Successive development of ischemic stroke and hemorrhagic stroke in a patient with essential thrombocythemia: a case report

Patients with essential thrombocythemia (ET) can experience hemorrhagic or ischemic vascular events. The prevention of these complications is challenging, and the overall risk of vascular events caused by ET is often overlooked. A 34-year-old man was admitted for a 10-day history of weakness and numbness in his right limbs. He had been diagnosed with ET in 2008 but had stopped receiving treatment half a year before admission. Physical examination showed a superficial sense of disturbance in the right limbs and decreased muscle strength in the right upper and lower limbs (4/5). His platelet count (459 × 10⁹/L) was elevated. Magnetic resonance imaging showed acute watershed infarction, and he was treated successfully. However, he was readmitted for headache and left limb weakness 14 months later. A head computed tomography scan revealed spontaneous subdural hemorrhage. He underwent subdural hematoma removal and decompressive craniectomy. Surgery and pathological investigation revealed no venous sinus thrombosis or vascular malformation. His condition improved, and he exhibited a stable condition 1 year after discharge. Successive development of ischemic stroke and spontaneous subdural hemorrhage is rare in a patient with ET. This case suggests that ET is not only a risk factor for stroke but can also cause highly heterogeneous strokes.     

Gastroesophageal varices in a patient presenting with essential thrombocythemia: A case report

BACKGROUNDGastroesophageal varices are a rare complication of essential thrombocythemia (ET). ET is a chronic myeloproliferative neoplasm (MPN) characterized by an increased number of blood platelets.CASE SUMMARYA 46-year-old woman, who denied a history of liver disease, was admitted to our hospital on presentation of hematemesis. Laboratory examination revealed a hemoglobin level of 83 g/L, and a platelet count of 397 × 10⁹/L. The appearance of gastric and esophageal varices with red colored signs as displayed by an urgent endoscopy was followed by endoscopic variceal ligation and endoscopic tissue adhesive. Abdominal computed tomography revealed cirrhosis, marked splenomegaly, portal vein thrombosis and portal hypertension. In addition, bone marrow biopsy and evidence of mutated Janus kinase 2, substantiated the onset of ET. The patient was asymptomatic with regular routine blood testing during the 6-mo follow-up period. Therefore, in this case, gastroesophageal varices were induced by ET.CONCLUSIONMPN should be given considerable attention when performing differential diagnoses in patients with gastroesophageal varices. An integrated approach such as laboratory tests, radiological examination, and pathological biopsy, should be included to allow optimal decisions and management.     

Elevated telomerase activity in essential thrombocythemia with extreme thrombocytosis

Introduction

We performed a comparative analysis of telomerase activity (TA) in patients with myeloproliferative neoplasm (MPN) and myelodysplastic syndrome (MDS). The relationships between TA and known prognostic factors were also analyzed.

Materials and methods

A telomeric repeat amplification protocol was performed with bone marrow hematopoietic cells from 96 normal controls, 44 MPNs, and 40 MDSs.

Result

TA (measured as molecules/reaction) showed no correlation with age in the control group (R² = 0.0057, p = 0.464). MPN showed elevated TA compared with controls (15,537.57 vs. 7775.44, p = 0.020). Patients with essential thrombocythemia showed markedly elevated TA (22,688.56, p = 0.030), particularly in cases with extreme thrombocytosis versus those without extreme thrombocytosis (34,522.19 vs. 9375.71, p = 0.041). MDS patients showed a TA value of 7578.50.

Conclusion

There was no association between age and TA in bone marrow hematopoietic cells. TA was elevated in MPN but borderline in MDS, probably because of differences in the nature of the diseases. Elevated TA in patients with essential thrombocythemia, especially those with extreme thrombocytosis, suggests that an anti-telomerase strategy could be beneficial in the prevention of thrombotic complications.     

Soluble CD40 ligand, high sensitive C-reactive protein and fetuin-A levels in patients with essential thrombocythemia

Background

CD40 ligand (CD40L) is expressed on the surface of activated platelets and activated T lymphocytes. Circulating soluble CD40 ligand (sCD40L) is formed from these molecules proteolytically. Fetuin-A is a potent antiinflammatory cytokine.

Aim of the study

In this study, we aim to investigate sCD40L levels to determine whether there is platelet activation and to measure high sensitive C-reactive protein (hs-CRP) levels to demonstrate if this leads to an inflammatory process and also to study fetuin-A levels to see if there is any concomitant antiinflammatory event in patients with essential thrombocythemia (ET).

Methods

We compared 30 patients with essential thrombocythemia with 30 control subjects and in these patients we measured levels of sCD40L, hs-CRP and fetuin-A.

Results

sCD40L levels were significantly higher in the ET group compared to the control group (30.6 ± 14.4 vs. 18.5 ± 8.9, p = 0.001). Although fetuin-A levels showed a slight trend to be increased in ET patients, the difference did not reach significance (4.5 ± 4.2 vs. 3.2 ± 2.1, p = 0.158). There were no statistically significant differences in hs-CRP levels (24.6 ± 4.9 vs. 25.0 ± 5.2, p = 0.750).

Conclusion

sCD40L was significantly higher in patients with an ET without any association with an inflammatory process and we believe this may be a marker of platelet regeneration.     

髋关节置换术后发生缺血性脑卒中的危险因素分析

目的探讨髋关节置换术后发生缺血性脑卒中的危险因素。方法采取回顾性病例对照研究方法,比较行髋关节置换术后并发缺血性脑卒中患者18例与同期随机142例无缺血性脑卒中事件患者(对照组)的临床资料。结果髋关节置换术后缺血性脑卒中的发病率为1 .8%。年龄、高血压、脑卒中病史、术中收缩压及舒张压的下降与对照组相比,有显著性差异(P<0 .05);而性别、心脏病史、糖尿病、高脂血症及术中的出血量与对照组相比,无显著性差异(P>0 .05)。结论年龄、高血压、术中血压的变化及术前脑卒中病史是髋关节置换术后缺血性脑卒中事件发生的重要危险因素。     

Antithrombotic Management in Ischemic Stroke with Essential Thrombocythemia: Current Evidence and Dilemmas

Thrombotic diseases like ischemic stroke are common complications of essential thrombocythemia (ET) due to abnormal megakaryopoiesis and platelet dysfunction. Ischemic stroke in ET can occur as a result of both cerebral arterial and venous thrombosis. Management of ET is aimed at preventing vascular complications including thrombosis. Acute management of ischemic stroke in ET is the same as that in the general population without myeloproliferative disorders. However, an ET patient with ischemic stroke is at high risk for rethrombosis and is therefore additionally managed with cytoreductive therapy and antithrombotic agents. Given abnormal platelet production in ET, there is suboptimal suppression of platelets with the standard recommended dose of aspirin for cardiovascular (CV) prevention. Hence, for optimal CV protection in ET, low-dose aspirin is recommended twice daily in an arterial thrombotic disease like atherothrombotic ischemic stroke in presence of the following risk factors: age >60 years, Janus kinase2 V617F gene mutation, and presence of CV risk factors. In the presence of the same risk factors, concurrent antiplatelet and anticoagulant therapy is suggested for venous thrombosis. However, increased risk of bleeding with dual antithrombotic agents poses a significant challenge in their use in cerebral venous thromboembolism or atrial fibrillation in presence of the above-mentioned risk factors. We discuss these dilemmas regarding antithrombotic management in ischemic stroke in ET in this case-based review of literature in the light of current evidence.     

Sufficient collateral blood supply from accessory middle cerebral artery in a patient with acute ischemic stroke

We reported a case of acute embolic occlusion of the middle cerebral artery with a patent accessory middle cerebral artery. Because of the presence of sufficient collateral blood supply from the accessory middle cerebral artery, the patient only underwent transient ischemic attack and did not need endovascular treatment. There was mild infarction in the basal ganglia and temporal lobe, NIHSS score of the patient at discharge seven days after stroke onset was 0, and modified Rankin scale score at 90 days was 0.     

Management of refractory essential thrombocythemia with anagrelide in a patient undergoing hemodialysis

Background: Management of essential thrombocythemia (ET) in high-risk patients is difficult because high platelet numbers can lead to vascular occlusive events and bleeding. Therapeutic interventions in ET are limited to hydroxyurea and anagrelide; however, in Europe, anagrelide is contraindicated in patients with chronic renal disease.Objective: The aim of this case report was to describe the use of anagrelide in a patient with ET and renal impairment.Case summary: A 73-year-old white female patient with severe renal impairment who was diagnosed with ET was receiving treatment with hydroxyurea 1 g/d since 2001. At this time she was also receiving aspirin 80 mg/d; calcium carbonate 1 g/d; pravastatin 40 mg/d; folic acid 5 mg/d; furosemide 40 mg/d; cetirizine 10 mg/d; erythropoietin 10,000 U once monthly; a vitamin B complex, 1 tablet a day; and iron tablets 105 mg/d. In February 2007, because her white blood cell count fell to 2.1 × 10⁹/L, myelodepression was suspected and hydroxyurea was stopped. This led to enhanced platelet levels and the introduction of anagrelide at an initial dose of 0.5 mg/d that was steadily increased to 2.5 mg/d. All other treatments were continued with some dosage adjustments. Sodium bicarbonate 1 g/d and vitamin D were added to her regimen. After 18 months of anagrelide treatment, a sudden but moderate fall of platelets to 142 × 10³/μL with severe anemia (hemoglobin, 6.5 g/dL) was observed. The patient had anemia since 2004, but the condition worsened due to bleeding related to an ulcer at the cecal valve. The patient refused blood and platelet transfusions and surgical intervention for religious reasons. Because of hemodynamic instability, she was admitted to the intensive care unit in December 2008 and died 24 hours after admission.Conclusion: We report a case of ET and chronic renal failure treated with anagrelide and low-dose aspirin in a patient who did not receive transfusion and surgical intervention due to religious reasons, and had a fatal outcome.     

Clinical factors in patients with ischemic versus hemorrhagic stroke in East China

BACKGROUND:

Stroke is one of the leading causes of mortality and morbidity of vascular diseases, and its incidence maintains at a high level around the world. In China, stroke has been a major public health problem. Because the pathogenesis of ischemic stroke is different from that of hemorrhagic stroke, their clinical factors would not be the same. Therefore to investigate the different effects of various effect factors on ischemic versus hemorrhagic stroke and then to enhance the prevention are crucial to decrease the incidence.

METHODS:

A total of 692 patients, consisting of 540 ischemic stroke patients and 152 hemorrhagic stroke patients from East China, were included in this study. The related factors of stroke subtypes were collected and analyzed.

RESULTS:

The factors significantly associated with ischemic stroke as opposed to hemorrhagic stroke were family history of stroke, obesity, atherosclerotic plaque of the common carotid artery, atrial fibrillation, hyperfibrinogenemia, transient ischemic attack (TIA), atherosclerotic plaque of the internal carotid artery, coronary heart, lower high-density lipoproteins (lower HDL), increasing age, diabetes mellitus, and gender (male) (P<0.05). Leukocytosis, hypertension and family history of hypertension were the significant factors associated with hemorrhagic stroke versus ischemic stroke. Smoking, drinking, kidney diseases and lower HDL-C were the significant factors contributing to ischemic stroke in man. Obesity, family history of hypertension, family history of stroke, hypercholesteremia and myocardial ischemia were the significant factors for females with ischemic stroke.

CONCLUSIONS:

The most prominent factors for overall stroke in East China were hypertension, followed by higher pulse pressure and hypercholesteremia. The factors for ischemic and hemorrhagic stroke are not the same. Different effects of risk factors on stroke are found in male and female patients.KEY WORDS: Ischemic stroke, Hemorrhagic stroke, Risk factors     

Hyperacute ischemic stroke without lesions on diffusion‐weighted imaging in a patient treated with rtPA thrombolysis

We report a comatose patient with severe neurological deficits who was without spontaneous language or movement. He had a good response to recombinant tissue plasminogen activator (rtPA) thrombolysis even though there were no detectable lesions on diffusion‐weighted imaging (DWI). DWI is very sensitive for diagnosing hyperacute ischemic stroke, and rtPA thrombolysis is the best treatment. However, rtPA thrombolysis in ischemic stroke patients without lesions on DWI has rarely been reported.     

Listeria rhombencephalitis mimicking stroke in a patient with giant cell arteritis

Listeria monocytogenes sometimes causes central nervous system infections. However, rhombencephalitis is a rare form of L. monocytogenes infection. Its clinical symptoms and magnetic resonance imaging (MRI) findings are often similar to those of vertebrobasilar stroke. We present the case of a 79-year-old woman with Listeria rhombencephalitis presenting with rhinorrhea and productive cough. She had giant cell arteritis (GCA) treated with prednisolone and methotrexate. She was admitted for loss of appetite, rhinorrhea, and productive cough. These symptoms were alleviated without specific treatment; however, she suddenly developed multiple cranial nerve palsies, and MRI showed hyperintense signals on diffusion-weighted imaging and hypointense signals on apparent diffusion coefficient in the brainstem. Ischemic stroke due to exacerbation of GCA was suspected, and treatment with intravenous methylprednisolone was initiated; however, seizures occurred, and a lumbar puncture was performed. Cerebrospinal fluid and blood cultures revealed L. monocytogenes, and she was diagnosed with Listeria rhombencephalitis. Although antibiotic treatment was continued, the patient died. Thus, when patients with rhinorrhea or productive cough develop sudden cranial nerve palsy, Listeria rhombencephalitis should be considered as a differential diagnosis, and lumbar puncture should be performed.     

Hematological relevance of JAK2 V617F and calreticulin mutations in Tunisian patients with essential thrombocythemia

BackgroundThe genetic investigation of essential thrombocythemia(ET) has highlighted the presence of driver mutations in ET. Janus kinase JAK2V617F and calreticulin(CALR) mutations are the most frequent driver mutations and have significantly improved the molecular diagnosis of ET. The impact of genetic heterogeneity on clinical features has not been fully elucidated.This is the first study which aimed to determine the frequency of JAK2V617F and CALR exon9 mutations in Tunisian ET patients and to establish the correlation between hematological characteristics and mutational status.MethodsThis study included Tunisian patients suspected with ET and was conducted between September 2017 and March 2021. Genomic DNA of patients was isolated from peripheral blood samples. JAK2V617F was detected by AS‐PCR and CALR mutations were detected by PCR/direct sequencing. Clinical and hematological characteristics were also analyzed.ResultsTwo hundred and fifty ET patients were enrolled in this study. JAK2V617F mutation was found in 166/250 (66.4%) of patients, whereas CALR mutations were detected in 27/84 (32.1%) patients without JAK2V617F. Compared with JAK2V617F‐positive patients, those with CALR mutations showed lower hemoglobin level and lower leucocytes count (p = 0.007 and p = 0.004,respectively). CALR type 2 was the most frequent mutation of CALR detected in 55.55% of CALR mutated. Six of seven patients with thrombotic events harbored JAK2V617F mutation.ConclusionThe prevalence of driver mutations JAK2V617F or CALR mutations was 77.2% in Tunisian ET patients. Moreover, patients with JAK2 V617F mutation had a higher risk of thrombosis. The mutational status is necessary to improve the diagnosis and contribute to the therapeutic decisions.     

Vertebrobasilar artery dissection manifesting as Millard-Gubler syndrome in a young ischemic stroke patient: A case report

BACKGROUND Millard-Gubler syndrome(MGS) is caused by a lesion in the brainstem at the level of the facial nerve nucleus, and it is also a rare ventral pontine syndrome.Vertebrobasilar artery dissection(VAD) is an uncommon cause of ischemic stroke. To the best of our knowledge, this is the first case report on the coexistence of MGS and VAD in a young acute ischemic stroke patient.CASE SUMMARY We herein describe an unusual case of young acute ischemic stroke patient,presenting with acute right peripheral facial palsy, right abducens palsy, and contralateral hemihypesthesia, manifesting as MGS. After receiving dual antiplatelet therapy with aspirin and clopidogrel, as well as rosuvastatin, the patient recovered significantly. The high-resolution magnetic resonance imaging(MRI) indicated a diagnosis of VAD.CONCLUSION Our finding further demonstrated that high-resolution MRI is a useful technique to early detect underlying dissection in posterior circulation ischemic stroke.     

缺血性脑血管病颅内动脉狭窄的危险因素

目的研究缺血性脑血管病颅内动脉狭窄的危险因素.方法对503例缺血性脑血管病患者进行经颅多普勒超声检查,化验总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯、血浆肌酐.结果有高血压、糖尿病的缺血性脑血管病患者容易发生颅内动脉狭窄,颅内动脉狭窄更常见于既有高血压又有糖尿病者,三者的相对危险度、卡方值、P值分别为2.138、2.152、2.610,23.344、5.610、13.251,0.000、0.018、0.000.有卒中史者也容易发生颅内动脉狭窄,其卡方值、P值为4.299、0.038.颅内动脉狭窄组高密度脂蛋白胆固醇(1.00±0.17 mmol/L)比非狭窄组(1.20±0.12 mmol/L)低(P＜0.01),低密度脂蛋白胆固醇(3.55±0.67mmol/L)比非狭窄组(3.30±0.66mmol/L)高(P＜0.01).结论缺血性脑血管病颅内血管狭窄的危险因素有高血压、糖尿病、卒中史、低密度脂蛋白胆固醇增高等,保护因素有高密度脂蛋白胆固醇.