Management of von willebrand disease in pregnancy in resource-limited settings: a case report

Open a cess: www.balimedicaljournal.org and ojs.unud.ac.id/index.php/bmj Management of von willebrand disease in pregnancy in resource-limited settings: a case report Wayan Losen Adnyana1* Background: Von Willebrand’s disease (VWD) is the most common autosomal dominant bleeding disorder. Pregnancy and delivery in patient with VWD possess significant clinical challenges. Case description: a 24-year-old woman who will undergo labor with a history of VWD. The patient was planned for induction of vaginal delivery and has been given intranasal desmopressin, cryoprecipitate, and factor VIII from before delivery to 5 days after delivery. Labor occurs without excess bleeding. The patient was monitored for 6 days after delivery, and there is no complication of


INTRODUCTION
Von Willebrand disease (VWD) is an autosomal dominant bleeding disorder caused by quantitative or qualitative disturbances in Von Willebrand factor (VWF), that act as platelet-binding adhesive protein in the exposed sub-endothelial region and carries factor VIII (FVIII) in the circulation. Clinical manifestations of VWD are bleeding from mucocutaneous and soft tissue. The severity of the bleeding depends on the level of VWF dan FVIII in circulations. 1, 2 The heterogenicity of the phenotypes and pathophysiological mechanisms associated with VWD, pregnancy, and delivery in VWD presents significant clinical challenges. There is a change in VWD disease pattern in pregnancy compared to patients with VWD in general, so a careful evaluation is needed to determine the appropriate therapy in VWD patients with pregnancy and delivery plans. 3,4 In this report, the author describes the experience of handling von Willebrand patient's case with pregnancy with limited examination and treatment options.

CASE REPORT
A female patient, 24 years old, with a history of VWD since 2014 when the patient was 17 years old planned for labor. The patient complained of frequent gum bleeding since childhood. There are no complaints about prolonged or excessive menstruation. There are no complaints regarding bruising of the joints.
The patient is the first of four children. The second and third children of the patient's family had the same complaint as the patient, namely gum bleeding that often occurred. The patient's first brother was a male with the same complaint but was said to have died from excessive bleeding from the nose and mouth. The patient's second brother is a male who also has the same complaint and has been diagnosed with VWD. The patient's parents were said not to have the same complaint as the patient.
In the first control at Sanglah General Hospital, the patient was 33 weeks pregnant with no abnormality at the fetal examination and movement. The patient was given tranexamic acid and was planned to reexamine VWF Antigen and prepare for delivery using vaginal delivery methods, preparation of desmopressin, and cryoprecipitate. Repeated VWF antigen was 2% (50% -160%).
The patient was then hospitalized at 40 weeks' gestation in preparation for delivery. Laboratory
On July 15 th , 2020, vaginal induction of labor was carried out, but there was no progress in labor, so the cesarean section was performed with indications of failed induction. A baby girl weighing 3,540 grams was born, and there was no excess bleeding in the patient. Desmopressin, cryoprecipitate, and factor VIII were given for 5 days after the patient gave birth. The patient and baby were then evaluated for 6 days at Sanglah General Hospital, and there was no excessive bleeding in the birth canal.

DISCUSSION
Women naturally have physiological changes in menstruation, pregnancy, and childbirth that can cause profuse bleeding without specific bleeding disorders. Pregnancy itself is classified as a hypercoagulable condition due to an increase in factor VII, X, fibrinogen, and plasminogen activator 1, accompanied by a decrease in protein S, which works as an adaptive mechanism to prepare for labor. During pregnancy, levels of VWF and FVIII increase significantly in normal women with the highest rates in the third trimester, with levels usually more than 100 IU/dL at delivery. 5, 6 One study showed that women with VWD have risk of experiencing antepartum bleeding 10 times more likely (OR 10.2; 95% CI 7.1-14.6). Based on this data, the management of VWD in pregnancy should not only focus on the time of delivery but during preconception, antepartum, delivery, and postpartum. 7 Delivery and postpartum period possessed a high risk of bleeding in VWD woman. The risk of bleeding during vaginal delivery or cesarean delivery is low if the VWF and FVIII levels are above 50 IU / dL. Women with mild type 1 VWD can give birth in a community hospital with a hematologist's direction. For patients with severe type 1, type 2, and 3 VWD, delivery should be done in a health facility with an obstetrician, hematologist onsite, has facilities for checking coagulant factors, supporting transfusion and adequate pharmacy and has appropriate hemostatic agents. 8 The method of delivery was chosen based on the consideration of the obstetrician. Vaginal and cesarean delivery have the same safety for mothers and babies if maternal coagulation factors are within normal limits. Intracranial bleeding in fetuses with VWD is rare; however, precautions must be taken. Delivery should be carried out by the traumatic method to a minimum by preventing a long secondstage phase or, if necessary, proceed to cesarean delivery. The use of forceps and vacuum should be avoided to minimize the risk of hematoma and intracranial bleeding. 9 In patients with VWD type 1 with FVIII or VWF levels <30 U / dL at delivery, desmopressin is required to increase coagulation factor levels prior to epidural injection delivery. Desmopressin has a maximal effect on coagulation factors 30-60 minutes after intravenous administration (0.3 µg / kgBW) and 90-120 minutes after intranasal administration (<50 kg, 150 µg;> 50 kg, 300 µg). Desmopressin is given 3-4 days postpartum because of the decrease in VWF levels that occur after delivery. 5, 10 In pregnant patients with type 2 VWD with levels of FVIII:C and VWF:Ag 30-50 IU / dL, desmopressin can be given after umbilical clamping and continued for 3-4 days after that. Patients with VWD type 2, FVIII / VWF concentrates for at least 3 days are required. In pregnant patients with Type 2B VWD there will be an increase in the multimers level, abnormally increasing the affinity of Ib on the platelet surface, causing thrombocytopenia. In this case, platelet transfusion in pregnant women indicated a platelet count <30.000 / µL. In pregnant patients with Type 2N VWD in whom late pregnancy FVIII levels do not reach normal values, desmopressin and VWF concentrates may be given if desmopressin is not sufficient. Patients with VWF type 3 do not have elevated levels of FVIII and VWF during pregnancy due to the absence of endothelial deposits. In this case, a VWF/FVIII concentrate is required during pregnancy and at delivery to prevent excessive bleeding. 5, 10 In areas where there is no VWF concentrate infusion, the use of cryoprecipitate which has about 80 units of FVIII in one standard unit, can be administered in life-threatening situations. Cryoprecipitate carries a risk of transmission of infectious agents, so its use is only given when concentrated plasma is not available. 11 In the postpartum condition, the VWF and FVIII levels fell below baseline immediately after delivery. VWF and FVIII levels should be monitored from the first to the fifth day postpartum. Bleeding complications in the postpartum period are minimal if the VWF and FVIII levels are above 50 IU/dL. Oral antifibrinolytic agents can be given during this period to prevent PPH due to excessive lochia. 12