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Mild Is The Most Dangerous Word In The Classification Of Hemophilia

The recent Rare Blood Disease Summit sponsored by Genentech highlighted a critical perspective pertinent to me: "Mild is the most dangerous word in hemophilia." I wholeheartedly agree with this statement as a person with mild hemophilia B and von Willebrand disease.

Mild hemophilia is distinguished by relatively higher clotting-factor activity when compared with moderate or severe hemophilia. In cases of severe hemophilia, patients often employ prophylactic treatment strategies to elevate their clotting factor levels up to 100%, essentially providing a protective shield against bleeding episodes. But prophylactic treatment is rarely attainable for those grappling with mild hemophilia.

We typically live with factor levels hovering at 40% or lower, necessitating vigilance and tailored management to address the inherent challenges posed by our condition.

The word 'mild' is dangerous

When I bleed as a complication of an injury or medical procedure, there's nothing mild about the experience. My condition's severity becomes painfully evident.

I vividly remember the moment a surgeon, with a mix of relief and astonishment, told me I was "lucky to be alive" after the intense bleeding complications I faced during surgery. At that moment, my hemophilia struggles were far from mild. The battle I fought against iron deficiency and anemia further emphasized that my bleeding was anything but mild.

These incidents underscored my condition's profound impact on my life, regardless of its classification.

The danger in the word "mild" lies in the misconceptions it can create. Those of us with mild disorders might not experience severe bleeding episodes regularly, but we still require careful management and support. Without proper education and awareness, we risk overlooking our hemophilia symptoms or underestimating the need to seek medical attention.

Women with mild hemophilia

Mild hemophilia disproportionately affects women, whose symptoms are often dismissed or attributed to other causes. Many face challenges in getting timely diagnoses of hemophilia and accessing appropriate care. For them, the term "mild" can be misleading and potentially dangerous. It might downplay the seriousness of their condition, leading to inadequate hemophilia treatment and a lack of understanding from both healthcare providers and society at large.

Raising awareness about the diverse ways bleeding disorders can manifest, especially in women, is crucial. It's not about just acknowledging the physical aspects, but also addressing the psychological and social effects these disorders can have on individuals and their families.

To ensure the well-being of everyone with bleeding disorders, we need to redefine our understanding of the "mild" classification. We must emphasize the importance of personalized, comprehensive care, regardless of the condition's severity. By doing so, we can create a healthcare environment where everyone, regardless of how their disorder is classified, receives the attention, understanding, and support they need to live healthy and fulfilling lives.

Note: Hemophilia News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Hemophilia News Today or its parent company, BioNews, and are intended to spark discussion about issues pertaining to hemophilia.

Evaluating WHO's Hemophilia Treatment Choices: Patient Safety, Access Challenges

A commentary questions the characterization of cryoprecipitate, which is not pathogen-reduced, as an alternative modality for treating hemophilia, despite its substantial risk of transmitting blood-borne pathogens to patients.

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Recent decisions made by the World Health Organization (WHO) regarding the inclusion and categorization of treatments for hemophilia in its Essential Medicines List (EML) have sparked concerns among patients and health care providers.

One of the primary concerns revolves around the characterization of cryoprecipitate (cryo), which is not pathogen-reduced (PR), as an alternative modality for treating hemophilia, despite its substantial risk of transmitting blood-borne pathogens to patients.

The decision to include cryo in the EML raises questions about patient safety and the potential transmission of infections in countries where blood safety standards might not be as stringent, according to a commentary article published in Haemophilia by Albert Farrugia, PhD, University of Western Australia.

PR-cryo: Affordable, Precise Treatment

Cryo was the first therapeutic product available for treating bleeding disorders and has long been utilized for conditions like hemophilia A, von Willebrand's disease, and fibrinogen deficiency. However, in developed countries, the unmodified version is considered outdated, with specific concentrates of the deficient proteins being the preferred mode of treatment.

The inclusion of cryoprecipitate [pathogen-reduced] (PR-cryo) in the EML is especially relevant for resource-poor conditions. PR-cryo, specified for Factor VIII (FVIII), von Willebrand Factor, and fibrinogen, offers a more affordable and accurate dosing option.

Pooled and aliquoted from individual cryoprecipitates, PR-cryo ensures the potency of the relevant factors, allowing for precise and effective treatment. This method is pivotal in areas where resources are limited, ensuring patients receive the necessary care without the burden of excessive costs.

The WHO Global Status Report on Blood Safety and Availability highlights a significant disparity in blood safety between low- to middle-income countries (LMIC) and high-income countries (HIC). It's reported that LMICs face a much higher prevalence of blood-borne viruses, posing a considerable risk to patients relying on blood products for treatment.

The commentary discusses how the availability of several commercial versions of PR-cryo might impact the cost-effectiveness of the therapeutic modality. Coagulation factor concentrates, especially for hemophilia A, have become more affordable in recent years, benefiting developing countries.

However, Farrugia referenced a recent report that suggests domestically sourced PR-cryo might offer a cheaper alternative demonstrating the importance of ongoing research and international cooperation to ensure the most cost-effective solutions reach those in need.

Categorization of Hemophilia Treatments

The decision to categorize FVIII and factor IX (FIX) concentrates as complementary rather than core medicines has raised concerns within the medical community. While these concentrates are recognized as the preferred route of replacement therapy for hemophilia A and B, their listing status might be influenced by cost perceptions, leading to reservations among health care providers.

Patients with hemophilia B, in particular, could experience disadvantages if a core-listed medicine is not specified, calling for careful reconsideration of these classifications to ensure equitable access to essential treatments.

Reconsidering Alternative Treatments

Another area of concern was noted from the inclusion of Prothrombin Complex Concentrate (PCC) as an alternative treatment to FIX concentrates for hemophilia B. Despite its historical use, evidence-based practice has shown that PCC does not align with the advancements made in hemophilia care.

This decision to list PCC as an alternative treatment, Farrugia wrote, contradicts established medical practices and warrants urgent reevaluation to ensure patients receive the best and safest treatments available.

The commentary acknowledged the WHO's recognition of the value of blood products in hemophilia treatment but stated there is a pressing need for a comprehensive review of the EML in the context of evolving medical advancements. Incorporating safer, more effective treatments while addressing the economic challenges faced by low-income countries should be at the forefront of decision-making.

Reference

Farrugia, A. The World Health Organisation's list of essential medicines and haemophilia treatment products. Haemophilia. 2023; 1-3. Https://doi.Org/10.1111/hae.14879

Damoctocog Alfa Pegol Demonstrates Safety And Efficacy In Hemophilia A

While clinical trials offer controlled data, real-world studies like HEM-POWR bridge gaps, confirming damoctocog alfa pegol's effectiveness and tolerance, establishing it as a valuable hemophilia A treatment option.

Set IV FluidImage Credit: Trsakaoe stock.Adobe.Com

In the ongoing real-world hemophilia A HEM-POWR study, previously treated patients receiving prophylactic damoctocog alfa pegol experienced a reduction in the number of infusions compared with their prior treatment regimens, according to findings published in the European Journal of Haematology.

The study, conducted across multiple countries, aimed to assess the annualized bleeding rate (ABR) in previously treated patients with hemophilia A. A total of 268 patients were included in the safety analysis set, and 161 patients were included in the full analysis set. The predominant dosing regimen observed was prophylaxis, administered every 3-4 days (twice weekly) with a median infusion dose of 37.5 IU/kg.

The study encompassed a diverse patient population primarily from Germany, Japan, Italy, and the United States, and among the 270 patients enrolled, approximately half were White, and 30% to 40% were Asian. The median age of participants was 35.0 years, and most had severe hemophilia A at diagnosis (82.5% in safety analysis; 87.6% in full analysis). Common concomitant conditions included hypertension, HIV positivity, and infections/infestations.

In the full analysis set, 82.6% of patients were previously treated with damoctocog alfa pegol, primarily on a prophylactic regimen (97%). The prescribed dose per infusion prior to enrollment ranged from 1000 to 8000 IU. During the observation period, prophylaxis remained the main dosing modality (98.1% in full analysis set), with twice-weekly administration being the most common regimen (49.4%).

Throughout the study, most patients maintained their treatment modality, although 46 patients adjusted their prophylaxis dose, and 30 general prescription changes occurred. Patients with non-severe hemophilia A initiated prophylaxis at a later age than those with severe disease. In the utilization subgroup, where patients had severe hemophilia A at diagnosis, the mean treatment duration was 11.0 months.

During the study period, a total of 31 patients (11.5%) discontinued participation. Reasons for discontinuation varied and included factors such as patients being lost to follow-up, withdrawal of consent, or switching to other therapies. The observation period duration was represented as a median of 233.5 days in the safety analysis set and 362 days in the full analysis set.

The median total ABR was 0.0 (with a range of 0.0 to 1.8), indicating a minimal annualized bleeding rate. The mean total ABR was 2.4 (SD, 8.2), suggesting a low overall incidence of bleeding episodes. The proportion of patients with no affected joints increased from the initial visit to the follow-up, indicating an improvement in joint health among participants.

The study found no cases of factor VIII inhibitors, treatment-related adverse events, or deaths among the participants supporting the conclusion that damoctocog alfa pegol demonstrated effectiveness, acceptable safety, and consistent utilization in real-world scenarios, even among patients with non-severe hemophilia and those with a history of inhibitors.

Unlike traditional treatments, damoctocog alfa pegol offers flexibility, allowing tailored therapy without compromising bleeding protection or joint health, according to the study. Administered twice weekly in nearly 40% of patients, it effectively managed bleeding episodes without increasing doses.

Over 33 months, the results showed decreased joint issues without higher resource usage, making damoctocog alfa pegol a promising long-term solution. This multinational study, inclusive of diverse patient groups and those with inhibitors, highlights its real-world viability.

While clinical trials offer controlled data, real-world studies like HEM-POWR bridge gaps, confirming damoctocog alfa pegol's effectiveness and tolerance, establishing it as a valuable hemophilia A treatment option, investigators noted. Ongoing analyses will provide further insights, enhancing the understanding of the therapy's practical application.

Reference

Reding, MT, Álvarez-Román, MT, Castaman, G, et al. Interim analyses of the multinational real-world prospective cohort HEM-POWR study evaluating the effectiveness and safety of damoctocog alfa pegol in patients with hemophilia A. Eur J Haematol. 2023; 1-10. Doi:10.1111/ejh.14114

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