Von Willebrand disease (VWD) is one of the most common inherited bleeding diseases. Based on a conservative estimate of prevalence (at least 100 per million persons) (1-7) and a population of 5.8 billion, there are at least 580,000 persons with symptomatic VWD worldwide who could benefit from appropriate diagnosis followed by replacement or pharmacological therapy. Approximately 80% of these persons live in the developing world. Because severe menorrhagia is common in VWD, the disease tends to cause greater morbidity in women of childbearing age. Consequently, VWD impairs the health of a critical segment of the population during a time of life when the demands of work and family are the greatest.

Impact, Diagnosis and Treatment of von Willebrand Disease*

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.

More than menorrhagia: a review of the obstetric and gynaecological manifestations of bleeding disorders

The effect of pregnancy on the components of the fibrinolytic enzyme system was determined by serial observations on 10 healthy women during normal pregnancy, labour, and the puerperium. The plasminogen level was substantially increased in the third trimester; the increase occurred pari passu with a pronounced increase in fibrinogen concentration. After allowing for the expansion of plasma volume in pregnancy a twofold increase in the absolute amounts of circulating fibrinogen and plasminogen was found. In late pregnancy and during labour the level of plasminogen activator was greatly decreased, whereas a normal or increased level was present in the first week of the puerperium. No alteration in the levels of inhibitors of plasminogen activation by urokinase was found during normal pregnancy. The thrombin time and platelet count remained unchanged during pregnancy and labour but the platelet count rose significantly during the first week of the puerperium.The haemostatic mechanism in pregnancy appears to be altered towards an enhanced capacity to form fibrin and a diminished ability to lyse fibrin. These changes may be a physiological development to ensure the integrity of the foetal and maternal circulations and provide rapid and effective haemostasis in the uterus during and after placental separation. Nevertheless, the changes may also establish a vulnerable state for intravascular fibrin deposition.

https://www.bmj.com/content/bmj/3/5667/387.full.pdf

Fibrinolytic enzyme system and pregnancy.

The obstetric experience of carriers of haemophilia.

Efficient treatment of von Willebrand's disease (vWD) is predicated not only on an accurate diagnosis but also on a basic understanding of the major types and subtypes of this heterogeneous group of bleeding disorders. This article deals with the general approach to these patients, control of superficial bleeding, appropriate use of adjunctive agents (i.e., antifibrinolytic drugs), and currently available measures to raise systemic levels of the von Willebrand factor/factor VIII complex. The bearing of specific types and subtypes of vWD on treatment is discussed. Handling of common bleeding problems encountered in vWD and recommendations for managing these patients during pregnancy and surgery are presented. Treatment of the acquired vWD is reviewed.

Aggeler Pm

Papers

Blood clotting factors in pregnancy: factor 8 concentrations in normal and ahf-deficient women.