Distribution of dipyridamole in blood components among post-stroke patients treated with extended release formulation

SummaryExtended release dipyridamole (ERD) is widely used in patients after ischaemic stroke; however, the ability of this antithrombotic agent to be stored in different blood cells has never been explored in post-stroke patients. We hypothesised that since ERD is known to be highly lipophilic, the drug may be present not only in plasma, but also accumulated in platelets, leukocytes, and erythrocytes. Fifteen patients after documented ischaemic stroke were treated with Aggrenox (ERD and lowdose aspirin combination) BID for 30 days, and 12 of them completed the study. ERD concentrations in blood cells and platelet-poor plasma were measured by spectrofluorimetry at Baseline, Day 14, and Day 30 after the initiation of therapy. The background level of spectrofluorometry readings differs slightly among the blood components (132–211 ng/ml) due to the differences in the preparation of samples and cell isolation techniques. As expected, two weeks of ERD therapy produced steady-state plasma concentration of dipyridamole already at Day 14 (1,680 ±542 ng/ ml), followed by a slight not significant decrease at one month (1,619 ±408 ng/ml). Two weeks of therapy was sufficient to achieve a consistent dipyridamole accumulation in erythrocytes (361 ±43 ng/ml), but not in platelets (244 ±78 ng/ml), or leukocytes (275 ±49 ng/ml).In fact, white blood cells continued dipyridamole intake beyond 14 days period, and this increase (398 ± 66 ng/ml) was significant (p = 0.02) at 30 days. Treatment with ERD in post-stroke patients resulted not only in achievement of therapeutic plasma dipyridamole concentrations, but also deposition of the drug in erythrocytes and leukocytes, but not in platelets. If confirmed, these data will affect our better understanding of dipyridamole pleiotropy, and may explain long-term benefit of ERD formulation.

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Comprehensive rationale for the use of immune plasma for septic patients

Vestnik of Russian military medical Academy ◽

10.17816/brmma62812 ◽

2020 ◽

Vol 22 (4) ◽

pp. 91-94

Author(s):

L. A. Skripay ◽

V. N. Vilyaninov ◽

A. A. Skripay

Keyword(s):

Blood Cells ◽

White Blood Cells ◽

Fresh Frozen Plasma ◽

Hospital Treatment ◽

Blood Components ◽

Septic Complications ◽

Military Medical Academy ◽

Medical Academy ◽

Fresh Frozen ◽

Modern Economic

Data of accounting and reporting documents of the Center (blood and tissues) are analyzed retrospectively) the Kirov military medical Academy for the period from 2017 to 2019 on the use of blood components in septic conditions of patients in clinics of the Kirov Military medical Academy. The volume of issued immune plasma for patients suffering from septic complications in 2017, it was 154 doses (33,9 l), in 2018, it was 196 doses (43,1 l), in 2019, it was 389 doses (72,1 l). It was found that in patients suffering from septic complications on the second day after transfusion of blood components, the levels of the studied indicators of the inflammatory process did not change unambiguously. Thus, in patients who received immune plasma transfusion, there was a decrease in white blood cells by 1,5109/l on the next day after the component was transfused. At the same time, there was a direct decrease in rod-shaped neutrophils, monocytes, erythrocyte sedimentation rate and a decrease in body temperature. In patients who were transfused fresh frozen plasma, white blood cells increased by 0,5109/l and slightly monocytes. A slight decrease in platelets in septic patients of group 1 after transfusion of immune plasma indicates the active participation of these cells in the reactions of antibacterial immunity. This can be considered as a favorable prognosis for a particular patient, since there is a direct relationship between the decrease in the number of platelets and the duration of stay in hospital treatment, as well as the overall outcome of the disease. The level of circulating immune complexes in patients of both groups after transfusions of blood components remained within normal values. Levels of fibrinogen, prothrombin, and albumin changed significantly in each group. At the same time, the level of fibrinogen after transfusions increased, and prothrombin changed in different directions. In the treatment of patients, the use of immune plasma activates the system of cells of the bodys antibacterial defense and improves the positive dynamics in treatment. In modern economic realities, testing plasma samples to suppress the growth of microbial colonies is justified, since it helps to reduce the volume of transfused blood components for severe septic patients.

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Therapeutic Plasma Exchange for Acute Hematologic Disorders

Mayo Clinic Critical and Neurocritical Care Board Review ◽

10.1093/med/9780190862923.003.0056 ◽

2019 ◽

pp. 359-362

Author(s):

Jill Adamski

Keyword(s):

Plasma Exchange ◽

Blood Cells ◽

Critical Care Unit ◽

White Blood Cells ◽

Buffy Coat ◽

Therapeutic Plasma Exchange ◽

Blood Components ◽

Hematologic Disorders ◽

First Line Therapy

Therapeutic plasma exchange (TPE) is a process by which whole blood is removed from a patient and separated into 3 components: red blood cells, white blood cells (buffy coat), and plasma. After separation, the plasma is discarded, and the other blood components are returned to the patient along with exogenous fluid to replace the removed plasma. TPE is an important tool to remove pathogenic substances (eg, antibodies) from plasma, and this technique is considered first-line therapy for numerous conditions that affect patients in the critical care unit. This chapter describes the role of TPE in management of hematologic disorders, some of which have neurologic manifestations.

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Interleukin-10 level is associated with post-stroke depression in acute ischaemic stroke patients

Journal of Affective Disorders ◽

10.1016/j.jad.2021.06.037 ◽

2021 ◽

Author(s):

Chu-Huai Chi ◽

Yuan-Yuan Huang ◽

Su-Zhen Ye ◽

Meng-Meng Shao ◽

Ming-Xia Jiang ◽

...

Keyword(s):

Ischaemic Stroke ◽

Acute Ischaemic Stroke ◽

Interleukin 10 ◽

Stroke Patients ◽

Post Stroke ◽

Post Stroke Depression

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Comparative Pharmacokinetics of Azithromycin in Serum and White Blood Cells of Healthy Subjects Receiving a Single-Dose Extended-Release Regimen versus a 3-Day Immediate-Release Regimen

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00852-06 ◽

2006 ◽

Vol 51 (1) ◽

pp. 103-109 ◽

Cited By ~ 44

Author(s):

Ping Liu ◽

Hameed Allaudeen ◽

Richa Chandra ◽

Kem Phillips ◽

Arvid Jungnik ◽

...

Keyword(s):

Single Dose ◽

Blood Cells ◽

Dose Regimen ◽

Extended Release ◽

Drug Exposure ◽

White Blood Cells ◽

Area Under The Curve ◽

Immediate Release ◽

Mononuclear Leukocytes ◽

Open Label

ABSTRACT The pharmacokinetic profiles of azithromycin given as a single-dose regimen (2.0-g extended-release microspheres) were characterized in serum and white blood cells (WBC) and compared with those of a 3-day regimen (a 500-mg immediate-release tablet once daily; total dose, 1.5 g) in an open-label, randomized, parallel-group study of 24 healthy adult subjects. Serial blood samples were collected up to 5 days after the start of dosing for both regimens. Safety assessments were conducted throughout the study. A single 2.0-g dose of azithromycin microspheres achieved significantly higher exposures in serum and WBC during the first 24 h after the start of dosing than a 3-day regimen: an approximately threefold higher area under the curve from time zero to 24 h postdose (AUC0-24) and an approximately twofold higher mean peak concentration on day 1. The single-dose regimen provided total azithromycin exposures in serum and WBC similar to those of the 3-day regimen, as evidenced by the similar AUC0-120 and trough azithromycin concentrations in serum and WBC (mononuclear leukocytes [MNL] and polymorphonuclear leukocytes [PMNL]). For both regimens, the average total azithromycin exposures in MNL and PMNL were approximately 300- and 600-fold higher than those in serum. Azithromycin concentrations in MNL and PMNL remained above 10 μg/ml for at least 5 days after the start of dosing for both regimens. This “front-loading” of the dose on day 1 is safely achieved by the extended-release microsphere formulation, which maximizes the drug exposure at the time when the bacterial burden is likely to be highest.

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Dynamic Change of Neutrophil to Lymphocyte Ratios and Infection in Patients with Acute Ischemic Stroke

Current Neurovascular Research ◽

10.2174/1567202617666200408091131 ◽

2020 ◽

Vol 17 (3) ◽

pp. 294-303 ◽

Cited By ~ 1

Author(s):

Lu Wang ◽

Wen Guo ◽

Changyi Wang ◽

Xue Yang ◽

Zilong Hao ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Blood Cells ◽

Temporal Change ◽

Dynamic Change ◽

White Blood Cells ◽

Secondary Outcome ◽

Stroke Patients ◽

Time Of Infection ◽

Interaction Term

Background: Neutrophil to lymphocyte ratio (NLR) on admission was reported to be a predictor of pneumonia after stroke. The aim of this study was to investigate the association between the temporal change of NLR and post-stroke infection and whether infection modified the effect of NLR on the outcome. Methods: We enrolled patients with acute ischemic stroke within 24 h after onset. The blood was collected on admission, day 1, 3, 7 after admission to detect white blood cells (WBC), neutrophils, and lymphocytes. Primary outcomes included pneumonia, urinary tract infection (UTI), other infection, and the secondary outcome was 3-month death. Results: Of 798 stroke patients, 299 (37.66%) developed infection with 240 (30.23%) pneumonia, 78 (9.82%) UTI, and 9 (1.13%) other infection. The median time of infection occurrence was 48 h (interquartile range 27-74 h) after onset. NLR reached to the peak at 36 h. For all outcomes, NLR at 36 h after stroke had the highest predictive value than WBC, neutrophil, lymphocyte. NLR was independently associated with the presence of any infection (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.17), pneumonia (OR 1.12, 95%CI 1.05-1.19), but not UTI (OR 0.95, 95%CI 0.89-1.01). Adding infection or the interaction term did not substantially change the OR of NLR predicting 3-month death (OR 1.09, 95%CI 1.01, 1.17). Conclusion: Increased NLR around 36 h after stroke was a predictor of infection in patients with acute ischemic stroke. The increased NLR value was associated with a higher risk of 3-month death, which was independent of poststroke infection.

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Short-duration hypothermia completed prior to reperfusion prevents intracranial pressure elevation following ischaemic stroke in rats

Scientific Reports ◽

10.1038/s41598-021-01838-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Daniel Omileke ◽

Sara Azarpeykan ◽

Steven W. Bothwell ◽

Debbie Pepperall ◽

Daniel J. Beard ◽

...

Keyword(s):

Intracranial Pressure ◽

Ischaemic Stroke ◽

Short Duration ◽

Infarct Volume ◽

Arterial Occlusion ◽

Reperfusion Therapy ◽

Artery Occlusion ◽

Experimental Stroke ◽

Stroke Patients ◽

Post Stroke

AbstractReperfusion therapies re-establish blood flow after arterial occlusion and improve outcome for ischaemic stroke patients. Intracranial pressure (ICP) elevation occurs 18–24 h after experimental stroke. This elevation is prevented by short-duration hypothermia spanning the time of reperfusion. We aimed to determine whether hypothermia-rewarming completed prior to reperfusion, also prevents ICP elevation 24 h post-stroke. Transient middle cerebral artery occlusion was performed on male outbred Wistar rats. Sixty-minute hypothermia to 33 °C, followed by rewarming was induced prior to reperfusion in one group, and after reperfusion in another group. Normothermia controls received identical anaesthesia protocols. ΔICP from pre-stroke to 24 h post-stroke was measured, and infarct volumes were calculated. Rewarming pre-reperfusion prevented ICP elevation (ΔICP = 0.3 ± 3.9 mmHg vs. normothermia ΔICP = 5.2 ± 2.1 mmHg, p = 0.02) and reduced infarct volume (pre-reperfusion = 78.6 ± 23.7 mm3 vs. normothermia = 125.1 ± 44.3 mm3, p = 0.04) 24 h post-stroke. There were no significant differences in ΔICP or infarct volumes between hypothermia groups rewarmed pre- or post-reperfusion. Hypothermia during reperfusion is not necessary for prevention of ICP rise or infarct volume reduction. Short-duration hypothermia may be an applicable early treatment strategy for stroke patients prior to- during-, and after reperfusion therapy.

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Hypothermia and rewarming prior to reperfusion, prevents intracranial pressure elevation after ischaemic stroke in rats: an investigation to define the importance of cooling during reperfusion

10.21203/rs.3.rs-846595/v1 ◽

2021 ◽

Author(s):

Daniel Omileke ◽

Sara Azarpeykan ◽

Steven W Bothwell ◽

Debbie Pepperall ◽

Daniel J Beard ◽

...

Keyword(s):

Intracranial Pressure ◽

Ischaemic Stroke ◽

Short Duration ◽

Infarct Volume ◽

Arterial Occlusion ◽

Reperfusion Therapy ◽

Artery Occlusion ◽

Experimental Stroke ◽

Stroke Patients ◽

Post Stroke

Abstract Reperfusion therapies re-establish blood flow after arterial occlusion and improve outcome for ischaemic stroke patients. Intracranial pressure (ICP) elevation occurs 18–24 h after experimental stroke. This elevation is prevented by short-duration hypothermia spanning the time of reperfusion. We aimed to determine whether hypothermia-rewarming completed prior to reperfusion, also prevents ICP elevation 24 h post-stroke. Transient middle cerebral artery occlusion was performed on male outbred Wistar rats. Sixty-minute hypothermia to 33℃, followed by rewarming was induced prior to reperfusion in one group, and after reperfusion in another group. Normothermia controls received identical anaesthesia protocols. ΔICP from pre-stroke to 24 h post-stroke was measured, and infarct volumes were calculated. Rewarming pre-reperfusion prevented ICP elevation (ΔICP = 0.3 ± 3.9 mmHg vs. normothermia ΔICP = 5.2 ± 2.1 mmHg, p = 0.02) and reduced infarct volume (pre-reperfusion = 78.6 ± 23.7 mm3 vs. normothermia = 125.1 ± 44.3 mm3, p = 0.04) 24 h post-stroke. There were no significant differences in ΔICP or infarct volumes between hypothermia groups rewarmed pre-or post-reperfusion. Hypothermia during reperfusion is not necessary for prevention of ICP rise or infarct volume reduction. Short-duration hypothermia is a broadly applicable potential early treatment strategy for stroke patients prior to- during-, and after reperfusion therapy.

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Prediabetes is associated with post-stroke cognitive impairment in ischaemic stroke patients

Brain Research ◽

10.1016/j.brainres.2017.12.034 ◽

2018 ◽

Vol 1687 ◽

pp. 137-143 ◽

Cited By ~ 5

Author(s):

Qiongzhang Wang ◽

Kai Zhao ◽

Yan Cai ◽

Xinjie Tu ◽

Yuntao Liu ◽

...

Keyword(s):

Cognitive Impairment ◽

Ischaemic Stroke ◽

Stroke Patients ◽

Post Stroke

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Fibrin and Platelet-Rich Composition in Retrieved Thrombi Hallmarks Stroke With Active Cancer

Stroke ◽

10.1161/strokeaha.120.032069 ◽

2020 ◽

Vol 51 (12) ◽

pp. 3723-3727

Author(s):

Chuan-Hsiu Fu ◽

Chih-Hao Chen ◽

Yen-Heng Lin ◽

Chung-Wei Lee ◽

Li-Kai Tsai ◽

...

Keyword(s):

Endovascular Treatment ◽

Blood Cells ◽

White Blood Cells ◽

Area Under The Curve ◽

Large Artery ◽

Stroke Patients ◽

Cancer Group ◽

Hematoxylin And Eosin ◽

Hematoxylin And Eosin Staining ◽

Active Cancer

Background and Purpose: We aim to investigate whether histopathologic examination of thrombi retrieved from acute ischemic stroke patients undergoing endovascular treatment could distinguish cancer-related stroke from other etiologies. Methods: Thrombi from patients undergoing endovascular treatment were analyzed. The etiology of stroke was divided into cardioembolism, large artery atherosclerosis, and active cancer groups. All selected thrombi were subjected to hematoxylin and eosin staining. The percentages of fibrin/platelets, red blood cells, and white blood cells within a thrombus were quantified. Results: One-hundred fifty-two patients (active cancer, 19; cardioembolism, 107; large artery atherosclerosis, 26) were included. Thrombi from the active cancer group exhibited a higher fibrin/platelet composition than did those from the cardioembolism and large artery atherosclerosis groups (median, 85.7% versus 43.9% and 42.5%; P <0.001). Fibrin/platelet composition was the only independent factor (odds ratio, 1.05 [95% CI, 1.02–1.08]) in differentiating cancer-related stroke from stroke caused by cardioembolism and large artery atherosclerosis. A fibrin/platelet proportion of ≥65% accurately predicted cancer-related stroke (area under the curve, 0.84; P <0.001). Conclusions: In thrombi retrieved from patients undergoing endovascular treatment, a high fibrin/platelet composition was a probable indicator of cancer-related stroke.

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