A Case of Thrombotic Vasculopathy in the Setting of High-Dose Hydroxyurea Use

This case study describes the presentation of a 76-year-old male with a past medical history that included atrial fibrillation, essential hypertension, coronary artery disease status post cardiac stent placement, heart failure, hyperlipidemia, thyroid cancer (with thyroid resection resulting in hypothyroidism), prostate cancer status post brachytherapy (in remission), and a history of JAK2-positive myeloproliferative disease. He presented with painful areas of hyperpigmentation appearing as purple discoloration to his neck, lower abdominal skinfold, and bilateral groin areas that progressed to painful ulcerations a few weeks after a myocardial infarction. Due to the patient’s multiple medical conditions and uncommon presentation of wounds, a multidisciplinary team was involved in his care. Differential diagnosis included antiphospholipid syndrome, symmetrical drug-related intertriginous and flexural exanthema, warfarin-induced necrosis, cutaneous thrombotic vasculopathy, myeloproliferative disorder, and high-dose hydroxyurea therapy. It was determined by the authors that the high-dose hydroxyurea therapy was the cause of the wounds. Because of the patient’s initial health status, treatment of the wounds included use of collagenase and sodium hypochlorite solution to reduce the risk of infection and attempt to promote autolytic debridement until surgical wound debridement could be done. The patient required multiple hospital stays, but ultimately his health status improved and the wounds resolved with the assistance of the combined efforts of the multidisciplinary team to diagnose and treat this complex patient and his uncommon wound presentation.

Guideline for management of non-Down syndrome neonates with a myeloproliferative disease on behalf of the I-BFM AML Study Group and EWOG-MDS

Not available.

Chronic Myeloid Leukaemia Presented with Extreme Isolated Thrombocytosis

CML presenting with isolated extreme thrombocytosis is rare. We reported a 47 years old man who presented with history of right sided lower abdominal pain, vomiting, significant lethargy and chest tightness. Patient was mildly anaemic and abdominal examination revealed no organomegaly. On investigation, he was found to have extreme thrombocytosis (2050x109/L) and mild leucocytosis (31.7 x109/L) with mild anaemia. In view of extreme thrombocytosis, he was investigated for myeloproliferative disease especially essential thrombocythemia. He was found to be positive for BCR-ABL by reverse transcription PCR (RT-PCR) and negative for JAK2, CALR, MPL mutations. Ultimately, he was diagnosed as a case of CML with an atypical presentation. He received imatinib 400 mg/day and achieve complete haematological response at 15 days.

Functional State of Liver in Patients with Progressing Chronic Myeloid Leukemia

Chronic myeloid leukemia is found in approximately 20% of newly diagnosed cases of leukemia in adults. In Europe and North America, chronic myeloid leukemia ranks third among leukemias (after acute leukemias and chronic lymphoblastic leukemia). The problem of diagnosis, treatment, rehabilitation and adaptation of patients with chronic myeloid leukemia is relevant, as there is a gradual increase in the incidence of this disease both in the world and in our country. Some progress has been achieved in the treatment of patients with oncohematological diseases, in particular chronic myeloid leukemia. Chronic myeloid leukemia is a clonal myeloproliferative disease in which as a result of specific translocation of chromosomal sites between 9 and 22 chromosomes, a khimeric BCR-ABL gene with tyrosine kinase activity is formed. The purpose of the study was to investigate the main biochemical parameters that characterize protein and pigment metabolism, the activity of key enzymes in patients with chronic myeloblastic leukemia at different stages of the disease for further prospects of optimizing diagnosis, predicting the course of the disease in clinical practice. Materials and methods. The functional state of liver in 77 patients at different stages of chronic myeloid leukemia was studied. All patients admitted to the hospital were examined with the use of clinical, laboratory, instrumental and special research methods, and were consulted by specialists of related specialties, if necessary. The main biochemical parameters that characterize protein and pigment metabolism, the activity of key enzymes in patients with chronic myeloid leukemia of peripheral venous blood was determined by the method of V. Menshikov (1987). Results and discussion. The content of biochemical parameters that characterize protein and pigment metabolism, the activity of key enzymes in patients with chronic myeloid leukemia has been studied. It was found that biochemical parameters that characterize protein and pigment metabolism, the activity of key enzymes in patients with chronic myeloid leukemia is associated with an increase in the studied indicator (p<0,05). The article discusses the possible causes and pathogenetic mechanisms of the identified changes. As the disease progressed the changes of protein, pigment and enzyme kinds of metabolism were revealed. The article discusses possible pathophysiological mechanisms of the identified changes. Conclusion. In patients with chronic myeloid leukemia, there is an imbalance in protein, pigment metabolism, and the activity of some liver enzymes. With the progression of chronic myeloid leukemia, the functional state of the liver deteriorates

Structural and functional analysis of target recognition by the lymphocyte adaptor protein LNK

The SH2B family of adaptor proteins, SH2-B, APS, and LNK are key modulators of cellular signalling pathways. Whilst SH2-B and APS have been partially structurally and biochemically characterised, to date there has been no such characterisation of LNK. Here we present two crystal structures of the LNK substrate recognition domain, the SH2 domain, bound to phosphorylated motifs from JAK2 and EPOR, and biochemically define the basis for target recognition. The LNK SH2 domain adopts a canonical SH2 domain fold with an additional N-terminal helix. Targeted analysis of binding to phosphosites in signalling pathways indicated that specificity is conferred by amino acids one- and three-residues downstream of the phosphotyrosine. Several mutations in LNK showed impaired target binding in vitro and a reduced ability to inhibit signalling, allowing an understanding of the molecular basis of LNK dysfunction in variants identified in patients with myeloproliferative disease.

Myeloproliferative Disease: Dealing With a Diagnostic Dilemma

Myeloproliferative neoplasms (MPNs) constitute a group of hematologic clonal diseases that affect one or more myeloid lineages with abnormal proliferation. It is rare disease entity and incidence is about 1.15 to 4.99/100 000 person-years among hematological neoplasms for all subtypes of MPNs combined. Patients who present with hepatosplenomegaly, hyperleukocytosis with monocytosis should have routine tests along with bone marrow morphology possibly biopsy, quantiferon TB Gold in tube test, Dengue fever IgM, IgG, NS-1 antigen, cytogenetics t(9;22), BCR cABL fusion gene, JAK-2 V617F, MPL mutations, CALR gene test done along with karyotyping and flowcytometry to evaluate and establish diagnosis towards management.

Head and Neck Reconstruction in Patients with Polycythemia Vera: Case Series and Literature Review

Background Polycythemia vera (PV) is a myeloproliferative disease with overproduction of erythrocytes, leukocytes, and platelets causing an increased risk of both thrombosis and hemorrhage. There are limited reports and no established guidelines for managing such patients undergoing reconstructive surgery. Methods We present four patients with PV and head and neck cancer who required reconstruction after resection and provide a review of the current literature. Results Preoperatively, patients on cytoreductive therapy continued with their treatment throughout their hospital course and had hematologic parameters normalized with phlebotomy or transfusions if needed. Two patients who underwent free flap surgery (cases 1 and 2) had postoperative courses complicated by hematoma formation and persistent anemia, requiring multiple transfusions. Cases 3 and 4 (JAK2+ PV and JAK2− PV, respectively) underwent locoregional flap without postoperative complications. Conclusion Concomitant presentation of PV and head and neck cancer is uncommon and presents unique challenges for the reconstructive surgeon. Overall, we recommend that patients should have hematologic parameters optimized prior to surgery, continue ruxolitinib or hydroxyurea, and hold antiplatelet/anticoagulation per established department protocols. It is essential to engage a multidisciplinary team involving hematology, head and neck and reconstructive surgery, anesthesia, and critical care to develop a standardized approach for managing this unique subset of patients.

912 Unusual Presentation Of JAK-2; A Degenerating Breast Neurofibroma

Introduction 29-year-old lady presented to ED with acutely enlarging painless right breast swelling. No history of trauma; diagnosis likely breast abscess. Significant growth during short inpatient admission with incidental clinical finding of multiple cutaneous skin nodules from childhood, mother had similar lesions. CT chest performed illustrating large anterior chest wall mass 15.2x15.7x24.7cm. Transferred to regional plastic surgery unit for resection. Haematological abnormality identified on routine bloods which was life changing. Description Attended ED following a three-day history of a rapidly progressive right breast mass causing necrosis and blistering of overlying skin with drop in haemoglobin from 138 to 94 overnight. Transferred to regional plastic surgery unit where she underwent an evacuation of breast haematoma and excision of neurofibroma and was transfused 2 units of blood. Pathology revealed a degenerating neurofibroma. Abnormal coagulation and blood film during inpatient stay prompted subsequent bone marrow biopsy which revealed diagnosis of myeloproliferative neoplasm later found to be JAK-2 V617F mutation positive. Discussion Patient moved to UK 6 years ago from Lithuania, previously lived within area affected by Chernobyl nuclear disaster. JAK-2 myeloproliferative disease typically presents in middle aged but also reported as radiation acquired. Risk benefit of anti-platelet therapy for myeloproliferative malignancy evaluated due to high probability of re-bleeding. Complex case of Neurofibromatosis-1 and Myeloproliferative disease; diagnosis presented as a breast lump. Multidisciplinary input from surgery, haematology, genetics and neurology for best outcome.