Glanzmann Thrombasthenia: treatment strategies | JBM
The Alabama Center For Childhood Cancer And Blood Disorders Research Programs
Taking on Life After Cancer (TLC)As a result of continued improvements in treating pediatric cancer, approximately 80% of children and adolescents diagnosed with cancer today will become long-term survivors. These survivors are at risk for late effects, or complications, related to their cancer diagnosis and/or treatment, and require lifelong monitoring. Potential late effects include impaired growth, heart and lung problems, secondary cancers, learning disabilities, and vision or hearing problems.
The Taking on Life after Cancer (TLC) Clinic, at the Alabama Center for Childhood Cancer and Blood Disorders, is the only childhood cancer survivorship clinic in Alabama designed specifically to help pediatric cancer survivors optimize their health and quality of life. The clinic strives to provide appropriate risk-based care for survivors and works to increase awareness among healthcare providers of the unique needs of childhood cancer survivors.
The TLC clinic provides detailed information for cancer survivors and their families regarding the patient's treatment and risks for late effects, psychosocial evaluation and support, risk-based screening for late effects, and referrals to other specialists, as needed. The program is devoted to participating in research and outreach initiatives to better understand and meet the needs of pediatric cancer survivors.
Hope and Cope Psychosocial ProgramWith the diagnosis and treatment of childhood cancer or blood disorders come many emotional and practical challenges for the entire family. The Hope and Cope Program, at the Alabama Center for Childhood Cancer and Blood Disorders, provides support and services from diagnosis onwards using a family-centered approach, where the family and healthcare providers are partners working together to best meet the needs of the patient.
Our interdisciplinary team of skilled and compassionate specialists, including social workers, child life specialists, pediatric psychologists, pediatric neuropsychologists, chaplains, hospital-based teachers, school liaisons, art, music, and rhythm therapists provide emotional, psychological, and spiritual support, and also assist with concrete needs. Our goal is to help families maximize their strength at all stages of their child's treatment journey.
To ease the stress and distress from frequent hospitalizations or lengthy outpatient visits, the Hope and Cope Program offers the following emotional health and well-being activities:
In addition to clinical services, Hope and Cope team members are actively engaged in health related clinical research. Through these research projects, the Hope and Cope team seeks to better the health and well-being of children diagnosed with cancer or a blood disorder and their families.
Until childhood cancer and blood disorders are eliminated, Hope and Cope is here to empower young people and their families and to foster a sense of healing throughout the medical journey.
Avi Madan-Swain, PHDProfessor, UAB Department of Pediatrics Director, Hope and Cope Psychosocial Program205-638-9285
Abnormal Uterine Bleeding May Be Caused By Clotting Factor Deficiencies
A new review article illuminates why physicians should keep coagulation disorders in mind when evaluating patients with heavy abnormal uterine bleeding.
Physicians treating patients with heavy menstrual bleeding (HMB) should consider the possibility that rare bleeding disorders and hemophilia carrier states are at play if other, more common causes of bleeding have been excluded, according to a new report.
The report, a literature review published in Life (Basel),1 outlines several coagulation disorders and offers physicians guidelines on how to spot and treat hemostatic disorders.
Authors explain that current literature suggests 10% to 35% of women experience HMB at some point during their reproductive years. There are several potential causes of such bleeding, and physicians can use the PALM-COEIN system to help identify the underlying cause.
This system of abnormal uterine bleeding classification, from the International Federation of Gynaecology and Obstetrics,2 includes structural causes like polyps, adenomyosis, leiomyoma, malignancy, and hyperplasia, and functional causes, including coagulopathy, ovulatory disorder, endometrial disorders, iatrogenic conditions, or not-yet-classified causes. The existing literature suggests that an underlying inherited bleeding disorder is at play for 10% to 62% of adolescents with HMB. The most common such disorder is von Willebrand disease, but the authors said several other, less-common conditions should also be considered. Those less-common conditions are the focus of the review article.
The authors first reviewed several rare coagulation factor disorders. For instance, they said factor I, or fibrinogen, is a soluble plasma glycoprotein that in some patients is absent (congenital afibrinogenemia) or reduced (hypofibrinogenemia). In the former, patients can have a wide range of clinical manifestations, from minimal bleeding to serious hemorrhages, the authors said. Such patients may also experience arterial or venous thrombosis. In coagulation tests, partial thromboplastin time (PTT), prothrombin time (PT), thrombin time (TT) are all "infinitely prolonged," the authors said, since all of the parameters require the formation of fibrin.
Patients with hypofibrinogenemia are often asymptomatic if their fibrinogen levels are above 1 g/L, but the authors said these patients sometimes experience bleeding or thrombotic complications.
"In affected individuals, PT, PTT, and TT are variably prolonged, with TT being the most sensitive assay," they said.
Factor VII deficiency is believed to make up about one-third of rare coagulation disorders. The factor is vitamin K dependent and, like factor I, is synthesized in the liver and secreted in the plasma, the authors said. Patients with a deficiency of factor VII can have a wide range of manifestations, the authors said, "from asymptomatic or mildly symptomatic cases—for example, easy bruising, gum bleeding, and epistaxis—to severe cerebral and gastrointestinal hemorrhage."
Unfortunately, there are no clear treatment guidelines for factor VII deficiency, the authors said, although the published literature suggests a number of potential treatments, including surgery and blood transfusions.
Factor XIII deficiency is one of the rarest coagulation disorders, with only 500 cases reported globally since 1960, the authors said.
"Factor XIII is a transglutaminase that cross-links fibrin fibers between amino acid residues, hence stabilizing a fibrin clot," they wrote.
Patients with the deficiency can present with abnormal uterine bleeding, umbilical bleeding, or severe ovulation bleeding, among other clinical manifestations. However, the authors said factor XIII deficiency can be difficult to diagnose because clotting factor tests and platelet counts are normal in patients with the deficiency.
"The diagnosis can be made by measuring FXIII antigen levels using enzyme-linked immunosorbent assays and/or by measuring its activity with functional methods," the authors said. "Genetic testing of the genes encoding FXIII A or FXIII B is also an option for more specific assessment."
The authors also described several other disorders, including deficiencies of factors V, VIII, X, and XI, and hemophilia.
The investigators said they hope their report serves as a "useful guide" for physicians investigating abnormal uterine bleeding.
"We hope that this review can serve as a roadmap for busy clinicians to familiarize themselves with coagulation factor disorders as a cause of heavy menstrual bleeding and guide them towards more targeted research," they said.
They added, however, that theirs was not a systematic review, and therefore it should not be considered an exhaustive guide to diagnostic decisions.
References
1. Livanou ME, Matsas A, Valsami S, Papadimitriou DT, Kontogiannis A, Christopoulos P. Clotting factor deficiencies as an underlying cause of abnormal uterine bleeding in women of reproductive age: a literature review. Life (Basel). Published online June 5, 2023. Doi:10.3390/life13061321
2. Munro MG, Critchley HOD, Broder MS, Fraser IS; FIGO Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011;113(1):3-13. Doi:10.1016/j.Ijgo.2010.11.011
Bleeding Disorders Community Depends On Plasma Therapies
"We are blessed to live in a time when there are revolutionary medical advances," said Sonji Wilkes of Denver, whose 5-year-old son, Thomas, has severe hemophilia A and has used a range of plasma protein therapies to treat his bleeding disorder. Yet with these advances come concerns over safety, cost, insurance coverage and lifetime insurance caps.
Wilkes and her husband, Nathan, discovered early that these issues, particularly lifetime caps, would play a huge role in their son's care. "Just minutes after learning of our son's disorder, the doctor asked if we had good insurance coverage," said Wilkes. "At a time when we were at our most vulnerable and needed to be focused on Thomas' health, we had to consider financial and business decisions. It wouldn't be the last time."
Many individuals suffer from the inability to produce these proteins in sufficient quantities and therefore require replacement or augmentation therapies depending on the degree of the deficiency. The diseases treated with plasma protein therapies are often life-threatening and always serious and chronic conditions. They rely on the plasma protein therapies, which include recombinant blood clotting factor to sustain their health and enjoy a productive quality of life.
"It was infuriating to have to base medical decisions on the basis of some outdated business model that has not been adjusted to meet today's inflated medical costs."
— Sonji Wilkes
Lifetime caps are an insurance plan feature that limits the liability of an insurance provider to a maximum ceiling. These caps were initially set at $1 million in the 1970s, but they have not been adjusted to keep up with inflation. Individuals and families affected with bleeding disorders often have extremely high medical bills that cause them to reach their lifetime caps within short periods of time. Once a lifetime cap is reached, an insurance provider can terminate the policy and leave the individual or family scrambling for alternative coverage or without insurance.
In Thomas' case, he had accumulated medical costs of more than $1 million by his third birthday. "Like any other parent, I consider my children priceless," Wilkes said. "The health insurance industry, however, has put a price tag on Thomas' 5-year-old head. And when he became too expensive for them, the insurance company implemented a $1 million lifetime cap." Faced with this precarious situation, Wilkes and her husband were forced to make difficult decisions about their son's care. They contemplated changing jobs to obtain better coverage and even getting divorced in order to qualify for government assistance. They debated whether or not to delay giving Thomas a dosage with the rationale that maybe they could "save some money on the cap."
"It was infuriating to have to base medical decisions on the basis of some outdated business model that has not been adjusted to meet today's inflated medical costs," said Wilkes. A bill currently before congress, the Health Insurance Coverage Protection Act, addresses lifetime caps. This legislation would increase the minimum lifetime cap required of insurance companies to $10 million and ensures an annual inflationary index.
The Hemophilia Federation of America (HFA), a national, nonprofit organization that assists and advocates on behalf of the bleeding disorders community, believes it is imperative that the consumer's voice is heard and has recently relocated its office to Washington to ensure that this happens. No parents should have to consider other, less efficacious treatment options for their child because of cost. We support legislation that makes certain these lifesaving therapies are safe and available to all individuals with bleeding disorders.
Thomas' story provides a glimpse into the complexities inherent to living with an expensive chronic condition like a bleeding disorder. This community relies on safety, availability and access to medically necessary clotting factor products to treat their bleeding disorders. Through outreach and personal stories of those such as Thomas, the HFA and its member organizations champion the quality of life for people with bleeding disorders and seek to raise awareness and support from the greater public.
Kimberly Haugstad is the executive director of the Hemophilia Federation of America.
Back to homepage
Shelly Mattson treats her von Williebrand disease, an inherited, genetic bleeding disorder, with a plasma protein therapy and shares her experiences with other young adults.
Comments
Post a Comment