Reduction In Platelet Count Research Articles

STUDY OF CHANGES IN PLATELET COUNT, PROTHROMBIN TIME AND ACTIVATED PARTIAL THROMBOPLASTIN TIME IN HIV POSITIVE PATIENTS

Aims And Objective: This study was conducted to assess % reduction in platelet count, prolongation of prothrombin time, activated partial thromboplastin time and relationship between CD4 count and changes in platelet count, prothrombin time and activated partial thromboplastin time. Material And Methods: Cross-sectional study was done on newly diagnosed HIV positive patients, attending ART center, Sir Takhtasinhji General Hospital, Bhavnagar in duration of one year from the ethics committee approval. Inclusion Criteria: Newly diagnosed HIV positive patients, age >18 years. Exclusion Criteria: All patients who have taken post-exposure prophylaxis. Ÿ History of previous ARTtreatment. Ÿ Drugs like aspirin, warfarin, heparin causing alteration in PTand aPTTand platelet count. Ÿ Patient with bleeding disorder like hemophilia. Ÿ Patient with liver disease. Results: Out of total 244 patients, 190 patients had CD4count (<200 cells/µL) and 54 patients had CD4count (≥200 cells/µL). From the 190 patients 36.3%, 86.3% and 94.2% showed reduction of platelet count, prolongation of prothrombin time and activated partial thromboplastin time respectively. Conclusion: Thrombocytopenia, prolonged prothrombin time and activated partial thromboplastin time is present in 28.7%, 68% and 74.6% patients respectively. Regular measurements of basic coagulation parameter could help to determine which patients are at greatest risk of disease progression, allowing these patients to be identied for closer monitoring or therapeutic interventions

Haematological Trends and Transfusion during Adult Extracorporeal Membrane Oxygenation: A Single Centre Study.

Patient demographics, haematological and coagulation parameters, plasma haemoglobin and fibrinogen concentrations, platelet count, the international normalised ratio (INR), the activated partial thromboplastin time (APTT), and blood product transfusion data from 138 patients who received ECMO in a single high-volume centre were analysed. Ninety-two patients received venoarterial (VA) ECMO and 46 patients received venovenous (VV) ECMO. The median (IQR) duration of VA, and VV ECMO was 8 (5-13) days and 13 (8-23) days, respectively. There were significant reductions in haemoglobin, the platelet count, and the fibrinogen concentration upon initiation of ECMO. On average, over time, patients on VV ECMO had platelet counts 44 × 109/L higher than those on VA ECMO (p ≤ 0.001). Fibrinogen and APTT did not vary significantly based on the mode of ECMO (p = 0.55 and p = 0.072, respectively). A platelet count < 50 × 109/L or a fibrinogen level < 1.8 g/L was associated with 50% chance of PRBC transfusion, regardless of the ECMO type, and packed red blood cell (PRBC) transfusion was more common with VA ECMO. APTT was predictive of the transfusion requirement, and the decrement in APTT was discriminatory between VVECMO survivors and nonsurvivors. ECMO support is associated with reductions in haemoglobin, platelet count, and fibrinogen. Patients supported with VA ECMO are more likely to receive a PRBC transfusion compared to those on VV ECMO. Thrombocytopaenia, hypofibrinogenaemia, and anticoagulation effect the likelihood of requiring PRBC transfusion. Further research is needed to define optimal blood management during ECMO, including appropriate transfusion triggers and the anticoagulation intensity.

Platelet Activation by Antisense Oligonucleotides (ASOs) in the Göttingen Minipig, including an Evaluation of Glycoprotein VI (GPVI) and Platelet Factor 4 (PF4) Ontogeny.

Antisense oligonucleotide (ASO) is a therapeutic modality that enables selective modulation of undruggable protein targets. However, dose- and sequence-dependent platelet count reductions have been reported in nonclinical studies and clinical trials. The adult Göttingen minipig is an acknowledged nonclinical model for ASO safety testing, and the juvenile Göttingen minipig has been recently proposed for the safety testing of pediatric medicines. This study assessed the effects of various ASO sequences and modifications on Göttingen minipig platelets using in vitro platelet activation and aggregometry assays. The underlying mechanism was investigated further to characterize this animal model for ASO safety testing. In addition, the protein abundance of glycoprotein VI (GPVI) and platelet factor 4 (PF4) was investigated in the adult and juvenile minipigs. Our data on direct platelet activation and aggregation by ASOs in adult minipigs are remarkably comparable to human data. Additionally, PS ASOs bind to platelet collagen receptor GPVI and directly activate minipig platelets in vitro, mirroring the findings in human blood samples. This further corroborates the use of the Göttingen minipig for ASO safety testing. Moreover, the differential abundance of GPVI and PF4 in minipigs provides insight into the influence of ontogeny in potential ASO-induced thrombocytopenia in pediatric patients.

Platelet Transfusions in a Multi-Neonatal Intensive Care Unit Health Care Organization Before and After Publication of the PlaNeT-2 Clinical Trial

To evaluate whether implementing more restrictive neonatal intensive care unit (NICU) platelet transfusion guidelines following the Platelets for Neonatal Transfusion - Study 2 randomized controlled trial (transfusion threshold changed from 50 000/μL to 25 000/μL for most neonates) was associated with fewer NICU patients receiving a platelet transfusion, without adversely affecting outcomes. Multi-NICU retrospective analysis of platelet transfusions, patient characteristics, and outcomes during 3 years before vs 3 years after revising system-wide guidelines. During the first period, 130 neonates received 1 or more platelet transfusions; this fell to 106 during the second. The transfusion rate was 15.9/1000 NICU admissions in the first period vs 12.9 in the second (P=.106). During the second period, a smaller proportion of transfusions was administered when the platelet count was in the 50 000-100 000/μL range (P=.017), and a larger proportion when it was <25 000/μL (P=.083). We also saw a fall in the platelet counts that preceded the order for transfusion from 43 100/μL to 38 000/μL (P=.044). The incidence of adverse outcomes did not change. Changing platelet transfusion guidelines in a multi-NICU network to a more restrictive practice was not associated with a significant reduction in number of neonates receiving a platelet transfusion. The guideline implementation was associated with a reduction in the mean platelet count triggering a transfusion. We speculate that further reductions in platelet transfusions can safely occur with additional education and accountability tracking.

Effect of Temperature on Thrombogenicity Testing of Biomaterials in an In Vitro Dynamic Flow Loop System.

To develop and standardize a reliable in vitro dynamic thrombogenicity test protocol, the key test parameters that could impact thrombus formation need to be investigated and understood. In this study, we evaluated the effect of temperature on the thrombogenic responses (thrombus surface coverage, thrombus weight, and platelet count reduction) of various materials using an in vitro blood flow loop test system. Whole blood from live sheep and cow donors was used to assess four materials with varying thrombogenic potentials: negative-control polytetrafluoroethylene (PTFE), positive-control latex, silicone, and high-density polyethylene (HDPE). Blood, heparinized to a donor-specific concentration, was recirculated through a polyvinyl chloride tubing loop containing the test material at room temperature (22-24°C) for 1 hour, or at 37°C for 1 or 2 hours. The flow loop system could effectively differentiate a thrombogenic material (latex) from the other materials for both test temperatures and blood species ( p < 0.05). However, compared with 37°C, testing at room temperature appeared to have slightly better sensitivity in differentiating silicone (intermediate thrombogenic potential) from the relatively thromboresistant materials (PTFE and HDPE, p < 0.05). These data suggest that testing at room temperature may be a viable option for dynamic thrombogenicity assessment of biomaterials and medical devices.

Therapeutic effect of the combination of eltrombopag and low dose hormone in patients with primary immune thrombocytopenia

Purpose: To investigate the clinical effect and side effects of early addition of small-dose eltrombopag in initial treatment of primary immune thrombocytopenia (ITP) patients with decreased platelet count and hormone reduction, and patients with persistent ITP.&#x0D; Methods: Thirty ITP patients newly diagnosed with poor hormonal levels were recruited, along with 36 patients with persistent ITP. The ITP patients were given prednisone in combination with eltrombopag. Blood routine tests, blood pressure, blood sugar, liver and kidney function, and serum ion levels were monitored every two weeks. Adverse events were recorded at 2, 4, and 8 weeks after eltrombopag treatment.&#x0D; Results: After treatment for 2, 4, and 8 weeks, there was obvious effectiveness in 45.0, 39.4, and 40.9 % of patients, respectively, while effectiveness was good in 22.7, 37.9, and 50 % of patients, respectively. Treatment was ineffective in 31.8, 22.7, and 9.1 % of patients, respectively. In the 8th week, 15 patients (22.7 %) had to use prednisone at a dose of more than 20 mg/day to keep their platelet level above 30 x 109/L, while 7 patients (10.6 %) stopped using prednisone completely. Moreover, 4 patients (6.1 %) had their platelet counts maintained above 30 x 109/L after stopping the use of eltrombopag for more than 2 weeks.&#x0D; Conclusion: The combined use of eltrombopag and low-dose hormone is an effective treatment for ITP patients. It produces only a slight side effect, and it is affordable. A larger population study will be required to validate these findings of this new therapeutic option.

Alteration of Coagulation Profile in Preeclampsia And Eclampsia Patients At Tertiary Level Hospital

Background: Preeclampsia and eclampsia is associated with a risk of abnormal hemostasis that occurs most commonly secondary to thrombocytopenia. Automated analyze technique measures whole blood coagulation and has been used to manage coagulation defects in obstetric patients. Objective: To find out the alteration of coagulation profile beyond physiological level in preeclampsia and eclampsia patients for early detection and planning of management. Method: It was a observation type of cross sectional study carried out Department of Obs&amp; Gynae, Dhaka Medical College Hospital, Dhaka. Severe pre-eclamptic and eclamptic patients admitted in the department of Obstetrics &amp;Gynaecology, Dhaka Medical College Hospital during the period of July 2018 to December 2018. Data were collected as predesigned data collection sheet and for coagulation profile. Collection of venous sample about 5ml of blood were done without a pressure cuff allowing the blood to enter the syringe by continuous free flow and sending to the laboratory for coagulation assay by automated analyzer Sysmex CA500. Results: In this study mean age was 26.94 years, majority 56% age group was 26-30 years of age. The mean gestational age was 32.36 weeks. All the coagulation parameters were altered in 6% of the patients, 4 parameters were altered in 10% of the patients, 3 parameters were altered in 16% of the patients 2 and 1 parameters were altered in 24% and 44% patients respectively. Regarding coagulation profile, thrombocytopenia was present in 22% patients, prothombin time was prolonged in 10% of the patients, APTT was prolonged in 20% of the patients, and fibrinogen level was reduced in 40% of the patients and FDP was elevated 32% of the patients. Out of 50 severe preeclamptic and eclamptic patients, 6% of the patients developed DIC in whom all the coagulation parameters were altered. Conclusion: In this study, in patients of severe pre-eclampsia and eclampsia 22% patients had thrombocytopenia. 6% of the patients had alteration of all the coagulation parameters. Coagulation indices were altered not only in the patients with reduced platelet count but also in the patients with normal platelet count. Among the patients, 6% of the patients developed DIC, PPH developed in 12% of the patients and maternal death occurred in 4% of the patients. J Dhaka Med Coll. 2021; 30(2) : 214-219

Molecular analysis of phenotypic heterogeneity in JAK2V617F-positive myeloproliferative neoplasms reveals a potential target for therapy.

JAK2V617F is the most frequent mutation in BCR-ABL-negative myeloproliferative neoplasms (MPNs). It is an important but not the only determinant of MPN phenotype. We performed high-throughput sequencing on JAK2V617F+ essential thrombocythaemia (ET) and polycythaemia vera (PV) patient samples to unveil factors involved in phenotypic heterogeneity and to identify novel therapeutic targets for MPN. Two concurrent mutations that may affect phenotype were identified, including mutations in SH2B3, which is primarily prevalent in PV, and SF3B1, which is more commonly mutated in ET. Next, we conducted transcriptomic analysis at the haematopoietic stem cell (HSC) and megakaryocyte (MK)-erythroid progenitor (MEP) levels. Inflammatory signalling pathways were elevated in both ET HSCs and MEPs, unlike in PV HSCs and MEPs. Notably, Wnt/β-catenin signalling was uniquely upregulated during ET haematopoietic differentiation from HSC to MEP, and inhibiting Wnt/β-catenin signalling blocked MK differentiation in vitro. Consistently, Wnt/β-catenin inhibitor administration decreased platelet counts in JAK2V617F+ MPN mice by blocking MEPs and MK progenitors and by inhibiting maturation of MKs, while in wild-type mice, Wnt/β-catenin inhibitor did not significantly reduce platelet counts. In conclusion, our findings provide new insights into the mechanisms underlying phenotypic differentiation of JAK2V617F+ PV and ET and indicate Wnt/β-catenin signalling as a potential therapeutic target for MPN.

Optimization of Radium-223 Treatment of Castration-resistant Prostate Cancer Based on the Burden of Skeletal Metastasis and Clinical Parameters.

Radium-223 dichloride (Ra-223) is now frequently used to treat prostate cancer that has metastasized to bone, although patient selection continues to be suboptimal for determining who will benefit most from this novel treatment modality. Seventy-nine patients with metastatic castration-resistant prostate cancer (mCRPC) were treated with Ra-223 from 2012 to 2016. The burden of skeletal metastasis was determined for each using the Bone Scan Index (BSI) as a ratio of diseased to normal bone. Clinical, laboratory, and survival data were collected and examined for associations with BSI, and treatment tolerability was assessed. Chemotherapy-naïve patients were significantly more likely to complete the full course of treatment. Median follow-up was 31 months (range 0.7-38.8 months) and median overall survival was 15.4 months (range 9.5-20.6 months). Overall survival was significantly associated with findings on bone scans (P < .05). Patients with higher BSI tended toward poorer outcomes. Nearly half the patients with low baseline BSI survived 3 years or more following Ra-223 treatment. By contrast, only 20% of the patients with high baseline BSI lived for 1 year, and none lived for an additional 3. Baseline BSI was significantly associated with decreased hemoglobin, higher serum PSA and alkaline phosphatase levels, and treatment-associated reductions in platelet and absolute neutrophil counts. Our results suggest better outcomes to Ra-223 therapy for patients who are chemotherapy-naïve and who undergo treatment earlier in the course of their disease as reflected by low BSI and concordant laboratory parameters.

Efficacy and safety of sitagliptin treatment in older adults with moderately controlled type 2 diabetes: the STREAM study

Sitagliptin has been suggested as a treatment option for older adults with type 2 diabetes (T2D). However, no randomized controlled trial has been performed to evaluate the efficacy and safety of sitagliptin treatment in older Japanese patients with T2D. The STREAM study was a multicenter, open-label, randomized controlled trial. T2D outpatients aged 65–80 years with moderately controlled glycemic levels (HbA1c 7.4–10.4%) under lifestyle interventions without or with oral anti-diabetic drugs excluding DPP4 inhibitors or GLP-1 receptor agonists were recruited (n = 176). The participants were randomized into sitagliptin group (n = 88) who received sitagliptin as an initial or an additive anti-diabetic drug and control group (n = 88) who did not. The treatment goal was HbA1c level < 7.4%. Efficacy and safety during 12-month treatment period were investigated. The mean (± SD) ages were 70.6 ± 3.9 and 71.9 ± 4.4 years old in sitagliptin and control groups, respectively. According to a mixed-effects model analysis, average changes from baseline over the treatment period in fasting plasma glucose (FPG), HbA1c, and glycated albumin (GA) were − 27.2 mg/dL, − 0.61%, and − 2.39%, respectively, in sitagliptin group, and 0.50 mg/dL, − 0.29%, and − 0.93%, respectively, in control group. The reductions in FPG, HbA1c, and GA were significantly greater in sitagliptin group (P < 0.0001, P < 0.01, and P < 0.0001, respectively). There were no differences in the incidence of adverse effects, except for cystatin C elevation and platelet count reduction in sitagliptin group. Sitagliptin treatment effectively improved the glycemic profile without any serious adverse effects in older T2D patients.Trial registration number: UMIN000010376.

Evaluation of keeping quality of canine platelet rich plasma under different storage conditions

Platelet rich plasma (PRP) therapy is an integral part of regenerative medicine as the platelets possess a good healing capacity owing to the presence of a wide variety of growth factors in the platelet granules found in the cytoplasm of the platelet. Autologous PRP was prepared from the blood of the patient itself, without any preservatives. Storage of PRP was one of the main hurdles of the treatment modality. During storage, the platelet counts may get reduced, undergo activation or get contaminated with bacteria as no preservatives are used in the preparation of autologous PRP. Cytological changes and microbial quality of the PRP during storage at 4oC and -20oC for seven days were analysed in this study. Reduction in platelet count and the chance of microbial contamination were less when autologous PRP was stored at -20°C compared to 4°C.

Protective Effect of Vitamin D Supplementation on Some Hemogram Derived Inflammatory Indices in Normal and High-Fat Diet Fed Male Wistar Rats.

Hematological inflammatory indices are currently suggested to assess systemic inflammation. This study aims to investigate a vitamin D supplementation effect on hematological indices of inflammation in rats. Forty-eight middle-aged male rats were allocated into a normal diet (ND) group (10% fat) and a high-fat diet (HFD) group (60% fat). The animals were fed for 26 weeks. After this period, each group was randomly divided into three subgroups, each of 8 rats: Group (1): animals were fed the ND and HFD containing 1 IU/g vitamin D for 4 months, group (2): animals were fed the ND and HFD containing 6 IU/g vitamin D for 4 months and group (3): animals were euthanized to evaluate the HFD effect. Serum 25-hydroxyvitamin D level, white blood cell count (WBCs), platelet count, platelet crit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) were measured. The HFD, significantly increased body weight, PCT, PDW, PLR, NLR, and MLR and significantly reduced serum vitamin D levels compared to the ND (P < 0.05). There was a significant decrease in food intake, MPV, PDW, and NLR after vitamin D supplementation in the ND-fed group (P < 0.05). A significant reduction in platelet count, PCT, and MLR was observed after vitamin D supplementation in HFD-fed rats (P < 0.05). In our study, some hemogram-derived inflammatory indices were higher in the HFD-fed group, and vitamin D supplementation lowering effects on some hematological indices were seen in both ND and HFD groups.

A case of rectal cancer with immune thrombocytopenic purpura that achieved a complete response to continued chemotherapy with eltrombopag

A 73-year-old male patient with postoperative recurrent rectal cancer developed thrombocytopenia after XELOX therapy. Thrombocytopenia persisted despite chemotherapy discontinuation;therefore, he was referred to our department for further evaluation. Bone marrow specimen examination revealed increased immature megakaryocytes and blood test results revealed elevated platelet-associated immunoglobulin G (PA-IgG) levels, leading to immune thrombocytopenic purpura diagnosis. His platelet count recovered after prednisolone therapy. Eltrombopag treatment was introduced considering thrombocytopenia secondary to chemotherapy resumption for rectal cancer. FOLFIRI therapy was continued without platelet count reduction, and PA-IgG levels decreased over time. The patient continued chemotherapy with eltrombopag and achieved a complete treatment response.

Лечение пациентов с хронической HDV‑инфекцией – опыт реальной клинической практики в Московской области

Objective. This study aims to analyze the results of using bulevirtide, an HBV and HDV entry inhibitor, in real-world practice in patients with chronic hepatitis D in the Moscow region. The analysis focuses on the effectiveness and safety of bulvertide treatment, both as monotherapy and in combination with peginterferon, during the compensated and decompensated stages of liver cirrhosis. Patients and methods. The study evaluated the efficacy and safety of bulevirtide treatment in two patient groups. The first group consisted of 61 patients with compensated disease, including 27 individuals with Child–Pugh class A liver cirrhosis. The second group included 8 patients with Child–Pugh class B cirrhosis. Results. Among patients with compensated disease, a 48-week treatment with bulevirtide resulted in a significant decrease in HDV RNA levels from 6.9 log10 to undetectable (p &lt; 0.001). Furthermore, alanine aminotransferase (ALT) levels decreased from 64.0 to 37.0 U/l (p &lt; 0.001). The median reduction in HDV RNA levels from baseline was -5.1 log10 (monotherapy: -4.2 log10, dual therapy: -5.7 log10). The virological response rate was 94% (monotherapy: 88%, dual therapy: 96%) with «full virological response» (aviremia) observed in 66% of patients and normal ALT levels in 59% of patients (compared to 22% at baseline). Virological efficacy improved over the course of treatment. Similar virological response dynamics were observed in patients with compensated cirrhosis compared to the overall group. In patients with decompensated cirrhosis, a virological response was observed in 6 out of 8 patients during treatment, and a biochemical response (a decrease in ALT levels from 60.0 U/I to 45.0 U/l) in 5 out of 8 patients. After 48 weeks of treatment, all 5 patients who reached this point achieved a virological response (decrease in HDV RNA levels from 5.1 log10 to 3.0 log10, median decrease of -2.5 log10 from baseline). One patient on monotherapy achieved «full virological response» (aviremia). Improvement of liver function was observed, including a reduction in liver damage severity based on Child–Pugh score to the compensated cirrhosis level (6 points), down-staging from Child–Pugh class B to A in 3 patients, and clinical resolution of ascites in 7 out of 8 patients and hepatic encephalopathy in 3 out of 5 patients. Bilirubin, albumin, INR, prothrombin time remained stable. The treatment was well tolerated, no serious adverse events, cases of treatment withdrawal were registered. The reduction in leukocyte and platelet counts, related to interferon, did not necessitate treatment adjustment. Conclusion. The analysis of bulevirtide use in patients with CHD in real-world practice demonstrated high treatment efficacy, safety and good tolerability, even in cases of compensated and decompensated liver cirrhosis. This study also presents the first experience of antiviral therapy for decompensated liver cirrhosis in Russia, supporting the recommendation of bulevirtide for patients with impaired liver function. Furth er development of an optimal treatment algorithm, including for patients with impaired liver function, is needed, as well as clarification of the treatment effect on clinical outcomes and disease prognosis. Key words: bulevirtide, chronic hepatitis D, compensated cirrhosis, decompensated cirrhosis, chronic liver failure

Thrombocytopenia after Implantation of the Perceval, Intuity, and Sapien Aortic Valve Prostheses.

An increased incidence of thrombocytopenia was reported after implantation of the LivaNova Perceval and the Edwards Sapien aortic valve bioprostheses. Aim of this study is to assess the perioperative platelet count and bleeding complications in three different types of aortic valve bioprostheses intended for high-risk patients, the sutureless LivaNova Perceval, the rapid deployment Edwards Intuity, and the transcatheter Edwards Sapien. We performed a retrospective analysis of the perioperative data of patients receiving the Perceval, Intuity, and Sapien aortic valve bioprosthesis. The platelet count was collected preoperatively, at nadir postoperatively, and at discharge. The bioprostheses were compared for between-group differences in platelet count and postoperative bleeding complications. Overall, 37 patients received the Perceval, 42 the Intuity, and 58 the Sapien bioprosthesis. There was no significant between-group difference in the preoperative platelet count [Perceval 203(178-246)G/l, Intuity 214(190-232)G/l, Sapien 201(178-275)G/l, p = 0.800]. There was a significant between-group difference in the postoperative platelet count, both at nadir value [Perceval 57(37-80)G/l, Intuity 91(73-109)G/l, Sapien 126(105-170)G/l, p < 0.0001] and at discharge [Perceval 150(83-257)G/l, Intuity 239(200-343)G/l, Sapien 232(179-284)G/l, p = 0.001]. There was no significant between-group difference regarding red blood cell transfusions (p = 0.242), platelet transfusions (p = 0.656), and rethoracotomy for bleeding (p = 0.847). We found a significant platelet count reduction in all three bioprostheses which was more marked in the Perceval group. The platelet count reduction was transient and fully recovered in the Intuity and Sapien groups, whereas the Perceval group showed only a partial platelet count recovery. However, bleeding complications were not different between the three bioprostheses.

Efficacy of Normal Saline as Flushing Solution to Maintain Indwelling Arterial Catheter Patency after Cardiac Single Valve Surgery

Introduction: Arterial catheters include radial, brachial, femoral, dorsalis pedis and axillary artery are used in the intensive care unit for continuous blood pressure monitoring, repeated blood sampling. Normal saline solution can maintain patency of arterial and central venous pressure monitoring catheters. Heparinized solutions had no effect on prolonging patency and improving function of catheters while the normal saline solution increases accuracy of coagulatory tests. Aim of the Study: The aim of this study was to examine the efficacy of Normal saline as flushing solution to maintain indwelling arterial catheter patency among patients after cardiac single valve surgery. Methods: This was a prospective cross-sectional study conducted in the Department of Cardiac surgery of National Institute of Cardiovascular Disease (NICVD), Sher-E-Bangla Nagar, Dhaka, Bangladesh during the period from July 2016 to June 2017. This study included sixty patients who underwent single valve replacement surgery and shifted to the ICU with arterial line catheter. The patients who fulfilled the inclusion criteria were divided into two groups- Group 1 (with heparin solution) and Group 2 (with normal saline). Result: In our study we found the mean ± SD of age among Group 1 &amp; 2 was (36.3±6.7) &amp; (35.7±10.3) respectively. We found 100% patients had arterial line patent in 1st POD in both groups. In 2nd POD 86.8% &amp; 76.7% and at 3rd POD 50.0% &amp; 43.3% patients had patency in Group 1 &amp; Group 2 respectively. We found the mean± SD of platelet count at 1st POD was (206530±64441) &amp; (212543±48768); at 3rd POD was (226517±60185) &amp; (245957±52826); at 7th POD was (240517±57379) &amp; (257713±53655); at 14th POD was (245850±52680) &amp; (244337±56796) in Group 1 &amp; 2 respectively which was significantly higher in Group 2. Conclusion: The use of heparin in normal saline for arterial line flushing does not significantly reduce platelet counts in cardiac valve surgery patients in comparison to use of normal ....

A dual-action nitric oxide-releasing slippery surface for extracorporeal organ support: Dynamic in vitro hemocompatibility evaluation.

Numerous biomaterials have been developed for application in blood-contacting medical devices to prevent thrombosis; however, few materials have been applied to full-scale devices and evaluated for hemocompatibility under clinical blood flow conditions. We applied a dual-action slippery liquid-infused (LI) nitric oxide (NO)-releasing material modification (LINO) to full-scale blood circulation tubing for extracorporeal lung support and evaluated the tubing ex vivo using swine whole blood circulated for 6h at a clinically relevant flow. LINO tubing was compared to unmodified tubing (CTRL) and isolated LI and NO-releasing modifications (n=9/group). The primary objective was to evaluate safety and blood compatibility of this approach, prior to progression to in vivo testing of efficacy in animal models. The secondary objective was to evaluate coagulation outcomes relevant to hemocompatibility. No untoward effects of the coating, such as elevated methemoglobin fraction, were observed. Additionally, LINO delayed platelet loss until 6h versus the reduction in platelet count in CTRL at 3h. At 6h, LINO significantly reduced the concentration of platelets in an activated P-selectin expressing state versus CTRL (32 ± 1% decrease, p=.02). Blood clot deposition was significantly reduced on LINO blood pumps (p=.007) and numerically reduced on tubing versus CTRL. Following blood exposure, LINO tubing continued to produce a measurable NO-flux (0.20 ± 0.06 × 10-10 mol cm-2 min-1 ). LINO is a potential solution to reduce circuit-related bleeding and clotting during extracorporeal organ support, pending future extended testing in vivo using full-scale extracorporeal lung support devices.

Immune Thrombocytopenia Purpura Relapse in Patients Who Received mRNA COVID-19 Vaccines

Background: Immune thrombocytopenic purpura (ITP) is a syndrome in which platelets become coated with autoantibodies to platelet membrane antigens. The mononuclear macrophage system of the spleen is responsible for removing platelets in ITP. This leads to a decrease in circulating platelet count and propensity for bleeding. Patients usually present with bruising and mucosal bleeding, with a minority of cases developing major bleeding complications such as intracranial hemorrhage. Cases of ITP and ITP relapse have been reported in people who received the mRNA SARS-CoV-2 vaccine, most reported cases present with bruising and mucosal bleeding in the first few weeks after receiving the vaccine, nevertheless, the causal relationship is not yet proved. Objectives: This study aims to prove the causal relationship betweenITP relapse in known ITP patients and the mRNA covid vaccine. And to evaluate the long-term effect of the vaccine on ITP patients > 6 months after receiving the second dose. Methods a retrospective study was conducted to check platelet count in 67 patients known for immune thrombocytopenia purpura, who are >18-year- old, and not known for any other causes of thrombocytopenia (including congenital thrombocytopenia, malignancy, SLE, anti-phospholipid syndrome). The platelet count was identified at baseline before receiving the vaccine and within 3 months, 6 months, and after 6 months after receiving the vaccine. Results: The results showed that 6% of ITP patients had ITP relapse within the first 3 months after the mRNA covid vaccine, 10% of patients had a relapse within the first 6 months and another 8% had a relapse more than 6 months after receiving the vaccine. on follow-up for the patient who didn't have a frank relapse, within the first 6 months after receiving the vaccine 8% of patients had more than 50% reduction from their baseline platelet count and 6% had a 25-50% reduction in the platelets count. on follow-up more than 6 months after the vaccine,4% of patients had more than 50% reduction in platelet count and 3% had a 25-50% reduction from their baseline platelet count. There was no statically significant difference between Moderna and Pfizer vaccine on ITP relapse rate or platelet count reduction. Conclusion mRNA covid vaccine increases the risk of ITP relapse and leads to a reduction in platelets count compared to the baseline count before receiving the vaccine, with no statically significant difference between Pfizer and Moderna vaccines. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Shear Stress Promotes Platelet Surface Desialylation, Platelet Count Drop, and Microvesiculation: Do Platelets Need to be Sugar-Coated?

Introduction. Mechanical circulatory support (MCS) devices restore hemodynamics and are lifesaving for patients with advanced heart failure and, recently, for patients with severe COVID-19. Long-term MCS is associated with bleeding complications, often requiring multiple transfusions of blood products or reoperations. To date, due to undefined etiology, device-related bleeding lacks efficient therapeutic management. We have shown that hypershear stress, existing within device-supported circulation promotes platelet dysfunction associated with pro-apoptosis, downregulation of key adhesion receptors, impaired platelet aggregation, and microvesiculation - all contributors to bleeding. Recent studies have also shown that glycosylation of platelet surface receptors, i.e. the platelet "sugar coat," plays a major role in the regulation of platelet function and lifespan. Here, we tested the hypothesis that hypershear stress promotes platelet surface desialylation, thus facilitating platelet count drop and increased microvesiculation. Methods. Human platelets were obtained from ACD-anticoagulated blood of healthy volunteers via gel filtration on Sepharose 2B. Gel-filtered platelets were exposed to neuraminidase and continuous shear stress (30 or 70 dyne/cm2,10 min) in a hemodynamic shearing device. Optionally, platelets were pretreated with oseltamivir, a common neuraminidase inhibitor. Platelets were co-stained with fluorophore-conjugated SNA lectin, binding terminal 2,6-linked sialic acid moieties, and anti-CD41 antibody. Multi-colored flow cytometry was performed to quantify platelet surface sialylation, platelets, and microparticles; fluorescent nanobeads SPHEROTM were used as a size standard. The surface density of platelet sialylation was calculated as median fluorescence intensity normalized to forward scatter indicating platelet size. The platelet neuraminidase activity was quantified using fluorogenic substrate 4-methylumbelliferyl-N-acetylneuraminic acid (MUNANA) and was presented as µM of substrate per min. Results. Platelet exposure to both hypershear stress and neuraminidase-1 induced platelet surface desialylation as indicated by the significant decrease of SNA lectins' binding density on platelets (Fig.1A). Platelet desialylation induced by shear stress and neuraminidase was associated with a notable decrease in platelet count and an increase in platelet-derived microparticles (Fig.1B). Interestingly, neuraminidase reinforced shear-mediated desialylation, platelet count drop, and microvesiculation. Oseltamivir slightly inhibited shear-mediated desialylation, preserved platelet count (30% increase vs. shear), and decreased microparticle generation (29% decrease vs. shear). Exposure to 70 dyne/cm2 shear stress resulted in a 9.5-fold increase in platelet neuraminidase activity as compared to basal level: 0.85 ± 0.61 µM/min vs 0.05 ± 0.03 µM/min, respectively (Mean ± SD, p < 0.01, one-way ANOVA). Conclusions. Shear stress promotes platelet surface desialylation with the associated reduction in platelet count and increased microvesiculation. Neuraminidase inhibition restores platelet count and decreases microparticle generation caused by hypershear. Shear-mediated increase of platelet neuraminidase activity is considered a plausible mechanism for shear-mediated platelet deglycosylation. Developing therapeutic strategies for preservation of platelet sialylation offers significant translational potential for pharmacologic management of MCS-related platelet dysfunction and bleeding coagulopathy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Challenges of Diagnosing Headache in Sickle Cell Disease, a Unique Case of Polycythemia Vera and Essential Thrombocytosis in a Patient with Sickle Cell beta0 Thalassemia

Introduction: Little is known of the relationship between myeloproliferative neoplasm (MPN) and sickle cell disease (SCD), possibly due to under diagnosis from symptom overlap. Few studies exist documenting cases of concomitant MPN in SCD patients, likely because the confounding presence of reactive thrombocytosis in SCD and masking of polycythemia in SCD making the diagnosis of essential thrombosis (ET) and polycythemia vera (PV) difficult. Case Presentation: Here, we report a case of a 38-year-old male with beta 0 thalassemia (HbSB0) SCD who developed a chronic, and unremitting headache of 2 months. Neurological workup of his headache was unremarkable and headache remained unresponsive to various pain medications used by the patient for sickle cell associated pain crises. Laboratory values on presentation were remarkable for WBC 11 k/uL, HgB 10.9 g/dL, platelets 994 k/uL, MCV 72, reticulocyte count 7.0%. A thorough analysis of vasomotor symptoms and laboratory values, when trended over 20 years (table 1), demonstrated that headaches were likely secondary to hyperviscosity, as noted by platelet uptrend and inappropriate hemoglobin elevation for his SCD genotype; in which the expected hemoglobin level is between 6-8g/dL. Laboratory studies demonstrated a JAK2 mutation in peripheral blood with no BCR-ABL mutation detected, excluding chronic myeloid leukemia (CML). Subsequent bone marrow biopsy demonstrated hypercellular marrow (90-95%) with marked erythropoiesis and relatively mild increased granulocytic and megakaryocytic hematopoiesis and mild increase in reticulin fibers, without dysmyelopoiesis; thus excluding myelodysplastic syndrome (MDS). Mutation analysis confirmed JAK2 Val617Phe mutation. Concurrent flow cytometry analysis showed no evidence for leukemia or lymphoproliferative disorder. Together with biopsy data, laboratory data and clinical presentation, the patient was diagnosed with polycythemia vera and essential thrombocytosis. The patient was subsequently managed with Hydroxyurea, with resolution of symptoms presumably due to improvement in blood viscosity due to lowering of platelet levels to 464k/uL. Discussion: Our report highlights a unique association between MPN in a patient with SCD, diagnostic challenges, and its multifaceted treatment. Our patient presented with unremitting headaches, which can be secondary to either SCD or MPN alone. In patients with SCD severe headache can be associated with ischemic stroke due to vaso-occlusion, hemorrhage, venous sinus thrombosis, aneurysms, meningitis, medication withdrawal or tolerance, bony infarcts, and osteomyelitis. The wide differential diagnosis of headaches in SCD complicates the finding of MPN amongst these patients, and without frequent laboratory monitoring, concomitant vasomotor symptoms would likely remain unnoticed in the patient. Furthermore, our report describes the first documented association of a JAK2 Val617Phe mutation in a patient with SCD. Our case also outlines the use of hydroxyurea as a double edged sword. Interestingly in our patient, hydroxyurea initiation acted as a dual therapy for the management of SCD, through reducing pain crisis episodes, and MPN via platelet count reduction, thereby preventing symptoms of hyperviscosity. Overall, this case highlights a distinctive example of PV and ET in a patient with SCD and its diagnostic challenges, and the first case in the literature to describe JAK2 Val617Phe mutation. Further, our case emphasizes the need to consider vasomotor symptoms and perform a critical analysis of laboratory trends in SCD patients. Future studies may consider a multi-institution retrospective analysis of thrombocytosis in SCD patients to determine if MPN is underdiagnosed in SCD patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal