Hematology

Treatment for ITP is recommended for a platelet count less than 30×109/L. Corticosteroids are considered first-line treatment, with the addition of IVIG reserved for severe ITP in the setting of serious bleeding, when a rapid rise in platelets is required, or when corticosteroids are contraindicated. There is no evidence of benefit of IVIG in combination with corticosteroids for first-line treatment of asymptomatic ITP. If IVIG is required, the dose should initially be 1g/kg as a single time dose. This dose may be repeated if necessary. The financial implications of IVIG use are substantial: a single infusion cost between 5,000 to 12,000 CAD, and for patients requiring monthly infusions may incur annual costs of 60,000 to 100,000 CAD placing a significant burden on our healthcare system. Unnecessary IVIG infusions can result in multiple adverse effects, including acute hemolytic or anaphylactic reactions, thromboembolic events, and aseptic meningitis.

Hypogammaglobulinemia (IgG < 4g/L) due to secondary immunodeficiency is common in patients with hematologic malignancies (such as multiple myeloma, or lymphoproliferative disorders). Different societies recommend against the use of immunoglobulin replacement (whether subcutaneous or intravenous) for patients with hematologic malignancies and severe deficiency of Ig in the absence of complications such as recurrent bacterial infections requiring antibiotics or hospitalization. Some guidelines recommend Immunoglobulin replacement with failure of antibiotic prophylaxis or appropriate antibody response to vaccinations. Regardless, these are recommendations based on weak evidence, with lack of clear guidance to dose, when to start or stop treatment. If IVIG is used, the recommended dose is 0.4-0.6g/kg every 4 weeks. Equivalent Subcutaneous Ig dose can be used.

Immunoglobulin replacement has financial and ethical implications without clear positive QoL impact. Canada is the third highest consumer of Ig amongst developed nations with 232g per 1000 population, costing 60,000 to 100,000 CAD annually per patient, placing a significant burden on our healthcare system.

Meta-analyses of controlled trials conclude that immunoglobulin replacement offers no advantage for infection prevention and overall survival, and may predispose to a higher risk of hepatic sinusoidal obstruction syndrome, venous thromboembolism, and impair the efficacy of post-transplant vaccinations. There may be subsets of patients where prophylactic immunoglobulin replacement may be considered, such as in umbilical cord blood transplant recipients, in children undergoing transplantation for inherited or acquired disorders associated with B-cell deficiency, and in chronic graft-versus-host disease patients with recurrent sino-pulmonary infections.

Decisions to transfuse should be based on assessment of an individual patient including their underlying cause of anemia. There is high quality evidence that demonstrates a lack of benefit and, in some cases, harm to patients transfused to achieve an arbitrary transfusion threshold. For hospitalized adults who are hemodynamically stable, a restrictive transfusion strategy is recommended, with transfusions potentially considered when hemoglobin falls below 70 g/L. Higher thresholds may be used for patients undergoing cardiac (75 g/L), orthopedic surgery (80 g/L), those with ongoing cardiovascular disease (80 g/L) or acute myocardial infarction (90-100g/L). For hospitalized patients with hematologic or oncologic disorders, a similar restrictive approach is recommended, using the <70 g/L threshold. In addition, for hospitalized patients without active bleeding, transfuse only one unit of red cells. Risks of red blood cell transfusions include allergic reactions, fever non-hemolytic transfusion reactions, bacterial infection, volume overload, transfusion-related acute lung injury and hemolytic reactions.

Analyses of randomized controlled trials of patients with hypoproliferative thrombocytopenia (such as those receiving chemotherapy or undergoing allogenic stem cell transplant) show that restrictive platelet transfusion strategies do not significantly increase risks of bleeding or mortality. Specifically, there were no meaningful differences in WHO grade 2–4 bleeding, WHO grade 3–4 bleeding, or mortality with absolute risk differences remaining small and confidence intervals overlapping. There is no need to increase the threshold above 10 x 10⁹/L except if there is active bleeding, an imminent invasive procedure, or there is a recent intracranial/intraocular/spinal hemorrhage.

Running a CBC and electrolyte panel on a patient produces 0.3597kg CO2e (1.75km by car). Daily bloodwork seldom changes outcomes, exposes patients to harms (venipuncture associated pain, wake from sleep), and is associated with negative outcomes including anemia and need for transfusions. Routine and repetitive bloodwork can be safely discontinued through targeted interventions without increasing outcomes like re-admission, ICU admission, or mortality. Guidelines make a strong recommendation for the use of small-volume collection tubes to reduce the burden of iatrogenic anemia.

Patients on warfarin with a low-risk for thrombotic events do not require bridging anticoagulation when they have a procedure. If interruption is necessary, warfarin can be stopped 5 days prior to a planned procedure and resumed when it is felt to be safe to do so afterwards. Bridging with LMWH or UFH has been shown to cause excess bleeding when compared with no bridging and may ultimately delay resumption of warfarin. High-risk patients (e.g. mechanical mitral valve, venous thromboembolism within the last 3 months or atrial fibrillation with recent stroke/TIA) should be considered for bridging if the risk of thrombosis is higher than the risk of peri-procedural bleeding. Furthermore, patients who are taking Direct Oral Anticoagulants and require an elective surgery or procedure can benefit from a standardized protocol that does not require bridging with heparin.

Early pregnancy losses are common amongst healthy women. Current guidelines do not support the routine screening of women with early or recurrent pregnancy loss for inherited thrombophilias. Moreover, there are recommendations against instituting thromboprophylaxis (LMWH) in women with inherited thrombophilias wishing to achieve a successful term pregnancy. By performing testing for inherited thrombophilias, patients may be unnecessarily exposed to the harms of thromboprophylaxis, inappropriately labeled with a disease-state, and may unnecessarily modify future plans for travel, pregnancy or surgery based on detection of an “asymptomatic” thrombophilia. Lastly, patients with negative testing may receive false reassurance.

Specialty societies support the use of oral anticoagulation as initial therapy for many disease states. Evidence also suggests that patients prefer oral anticoagulants over subcutaneous formulations (most commonly, heparinoids) as the oral route is considered easier, less painful and less expensive. Heparinoids are also a highly carbon-intensive medication. The only Health Canada approved source of heparin is porcine mucosa; heparin cannot be synthesized artificially. Approximately 1.1 billion pigs are raised each year to meet the worldwide demand for heparin. It is estimated that 1 kg of intestinal mucosa will produce 160–260 mg of crude heparin. The carbon footprint of raising a heparin swine to maturity is 6.1kg CO2e (30km by car) per kg of pig which amounts to 668 million tonnes CO2e annually (over 3 trillion km by car). Heparin manufacturers have not been forthcoming on how the remains of heparin swine are handled. As such, it remains unclear whether these are subsequently used for dietary pork consumption. The environmental impact associated with processing, manufacturing, transport, and packaging is unpublished but add to heparin’s substantive carbon footprint.

The diagnosis of lymphoma requires specimens with intact cellular architecture for accurate histopathologic and immunophenotypic classification.  FNA is associated with a low sensitivity and potentially results in delays in lymphoma diagnosis. Although excisional biopsy is the gold standard for lymphoma diagnosis, depending on the lymph node location, excisional biopsy may be associated with complications and the need for general anesthesia. At a minimum, an imaging-guided core biopsy should be obtained to improve the accuracy and timeliness of lymphoma diagnosis.

Medical imaging is estimated to account for 1% of global GHG emissions. For example, a single MRI abdomen is estimated to generate emissions equivalent to driving a motor vehicle almost 300km. The annual energy requirements and carbon emissions associated with commonly used investigations in increasing order are: ultrasound system (2500 kWh, 0.74 tCO2e), CT scanner (20 000 – 35 000 kWH, 5.9-10.4 tCO2e), PET-CT scanner (52 000 kWH, 15.4 tCO2e), and MRI scanner (80 000-170 000 kWh, 23.7-50.3 tCO2e). Data for onboard imaging and picture storage is currently limited but an active area of research.

In patients with asymptomatic, early-stage chronic lymphocytic leukemia (CLL), baseline and routine surveillance computed tomography (CT) scans do not improve survival and are not necessary to stage or prognosticate patients. CT scans expose patients to small doses of radiation, can detect incidental findings that are not clinically relevant but lead to further investigations, and are costly. For asymptomatic patients with early-stage CLL, clinical staging and blood monitoring is recommended over CT scans.