History Of Polycythemia Vera Research Articles

Portal vein thrombosis and non-compliance in a high risk patient – a case study

Portal vein thrombosis is a pathological process that refers to the obstruction of blood flow secondary to thrombus formation. It may be caused by a variety of conditions including cancer, cirrhosis, myeloproliferative neoplasms (eg. polycythemia vera) or surgery in the area of the portal vein (eg. splenectomy). Recent studies suggest that patients with a positive history of SARS-CoV-2 infection have a higher risk of thromboembolic incidents. According to current procedures patients with increased thromboembolic risk should receive anticoagulants. Non-compliance to medical recommendations may develop a disease, directly threatening the patient's health and life. We present a case report of a 69 year old woman with a history of polycythemia vera, recent splenectomy, and SARS-CoV-2 infection who developed massive portal vein thrombosis two days after discontinuation of enoxaparin.

Lemierre’s Syndrome in an Elderly Female Patient with Polycythemia Vera: Does Polycythemia Vera Predispose to Lemierre’s Syndrome?

Patient: Female, 66-year-old Final Diagnosis: Lemierre’s syndrome Symptoms: Chills • neck pain • odynophagia • rigors • trismus Medication: — Clinical Procedure: Computed tomography Specialty: Cardiology • Hematology • Infectious Diseases • General and Internal Medicine Objective: Unusual clinical course Background:Lemierre’s syndrome (LS), a potentially fatal condition, is characterized by thrombophlebitis of a head or neck vein secondary to a head or neck infection, most commonly involving Fusobacterium necrophorum. Its association with polycythemia vera (PV) is not well reported despite the predisposition to thrombogenesis.Case Report:We present the case of a 66-year-old woman with a known history of polycythemia vera (PV) who presented with 4 days of worsening right-sided neck pain and odynophagia. The physical examination revealed poor oral dentition, mild erythema of the posterior pharyngeal mucosa, and non-erythematous tonsils without exudate. A computed tomography with i.v. contrast of the neck revealed complete thrombosis of the right internal jugular vein (IJV). Treatment was initiated with i.v. antibiotics and anticoagulation, with symptoms improving rapidly within 24 h. She was eventually discharged on apixaban and clindamycin and was encouraged to follow up with her hematologist.Conclusions:PV predisposes patients to a hyper-viscous and prothrombotic state, which may warrant a stronger suspicion of Lemierre’s syndrome. In addition, lack of aspirin use for prophylaxis of thrombosis and undiagnosed oral infection are factors to consider when assessing risk factors for Lemierre’s syndrome in PV patients.

Advanced forms of MPNs are accompanied by chromosomal abnormalities that lead to dysregulation of TP53

AbstractThe Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (PMF), frequently progress to more overt forms of MF and a type of acute leukemia termed MPN-accelerated phase/blast phase (MPN-AP/BP). Recent evidence indicates that dysregulation of the tumor suppressor tumor protein p53 (TP53) commonly occurs in the MPNs. The proteins MDM2 and MDM4 alter the cellular levels of TP53. We investigated in 1,294 patients whether abnormalities involving chromosomes 1 and 12, which harbor the genes for MDM4 and MDM2, respectively, and chromosome 17, where the gene for TP53 is located, are associated with MPN disease progression. Gain of 1q occurred not only in individuals with MPN-BP but also in patients with PV and ET, who, with further follow-up, eventually evolve to either MF and/or MPN-BP. These gains of 1q were most prevalent in patients with a history of PV and those who possessed the JAK2V617F driver mutation. The gains of 1q were accompanied by increased transcript levels of MDM4. In contrast, 12q chromosomal abnormalities were exclusively detected in patients who presented with MF or MPN-BP, but were not accompanied by further increases in MDM2/MDM4 transcript levels. Furthermore, all patients with a loss of 17p13, which leads to a deletion of TP53, had either MF or MPN-AP/BP. These findings suggest that gain of 1q, as well as deletions of 17p, are associated with perturbations of the TP53 pathway, which contribute to MPN disease progression.

Ischemic colitis caused by polycythemia vera: A case report and literature review.

Polycythemia vera (PV) is a chronic myeloproliferative disorder originating from hematopoietic stem cells and complicated by thrombosis and bleeding. This report describes a case of ischemic colitis (IC) caused by PV and includes a review of the relevant literature. The patient was a 59-year-old male with a history of PV who presented with abdominal pain and hematochezia. Colonoscopy and histopathological examination results indicated suspected ischemic bowel disease. Following experimental anticoagulant therapy for 7 days, the patient no longer experienced abdominal pain and hematochezia had resolved. Colonoscopy review showed no obvious anomalies 1 month later. These data demonstrated that PV is an uncommon cause of IC.

Erythrocytosis caused by giant chromophobe renal cell carcinoma: a case report indicating a 9-year misdiagnosis of polycythemia vera

BackgroundErythrocytosis, a rare paraneoplastic syndrome, generally occurs in patients with clear cell renal cell carcinoma and has never been reported in patients with chromophobe renal cell carcinoma.Case presentationWe report a case of a young man suffering from a giant (22-cm) mass on his left kidney. Because of a history of polycythemia vera, the patient had been treated for the condition for 9 years. Radical nephrectomy was successfully performed, and the postoperative pathologic examination confirmed a diagnosis of chromophobe renal cell carcinoma. Unexpectedly, the symptom of erythrocytosis disappeared after the surgery. Further examination and analysis were performed, and we finally attributed his erythrocytosis to chromophobe renal cell carcinoma.ConclusionsChromophobe renal cell carcinoma could cause erythrocytosis, but the clear-cut mechanism needs further research. Secondary erythrocytosis such as those related with renal tumors should be taken into consideration during the diagnosis of polycythemia vera.

Extramedullary haematopoiesis presenting with cardiac tamponade in a patient with polycythaemia vera

A 71-year-old man with a history of polycythaemia vera, diagnosed 4 years ago, presented to the emergency room with shortness of breath. A bedside echocardiogram revealed a large pericardial effusion...

A patient case highlighting the myriad of cutaneous adverse effects of prolonged use of hydroxyurea

Hydroxyurea is an antimetabolite primarily used to treat myeloproliferative disorders, and chronic treatment is associated with many cutaneous adverse effects ranging in severity from ichthyosis to aggressive nonmelanoma skin cancer. We report a 67-year-oldman with a history of polycythemia vera who was referred for management of progressively worsening dorsal hand lesions. The patient presented withhyperpigmentation, ichthyosis, plantar keratoderma, dermatomyositis-like eruptions, two squamous cell carcinomas, and actinic keratoses. The adversereactions observed were acknowledged to be related to chronic hydroxyurea use. The patient underwent Mohs excision of the squamous cell carcinomas and thehydroxyurea was promptly discontinued; subsequent cutaneous improvement of the dermatomyositislike lesions ensued. Another clinically suspicious aggressive squamous cell carcinoma was suspected and the patient was referred to the plastic surgery department for complete excision because of the size of the lesion. The patient remains on periodic dermatology follow up. We report a case that exemplifies the cutaneous adverse effects of chronic hydroxyurea therapy. Although many cases improve after drug discontinuation, strict photoprotection and ongoing surveillance are indicated given the recently proposed premalignant potential of dermatomyositis-like eruptions and the aggressive nature of hydroxyurea-induced nonmelanoma skin cancer.

Intimal exfoliation following abnormal circular proliferation as a cause for acute coronary syndrome in a patient with polycythemia vera

A 78-year-old female with a history of polycythemia vera (PV) was admitted due to sudden severe chest pain at rest. She had been treated with 500 mg/day of hydroxycarbamide for PV (platelet counts ranging from 480,000 to 600,000/μl, leukocyte counts ranging from 14,500 to 18,000/μl, and hematocrit levels ranging from 37 to 42%), and 100 mg/day of cilostazol for previous cerebral transient ischemia attack. Physical examination revealed no specific findings except splenomegaly. Anterior ST-segment elevation myocardial infarction (STEMI) was diagnosed by electrocardiography. Echocardiography

Thrombocytopenia and hemorrhagic pleural effusion as an initial presentation of polycythemia vera

Polycythemia vera (PV) is a chronic myeloproliferative disorder in which there is an alteration in the pluripotent progenitor cell leading to excessive clonal proliferation of erythroid, myeloid and megakaryocytic progenitor cells. The natural history of PV can be divided into several stages, beginning with asymptomatic, isolated erythrocytosis, progressing to more generalized myeloid proliferation, splenomegaly, and thrombosis, followed by myelofibrosis, leukoerythroblastosis, cytopenia, and myeloid metaplasia and sometimes, acute leukemia. Isolated erythrocytosis, leukocytosis, or thrombocytosis or in combination are usually present at the onset of disease. We present the case of a 65-year-old man, who developed thrombocytopenia and hemorrhagic pleural effusion as an initial presentation of PV that is extremely rare.

A Rapidly Progressive Case of Hemorrhagic Pancreatitis in a Patient with Polycythemia Vera, or Not?

Introduction: Acute pancreatitis and polycythemia vera are risk factors for mesenteric vein thrombosis. Rates of significant thrombosis and hemorrhage are reported as approximately 25% for either in patients with PCV. The case describes the difficult dilemma that occurs when clinical presentation includes both thrombo-hemorrhagic complications simultaneously. Case: A 62-year-old woman with a history of polycythemia vera was admitted for severe upper abdominal pain, nausea, vomiting and CT findings consistent with acute pancreatitis and small pelvic hematoma. She had no other risk factors for pancreatitis such as gallstones, alcohol use, hypertriglyceridemia, drugs, or autoimmune phenomena. Admission laboratory evaluation was notable for white blood cell count of 50,000, platelet count of 2.4 million, and a normal lactate. Interestingly, amylase and lipase were also normal as well as CT abdomen/pelvis obtained 3 days prior. Conservative management for pancreatitis was initiated. Unfortunately, the patient deteriorated over the next 2 days, with worsening pain and peritoneal signs. A repeat CT abdomen/pelvis showed a peripancreatic hematoma compressing the portal vein, progressive pelvic hematoma, superior mesenteric vein thrombus, and new ileus. She was taken emergently to the operating room for evacuation of peripancreatic hematoma, oversewing of bleeding vessels in right retroperitoneum, and packing of abdomen with temporary closure. Plasma exchange (PLEX) and hydroxyurea were initiated for cytoreduction of the dysfunctional platelet load in hopes of preventing further bleeding or thrombotic complications. Platelets improved to 1 million. Anticoagulation was held despite her prothrombotic state and mesenteric thrombosis in the setting of large retroperitoneal hematoma. Discussion: The diagnostic criteria for pancreatitis include two of the following: characteristic abdominal pain, elevated pancreatic enzymes, or imaging consistent with the diagnosis. Our patient met the criteria without an elevated amylase or lipase. However, upon review of the clinical picture and laparotomy findings, the peripancreatic changes were not consistent with acute pancreatitis. Instead, local hemorrhage and inflammatory changes related to the disease process of polycythemia vera were mimicking pancreatitis. In evaluating patients with presumed pancreatitis special attention should be paid to the overall clinical picture to avoid overdiagnosis. Similarly, early recognition of alternative diagnoses would allow prompt institution of appropriate therapy.

Polycythemia Vera Terminating in Refractory Ascites

A 64-year-old woman,with more than a 20 year history of polycythemia vera(PV),developed portal hypertension,myelofibrosis and extramedullary hematopoiesis accompanied by massive ascites. Portal hypertension resulted not only from infiltration of the liver sinusoids by hematopoietic cells but also from nodular regenerative hyperplasia of the liver. Wright-stained smears of ascites samples consisted of mesothelial cells and macrophages. However,cultures of mononuclear cells from the ascites showed the presence of hematopoietic progenitor cells including megakaryocyte colony formation and burst forming units. The JAK2-V617F mutation was positive in granulocytes. Contrary to other reports,radiation therapy was not effective and severe myelosuppression continued for more than one month. We present the unusual clinical course for this case of PV and discuss the pathophysiology of refractory ascites. (Kitakanto Med J 2012;62:159~162)

From Vaquez to Dameshek through JAK…2 much for polycythemia vera to be feared?

Clinical practice in modern medicine is a gift that comes from afar. It comes sometimes from a lucky discovery, or sometimes from brave attempt chasing what at that time seemed crazy theories. Anyway, the gift we currently enjoy is the result of careful observation at first, and then like a sculptor with his chisel that free from marble an hidden figure, doctors and researchers carve during the years the features of many diseases. In this number of the Internal and Emergency Medicine Journal, Landolfi and his co-workers [1] reviewed the principal characteristics of polycythemia vera (PV), starting from the history of the first published description by Luis Henry Vaquez in 1892 [2]. Since this first description something other than plethora and cyanosis were soon identified: the high risk of major thrombotic events potentially leading to death, both in arterial district (acute myocardial infarction, stroke or transient ischemic attack, TIA), and in venous district (deep vein thrombosis, pulmonary embolism, and splanchnic thrombosis). The mortality rate of PV, as reassessed in the ECLAP study [3] is about 3.7/100 patients/year due not only to the vascular complications but also for a possible evolution to malignancy. The history of PV went through the recognition of an absolute increase of blood cells, due to an abnormal erythropoiesis as the result of a pluripotential stem cell being erythropoietin hypersensitive and independent [4]. The related clinical condition must be differentiated from secondary erythrocytosis and this exercise has challenged haematologist for decades. So, like industrious sculptors, haematologist has learnt to use diagnostic criteria like chisels to carve for each patient the hidden truth of primary or secondary hyperglobulia. But not all sculptors are the same. Amedeo Modigliani, the great painter and sculptor used to say that he could see at a glance what was inside a piece of marble, and that he just had to free it. In the same way, Dameshek [5] in 1951 described his vision ‘‘from outside’’ and speculated that PV has the same origin of essential thrombocythemia (ET), chronic idiopathic myelofibrosis (IMF) and chronic myeloid leukemia (CML). What was really inside, and Dameshek had seen, was proved more than 50 years later with the discovery of the mutation at position 617 in the JH2 domain of the Janus Kinase 2 (JAK2) cytoplasmic tyrosine kinase [6–9]. This gainof-function mutation, recognizable in almost 90% of PV patients, is acquired and present in clonal hemopoietic stem cells and responsible for the activation of Epo-signaling pathway, leading to hypersensitivity and uncontrolled growth of cells. The JAK2V617F mutation is also found in about 50% of patients with ET and IMF, in atypical myeloproliferative disorders, but it has been described also in some patients with CML and in patients with portal vein thrombosis but without hematological abnormalities. From these observation, recent theories and hypothesis have been explained, such as different intensity of JAK2 signaling, presence of pre-JAK2 event that will result in different myeloproliferative disorders, different host modifier polymorphisms [10], just to cite some of them. M. Carpenedo (&) E. M. Pogliani Hematology and Bone Marrow Transplantation Unit, San Gerardo Hospital, University of Milan Bicocca, Via Pergolesi 33, 20035 Monza, Italy e-mail: mcarpenedo@katamail.com

P0229 RS3PE (REMITTING SERONEGATIVE SIMETRICAL SYNOVITIS WITH PITTING EDEMA) SYNDROME ACCOMPANIED BY POLYCYTHEMIA VERA

Introduction: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome was originally reported by McCarty et al in 1985, and it is characterized by symmetrical arthritis with prominent pitting edema of the dorsum of the hands and/or feet. The aetiology of the syndrome is still unknown, but has been linked to infections, tumors and autoimmune diseases. The diagnosis is clinical, but must be differentiated from other rheumatic diseases. It has a fast response with steroid therapy and excellent prognosis. Objectives: Provision of a clinical case and literature review Materials & methods: Description of a case report Results: A 59-year-old man was admitted to our hospital for a three week history of fever, myalgia and arthralgia without response to treatment with antibiotics. He had a history of polycythemia vera treated with hydroxyurea. Physical examination showed the tender articular joints sacroiliac and back pain. Two weeks later, started with morning stiffness in wrists, hands, shoulders and ankles of 3-4 hours, with edema of hands and ankles. Laboratory studies revealed elevation of white blood cell count: WBC 16,000 (76% N, 6% L, M 2%, Eo 12%, 4% B), the erythrocyte sedimentation rate was increased at 55 mm in the first hour. Liver function, renal function, and electrolytes were normal. Serum ferritin 403 mg/dL, C reactive protein at 283 mg/dL. Electrophoresis demonstrated acute inflammatory pattern. Rheumatoid factor was negative. Antinuclear antibody titer was 1/160, and the rest of the serum antibodies were negative. Tumour markers were all negative. Microbiological studies (blood, cultures, stool, sputum and serology) were negative. Chest X-ray, abdominal ultrasound and thoracoabdominal CT were normal. Radiograph hands, elbows, ankles, knees, feet and shoulders showed increased density of soft parts. Echocardiogram was normal. Bone marrow aspirate showed myeloproliferative syndrome. Temporal artery biopsy was normal. A diagnosis of RS3PE was made and the patient was treated with low-dose prednisone with a rapid clinical response Discussion & conclusion: Our patient met 6 of 7 criteria for RS3PE established by Olivo (rheumatoid factor negative, polisinovitis symmetrical, edema with fovea, morning stiffness, response to steroid treatment, the exclusion of other diseases). Fever is not a frequent symptom in this syndrome, so we must rule out infectious processes. As in our case, there is often a rise of acute phase reactants and sometimes can be elevated antinuclear antibody titer low. It has described its association with solid tumors (lung, prostate, stomach, kidney) and hematologic (leukemia, lymphoma and myelodysplastic syndromes), but we have not found any literature associated with polycythemia vera described as in this patient

Incidental finding of a left persistent subclavian vein during a routine insertion of an indwelling venous catheter

The embryological development of the systemic venous system is a complex process during which developmental abnormalities may occur. One variation is the persistence of a left superior vena cava (LSVC). When present, it usually drains into the right atrium via the coronary sinus. In 8% of the cases, however, the anomalous vein directly drains into the left atrium. We describe a patient with a history of polycythemia vera who received multiple infusions of blood products each month and who required the placement of an indwelling venous catheter. A persistent left superior vena cava draining into the left atrium was diagnosed during the insertion of the catheter.

Detection of the Single Hotspot Mutation in the JH2 Pseudokinase Domain of Janus Kinase 2 in Bone Marrow Trephine Biopsies Derived from Chronic Myeloproliferative Disorders

The recent discovery of a single point mutation in the JH2 pseudokinase domain of Janus kinase 2 (JAK2) in a considerable fraction of patients has shed light on the molecular pathomechanism in Philadelphia chromosome-negative chronic myeloproliferative disorders (Ph- CMPDs). We established a robust and reliable method for detection of the JAK2 mutation in bone marrow cells derived from archival bone marrow trephines based on polymerase chain reaction and subsequent restriction site analysis. In a series of proven Ph- CMPDs classified according to World Health Organization criteria (n = 79), we detected the JAK2 mutation in 90% of polycythemia vera, 22% of cellular prefibrotic chronic idiopathic myelofibrosis, 60% of advanced chronic idiopathic myelofibrosis, and 27% of essential thrombocythemia. JAK2 mutation was not detected in Ph+ chronic myeloid leukemia (n = 5), acute myeloid leukemia (n = 10), acute lymphoblastic leukemia (n = 10), secondary erythrocytosis (n = 10), or normal bone marrow (n = 10). Restriction site analysis was also suitable for unfixed cell populations derived from peripheral blood and bone marrow aspirates. Besides providing support in the differential diagnosis of reactive versus neoplastic myeloproliferations, this newly developed assay reveals considerable overlaps between histologically different disease entities, indicating that additional genetic alterations might be responsible for the established differences of CMPD subentities.

A Right Atrial Mass in the Presence of a Permanent Pacemaker Electrode in a Patient with Polycythemia Vera

A case of a huge right atrial mass that developed 2 years after a permanent pacemaker implantation is described. The patient had a history of polycythemia vera, which is known to present a high tendency towards the development of thrombosis. In light of this fact, we suggest that in similar cases a full echocardiography follow-up should be performed, and long-term anticoagulant therapy should be considered in selected cases.

Myelodysplastic transformation of polycythemia vera: Case report and review of the literature

We report a case of refractory anemia with excess blasts (RAEB) developing in a 67-year old man with a history of polycythemia vera; results of cytogenetic and immunophenotyping studies are described. In this report the clinical, cytogenetic and hematologic features of myelodysplasia complicating polycythemia vera are reviewed. Results of immunophenotyping and cytogenetic studies, and the preponderance of cases developing after myelosuppressive therapy suggest that in the majority of cases myelodysplasia is treatment-related.

Transformation of polycythemia vera to acute nonlymphocytic leukemia accompanied by t(1;3)(p36;q21) karyotype

The case of a patient with a history of polycythemia vera and 46,XX karyotype who transformed into acute nonlymphocytic leukemia with 46,XX,t(1;3)(p36;q21) rearrangement is reported. Significant percentages of the circulating blasts in the peripheral blood were positive on immunocytochemical stains for megakaryocyte markers, anti-Factor VIII, and antiglycoprotein IIb/IIIa. On the basis of our studies and published reports, trilineage hematopoietic abnormalities and a poor response to therapy may represent typical features of patients with t(1;3).

Myelopoietic effect of bone marrow fibroblasts cultured from patients with myelofibrosis.

Bone marrow fibroblasts (BMF) have been shown to be able to support granulopoiesis. The present studies were designed to see whether BMF in patients with agnogenic myeloid metaplasia (AMM) are also able to support granulopoiesis. Myeloid colony-stimulating activity (CSA) was assayed in BMF derived from the three groups of patients. 1) Group I: Patients with hip fracture but without underlying hematological disease; patients with solid tumor but without bone marrow metastasis; and patients with iron deficiency anemia. 2) Group II: Patients with myeloproliferative disorders other than AMM. 3) Group III: Patients with AMM or myelofibrosis with prior history of polycythemia vera. CSA was determined in a bilayer agar culture system in which BMF served as a feeder layer and either mouse or human marrow cells were employed as target cells. There was no difference of CSA production by BMF among these three patient groups. These studies suggest that BMF cultured from patients with myelofibrosis exhibit similar myeloid stimulating activity as do BMF from other patients. A significant correlation was also found between CSA production by BMF and white blood cell counts in patients with myelofibrosis (group III). This suggests that BMF may have a role in either supporting or producing CSA for granulopoiesis in myelofibrosis.

Polycythaemia vera and myelofibrosis.

Bone marrow biopsies were made in 63 patients with polycythaemia vera and in three patients with primary myelofibrosis having polycythaemic blood pictures. The histological findings in polycythaemia vera were classified as follows: normal bone marrow in 14, hyperplastic bone marrow in 17, hyperplastic bone marrow with increased reticulin fibers in 19, early myelofibrosis in 9 and advanced myelofibrosis in 4 patients. In 12 of the polycythaemic patients bone marrow biopsy was repeated after nine to 32 months. In eight patients the histological picture was unchanged, three showed progression of myelofibrosis, and in one fibrotic changes possibly due to a miselading biopsy specimen had disappeared.The histological findings were in good correlation with clinical parameters and in only three polycythaemia vera patients with early myelofibrosis in histological specimens no clinical or laboratory signs of myelofibrosis were detected. Myelofibrosis was more often encountered in patients with a long history of polycythaemia vera and at the time of the diagnosis of the disease patients with increase in reticulin fiber content and with myelofibrosis in marrow sections had shown slightly more often leukocytosis, circulating normoblasts and splenomegaly than the other patients.The reliability of bone biopsy from the iliac crest and its value in polycythaemia vera are evaluated. The relationship between polycythaemia vera and myelofibrosis is discussed in the light of the concept of myeloproliferative diseases.