Managementul sarcinii la o pacientă cu boală Von Willebrand: prezentarea unui caz de îngrijire adaptată

Introduction

The Von Willebrand disease (VWD) is a clotting condition that is defined by a quantitative or qualitative deficit⁽¹⁾. VWF is synthesized in megakaryocytes and endothelial cells, and through its interactions with several platelet adhesion and aggregation receptors, it is essential for both primary and secondary hemostasis. Additionally, it takes part in secondary hemostasis by serving as a transporter for factor VIII (FVIII) to prevent the latter’s breakdown in plasma due to activated protein C^(2,3). Von Willebrand disease affects females⁽⁵⁾ with a mean age of 19 years old at the time of diagnosis, the prevalence of all forms of the illness beeing estimated between 0.6% and 1.3%. The symptomatic form of the condition, on the other hand, requires particular therapy. There are three types of illness, with type 1 accounting for 70-78% of patients and exhibiting partial quantitative VWF deficit. Subtypes A, B, M and N of type 2 are VWF deficient, and their VWF affinity for factor VIII is very low. Type 2 is characterized by a qualitative VWF deficit. Lastly, a full quantitative VWF deficit is the hallmark of VWD type 3⁽¹⁾. Types 2N and 3 of the illness have an autosomal recessive inheritance pattern, while types 1, 2A, 2B and 2M have a dominant autosomal pattern^(3,4,6). Early diagnosis is typically suspected after symptoms such abnormal uterine bleeding, gum bleeding, epistaxis and, in more severe cases, gastrointestinal bleeding. VWF quantification based on antigen levels or VWF and clotting factor VII activity are used to validate the diagnosis. The diagnosis is made based on VWF levels less than 30% or less than 50% when bleeding symptoms are present, suggesting the necessity to refer to hematology centers for appropriate categorization^(3,7). In order to produce the preventive changes required to ensure a lower probability of postpartum bleeding, estrogens increase protein synthesis in the liver as part of the physiological changes during pregnancy. This increases clotting factors VII, VIII, X, XII, VWF and fibrinogen. It also shortens the thromboplastin time and lowers protein S levels⁽⁸⁾. Consequently, VWF and factor VIII may rise to normal levels, primarily in cases of type 1 and type 2 illnesses. These levels tend to decrease throughout the postpartum period, increasing the risk of bleeding and the requirement for blood products to be transfused. This can lead to secondary problems, including acute renal damage, pulmonary edema, respiratory failure, and even maternal mortality⁽⁹⁾. During labor and the postpartum period, desmopressin or factor VIII and VWF replacement therapy are the two available therapeutic choices for this medical state⁽¹⁰⁾. Nevertheless, no research has demonstrated that any of these methods is better during pregnancy⁽¹¹⁾. The aim of this article is to present the case of a pregnant 35-year-old female diagnosed with Von Willebrand disease, who had an adequate perinatal outcome, and to describe the institutional protocol used for the management of this condition during childbirth and the postpartum period.

Case presentation

A 35-year-old female, primigravida, at 38 weeks of gestation, was admitted at our hospital for caesarean section. She had a history of Von Willebrand type 1 diagnosed at 17 years of age, when she had gum bleeding on multiple occasions. She had a history of sustained pelvic injury where she needed blood transfusion on being operated. She also had a history of pelvic hemoperitoneum with corpus lu­teum hematoma, and she required surgery with fresh frozen plasma and packed red cell transfused. Also, she had a history of hematoma in right knee requiring aspiration with multiple aspirations needed. She always had menorrhagia for 10 days from the age of menarche. She did not require factor VIII administration during the postpartum period after delivering a term baby. To implement the childbirth care protocol designed for females with VWD (Table 1), a multidisciplinary meeting, including gynecology, maternal-fetal medicine, hematology and anesthesia, was called. The goal of the protocol is to reduce the risk of bleeding by using prophylaxis with Von Willebrand factor and clotting factor VIII concentrate. Laboratory findings for 30 weeks prior to admission to the maternal-fetal unit revealed 25.45% Von Willebrand factor activity and 27% clotting factor VIII antibodies (Table 2). Upon physical examination, the patient had a 10/10 biophysical profile and concordant fetal well-being as assessed by fetal biometrics. The patient was also hemodynamically stable. Elastography report in the patient before caesarean section suggested that the liver’s stiffness was within the normal range, indicating no significant fibrosis or liver pathology. A baby weighing 2760 g and measuring 47 cm was delivered by caesarean delivery without complications. The baby had an Apgar score of 9-9-10. Uterotonic drugs used included intravenous methylergonovine 0.2 mg and sublingual misoprostol 600 mcg. The postpartum period evolved without complications, and the patient was discharged on the seventh hospitalization day. No additional bleeding episodes occurred during outpatient follow-up.

 

Discussion

Von Willebrand disease is a common condition in wo­men who are fertile. It is linked to increased risk of postpartum hemorrhage, exposure to extensive transfusion protocols, acute renal injury, pulmonary edema, maternal mortality linked to postpartum hemorrhage, and complications related to transfusions during pregnancy⁽¹⁰⁾. In order to plan for delivery, factor VIII and VWF levels during the prenatal period, especially in the third trimester, need to be closely monitored⁽¹²⁾. This is because elevated levels of procoagulant factors, which typically fall within the normal range⁽¹¹⁾, can have values as high as 100 IU/dL⁽¹²⁾, indicating pathophysiological changes. High-complexity centers with hematology and transfusion services should be the place where care is given during birth. It is important to make sure that drugs like VWF, clotting factor VIII, uterotonics, antifibrinolytics and blood products are accessible ahead of time. VWF and factor VIII levels must be greater than 50 UI/dL in order for females to give birth vaginally; in the event that a caesarean section is necessary, Von Willebrand factor levels must be greater than 50 UI/dL and factor VIII levels above 80 UI/dL⁽¹⁾ in cases of type 1 illness. VWF objectives, however, have to be greater in females with type 2 or type 3 illness, aiming for levels over 100 UI/dL⁽¹³⁾. There is no need for pharmaceutical prophylaxis if the levels are within normal ranges. The prescribed therapies for this illness during the intrapartum period include 300 mcg administered intravenously or intravenous desmopressin at a dosage of 0.3 mcg/kg (maximum dose: 25-30 mcg), which peaks 30-90 minutes after delivery and must be given every 12-24 hours⁽¹³⁾. On the other hand, type 1 Von Willebrand disease is considered to be treated with this medicine as first line, while type 3 disease has not demonstrated any efficacy⁽⁹⁾. It has also been reported that VWF and factor VIII can be managed at a loading dose of 40-60 IU/kg (as VWF/FVIII 500/200 IU 10/mL). Since our patient had previously received treatment with VWF and factor VIII, and she had an excellent response, the same treatment plan was maintained during pregnancy. Antifibrinolytics, such as tranexamic acid (1000 mg, three times a day)⁽¹³⁾ or epsilon-aminocaproic acid (100-150 mg/kg loading dose, followed by infusion of 10-15 mg/kg/hour⁽¹⁾), may also be added to these therapies to increase their effectiveness. Nevertheless, there is little literature on the preventive use of uterotonics as part of the strategy for controlling bleeding after labor. Therefore, in the event that uterine atony is the cause of postpartum hemorrhage, these kinds of drugs ought to be administered. Given the hereditary inheritance of this condition, it is particularly crucial to prevent instrumentation at the moment of delivery, since it increases the risk of bleeding in both the mother and the newborn^(14,15). In these females, prenatal genetic counseling is recommended. For females without VWD, the standard procedure for giving oxytocin during an active delivery can be followed; however, due to the higher risk of hyponatremia, oxytocin in combination with desmopressin should be administered with caution⁽⁹⁾. Given that women are more likely to experience delayed postpartum bleeding, close in-hospital monitoring is necessary for 5-7 days. During this time, there is a greater risk of VWF depletion, which increases the risk of obstetric bleeding in the 48 hours following delivery. The pharmacological management can involve desmopressin or combined VWF/FVIII medications⁽¹⁶⁾. Our procedure calls for a term delivery, which occurs between 38 and 39 weeks, to prevent an unplanned labor due to the possibility of obstetric hemorrhage.

Conclusions

Patients with Von Willebrand disease who are pregnant need specialist treatment in gynecology, hematology, critical care, maternal-fetal medicine and transfusion medicine from a multidisciplinary team in centers specifically designed for this purpose. The best course of action is to diagnose the type of Von Willebrand disease in advance. Desmopressin is the chosen course of action; if not, VWF and factor VIII are used for early therapy. Considering the highest risk of postpartum hemorrhage, observation in the critical care unit is essential for at least 48 hours. For these individuals, a clear plan for managing labor is essential.   

 

Corresponding author: Smit Bharat Solanki E-mail: drsmitbharat@gmail.com

Conflict of interest: none declared.

Financial support: none declared.

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