Focus on suspected hemorrhagic diathesis

Michael Iarossi, MD, Cédric Hermans, MD, PhD, FRCP (Lon, Edin) Published in the journal : September 2023 Category : Hematology/Oncology

Clinical bleeding manifestations are commonly encountered reasons for medical consultations in both general and specialized fields. A comprehensive medical history, encompassing personal and familial contexts, plays a pivotal role in predicting a bleeding disorder. Employing a bleeding clinical score constitutes the primary approach. While routine coagulation tests are useful, they are inadequate for definitively ruling out a potential hemostatic abnormality. If a strong suspicion of hemostasis dysfunction exists, a comprehensive array of biological assessments must be requested. This evaluation should encompass primary hemostasis, coagulation factors, and fibrinolysis. This combined clinical and biological strategy is instrumental in recognizing whether a coagulation disorder is acquired or hereditary, in elucidating its underlying cause, and in gauging its severity. The commonly encountered congenital causes comprise platelet functional disorders, von Willebrand disease, hemophilia A/B, and deficiencies in coagulation factors like Factor VII and Factor XI, as well as hyperfibrinolysis. Nonetheless, a notable subset of patients is unlikely to benefit from this diagnostic approach. This prompts us to an undetermined source of the bleeding tendency, necessitating cautious attention to its potential implications. For hemostatic interventions, it is crucial to exercise vigilance. Indeed, the aim of such procedures is to attain effective management or bleeding prevention, while sidestepping unnecessary treatments with inherent risks, such as allergies, immunization, infections, and even thrombotic complications.


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Innovations 2022 in the field of hemostasis-thrombosis

Sarah Bailly1,2, Eric Van Den Neste1, Stefan N. Constantinescu1,2,3,4 Published in the journal : February 2023 Category : Hematology/Oncology

The specific characteristics of the CD19 cell marker make it an ideal therapeutic target in the treatment of B-cell lymphoma. Several molecules targeting CD19 have recently been made available, or are currently being developed, and show promising results for this therapeutic indication. This seems to be particularly true in the management of relapsing or refractory diffuse large B-cell lymphoma, as demonstrated by the results of the different studies described in this article. The choice of the right molecule and the best sequence for these treatments is still to be defined.

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Platelet factor 4 (PF4): roles and pathophysiological implications

Hélène Georgery, Cédric Hermans Published in the journal : January 2023 Category : Hematology/Oncology

Platelet factor 4 (PF4) is a positively charged molecule stored in the alpha granules of blood platelets and secreted during platelet activation, endothelial breach, or in the presence of microorganisms. PF4 binds to glycosaminoglycans on the endothelial surface and neutralizes their anticoagulant properties. Moreover, PF4 can combine with heparin, mainly unfractionated, in heparin-induced thrombocytopenia (HIT), with cartilage components or other negatively charged polyanions (so-called spontaneous HIT), and with some constituents of the SARS-CoV-2 adenovirus vaccine, resulting in post-vaccination thrombocytopenia. The common feature of these molecules is their negative charges which induce their binding to PF4 and a conformational change of the latter. This complex is recognized by anti-PF4 antibodies, which activate platelets and inflammatory cells via the Fc receptor, induce a pro-thrombotic state, and venous, arterial, or microcirculation thrombosis. The diagnosis of HIT is based on the detection of anti-PF4-heparin antibodies by immunoassay in cases of clinical suspicion and intermediate or high pre-test probability, estimated by different scores, the 4T score being the most common. Functional tests may also be performed. HIT management consists in stopping heparin and starting non-heparin anticoagulant therapy.

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Anticoagulation in antiphospholipid syndrome

Catherine Lambert Published in the journal : April 2022 Category : Hematology/Oncology

Antiphospholipid syndrome is a severe thrombotic disorder with a high risk of recurrence. For many years, the standard treatment for thrombotic complications of antiphospholipid syndrome has been anticoagulation with anti-vitamin K drugs. Over the past decade, direct oral anticoagulants have emerged as the anticoagulant treatment of choice for venous thromboembolic disease in the general population. The purpose of this article has been to review the modalities and objectives of anticoagulant therapy in antiphospholipid syndrome and to discuss the potential place of direct oral anticoagulants in this indication

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VEXAS syndrome: a new entity at the crossroads of rheumatology and hematology

Séverine Wautier*, Hélène Houssiau*, Nicole Straetmans (1) Published in the journal : April 2022 Category : Hematology/Oncology

VEXAS (Vacuoles, Enzyme E1, X-linked, Autoinflammatory, Somatic) syndrome has been recently described as a late-onset inflammatory disease caused by a somatic mutation in UBA1 in myeloid cells. It mostly affects men over 40 years of age with inflammatory symptoms (recurrent fever, dermatitis), rheumatologic disorders (arthritis, chrondritis), or hematologic abnormalities for several years. The presence of vacuoles in bone marrow myeloid cells is a characteristic (yet non-specific) sign of the disease. VEXAS syndrome may be associated with hematologic diseases, such as myelodysplasia and multiple myeloma, as well as an increased risk of thromboembolic event. The mortality is about 25-35% at 5 years. The disease is usually steroid-resistant. Studies with JAK2 inhibitors have shown promising results and are currently ongoing. Allogeneic stem cell transplantation is currently the only curative option for young, otherwise healthy patients.

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Clinical work-up of adenopathy in general medicine : when should we reassure the patient and when refer the patient for further evaluation?

Inès Dufour1, Géraldine Verstraete1, Juliette Raedemaeker1, Fabio Andreozzi1, Sarah Bailly1, Eric Van Den Neste1, Cédric Hermans1, Marie-Christiane Vekemans1 Published in the journal : March 2022 Category : Hematology/Oncology

Adenopathy investigation requires a systematic approach in order to determine the benign or malignant character of the adenopathy. It is essential to be able to recognize severity signs, which should orientate towards additional assessments, usually consisting of a biopsy. The article was aimed to help the general practitioner in the adenopathy work-up, as well as to review the main differential diagnoses in this setting.

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2021 Innovation in hematology

Marie-Christiane Vekemans, Violaine Havelange, Eric Van Den Neste, Sarah Bailly, Catherine Lambert,Nicole Straetmans, Xavier Poiré, Stefan N. Constantinescu, Cédric Hermans Published in the journal : February 2022 Category : Hematology/Oncology

The year 2021 was rich in innovations in regard to both malignant and benign hematological diseases, with the most relevant of which discussed below.

- In recent years, the prognosis of multiple myeloma has been greatly improved, yet the disease remains as yet incurable. Current strategies aim to achieve optimal disease control at diagnosis using four-drug regimens designed to delay relapse, while in relapsed patients, innovative alternatives like immunotherapy are being employed to effectively re-arm the immune system, and this represents a real hope for patients suffering from this chronic disease.

- The management of chronic myeloid leukemia is still evolving. Since 2001, tyrosine kinase inhibitors have revolutionized its prognosis, but they are also responsible for toxicities. One of the current therapeutic goals is to achieve a sufficiently deep and prolonged response, thereby enabling tyrosine kinase inhibitors to be discontinued and remission maintained.

- Myelofibrosis is a myeloproliferative neoplasm with poor prognosis. The only curative treatment available to date is peripheral stem cell allograft, which can be applied at least for some patients. New therapeutic agents are currently being investigated, which are highly promising not only on account of their efficacy on symptoms and splenomegaly, but also for their potential anti-fibrotic and reducing effect on the mutated clone. Certain agents are in clinical assays in combination with JAK2 inhibitors.

- Several recent studies have suggested that CAR-Ts were likely to emerge as the second-line treatment of choice for patients suffering from aggressive lymphomas, while secondarily reducing the number of autologous stem cell transplants.

- Patients with acute myeloid leukemia and TP53-mutated myelodysplastic syndromes still represent a challenging population to treat with low and only short-lived response rates. The advent of APR-246, which restores TP53 activity, is likely to increase the number of responders among these very high-risk patients.

- Beyond its well-known involvement in heparin thrombocytopenia, platelet factor 4 (PF4) plays a major role in the very rarely observed thrombosis with thrombocytopenia occurring in association with COVID-19 adenoviral vector vaccines. Inhibition of FXI is expected to emerge as a promising anticoagulation strategy with reduced bleeding risk, while induction of antithrombin deficiency by interfering RNA is likely to prevent bleeding in hemophilia A and B patients, either with and without inhibitors.

- Concerning the management of immune thrombocytopenic purpura, targeted therapies are currently being favored owing to their lower toxicity and individualized platelet count targets.

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What to do about hyperferritinemia?

Géraldine Verstraete Published in the journal : January 2022 Category : Hematology/Oncology

Regularly dosed upon routine biological work-ups, ferritin is revealed increased in a certain proportion of the population. At times, detection of hyperferritinemia leads to exhaustive and useless work-up, often including HFE genotyping. Although hemochromatosis is the most common genetic disease, this condition is not the primary cause of hyperferritinemia. In Western countries, metabolic syndrome and consumption of alcoholic beverages are the first etiologies to be considered. In general, a complete diagnostic approach, including complete medical history, clinical examination, and biology with a complete martial assessment, allows for identifying, without any specialized consultation required.

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Thrombosis and vaccines: a new challenge of the COVID-19 pandemic

Cédric Hermans, Michel Goldman Published in the journal : April 2021 Category : Hematology/Oncology

Venous thromboses at unusual locations, such as cerebral and visceral sites, along with thrombocytopenia have been detected in patients who received COVID-19 vaccines using adenovirus vectors. The concomitant presence of antibodies targeting platelet factor 4 is suggestive of an autoimmune process associated with heparin thrombocytopenia. These thromboses, although very rare, significantly impact the vaccination strategy.

This article seeks to review the available data on this topic. Accordingly, the observations that led to its identification, its hypothetical mechanisms, the diagnostic approach, as well as the therapeutic strategies to implement are presented in a concise and practical manner.

This article should help any health professional to better understand this rare vaccination-related complication and answer the patients' many questions.

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Management of relapsed/refractory diffuse large B-cell lymphomas in 2020 in Belgium. A 1-year experience with tisa-cel (Kymriah®), the first anti-CD19 CAR-T cell to be reimbursed

Sarah Bailly, Xavier Poiré, Nicole Straetmans, Violaine Havelange, Marie-Christiane Vekemans, Eric Van Den Neste Published in the journal : February 2021 Category : Hematology/Oncology

Recently, the management of relapsed/refractory diffuse large B-cell lymphoma has been revolutionized by the introduction of of anti-CD19 CAR-T cells. These treatments have been available in Belgium since mid-2019.

What to remember after one year of experience?

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