Effect of Oral Administration of Ibuprofen on Prothrombin Time, Activated Partial Thromboplastin and Platelet Count in Wistar Albino Rats

Aim:Ibuprofen is analgesic, antipyretic and anti-inflammatory drug, which is widely used as a cheap over-the counter drug(OTC); however, this drug accompanies anti coagulation/anti platelets effects which sometimes might illicit adverse effects. In this study, we investigated effect of ibuprofen on prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet count using wistar albino rats.Methods:A total of 21 rats grouped into 3(control, acute and chronic exposure groups, with all consisting of 7rats each) was used. The acute and chronic exposure group were given 0.7mg of ibuprofen orally for 1 and 21 days, respectively. Blood sample was collected via cardiac puncture thenanalyzed.Results:PT was significantly higher in both group 2 and 3 (acute and chronic exposure, respectively)than that of the control. Acute exposure group showed the highest PT rise.A PTT was not significantly different between group 2 and 3 versus the control group. Platelet count was significantly lower in both group 2 and 3than that in the control group (p<0.05). Group 3 (chronic exposure) showed the lowest platelet count.Conclusion:Oral administration of ibuprofen affected coagulation parameters and a longer exposure reduce platelets count. A strictly prescription for this drug may be needed to prevent its indiscriminate use

In Vitro Assessment of Coagulation Activities in Human Plasma Treated With Ajwa Date (Phoenix dactylifera L.) Extracts

Abstract@#Introduction: Arterial and venous thromboses contribute to significant morbidity and mortality rate, thus an antithrombotic agent is needed for prevention and treatment of thrombosis. Ajwa dates (Phoenix dactylifera L.) reportedly contain a high level of salicylic acid which is a compound responsible for anticoagulation via antagonism of vitamin K. The present study was designed to assess coagulation activities in human plasma treated with Ajwa date extracts in vitro. Methods: Platelet-poor plasma samples from 27 donors were treated with ethanol crude date extract (ET) or aqueous crude date extract (AQ) of Ajwa dates at different concentrations to generate the following seven test groups from each donor: control (normal saline), ET-I (0.1 g/mL), ET-II (0.5 g/mL), ET-III (1.0 g/mL), AQ-I (0.1 g/ mL), AQ-II (0.5 g/mL) and AQ-III (1.0 g/mL). In vitro coagulation activities of Ajwa dates were assessed based on prothrombin time (PT, an assessment of extrinsic coagulation pathway), activated partial thromboplastin time (APTT, an assessment of the intrinsic coagulation pathway), and thrombin time (TT, an evaluation of level and function of fibrinogen). Results: A very significant prolongation of PT, APTT and TT were observed for the ET-II and ET-III groups and very significant prolongation of PT and TT was observed for the AQ-II and AQ-III groups. Significant prolongation of TT was observed in the AQ-I group. Conclusion: In conclusion, Ajwa date extracts had an anticoagulation effect on human plasma.

Biological activity and hydroxy safflor yellow A content of intermediates in preparation of Safflower Injection / 中国中药杂志

In order to investigate the effect of various production processes on the quality of Safflower Injection, the biological activities of the intermediates were evaluated by measuring activated partial thromboplastin time (APTT) and adenosine diphosphate (ADP) induced platelet aggregation in vitro. Intermediates were produced by key processes, such as extraction, concentration, twice alcohol precipitation, water sedimentation and two sterilizations during the production of Safflower Injection. The content of main chemical components in intermediates was determined by HPLC. The results showed that with the advance of the preparation process of Safflower Injection, the inhibition of ADP-induced platelet aggregation rate of each intermediate decreased gradually, and the trend of extending APTT activity decreased first and then increased. Meanwhile, the content of hydroxy safflor yellow A (HSYA) was gradually lowered, the content of p-hydroxy-cinnamic acid was increased, and new chemical component p-hydroxybenzaldehyde was produced. In conclusion, sterilization played a key role in the biological activity and HSYA content of Safflower injection.

Establishing the heparin therapeutic range using aPTT and anti-Xa measurements for monitoring unfractionated heparin therapy

BACKGROUND: Unfractionated heparin (UFH) has unstable pharmacokinetics and requires close monitoring. The activated partial thromboplastin time (aPTT) test has been used to monitor UFH therapy for decades in Korea, but its results can be affected by numerous variables. We established an aPTT heparin therapeutic range (HTR) corresponding to therapeutic anti-Xa levels for continuous intravenous UFH administration, and used appropriate monitoring to determine if an adequate dose of UFH was applied. METHODS: A total of 134 ex vivo samples were obtained from 71 patients with a variety of thromboembolisms. All patients received intravenous UFH therapy and were enrolled from June to September 2015 at Gyeongsang National University Hospital. All laboratory protocols were in accordance with the Clinical and Laboratory Standards Institute guidelines and the College of American Pathologist requirements for aPTT HTR. RESULTS: An aPTT range of 87.1 sec to 128.7 sec corresponded to anti-Xa levels of 0.3 IU/mL to 0.7 IU/mL for HTR under our laboratory conditions. Based on their anti-Xa levels, blood specimen distribution were as follows: less than 0.3 IU/mL, 65.7%; 0.3–0.7 IU/mL (therapeutic range), 33.6%; and more than 0.7 IU/mL, 0.7%. No evidence of recurring thromboembolism was observed. CONCLUSION: Using the conventional aPTT target range may lead to inappropriate dosing of UFH. Transitioning from the aPTT test to the anti-Xa assay is required to avoid the laborious validation of the aPTT HTR test, even though the anti-Xa assay is more expensive.

A Case of Abdominal Aortic Aneurysm in Association with Congenital Factor XI Deficiency / 日本心臓血管外科学会雑誌

Congenital factor XI deficiency is a rare intrinsic coagulation factor. We treated a 67-year-old man with abdominal aortic aneurysm, in whom activated partial thromboplastin time (APTT) found to be prolonged preoperatively. After fresh frozen plasma (FFP) was given before surgery, aneurysm was successfully replaced by a woven Dacron graft. No bleeding tendency was noted during the operation and FFP was also administered during and after surgery. The patient recovered without incident and left the hospital 13 days after the operation. Since several days are required to determine factor XI activity, APTT is useful as a parameter of coagulation factor activity in the perioperative period.

Evaluation of the activated partial thromboplastin time (aPTT) sensitivity to unfractionated heparin using three commercial reagents: Implication for therapeutic range.

At present, we are using the proposed therapeutic range for monitoring unfractionated heparin therapy which is the aPTT ratio of 1.5-2.5. However, the aPTT value is influenced by reagents and methods of detection. The College of American Pathologists and the American College of Chest Physicians recommended that site-specific validation of heparin therapeutic range should be established. The aim of this study was to determine the appropriate therapeutic range of unfractionated heparin therapy of our aPTT system by ex vivo study. For comparison, two other commercial reagents were also determined to observe the differences. Blood samples were drawn from 21 healthy blood donors who were not taking any medication and from other 24 patients suffering from either arterial or venous thrombosis, receiving continuous intravenous infusion of unfractionated heparin without concomitant oral anticoagulant therapy. Correlation coefficients between aPTT ratios and plasma heparin concentration varied between 0.722 (Actin FSL) to 0.817 (Actin FS). Calculated therapeutic ranges of aPTT ratios corresponding to the heparin level of 0.29 – 0.47 U/ml were 1.8 – 2.5, 1.9 - 2.5 and 2.7 - 4.6 for Actin FS, Actin FSL and Pathromtin SL, respectively. Therefore, the appropriate therapeutic range of our system obtained from this study might be aPTT ratio between 1.8 and 2.5 which is very closed to the ratio that we are using now.

Research on pharmacokinetics of D-polymannuronicate in rats / 中国海洋药物

Objective To investigate the pharmacokinetics of D-polymannuronicate after single and successive administrations for 7 days by means of intravenous injection and intragastric administration.Methods Bioanalysis for the determination of D-polymannuronicate plasma concentration was applied in rats,and parameters of pharmacokinetics were calculated by DAS2.1.1 software.Results The well linearity(r=0.9991) in 0.05～150mg?L~(-1) of plasma concentrations.The recovery rate was between 94.72%～103.21%,the derivations withinday and between-days were less than 15%.Zata were 0.89,1.06,0.93,0.85 h~(-1) and t_(1/2z) were 0.78,0.69,0.75,0.87h corresponding with the four methods of administration.The bioavailabilities were 3%～5%.Conclusion The bioavailability was low.The ends of the elimination of two means of intravenous injection and intragastric administration were same. There was no significant difference in pharmacokinetic parameters of single and successive administrations.