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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.

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.

Three reports recently presented clinical data and comments on a 65-year old woman in whom hereditary haemorrhagic teleangiectasia (HHT; Osler's disease) and hepatocellular carcinoma (HCC) coincided, leading to listing for liver transplantation (LT) (1-3). Consensus existed on the usefulness of LT in patients with HHT, particularly when complicated by HCC, but there was debate over the right timing for LT in such patients who are usually well besides the complications of vascular malformations (VM). This article is protected by copyright. All rights reserved.

Thoracic aortic mural thrombus (TAMT) is a rare pathology and potential source of cerebral, visceral, and peripheral emboli. We present a 62-year-old male in a hypercoagulable state due to primary polycythemia vera (PV) developed TAMT and catastrophic thromboembolisms despite aggressive medical and surgical management. The outcomes and adverse events of endovascular exclusion of TAMT in the presence of PV are unknown. We would recommend proceeding with extreme caution when performing endovascular exclusion of TAMT, as PV may be a prohibitive risk.

Arterial catheterization is an invasive technique commonly used for continuous monitoring of arterial blood pressure and for analysis of arterial blood gases. Arterial catheterization is a relatively safe procedure; however, vascular occlusion and ischaemia is a known complication of the procedure. We experienced a case of microvascular disease in the hand of a patient who underwent radial artery catheterization and was diagnosed with polycythemia vera during treatment.

Osler's disease, also known as hereditary hemorrhagic telangiectasia (HHT) and Osler-Weber-Rendu syndrome, is an autosomal dominant disorder leading to abnormal blood vessel formation in the skin, mucous membranes and often in organs, such as the lungs, liver and brain (arteriovenous malformations AVM). Various types are known. Patients may present with epistaxis. Teleangiectasia can be identified by visual inspection during physical examination of the skin or oral cavity or by endoscopy. Diagnosis is made after clinical examination and genetic testing based on the Curacao criteria. Modern imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI) have become more important as they can depict the AVMs. Pulmonary AVMs can be depicted in CT imaging even without the use of a contrast agent while other locations including the central nervous system (CNS) usually require administration of contrast agents. Knowledge of possible clinical manifestations in various organs, possible complications and typical radiological presentation is mandatory to enable adequate therapy of these patients. Interventional procedures are becoming increasingly more important in the treatment of HHT patients.

CASE REPORT A 72-year-old woman with a 30-year history of iron deficiency anaemia was admitted for fatigue and increasing weakness. On physical examination, the patient appeared dyspneic and pallor. The tongue showed angiodysplasias. Laboratory analysis showed a microcytary anaemia with an iron deficiency. Firstly a routine ultrasound examination (iU22, Philips Medical Systems) was performed. A left accessory artery, a dilated common hepatic artery and ectatic tortuous intrahepatic liver arteries were found. A contrast-enhanced ultrasound (CEUS) detected two intrahepatic arteriosystemic shunts in the left liver lobe. Endoscopy revealed multiple angiodysplasias of the stomach and the duodenum, 4 isolated angiodysplasias in the colon and telangiectasias in the oropharyngeal region. The angiodysplasias were treated with argon plasma coagulation. Osler's disease was diagnosed based on the Curacao criteria. CONCLUSION Transabdominal B-mode sonography in combination with colour Doppler, pulsed wave Doppler and contrast-enhanced ultrasound is a very important tool to detect hepatic vascular malformations. It is an excellent procedure for the screening of patients with an iron deficiency anaemia. For the first time, we have demonstrated CEUS as an additional approach in the diagnosis of liver involvement in patients with Osler's disease.

Anamnese und klinischer Befund: Eine 38-jahrige Patientin wurde wegen progressiver Kopfschmerzen, einhergehend mit Sehstorungen am rechten Auge seit mehr als 24 Stunden sowie einer zunehmenden Sprachstorung und Schwache des rechten Armes aufgenommen. Das klinische Bild mit milder, armbetonter Hemiparese rechts sowie expressiver Aphasie legte den Verdacht auf eine intrakranielle Raumforderung nahe. Untersuchngen: Im Schadel-CT wurde frontoparietal links eine 2,5 cm grose Raumforderung mit perifokalem Odem und einer Mittelstrukturenverschiebung festgestellt, die einen Hirnabszess oder Hirntumor vermuten lies. Die Kernspintomographie bestatigte einen Hirnabszess. Therapie und Verlauf: Es wurde eine parenterale Antibiotikatherapie mit Metronidazol 1,5 g/d und Chloramphenicol 8 g/d eingeleitet und notfallmasig eine Kraniotomie mit Abszessevakuation vorgenommen sowie bei progredientem Abszess eine zweite Kraniotomie. Mikroskopisch fanden sich grampositive Kokken (spater als Streptococcus constellatus identifiziert), gramnegative Stabchen (spater als Aggregatibacter aphrophilus identifiziert) und Fusobacterium spp. Da ein polymikrobieller Hirnabszess typischerweise durch pulmonale arteriovenose Malformationen (AVM) ausgelost werden kann, wurde elektiv eine CT-Angiographie der Lunge durchgefuhrt. In den kaudalen Lungensegmenten stellten sich kleine AVM dar, die komplikationslos embolisiert wurden. Erst retrospektiv wurden bei der Patientin kutane Teleangiektasien erkannt. Zurzeit unterziehen sich die Patientin und ihre Familienmitglieder einer genetischen Testung. Folgerung: Der Morbus Rendu-Osler-Weber (hereditare hamorrhagische Teleangiektasie, HHT) ist eine seltene vererbte Erkrankung. Wie im beschriebenen Fall kann ein polymikrobieller Hirnabszess zur Diagnose einer HHT fuhren.

This immunohistochemical study of estrogen and progesterone receptors could not confirm a significant expression in nasal telangiectasias. Thus, a specific effect of these hormones or anti-hormone therapy on malformed nasal vessels has to be questioned and only offered under strict clinical control.The efforts to control recurrent epistaxis in hereditary hemorrhagic telangiectasia (HHT) using alternative methods are very intense. Hormone or anti-hormone therapy has frequently been postulated and the reported results are controversial. Therefore it was important to find an explanation regarding a possible impact of hormonal therapies by immunohistochemical evaluation of progesterone and estrogen receptor expression on nasal telangiectasias of affected patients.Tissue samples of nasal mucosa with evidence of telangiectasias from 14 patients with HHT were analyzed for the expression of progesterone and estrogen receptors on the nuclei of endothelial cells of the malformed vessels using immunohistochemistry.Progesterone receptors were not detected in any of the cases and only two cases showed a weak expression of estrogen receptors with an immunoreactive score of 2/12.

Extramedullary hematopoiesis in central nervous system is a rare condition that can present in association with hematologic conditions. In this single-center retrospective study from 1988 to 2010, we identified 8 cases of extramedullary hematopoiesis involving the central nervous system or meninges. Most were incidental autopsy findings, usually microscopic collections of cells in the meninges or around blood vessels in the brain of infants (4 cases; age, 10 days to 5 months), in 1 young child (age, 6.5 years with anemia), and 1 elderly adult (age, 81 years with end-stage idiopathic myelofibrosis). Two individuals (both with polycythemia rubra vera) presented with symptomatic intracranial or spinal canal lesions (age, 67 and 68 years). Mixed populations of immature hematopoietic cells were identified by characteristic morphology and appropriate immunohistochemistry. The precise pathogenesis of extramedullary hematopoiesis in central nervous system is unknown. In infants, extramedullary hematopoiesis is unlikely to be pathologic and most likely represents a resolving fetal state. The older children and adults with incidental or symptomatic extramedullary hematopoiesis usually have some underlying hematologic condition, which should be sought if not already recognized.

AIMS AND OBJECTIVES- This study was done to study the various etiologies associated with stroke in young , the Neurodeficit on admission and the outcome of the stroke. MATERIALS AND METHODS- A detailed history and risk factor evaluation and neurological examination was done .Total 50 patients of age group 15 - 45 years were studied for 24 months. . Exclusion criteria -trauma and SOL. Inves- tigation were done to elicit the possible causes of the stroke. Investigations: Hematological, biochemical and Serological tests like VDRL, RA, HIV ELISA were done . ECG, CXR, CT / MRI, 2D ECHO were done in all patients.. MR Angiography, MR venography CSF analysis ,Prothrombin time, APLA, ANA, Anti ds DNA Lipid profile, Blood culture and sensitivity, USG abdomen, Bone marrow studies, CT thorax, Colour Doppler, TEE, and DSA were done according to the indications. OBSERVATIONS- Commonest age group 20 - 30 years.Right hemiplegia was the commonest neurodeficit , subtypes were : Thrombotic 28%, Embolic 36 % , hemorrhagic 10% and Cortical Venous sinus thrombosis 26%.Female patients predomi- nated in all subtypes of strokes. Ischaemic stroke constituted 64% of total stroke. Cardiogenic embolic stroke constituted 60%, of these and .RVHD and its complication accounted for majority of cases .Other etiologies were tuberculous vascu- litis,1, lupus vasculitis 2,, hyperhomocysteinemia ,1 sickle cell disease 1, postpartum CVST 10,, polycythemia rubra vera 1, protein C & s def 1, AV malformation1, Moya Moya disease 1, and preeclampsia 1. Cause could not be identified in 8% cases . Mortality was 20% and was common with hemorrhagic stroke (40%) Prognosis was best in CVST and embolic stroke. CONCLUSION-strokes are common in young adults and knowing the right etiology will help in better management.

Background. Chronic myeloproliferative neoplasms are derived from myeloproliferation of a single hematopoietic stem cell and result in either erythrocythemia or thrombocytosis. Polycythemia Vera (PV) is defined by persistent proliferation of red cell mass in the peripheral blood and bone marrow with hemoglobin more than or equal to 16.5 gr/dL (49% Hematocrit) in males and 16 gr/dL (48% Hematocrit) in females. Around 98% of patients with PV harbor an acquired Janus Kinase 2 mutation, namely JAK2V617F. Other well described mutations in PV patients include the EPOR gene, Hypoxia-inducible factor 2 alpha (HIF2A) gene, PHD2 gene mutations and the rare Hemoglobin Tarrant. These mutations and other identified predisposing gene variants have all accounted for familial cases of PV. Presence of specific mutations can be associated with increased risk of myelodysplastic syndrome, progression of disease, and neoplasms which causes a decreased overall survival. Methods: We reviewed the charts and collected clinical information of 3 generations of one family with erythrocythemia, including PV diagnostic testing. Results: The proband, a 3-year-old female, presented to our clinic at 6 months of age with a hemoglobin of 16 gr/dL (upper limit of normal for age is 12.5 gr/dL). Family consisted of 3 generations of related females (maternal grandmother, mother and daughter) with the clinical characteristics of PV as described above, requiring frequent phlebotomy. Genetic testing, for known PV mutations, on the proband revealed no identifiable mutations, similar to the mother's and grandmother's prior genetic testing. The proband had no other laboratory abnormalities, and a bone marrow biopsy and aspirate examination was normal. Now 3 years of age, she has been undergoing phlebotomy every 3 months since diagnosis; further testing with exome gene sequencing showed c.136G>A mutation on EPO gene, a variant of unknown significance. Discussion. Literature review showed 2 previous reports of c.136G>A mutation in the EPO gene. In 2015, Taylor et al described the mutation in two families with erythrocytosis. Their project was aimed at evaluating whole-genome sequencing for diagnosis of families with high suspicion of a genetic component to their clinical presentation with no previously identified pathogenic variants. They concluded that c.136G>A is of autosomal dominant inheritance. Later described in 2016 by Camps et al., the variant was also found in 4 different non-related patients after whole genome sequencing. None of the previous citations demonstrated causality. Determination of predisposing gene mutations, using exome gene sequencing specifically for families with an unknown mutation may help clinicians with prognosis, genetic counseling, and possibly specific treatments. Although an interesting result, a causality between the variant identified and the patient in this report has not yet been verified. Therefore, more testing and reports of this mutation are needed. Further steps in our case will include whole exome sequencing of the proband's family members with idiopathic erythrocytosis to assess the presence of this variant in the whole family. Identification of a specific familial inherited gene mutation resulting in PV can help classify patients based on the mutation. This will help predict disease course, improve quality of life and determine risk of disease transformation. Disclosures No relevant conflicts of interest to declare.

Introduction: Myeloproliferative Neoplasms (MPNs) represents a disorder that involves abnormal proliferation of cells originating from the myeloid line. The proliferation of these cells can lead to complications that are at times fatal. Despite its potential to cause life threatening complications, there is little data on this disease in Southeast Asia. As Singapore is a multiracial country in Southeast Asia, there may be some disease characteristics exclusive to patients here due to its unique population composition. The data from this Southeast Asian cohort would be useful to determine disease homogeneity in Asian countries. Methods: A retrospective review of the MPN database from National University Hospital, Singapore (NUHS) revealed 320 patients who were clinically diagnosed with MPN from 2008 to 2017. This data included patients with Essential Thrombocythemia (ET), Polycythemia Rubra Vera (PRV), Primary Myelofibrosis (PMF), Myeloproliferative Neoplasm, unclassifiable (MPN-U) and Chronic Eosinophilic Leukemia (CEL) (Figure 1A) as per the 2017 WHO classification. For this analysis, we included only the classical Philadelphia chromosome negative MPN and focused on the epidemiology, transformation and overall survival rate. Results: There was a slight male predominance with a male to female ratio of 1.3:1. The ethnic groups within this cohort consisted of 65.8% ethnic Chinese, 20.7% Malay, 5.5% Indian and the rest were made up of other ethnic groups within the region such as Eurasians, Thai, Filipinos, Burmese, Indonesians, Bangladeshi, Vietnamese and Arabian patients. The mean age at diagnosis for this group was 60.5. The mean age was 59.2 years for ET, 61.2 for PRV and the mean age of PMF was the oldest at 63.8. The mean age of diagnosis for ET and PMF patients in our cohort was slightly older compared to the Korean cohort (55.4 and 59.5 years) (Byun, et al., 2016). The majority of this cohort was made up of ET patients (53.1%) followed by PRV (35.3%) and PMF (11.6%). 77.5% of these patients were JAK2 V617F mutation (JAK2) positive. The percentage of patients who were JAK2 positive for ET, PRV and PMF were 69.2%, 96.9% and 56.3% respectively. The percentage of JAK2 positive patients for the three subtypes were higher in our local population compared to the Chinese and Japanese cohorts. Only 120 patients were tested for Calreticulin Exon 9 (CALR) mutations as this molecular test was only available in our institution from 2015 onwards. ET patients make up 68.4% of CALR positive patients. It was noted that CALR positive patients had comparatively higher mean platelet counts of 925.2 than CALR negative patients with mean platelet counts of 691.7. This phenomenon is seen in both CALR positive ET and CALR positive MF patients. In the 10-year period, 25 patients were lost to follow up and 8 patients transferred their care to another institution. Overall, 27 patients were deceased, with a mean survival of 3.5 years. The death-to-case ratio was 11.5 per 100 cases. The death-to-case ratio for ET, PRV and PMF is 6.1 per 100, 8.2 per 100 and 31.3 per 100 respectively. During this period, only 6 patients had transformation. Three patients progressed to post-ET myelofibrosis and 3 had leukemic transformation. Those who had leukemic transformation were initially diagnosed with PRV (1 patient) and PMF (2 patients). All patients who had leukemic transformation were deceased and had a mean survival of 1.4 years from the transformation event. Conclusion: Whilst there were some observable differences between our data and existing Asian data, there is still insufficient information to determine disease homogeneity. This is partly due to the rapid growth of molecular knowledge in this field and the regular revision of the WHO diagnostic criteria of MPNs over the last decade or so. There needs to be coordinated efforts within the region to ensure that our patients have equal access to these diagnostic platforms and that they receive an accurate diagnosis. Disclosures Chng: Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Aslan: Research Funding; Merck: Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, accommodation, expenses; Celgene: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel, accommodation, expenses.

INTRODUCTION: Cerebral venous thrombosis is a rare initial presentation of polycythemia. If diagnosed early, treatment can reduce mortality and morbidity significantly. Often it may present with headache as the only complaint, and thus the diagnosis is likely to be missed. CASE PRESENTATION: A medically stable 31-year-old male, a chronic smoker with a ∼17 pack-year history of smoking, was admitted to the emergency room with a 2-week history of gradually worsening, severe, throbbing headache in the occipital region sensitive to light. Initial neurological examination was positive only for some involuntary motor tics of the left leg. Initial laboratory workup showed hemoglobin of 20 g/dl and hematocrit of 56.5%. The carboxyhemoglobin level was normal, but the oxygen dissociation curve was shifted to the left. Further evaluation by MRI and MRA of the brain suggested extensive and complete thrombosis of the superior sagittal sinus, right transverse sinus and right sigmoid sinus with a small venous infarct in the right parafrontal region. Given that the patient first presented with a thrombotic event, workup for primary polycythemia and hypercoagulable disorders was carried out, including JAK2 mutation evaluation, which was negative. This left us with smoking as the only risk factor and possible cause for secondary polycythemia. He improved significantly with phlebotomy and anticoagulation treatment. CONCLUSION: This case illustrates a rare but severe complication of secondary polycythemia stressing the importance of being aware of the risk of developing cerebral thrombosis in patients with chronic smoking exposure.

Pyoderma gangrenosum (PG) is a rare, noninfectious neutrophilic dermatosis. Clinically, it begins with sterile pustules that rapidly progress into painful ulcers of variable depth and size with undermined violaceous borders. The diagnosis of PG is based on the history of an underlying disease, a typical clinical presentation, histopathology, and exclusion of other diseases. The peak incidence occurs between the ages of 20 to 50 years with women being more often affected than men. There have been very few reports of pyoderma gangrenosum with oral mucosal involvement. Oral lesions in previously reported cases have included ulcers of varying sizes from a few mm to several cm and have been reported to have been found on the tongue, soft and hard palate, buccal mucosa, and gingiva. Some of these oral lesions have been associated with ulcerative colitis, inflammatory bowel disease, and polycythemia rubra vera. A few cases were reported with biopsy findings, the histological picture being nonspecific, showing ulceration, and necrosis with inflammatory cell infiltrate. A peculiar case of pyoderma gangrenosum with an oral lesion is presented here, and the differential diagnosis is discussed.

A patient with Osler's disease (hereditary haemorrhagic telangiectasia) was admitted to hospital because of obstinate, profuse conjunctival bleeding occurring without any known preceding trauma. Extensive examination of the haemostatic mechanism revealed an impaired platelet function reflected in defective platelet aggregation by ADP, collagen, adrenalin and defective clot retraction. This platelet dysfunction, whose association with conjunctival telangiectasia was hitherto unknown, impaired the patient's already deficient primary haemostasis following the vascular anomaly and apparently contributed to the severity of the bleeding which could only be checked surgically. The findings seem to warrant investigation of the platelet function in patients with Osler's disease. In the event of platelet dysfunction drugs, such as acetylsalicylic acid (aspirin), indomethacin, dextrans as well as transfusions with bank blood are contra-indicated.

In the investigation of haemostasis in a 37-year-old woman with Osier's disease the Ivy bleeding time proved to be prolonged. Platelet adhesiveness, measured both by Hellem's and Salzman's methods, was decreased and platelet aggregation was clearly reduced after addition of ADP, but only slightly after collagen and epinephrine. Platelet factor 3 activity was normal, as was clot retraction. The therapeutic consequences of the platelet defect, including the risk of using drugs affecting platelet function, are stressed. It is concluded that in cases of Osier's disease the possibility of functional disorders of platelets should be borne in mind.