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IACH NEWS OF THE WEEK

March 6, 2026
Prepared by Dr Edwin Uriel Suárez

Hairy cell leukemia: a chronic B-cell lymphoma with unique clinicopathological features and unresolved molecular mechanisms [Review].

Key points:

●      Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder that is characterized by pancytopenia, splenomegaly, and hepatomegaly, resulting from the organ-specific infiltration of “hairy” leukemic cells.

●      HCL, constituting ~2% of all leukemia cases, exhibits a sex bias, with a male-to-female ratio of 4:1.

●      HCL, together with HCL variant and splenic marginal zone lymphoma, is characterized by overlapping features, including splenomegaly, absence of lymphadenopathy, and a presence of “hairy” B cells.

●      At present, immunophenotyping using flow cytometry has become a cornerstone in HCL diagnosis, which detects characteristic surface markers such as CD11c, CD25, CD103, and CD123.

●      The B-rapidly accelerated fibrosarcoma (BRAFV600E) mutation can serve as a promising marker for HCL diagnosis, which is detected in fresh bone marrow and peripheral blood samples by polymerase chain reaction and Sanger sequencing. Alternatively, BRAFV600E could be detected in routine paraffin sections by immunostaining with anti-BRAFV600E monoclonal antibodies.

●      Hairy cells selectively accumulate in bone marrow, splenic red pulp, and hepatic sinusoids rather than lymph nodes, a process fine-tuned by the expression of chemokines, adhesion receptors, and cytokines in tissue microenvironments, as well as their receptors or ligands on hairy cells.

●      Except for the origin of hairy cells, genetic drivers in HCL have also been obscured for a long time due to lack of recurrent chromosomal aberrations and genetic events. It was not until 2011 that genomic studies identified a gain-of-function mutation, BRAFV600E, present in all patients with HCL. This mutant aberrantly activates downstream extracellular signal-regulated kinase MAPK signaling, which is responsible for molecular pathogenesis and “hairy” morphology of HCL. It is worth noting that BRAFV600E can be either heterozygous or hemizygous, resulting from a heterozygous loss of chromosome 7q.

●      Therapy is generally initiated when hemoglobin level is <11 g/dL, platelet counts are <1.0 × 109 /L, and/or neutrophil counts are <1.0 × 106 /L.          

●      The initial standard treatment for HCL was splenectomy, which achieved 5-year survival rates of 86%. Despite tremendous therapeutic advances with purine analogs and interferon, approximately half of patients with HCL relapse after initial treatment.

●      For patients with relapsed HCL, retreatment with a purine analog, with or without rituximab, remains the standard of care for first relapses.

●      In line with the discovery of BRAFV600E, its inhibitors have proven effective in treating patients with HCL, including vemurafenib and dabrafenib.

●      Allogeneic hematopoietic cell transplantation has been reported as a treatment option for patients with refractory or relapsed HCL. 
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Guideline on the emergency management of critical bleeding in patients with immune thrombocytopenia

In patients with immune thrombocytopenia (ITP), a critical bleed such as intracranial hemorrhage or bleeding causing hemodynamic instability, requires urgent treatment to rapidly raise the platelet count and restore hemostasis. There is no standardized approach to this hematological emergency. The McMaster ITP Emergency Management Guideline Group developed evidence-informed recommendations for the management of a critical bleed in adults and children with ITP.

 

Key points: See Table 4 in original paper.

●      The panel made strong recommendations for the combined use of High-dose corticosteroids (e.g., intravenous [IV] dexamethasone 40 mg/day for 4 days; or IV methylprednisolone 1 g/day for 3 days); High-dose IV immunoglobulin (e.g., 1g/kg for 1 or 2 consecutive days); Platelet transfusion (e.g., one or more doses of platelets); Tranexamic acid (e.g., 1g IV every 6-8 hours for 1-3 days) Thrombopoietin receptor agonists (e.g., romiplostim 5–10 μg/kg administered subcutaneously) for the treatment of critical ITP bleed.

The panel made a conditional recommendation for Urgent splenectomy when other treatments have failed. Due to the risk of thrombosis, a conditional recommendation against the use of recombinant factor VIIa, unless there are no other options for treatment or if recommended treatments fail.
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Immunoglobulin Light Chain Amyloidosis: 2026 Update on Diagnosis, Prognosis, and Treatment [Review].

Key points:

-        Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and “atypical smoldering multiple myeloma or monoclonal gammopathy of undetermined significance.”

-        Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. See Box in original paper (Required Diagnostic Evaluation After Amyloidosis Is Established).

●      Mass spectrometry can confirm the amyloid protein composition, and it is considered the standard for typing the protein subunit in amyloid deposits. Mass spectroscopy is superior to immunohistochemistry in identifying the protein subunit.

-        N-terminal pro–brain natriuretic peptide, serum troponin T or I, and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5 year survivals are 82%, 62%, 34%, and 20%, respectively.

-        All patients with systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. See Figure 2 and 3 in original paper.

●      Current first line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone.

●      The goal of therapy is a ≥very good partial response.

●      In patients failing to achieve this depth of response, options for consolidation include pomalidomide, stem cell transplantation, and venetoclax.

●      T-cell redirecting therapies, both bispecific antibodies and chimeric antigen receptor T-cell therapy, show high level activity and may soon become standard second-line therapy.

-        Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. An antibody (CAEL-101) to deplete deposited κ fibrils has reported benefit in patients with cardiomyopathy. 
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2026 AHA/ACC/ACCP/ACEP/CHEST/ SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults.

Key points:

-        Quantify clinical probability of acute pulmonary embolism (PE) using a validated tool (such as the Wells score, revised Geneva score, or clinical gestalt [intuitive impression]). See Figure 1 in original article.

●      If clinical probability <15% (Low): Assess PE Rule Out Criteria (PERC); if all criteria met = Very low clinical probability of PE and No further testing.

●      If clinical probability 15-50% (Intermediate) or any of the PERC criteria are not met: Perform D-dimer testing and assess YEARS criteria. If 0 YEARS criteria and D-dimer <1000 ng/mL = PE diagnosis excluded. Likewise, if YEARS criteria is ≥ 1 AND D-dimer <500 ng/mL or age-adjusted threshold = PE diagnosis excluded.

○      Age-adjusted D-dimer (age × 10 ng/mL) strategy is safe in patients with low or intermediate clinical probability of PE.

●      If clinical probability >50% (High) or 0 YEARS criteria and D-dimer ≥1000 ng/mL or ≥1 YEARS criteria and D-dimer ≥500 ng/mL or age-adjusted threshold: Perform diagnostic imaging.

-        In patients undergoing imaging evaluation for suspected PE, a positive computed tomography pulmonary angiography (CTPA) or high probability ventilation/perfusion (V/Q) scan is sufficient to diagnose PE. CTPA is recommended in preference to a V/Q scan.

●      In pregnant patients presenting with symptoms, YEARS criteria suggestive of acute PE, and a normal chest x-ray, imaging evaluation with low-radiation dose CTPA is reasonable over low-dose perfusion scintigraphy.

●      In patients with confirmed acute PE, obtaining lower extremity venous duplex ultrasound examination may be reasonable in patients with clinical findings suggestive of deep venous thrombosis (DVT) or if the presence of DVT will change management or inform prognosis.

-        See Figure 2 in original paper for AHA/ACC Acute PE Clinical Categories.

●      A = Subclinical: Incidental and asymptomatic.

●      B = Symptomatic: Low clinical severity score.

○      Low Clinical Severity Score includes PESI  (Pulmonary Embolism Severity Index) ≤85 or simplified PESI = 0 or Bova ≤ 4.

●      C = Symptomatic: Elevated clinical severity score.

●      D = Incipient Cardiopulmonary Failure.

○      D1: Transient hypotension= Systolic blood pressure <90 or decrease >40 mm Hg lasting <15 min or responding to IV fluids.

○      D2: Normotensive shock= Any: Lactate >2 mmol/L, acute kidney injury, urine output <0.5 mL/kg/hr, mental status change, cardiac index <2.2 L/min/m2 , mean arterial pressure <60 mm Hg, increased shock score/stage (Society for Cardiovascular Angiography & Interventions [SCAI], Composite Pulmonary Embolism Shock [CPES] score).

○      With or without R (respiratory modifier): >6L nasal cannula or use of a nonrebreather mask.

●      E= Cardiopulmonary Failure.

-        In patients with acute PE and an elevated clinical severity score but without evidence of shock (ie, PE Categories C-D), right ventricular (RV) imaging is recommended for short-term risk stratification.

-        In patients diagnosed with acute PE in a clinic or an emergency department, it is reasonable to use a decision tool (Hestia rule, the PESI, and the sPESI) to identify suitability for outpatient (OP) treatment. Patients suitable for discharge from the OP or emergency setting must have immediate access to anticoagulant medication and rapid, reliable, expert follow-up in place.

-        In patients with acute PE in PE Categories A-C, quantification of angiographic thrombus burden for short-term risk stratification is not recommended.

-        See Figure 3 in original paper for Initial Assessment and Management by AHA/ACC Acute PE Clinical Categories.

-        In patients with acute PE in category E1 (Cardiopulmonary Failure), catheter-directed thrombolysis plus anticoagulation is reasonable to prevent further clinical deterioration and early mortality.

●      Weak recommendation (2b): In patients with acute PE in category

-        In patients with acute PE categories C3-E2 who have evidence of free-floating right atrial and/or RV clot-in-transit, the utilization of advanced therapies (including systemic thrombolysis, catheter-based thrombolysis, mechanical thrombectomy, and surgical embolectomy) over anticoagulation alone is reasonable to reduce the risk of clinical deterioration.

-        In patients with acute PE who are eligible for oral anticoagulation, direct oral anticoagulants (DOACs) are recommended over vitamin K antagonists (VKAs), unless contraindicated, to prevent recurrent venous thromboembolism (VTE) disease and reduce major bleeding.

-        In patients with acute PE and established thrombotic antiphospholipid antibody syndrome, a VKA is recommended in preference to a DOAC for the prevention of venous and arterial thrombosis.

-        In patients with severe kidney disease (stage 4-5) or end-stage kidney disease on hemodialysis and confirmed PE who require oral anticoagulant therapy, it is uncertain whether apixaban is better than VKA to reduce major bleeding.

-        In patients with primary or metastatic brain tumors and acute PE who are otherwise eligible for oral anticoagulation, a DOAC may be considered over low molecular weight heparin (LMWH) to reduce the risk of intracerebral hemorrhage.

-        In patients with Child-Pugh class C chronic liver disease and acute PE, treatment with a DOAC instead of a VKA is not recommended due to potential for increased bleeding.

-        In patients with a first acute PE and no major reversible risk factor, continuing anticoagulation beyond the initial treatment phase (3-6 months) into the extended treatment phase (anticoagulation beyond the initial 3 to 6 months without an anticipated stop date) is beneficial to prevent recurrent VTE.

-        For patients with a PE who are offered anticoagulation beyond the initial treatment phase (3-6 months) into the extended treatment phase, treatment with a DOAC, unless contraindicated, is recommended over a VKA to reduce the risk of bleeding.

-        For patients with a PE and with cancer who are offered anticoagulation beyond the initial treatment phase (3-6 months) into the extended treatment phase, either a DOAC or LMWH is recommended over VKA to reduce the risk of recurrent VTE.

-        For patients with a PE who are offered anticoagulation beyond the initial treatment phase (3-6 months) into the extended treatment phase, treatment with half-dose apixaban or rivaroxaban is recommended to reduce the risk of bleeding. 
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