Chronic Myeloproliferative Disorders Research Articles

Digital gangrene: can be the first manifestation of essential thrombocythemia? a case report

Introduction and importance: Essential thrombocythemia (ET) is a rare chronic myeloproliferative hematologic disorder, leading to an elevated platelet count. Two-thirds of patients are asymptomatic during their lifetime, while others may experience symptoms like redness, congestion, and erythromelalgia after long symptom-free intervals. Case presentation: The authors present a rare instance of a 55-year-old female who, despite receiving aspirin and losartan treatment, eventually developed digital gangrene. In further work-ups, she had an elevated platelet count and a positive JAK 2 mutation. Her platelet count was reduced throughout treatment with aspirin, hydroxyurea, and heparin, which was followed by the necrotic tip of her index finger being surgically debrided. Clinical discussion: Significant symptoms, such as severe acrocyanosis and even peripheral gangrene, can be treated with a single dose of aspirin. Daily aspirin consumption withstanding, this case developed the severe form of ET. In addition, while thrombocytosis predisposes patients to thrombotic complications in theory, there is little evidence to support a correlation between absolute platelet count and thrombosis. Conclusion: The initial symptom of ET could be such severe and uncommon that may develop arterial acral thrombosis despite previous daily low-dose aspirin consumption.

Clinical-radiological-pathological correlation in pulmonary hypertension with unclear and/or multifactorial mechanisms.

Ever since the second world symposium on pulmonary hypertension (PH) held in Evian, France, in 1998, PH has been classified into five major clinical groups. Group 5 PH includes a variety of distinct conditions with unclear and/or multifactorial underlying pathologies. Management of these patients is challenging as the number of patients within these groups is often small, not all individuals with certain underlying conditions are affected by PH and patients exhibit distinct symptoms due to different underlying diseases. Studies and clinical trials in these groups are largely lacking and mostly restricted to case series and registry reports. Nonetheless, the worldwide burden of group 5 PH is estimated to be significant in terms of the prevalence of some associated diseases. Group 5 PH encompasses six subgroups, including haematological disorders (inherited and acquired chronic haemolytic anaemia and chronic myeloproliferative disorders), systemic disorders (sarcoidosis, pulmonary Langerhans's cell histiocytosis and neurofibromatosis type 1), metabolic disorders (glycogen storage diseases and Gaucher disease), chronic renal failure with or without haemodialysis, pulmonary tumour thrombotic microangiopathy and fibrosing mediastinitis.

Concurrent diagnosis of Sjogren’s syndrome and polycthemia vera: a rare co-existence

Primary Sjogren's Syndrome(pSS) is a chronic autoimmune disease and focal lymphocytic infiltration of the exocrine glands is the key pathological feature (1). Polycythemia vera(PV) is a chronic myeloproliferative disorder characterized by JAK-2 mutations and increased red blood cell mass(2,3). Autoimmune diseases and hematological malignancies can often be observed together. Patients with SS are at a higher risk of developing lymphoproliferative diseases mainly low-grade B-cell lymphomas and predominantly marginal zone lymphoma. Moreover, PV can rarely be presented with paraneoplastic events including small vessel vasculitis (2). However, PV and pSS co-existence had never been reported. We here want to present a case of concurrently diagnosed PV and pSS.

Low Dose Splenic Radiotherapy for Myeloproliferative Neoplasms prior to Allogeneic Hematopoietic Stem Cell Transplant.

Myeloproliferative neoplasms including primary and secondary myelofibrosis (MF) are a rare spectrum of chronic myeloproliferative disorders in which nearly 90% of patients experience splenomegaly. Importantly, splenic radiotherapy (SRT) may be used in combination with allogeneic stem cell transplant (alloSCT) to improve symptoms related to splenomegaly, though there currently is no consensus SRT dose/fractionation protocol reported in the literature for use in combination with alloSCT. We sought to report our institutional experience utilizing low dose SRT prior to alloSCT in the post-Jakafi era. We performed a retrospective review of all patients diagnosed with MF at our institution from 2017-2022 who received reduced intensity alloHCT. Patients who underwent total lymphoid or body irradiation were excluded. Descriptive demographic and clinical characteristics of patients were summarized by means, medians, standard deviations, ranges and proportions as appropriate. We identified 39 patients with MF who underwent reduced intensity conditioning (RIC) consisting of fludarabine/melphalan in preparation for alloHCT (median age 64.5, 12/16 males, median follow up 21 months). 16 patients with Jakafi-resistant splenomegaly completed low dose SRT prior to transplant (median spleen size: 24.5cm) with a median dose of 5Gy delivered in 5 fractions. 3D conformal therapy was used for all patients. All patients completed the planned total radiation course without treatment break or dose limiting acute toxicity. Thrombocytopenia was the most reported toxicity (CTCAE v5.0; 2 patients experienced grade 1, 1 patient experienced grade 2). No patients experienced grade 3 or higher acute cytopenias nor required transfusion during radiotherapy. All patients successfully received alloHCT a median of 7 days (range: 2-11) after the completion of SRT with a 94% (15/16) engraftment rate. Median neutrophil recovery (ANC > 500 × 3 days) time was 18 days (range: 13-31); median length of hospital stay was 23 days (range: 20-129). Overall survival was 75% in the SRT cohort (12/16, 2 with persistent disease, 2 due to other causes). Symptom burden data was available for 14/16 patients; 79% (11/14) of patients reported improvement in symptoms associated with splenomegaly or reduction in splenic size on physical examination. In the largest reported experience of a low dose SRT only cohort to date, we observe low dose SRT is feasible, safe in combination with alloHCT with high engraftment rates, and may reduce symptoms related to splenomegaly thereby improving patient quality of life without compromising transplant related outcomes. A prospective study validating this protocol is currently underway.

Abdominal Aortic Aneurysm with Essential Thrombocythemia: A Case Report Describing Perioperative Management in Open Surgery

We report perioperative management and open surgery to treat a case of infrarenal abdominal aortic aneurysm with essential thrombocythemia (ET), a chronic myeloproliferative disorder associated with arterial or venous thrombosis, idiopathic bleeding, and heparin-resistant diathesis. Following careful preoperative management, including assessment of heparin resistance, open surgery was successfully performed to treat the aortic aneurysm of our patient. This report shows that optimal preparation for surgery is important to safely perform abdominal aortic aneurysm repair and prevent perioperative thrombosis and bleeding in patients with abdominal aortic aneurysm with ET.

Polycythemia Vera Associated with Diffuse Large B-Cell Lymphoma: A Case Report

Diffuse Large B-cell Lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma, accounting for more than 30% of cases, particularly in developing countries. Polycythemia Vera (PV) is a chronic myeloproliferative disorder characterized by an increase in the number of red blood cells, and often leukocytes and peripheral blood platelets. PV is most commonly diagnosed in individuals around the age of 60, and slightly more common in women, the clinical course is long and can lead to thrombotic complications, which may be the first symptom of the disease. In approximately 10% of patients, PV may progress to Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML). The co-occurrence of DLBCL with a JAK2V617F-positive Myeloproliferative Neoplasm (MPN) is rarely documented in the literature. Here we describe a 64-year-old patient diagnosed with both DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) and polycythemia, with a particularly short time between identification of these conditions.

Multiple cardiac surgical procedures in a case of an octogenarian with essential thrombocythemia

BackgroundEssential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by an elevation of platelet counts with a tendency for thrombosis and hemorrhage. The perioperative management of cardiovascular surgery of an ET patient is complicated. There is limited literature on the perioperative management of patients with ET undergoing cardiovascular surgery, particularly those requiring multiple procedures.Case presentationAn 85-year-old woman with a history of essential thrombocythemia (ET), which resulted in an abnormally high platelet count, was diagnosed with aortic valve stenosis, ischemic heart disease and paroxysmal atrial fibrillation. She underwent aortic valve replacement, coronary artery bypass grafting, and pulmonary vein isolation. The postoperative course was uneventful, nor hemorrhage and thrombosis.ConclusionsWe represent a case of perioperative management and successful treatment of three combined cardiac surgery for an octogenarian ET patient who is the oldest case ever reported.

The atherogenic index of plasma complicates the thrombotic tendency of chronic myeloproliferative disorders: A retrospective cohort study

Objectives: Chronic myeloproliferative diseases (CMPD) are neoplastic disorders leading to hypercoagulability and thrombosis. The critical hemostatic abnormalities include alterations in the blood viscosity and a history of recent thrombus. The aim of this study is to assess the interrelationships among the atherogenic index of plasma (AIP) and thromboembolism of CMPD with JAK2 V617F mutation. 
 Methods: Ninety-two patients diagnosed as CMPD with JAK2 V617F mutation and 73 controls were included into the study. The patients were evaluated for the presence of any venous or arterial thromboembolic events. AIP was calculated by using the formula log (Tg/HDL) from serum triglyceride and high-density lipoprotein values.
 Results: The study group consisted of 30 patients (33%) with myelofibrosis (MF), 42 patients (46%) with polycythemia vera (PV) and 20 patients (21%) with essential thrombocythemia (ET). Two study groups were similar in terms of sex, age and other comorbidities (p > 0.05). CMPD group had higher levels of right blood cell count (RBC), red blood cell distribution width (RDW), platelets (PLT), hemotocrit (Hct) and AIP. Univariate and multivariate logistic regression analysis revealed that platelet count, RBC and AIP were independent predictors for thrombosis in both groups. The comparison of ROC curve analysis disclosed that AIP was superior to platelet count and RBC in predicting thrombosis.
 Conclusion: AIP can be used to determinate higher risk of thromboembolism in patients with CMPD. As a reliable and ‘easy-to-assess’ diagnostic tool, AIP could be useful for the determination of thrombotic events in CMPD clinicobiological disease course.

Risk of Unemployment Among Chronic Myeloproliferative Disorders Patients

Overall survival of chronic myeloproliferative disorders (CMPD) such as Policytemia Vera (PV), Essential Thrombocitemia (ET), Myelofibrosis (MF), Chronic Myeloid Leukemia (CML) and Myelodysplastic Syndrome (MDS) is often long term because of their natural history and therapeutic improvement (ie: TKI, RH-EPO, JAK2 inhibitors). On the other hand, quality of life may be often compromised by persistent symptomatologic burden and chronic therapy (TX) that may worsen work ability. Although the highest incidence falls between 60 and 70 years old, prevalence studies show that nearly 50% of such patients (PTS) are less than 70 YO, hence in their working age. To the best of our knowledge no data have been collected to explore the rate of loss of employment among this group of PTS. Aim of this study is to collect data to estimate among CMPD PTS: rate of long term loss of employment, impact of diagnostic work-up, correlation between loss of employment and diagnosis. METHODS From febbruary 01 until april 30, 2022 all outpatients complying with the following criteria were recruited: CML, PV, TE, MDS, MF diagnosis; life expectancy of more than 5 years based on currently used prognostic scores (CML: ELTS, MF: IPSS, MDS: R-IPSS, PV: IWG-PV score, TE: IPSET); age > 18 years old, ≤ 70 years old. Loss of employment was defined as any modality of abandonement of work after disease diagnosis (retirement, dismissal, abandonment). Demographic and basic disease data were collected. A 29 items questionnaire (QST) mainly based on the "Work Ability Index" was prepared for the purpose of this study. After informed consent acquisition, the QST was administered with psyco-oncology support to PTS planned for routine control. PTS missing control for any reason, were contacted by phone and QST was subsequently administered after informed consent reading. RESULTS 104 PTS have been recruited (M/F: 47/57); mean age at diagnosis was 52,1 for M (range 24-69) and 50,2 for F (range 18-69). PTS diagnosis were: 30 CML, 26 MF, 24 ET, 9 PV, 7 Low-Risk MDS, 4 other CMPD, 4 NA. 68/104 PTS were on active specific TX for their disease (66 on oral TX, 2 on parenteral TX). At diagnosis 58/104 PTS (55,8%) were employed 32 M (55,2%) and 26 F (44,8%). 29 had a permanent employment, 12 had a fixed term employment, 8 flexible employment. Only 8/58 (13.8%) suspended their job during work up (sick leave). 28 of 105 pts (26.7%) (retired, employed, unemployed and housewives) reduced their daily activity and 14 of them haven't recovered yet 1 to 13 YY after diagnosis. 15 of 58 PTS (25,9%) left their employment definitively: 7 could retire because of age; 8 (13,8%), 4M and 4F, left their employment earlier after diagnosis of CMPD (4 LMC, 3 MF, 1 ET). Their jobs were distributed as follows: blue collars (3 F/2 M), driver (1M), white collars (1M/1F). Main reasons for loss of employment were: desease symptoms (10/15), TX side effects (6/15), job characteristics (6/15), anxiety/depression (5/15). Loss of employment caused depression in 9/15 PTS, and in 6/15 PTS echonomic issues and loss of social well being. We could not find any correlation between loss of employment and diagnosis probably due to the low numeber of PTS recruited. CONCLUSIONS In our cohort of 105 retrospectively analyzed good prognosis CMPD PTS, loss of employment rate was quite high soon after diagnosis (25,9%); 13,8% could retire because of age. Surprisingly, also CML PTS left their employment despite the well known prognostic improvement. Most of the early retired PTS were blue collars or drivers (requiring higher phisical commitment). Depression, echonomic issues and loss of social well being were the main consenquences of loss of employment. The high rate of loss of employment may be related to overestimation of disease severity and limited social assistance support. A careful early multidisciplinary approach (hematologist/occupational doctor/psyco-oncologist) could probably help to avoid unnecessary unemployment, improve psycho-social well-being and reduce echonomical anxiety. Further studies are warranted to increase population sample and address methodology biases that limit our study. A specific questionnaire should be validated.

Chronic Myeloid Leukemia: A retrospective study of clinical and pathological features

Chronic myeloid leukemia (CML), is one of the myeloproliferative disorders with a characteristic cytogenetic abnormality resulting in the BCR-ABL fusion gene. Imatinib Mesylate is an effective agent for treating patients in all stages of CML. According to the annual Iraqi cancer registry 2019, the total number of chronic myeloproliferative disorders was 338. The percentage and incidence rates were 0.94% and 0.86%, respectively, with a higher incidence rate in males than females (1.12 in males and 0.60 in females). In this registry, no details about CML, so this study aimed to estimate the number of CML patients who attended the national center of hematology from 2005 until 2020 and investigate their epidemiological and clinic-pathological data. All data were obtained from the National Center of Hematology /Baghdad. Data regarding annual admission, number of deaths, and information about age, regions, and sex, were collected from patient cards. Interview and history taking from the patient and reviewing their clinical features at diagnosis were performed, and then statistical analysis was achieved. Two hundred sixteen patients were registered as CML; among them, 163 are still alive, while 53 died. The mean age at diagnosis was 40.39 ±14.30, with a male-to-female ratio of 1:1.16. The pediatrics age group comprises 3.7% of total cases and 1.8 % and 9.4% in the alive and dead groups, respectively. The percentages of death were higher in the pediatric age group, 62,5%( 5 /8), followed by the patient group who were ≥60 years, 42.1%(8/19), while it was the least in adults < 60 years, 21.1% (40/189). In conclusion, the studied patients with CML were younger than the globally reported ages at diagnosis, with predominant female patients. Females had better survival, while children and the elderly were the worse. Most patients were symptomatic at diagnosis; however, a good outcome is achieved when treated with IM. Keywords: CML, Imatinib, leukemia,

Башкирский государственный медицинский университет, Уфа, Россия

Chronic myeloproliferative disorders (CMPD) include hemoblastoses with abnormal proliferation of myeloid lineages and concomitant alterations in the peripheral blood indicators. The aim of this study was to assess the frequency and structure of ophthalmic complications as a quality of life factor in patients with CMPD. A group of patients with hemoblastoses of this type (n = 41) were surveyed using National Eye Institute Visual Function Questionnaire-25 along with a comprehensive examination by noninvasive ophthalmological techniques. The patients typically reported impaired visual acuity, visual discomfort and foreign body sensation in the eyes. Though many of the patients assessed their general health and vision as satisfactory, the vast majority (68.3%) expressed serious concerns about their visual abilities. The ophthalmological examination revealed various defects including refractive errors (61%), corkscrew dilation and tortuosity of conjunctival and retinal vessels (77.9%), recurrent subconjunctival hemorrhages (39%) and dilated optic nerve sheaths (36.6%). The survey data indicate that visual impairments significantly affect quality of life in patients with CMPD. Overall, the results underscore the importance of interdisciplinary approach in the management of patients with CMPD to enable early diagnosis and feasible correction of the ophthalmic component.

CYTOLOGICAL DIAGNOSIS OF CUTANEOUS MYELOID SARCOMA-A RARE CASE REPORT

Introduction: Granulocytic sarcoma or myeloid sarcoma also known as chloroma is a rare extramedullary tumour which may occur as a manifestation of acute myeloid leukaemia, myelodysplastic syndrome or blast crisis in chronic myeloproliferative disorder or may precede systemic leukaemia. Most common site includes skin, soft tissue and lymph nodes. Orbit is most commonly involved in paediatric age group. Case Report: A case of 51 years old female was admitted in department of haematology, presented with multiple nodules in nasal cavity, forehead, bilateral arms and whole abdomen. Bone marrow aspiration cytology shows 21% myeloid blast with transformation of the CML to AML.FNAC was done from multiple nodules which showed plenty of myeloid precursors and blast and diagnosis of granulocytic sarcoma was given. BCR-ABL study came out positive and karyotyping for haematological malignancy showed t (5; 12)(q31;24.3). Patient was given chemotherapy, but showed no improvement. Conclusion: Granulocytic sarcoma (GS) is a rare malignant solid tumour in adults. Diagnosis of GS has been a problem for pathologist because of relatively immature nature of tumour cells and mostly misdiagnosed as Non Hodgkin's lymphoma. Diagnosis of GS is considered as an adverse prognostic factor but early conrmation of diagnosis and treatment initiation might improve the prognosis.

IL-4 Serum Level Estimation in Myeloproliferative Neoplasm Patients

Back Ground: Myeloproliferative neoplasm (MPN) is a long-term blood disease that has an excess production of mature hematopoietic pluripotent stem cells in the bone marrow. In the early fifties, W. Dameshek structured the Myeloproliferative disorders that are at present the World Health Organization (WHO) changed it to Myeloproliferative Neoplasms (MPNs). According to the Iraqi cancer registry, Chronic Myeloproliferative disorders in the male is 0.62% and the incidence rate is 0.36, in female Chronic Myeloproliferative disorders (45 case) is 0.31% and the incidence rate is 0.24. The JAK2-V617F genetic mutation is approximately seventy percent of the Myeloproliferative Neoplasm cases. Interleukin-4 plasma and serum levels are significantly increased in MPNs different types. 
 Objectives: The goal of this study is to estimate the IL-4 serum levels in the JAK2-V617F negative and positive mutation in the Iraqi MPNs patients.
 Materials and Methods: Total of (60) patients screened by cohort prospective study of having MPN who are patients presented to the National Center of Hematology / Al-Mustansiriyah University. Depending on the JAK2-V617F genetic mutation we classified our MPNs cases into 3 groups: JAK2-V617F negative (N: 20), JAK2-V617F positive (N: 40) and control group (10). Blood sample (5) ml was obtained from each individual in each group, by venipuncture using disposable syringes for IL-4 serum estimation by Enzyme Linked ImmunoSorbent Assay (ELISA) technique. 
 Results: A clear indication of significant differences was observed between IL-4 serum level in JAK2-V617F negative samples and control samples (P < 0.05). 
 Conclusion: The IL-4 serum level is high in MPNs patients, which is one of the immune evading mechanisms of the cancerous acting to imbalance the Th1/Th2 ratio and enhancing the anti-apoptotic activity inside those cells.

Development of Therapy Approach in Patient with Chronic Granulocity Leukemia: Case Report

Abstract Chronic granulocytic leukemia (CGL), Ph + is a chronic myeloproliferative disorder, which, due to its specificity for many decades, has attracted the attention of researchers of specialties. This disease was among the first malignant haemopathies that received their “ID card” since molecular precisely defined the basic pathological substrate, that origin of the disease. Over the past decades we have witnessed the evolution of the therapeutic approach in the treatment of from oral cystostatic therapy, radiotherapy, through recombinant interferon alpha (IFN-alpha), haematopoeza stem cell transplantation, to the targeted molecular therapy of the tyrosine inhibitor (TKI). In this report we present patient with a diagnosis of Ph + in the early chronic phase at the age of 13 all relevant analyzes. During the past 26 years, all modalities of CGL treatment were applied in patients, according to the time period, concluding with the second generation resulting in complete remission of diseases with excellent quality of life and identical expectations for the future, as well as in healthy population.

STUDY OF PLATELET FUNCTION DEFECTS IN CASES OF CHRONIC MYELOID LEUKAEMIA

AIM: Chronic myeloid leukaemia (CML) is one of the chronic myeloproliferative disorders. The emerging data overwhelmingly suggests that study of platelet defects in CML would be useful for comprehensive management of CML. This study was conducted to identify the platelet function defects and to correlate the results with clinical symptoms in cases of CML. METHODS: Clinical and laboratory data of CMLpatients, diagnosed and managed at a tertiary centre from January 2018 to September 2019 were analyzed. Patient's platelet rich plasma was subjected to platelet function tests (PFT) with Chronolog Dual Channel Platelet Aggregometer using arachidonic acid, epinephrine, adenosine diphosphate (ADP) and ristocetin as agonists. RESULTS: Most cases of CML(30%) were from age range of 51 to 60 years and 83% of cases were male. Splenomegaly was seen in 97% of cases. 3 Median haemoglobin was 13 g/dl and median total WBC count was 6.315 x 10 /µL. About 64% of all cases showed the total platelet count of 201- 3 300 x 10 /µL. Median platelet distribution width (PDW) was 10.7 and median value of mean platelet volume (MPV) was 9.4. There was signicant association between platelet aggregation response with ADP and bleeding manifestations. In 98% of cases showing normal platelet aggregation responses with ADP, bleeding manifestation were absent. CONCLUSION: The present study suggests that platelet function defects are seen in CML. Platelet aggregation study can be useful especially in those patients exhibiting bleeding manifestations with normal or increased platelet counts. This would enable a comprehensive management in cases of CML.

Chronic Myeloid Leukemia: Clinico-Hematological Profile from Southern Pakistan

Background: Chronic myeloid leukemia is a form of chronic myeloproliferative disorder described by the presence of specific haematological and cytogenetic markers. It is a very common blood neoplasm that usually requires a basic clinical history, review, and regular blood examination to diagnose. If detected early, it has a high cure rate. Objective: To assess the clinical and laboratory features of chronic phase chronic myeloid leukemia patients. Study Design: Cross-sectional study Place and Duration of Study: Department of Haematology, Liaquat National Hospital and Medical College, Karachi 1st January 2012 to 31st December 2016 Methodology: One hundred and forty four chronic myeloid leukemia patients visited the study site during this period, of which 132 were in the chronic phase and met the eligibility criteria. The patient’s data, including age, gender, clinical and laboratory parameters were obtained. Results: One hundred and fifteen (87.1%) had constitutional symptoms, predominantly fatigue and abdominal discomfort. The clinical presentation displayed splenomegaly among 89.3% of patients with a mean spleen span of 18.9±3.7 cm and massive splenomegaly in 32.5% of patients. Haematological presentation at baseline showed that the mean haemoglobin level of the enrolled patients was 9.6±2.0g/dl, TLC was 167.6±123.3x109/l, and platelet count was 398.7±281.9x109/l. Furthermore, 19.4%of patients were anaemic, and hyperleukocytosis was detected in 24.2%. High LDH, hyperuricemia and elevated serum creatinine were present in 38.6%, 40.9%, and 14.3%, respectively. Conclusion: Unlike the western countries, chronic myeloid leukemiais more prevalent in a very young age group in Pakistan. The chronic myeloid leukemia patients displayed variable clinical and haematological presentation. Constitutional symptoms and splenomegaly were consistent features among the majority of patients. Keywords: Chronic myeloid leukemia, Clinico-hematological, Pakistan

Platelet Function, Role in Thrombosis, Inflammation, and Consequences in Chronic Myeloproliferative Disorders.

Platelets are conventionally defined as playing a vital role in homeostasis and thrombosis. This role has over the years transformed as knowledge regarding platelets has expanded to include inflammation, cancer progression, and metastasis. Upon platelet activation and subsequent aggregation, platelets release a host of various factors, including numerous pro-inflammatory factors. These pro-inflammatory factors are recruiters and activators of leukocytes, aiding in platelets’ immune regulating function and inflammatory function. These various platelet functions are interrelated; activation of the inflammatory function results in thrombosis and, moreover, in various disease conditions, can result in worsened or chronic pathogenesis, including cancer. The role and contribution of platelets in a multitude of pathophysiological events during hemostasis, thrombosis, inflammation, cancer progression, and metastasis is an important focus for ongoing research. Platelet activation as discussed here is present in all platelet functionalities and can result in a multitude of factors and signaling pathways being activated. The cross-talk between inflammation, cancer, and platelets is therefore an ideal target for research and treatment strategies through antiplatelet therapy. Despite the knowledge implicating platelets in these mentioned processes, there is, nevertheless, limited literature available on the involvement and impact of platelets in many diseases, including myeloproliferative neoplasms. The extensive role platelets play in the processes discussed here is irrefutable, yet we do not fully understand the complete interrelation and extent of these processes.

Polycythemia Vera and Heart Failure: Association and Outcomes- a Propensity Matched Analysis in Hospitalized Patients

▪Polycythemia Vera (PV) is a rare chronic myeloproliferative disorder (MPN), a hematopoietic stem cell-derived malignancy that is characterized by clonal proliferation of myeloid cells with variable degrees of morphologic maturity. PV is distinguished from other MPNs by the presence of an elevated red blood cell mass (ie, erythrocytosis), and is associated with an increased risk for thromboembolic events, leukemic transformation, and/or myelofibrosis. This translates to sludging of blood flow due to hyperviscosity. Patients with PV have increased risk of both arterial and venous thrombosis as well as hemorrhage. Acute coronary syndrome and cardiac thrombotic events are well known complications of PV, however there is insufficient data on PV associated with heart failure (HF) and its repercussions. Through this study we aim to determine baseline characteristics of PV patients with and without HF and its impact on morbidity, mortality and overall hospital length of stay.We identified all hospitalized adult patients with PV from the National Inpatient Sample Database between January 2016 to December 2018 using ICD-10-CM codes, and divided them into groups with and without heart failure. We compared patient's baseline characteristics, associated comorbidities, mortality, length of stay and hospitalization costs among PV patients with and without HF. Propensity-score 1:1 matching for age, sex, race, and co-morbidities was performed among both groups. SAS 9.4 software was used for statistical analysis.Out of 61265 patients hospitalized with PV, 16900(27.6%) patients were found to have HF. The patients in HF group were noted to have higher mean age (74.7±12.3 vs 69±14.3 years), and higher prevalence of comorbidities such as diabetes mellitus (27.5 vs 20.4%), coronary artery disease (47.2 vs 22.4%), peripheral vascular disease (12.1 vs 9.9%), chronic pulmonary obstructive disease (33.9 vs 20.6%), Renal failure (20.2 vs 9.4%) and obesity (13.6 vs 10.5%). In terms of propensity matched outcomes, the group with PV and coexisting HF had higher inpatient mortality (5.9 vs 3.6%), higher total length of stay (6.5 ± 7.3 vs 5.2 ± 5.3 days), and higher total hospitalization cost (18081 ± 27506 vs 14529 ± 18412 $) (p<0.001).Our study noted that almost 27.6% of hospitalized PV patients had concurrent HF. We observed that presence of HF in patients with PV significantly increased mortality, hospitalization costs and total length of stay. Despite major advances in Heart failure (HF) treatment strategies, morbidity and mortality remains high. With regard to the etiology, there are different causes of HF, and their recognition can be crucial for treatment optimization. With mounting epidemiological evidence of association and fatal outcomes, our study also shines light on a significant knowledge gap in the field of MPN such as PV and concurrent HF, and warrants further studies to better delineate pathogenesis and early diagnostic and treatment strategies specifically curated for PV associated HF. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical and Pathological Features of Renal Presentations in Polycythemia Vera

BackgroundPolycythemia vera (PV) is a common type of Philadelphia chromosome-negative chronic myeloproliferative disorder. PV-associated kidney disease is rarely reported and remains poorly understood. It has been observed that chronic kidney disease could be a risk factor for poor prognosis in PV. MethodsWe retrospectively analyzed the clinicopathological features of renal presentations in eight patients with confirmed PV-associated kidney disease. ResultsThe eight patients were 6 males and 2 females, with a mean age of 46.4 ± 16.8 years. Six patients had a history of PV, with a duration range 0.5–16 years. The other two patients were newly diagnosed with PV simultaneously with glomerular disease. Seven patients conducted a JAK2 V617F mutation test, with a positive result in five. Proteinuria and renal dysfunction were the patients' main complaints, with only one having nephrotic syndrome and three having microscopic hematuria. The level of proteinuria ranged from 0.52–10.96 g/day. Three patients had advanced chronic kidney disease (CKD), two in stage 3b and one in stage 4, but only one patient had anemia. Three patients had monoclonal immunoglobulinemia, one patient with immunoglobulin (Ig) G kappa plus light chain lambda, one patient with IgG kappa, and one patient with IgG lambda. Five patients underwent a renal biopsy. The pathological diagnosis was IgA nephropathy in three, non-IgA mesangial proliferative glomerulopathy in one, and glomerular hypertrophy with ischemic renal injury in one patient. Glomerular ischemia, ischemic shrinkage, focal segmental sclerosis, and glomerulomegaly were common pathological features. Glomerular crescents and endocapillary proliferation were also observed. All patients were administered hydroxyurea, and seven were administered renin-angiotensin system inhibitors. During follow-up, one patient with uncontrolled PV developed secondary myelofibrosis and died, three patients were lost to follow-up, and four patients remained alive with CKD. ConclusionsPatients with untreated or uncontrolled PV could have massive proteinuria and advanced CKD, pathologically showing ischemic, sclerosing glomerular lesions with hypercellurity, glomerular crescents and endocapillary proliferation. IgA nephropathy was most commonly diagnosed. These findings deserve attention because early screening and effective control of PV may benefit the long-term kidney prognosis.

ACUTE MYOCARDIAL INFARCTION: AN UNUSUAL INITIAL PRESENTATION OF POLYCYTHEMIA VERA

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Polycythemia Vera (PV) is a chronic myeloproliferative disorder that affects the hematopoietic progenitor cells and increases the production of red cells, platelets and granulocytes1. The incidence of PV is around 2.3 per 100,000 persons/year2. Major cause of morbidity and mortality in PV patients is thrombosis that is either microcirculatory or arterial4. Hyperviscosity and thrombocytosis lead to coronary thrombosis resulting in acute myocardial infarction (AMI)4. However, the initial presentation of PV as AMI is extremely rare, with less than 10 cases reported in literature4. This is a unique case of a young healthy male with no cardiovascular risk factors, who presented with an AMI with the ultimate diagnosis of PV. CASE PRESENTATION: A 42-year-old French male presented with severe substernal chest pain radiating to the left arm, nausea, diaphoresis and left arm numbness ongoing for an hour. He had no significant medical, social or family history. He had a HR of 101 BPM and a BP of 137/92 mmHg. Labs included: high sensitivity troponin 701 pg/mL, LDL 111mg/dL, WBC 11.7K, platelets 357K, Hgb 22.5 g/dL and Hct 67.6%. An EKG was suggestive of an antero-septal STEMI. A cardiac catheterization with a drug eluting stent was deployed in the left anterior descending artery that was 99% occluded. The findings of an elevated hemoglobin and hematocrit triggered a cascade of investigations. Erythropoietin level was unremarkable, while bone marrow biopsy displayed panmyelosis. Imaging demonstrated hepatosplenomegaly. Ultimately, the diagnosis of PV was established when genetic testing revealed a JAK2 V617F mutation. Post-MI and PV treatment with hydroxyurea and therapeutic phlebotomies to maintain a hematocrit goal of less than 45% was initiated. DISCUSSION: Coronary events in PV patients occur at a rate of 11.4% in 10-year follow-up4. The two most important risk factors for thrombosis are advanced age and prior history of thrombosis1. Although not clearly established, overproduction of thromboxane A2, endothelial dysfunction, platelet and leukocyte activation are believed to contribute to vascular events4. The mainstay of treatment of PV is antiplatelet medications, therapeutic phlebotomies and cytoreductive drugs4. There are no current guidelines for risk reduction of stent restenosis or the treatment of AMI in PV1. CONCLUSIONS: This case emphasizes the need to consider PV in the differential diagnosis of acute coronary syndrome in young patients without any cardiovascular risk factors. Furthermore, it re-affirms the need for an annual examination to identify abnormal studies and the benefit of timely intervention. REFERENCE #1: Adel G. Polycythemia Vera and Acute Coronary Syndromes: Pathogenesis, Risk Factors and Treatment. J Hematol Thromboembolic Dis. 2013;01(01). doi:10.4172/2329-8790.1000107 REFERENCE #2: Bahbahani H, Aljenaee K, Bella A. Polycythemia vera presenting as acute myocardial infarction: An unusual presentation. J Saudi Hear Assoc. 2015;27(1):57-60. doi:10.1016/j.jsha.2014.07.003 REFERENCE #3: Tefferi A, Rumi E, Finazzi G, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: An international study. Leukemia. 2013;27(9):1874-1881. doi:10.1038/leu.2013.163 DISCLOSURES: No relevant relationships by Madeeha Banu, source=Web Response No relevant relationships by Rohan Bodapati, source=Web Response No relevant relationships by palak desai, source=Web Response No relevant relationships by Brendan Gilmore, source=Web Response No relevant relationships by Kenneth Joseph, source=Web Response No relevant relationships by nitish singh nandu, source=Web Response No relevant relationships by Swetha Paduri, source=Web Response No relevant relationships by Nehal Patel, source=Web Response