IN THE NAME OF GOD

1. IN THENAMEOF GOD

2. حاملگی و زایمان در خانم های مبتلا به اختلالات خونریزی دهنده دکترزهرابدیعی شیراز 28-29 خرداد 93

3. Preconception counselling • This is most important for women with severe bleeding disorders or those who could potentially carry a severely affected baby, such as carriers of hemophilia • It provides adequate information for women and their family about - genetic implications of their disorder - the available reproductive choices, - and options for prenatal diagnosis.

4. planning for pregnancy • establishing howand where the pregnancy can best be managed. • immunization against hepatitis A and B for those likely to require blood transfusion • general advice such as folic acid supplementation. • A DDAVP test dose can also be carried out to assess response. • the opportunity to speak with a pediatric hematologist regarding the care of a potentially affected child.

5. Antenatal management Normal pregnancy is accompanied by • Increased concentrations of several coagulation factors including VIII, VWF, and a pronounced increase in fibrinogen • reduced fibrinolytic activity secondary to increased levels of plasminogen activator inhibitors, especially during the third trimester • All of these changes contribute to the hypercoagulable state of pregnancyand, in women with bleeding disorders, to improved hemostasis

6. however, women with bleeding disorders oftendo not achieve the same levels of clotting factors that other women do and, therefore, are still at an increased risk of bleeding complications. Except : Carriers of Hemophilia A vWD type 1

7. Baseline factor VIII and von Willebrand factor levels should be checked at some stage early in the pregnancy, such as during the first consultation with an obstetrician and in the third trimester(ideally at around 34 weeks). • The level of vWFmay notrise significantly during the first or even second trimesterand therefore an early miscarriage may be accompanied by significant bleeding

8. There is a profound increase in the risk of miscarriage and placentalabruption resulting in fetal loss or preterm delivery in women with deficiencies of fibrinogen or factor XIII • Factor replacement is recommended and used to reduce the risk of miscarriage and fetal loss in these women

9. in women with other bleeding disorders is less clear the risk of: • miscarriage, • antepartumbleeding, • and adverse outcome • Also consider obstetric causes as a reason for bleeding

10. labour and delivery • There is no consensus on the factor levels that are safe for regional anesthesia, • but if levels are at least 50% and the rest of the coagulation studies are normal, regional anesthesia may be considered safe. • It is often difficult to obtain factor levels during labourand is therefore acceptable to use third trimester levels to formulate an appropriate plan.

11. If the factor level is low, intravenous access should be established and prophylactic treatment administered • The management of childbirth will depend on the needs of the mother and her potentially affected infant at the time of delivery • Caesarean section is not routinely indicated merely because of possibility of fetal involvement

12. DDAVP • may be used to raise factor VIII and vWF levels in carriers of hemophilia A and type I VWD prior to invasive procedures. • It is generally thought to be safe for mother and fetus, but care must be taken in its administration at the time of childbirth. • At the time of childbirth, administration of DDAVP, combined with fluids and oxytocin, may result in life-threatening hyponatremia. Therefore, fluid balance and electrolyte levels should be strictly monitored.

13. In pregnancies with potentially affected fetuses should be avoided : • Invasive intrapartum monitoring techniques (e.g. fetal scalp electrode,fetalblood sampling) • instrumental deliveries (ventouse, midcavity or rotational forceps, as serious head bleeding may result from these procedures.

14. Normal vaginal delivery is not absolutely contraindicated in these pregnancies, • but prolonged labourshould be avoided • and delivery achieved by the least traumatic method.

15. Although cesarean section may not completely eliminate the risk of serious neonatal bleeding complications ,early recourse to cesarean section should be considered to minimize the risk of neonatal bleeding complications. • Low forceps delivery may be considered less traumatic than cesarean section when the head is deeply engaged in the pelvis and an easy outlet delivery is anticipated

16. A cord blood sample should be collected from neonates at risk of moderate or severe inherited bleeding disorders to assess coagulation status and clotting factor levels. • If delivery has been traumatic or if there are clinical signs suggestive of head bleeding,acranial ultrasound should be performed • It is also advisable to consider prophylactic coverin these cases.

17. Intramuscular injections should be avoided in neonates at risk until the coagulation status is known. • Vitamin K may be given orally • routine immunizations given intradermally or subcutaneously. • If vitamin K is given intramuscularly (IM),apply firm pressure to the site for five to ten minutes. • Heel sticks should also have pressure applied for five minutesand close observation of the site for 24 hours. • Any surgical procedures (e.g. circumcision) should be delayed until the coagulation status of the neonate is known.

18. assessing neonatal clotting factor levels • It should be appreciated that the levels of vitamin K dependent factors (FII, FVII, FIX, and FX) correlate with gestational age due to liver immaturity and reach adult levels at six months of age. • It is therefore notreliable to diagnose mild forms of inherited bleeding disorders at birth.

19. It is almost impossible to diagnose the much commoner, milder formsof vWDin a newborn as the level of vWF rises significantly during birth and an apparently normal result may thus mask a mild form of vWD. • Hemophilia A can be diagnosed at birth. • Severe forms of RBDs.

20. Postpartum management • Postpartum hemorrhage (PPH) is a major cause of maternal morbidity and mortality • an estimated 140,000 maternal deaths each year worldwide • the most common causes of PPH are • uterine atony • retained placenta or placenta pieces, • genital tract trauma, • Coagulation disorders

21. Postpartum management • After the delivery, the elevated coagulation factors return to pre-pregnancy levels within 14 to 21 days of delivery. • Risk of primary PPH (blood loss of more than 500 mL in the first 24 hoursafter delivery) • Secondary PPH (excessive bleeding occurring between 24 hours and six weeks post delivery), • especially those with severe disorders

22. Perineal/vaginal hematoma are rarecomplications of vaginal birth, • but are also more likely to occur in women with bleeding disorders, especially after operative vaginal deliveries

23. Reducing the risk of PPH • prophylactic replacement therapy is recommended to cover labour, delivery, and the immediate postpartum period (at least three to four days for vaginal delivery and five to seven days for C/S ) • Active management of the third stage of labouris associated with a significant reduction in blood loss during childbirth. • It entails the administration of prophylactic uterotonics(agents that increase uterine muscle contractility), • early cord clamping, • and controlled traction of the umbilical cord.

24. 3- During C/S : meticulous surgical hemostasisshould be practiced to minimize blood loss. 4- Care must also be taken to minimizematernal genital and perinealtrauma,for prevention of perineal hematoma

25. Oral tranexamic acid can be used for the prevention and management of secondary PPH. • Combined oral contraceptive pills, if not contraindicated, are an option for preventing excessive bleeding in the late postpartum period. • It is important to keep in mind the obstetric risk factors and causes of PPH in women with inherited bleeding disorders.

27. متولد 1364 / تشخیص در 21 سالگی / کمبود فاکتور 7 • شر ح حال : سابقه عمل جراحی ندارد ، کبودی , اپیستاکسی ,گاهی خونریزی در مفاصل آرنج ، مچ پا و ... • 3 نوبت سقط در سه ماهه اول/ PT = 48 و FVII=2.8% • والدین درجه یک • تشخیص 1385/8، • حامله شدن 1385/10 • عدم وجود فاکتور هفت • تحت تزریق هفتگی FFPقرار گرفت تا ماه هفتم حاملگی (10cc/kg)، • بعد هر هفته 1.2mg نووسون (با وزن 57 معادل 20μ/kg ) • زایمان طبیعی با تزریق مجموعا 3-4 ویال ، 1.2 mg انجام شد ، بعد از زایمان علیرغم توصیه به مصرف فاکتور خودش تزریق نکرد و خونریزی هم نداشت! • مجددا سال 1389 ) 3 سال بعد ) با حاملگی مراجعه کرد در سن 7 هفته • تحت درمان هر هفته 1.2 mg قرار گرفت • قبل از زایمان سطح فاکتور 3.9 • زایمان بدون عارضه ،

28. متولد : 1369 / تشخیص 9 سالگی / کمبود فاکتور 13 • علایم: خونریزی از بند ناف / با تروما خونریزی و تزریق FFP ، عادت ماهیانه طبیعی / بعد از تشخیص در تهران تحت تزریق کرایو هر 4 هفته یک بار • حاملگی سال 1388 با تزریق کرایو هر 2 هفته یک بار تا 8 ماهگی ، بعد از تهیه فاکتور 500 واحد هر دو هفته (وزن 52 ) ، • زایمان طبیعی بدون عارضه • برای زایمان فقط 2 ویال فاکتور دریافت کرد • حاملگی مجدد سال 1392

29. متولد 1365 / تشخیص در 23 سالگی (سال 88)، فون ویلبراند شدید • سابقه : اپیستاکسی های شدید در طفولیت + کوتر بینی ، خونریزی از محل پر کردن دندان + بریدن دست + منوراژی • علائم در پدر، مادربزرگ پدری و عمو • (قصد حاملگی داشت ) • کنترل منوراژی : عدم پاسخ به ترانس آمین و نیاز به تزریق فاکتورهیومت طی سه روز اول • وزن 48 کیلو / • در حاملگی هر هفته دو نوبت دو ویال فاکتور ، • زایمان طبیعی انجام شد • هفته اول هر روز دو ویال ، هفته دوم روز در میان دو ویال و درهفته سوم قطع دارو توسط خود بیمار • روز 25 بعد از زایمان ، مراجعه با خونریزی / از مرداد تا آذر1391 چند نوبت بستری و دریافت درمانهای هورمونی مختلف ، گاهی کرایو / گاهی فاکتور / در آخرین سونو گرافی متریال اکوژن در رحم و احتمال لخته مطرح شد ، کاندید کورتاژ ، بررسی مهارکننده های منفی / خود بخود نسجی دفع کرد ، بافت دسی دوآل دژنره ( باقیمانده جفت ) و نهایتا قطع خونریزی

30. THANK YOU