Hemophilia A and B predominantly attracts clinical attention in males due to X‐linked inheritance, introducing a bias toward female carriers to be asymptomatic. This common misconception is ...contradicted by an increasing body of evidence with consistent reporting on an increased bleeding tendency in hemophilia carriers (HCs), including those with normal factor VIII/IX (FVIII/IX) levels. The term HC can hamper diagnosis, clinical care, and research. Therefore, a new nomenclature has been defined based on an open iterative process involving hemophilia experts, patients, and the International Society on Thrombosis and Haemostasis (ISTH) community. The resulting nomenclature accounts for personal bleeding history and baseline plasma FVIII/IX level. It distinguishes five clinically relevant HC categories: women/girls with mild, moderate, or severe hemophilia (FVIII/IX >0.05 and <0.40 IU/ml, 0.01–0.05 IU/ml, and <0.01 IU/ml, respectively), symptomatic and asymptomatic HC (FVIII/IX ≥0.40 IU/ml with and without a bleeding phenotype, respectively). This new nomenclature is aimed at improving diagnosis and management and applying uniform terminologies for clinical research.
IMPORTANCE: Recent studies have documented increased bleeding symptoms and related complications in patients with low von Willebrand factor (VWF), highlighting the clinical significance of this ...entity. Because children and adolescents with VWF deficiencies often present to primary care physicians with bleeding symptoms, physicians need to be aware of this condition for early detection. OBSERVATIONS: Studies have found that children and adolescents with low VWF (VWF levels of 30-50 IU/dL) can present with clinically significant bleeding, including mucosal, menstrual, postsurgical, and posttraumatic bleeding, leading to complications such as anemia, iron deficiency, transfusion, hospitalization, and poor quality of life. Detecting and promptly managing low VWF in children and adolescents with bleeding are essential because failure to do so can lead to significant morbidity in adulthood, especially among female patients, including continued heavy menstrual bleeding; postpartum hemorrhage; related gynecologic complications, such as hemorrhagic ovarian cysts; and surgical interventions for heavy menstrual bleeding, including hysterectomy. This narrative review summarizes the observations of several studies that have shed light on the pathophysiologic mechanisms of low VWF and bleeding in these patients and the available diagnostic modalities and treatment options. CONCLUSIONS AND RELEVANCE: Studies in children and adolescents have provided important insights into the clinical phenotype, complications, pathophysiologic mechanisms, evaluation, and management of low VWF, now recognized as an important clinicopathologic entity, as presented in this review. As gatekeepers, primary care physicians play an important role in guiding patients with this recently recognized clinicopathologic entity toward appropriate specialty care and providing continued comanagement to prevent future complications as the patients enter adulthood.
Purpose of review
To summarize the recent literature related to female hemophilia A carriers with respect to prevalence in the population, the impact of baseline factor VIII levels and other ...influences on bleeding phenotype, and clinical management needs.
Recent findings
Many female hemophilia A carriers are at risk for abnormal bleeding, yet they are underrecognized by healthcare providers and their bleeding symptoms are underreported. Low FVIII levels are consistently associated with clinically significant bleeding and correlate well with skewed X chromosome inactivation (XCI). Most interestingly, bleeding tendency is also observed in some hemophilia A carriers with normal factor VIII levels and requires further investigation. Well controlled studies investigating peripartum and periprocedural FVIII levels and adequate hemostatic treatment are necessary to inform management guidelines.
Summary
Prevalence and bleeding tendency of hemophilia A carriers remain underreported, despite a significant proportion having low FVIII levels. Skewed XCI may explain low FVIII but does not explain the bleeding risk encountered in a larger proportion of hemophilia A carriers with random XCI and borderline/normal FVIII.
Women and girls with bleeding disorders face multiple bleeding challenges throughout their life. The most significant morbidity and mortality are due to heavy menstrual bleeding and postpartum ...hemorrhage in their reproductive years. The ASH/ISTH/NHF/WFH 2021 guidelines on diagnosing and managing von Willebrand disease (VWD) provide several new updates.
Women with VWD have a higher prevalence of heavy menstrual bleeding. The subpopulation of adolescents is particularly vulnerable, as the diagnosis is often delayed with increased comorbidity of iron deficiency anemia and associated symptoms. A detailed review is done on the prevalence of bleeding-related complications, especially heavy menstrual bleeding (HMB) and post-partum hemorrhage (PPH). The management strategies are also reviewed in detail, with a specific focus on the target factor levels and the use of antifibrinolytics.
The 2021 ASH/ISTH/NHF/WFH diagnostic and management recommendations are reviewed with a specific focus on hormonal methods of HMB management and antifibrinolytics in this situation. The reviewed topics include neuraxial anesthesia, factor cutoff, and tranexamic acid use in the postpartum period.
Objective:
To report a case of dabigatran-induced overanticoagulation in a patient who developed acute renal failure and to inform health care providers of the need for appropriate patient selection ...and periodic monitoring of renal function in the elderly.
Case Summary:
A 66-year-old woman treated with dabigatran for atrial fibrillation developed acute renal failure and upper gastrointestinal bleeding. She had been taking dabigatran 150 mg twice daily for 2 months, with intermittent renal insufficiency during the previous 6 months. On admission, laboratory values included serum creatinine 3.6 mg/dL, hematocrit 21%, and international normalized ratio greater than 10. She was treated with packed red blood cells, prothrombin complex concentrate, and multiple sessions of dialysis. There were no further bleeding events or additional transfusions for the remainder of the hospitalization. Her renal function never recovered and she remained hemodialysis-dependent. After a 47-day length of stay, she was transferred to a nursing home where she died 2 months later.
Discussion:
Renally eliminated drugs such as dabigatran place elderly patients at increased risk of drug accumulation and adverse drug events due to age-related decline in renal function. In a recent case series, dabigatran toxicity in the elderly with renal impairment was described with 1 fatal outcome. Recent literature, including the package insert, advises intermittent monitoring of renal function in the elderly and those with moderate renal impairment. Consideration should also include the appropriateness of dabigatran therapy in patients with fluctuating renal function. In our patient, the Naranjo probability scale indicated a probable cause between the bleeding event and dabigatran use.
Conclusions:
Our case report, along with 2 other recent reports on dabigatran toxicity, illustrates the importance for appropriate patient selection and the need to periodically monitor renal function in elderly patients receiving dabigatran.
PURPOSE OF REVIEWThe morbidity and mortality of postpartum hemorrhage (PPH) in women with an underlying bleeding disorder requires vigilance by the hematologist.
RECENT FINDINGSRecent studies suggest ...that women with underlying bleeding disorders may be ‘undertreated’ at the time of delivery in aiming for too low a target elevation that historically per numerous society guidelines has aimed for VWF/FVIII:C levels to be ‘only’ greater than 50% when in actuality the levels should be akin to what is achieved in a normal pregnancy. The result appears to be an increase in the rate and degree of PPH. In this context, although recent studies imply DDAVP is well tolerated, DDAVP may not be appropriate because it may not raise the levels into the normal supraphysiological range nor maintain it for several days. Particularly in women with rare bleeding disorders, i.e., non-FVIII:C or VWF deficient, adjunctive antifibrinolytic therapy, e.g., tranexamic acid, appears to be in order as a prophylactic measure.
SUMMARYWomen with an underlying bleeding disorder appear to be at a heightened risk for PPH if the respective coagulation factor level is not appropriately replaced to the level that is physiologically achieved in a normal pregnancy. Furthermore, there appears to be underuse of tranexamic acid for prophylaxis of PPH in this population.
For reproductive-aged women, the symptom of heavy menstrual bleeding is highly prevalent and a major contributor to iron deficiency and its most severe manifestation, iron deficiency anemia. It is ...recognized that these 2 clinical entities are not only highly prevalent, but their interrelationship is poorly appreciated and frequently normalized by society, healthcare providers, and affected girls and women themselves. Both heavy menstrual bleeding and iron deficiency, with or without anemia, adversely impact quality of life—heavy menstrual bleeding during the episodes of bleeding and iron deficiency on a daily basis. These combined issues adversely affect the lives of reproductive-aged girls and women of all ages, from menarche to menopause, and their often-insidious nature frequently leads to normalization. The effects on cognitive function and the related work and school absenteeism and presenteeism can undermine the efforts and function of women in all walks of life, be they students, educators, employers, or employees. There is also an increasing body of evidence that suggests that iron deficiency, even in early pregnancy, may adversely impact fetal neurodevelopment with enduring effects on a spectrum of cognitive and psychological disorders, critically important evidence that begs the normalization of iron stores in reproductive-aged women. The authors seek to raise individual, societal, and professional awareness of this underappreciated situation in a fashion that leads to meaningful and evidence-based changes in clinical guidance and healthcare policy directed at preventing, screening, diagnosing, and appropriately managing both disorders. This manuscript provides evidence supporting the need for action and describes the elements necessary to address this pervasive set of conditions that not only affect reproductive-aged girls and women but also the lives of children everywhere.
Depression and anxiety in persons with Von Willebrand disease Roberts, Jonathan C.; Kulkarni, Roshni; Kouides, Peter A. ...
Haemophilia : the official journal of the World Federation of Hemophilia,
March 2023, 2023-Mar, 2023-03-00, 20230301, Letnik:
29, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Objective
We assessed sociodemographic and clinical characteristics associated with depression and anxiety in individuals with Von Willebrand disease (VWD) aged ≥12 years.
Methods
The study collected ...data on patients’ sociodemographic, joint problems and health‐related quality of life (HRQoL) using EQ‐5D‐3L, 8‐item patient health questionnaire for depression and 7‐item Generalized Anxiety Disorder Questionnaire from participants in seven geographically diverse US haemophilia treatment centres.
Results
Analyses included 77 participants. The rates of depression and anxiety were 63.6% and 58.3%, respectively. Persons with low VWF displayed higher rates of depression (86.7%) or anxiety (69.2%) compared to those with VWD (58.1%, p = .04 for depression, and 55.9%, p = .38 for anxiety). Logistic regression analyses demonstrated that having joint problems (odds ratio OR = 6.3, confidence interval CI = 2.0–20.1) was the most important variable associated with depression, followed by being single, divorced, widowed, or separated in adult participants or parents of participants age < 18 years (OR = 7.0, CI = 1.7–29.0. The most important variable associated with anxiety was being single or lacking a partner (OR = 10.8, CI = 2.5–47.5), followed by age 12–17 years old (OR = 6.7, CI = 1.6–26.9), or having worse health compared to 3‐months ago (OR = 12.3, CI = 1.3‐116.2). Mean covariates adjusted EQ visual analogue scale score was significantly lower among persons with depression (68.77 ± 3.15 vs. 77.58 ± 4.24, p = .03) than those without depression.
Conclusions
Our study revealed concerning levels of depression and anxiety in this VWD sample. Lack of social support was determined an important factor associated with depression and anxiety in this sample. Mental health screening is critical in VWD clinical evaluation and care.
von Willebrand disease (VWD) type 2B is a rare bleeding disorder, presenting with moderate-to-severe lifelong bleeding. We present the case of a 61-year-old woman who was misdiagnosed as immune ...thrombocytopenic purpura during her three pregnancies resulting in a delayed diagnosis of VWD type 2B. This genetically confirmed diagnosis resulted in testing and the establishment of the diagnosis in her otherwise asymptomatic adult son as well. VWD may not be diagnosed till beyond mid adulthood in women with thrombocytopenia previously attributed to pregnancy and should be considered as a differential in female patients developing thrombocytopenia less than 100 × 10/μl with an increased bleeding assessment tool score.
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