Thrombosis

Short and Medium-Term Evaluation of Patients in Coronary Post-Angioplasty: Préliminary results at the Cardiology Department of the Hospital University Aristide Le Dantec of Dakar (Senegal): Study on 38 Cases

Published on: 20th February, 2017

OCLC Number/Unique Identifier: 7286354250

Introduction: Coronary angioplasty is a safe therapeutic method for coronary disease. However, its major obstacles remain the occurrence of stent thrombosis (ST) and in-stent restenosis (ISR). The aim of this study was to evaluate the short-term and medium-term results of coronary angioplasty patients in the cardiology department of Aristide Le Dantec hospital in Dakar. Methodology: It was a longitudinal, descriptive and analytical study over a period of 12 months (April 2014 to April 2015) with a follow-up at 6 months. Was included any patient who had a coronary angioplasty with stent placement. Results: Thirty-eight patients had been included with a male predominance and a sex ratio of 5.32. The average age was 57.94 years. Cardiovascular risk factors were mainly smoking (57.9%) and coronary heredity (42.1%), followed by hypertension (39.5%) and diabete (34.2%). The indications for angioplasty were acute coronary syndromes TS(+) and TS(-) respectively (50%) and (23.7%) and stable angina (26.3%). The right femoral approach was almost exclusive (97.4%). Coronary angiography revealed a predominance of anterior interventricular affection (84.2%). Type B lesions were the most frequent (68.4%). The single-truncal valve affection was predominant (76.3%). Direct stenting accounted for 63.2% of procedures. Twenty-one bare stents (55.3%) and 17 active stents (44.7%) were implanted. The results were excellent (94.7%). One case of acute stent thrombosis was noted. Echocardiography of dobutamine stress during follow-up was positive in 04 patients (12.5%). The control coronary angiography performed in two patients revealed an ISR. The predictive factors for restenosis were dominated by a deterioration in the segmental kinetics (p=0.009), in the diastolic function (p=0.002), the systolic function (p=0.003), a high post angioplasty troponin (p=0.004), the presence of calcifications (p=0.004) and a high SYNTAX score (p=0.021). Conclusion: According to these results, Angioplasty is an effective therapy for coronary disease. However, a correct intake of double platelet antiaggregants and clinical and non-invasive screening are required for follow-up to avoid stent thrombosis or restenosis.
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Numerical Simulation of Thrombotic Occlusion in Tortuous Arterioles

Published on: 6th December, 2017

OCLC Number/Unique Identifier: 7666340975

Tortuous microvessels alter blood flow and stimulate thrombosis but the physical mechanisms are poorly understood. Both tortuous microvessels and abnormally large platelets are seen in diabetic patients. Thus, the objective of this study was to determine the physical effects of arteriole tortuosity and platelet size on the microscale processes of thrombotic occlusion in microvessels. A new lattice-Boltzmann method-based discrete element model was developed to simulate the fluid flow field with fluid-platelet coupling, platelet interactions, thrombus formation, and thrombotic occlusion in tortuous arterioles. Our results show that vessel tortuosity creates high shear stress zones that activate platelets and stimulate thrombus formation. The growth rate depends on the level of tortuosity and the pressure and flow boundary conditions. Once thrombi began to form, platelet collisions with thrombi and subsequent activations were more important than tortuosity level. Thrombus growth narrowed the channel and reduced the flow rate. Larger platelet size leads to quicker decrease of flow rate due to larger thrombi that occluded the arteriole. This study elucidated the important roles that tortuosity and platelet size play in thrombus formation and occlusion in arterioles. 
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Dapt Review

Published on: 25th March, 2020

OCLC Number/Unique Identifier: 8576364795

Dual antiplatelet therapy (DAPT) combining aspirin and a P2Y12 receptor inhibitor has been consistently shown to reduce recurrent major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) compared with aspirin monotherapy but at the expense of an increased risk of significant bleeding. Among patients with stable CAD undergoing PCI with drug-eluting stents (DES), shorter duration of DAPT (3–6 months) were shown non-inferior to 12 or 24 months duration concerning MACE but reduced the rates of major bleeding? Contrariwise, prolonged DAPT durations (18–48 months) reduced the incidence of myocardial infarction and stent thrombosis, but at the cost of an increased risk of majör bleeding and all-cause mortality. Until more evidence becomes available, the choice of optimal DAPT regimen and duration for patients with CAD requires a tailored approach based on the patient clinical presentation, baseline risk profile and management strategy. Patients with acute coronary syndromes (ACS) and a history of atrial fibrillation (AF) have indications for both dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC). Triple therapy (TT), the combination of DAPT and OAC, is recommended in guidelines. This article provides a contemporary state-of-the-art review of the current evidence on DAPT for secondary prevention of patients with CAD and its future perspectives.
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Femoral venous closure: A single-centre retrospective analysis in real world all comers with MynxGrip® vascular closure device

Published on: 18th June, 2020

OCLC Number/Unique Identifier: 8628667812

Background: Vascular closure devices (VCD) are routinely used to achieve haemostasis following percutaneous arterial procedures. The extravascular polyethylene-glycol based MynxGrip® device (Cardinal Health) received FDA approval for use in the closure of femoral veins, but so far limited data is available on its use, especially with concomitant use of anticoagulants. Method: This is a retrospective analysis of data from a single-centre on the effectiveness and complication rates following the use of the MynxGrip® device for femoral venous closure in patients undergoing diagnostic/interventional (temporary pacing during balloon aortic valvuloplasty, or electrophysiology) procedures utilising 5-7F sheaths. Results: 85 patients (mean age 74 years) underwent femoral venous closure with the MynxGrip® device. 51.8% were male. The rate of concomitant anticoagulant or antiplatelet use was 52.9%. Device deployment was 100% successful with full haemostasis in all cases. There were no major vascular complications (bleeding, thrombosis, or infections). There was one case of a minor small venous hematoma which did not require treatment. The mean length of stay was less than 1 day (67.1% patients discharged the same day) and overnight stay only indicated by interventional procedure. Conclusion: These data support safety and efficacy of the MynxGrip® device for femoral venous closure with same-day discharge, even with concomitant aggressive antiplatelet and anticoagulant use. It has the potential for use in other large bore venous access sites. 
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Intravascular leiomyoma misdiagnosed as deep vein thrombosis: A case report

Published on: 30th June, 2021

OCLC Number/Unique Identifier: 9272372470

Background: Leiomyoma itself is not a rare disease, but it is rarely found intravascularly. Case presentation: A 54-year old female sought medical help after noticing her leg being swelling. A diagnosis of deep vein thrombosis (DVT) was made and antithrombotic treatment was given after her initial imaging exam. Several days later, a contrast CT and sequential pathology revealed the real diagnosis was intravascular leiomyoma. The patient was discharged after a successful surgery. Conclusion: Intravascular leiomyoma should not be confused with DVT.
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Haemostasis with suture-tourniquet technique following removal of large-bore venous sheaths for endovascular recanalization of acute thrombosis in native arteriovenous fistula

Published on: 26th August, 2019

OCLC Number/Unique Identifier: 8277769392

Purpose: To investigate the suture-tourniquet technique for haemostasis in patients with acute thrombosis of native arteriovenous fistula (AVF) whom underwent manual aspiration thrombectomy using large-bore venous sheaths and high dose heparin. Methods: Between January 2016 and May 2018, patients with acute AVF thrombosis performed successful manual aspiration thrombectomy by using large bore venous sheaths and high dose heparin were included in this retrospective study. Success rate for haemostasis, procedural complications clinical and imaging follow up was reported descriptively. Results: A total of 52 patients with 64 procedures met the inclusion criteria. In 60(94%) of 64 procedures, successful haemostasis was achieved with suture-tourniquet technique. In 2(3.1%) of the 64 procedures, the suture broke while turning the tourniquet and haematoma occurred in another 3 procedures (4.7%) although suture-tourniquet technique was applied appropriately. Manual compression was performed in these patients. There were 3 major complications unrelated the suture-tourniquet technique. Conclusion: The suture tourniquet technique can achieve haemostasis rapidly and can be safely used with low complication rates without fistulae thrombosis after large-bore venous sheath removal following treatment of AVF thrombosis.
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AngioJetTM rheolytic thrombectomy induced intravascular haemolysis leading to Acute Kidney Injury requiring Dialysis

Published on: 3rd August, 2018

OCLC Number/Unique Identifier: 7815114583

Background: AngioJetTM rheolytic thrombectomy has been used in the treatment of deep vein thrombosis (DVT) to prevent post-thrombotic syndrome. Though not widely appreciated, it has the potential to cause intravascular haemolysis. Report: A 37 year old man with no previous medical history presented to his GP with a three week history of progressive right upper limb swelling. Doppler imaging confirmed right upper limb DVT and CT scan demonstrated thoracic outlet syndrome. The patient underwent AngioJetTM thrombectomy followed by IV heparin infusion. Successful revascularisation of the occluded vein was achieved. Overnight he developed haematuria, which was initially attributed to IV heparin. Urinalysis however revealed no red cells or casts. Apart from an Hb drop from 134 to 117 his blood profile and blood film showed no abnormality. He subsequently developed progressive oliguria with marked oedema and acute kidney injury (AKI). His creatinine peaked at 1070umol/l at 96 hours post procedure and he was started on intermittent dialysis. He remained dialysis dependent for 6 days. Ultrasound imaging excluded urinary obstruction. Autoimmune and vasculitic serology were negative. Intravascular haemolysis and haemoglobinuria was confirmed by raised LDH (1714u/L) and low haptoglobin (<0.1units). Direct Coomb’s test, Cold agglutinin test and paroxysmal nocturnal haemoglobinuria screen were negative. The patient’s renal function normalised over 3 months. Conclusions: The likely cause of this man’s AKI is heme pigment nephropathy from intra-vascular haemolysis. Increased awareness of this condition may allow early identification and intervention to reduce the risk of renal injury from AngioJetTM associated haemolysis.
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Preservation of Haemostasis with Anti-thrombotic Serotonin Antagonism

Published on: 18th September, 2017

OCLC Number/Unique Identifier: 7355973980

An enquiry into the lack of attention awarded to serotonin antagonism in the treatment of arterial thrombosis revealed that the mode of action of serotonin and its platelet receptor antagonists was an action upon thrombus growth, and not, as with other anti-platelet drugs upon the initiation of thrombosis. This lack of effect could explain why this approach has been considered not to be effective. However under conditions of arterial stenosis in which there is platelet activation by increased shear stress, and during the growth phase of arterial thrombi, serotonin 5HT2A antagonism has been demonstrated to have great potentcy in dispersing thrombotic obstruction to blood flow. This mode of action, the lack of participation of serotonin in haemostasis, and the absence of serotonin in wounds accounts for the proven lack of effect of effect of pure specific 5HT2A antagonists (i.e., not those with other actions) on operative bleeding and skin bleeding times. This lack of effect on haemostasis solves the dosing problem encountered with other anti-thrombotic drugs, with which drug concentration cannot be controlled with single fixed doses, leading to the association between increased anti-thrombotic efficacy and increased bleeding complications. Thus 5HT2A antagonism appears to be the preferred approach, from the point of view of safety and lack of bleeding risk; this consideration applies particularly to thrombosis therapy in the context of traumatic accidents, surgical operations and invasive procedures such as angioplasty.
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A study of coagulation profile in patients with cancer in a tertiary care hospital

Published on: 10th February, 2021

OCLC Number/Unique Identifier: 8999933050

The complicated process of cancer triggers many physiological systems like vascular endothelial functions and hemostasis, which signifies the increased risk of thrombosis, which triggers thromboembolic events resulting in increased mortality and morbidity [1-3]. Tumorigenesis contributes by activation of coagulation around the perivascular region [4].
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Otogenic lateral sinus Thrombosis: a rare complication of chronic Otitis media

Published on: 22nd August, 2017

OCLC Number/Unique Identifier: 7317596429

Since the advent of antibiotics, lateral sinus thrombosis is an infrequent complication of otitis media. Lateral sinus thrombosis may occur by thrombophlebitis or penetration by offending pathogens through the dura of middle and posterior cranial fossae. We present a case of right-sided sigmoid and transverse venous sinus thrombosis as a rare complication of chronic suppurative otitis media in an adult. We discuss the patient’s imaging, management and relevant literature to offer clinical recommendations. A 39-year-old woman presented with headache, neck pain, vomiting, fever and photophobia with a tender right mastoid on examination. Computerised Tomography, Magnetic Resonance Imaging and Magnetic Resonance Venogram of the head revealed complete opacification of the right mastoid air cells and middle ear, with absent flow void in the right transverse and sigmoid sinus, consistent with thrombosis. After discussion with neurosurgery, she was commenced on anticoagulants. The patient was readmitted with right otalgia and otorrhea refractory to medical treatment, and ultimately underwent right mastoid exploration. Conclusion: Lateral sinus thrombosis may occur with other intracranial or extracranial complications of otitis media. Clinicians should approach any complication of otitis media with vigilance as antibiotics may mask some signs and symptoms of mastoiditis, which can progress to otogenic brain abscess.
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The SARS CoV-2 spike domain, RGD and integrin binding effect-relationship for vaccine design strategy

Published on: 20th July, 2021

OCLC Number/Unique Identifier: 9244748101

Related the need to search new strategy in vaccine design in order to reduce also some rare effect like trombosys for some registered products it is interesting the role played by the SPIKE RGD domain. The binding with molecules like Fibronectin is a process that must to be deeply investigated. A better understanding in this process can be used to improve safety of the new generation of COVID vaccine. The rare effect like thrombosis recognized by regulatory agency produced a modification of technical data sheet of some vaccine so the phenomena Is interesting to be more investigated. Spike protein and its domains are involved in producing pathological effect of the COVID-19 disease. What it is interesting is that some pathological effect of this pathology are similar to some rare side effect produced by some COVID-19 vaccine classes. After a review of interesting literature related this topics is submitted an experimental projects able to verify in vitro the spike procoaugulant property.
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Endothelial Repair and Endothelial Cell-Derived Secretome

Published on: 9th January, 2017

OCLC Number/Unique Identifier: 7317594407

Growing evidence supports the hypothesis that endothelial cell-derived microparticles (MPs) might contribute to the pathogenesis of cardiovascular (CV) disease. Endothelial cell-derived MPs play a pivotal role in the regulation of the endogenous repair system, thrombosis, coagulation, inflammation, immunity and metabolic memory phenomenon. There is evidence that the MPs are secreted actively accompanied to other regulatory molecules. All these actively synthetizing and secreting factors include proteins, adhesion and intercellular signal molecules, peptides, lipids, free DNAs, microRNAs, and even microparticles (MPs) are defined as cellular secretome. The proteomic profile of secretome is under tightly control of genetic and epigenetic mechanisms, which may altered a secretion of the proteins involved into MPs’ organization. Finally, this may contribute the modification of MP’s after their secretion and throughout transfer to the target cells. As a result, communicative ability of endothelial cell-derived MPs may sufficiently worse. Subsequently, cross talk between some components of secretome might modulate delivering cargos of MPs and their regenerative and proliferative capabilities via intercellular signaling networks. The aim of the review is to discuss the effect of various components of secretome on MP-dependent effects on endothelium.
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Association of Toll-like receptor 2, 4, and 9 gene polymorphism with high altitude induced thrombosis patients in Indian population

Published on: 8th February, 2019

Venous Thromboembolism (VTE) is a multifactorial disease that is influenced by individual genetic background and various environmental factors, high altitude (HA) being the one. HA exposure may cause release of several damage associated molecular patterns (DAMPs), which act as ligand for various immune receptors. Previous studies on western population involving SNPs analysis of TLRs demonstrated that TLRs are involved in development and progression of several cardiovascular diseases. But, no such study has been done in Indian population in context of HA exposure. TLRs, being receptors play a significant role in manifestation and elimination of diseases by recognition of specific ligands and downstream signal transduction therefore; the genetic variation in TLRs could be implicated for imparting varying response of individuals to discrete diseases. Therefore, in accordance with it, in present study changes in protein structures of TLR2 and TLR4 due to presence of SNP were accessed by in-silico tools to observe whether the mutation has effect on protein structure and integrity which further influencing its function. The results showed that SNP harbouring protein has decreased functional pockets, thus may be protective for disease. Taking this lead further to genotypic level, first time association between Toll-like receptor genes polymorphism and risk of high altitude induced venous thrombosis is analyzed in Indian population by PCR RFLP method. Though the result showed initial trend that TLR2 and TLR9 SNP are monomrphic in distribution and for TLR4 there was no significant difference in distribution of SNP between healthy and HA-DVT group, these SNPs have potential to be used as susceptibility markers if studied in large population size. 
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RBD targeted COVID vaccine and full length spike-protein vaccine (mutation and glycosylation role) relationship with procoagulant effect

Published on: 26th April, 2021

OCLC Number/Unique Identifier: 9026719857

Related COVID vaccine production many different strategies was followed by the producers. Observing some rare event of thrombosis after some COVID-19 vaccination, it is interesting to verify if the Target used for the manufacturing can be involved in a different procoagulant activity or not. Some vaccine are suspended in some country or under a deep new verify- investigation by the regulatory agency. (EU or USA). This fact it is relevant. The target SPIKE-PROTEIN FULL LENGTH modified or not or towards the RBD domain can be a relevant factor.
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A fatal portal vein thrombosis: A case report

Published on: 27th July, 2019

OCLC Number/Unique Identifier: 8207291083

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematologic condition which could be revealed by deep venous thrombosis. It could be fatal unless correctly treated. Case report: We report here the case of a 28 year-old male with no medical history who was admitted to the emergency room for severe abdominal pain. Computerized Tomography angiography (CT) scan revealed portal vein thrombosis. Laboratory findings showed pancytopenia with severe regenerative normocytic anemia resulting in PNH. Because of the lack of Eculizumab, treatment was first based on curative anticoagulation until bone marrow transplant, with no success. Conclusion: PNH remains a severe disease with bad prognosis unless treated with Eculizumab.
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Atypical manifestations of pulmonary embolism

Published on: 16th April, 2020

OCLC Number/Unique Identifier: 8582359318

Pulmonary embolism (PE) is an age-related disorder which is potentially fatal, but frequently misdiagnosed. However, the true prevalence of pulmonary embolism is unknown. Inaccurate estimates of PE prevalence might, in part, be attributable to underrecognition of atypical presentations of this disorder. If true prevalence is unknown, the positive predictive values of both typical and atypical symptoms and signs of PE will be unreliable. The negative predictive value of those parameters will, likewise, be unreliable. The aim of this review is to make clinicians more aware of atypical manifestations of PE, thereby increasing the likelihood of correct diagnosis and, hence, ascertainment of the true prevalence of PE. The range of atypical manifestations was explored by a literature search, using MEDLINE from 1946 to February 2019, and EMBASE, from 1947 to February 2019, and Pubmed, from February 2014 to February 2019, using the search terms atypical, uncommon, unusual, pulmonary embolism, lung embolism, pulmonary thromboembolism. This search revealed atypical presenting features such as non pleuritic retrosternal pain, abdominal pain, atypical breathing patterns, pulmonary oedema, Dressler’s syndrome, atypical radiographic manifestations, atypical electrocardiographic features, manifestations associated with oxygen saturation of 95% or more, coexistence of acute myocardial infarction and pulmonary embolism, coexistence of thoracic aortic dissection and pulmonary embolism, neurological manifestations other than stroke, paradoxical embolism, acute venous thrombosis of atypical location, and pulmonary embolism with normal D-dimer levels.
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Clinical characteristics in STEMI-like aortic dissection versus STEMI-like pulmonary embolism

Published on: 31st July, 2020

OCLC Number/Unique Identifier: 8660373629

Dissecting aortic aneurysm with ST segment elevation, and pulmonary embolism with ST segment elevation are two of a number of clinical entities which can simulate ST segment elevation myocardial infarction. Objective: The purpose of this review is to analyse clinical features in anecdotal reports of 138 dissecting aortic aneurysm patients with STEMI-like presentation, and 102 pulmonary embolism patients with STEMI-like presentation in order to generate insights which might help to optimise triage of patients with STEMI-like clinical presentation. Methods: Reports were culled from a literature search covering the period January 2000 to March 2020 using Googlescholar, Pubmed, EMBASE and MEDLINE. Reports were included only if there was a specification of the location of ST segment elevation and an account of the clinical signs and symptoms. Search terms were “ST segment elevation”,”aortic dissection”, “pulmonary embolism”, “myocardial infarction”, and “paradoxical embolism”. Fisher’s exact test was utilised for two-sided comparison of proportions. Proportion was calculated for each group as the number of patients with that parameter relative to the total number of patients assessed for that parameter. Findings: There were 138 patients with aortic dissection, 91 of whom were either fast-tracked to coronary angiography (81 patients) or fast-tracked to thrombolytic treatment (10 patients). There were 47 patients managed with neither of those strategies. There were 102 patients with pulmonary embolism, 71 of whom were fast tracked to coronary angiography, and 31 who did not receive that evaluation. Compared with their dissecting aortic aneurysm counterparts, those dissecting aortic aneurysm patients initially managed by percutaneous coronary intervention or by thrombolysis were significantly (p = 0.0003) more likely to have presented with chest pain, and significantly (p = 0.018) less likely to have presented with breathlessness. The preferential fast-tracking to coronary angiography prevailed in spite of comparable prevalence of back pain in fast tracked and in non-fast tracked subjects. Use of transthoracic echocardiography was also comparable in the two subgroups of dissecting aortic aneurysm patients. Pulmonary embolism patients fast tracked to percutaneous coronary intervention were significantly (p = 0.0008) more likely to have presented with chest pain than their pulmonary embolism counterparts who were not fast-tracked. The prevalence of paradoxical embolism was also significantly (p = 0.0016) higher in fast-tracked patients than in counterparts not fast-tracked. Cardiac arrest was significantly (p = 0.0177) less prevalent in fast-tracked pulmonary embolism patients than in pulmonary embolism patients who were not fast-tracked. Preferential fast-tracking to coronary angiography prevailed in spite of the fact that prevalence of documented deep vein thrombosis was comparable in fast-tracked subjects and in subjects not fast-tracked. The prevalence of use of transthoracic echocardiography was also similar in fast-tracked pulmonary embolism patients vs counterparts not fast tracked. Overall, however, transthoracic echocardiography had been utilised significantly (p = 0.007) less frequently in dissecting aneurysm patients than in pulmonary embolism patients. Conclusion: Given the high prevalence of STEMI-like presentation in aortic dissection there is a need for greater use of point-of-care transthoracic echocardiography to mitigate risk of inappropriate percutaneous coronary intervention(which might delay implementation of aortic repair surgery) and inappropriate thrombolysis(which might precipitate hemorrhagic cardiac tamponade) (75) during triage of patients presenting with ST segment elevation simulating ST segment elevation myocardial infarction (STEMI). Furthermore, during triage of patients with STEMI-like clinical presentation, the combined use of point-of -care echocardiography and evaluation for deep vein thrombosis will facilitate the differentiation between acute myocardial infarction, STEMI-like aortic dissection, and STEMI-like pulmonary embolism. Among STEMI-like patients in whom DAA has been ruled out by point of care TTE, fast tracking to PCI might generate an opportunity to identify and treat paradoxical coronary artery embolism by thrombectomy. Thereby mitigating the mortality risk associated with coronary occlusion. Concurrent awareness of PE as the underlying cause of paradoxical embolism also generates an opportunity to relieve the clot burden in the pulmonary circulation, either by pulmonary embolectomy or by thrombolysis. Above all, frontline clinicians should have a greater awareness of the syndrome of STEMI-like presentation of aortic dissection and STEMI-like pulmonary embolism so as to mitigate the risk of inappropriate thrombolysis and inappropriate percutaneous coronary angiography which seems to prevail even in the presence of red flags such as back pain (for aortic dissection) and deep vein thrombosis(for pulmonary embolism). 
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Bone marrow histology in CALR mutated thrombocythemia and myelofibrosis: Results from two cross sectional studies in 70 newly diagnosed JAK2/MPL wild type thrombocythemia patients

Published on: 21st June, 2019

OCLC Number/Unique Identifier: 8180078896

The clinical phenotypes in 268 JAK2V617F mutated MPN patients in the Seoul study were PV in 101, ET in 95 and MF in 78 and 56 CALR mutated MPN consisted of PV in none, ET in 40 and MF in 16 cases. CALR mutated MPN patients were younger than JAK2V617F mutated MPN patients (mean ages 57.5 and 66 years), had lower values for values for leukocytes (8.6 vs 11.9x109/L) and higher values for platelets (898 vs 643x109/L respectively). Bone marrow histopathology in 268 JAK2V617F mutated MPN patients in the Seoul study was featured by an increased erythropoiesis and megakaryopoiesis (EM) in 13.5%, an increased erythropoiesis, megakaryopoiesis and granulopoiesis (EMG) in 31.3%, a normocellular megakaryocytic (M) proliferation in 29,1%, a megakaryocytic and granulocytic (MG) proliferation with a relative reduction of erythropoiesis in post-ET and Post-PV myelofibrosis in 26.2%. The bone marrow histology in 56 cases of CALR mutated MPN show a predominantly increased megakaryopoiesis (M) in two thirds and an increased megakaryopoiesis and granulopoiesis (MG) with a decreased erythropoiesis in one third. Thirteen consecutive CALR MPN patients in the Belgian & Dutch cross sectional study presented with thrombocythemia associated with a typical PMGM bone marrow histology in 11 and myelofibrosis in 2 cases. All 11 thrombocythemia and 2 myelofibrosis CALR mutated MPN patients did not have constitutional symptoms and did not suffer from microvascular erythromelalgic disturbances, major thrombosis at platelet counts between 400 and 1000x109/L. There was an occurrence of hemorrhages at platelet counts above 1000x109/L in two CALR thrombocythemia cases. Bone marrow histology of CALR mutated thrombocythemia in the Seoul and Belgian/Dutch study showed loose clusters of large megakaryocytes (M) with bulky, cloud-like nuclei with a normal or a minor reduction of erythropoiesis and no increase in reticulin fibers grade 0 or 1 (RF 0 or 1). CALR thrombocythemia patients show various degrees of increased bone marrow cellularity due to dual megakaryocytic and granulocytic (MG) proliferation featured by large megakaryocytes with roundish bulky nuclear forms and cloud-like clumsy nuclei, which are almost never seen in JAK2V617F ET and PV. Assessment of allele burden is an independent and most important factor for all molecular variants MPN disease burden. Overt myelofibrosis with advanced post PV and or ET myelofibrosis at the bone marrow level occurred in one third (30%) of 208 evaluable JAK2 MPN patients and in 8 (14%) of 56 CALR MPN patients in the Seoul study.
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Cortical spreading depolarizations in the context of subarachnoid hemorrhage and the role of ketamine

Published on: 23rd March, 2021

OCLC Number/Unique Identifier: 9026724760

Delayed cerebral ischemia (DCI) is one of the main complications of spontaneous subarachnoid haemorrhage and one of its causes is the cortical spreading depolarizations (CSDs). Cortical spreading depolarizations are waves of neuronal and glial depolarizations in which there is loss of neuronal ionic homeostasis with potassium efflux and sodium and calcium influx. In damaged brain areas and brain areas at risk, such as those adjacent to subarachnoid haemorrhage (SAH), CSDs induce microvascular vasoconstriction and, therefore, hypoperfusion and spread of ischemia. Several studies have been devoted to minimize secondary injuries that occur hours to days after an acute insult. Ketamine, a drug until recently contraindicated in the neurosurgical population for potentially causing intracranial hypertension, has re-emerged as a potential neuroprotective agent due to its pharmacodynamic effects at the cellular level. These effects include anti-inflammatory mechanisms, and those of microthrombosis and cell apoptosis controls, and of modulation of brain excitotoxicity and CSDs. A literature review was performed at PubMed covering the period from 2002 to 2019. Retrospective studies confirmed the effects of ketamine on the control of CSDs and, consequently, of DCI in patients with SAH, but did not show improvement in clinical outcome. The influence of ketamine on the occurrence/development of DCI needs to be further confirmed in prospective randomized studies
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