Haemophilia

Summary.  Lack of detailed natural history and outcomes data for neonates and toddlers with haemophilia hampers the provision of optimal management of the disorder. We report an analysis of prospective data collected from 580 neonates and toddlers aged 0–2 years with haemophilia enrolled in the Universal Data Collection (UDC) surveillance project of the Centers for Disease Control and Prevention (CDC). This study focuses on a cohort of babies with haemophilia whose diagnosis was established before the age of two. The mode of delivery, type and severity of haemophilia, onset and timing of haemorrhages, site(s) of bleeding, provision of prophylaxis with coagulation factor replacement therapy, and the role played by the federally funded Haemophilia Treatment Centers (HTC) in the management of these infants with haemophilia were evaluated. Seventy‐five per cent of haemophilic infants were diagnosed early, in the first month of life, especially those with a family history or whose mothers were known carriers; infants of maternal carriers were more likely to be delivered by C‐section. Involvement of an HTC prior to delivery resulted in avoidance of the use of assisted deliveries with vacuum and forceps. Bleeding from the circumcision site was the most common haemorrhagic complication, followed by intra‐ and extra‐cranial haemorrhages and bleeding from heel stick blood sampling. Eight per cent of the infants were administered factor concentrate within 24 h of birth; more than half were treated to prevent bleeding. This study highlights the significant rate and the sites of initial bleeding unique to very young children with haemophilia and underscores the need for research to identify optimal evidence‐based recommendations for their management.

Summary. In women, menorrhagia may be the most common manifestation of a bleeding disorder, but it is not the only reproductive tract abnormality that women with bleeding disorders experience. Women with bleeding disorders appear to be at an increased risk of developing haemorrhagic ovarian cysts and possibly endometriosis. As they grow older, they may be more likely to manifest conditions, which present with bleeding such as fibroids, endometrial hyperplasia and polyps. Women with bleeding disorders are more likely to undergo a hysterectomy and are more likely to have the operation at a younger age. During pregnancy, they may be at greater risk of miscarriage and bleeding complications. At the time of childbirth, women with bleeding disorders appear to be more likely to experience postpartum haemorrhage, particularly delayed or secondary postpartum haemorrhage. Vaginal or vulvar haematomas, extremely rare in women without bleeding disorders, are not uncommon. While women with bleeding disorders are at risk for the same obstetrical and gynaecological problems that affect all women, they appear to be disproportionately affected by conditions that manifest with bleeding.

Summary.  The gynaecological and obstetric management of women with inherited coagulation disorders requires close collaboration between obstetrician/gynaecologists and haematologists. Ideally these women should be managed in a joint disciplinary clinic where expertise and facilities are available to provide comprehensive assessment of the bleeding disorder and a combined plan of management. The haematologist should arrange and interpret laboratory tests and make provision for appropriate replacement therapy. These guidelines have been provided for healthcare professionals for information and guidance and it is also intended that they are readily available for women with bleeding disorders.

The case records of 13 patients (24 pregnancies) with von Willebrand's disease (vWD) were studies rettospectively. The overall incidence of primary and secondary post‐partum haemorrhage (PPH) was 15.8% and 25% respectively, all primary PPH occurring in tyre 2 discase (3/14 deliveries, 21.4%). The risk of primary PPH in type 2 patients who did not receive prophylactic factor VIII was 37.5% (3/8 deliveries).

Factor VIII coagulant activity (VIII:C) and von Willebrand factor antigen (vWF:Ag) rose above bascline values by a factor of at least 1.5 during the pregnancy in most case. More severely affected patients were less likely to benefit significatntly. A baseline VIII:C of <15 iu/dl (4/14 cases) was predictive of a third trimester level of <15 iu/dl. Improvements in the von Willebrand factor activity were less marked. The baseline von Willebrand factor activity was <15 iu/dl in all patients with serial data, none of whom achieved a third‐trimester von Willebrand factor activity of >50 iu/dl. The bleeding times were unaltered significantly in all but one of the cases, reflecting a general failure of the primary haemostatic defect to improve with pregnancy.

The findings demonstrate that coagulation parameters do not universally improve in pregnancy in vWD, especially when preconception levels are low. The risk of primary PPH is generally higher in type 2 diseases. The level of factor VIII:C is not a good predictor of the risk of primary PPH in type 2 patients. Secondary PPH is a significatnt risk in both type 1 and type 2 patients.

Summary.  von Willebrand disease (VWD) is a commonly encountered inherited bleeding disorder affecting both males and females, causing mucous membrane and skin bleeding symptoms, and bleeding with surgical or other haemostatic challenges. VWD may be disproportionately symptomatic in women of child‐bearing age. It may also occur less frequently as an acquired disorder (acquired von Willebrand syndrome). VWD is caused by deficiency or dysfunction of von Willebrand factor (VWF), a plasma protein that mediates platelet haemostatic function and stabilizes blood coagulation factor VIII. The pathophysiology, classification, diagnosis and management of VWD are relatively complex, but understanding them is important for proper diagnosis and management of patients with VWD. These evidence‐based guidelines for diagnosis and management of VWD from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel (USA) review relevant publications, summarize current understanding of VWD pathophysiology and classification, and present consensus diagnostic and management recommendations based on analysis of the literature and expert opinion. They also suggest an approach for clinical and laboratory evaluation of individuals with bleeding symptoms, history of bleeding or conditions associated with increased bleeding risk. This document summarizes needs for further research in VWF, VWD and bleeding disorders, including clinical research to obtain more objective information about bleeding symptoms, advancements in diagnostic and therapeutic tools, and enhancement in the education and training of clinicians and scientists in bleeding and thrombotic disorders. The NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/vwd) has a more detailed document, a synopsis of these recommendations, and patient education information.

Summary.  von Willebrand disease (VWD) is the commonest inherited bleeding disorder. The aim of therapy for VWD is to correct the two defects of haemostasis in this disorder, impaired primary haemostasis because of defective platelet adhesion and aggregation and impaired coagulation as a result of low levels of factor VIII. The objective of this guideline is to inform individuals making choices about the treatment and management of VWD including the use of therapeutic products. This is the second edition of this UK Haemophilia Centre Doctors' Organization (UKHCDO) guideline and supersedes the previous edition which was published in 1994.

Summary.  The rare coagulation disorders are heritable abnormalities of haemostasis that may present significant difficulties in diagnosis and management. This review summarizes the current literature for disorders of fibrinogen, and deficiencies of prothrombin, factor V, FV + VIII, FVII, FX, the combined vitamin K‐dependent factors, FXI and FXIII. Based on both collective clinical experience and the literature, guidelines for management of bleeding complications are suggested with specific advice for surgery, spontaneous bleeding, management of pregnancy and the neonate. We have chosen to include a section on Ehlers‐Danlos Syndrome because haematologists may be consulted about bleeding manifestations in such patients.

Summary.  Menorrhagia at the time of menarche is relatively common and historically attributed primarily to immaturity of the pituitary–ovarian–uterine axis. Intuitively, a proportion of these patients should have an underlying disorder of haemostasis, given the 5–20% prevalence of von Willebrand’s disease and the ≥20% prevalence of platelet dysfunction in light of recent epidemiological studies in menorrhagia, although the average age of the patients in those studies has been ∼35 years. However, there are a few comprehensive studies in the adolescent population determining whether widespread haemostasis evaluation should be carried out in adolescents presenting with menorrhagia. A retrospective chart review study of disorders of haemostasis was carried out in 61 consecutive adolescent patients, ages 11–19 at the time of evaluation referred to the Hemophilia Treatment Center (HTC)/Hematology unit. The mean and median ages were 15 ± 2.2 and 14 years (11, 19), respectively. Standard evaluation included complete blood count, prothrombin time, partial thromboplastin time, von Willebrand factor (VWF) levels and platelet aggregation. The proportion of patients with VWF deficiency was 22/61 (36%) [95% confidence interval (CI), 24–49%]; the proportion of patients with platelet aggregation abnormalities was 4/61 (7%) (95% CI, 2–16%). There was no difference in the frequency of additional muco‐cutaneous bleeding symptoms. A relatively high proportion of adolescents are identified with an underlying disorder of haemostasis when referred to an HTC for evaluation of menorrhagia. This involves in part a selective referral bias, but underscores the role of the HTC in evaluating adolescents referred with menorrhagia for an underlying bleeding disorder, given the relatively high yield of haemostatic disorders detected in this setting.

Summary.  Evidence‐based guidelines are presented on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders. They include details of therapeutic products available in the UK and they update and replace previous United Kingdom Haemophilia Centre Doctors’ Organisation guidelines.