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Pampiniform venous plexus (PVP) thrombosis is exceedingly rare, with fewer than 25 cases described. Thus, the etiology and pathophysiology remain largely unknown. A 38-year-old male with no known risk factors incidentally noted a 10-day history of right testicular discomfort prompting evaluation. Findings included extensive right PVP thrombus, critically elevated hematocrit, and a JAK2 V617F gene variant. Despite no treatment guidelines, conservative management was initiated with therapeutic apixaban, and therapeutic phlebotomy and hydroxyurea for newly diagnosed primary polycythemia vera (PV), sparing exploratory genitourinary surgery. This represents the first reported case of PVP thrombosis as the initial manifestation of a JAK2 V617F positive PV and the first documented report of PVP thrombosis associated with an acquired hypercoagulable state. Of the 8 previous cases with hypercoagulable testing performed, 2 involved inherited hypercoagulable states, suggesting hereditary and acquired prothrombotic disorders should be considered as predisposing factors. Testing for the JAK2 V617F variant in patients with mesenteric, cerebral, and splanchnic venous thromboses is currently recommended, but testing patients with venous thromboses in other anatomical locations remains controversial. We reviewed all previously described cases to expound upon this diagnosis, potential association with hypercoagulable disorders, treatment options, and observed clinical outcomes. This case adds to the minimal literature and supports genetic testing all patients with spontaneous PVP thrombosis for the JAK2 V617F variant and other hypercoagulable conditions. Additionally, conservative management with therapeutic anticoagulation and treatment of the underlying precipitating disease state may be acceptable in select patients, following exclusion of surgical emergencies.

Background/aim Polycythemia rubra vera (PRV) is a myeloproliferative disease, which is characterized by the proliferation of all three major hematopoietic groups (erythrocytes, leucocytes and platelets). This hematological condition presented with different clinical manifestations depending on the thrombohemorrhagic status of the patient. It is suggested patient with preexisting PRV may suffer complication during periodontal treatment. Thus, this case would therefore demonstrate periodontal management outcome in PRV patient. Case presentation A 60-year-old Malay gentleman presented to the Periodontic Clinic, Universiti Kebangsaan Malaysia. He was a known case of primary PRV for the past 5 years. Intraoral examination showed generalized periodontal deep pockets ranging from 5 to 10 mm. He was diagnosed as Stage III Grade C periodontitis. Nonsurgical periodontal therapy was provided, followed by surgical correction of residual periodontal deep pockets on teeth 17, 11, and 23. He was reviewed at 4-month intervals for supportive periodontal therapy after stabilization of his periodontal condition. Conclusion Polycythemia rubra vera (PRV) patients should have preoperative therapeutic control for more than 4 months and have been treated with myelosuppressive agents prior to periodontal surgery. Good oral hygiene and periodical supportive periodontal therapy are the key factors for successful periodontal treatment outcomes in well-controlled PRV patients.

The presence of erythrocytosis along with the diagnosis of chronic obstructive pulmonary disease (COPD) may veer a primary care clinician in a busy clinic towards attributing the erythrocytosis to hypoxia secondary to COPD; however, this is not always the case. This case highlights the importance of investigation and the significance not excluding a primary cause in COPD patients with erythrocytosis. A 57-year-old male, presenting with chronic cough, was subsequently diagnosed with COPD clinically and confirmed by spirometry. Erythrocytosis was also incidentally noted. The patient did not have any symptoms of polycythemia or hepatosplenomegaly. Therefore, the erythrocytosis was initially thought to be caused by hypoxia secondary to COPD. However, the JAK2 V617F gene mutation was detected and hence the diagnosis of polycythemia vera was made. Although the erythrocytosis was initially attributed secondary to the underlying pulmonary disease, investigations proved it to be primary in origin. This case report highlights the importance of investigating the underlying cause and to confirm the diagnosis of erythrocytosis as primary and secondary polycythemia differ in their management approach. This will avoid inappropriate diagnosis, treatment, and undesirable outcomes.

Objective Polycythemia is a rare condition in which an increase in erythrocyte mass is observed. It can be primary or secondary. Primary polycythemia occurs as a result of congenital or acquired mutations that regulate erythroid development. Although secondary polycythemia is mostly seen secondary to hypoxia due to cardiac/pulmonary reasons, it also develops as a result of congenital mutations. Globin gene mutations that increase the affinity of hemoglobin for oxygen are one of these rare causes. Materials and Methods We present a male case who was referred to us for polycythemia. Results A 15-year-old male patient with no known disease was referred to us after his school screening revealed high hemoglobin (18 g/dL). In complete blood count, other series were normal (wbc 5.8 × 103/µL neu 3.3 × 103/µL plt 174 × 103/µL), bilirubins and liver functions were within normal limits. On physical examination, conjunctiva and hands were pletoric, there was no hepatosplenomegaly, intermittent headaches were present, and neurological examination was normal. The patient was examined for the etiology of polycythemia. Hyperchromic erythrocytes were found in peripheral smear, no signs of hemolysis were observed. EPO level (8 mIU/ml) was in the normal range and JAK2 (V617F) mutation was negative. The patient's cardiac and pulmonary functions were within normal limits. Hemoglobin electrophoresis was sent from the patient. HbA was determined as 59.2, HbA2 2.8, Variant Hb 38. c.435G>T mutation was detected in the HBB genetic analysis, and this was considered to be compatible with Hemoglobin Andrew-Minneapolis. It was learned that the patient's mother and her cousins had similar findings, and some of them had undergone phlebotomy. Phlebotomy was planned in the presence of the patient's hemoglobin value > 18 g/dL and clinical findings. Phlebotomy was performed 3 times, aspirin was not started because there was no history of thromboembolism. In our 1-year follow-up, the hemoglobin value was 17-17.5 g/dL. Conclusion More than a hundred globin gene mutations associated with erythrocytosis have been described. Hemoglobin Andrew-Minneapolis mutation is one of them. Hemoglobin's affinity for oxygen has increased and EPO level is normal/increased. Due to the low number of cases, treatment recommendations were prepared based on polycythemia vera guidelines. Patients should be closely monitored in terms of hyperviscosity and thromboembolism, aspirin prophylaxis and phlebotomy are recommended according to symptoms. While investigating the etiology of polycythemia, hemoglobin electrophoresis is necessary, although it is very rare.

Purpose Patients with polycythemia, either primary or secondary, are at elevated risk for thrombotic complications, including stroke. We aimed to investigate the clinical and radiological characteristics of cerebrovascular disease (CVD) in polycythemia, and describe other neurologic manifestations. Methodology We conducted a cross-sectional study of patients diagnosed with polycythemia between 2014 and 2019 at a tertiary care center and collected relevant medical data with a special focus on cerebrovascular disease and neurologic manifestations. We performed descriptive and inferential analyses. We have also described and analyzed the available neuroimaging features. Results We analyzed data from 56 patients. 20 patients (35.7%) had ischemic stroke. The incidence of CVD was higher in those with primary polycythemia (43%) than in those with secondary polycythemia (8%). The most common subtype of stroke was large vessel disease, and the most common arterial territory was the anterior circulation. There was no statistically significant difference in the hematocrit level between those with or without CVD. Neuroimaging revealed multiple large vessel intracranial stenoses on MR Angiography, and hyperdense vessels on plain CT. Other neurologic manifestations included headache, seizures, dizziness, visual symptoms and papilledema, and these were significantly more common in primary polycythemia. Conclusions CVD is common in patients with polycythemia. The most common type observed was large vessel occlusion, predominantly in the anterior circulation. In stroke patients, multiple vessel stenosis and hyperdense vessels may be clues to polycythemia.

The classical myeloproliferative neoplasms (MPN) are characterized by clonal expansion of one or more hematopoietic cell lineages and are driven by mutations that activate constitutive signaling via JAK2 pathway. The criteria for diagnosis have now been defined by the World Health Organization (WHO) and the term MPN as is currently used encompasses the entities of primary myelofibrosis, polycythemia vera, and essential thrombocytosis. There is imperfect correlation between the genotype and disease phenotype in MPN and the latter is determined by a variety of patient factors that are independent of the driver mutation. The disease course in MPN can span decades and accurate risk assessment is critical in the choice of therapy and treatment is largely geared toward prevention of complications and providing symptomatic relief. Although new agents have been approved in recent years, no therapy has been convincingly shown to alter disease progression and allogeneic hematopoietic stem cell transplantation (HCT) remains the only curative therapy known to date.

Polycythemia indicates an absolute increase in total red blood cell mass. Polycythemia has primary, secondary and mixed types. Polycythemia Vera (PV), a clonal disorder of hematopoietic stem/progenitor cells, is the most common form of primary polycythemias. PV is a neoplasm with gene mutations leading to overproduction of morphologically and functionally normal blood cells. The perioperative complications of polycythemia include thromboembolic events leading to stroke, acute myocardial infarction, and peripheral vascular occlusions. Patients with PV may also suffer from hemorrhagic complications. Patients with PV with low cardiovascular risk can be treated with aspirin and phlebotomy with a target hematocrit

An 84-year-old woman presented to an outside institution with a 1-month history of generalized malaise, anorexia, abdominal distension, shortness of breath, and unintentional 20-pound weight loss. She had a past medical history of JAK2-positive polycythemia rubra vera, stage 4 chronic kidney disease

Aim: The aim of this retrospective single-centre study was to evaluate whether mutations in the ENG, ACVRL1, and SMAD4 genes were associated with different phenotypes in hereditary haemorrhagic telangiectasia (HHT). Methods: The case records of 21 HHT patients with verified mutations in ENG, ACVRL1, or SMAD4 genes were reviewed. The numbers of HHT diagnostic criteria fulfilled for the three genotypes were compared, as was the prevalence of complications such as iron deficiency anaemia, gastrointestinal haemorrhage, stroke, and cerebral abscess. Results: Our results indicate that mutations in the ENG (HHT1), ACVRL1 (HHT2), and SMAD4 genes result in different HHT phenotypes. Epistaxis debuts earlier and may be more severe in HHT1 than in HHT2. The prevalence of pulmonary arteriovenous malformations (AVM) is higher in HHT type 1, whereas hepatic AVMs are more common in HHT2. One patient with mutations in both ENG and ACVRL1 genes was identified, as were two SMAD4-mutated patients suffering from the overlapping juvenile polyposis-HHT syndrome. Nearly one in five patients in our HHT population has been diagnosed with stroke or cerebral abscess, indicating a high prevalence of cerebral complications. Conclusion: Our results showing that ENG and ACVRL1 gene mutations result in different HHT phenotypes confirm the results from other HHT centres worldwide. Cerebral complications of HHT are common, underscoring the importance of regular screening for pulmonary AVMs and early intervention against such AVMs. We have identified an HHT patient with simultaneous mutations in the ENG and ACVRL1 genes. Surprisingly, this patient has had a mild course of the disease.

Osler's disease is an autosomal dominant hereditary syndrome which belongs to the group of orphan diseases. Affected patients suffer primarily from severe epistaxis. Diagnosis is based on the Curacao criteria and molecular genetic tests. Organ manifestations can be found in the form of arteriovenous shunts in the lung, liver, and gastrointestinal tract; more rarely also in the central nervous system (CNS) and other parts of the body. Many patients with gastrointestinal and other organ manifestations are frequently clinically asymptomatic; therefore, organ screening is essential to avoid later complications and should be performed in centers with particular expertise. No curative therapy currently exists. From the otolaryngologist's perspective, nasal mucosa treatments and endonasal laser applications are important and effective therapeutic approaches to epistaxis. Pharmacological interventions are focused on compensation of haploinsufficiency as well as antiangiogenetic approaches. Severe side effects have to be considered.

Polycythemia vera (PV) is a myeloproliferative disorder most commonly associated with JAK2V617F mutation. Cerebral venous sinus thrombosis (CVST) has a wide range of etiologies and PV is one of them. CVST associated with PV has a poor prognosis. Some patients with classical PV lack JAK2V617F mutation and the molecular basis of JAK2V617F-negative PV is not known. We hereby report a case of a young man who presented with headache, vomiting and altered sensorium and was found to have recurrent CSVT. The patient had primary polycythemia and was subsequently diagnosed to have JAK2-negative PV.

Thromboembolic events and bleeding episodes are the main complications of myeloproliferative neoplasms (MPNs). JAK2V617Fmutation is a known thrombotic risk factor in MPNs, while few data correlate JAK2V617F with bleeding risk. Therefore, the thrombosis/hemorrhage risk reassessment in MPN patients should be reappraised. The aim of our study is to evaluate the impact of JAK2V617V mutation positivity on bleeding complications in MPNs. A cross-sectional study was performed at two tertiary centers in upper Egypt, Assiut and Qena University Hospitals, from January 2019 to December 2020. Newly diagnosed MPN patients underwent history taking, physical examination, basic laboratory work, and molecular assessment of both the JAK2V617Vmutation and Philadelphia chromosome. The cohort included 78 Philadelphia-negative MPN patients, 55% of whom were female, and the median age was 57 (range 40–85). Half of the patients were polycythemia rubra vera (PRV; n=40, 51%), while one-third were primary myelofibrosis (PMF; n=28, 36%), and only 13% were essential thrombocytosis (ET; n=10). The median total leukocytic count (TLC) was 9.6 (range: 0.3–190) × 109/L, median hemoglobin level (HB) was 15 (range: 4–21) g/dl, and median platelet count was 359 (range: 3–2960) × 109/L. Almost half of the patients (n=35; 45%) harbor JAK2V617F. Regarding patients’ clinical criteria based on JAK2V617V mutation, there was no significant difference in itching (6% for JAK2V617F-positive group vs 9% JAK2V617F-negative group, P=0.6) and splenomegaly (71% vs 67%, P=0.8). Erythema was significantly higher in the JAK2V617F-positive group (34% vs 14%; P=0.0008). The main observation was that thrombosis occurred significantly more often in the JAK2V617V-positive group (49% vs 16%; P=0.0003). On the contrary, there was no significant difference in bleeding between the JAK2V617F-positive (23%) and JAK2V617F-negative groups (28%; P=0.6). A multivariate model was performed to identify the significant independent variables that lead to bleeding, which showed that only platelets (odds ratio=1) and splenomegaly (odds ratio=8.5) had significant effects. In conclusion, the data confirmed that JAK2V617V mutation is associated with an increased risk of thrombosis in MPNs, but it does not have a role in increased bleeding risk in MPNs. Large prospective studies are needed to confirm the role of JAK2V617V in bleeding during the course of MPNs and its relation to different lines of treatment.

Key Clinical Message Primary polycythemia (PCV) may coexist in otherwise asymptomatic patients particularly in the presence of unsuspecting conditions such as Thrombotic thrombocytopenic purpura (TTP). In presumed “idiopathic TTP,” autoimmune conditions such as rheumatoid arthritis (RA) should be investigated as a possible etiology for TTP. Standardization of targeted therapy with immunomodulatory agents may be recommended for this subset of patients.

Objective: Polycythemia is a rare and often unrecognized manifestation of a functional gonadotroph adenoma. Although silent gonadotroph macroadenomas are relatively common, functional gonadotroph adenomas are rare.Methods: We report a case of a 66-year-old patient treated for chronic idiopathic polycythemia for at least 10 years, in whom a large pituitary lesion in a cerebral computed tomography (CT) scan was incidentally discovered in a cerebral computed tomography (CT) scan.Results: The patient presented with nasal erythromelalgia and facial erythrosis while being treated with hydroxyurea for primary polycythemia. CT findings and biochemical analyses revealed a large pituitary tumor and increased testosterone and luteinizing hormone (LH) levels. Following resection of the tumor, immunostaining confirmed positive staining for follicle-stimulating hormone and LH, leading to the diagnosis of a functional gonadotroph adenoma. Due to persistent radiologic and biochemical disease after surgical resection, tumoral and secretory control was achieved with combination treatment with long-acting octreotide and cabergolide. Polycythemia was resolved after the initiation of the treatment for the gonadotroph adenoma.Conclusion: This case of a rare LH-secreting pituitary adenoma illustrates that physicians should be aware of rare causes of polycythemia. Testosterone measurement should always be considered, especially in cases of polycythemia of unknown origin. In our case, the combination of treatment with somatostatin analogues and dopaminergic agonists was efficacious in reducing both the secretory and tumoral component that led to resolution of polycythemia.Abbreviations: FSH = follicle-stimulating hormone; Hb = hemoglobin; Hct = hematocrit; IHC = immunohistochemistry; LAR = long-acting release; LH = luteinizing hormone; MRI = magnetic resonance imaging

Case Presentation A 38-year-old male with a prior diagnosis of severe OSA (apnea-hypopnea index [AHI] 99/h) presented for transfer of care. He was successfully titrated to CPAP of 10 cm H2O at an outside laboratory and was compliant with therapy with residual AHI 1.9/h. On presentation, he was polycythemic, with negative evaluation for primary polycythemia, and evaluation for hypoxemia was initiated.

Background Identification of janus kinase 2 (JAK2) mutation even in absence of myeloproliferative disorders (MPNs) was found to be related to venous thromboembolism occurrence. Venous thrombosis screening is not routinely requested in patients with myeloproliferative neoplasms unless the patient is symptomatic. It has been reported that the incidence of thrombosis in elderly patients is much higher than in young patients. The aim of this work was to screen MPN patients for venous thrombosis and study its correlation with JAK2 allele burden and with MPN 10 score. Patients and Methods We enrolled 73 patients with JAK2-positive MPN from our Hematology Clinic in the period August 2015 to Feb 2017. All patients had been screened for thrombosis in the venous system in lower limbs (LLs), upper limbs, portal, and mesenteric systems using color Doppler ultrasound imaging. Results Fifty-three (72.6%) patients were younger than 60 years. Twenty-two (30%) had essential thrombocytosis, 35 (47.9%) had polycythemia rubra vera, and 16 (22%) had idiopathic myelofibrosis. Twenty-seven venous thrombotic attacks were reported in 22 (30.1%) patients. Five (6.8%) had thrombosis in 2 sites. Seventeen (23%) had superior mesenteric and portal vein thrombosis. Six (8%) had iliofemoral (8%) and 4 (5%) had combined LL and portal thrombosis. Eight (10.8%) had active thrombosis at screening. Only 3 patients (4%) were symptomatic with abdominal pain during screening. Pruritis (P = .02) and abdominal pain (P = .039) were significantly different between cases with and without thrombosis. There was no significant difference in MPN 10 score between cases with active or previous thrombosis. Conclusion We recommend routine screening for venous thrombosis in any case of MPN when diagnosed and screening for MPNs in any patient with venous thrombosis especially of the portal vein or atypical sites. If MPN patients present with increasing pruritus or abdominal pain, they also should be screened for venous thrombosis. Further research on a large scale in MPN age groups younger than 60 years regarding pathogenesis of thrombosis is highly recommended.

Introduction The occurrence of primary pulmonary arterial hypertension (PAH (in primary myeloid proliferation neoplasms seems quite high, up to 22% in polycythemia vera. Polycythemia rubra vera (PRV) is one of the myeloproliferative neoplasms. We aimed to study the incidence of PAH among patients with PRV. Patients and methods A prospective cross-section study was performed on 60 (PRV) patients with PRV confirmed by bone marrow and JAK2 positivity. Abdominal ultrasonography, transthoracic echocardiography, and computed tomography chest were done to estimate the pulmonary hypertension (HTN) and exclude other chest diseases. Results Among the studied 60 patients, we found 14 patients with pulmonary HTN (23.4%) who had significantly increased incidence of comorbidities than patients with normal pulmonary pressure (P=0.009). Moreover, there were statistically significant differences in the size of spleen by ultrasound between the two groups (P=0.008). Patients with pulmonary HTN had a higher hemoglobin level compared with those with normal pulmonary pressure (P=0.006). There was a significant positive correlation between pulmonary pressure and existing comorbidities (diabetes mellitus, HTN, or both) but no correlation with the size of the spleen, hemoglobin level, or white blood cells. Conclusion The prevalence of PAH in JAK2-positive patients with PRV is 76.6%, and there was significant relationship between hematological parameters (hemoglobin, white blood cells, lactate dehydrogenase, and urea level and PAH in JAK2-positive patients with PRV.

A 42-year-old male presented with complaints of pain in the left hypochondriac region and diffuse headache and gradual painless loss of vision in both eyes. Ocular examination revealed BCVA was 20/40 in the right eye and 20/60 in the left eye and Grade 5 Papilledema noticed in both eyes. Blood investigation revealed polycythemia and positive JAK2 mutation. Primary polycythemia was diagnosed. Immediate treatment with low molecular heparin was initiated, and regular phlebotomies were performed until the hematocrit dropped to 45%. This case reveals, papilledema as an important sign of polycythemia and as a guide to the diagnosis of cerebral venous sinus thrombosis (CVT).

Background Use of reliable grading scores to measure epistaxis severity in hereditary hemorrhagic telangiectasia (HHT) is essential in clinical routine and for scientific purposes. For practical reasons, visual analog scale (VAS) scoring and the Epistaxis Severity Score (ESS) are widely used. VAS scores are purely subjective, and a potential shortcoming of the ESS is that it is based on self-reported anamnestic bleeding data. The aim of this study was to validate the level of correlation between VAS scores, the ESS, and actual bleeding events, based on detailed epistaxis diaries of patients. Methods Records from daily epistaxis diaries maintained by 16 HHT patients over 112 consecutive days were compared with the monthly ESS and daily VAS scores in the corresponding time period. The Spearman rank correlation coefficient, analysis of variance models, and multiple R2 measures were used for statistical analysis. Results Although the ESS and VAS scores generally showed a high degree of correlation with actual bleeding events, mild events were underrepresented in both scores. Conclusions Our results highlight the usefulness of the ESS as a standard epistaxis score in cohorts with moderate to severe degrees of epistaxis. The use of detailed epistaxis diaries should be considered when monitoring patients and cohorts with mild forms of HHT.

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.

Postoperative pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterized by PG at surgical incisions. It is often misdiagnosed as wound infection, and pathergy may complicate wound debridement. From September 1, 2013, through November 30, 2013, a literature search was conducted of articles published from January 1, 1978, through December 31, 2012. We referenced PubMed, MEDLINE, and Mayo Clinic Libraries using the keywords pyoderma gangrenosum, postoperative pyoderma gangrenosum, postsurgical pyoderma gangrenosum, superficial granulomatous pyoderma, pathergic pyoderma, and pyoderma gangrenosum associated with surgery, incision, breast, and wound dehiscence. In addition, all titles from PubMed with the words pyoderma gangrenosum were reviewed manually for postoperative cases. Of 136 patients, 90 (66%) did not have associated systemic diseases. If a comorbidity was present, hematologic disorders were most common. In addition, 29% (28) of women had predisposing disease vs 53% (19) of men. Women had more frequent breast involvement (P

OBJECTIVE: The Janus associated kinase-2 (JAK2 mutation V617F and exon 12) is detected in most polycythemia vera (PV) patients. It can easily be picked up by real-time polymerase chain reaction (PCR). This technique is easy to perform and is very sensitive requiring minimally invasive techniques. The decision when to order JAK2 mutation test by PCR is important to curb its wastage. To save precious laboratory resources, a peripheral blood finding-based algorithm adjusted to hemoglobin levels of patients (PV) in Pakistan has been purposed, which is a modification of algorithm recently developed by Mahe et al. for the rationalization of JAK2 analysis. METHODS: To assist with the screening of patients being considered for JAK mutation for PV patients in the Pakistani population, we modified clinical decision rule “JAK2-tree” as modified JAK2-tree based on patients' full blood count. RESULTS: We tested both classical and modified JAK2-tree algorithms on two independent data sets, one an unselected population-based sample comprising 51 individuals and other on historical clinical laboratory referral set comprising 51 JAK2-positive cases of PV. Sensitivity for both the algorithms was calculated and compared. CONCLUSION: Our work supports a “modified” decision-tree-based screening approach for Pakistani population to optimize the selection of patients most appropriate for JAK2 V617F testing.

Case Report : We report herein on the case of a 75 years old woman with refractory epistaxis associated with Osler’s disease. Anemia and recurrent epistaxis occurred 10 years previously, and anemia was treated by a physician near the patient’s home. Because she had gradually become unable to control her epistaxis, she visited our hospital. We diagnosed Osler’s disease based on her family history, past history, and dilatory changes in the peripheral and nasal mucosa vessels. A skin graft failed and ultrasonic coagulation was not so effective. The refractory epistaxis was due to a connected arteriovenous fistula of the right upper nasal valve. Following ethanol injection sclerotherapy and an adhesion maneuver, the epistaxis was well controlled.

Objective: To evaluate the frequency of adulthood hematological malignancies in Khyber Pakhtunkhwa population. Material and Method: Descriptive observational study was conducted at diagnostic laboratory Rehman Medical Institute (RMI) and Hayatabad Medical Complex, Peshawar Pakistan, from December 2014 to December 2017. A total of 571 adult patients who suspected to have Hematological malignancies were included in the study. All these patients were examined in clinics by different physicians and referred to pathology department for bone marrow aspiration and trephine biopsy. Two ml of peripheral blood was collected in EDTA vacutainer tube and complete blood count, retic count along with peripheral film examination was done. Bone marrow aspiration and trephine biopsy samples were taken from all patients. Aspiration and trephine biopsy slides were examined and further immunohistochemistry and flowcytometry was done for complete diagnosis. All data was recorded, analyzed and presented in tables. Results: Out of 571 suspected patients, 259 adult patients were diagnosed with different types of hematological malignancies. Out of total 186 (71.8%) were male and 73 (28.2%) were female. The age ranges of studied population were from 18 to 84 year with average age of 46.21 years. Out of them 96 (37.1%) were diagnosed with myeloid hematological malignancies and 163 (62.9%) were diagnosed with lymphoid hematological malignancies. Acute myeloid leukemia (22.3%), acute lymphoblastic leukemia (21.6%) and chronic lymphocytic leukemia (18.9%) were more prevalent hematological malignancies in this region while plasma cell leukemia, polycythemia rubra vera and hairy cell leukemia were least common hematological malignancies were found in adults. The frequencies of other hematological malignancies were lymphoma (10.4%), multiple myeloma (9.7%), chronic myeloid leukemia (7.3%), primary myelofibrosis (2.7%), Myelo dysplastic syndrome (2.7%) and essential thrombocythemia (1.1%) in total hematological malignancies.

Janus Kinase 2 (JAK2) protein controls the signal transduction of the erythropoietin, thrombopoetin, and related receptors that control erythrocyte and megakaryocyte expansion. A somatic mutation of JAK2-V617F in the exon 14 of the JAK2 gene (9p24) is the most common cause of myeloproliferative

Ruxolitinib is the first JAK kinase inhibitor registered for the treatment of primary myelofibrosis and post-polycythaemia vera myelofibrosis and post-essential thrombocytaemia myelofibrosis. The article is a summary of current clinical data with ruxolitinib therapy both in myelofibrosis and in other Ph-negative myeloproliferative neoplasms.

Dear Sir: Cerebral venous thrombosis (CVT) is a rare variety of cerebrovascular disease that can occur at any age and generally has a favorable outcome. However, poor outcome in CVT has been documented [1]. It is caused by a wide range of etiologies, polycythemia is one among them. Polycythemia is a myeloproliferative disorder that is caused by a variety of etiologies [2]. The occurrence of malignant CVT as a presenting manifestation of polycythemia has not been reported so far. Here, we report a 58-year-old man, who presented with status epilepticus and had mixed density lesion in left fronto-parietal region, which rapidly progressed within 24 hours to cause transtentorial herniation, requiring decompressive surgery. A 58-year-old man was brought with history of 2 episodes of generalized tonic-clonic seizures (GTCS) with no regaining of consciousness in between the episodes of 1 day duration. There was preceding history of holocranial headache with vomiting 1 day prior, which lasted for 2 hours and subsided with analgesics. He did not have fever or loose stools. In the emergency room, he had 1 more episode of GTCS. He was a smoker and used to consume alcohol. On examination, he was stuporous. Pupils were equal but reacting sluggishly to light. There was bilateral papilledema. Gaze preference to left was present. Motor examination showed paucity of movement in right upper and lower limb with right plantar extensor response. Hematological investigations revealed high hemoglobin (Hb) level (22 g/dL) and a hematocrit of 57.5%. Total leukocyte and platelets counts were normal. Renal, hepatic and thyroid function tests, serum electrolytes were normal. Computed tomography (CT) brain at admission showed mixed density lesion in left fronto-parietal region with hemispheric edema and anterior inter-hemispheric fissure bleed (Figure 1). Magnetic resonance venography (MRV) brain showed non-visualization of left transverse, sigmoid sinuses and internal jugular vein (Figure 2). Serum homocysteine, protein C, S, anti-thrombin III and factor V leiden levels were normal. Anti-phospholipid and anti-nuclear antibodies were negative. Serum erythropoietin level was normal and JAK2 mutation was negative. Abdominal ultrasonography was normal. Therapeutic phlebotomy was carried out. He was started on heparin anticoagulation and anti-edema measures (mannitol, oral glycerol). Figure 1. Non-contrast CT brain (A) & (B) at time of admission shows bleed in anterior interhemispheric fissure (red arrow) (A); (B) hemorrhagic lesion in left fronto-parietal region with hemispheric edema; (C) At 12 hours after admission shows increase ... Figure 2. MRV brain (A) & (B) showing non-visualization of left transverse, sigmoid sinuses and left internal jugular vein. His sensorium remained the same and repeat CT brain after 12 hours revealed increase in the size of the lesion with mass effect. Anti-edema measure was intensified and was put on ventilator for hyperventilation. He developed pupillary asymmetry within the next 12 hours. Repeat CT brain showed worsening of lesion with mass effect and midline shift suggestive of trans-tentorial herniation (Figure 1). Patient was taken up for emergency decompressive craniectomy. There was no improvement in sensorium following surgery. Post operative Hb level was 16 g/dL. Within the next 24 hours, his Hb level rose to 21 g/dL. Therapeutic phlebotomy was carried out. The expertise for endovascular intervention was not available. Patient succumbed to illness within 36 hours of surgery. A wide range of etiologies have been implicated in the causation of CVT. Hypercoagulable disorders, like factor V Leiden mutation, presence of anticardiolipin antibody, antithrombin gene mutation and myeloproliferative neoplasms like polycythemia vera and essential thrombocythemia are one among them [2,3]. Thrombosis is a serious complication of polycythemia and can lead to death in up to 8.3% of patients as reported by Ferro et al. [4]. Polycythemia can be primary (caused mainly by mutation in the JAK2 gene) or secondary [5]. Chronic hypoxia causes secondary polycythemia by increasing serum erythropoietin levels leading to excess production of erythrocytes from the bone marrow [6]. Polycythemia causes stasis of blood that result in hyperviscosity leading to the development of thrombosis. Thrombosis of cerebral veins or sinuses results in raised venular and capillary pressure. As local venous pressure rises, there is decrease in cerebral perfusion causing ischemic injury and cytotoxic edema. Along with cytotoxic edema, disruption of the blood-brain barrier leads to vasogenic edema, and venous and capillary rupture culminates in parenchymal hemorrhage. Thrombosis of cerebral sinuses impairs CSF absorption, leading to increased intracranial pressure. Consequently, increased intracranial pressure worsens venular and capillary hypertension and contributes to parenchymal hemorrhage and vasogenic and cytotoxic edema [7]. CVT has a favorable outcome with timely diagnosis and intervention. However, unfavorable outcome do occur. Factors related to acute mortality in CVT includes advanced age, disturbed consciousness, focal neurological deficits, recurrent seizures, and hemorrhagic infarct [8]. In the prospective International Study on CVT (ISCVT) cohort of 624 patients, death occurred in 8% and moderate to severe disability in 5.1% of patients, despite the use of anticoagulant treatment [4]. Transtentorial herniation is the most frequent cause of death. Endovascular treatment appears to be reasonably safe and can be considered in severe cases that do not respond to heparin therapy. However, impending transtentorial herniation does not benefit from endovascular thrombolysis and needs cranial decompressive surgery. But, Coutinho et al. [9] reported successful treatment of CVT with impending herniation with decompressive hemicraniectomy followed by endovascular thrombosuction. Malignant CVT refers to supratentorial cortical lesions attributable to superficial venous system thrombosis with or without sinus involvement; with clinical or radiological signs of transtentorial herniation; either at onset or after worsening despite anticoagulation [10]. In a series by Theaudin et al. [10] regarding the performance of decompressive surgery in malignant CVT, none of the 12 patients with malignant CVT had polycythemia as a risk factor. The only identifiable risk factor for CVT in our patient was polycythemia. Even though JAK2 mutation results were negative, primary polycythemia cannot be ruled out as 20% of cases of polycythemia vera possess a negative JAK2 mutation, and serum erythropoietin levels were normal. Bone marrow studies could not be done in view of poor general condition. The possible etiology for polycythemia may be smoking. Smoker’s polycythemia presenting as CVT is uncommon, and there is a paucity of evidence suggesting such an association. Smoker’s polycythemia is diagnosed after exclusion of other causes of primary polycythemia, such as JAK2 mutation and erythropoietin level. Polycythemia is one of the causes for occurrence of the CVT. However, the occurrence of malignant CVT in association with polycythemia has not been reported so far.

Background Polycythemia rubra vera (PV), being a primary polycythemia, is caused by neoplastic proliferation of erythroid, megakaryocytic and granulocytic lineages which result in panmyelosis. PV patients have a somatic acquired mutation in the Janus kinase (JAK2) pathway, rendering cell proliferation independent of the normal regulatory mechanisms that regulate erythropoiesis. The rational of this study was to determine the prevalence of the JAK-2 V617F mutation in Pakistani patients with PV. Materials and methods In this cross sectional study, 26 patients with PV were enrolled from January 2010 to December 2014. Patients were diagnosed based on WHO criteria for PV. All were screened for G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by an allele specific PCR. Results The mean age was 53.4±9.31 years (range 36-72) and the male to female ratio was 2:1. The frequency of JAK2 V617F positivity in our PV patients was found to be 92.3%. Overall 30.7% of patients were asymptomatic and remaining 69.3% presented with symptomatic disease. The mean hemoglobin was 18.1±1.9g/dl with the mean hematocrit of 55.6±8.3%. The mean total leukocyte count was 12.8±7.1x109/l and the platelet count was 511±341.9x109/l. A positive correlation of JAK2 V617F mutation was established with high TLC count (P=0.01). No correlation of JAK2 V617F could be established with age or gender (P>0.05). Conclusions The JAK2 V617F mutation frequency in our PV patients was similar to those reported internationally. Screening for the mutation in all suspected PV cases could be beneficial in differentiating patients with reactive and clonal erythrocytosis.