Delayed manifestation and slow progression of cerebral infarction caused by polycythemia rubra vera

BACKGROUND: Polycythemia rubra vera is often found after the manifestation of cerebral infarction, though the pathogenesis is still controversial. We present a case of cerebral infarction secondary to polycythemia rubra vera, which presented a slow expansion on magnetic resonance imaging despite severe hemiplegia. This case suggests a possible mechanism for development of cerebral infarction in polycythemia rubra vera. METHODS: This case report was conducted in a university hospital. Magnetic resonance imaging and diffusion-weighted imaging were performed to assess the evolution of infarction, and the total blood volume and cerebral blood flow were determined with the use of isotopes, Cr and Tc, respectively. Phlebotomy was performed, but intervention was not applicable. The manual muscle test and sensory disturbance were assessed by the same physiotherapist throughout the clinical course. RESULTS: A 64-year-old male patient with polycythemia rubra vera had a cerebral infarction. A subtle change was observed on CT scan on the third day after the onset of infarction, and a small signal was demonstrated on magnetic resonance imaging on the fourth day. The cerebral infarction expanded slowly in size and reached a maximum on day 24. A diagnosis of cerebral infarction secondary to polycythemia rubra vera was made, and treatment by phlebotomy, hydration, and hydroxyurea was begun. Though the hemiplegia remained, he became ambulatory with a brace, as do patients with atherosclerotic infarction. CONCLUSIONS: It is suggested that the delayed manifestation and slow expansion of cerebral infarction caused by elevated hematocrit might be derived from a pathogenesis different from atherosclerotic infarction.     

Polycythemia vera presenting as acute myocardial infarction: An unusual presentation

Acute myocardial infarction (AMI) is usually seen in the setting of atherosclerosis and its associated risk factors. Myocardial infarction in the young poses a particular challenge, as the disease is less likely, due to atherosclerosis. We report the case of a 37-year-old female patient who presented with ST segment elevation anterolateral AMI. The only abnormality on routine blood investigation was raised hemoglobin and hematocrit. After further testing, she was diagnosed according to the World Health Organization (WHO) criteria with polycythemia vera. This case illustrates the importance of recognizing polycythemia vera as an important cause of thrombosis, which can present initially as AMI, and to emphasize the early recognition of the disease in order to initiate appropriate management strategies.     

Anticoagulant-resistant thrombophilia in a patient with polycythemia vera: a case report

Mechanical valve thrombosis is a rare condition in an adequately anticoagulated patient in the absence of underlying thrombophilia. We report a case of a 76-year-old male with mechanical prosthetic mitral valve thrombosis as the presenting feature of polycythemia vera. The patient was treated with thrombolysis at the time of acute presentation and subsequently maintained on low molecular weight heparin, low-dose aspirin, phlebotomy and hydroxyurea. Hemoglobin, leucocytosis and platelet count were controlled for almost 4 years after which the patient suffered a second, fatal episode in the setting of therapeutic anti-Xa level. This case report highlights the thrombotic risks associated with polycythemia vera. The proposed mechanisms of hypercoagulability in polycythemia vera are reviewed. To the best of our knowledge, mechanical valve thromboses as the presenting feature of polycythemia vera has not been reported previously.     

Familial polycythemia vera with Budd-Chiari syndrome in childhood

Polycythemia vera is a myeloproliferative disorder that, in most cases, occurs sporadically with a median age at presentation of 60 years. Familial cases are very rare and usually manifest in elderly family members. The Budd-Chiari syndrome, characterized by the obstruction and occlusion of the suprahepatic veins, is a rare typical complication in polycythemia vera patients. To date, only two children or adolescents with polycythemia vera and Budd-Chiari syndrome have been described. Here, we report an 11-year-old girl with Budd-Chiari syndrome as the initial symptom of familial polycythemia vera, which was also found in the girl's grandmother. Details of the diagnostic procedures used and the clinical course are reported. The patient underwent orthotopic liver transplantation and is being treated with hydroxyurea. The available literature on familial polycythemia vera and polycythemia vera in childhood with and without Budd-Chiari syndrome is reviewed.     

Paraneoplastic eosinophilic fasciitis: a case report

A 60-year-old white woman with polycythemia rubra vera post splenectomy in November 2001 was found to have peripheral white blood cell counts increasing over 3 months. Cytogenetics revealed trisomy of chromosomes 8 and 9, and bone marrow biopsy showed hypercellular, fibrotic bone marrow consistent with myelofibrosis of polycythemia rubra vera. Two months later, the patient developed acute swelling and pain in her lower extremities. The clinical symptoms along with confirmatory histology supported the diagnosis of eosinophilic fasciitis. This is the first reported case in the English literature of an association between polycythemia vera and eosinophilic fasciitis.     

Extent of hematopoietic involvement by TET2 mutations in JAK2V⁶¹⁷F polycythemia vera

TET2 mutations are found in polycythemia vera and it was initially reported that there is a greater TET2 mutational burden than JAK2(V617F) in polycythemia vera stem cells and that TET2 mutations precede JAK2(V617F). We quantified the proportion of TET2, JAK2(V617F) mutations and X-chromosome allelic usage in polycythemia vera cells, BFU-Es and in vitro expanded erythroid progenitors and found clonal reticulocytes, granulocytes, platelets and CD34(+) cells. We found that TET2 mutations may also follow rather than precede JAK2(V617F) as recently reported by others. Only a fraction of clonal early hematopoietic precursors and largely polyclonal T cells carry the TET2 mutation. We showed that in vitro the concomitant presence of JAK2(V617F) and TET2 mutations favors clonal polycythemia vera erythroid progenitors in contrast with non-TET2 mutated progenitors. We conclude that loss-of-function TET2 mutations are not the polycythemia vera initiating events and that the acquisition of TET2 somatic mutations may increase the aggressivity of the polycythemia vera clone.     

A case of Budd-Chiari syndrome secondary to multiple thrombogenic conditions: a case report and review of literature.

This report describes a case of Budd-Chiari syndrome caused by latent polycythemia vera and factor V Leiden mutation. This syndrome usually occurs due to thrombosis of hepatic veins or membranous obstruction of inferior vena cava. The most common reasons for thrombosis are manifest polycythemia vera and the other prothrombotic conditions. Recently, latent polycythemia vera and factor V Leiden mutation have been reported in increasing frequency. In this report, we aimed to emphasize that all prothrombotic conditions must be evaluated while investigating the etiology of Budd-Chiari syndrome, including latent polycythemia vera and factor V Leiden mutation, and appropriate antithrombotic and surgical therapies must be performed without delay.     

The familial occurrence of polycythemia vera: report of a father and son, with consideration of the possible etiologic role of exposure to organic solvents, including tetrachloroethylene

The occurrence of polycythemia vera in a father and son, both of whom had intermittent exposure to organic solvents, including tetrachloroethylene and Stoddard solvent, is reported. Only three other well substantiated familial occurrences of polycythemia vera, none encompassing successive generations, were found among many reported instances.     

Pulmonary vein thrombosis in a patient with polycythemia vera

Pulmonary vein thrombosis(PVT) is a rarely encountered disease entity with varied clinical presentations. It is usually associated with lung carcinoma, lung surgeries and as a complication of the radiofrequency catheter ablation procedure for atrial fibrillation. Its clinical manifestations can vary from mild hemoptysis to lung infarction with hemodynamic compromise. A 76-year-old male presented with a 2-d history of pleuritic left sided chest pain. His past medical history included polycythemia vera, atrial fibrillation, coronary artery disease, pulmonary embolism and pulmonary hypertension. Chest radiograph was normal, troponins were normal and the 12-lead electrocardiogram did not show any ischemic changes. A computerized tomography pulmonary angiogram revealed a filling defect in the left lower lobe pulmonary vein. He was treated with subcutaneous enoxaparin and his symptoms improved. This case highlights a rare etiology of chest pain and the first reported case of the association of polycythemia vera and pulmonary vein thrombosis. A high index of suspicion is required for appropriate diagnostic work up. PVT can mimic pulmonary embolism. The diagnostic work up and treatment strategies depend on acuity of presentation.     

JAK2 mutation and acute coronary syndrome complicated with stent thrombosis

Acute coronary syndrome (ACS) could be a precious opportunity for patients to reveal concealed diseases other than conventional risk factors for ACS, such as hypertension, dyslipidemia, diabetes mellitus, etc. In the setting of ACS, the intracoronary and systemic prothrombotic environment has led to an increase in the risk of stent thrombosis of which mortality was higher among patients with ACS, especially with the highest mortality in patients with ST elevation myocardial infarction. The some specific conditions which were concealed beyond the cardiovascular pathophysiology except well-known risk factors for ACS and stent thrombosis might involve the onset of ACS. We describe a case of a 64-year-old man who was admitted to intensive care unit for chest pain. This case found the possibility that polycythemia vera with Janus kinase 2 (JAK2) V617F mutation might be a underlying disease of ACS with stent thrombosis, and highlighted the importance of recognizing polycythemia vera with JAK2 V617F mutation as concealed disease for cardiologists. We would like to report and review the relationship between ACS and polycythemia vera with JAK2 V617F mutation.     

Cytogenetic studies in polycythemia vera

A group of 54 patients with the original diagnosis of polycythemia vera were subjected to cytogenetic examination. Six (17.6%) of the 34 cases examined in the period of the advanced phase of the polycythemia vera had a chromosomal change. Thirteen (65%) of the 20 patients undergoing the cytogenetic examination in the period when the polycythemia vera turned into another myeloproliferative disease showed chromosomal aberration. This suggests a relationship between the number of chromosomal changes and the transformation of the disease. No connection between the cytogenetic changes and myelosuppressive cures could be confirmed in our material. The chromosomal change 20q- considered to be the most frequent kind in the polycythemia vera was not discovered until in patients with the polycythemia vera transformed into a different myeloproliferative disease.     

Pulmonary hypertension in polycythemia vera

Thromboembolic events occur in about 27% of the patients with polycythemia vera and account for 31% of the deaths. These include cerebrovascular accidents, myocardial infarction, peripheral vascular occlusions, pulmonary infarctions, and venous thrombosis. We report two cases with polycythemia vera who presented with pulmonary hypertension in the absence of previous thromboembolic complications of any kind. One patient died suddenly, with evidence of extensive bilateral thrombosis of prelobular pulmonary arteries at autopsy. In the second patient, local thrombosis in the pulmonary vasculature or recurrent silent pulmonary emboli appear to be responsible for the development of pulmonary hypertension. After institution of anticoagulant therapy, he is able to maintain his functional status. The purpose of this report is to alert clinicians to the development of this insidious, but potentially fatal complication in patients with polycythemia vera. © 1994 Wiley-Liss, Inc.     

Tissue plasminogen activator levels in different types of polycythemia

The plasma level of tissue plasminogen activator antigen (t-PA-Ag) was examined in 86 patients with polycythemia (29 polycythemia vera, 11 secondary polycythemia and 46 with spurious polycythemia) and 24 healthy volunteers. Tissue plasminogen activator antigen was significantly decreased in patients with polycythemia vera in comparison with healthy controls. On the other hand, in patients with spurious polycythemia and secondary polycythemia t-PA-Ag concentration was significantly increased. There was no significant difference in t-PA-Ag levels in polycythemic patients with or without thromboembolic disease. A significant correlation was detected between t-PA-Ag level and hemoglobin or hematocrit concentration in patients with polycythemia vera (p = 0.02, r = 0.43). However, in patients with secondary polycythemia and spurious polycythemia, no significant correlation between t-PA-Ag and hemoglobin level was found. Plasminogen activator inhibitor (PAI) levels in patients with polycythemia vera and healthy volunteers did not differ significantly.     

Intraventricular thrombosis in polycythemia vera: A cause of intractable cardiac failure

The occurrence of thrombotic events is central to the course of polycythemia vera.^1–5 Myocardial, cerebral, peripheral, and pulmonary infarctions are frequent and are consequences of thromboses in small and medium caliber arteries. Thrombosis in large caliber arteries is a rare event. Thrombosis within the chambers of the heart has not been hitherto reported.This report documents the occurrence of massive left ventricular thrombosis in a patient with polycythemia vera. The thrombus reduced the left ventricular capacity by about 75% and caused intractable congestive heart failure.     

Aspirin-responsive painful red,blue, black toe,or finger syndrome in polycythemia vera associated with thrombocythemia

Five patients with red, purple blue, or black toes or fingers due to thrombocythemia associated with polycythemia vera (polycythemia and thrombocythemia vera) in four and essential thrombocythemia (thrombocythemia vera) in one are described. The microvascular erythromelalgic syndrome of thrombocythemia was overlooked and progressed to cold blue swollen and painful fingers or black toes in three patients with polycythemia and thrombocythemia vera due to arteriographically documented occlusions of digital or large peripheral arteries with no evidence of preexistent atherosclerotic vascular disease. Concomitant erythromelalgia of the hand palm could be confirmed by the histopathological findings of arteriolar thrombotic lesions in the reticular dermis in two patients with polycythemia and thrombocythemia vera. The increased hematocrit in the presented patients with polycythemia and thrombocythemia vera contributed to the progression of the microvascular syndrome of thrombocythemia to major occlusive ischemic events of the extremities. Standard therapy with oral anticoagulants and reduction of the hematocrit to normal by bloodletting did not affect the platelet-mediated microvascular erythromelalgic, ischemic symptoms in the patients with polycythemia vera because thrombocythemia vera persisted. Complete relief of pain and restoration of the ischemic acral circulation disturbances in patients with thrombocythemia vera or thrombocythemia associated with polycythemia vera in maintained remission by bloodletting could be obtained by long-term treatment with low-dose aspirin.     

Aquagenic pruritus in polycythemia vera: Characteristics and influence on quality of life in 441 patients

Aquagenic pruritus (AP) is a symptom typical for polycythemia vera, but very little is known about its exact frequency, characteristics, influence on quality of life, and proper treatment. Therefore, we investigated these aspects in a large cohort of German patients with polycythemia vera using a patient directed questionnaire. Our analysis revealed that 301 of 441 analyzed patients suffered from AP. In 64.8%, AP occurred on average 2.9 years prior to diagnosis of polycythemia vera. Only in 15.4% did this lead to a hematological investigation. AP occurs primarily on the trunk and proximal parts of the extremities. Most patients complain about itching (71.8%), the remainder about tickling, stinging, or burning sensations. Forty‐four patients (14.6%) classified the pruritus as “unbearable.” Patients with AP reported reduced global health status and higher fatigue, pain, and dyspnea. Only 24% of patients received pruritus specific treatment for pruritus consisting mostly of histamine antagonists, which ameliorated symptoms in about half of the patients. In 5.6% of patients, polycythemia vera directed therapy (phlebotomy/cytoreduction) resolved the symptoms. In summary, AP is a serious symptom in patients with polycythemia vera, which until recently was difficult to treat. The advent of the novel JAK2 inhibitors, however, may open new ways for therapy. Am. J. Hematol. 88:665–669, 2013. © 2013 Wiley Periodicals, Inc.     

Pseudohyperkalemia in patients with increased cellular components of blood

OBJECTIVE: We performed a study to investigate the difference between serum and plasma potassium concentration in patients with increase in one or more of the cellular components of blood. DESIGN AND METHODS: This study was performed in two phases. During the first phase, we performed a cross-sectional comparison of the difference between serum and plasma potassium concentration (Dk) in 341 patients with the various clinical conditions where pseudohyperkalemia has been described, as well as with secondary or spurious erythrocytosis and in 30 normal controls. A cut-off value of Dk discriminating polycythemia vera from other erythrocytoses was estimated. In the second phase we studied the significance of this cut-off value as predictor of polycythemia vera in 90 naive patients who were referred with an elevated hematocrit. RESULTS: Dk was significantly increased in the groups with platelet, erythrocyte or with a mixed type disorder compared to the controls (P < 0.01). Among these groups, Dk was significantly increased in the groups with thrombocytosis and mixed type disorder, compared to the group with erythrocytosis (both P < 0.01). A cut-off value of Dk discriminating polycythemia vera from other erythrocytoses was estimated (0.70 mmol/L). Dk (> or = 0.70 mmol/L), platelet and white blood cell count were identified as significant independent predictors of polycythemia vera. CONCLUSIONS: The Dk is increased in patients with erythrocytoses, thrombocytoses or both. This phenomenon is more profound in patients with a mixed type disorder, such as polycythemia vera patients, compared to those with erythrocytoses alone.     

Successful anticoagulation with hirudin in a patient with mesenteric venous thrombosis and multiple coagulation abnormalities

A case of multiple thrombotic diatheses discovered in the setting of mesenteric venous infarction is discussed. The patient had deficiencies of protein C, protein S, antithrombin III; was heterozygous for factor V Leiden; and had polycythemia vera. Adequate anticoagulation could not be established with heparin administration and hirudin was used. The diagnosis of mesenteric venous infarction, thrombotic tendency of multiple coagulation diatheses, and use of hirudin are discussed.     

Budd-chiari syndrome complicating restorative proctocolectomy for ulcerative colitis

PURPOSE: This is a case of hepatic vein thrombosis presenting in a delayed fashion after proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Search for a causative thrombotic condition resulted in the diagnosis of polycythemia vera, a myeloproliferative disorder associated with hypercoagulability. The polycythemia was masked by an iron deficiency associated with the ulcerative colitis. METHODS: The history, physical, diagnostic modalities, and treatment for this patient are described, and the literature of Budd-Chiari syndrome associated with ulcerative colitis is reviewed. RESULTS: Six cases of Budd-Chiari syndrome in the setting of ulcerative colitis are reported in the literature from 1945 to 1997. CONCLUSIONS: Hepatic vein thrombosis is a rare complication of ulcerative colitis. The diagnosis of Budd-Chiari syndrome demands a thorough search for a hematologic condition predisposing to thrombosis. Our patient had a myeloproliferative disorder, polycythemia vera, that is associated with a hypercoagulable state. The disorder was masked by an iron deficiency associated with the ulcerative colitis. Recognition of the entity will permit successful treatment.     

Terminal lymphoblastic transformation in polycythemia vera

A patient with polycythemia vera and lymphoblastic transformation is discussed. Phenotypic characterization revealed that the predominant leukemic cells were classic "null" lymphoid cells with a minority component of pre-B cells. This case provides evidence that the stem cell disorder in polycythemia vera may involve the lymphocyte early in development.