Myeloproliferative neoplasm (MPN) patients are at risk of splanchnic vein thromboses (SVT). Prior studies have failed to demonstrate a benefit of hydroxyurea therapy in preventing recurrent thrombosis after SVT, but are limited by small sample sizes and inability to account for starting, stopping, or switching of cytoreductive therapies. To better assess the impact of cytoreductive therapy on thrombosis recurrence, we performed a retrospective cohort study of MPN-SVT patients from the international GASTRO-MPN Consortium, treating cytoreductive therapy as a time-dependent covariate. We identified 757 patients, of which 43% were treated with cytoreductive therapy. During a median follow-up of 7.4 years, 256 patients (34%) had thrombosis recurrence; 145 (19%) had SVT extension/recurrence/TIPS thrombosis, 138 (18%) an thrombosis recurrence outside the splanchnic bed (74% were venous). Additionally, 262 patients (35%) experienced clinically relevant bleeding and 170 (22%) died. After adjusting for age, sex, prior thrombosis, timing of MPN diagnosis relative to SVT, anticoagulation initiation within 30 days of SVT diagnosis, MPN type, JAK2 status, other cancers and cirrhosis, cytoreductive therapy was associated with a decreased risk of recurrent thrombosis (HR 0.67 95%CI 0.50-0.89, p=0.01). This was driven by a lower risk of SVT extension/recurrence (HR 0.62 95%CI 0.42-0.90, p=0.01) but not by extra-splanchnic thrombosis recurrence (HR 0.97 95%CI 0.72-1.30, p=0.82). In a subgroup of patients without erythrocytosis/thrombocytosis at initial SVT (n=275), cytoreductive therapy was associated with a HR 0.65 (95%CI 0.40-1.07, p=0.09) for recurrent thrombosis. These data support the use of cytoreductive therapy in MPN-SVT patients to prevent recurrent thrombosis, particularly SVT extension/recurrence.

Not available.

Primary immune thrombocytopenia (ITP) in pregnancy presents significant therapeutic challenges, particularly when refractory to standard treatments such as corticosteroids, intravenous immunoglobulin, and immunosuppressants. Data on thrombopoietin receptor agonists (TPO-RAs) during pregnancy remain scarce. This study reports four pregnancies in three women with refractory ITP who received Romiplostim during gestation. All cases were retrospectively analyzed, with detailed documentation of treatment courses, platelet trajectories, and maternal and neonatal outcomes. Romiplostim was introduced in the second or third trimester at doses ranging from 3.1 to 6.25 µg/kg/week, following inadequate response to conventional therapy. All patients demonstrated hematologic improvement, often within one to two weeks of initiation, enabling corticosteroid tapering and preparation for delivery. Delivery outcomes were favorable, including four term vaginal deliveries without major hemorrhagic or thromboembolic complications. Neonatal outcomes were reassuring, with all infants born healthy, exhibiting platelet counts between 73,000 and 233,000/µL and no evidence of bleeding or congenital anomalies. One patient experienced transient postpartum thrombocytosis managed with low-molecular-weight heparin prophylaxis. No maternal or neonatal adverse events were attributed to Romiplostim exposure. These findings are consistent with previous limited reports suggesting that Romiplostim may be a viable rescue therapy for severe, refractory ITP in pregnancy. The favorable hematologic responses and reassuring neonatal outcomes observed in this series highlight the potential role of Romiplostim as an alternative treatment in carefully selected cases, provided that therapy is conducted under close multidisciplinary supervision.

A middle-aged adult presented with non-severe alcoholic hepatitis after 3 years of daily whisky intake (80-100 mL/day). He was noted to have persistent erythrocytosis (haemoglobin 186 g/L; haematocrit 53.8%) without leucocytosis or thrombocytosis and with normal serum erythropoietin. Secondary causes were evaluated, including hypoxia, cardiac and renal disease, and myeloproliferative neoplasms; Janus Kinase 2 Valine 617 Phenylalanine (JAK2 V617F) and JAK 2 exon 12 testing were negative. Despite intravenous hydration and reported complete alcohol abstinence, erythrocytosis persisted for several weeks after hepatic biochemistry improved. A bone marrow biopsy was planned but deferred when haemoglobin and haematocrit normalised spontaneously by 10 weeks. Overall, the presentation was most consistent with presumed alcohol-associated stress (relative) erythrocytosis, which may show delayed resolution after cessation, and careful longitudinal follow-up may avoid premature invasive investigations once polycythaemia vera and clinically important secondary causes have been reasonably excluded.

Classic myeloproliferative neoplasms, including essential thrombocythemia, polycythemia vera, and primary myelofibrosis, are chronic, clonal hematopoietic stem-cell disorders. These disorders are driven by gain-of-function mutations in the genes Janus kinase 2 (JAK2), calreticulin (CALR), or the thrombopoietin receptor (MPL) that activate cytokine signaling. These mutations arise decades before clinical disease develops and confer a clonal advantage that is further shaped by comutations in epigenetic, splicing, or signaling genes. Inflammation enhances clonal dominance, favoring the development of myelofibrosis and thrombotic complications. Disease evolution may culminate in secondary acute myeloid leukemia, which has a poor prognosis. Current therapies primarily aim to control symptoms, thrombosis, and splenomegaly, but they have limited disease-modifying effects, except for pegylated interferon alfa and JAK2 inhibitors in some patients. Emerging therapies that selectively target mutant CALR and JAK2 V617F using immunotherapy and selective inhibitors could be a breakthrough in the treatment of persons with myeloproliferative neoplasms, with the expectation of achieving durable disease modification and potentially clonal eradication.

Calreticulin (CALR) frameshift mutations drive the majority of JAK2/MPL-wild-type cases of essential thrombocythemia and myelofibrosis, producing a shared novel C-terminus that activates the thrombopoietin receptor and leads to constitutive Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling. CALR mutations transform the multifunctional endoplasmic reticulum (ER)-resident protein into an oncogenic driver that aberrantly traffics to the cell surface, activates the thrombopoietin receptor, MPL, and promotes MF megakaryocytic proliferation and hemopoietic stem cell fitness. Clinically, CALR-mutated MPNs affect younger patients, exhibit thrombocytosis and progressive anemia, and, in MF patients, are associated with a superior survival compared with JAK2- or MPL-mutated disease, yet responses to hydroxyurea and ruxolitinib remain inferior. The C-terminal motif shared between CALR mutations is presented extracellularly on major histocompatibility complex (MHC) Class I molecules and in complex with the thrombopoietin receptor enabling targeting with vaccination and antibody based therapeutic platforms, respectively. Mutant CALR peptide vaccines induce T cell responses but have failed to result in hematologic or molecular responses. Mutant CALR-specific monoclonal antibodies, such as Fc-silent antagonists, can block mutant-CALR-MPL signaling, suppress hematopoietic stem and progenitor cells (HSPC) proliferation and megakaryopoiesis, and achieve rapid, durable hematologic remissions with minimal toxicity in early-phase trials. Preclinical antibody-drug conjugates, bispecific T-cell engagers, and chimeric antigen receptor T cell (CAR-T) cells also show potent, selective mutant-cell killing. Here we review the basis and ongoing translational and clinical efforts in the development of CALR-targeted immunotherapies that offer a potential shift from symptom management to disease-modifying treatment in this molecularly defined MPN subset.

Polycythemia vera (PV) is a clonal myeloproliferative neoplasm primarily caused by the JAK2V617F mutation, present in 95% of patients. It results in erythropoietin-independent hematopoietic proliferation, erythrocytosis, increased hematocrit (Hct), leukocytosis, thrombocytosis, and hyperviscosity, predisposing patients to thrombotic events and neurologic deficits, including erythromelalgia and pruritus. Neurologic manifestations can occur, such as transient ischemic attack (TIA) and stroke. We report an 83-year-old woman, PV patient who presented with chorea and magnetic resonance imaging (MRI) of her brain showed pachymeningeal enhancement (dural-arachnoid enhancement); this radiological finding is most commonly described in intracranial hypotension, autoimmune conditions, infection, and neoplastic processes and has not been reported in PV. Laboratory findings included complete blood count (CBC) showed severe erythrocytosis, moderate leukocytosis with moderate, mild thrombocytosis; bone marrow (BM) aspiration and biopsy showed hypercellular BM and marked megakaryocytic hyperplasia; and positive JAK2V617F mutation with 80% JAK2 DNA, suggestive of PV as the underlying cause. The patient underwent phlebotomy and was started on Aspirin. Following treatment, she showed dramatic improvement in choreiform movements. Hydroxyurea 500 mg three times daily was subsequently added, leading to complete hematologic response and resolution of pachymeningeal thickening on follow up MRI. This case suggested association between polycythemia vera and choreiform movements and a possible mechanism is proposed.

Left atrial appendage occlusion is an alternative therapy to oral anticoagulation for patients with non-valvular atrial fibrillation. Despite design refinements, device-related thrombus (DRT) remains a clinical concern, even with the latest WATCHMAN FLX Pro device (Boston Scientific, Marlborough, MA, USA). We report a case of surgical removal of the WATCHMAN FLX Pro device due to DRT. Despite appropriate antithrombotic therapy, a 77-year-old patient developed DRT leading to cardioembolic cerebral infarction. The thrombus was initially small and nonmobile but rapidly progressed over 45 days to a large, pedunculated, highly mobile thrombus with minimum attachment to the device, necessitating urgent surgical intervention. Subsequent hematologic evaluation revealed previously unrecognized essential thrombocythemia as the underlying prothrombotic condition. This case demonstrates that DRT can occur in patients with unrecognized prothrombotic conditions. Preprocedural thrombophilia screening should be considered in patients with suggestive clinical or laboratory findings, such as unexplained thrombocytosis, along with careful post implantation monitoring.

Myeloproliferative neoplasms (MPNs) are broadly classified into BCR::ABL1-positive chronic myeloid leukaemia (CML) and BCR::ABL1-negative subtypes such as polycythaemia vera (PV), essential thrombocythaemia and primary myelofibrosis. Although traditionally considered mutually exclusive, rare cases of coexisting BCR::ABL1 rearrangement and Janus kinase 2 (JAK2) mutation have increasingly been recognised.We report the first Philippine case series of three patients with concurrent CML and JAK2-positive MPNs. Two patients developed PV 6-9 years after the initial diagnosis of CML despite ongoing tyrosine kinase inhibitor (TKI) therapy and molecular response, while a third patient had persistent thrombocytosis and was later found to have a concomitant JAK2-mutated MPN with fibrotic marrow features after 4 years.Compared with previously reported cases, our series demonstrates similarly delayed emergence of JAK2-mutated clones while highlighting real-world challenges in TKI intolerance, sequential TKI use and the need for combined cytoreductive strategies in a resource-limited setting.

Mixed-pathogen infective endocarditis is uncommon and may be difficult to recognize when the clinical course is prolonged and nonspecific. We report a case of mixed Candida albicans and Brucella melitensis native aortic valve endocarditis in a 37-year-old previously healthy man who presented with five months of intermittent fever, chills, anorexia, fatigue, 7 kg weight loss, progressive dyspnea, and intermittent chest pain. Physical examination revealed fever, sinus tachycardia, wide pulse pressure, elevated jugular venous pressure, bibasilar crackles, and a loud early diastolic murmur. Laboratory testing was notable for leukocytosis, anemia, mild thrombocytosis, and elevated inflammatory markers. A transthoracic echocardiogram demonstrated severe aortic regurgitation with a large 19 mm aortic valve vegetation causing holodiastolic flow reversal in the descending thoracic aorta. A transesophageal echocardiogram revealed two large mobile vegetations causing severe leaflet malcoaptation with possible periannular extension. A cardiac CT scan revealed thickening of the aortic root consistent with abscess formation. Blood cultures were positive for Candida albicans and Brucella melitensis. Brucella serology was positive, with an agglutination titer of 1:640. The patient developed pulmonary edema requiring an urgent Bentall procedure with a mechanical composite graft. Valve tissue cultures were positive for Candida albicans, and histopathology from the resected valve was consistent with acute-phase infective endocarditis with features of necrosis, fibrin, and debris. The patient was placed on postoperative antifungal treatment with caspofungin followed by fluconazole suppression, and on Brucella-directed treatment with doxycycline, rifampin, and levofloxacin for a planned six-month course of therapy. A postoperative whole-body PET/CT scan using fluorine-18 fluorodeoxyglucose (18F-FDG) did not demonstrate any residual cardiac infection or extracardiac infectious foci. The patient was doing well clinically at the three-month follow-up, with no signs or symptoms of heart failure and no evidence of relapse or recurrence of fever. This is a rare case of destructive native aortic valve endocarditis with mixed fungal and zoonotic bacterial etiologies that required urgent surgical source control and prolonged combined antimicrobial therapy.

Persistent fever as an initial manifestation of polycythemia vera (PV) is uncommon and may lead to diagnostic delay. We report a 72-year-old woman with recurrent low-grade fever for 1 month, with a maximum temperature not exceeding 38.0 °C. Although this presentation did not meet the classic fever-of-unknown-origin temperature threshold, it prompted an FUO-like diagnostic evaluation because routine infectious and autoimmune investigations were unrevealing and empirical antimicrobial therapy was ineffective. Laboratory evaluation revealed elevated hemoglobin and hematocrit levels, accompanied by leukocytosis and initially high-normal platelet counts that later progressed to thrombocytosis. Chest CT/PET-CT showed diffuse ground-glass/interstitial pulmonary changes; active bacterial pneumonia was considered unlikely based on the absence of respiratory symptoms, procalcitonin at the upper limit of the normal range, negative cultures and sputum smears, and absence of FDG-avid pulmonary consolidation, although a concomitant viral or noninfectious inflammatory pulmonary process could not be completely excluded. Bone marrow biopsy showed hypercellular marrow with panmyelosis and megakaryocytic proliferation, and molecular testing identified a JAK2 V617F mutation with a high allele burden. The diagnosis of PV was established based on the 5th edition of the World Health Organization (WHO) diagnostic criteria. The patient was treated with hydroxyurea and aspirin, resulting in gradual resolution of fever and improvement in hematological parameters. This case highlights that PV should be considered in the differential diagnosis of persistent unexplained low-grade fever when erythrocytosis and other myeloproliferative features are present, while alternative pulmonary causes should be assessed carefully.