Journal Logo

HemaBites

HemaBites showcase hematology news & short commentaries on recent high-impact articles published in international journals. This blog will keep you up to date with the latest discoveries in the field of hematology as well as other related hematology news.

Monday, June 21, 2021

Stephen Hibbs: St. Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom

Utako Okamoto was the Japanese scientist who invented the antifibrinolytic compound tranexamic acid (TxA) in 1962 and her life aspiration was to reduce death from childbirth. Complications of childbirth still kill several hundred thousand mothers each year and the leading cause is postpartum haemorrhage (PPH). The 2017 World Maternal Antifibrinolytic (WOMAN) trial demonstrated a significant risk reduction of bleeding deaths in women with PPH who were randomised to TxA compared to placebo (risk ratio 0.81). Most of the 20,000 mothers enrolled to WOMAN were from low and middle income countries (LMIC) where most maternal deaths occur.

However, the benefits of TxA in acute bleeding are limited to those who receive it early, so should TxA be used pre-emptively, before significant PPH is established? This was the question considered in the Tranexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery (TRAAP2) study, recently published in the New England Journal of Medicine (Sentilhes et al, 2021). TRAAP2 randomised women having Caesarean section at French hospitals to receive either TxA or placebo administered immediately after cord clamping. There was a significant benefit in the primary outcome of estimated blood loss greater than 1L or receipt of red blood cell transfusion within two days (26.7% in the TxA group vs 31.6% with placebo). There were no differences in secondary outcomes of morbidity including transfusion rate, or in adverse effects apart from nausea and vomiting.

What does TRAAP2 add to WOMAN? It confirms that TxA reduces obstetric bleeding and demonstrates that a pre-emptive approach is safe. In the high-income healthcare setting of TRAAP2 this bleeding reduction makes limited difference to other outcomes of morbidity and mortality, but in the LMIC setting the impact would be far greater. Three questions need answering for wider application in LMIC settings: 1) Could other routes of administration of TxA be used where intravenous access is limited? 2) Is it safe to the fetus to administer TxA prior to cord clamping? 3) Are the benefits of pre-emptive TxA seen in all types of deliveries?

Utako did not get to see her hopes confirmed: she died aged 98 the year before the WOMAN study was published, but her work leaves a remarkable legacy, which TRAAP2 builds upon.

For further reading:
Hibbs SP, et al. Br J Haematol. 2018;180(6):799-807.

 



Tuesday, June 1, 2021

Melania Tesio: Laboratory of Onco-Hematology, Institut Necker Enfants Malades (INEM), Institut National de la Recherche Médicale (INSERM) U1151, Paris, France

SYK is a tyrosine kinase that plays crucial roles in B-cells. Activated following engagement of the B-cell receptor (BCR), SYK initiates the proximal BCR signaling by triggering two distinct downstream pathways, namely the Ca2+/NFAT signaling via BLNK and BTK, and the PI3K-AKT signaling via CD19.  In autoreactive B-cells or premalignant B-cells presenting an oncogenic activation of the BCR signaling, SYK-mediated BCR hyperactivation triggers negative selection and cell death.

Structurally similar to SYK is ZAP70, a tyrosine kinase initiating the TCR signaling in T-cells. Despite SYK and ZAP70 play analogous roles in B and T-cells, their expression is strictly segregated respectively in the B and T lineages. Reporting in Molecular Cell, Teresa Sadras and colleagues demonstrate that this developmental segregation is required to prevent B-cell malignancies.

The authors demonstrated that ZAP70 is aberrantly expressed in multiple B-cell malignancies, where it competes with SYK for binding common BCR signalosome substrates, such as BLNK and BTK. In this way, ZAP70 reduces the activation of the Ca2+-NFAT pathway thus altering the signaling threshold required to trigger the negative selection. In parallel, ZAP70 promotes SYK-mediated activation of the CD19-PI3K pathway, which mediates a tonic survival signal (Figure). Hence, by diverging SYK signaling from Ca2+-NFAT to PI3K activation, ZAP70 re-wires the BCR signaling to subvert the negative selection and promote cell survival.

Reference:
Sadras T, et al. Mol Cell. 2021;81(10):2094-2111.e9.




Tuesday, May 25, 2021

Jessica Mastrodomenico: EHA/HemaSphere, The Hague, The Netherlands

HemaSphere is incredibly pleased to announce our forthcoming June issue, specifically linked to the cutting-edge scientific program of this year’s European Hematology Association (EHA) Annual Congress. Select presenters from EHA2021 have expanded upon their congress presentations by submitting review and perspective manuscripts. We are thrilled to say that HemaSphere’s June issue, comprised of 16 EHA2021 presenter-authored publications plus 3 additional related papers, will be released in full on June 7th - just before EHA2021 begins on the 9th. In the meantime, please find below the June issue manuscript titles and lead author names. We can’t wait to share the exciting collection of articles with you – stay tuned!​

  • ​Immune Thrombocytopenia: Recent Advances in Pathogenesis and Treatments (Sylvain Audia)
  • Biology of Germinal Center B Cells Relating to Lymphomagenesis (Katia Basso)
  • Functional Consequences of Mutations in Myeloproliferative Neoplasms (Stefan Constantinescu)
  • Innovative Treatments for Rare Anemias (Maria Domenica Cappellini)
  • The Fifth Year of HemaSphere (Jan Cools & Andreas Engert)
  • The EHA2021 Annual Congress Award Winners: Celebrating Excellence in Hematology (John Gribben)
  • Hijacking the Pathway: Perspectives in the Treatment of Mature T-cell Leukemias (Marco Herling)
  • Targeting Chromatin Regulation in Acute Myeloid Leukemia (Brian Huntley)
  • Allogeneic Stem Cell Transplantation Platforms With Ex Vivo and In Vivo Immune Manipulations: Count and Adjust (Jürgen Kuball)
  • New Developments in Diagnosis and Management of Acquired Hemophilia and Acquired von Willebrand Syndrome (Frank Leebeek)
  • Pathophysiology of Coagulopathy in Hematological Malignancies and in COVID-19 (Marcel Levi)
  • The Fibrinolytic System: Mysteries and Opportunities (Robert Medcalf)
  • The Premalignant Ancestor Cell of t(14;18)+ Lymphoma (Bertrand Nadel)
  • Understanding the Mechanisms of Resistance to T Cell-based Immunotherapies to Develop More Favorable Strategies in Multiple Myeloma (Paola Neri)
  • Splicing Factor Mutations and Disease Phenotype: Searching for a Needle in a Haystack (Kevin Rouault-Pierre)
  • Research in Sickle Cell Disease: From Bedside to Bench to Bedside (Swee Lay Thein)
  • Treatment for Relapsed/Refractory Acute Myeloid Leukemia (Felicitas Thol)
  • Targeting IDH1 and IDH2 Mutations in Acute Myeloid Leukemia: Emerging Options and Pending Questions (Bas Wouters)
  • Immunomodulatory Therapies for the Treatment of Graft-versus-Host Disease (Robert Zeiser)


Tuesday, May 11, 2021

Stephen Hibbs: St. Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom

One of the worst parts of my training as a haematologist has been learning how to perform bone marrow aspiration and trephine. It was close to the archaic adage of “see one, do one, teach one". Many of my early samples were inadequate and I feared the next procedure, knowing that I would often cause significant pain and anxiety to my patients. With time and experience, my technique has improved, my samples are better, and the experience of my patients is less traumatic. But I am still aware that bone marrow procedures can be traumatic to patients and that our acceptance of this is likely to be a failure of imagination and empathy.

Enter an imaginative trial, in which Abbaszadeh and colleagues have shown a significant benefit from a very unlikely tool: lavender oil. They enrolled 80 patients undergoing bone marrow biopsy and randomised them to 15 minutes of aromatherapy from a ball of cotton wool with either lavender oil or water.1 Following this, a bone marrow biopsy was performed and a Visual Anxiety Scale assessed immediately afterwards. The mean anxiety score in the placebo group was 6.3 (classified as moderate-severe) compared to 3.75 (mild-moderate) in the lavender group. This is significant, and consistent with studies of lavender oil in other procedural settings, where it has been shown to be at least as effective as benzodiazepines at reducing anxiety.

This is not the first time that the Iranian haematology community have shown that unconventional interventions can improve bone marrow biopsy experience. Shabanloei and colleagues (2010) previously demonstrated that instrumental music during a bone marrow biopsy significantly reduced pain and anxiety.2 At my hospital, we have now begun using instrumental music with all procedures. Anecdotally patients and clinicians report improved experience, and it has certainly reduced my own anxiety as the operator. The Abbaszadeh study now engages the sense of smell – perhaps the next step will be to paint something calming on our procedure room which has no natural light and drab hospital walls. It may be that these interventions have a second benefit – to communicate to the patient that we acknowledge the unpleasantness of the procedure, that we are making an effort to improve their experience and that their pain is not just to be accepted as “business as usual".

References:
1. Abbaszadeh R, et al. Asian Pac J Cancer Prev. 2020;21(3):771-775.
2. Shabanloei R, et al. AORN J. 201091(6):746-51.



Thursday, April 29, 2021

​Jessica Mastrodomenico: EHA/HemaSphere, The Hague, The Netherlands

Are you interested in basic and molecular hematology? Erasmus Medical Center, based in Rotterdam, the Netherlands, is hosting an ongoing series of weekly virtual one-hour hematology lectures. Both established and rising star investigators from different hematologic fields have been invited to provide updates on their research. There is no cost and no pre-registration required; simply join the online session (most Mondays) and enjoy. As unpublished data might be discussed, the lectures are not recorded.

The next lecture will be on Monday, May 3rd and the series runs through early July. Each virtual lecture begins at 16:00 CET.

You can find the exciting lecture lineup here: http://bit.ly/EMC_lectures

If any questions, please contact Prof Dr Ruud Delwel ([email protected]) or Tessa Mannee ([email protected]).