Secondary Polycythemia and Non-Islet Cell Tumor-induced Hypoglycemia in Advanced Hepatocellular Carcinoma: A Case Report.

Continuously holding its position as the sixth most common cause of cancer and the third leading cause of cancer death, globally, Hepatocellular Carcinoma (HCC) remains as a healthcare priority. Production of various substances may result into systemic or metabolic complications, often known as paraneoplastic phenomena of HCC. A 56-year-old male with history of untreated chronic hepatitis B arrived with generalized weakness and intermittent headache in the last two days prior to admission. Laboratory findings demonstrated elevated hemoglobin (20.5 g/dl), alpha-fetoprotein (29,845 ng/dl), and d-Dimer (2,120 ng/ml) levels. Hypoglycemia (44 mg/dl) was documented with normal basal insulin level, confirming non-islet cell tumor hypoglycemia. Abdominal multiphasic CT-scan demonstrated a large solid lesion involving the whole right liver lobe, hyper-enhanced at arterial phase and wash-out pattern at venous and delayed phases, with portal vein thrombosis; thus, confirming HCC BCLC C. Further examinations revealed hypercellularity from bone marrow biopsy with the absence of JAK2 mutation. He underwent serial phlebotomy and received 80 mg acetylsalicylic acid orally, as well as cytoreductive agent to reduce the risk of thrombosis. Despite applications of different interventions, control of hypoglycemia could not be achieved without parenteral administration of high dextrose load. He was planned to receive oral multikinase inhibitor, however, he passed away due to severe hospital-acquired pneumonia. Paraneoplastic phenomena are common in HCC. Increased risk of blood hyper-viscosity and thrombosis attributed to polycythemia, as well as medical emergency resulting from hypoglycemia showed that both conditions should not be overlooked since they may worsen the patient's prognosis.

Significant thrombus in saccular aneurysm in a patient with polycythemia: a case report.

BACKGROUND: Morphologically, the risk of aortic aneurysm rupture is mainly evaluated based on its type (e.g., fusiform or saccular) and diameter. Based on the finite element analysis, peak wall stress has been identified as a more sensitive and specific predictor of rupture in recent years. Moreover, in finite analysis, the neck of aneurysm is the highest peak wall stress and is associated with the rupture point. CASE PRESENTATION: A saccular aortic aneurysm (84 mm) was incidentally detected during preoperative examination for chronic empyema in a 74-year-old male patient with a history of polycythemia. Aortic arch graft replacement using an open stent was performed. CONCLUSIONS: Morphologically, this case was associated with a very high risk of rupture; nevertheless, it did not rupture. In this case, a mural thrombus (likely formed due to polycythemia) covered the neck of aneurysm that is experiencing the highest peak wall stress and is associated with the rupture point. The mural thrombus decreased peak wall stress and could reduce the risk of rupture even for huge saccular aneurysms. Furthermore, the mural thrombus was fully occupied in aneurysms, such as during coil embolization. Thus, polycythemia could decrease the risk of rupture of huge saccular aneurysms.

Myomatous erythrocytosis syndrome: a uterine fibroid associated with polycythaemia.

Myomatous erythrocytosis syndrome (MES) is a rare form of secondary erythrocytosis seen with myomas. Here, we present a case of a postmenopausal, nulliparous woman in her 50s incidentally found to have asymptomatic erythrocytosis on routine laboratory work. She was found to have an 18.5 cm myoma and after surgical resection, the patient's haematological values returned to normal ranges after a few weeks. This established the diagnosis as MES. The aetiology of MES continues to remain unknown but is most likely caused by an autonomous production of erythropoietin from the myomatous tissue. This case highlights obtaining a detailed history and physical examination to differentiate between the different causes of erythrocytosis, considering MES as a rare cause of secondary erythrocytosis and to prevent unnecessary procedures such as phlebotomy as surgery is the mainstay of treatment.

Suspected renal interstitial cell tumor causing polycythemia in two dogs.

Here we report a case series of two dogs diagnosed as renal interstitial cell tumor (RICT) accompanied by elevated serum erythropoietin level and marked polycythemia. RICT is a rare tumor in dogs, originating from renal interstitial cells. While several renal tumors such as renal lymphoma, adenocarcinoma, carcinoma, sarcoma, fibrosarcoma and nephroblastoma may cause polycythemia, polycythemia caused by RICT has never been reported in dogs. The tumors in both dogs were solitary and lied within cortex or cortico-medullary junction. Histopathology revealed spindle-shaped cells suggesting mesenchymal origin, with no mitotic figures suggesting that the tumors in both dogs were benign. Following surgical removal of the affected kidney, serum erythropoietin level and polycythemia normalized in both dogs.

Falsely prolonged prothrombin time test in a patient with erythrocytosis: a case report.

The prothrombin time (PT) test is commonly used to monitor deficiencies in coagulation factors. A prolonged PT may indicate a deficiency of factors II, V, VII, X, and fibrinogen, or the presence of an inhibitor. However, further tests are required to differentiate between a true factor deficiency and the presence of an inhibitor. It is important to note that falsely prolonged PT can lead to misdiagnosis and inappropriate clinical intervention that can have life-threatening consequences. A 19-year-old woman with elevated hematocrit levels and prolonged PT was diagnosed with secondary erythrocytosis due to cyanotic congenital heart disease with ventricular septal defect (VSD). However, further investigation revealed that the prolonged PT result was false. Excess citrate in the blood sample, caused by polycythemia, led to this misleading outcome, resulting in unnecessary and potentially harmful treatment. This incident emphasizes the importance of laboratory personnel and clinicians being aware of the test's limitations. Not only should specialists in thrombosis and hemostasis possess this knowledge, but it is also pertinent for general laboratory staff, as well as laboratory directors and specialists. The significance of accurate laboratory testing for the proper diagnosis and treatment of patients is highlighted in this case.

Polycythemia Secondary to Renal Hemangioblastoma: A Case Report and Literature Review.

Secondary polycythemia is a paraneoplastic syndrome observed in tumors with excessive erythropoietin (EPO) production. Renal cell carcinoma (RCC) and cerebellar hemangioblastoma are the 2 most well-known tumors to induce secondary polycythemia. Hemangioblastomas occurring in the kidney are rare. In this work we present a case of renal hemangioblastoma that caused erythrocytosis in a 19-year-old man. We demonstrated intratumoural EPO production by immunohistochemistry, and conducted whole-exome sequencing to evaluate possible genetic alterations that reported to induce tumor-related polycythemia. In spite of an indolent clinical behavior, renal hemangioblastoma is difficult to differentiate from RCC not only clinically, but also histopathologically. Given that RCC is the most well-known renal tumor to induce erythrocytosis, the uncommon manifestation of polycythemia in renal hemangioblastoma, as shown in our case, can cause further diagnostic challenges. Renal hemangioblastoma should be listed in the differential diagnoses of renal tumors presenting with erythrocytosis, apart from the most common RCC.

Masked anemia and hematocrit elevation under sodium glucose transporter inhibitors: findings from a large real-world study.

AIMS: Sodium glucose transporter inhibitors (SGLT2i) therapy is associated with an increase in hematocrit as a class effect. There is a lack of information regarding the clinical magnitude and significance of hematocrit elevation, especially cardiovascular outcomes in patients with polycythemia and possible masking of lower hemoglobin levels as a sign of potential severe disease. METHODS: A retrospective study utilizing large community healthcare provider electronic database. Hematocrit levels and variables with potential effect on hematocrit change were compared before and during SGLT2i treatment in adults with type 2 diabetes mellitus. RESULTS: Study population included 9646 patients treated with Dapagliflozin or Empagliflozin between 01.2015 and 06.2019. Hematocrit levels were significantly higher after treatment initiation (2.1%), with higher median elevation among male vs female (2.3% vs. 1.8%). Anemia prevalence was significantly lower under treatment (20% vs. 31.6%). In multivariable model, gender, smoking status, SGLT2i type, pretreatment hematocrit, diabetes duration, body mass index and estimated glomerular filtration rate change significantly effected hematocrit change. CONCLUSIONS: In the current study SGLT2i treatment was associated with significant hematocrit elevation, polycythemia and lower anemia prevalence. Further studies are needed to determine the clinical significance and approach to patients with pretreatment or on treatment polycythemia and the approach to patients with lower-normal hemoglobin levels under SGLT2i treatment.

Polycythemia as an Underlying Cause of Digital Gangrene: A Rare and Unusual Case Presentation.

Digital gangrene is frequently encountered in patients who have diabetes with peripheral vascular compromise, with or without superimposed infection. Preoperative laboratory values and radiographic images are important to determine a proper course of action. Equally important is a thorough history taking to confirm or rule out systemic entities and preexisting conditions that can aggravate or predispose one to the development of digital gangrene. A patient with diabetes presented with a rare and unusual case of digital gangrene, as he clinically had strong pedal pulses. Preoperative workup revealed a suspicion of polycythemia, which was subsequently confirmed. The patient underwent several days of phlebotomy until his hemoglobin and hematocrit levels were brought down to optimized levels before a digital amputation was performed. He went on to heal uneventfully, and he is currently being closely followed by oncology/hematology colleagues with periodic phlebotomy.

ST-Segment Elevation Myocardial Infarction and Bleeding Complications in JAK2-Negative Polycythemia.

Thrombotic and bleeding complications are major causes of morbidity and mortality in patients with polycythemia vera, who predominantly present with an alteration in the JAK2 gene. Because of their hypercoagulable state and risk of hemorrhage, patients with polycythemia vera who present with an acute myocardial infarction pose a challenge to physicians. This case report describes the presentation and treatment of a Hispanic patient with JAK2 V617F-negative primary polycythemia who developed cardiac arrest and ST-segment elevation myocardial infarction owing to complete occlusion of the left anterior descending artery as well as bleeding complications and postmyocardial pericarditis.

Prevalence of, association with, severity of, and prognostic role of serum hemoglobin level in acutely decompensated heart failure patients.

BACKGROUND: The role of hemoglobin (Hb) level in the short-term prognosis of patients with acute decompensated heart failure (ADHF) remains a matter of debate. We aimed to declare the prevalence of, association with, severity of, and prognostic role of SHL with ADHF. METHODS: Using the data from the Persian Registry Of Cardiovascular Disease/ Heart Failure (PROVE-HF) study, we assessed the association between anemia and polycythemia (Hb < 13 g/dLit, > 16.5 g/dLit in males and < 12 g/dLit, and > 16 g/dLit in females, respectively) and short-term mortality using Cox proportional hazard modeling, with adjustment of clinically relevant variables. RESULTS: Of 3652 ADHF patients, anemia was seen in 1673 patients (48.40%). The prevalence of mild, moderate, and severe anemia was 42.33% (n = 1546), 3.23% (n = 118), and 0.24% (n = 9), respectively. Also, 422 patients (11.55%) had polycythemia. Compared to non-anemic patients, anemic patients were mainly male, older, and were more likely to have diabetes mellitus (DM), renal dysfunction, hypertension (HTN), and thyroid disease. Significant predictors of short-term mortality were lower systolic and diastolic blood pressure, lower Hb level, and higher blood urea nitrogen (BUN). Anemic patients had higher all-cause mortality [adjusted hazard ratio (aHR) 1.213, 95% confidence interval [CI] 1.054-1.396]. Moderate anemia increased mortality by approximately 80% in males (aHR 1.793, 95% CI 1.308-2.458) and females (aHR 1.790, 95% CI 1.312-2.442), respectively. Polycythemia had no association with short-term mortality in both genders (P-value > 0.05). CONCLUSIONS: This study revealed that anemia is an adverse prognostic factor for short-term mortality in ADHF patients, with higher mortality in moderately anemic patients.

Concomitant Cerebral Venous Thrombosis and Intracranial Hemorrhages in Presentation of a Patient with Secondary Polycythemia: A Case Report.

BACKGROUND Cerebral ischemia and hemorrhages were reported to be the main complications of polycythemia vera (PV). The relationship between PV and increased risk of the cerebrovascular events has been established. Some patients with secondary polycythemia have thromboembolic events comparable to those of PV. However, secondary polycythemia that leads to cerebrovascular events is uncommon. CASE REPORT A 35-year-old man without any prior medical history presented with mild clinical acute ischemic stroke and polycythemia. The patient then showed worsening neurological deficits that were later attributed to the concurrent cerebral venous thrombosis, which led to malignant cerebral infarction with hemorrhagic transformation, and subarachnoid hemorrhage. His polycythemia appeared to be secondary to bacterial infection. The treatments for the secondary polycythemia were first phlebotomy and intravenous hydration, followed by intravenous broad-spectrum antibiotics. PV was excluded because the JAK2 V617F mutation was absent, the patient's peripheral blood smear suggested secondary polycythemia due to bacterial infection, and there were improvements in hemoglobin, erythrocyte count, and hematocrit after intravenous antibiotics. At the 1-month follow-up, he was moderately dependent, and hemoglobin, erythrocyte count, and hematocrit were within normal limits, without receiving any further phlebotomy or cytoreductive agents. CONCLUSIONS This case highlights the plausible causation of secondary polycythemia that could lead to concomitant cerebral thrombosis and hemorrhagic events. The diagnosis of cerebral venous thrombosis should be considered in a patient who presents with headache, focal neurological deficits, polycythemia, and normal head computed tomography scan.

Tyrosine phosphorylation of band 3 impairs the storage quality of suspended red blood cells in the Tibetan high-altitude polycythemia population.

Due to environmental hypoxia on the Tibetan Plateau, local residents often exhibit a compensative increase in hemoglobin concentration to maintain the body's oxygen supply. However, increases in hemoglobin and hematocrit (Hct) pose a serious challenge to the quality of stored suspended red blood cells (SRBCs) prepared from the blood of high-hemoglobin populations, especially populations at high altitude with polycythemia in Tibet. To explore the difference in storage quality of SRBCs prepared from plateau residents with a high hemoglobin concentration, blood donors were recruited from Tibet (> 3600 m) and Chengdu (≈ 500 m) and divided into a high-altitude control (HAC) group, high-altitude polycythemia (HAPC) group and lowland control (LLC) group according to their hemoglobin concentration and altitude of residence. The extracellular acidification rate (ECAR), pyruvate kinase (PK) activity and band 3 tyrosine phosphorylation were analyzed on the day of blood collection. Then, whole-blood samples were processed into SRBCs, and storage quality parameters were analyzed aseptically on days 1, 14, 21 and 35 of storage. Overall, we found that tyrosine 21 phosphorylation activated glycolysis by releasing glycolytic enzymes from the cytosolic domain of band 3, thus increasing glucose consumption and lactate accumulation during storage, in the HAPC group. In addition, band 3 tyrosine phosphorylation impaired erythrocyte deformability, accompanied by the highest hemolysis rate in the HAPC group, during storage. We believe that these results will stimulate new ideas to further optimize current additive solutions for the high-hemoglobin population in Tibet and reveal new therapeutic targets for the treatment of HAPC populations.

Polycythemia as an Uncommon Finding in 2 Children, One With Systemic Capillary Leak Syndrome and the Other With Protein-losing Enteropathy Caused by CD55 Deficiency.

We report 2 children with distinct causes of polycythemia, 1 from systemic capillary leak syndrome (SCLS) and the other from protein-losing enteropathy (PLE) caused by CD55 deficiency. There is only a single case series about polycythemia in children with SCLS, but none on polycythemia in children with PLE. We present a 10-year-old girl with hypoalbuminemia, polycythemia, and edema who died as a result of an SCLS attack and a 1-year-old girl with PLE who was successfully treated with eculizumab. Our experience suggests that hematologists should be alert for SCLS and PLE in children with relative polycythemia.

Changes in expression levels of erythrocyte and immune-related genes are associated with high altitude polycythemia.

BACKGROUND: As a chronic mountain sickness(CMS) with the highest incidence and the greatest harm, the pathogenesis of high altitude polycythemia (HAPC) is still not fully understood. METHODS: 37 HAPC patients and 42 healthy subjects were selected from plateau, and peripheral venous blood samples were collected for transcriptome sequencing on Illumina NovaSeq platform. The sequenced data were analyzed by bioinformatics and phenotypic association analysis. RESULTS: The results showed significant differences in multiple clinical indicators including RBC and HGB et al. existed between HAPC and control. Based on the RNA-seq data, 550 genes with significant differential expression were identified in HAPC patients. GO and KEGG pathway enrichment analysis showed that the up-regulated genes were mainly enriched in processes such as erythrocyte differentiation and development and homeostasis of number of cells, while the down-regulated genes were mainly enriched in categories such as immunoglobulin production, classical pathway of complement activation and other biological processes. The coupling analysis of differential expression genes(DEGs) and pathological phenotypes revealed that 91 DEGs were in close correlation with in the phenotype of red blood cell volume distribution (width-CV and width-SD), and they were all up-regulated in HAPC and involved in the process of erythrocyte metabolism. Combined with the functional annotation of DEGs and literature survey, we found that the expression of several potential genes might be responsible for pathogenesis of HAPC. Besides, cell type deconvolution analysis result suggested that the changes in the number of some immune cell types was significantly lower in HAPC patients than control, implying the autoimmune level of HAPC patients was affected to a certain extent. CONCLUSION: This study provides an important data source for understanding the pathogenesis and screening pathogenic genes of HAPC. We found for the first time that there was a significant correlation between HAPC and the pathological phenotype of width-CV and width-SD, wherein the enriched genes were all up-regulated expressed and involved in the process of erythrocyte metabolism. Although the role of these genes needs to be further studied, the candidate genes can provide a starting point for functionally pinning down the underlying mechanism of HAPC.

Secondary polycythaemia from chronic hypoxia is a risk for cerebral thrombosis: a case report.

BACKGROUND: Secondary polycythemia is considered the usual complication of chronic hypoxia. It can theoretically increase the oxygen-carrying capacity, but this adaptive trait has a deleterious effect because the blood viscosity increases, which can induce significant morbidity and mortality, such as stroke and myocardial infarction. CASE PRESENTATION: A 55-year-old man with a history of a congenitally small main pulmonary artery presented to the emergency department with sustained unsteady walking, dizziness and vertigo. Evaluation revealed elevated hemoglobin and superior posterior circulation cerebral artery thrombosis. The patient was treated with high flux inhalation of oxygen and anti-platelet aggregation. CONCLUSIONS: The involvement of cerebral vessels has rarely been reported in chronic hypoxia cases. The present case is the first case of superior posterior circulation cerebral artery thrombosis due to chronic hypoxia in a patient with a congenitally small main pulmonary artery. This case demonstrates the importance of recognizing some chronic diseases that can lead to hypoxia and secondary polycythemia thereby leading to hypercoagulable state and subsequent thrombosis.

Testosterone and type 2 diabetes prevention: translational lessons from the T4DM study.

Testosterone acting via the androgen receptor, and via aromatisation to oestradiol, an activator of the oestrogen receptor, plays key roles in adipose tissue, bone and skeletal muscle biology. This is reflected in epidemiological studies associating obesity and disordered glucose metabolism with lower serum testosterone concentrations and an increased risk of type 2 diabetes (T2D) in men. Testosterone also modulates erythrocytosis and vascular endothelial and smooth muscle cell function, with potential impacts on haematocrit and the cardiovascular system. The Testosterone for the Prevention of Type 2 Diabetes (T4DM) study enrolled men aged 50 years and over with a waist circumference of 95 cm or over, impaired glucose tolerance or newly diagnosed T2D, and a serum testosterone concentration (as measured by chemiluminescence immunoassay) <14.0 nmol/L. The study reported that a 2-year treatment with testosterone undecanoate 1000 mg, administered 3-monthly intramuscularly, on the background of a lifestyle program, reduced the likelihood of T2D diagnosis by 40% compared to placebo. This effect was accompanied by a decrease in fasting serum glucose and associated with favourable changes in body composition, hand grip strength, bone mineral density and skeletal microarchitecture but not in HbA1c, a red blood cell-dependent measure of glycaemic control. There was no signal for cardiovascular adverse events. With the objective of informing translational science and future directions, this article discusses mechanistic studies underpinning the rationale for T4DM and translational implications of the key outcomes relating to glycaemia, and body composition, together with effects on erythrocytosis, cardiovascular risk and slow recovery of the hypothalamo-pituitary-testicular axis.

Association between polycythemia and risk of ischemic stroke in males based on the national health insurance service-health screening cohort.

BACKGROUND: Polycythemia, a state in which the hematocrit or hemoglobin (Hb) concentration in the peripheral blood increases, is associated with several thrombosis-related diseases, of which cerebral infarction is relatively common. This study aimed to investigate the association between ischemic stroke and polycythemia, as a potential risk factor. RESEARCH DESIGN AND METHODS: This study included men who had undergone national health checkups between 2002 and 2003; the data were extracted from the Korean National Health Insurance Service-Health Screening database. The primary outcome was the risk ischemic stroke; adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for ischemic stroke were calculated using Cox proportional hazards regression models. RESULTS: In total, 207,737 male participants aged 40-79 years were included in this study. At the baseline, 13972 (6.7%) participants met the polycythemia criteria (Hb >16.5 g/dL). During the study period, 897 and 12,440 cases of ischemic stroke occurred in the polycythemia and normocythemia (13.0 g/dL ≤ Hb ≤16.5 g/dL) groups, respectively. Compared with the normocythemia group, the polycythemia group showed an adjusted HR (95% CI) for ischemic stroke of 1.12 (1.04-1.20). CONCLUSIONS: The risk of ischemic stroke was higher in participants with polycythemia than in those with normocythemia.