84hrs for 2weeks) (C, control) Lopinavir/Ritonavir. All groups plus standard of Care.ResultsThe Days to COVID negativity [DTN] was significantly and dose dependently reduced by IV (p = 0.0066). The DTN for Control were, = 9.1+/−5.2, for A 6.0 +/− 2.9, and for B 4.6 +/−3.2. 2 Way repeated measures ANOVA of ranked COVID 19 + / − scores at 0, 84, 168, 232 hours showed a significant IV treatment effect (p=0.035) and time effect (p <0.0001). IV also tended to increase SPO2 % compared to controls, p = 0.073, 95% CI - 0.39 to 2.59 and increased platelet count compared to C (p = 0.037) 95%CI 5.55 - 162.55 × 103/ml. The platelet count increase was inversely correlated to DTN (r = −0.52, p = 0.005). No SAE was reported.Conclusions12 mg IV regime may have superior efficacy. IV should be considered for use in clinical management of SARS-Cov-2, and may find applications in community prophylaxis in high-risk areas.

scholarly journals In Vivo Safety of Tumor Treating Fields (TTFields) Applied to the Torso

2021 ◽  
Vol 11 ◽  
Author(s):  
Roni Blatt ◽  
Shiri Davidi ◽  
Mijal Munster ◽  
Anna Shteingauz ◽  
Shay Cahal ◽  
...  
Keyword(s):  
Electric Fields ◽  
Cellular Proliferation ◽  
Complete Blood Count ◽  
Malignant Tumors ◽  
Neurological Status ◽  
Recurrent Glioblastoma ◽  
Activity Level ◽  
Internal Organs ◽  
Tumor Treating Fields

BackgroundTumor Treating Fields (TTFields) therapy is a non-invasive, loco-regional, anti-mitotic treatment modality that targets rapidly dividing cancerous cells, utilizing low intensity, alternating electric fields at cancer-cell-type specific frequencies. TTFields therapy is approved for the treatment of newly diagnosed and recurrent glioblastoma (GBM) in the US, Europe, Israel, Japan, and China. The favorable safety profile of TTFields in patients with GBM is partially attributed to the low rate of mitotic events in normal, quiescent brain cells. However, specific safety evaluations are warranted at locations with known high rates of cellular proliferation, such as the torso, which is a primary site of several of the most aggressive malignant tumors.MethodsThe safety of delivering TTFields to the torso of healthy rats at 150 or 200 kHz, which were previously identified as optimal frequencies for treating multiple torso cancers, was investigated. Throughout 2 weeks of TTFields application, animals underwent daily clinical examinations, and at treatment cessation blood samples and internal organs were examined. Computer simulations were performed to verify that the targeted internal organs of the torso were receiving TTFields at therapeutic intensities (≥ 1 V/cm root mean square, RMS).ResultsNo treatment-related mortality was observed. Furthermore, no significant differences were observed between the TTFields-treated and control animals for all examined safety parameters: activity level, food and water intake, stools, motor neurological status, respiration, weight, complete blood count, blood biochemistry, and pathological findings of internal organs. TTFields intensities of 1 to 2.5 V/cm RMS were confirmed for internal organs within the target region.ConclusionsThis research demonstrates the safety of therapeutic level TTFields at frequencies of 150 and 200 kHz when applied as monotherapy to the torso of healthy rats.

COMPARISON OF HEPARIN DOSE RESPONSE TO ACTIVATED CLOTTING TIME IN INFANTS AND CHILDREN FOR CARDIAC SURGERY

1998 ◽  
Vol 86 (Supplement) ◽  
pp. 73SCA
Author(s):  
EB Mossad ◽  
K Marchant ◽  
PM Bokesch ◽  
JJ Niezgoda ◽  
RBB Mee ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Dose Response ◽  
Infants And Children ◽  
Clotting Time ◽  
Heparin Dose ◽  
Activated Clotting Time ◽  
In Infants And Children

Limitations of the Activated Partial Thromboplastin Time for Determination of Plasma Heparin Concentration and Half-Life in Human Subjects

1972 ◽  
Vol 27 (01) ◽  
pp. 107-113 ◽  
Author(s):  
G Baele ◽  
M De Broe ◽  
G. A De Weerdt ◽  
S Ringoir ◽  
F Barbier
Keyword(s):  
Partial Thromboplastin Time ◽  
Half Life ◽  
Human Subjects ◽  
Activated Partial Thromboplastin Time ◽  
Single Intravenous Injection ◽  
Heparin Concentration ◽  
Heparin Administration ◽  
Plasma Heparin

SummaryIn vivo heparin concentrations and half-life were estimated in 20 human subjects, after a single intravenous injection.The method, used for heparin determination, is based on the activated partial thromboplastin time. The test plasmas are diluted in plasma of the same subject obtained before heparin administration. In this way the heparin concentrations are reduced to measurable levels between 0.1 I. U./ml and 0.8 I. U./ml. Indeed a linear relationship between log activated partial thromboplastin time and heparin concentrations from 0.1 to 0.8 I. U./ml can be computed. Different half-lives were found in 13 of the 20 subjects examined when different dilution factors were used. This seems an important limitation for the examination of the pharmacokinetics of heparin.

scholarly journals Effect of Hemodilution in vitro and in vivo on the Hemostatic System (experimental study)

2021 ◽  
Author(s):  
Alexandr A. Kinzersky ◽  
Vladimir T. Dolgikh ◽  
Mikhail S. Korzhuk ◽  
Daria A. Kinzerskaya ◽  
Semyon V. Romanenko
Keyword(s):  
Platelet Count ◽  
Complete Blood Count ◽  
Maximum Amplitude ◽  
Coagulation Cascade ◽  
Control Group ◽  
Enzymatic Reactions ◽  
Hemostatic System ◽  
Reference Limits

The aim of the study was to determine experimentally the effect of hemodilution by the 2:1 sterofundin/gelofusine (SG) solution on hemostatic parameters in vitro and in vivo.Material and methods. Experiments were carried out on 75 male Wistar rats weighing 270-380 g and anesthetized with intramuscular tiletamine-zolazepam (40 mg/kg) + xylazine (10 mg/kg). Animals were divided randomly into 4 groups: Group 1 - in vitro 25-percent dilution of carotid blood samples by the SG solution (n=12), Group 2 - in vitro 37.5-percent dilution of similar samples (n=11), Group 3 - in vivo 25-percent dilution (n=10), Group 4 - the controls (n=42) with no dilution. The first stage of the study compared the in vitro dilution groups with the control group and with each other; the second stage compared the in vivo dilution group with the control group. The parameters of low-frequency piezoelectric tromboelastography (LFPTEG), clotting tests and complete blood count were studied to evaluate the effect of hemodilution.Results. At a 25-percent hemodilution with 2:1 CG solution in vitro and in vivo, the hemostatic parameters retained within the reference limits, but a trend to increased intensity of the enzymatic reactions of the coagulation cascade and a significant increase in clot polymerization in vitro due to relative anticoagulant deficiency became evident.In vitro 37.5-percent blood dilution significantly reduced the blood level of fibrinogen and platelet count, inhibited the intensity of the proteolytic stage of coagulation, reduced the clot density at the T3 gelation point, at 5 minutes after reaching it and the maximum amplitude (MA) of the LFPTEG curve, as well as significantly reduced anticoagulant activity of the blood. The observed changes in hemostatic parameters were significantly outside the reference limits, which may affect the interpretation of the experimental results and be clinically important. We found negative correlation between clot density and platelet activity at 25-percent dilution in vivo, whereas at 37.5-percent dilution in vitro an additional positive correlations between platelet count and fibrinogen levels were determined.Conclusion. A 25-percent hemodilution with 2:1 CG solution should be considered "safe" for the in vivo hemostatic system providing minimal effect on the in vitro parameters in the experiment.

scholarly journals Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double-blind, dose-response study in Lagos

QJM ◽  
2021 ◽  
Author(s):  
O E Babalola ◽  
C O Bode ◽  
A A Ajayi ◽  
F M Alakaloko ◽  
I E Akase ◽  
...  
Keyword(s):  
Platelet Count ◽  
Dose Response ◽  
Repeated Measures ◽  
Standard Of Care ◽  
Double Blind ◽  
Parallel Group ◽  
Clinical Benefits ◽  
Randomised Controlled

Abstract Introduction In vitro studies have shown the efficacy of Ivermectin (IV) to inhibit the SARS - CoV- 2 viral replication, but questions remained as to In-vivo applications. We set out to explore the efficacy and safety of Ivermectin in persons infected with COVID19. Methods We conducted a translational proof of concept (PoC) randomized, double blind placebo controlled, dose response, parallel group study of IV efficacy in RT - PCR proven COVID 19 positive patients. 62 patients were randomized to 3 treatment groups. (A) IV 6mg regime, (B)IV 12 mg regime (given Q84hrs for 2weeks) (C, control) Lopinavir/Ritonavir. All groups plus standard of Care. Results The Days to COVID negativity [DTN] was significantly and dose dependently reduced by IV (p = 0.0066). The DTN for Control were, = 9.1+/-5.2, for A 6.0 +/- 2.9, and for B 4.6 +/-3.2 . 2 Way repeated measures ANOVA of ranked COVID 19 +/- scores at 0, 84, 168, 232 hours showed a significant IV treatment effect (p = 0.035) and time effect (p &lt; 0.0001). IV also tended to increase SPO2% compared to controls, p = 0.073, 95% CI - 0.39 to 2.59 and increased platelet count compared to C (p = 0.037) 95%CI 5.55 - 162.55 × 103/ml. The platelet count increase was inversely correlated to DTN (r = -0.52, p = 0.005). No SAE was reported. Conclusions 12 mg IV regime may have superior efficacy. IV should be considered for use in clinical management of SARS-Cov-2, and may find applications in community prophylaxis in high-risk areas.

Sign in / Sign up

Export Citation Format

Share Document