Hereditary Coagulopathy Mohammad reza baghaipour, MD Pediatrician, ISTH Fellow Comprehensive Hemophilia Care Center, Tehran, Iran

Bleeding disorders May be: Acquired Inherited Atuoimmune Drug Thrombocytopenia Platelet function disorders Abnormal collagen Clotting factor deficiencies 1 in 5000 to 1m

Menorrhagia Menorrhagia most common symptom in women with bleeding disorders.( > 7days, > 80 ml ) vWD 74- 92% (13 % - vWD) BS 51% GT 98% Carriers 57% F XI Def 59% Rare BD 35-70% Adolescent girls and perimenopause women

Menorrhagia Assess hemoglobin content using the alkaline hematin method Pictorial blood assessment chart (PBAC)

Menorrhagia In most situations, practitioners must rely on menstrual history and clinical impression. Variables that can predict a menstrual blood loss of more than 80 mL are: Passage of clots greater than one inch (2.5 cm) Low ferritin The need for changing a pad or tampon more than hourly

Menorrhagia (Complete bleeding history): Menorrhagia since menarche Family history of a bleeding disorder Personal history of one, but usually several, of: *Epistaxis *Notable bruising without injury *Minor wound bleeding *Bleeding in the oral or gastrointestinal tract *Bleeding following dental extraction *Unexpected post-surgical bleeding *Recurrent midcycle pain due to ovulation bleeding *Hemorrhage requiring blood transfusion *Postpartum hemorrhage, especially secondary postpartum hemorrhage (after 24 hours).

Menorrhagia ( Lab test ) CBC B/G Ferritin level PTT PT vWF Ag / Act FVIII levels Platelet function test Specific Factor Assay

Other Gynecological Conditions Dysmenorrhea- NSAID (should be avoided) Acetaminophen Hormonal Therapy Hemorrhagic ovarian cysts conservative management with the use of appropriate hemostatic agents Endometriosis, fibroids (leiomyoma), polyps, or endometrial hyperplasia

Hemophilia Hemophilia is the commonest severe bleeding disorder Hemophilia A (factor VIII deficiency) Hemophilia B (factor IXdeficiency) X- linked disorders one in 5,000 men Women are affected as carriers Carriers may also have low factor levels Experience significant bleeding symptoms

von Willebrand disease (VWD) Most common inherited bleeding disorder Autosomal disorders and equally affect women and men Large epidemiological studies reported a 0.8-1.3% prevalence Women are more likely to be symptomatic due to the bleeding challenges of menstruation and childbirth

Management of menorrhagia (adolescent ) Counseling prior to menarche Preserving future fertility Immunization

Pregnancy in Women with Bleeding Disorders Preconception counselling: Specially important for: Women with severe bleeding disorders potentially carry a severely affected baby Benefits: Adequate information Available reproductive choices Options for prenatal diagnosis How and where to terminate the pregnancy Immunization Folic acid supplementation Option for bleeding treatment (A DDAVP test dose ) Psychological support Speak with a pediatric hematologist regarding the care of a potentially affected child.

Prenatal diagnosis (PND) PND is primarily considered in carriers of hemophilia A or B 50% Affected child 50% Female carrier Autosomal disorder Sever forms Consanguineous marriage CVS (11 -14 w) 1% risk Should receive prophylaxis prior to any invasive procedure Fetal sex determination ( Mother blood 5-10w) (Sono 12w) ( if F, avoid testing, if M, avoid instrumental deliveries ) Pre-implantation genetic diagnosis (PGD) using IVF (overall live birth rate 22%) Mother blood from 5 w to 10 w Sono 12 w

Antenatal management Normal pregnancy: Carrier and affected female: ↑ Several coagulation factors including VIII, VWF, fibrinogen ↓ Fibrinolytic activity due to ↑plasminogen activator inhibitors Carrier and affected female: This rise is not enough and still risk of bleeding Assay factor level at booking, 28w and 34w women with deficiencies of fibrinogen or factor XIII : ↑ Miscarriage and placental abruption resulting in fetal loss or preterm delivery Factor replacement is recommended Approximately 20% of all pregnancies are complicated by at least one bleeding episode

Management of labor and delivery Experienced Obstetrics Hematologist with expertise in hemostasis Laboratory Pharmacy Blood bank support

Management of labour and delivery Mother with Bleeding tendency: CBC, B/G, Factor level ( PT, PTT, PLT ) DDAVP ? ( safe for Mom & Inf, Water intoxication for OXY and Fluid ) Coagulation Factors are safe ( recombinant is preferred, PB19) V/D versus C/S Potentially affected fetuses: Avoid Invasive intrapartum monitoring technique(fetal scalp electrode, fetal blood sampling) Avoid instrumental deliveries (ventouse, midcavity or rotational forceps) Normal vaginal delivery is not absolutely contraindicated (Avoid prolonged labour) In situations where factor levels cannot be assessed, provided the f viii level is >50 IU dL in the third trimester, it is then sufficient to assess the plt, PTT and PT . Some Plasma derived has P B19 risk

Management of labour and delivery Potentially affected fetuses: Cesarean section may not completely eliminate the risk bleeding Early recourse to cesarean section should be considered to minimize the risk Cranial US If traumatic delivery Factor Replacement if clinical signs suggestive bleeding in neonate Intramuscular injections should be avoided ( oral Vit K, site Pressure) Heel sticks should also have pressure applied for five minutes Any surgical procedures (e.g. circumcision) should be delayed Some factors (eg. vit K dependent F ) take time to get normal (6-12 mo)

Postpartum management The most common causes of PPH: Uterine atony, retained placenta, placenta pieces, and genital tract trauma After the delivery, the elevated coagulation factors return to pre-pregnancy levels. ( Factor assay is necessary ) Therefore, the main risk of bleeding is after miscarriage or delivery Primary PPH (blood loss of more than 500 mL in the first 24 hours after delivery) Secondary PPH (excessive bleeding occurring between 24 hours and six weeks post delivery) Perineal/vaginal hematoma are rare complications Reducing the risk of PPH prophylactic replacement therapy three to four days for vaginal delivery five to seven days for cesarean section

Postpartum management Active management of the third stage of labor is very important Local causes should be excluded even in women with bleeding dis. Administration of prophylactic uterotonics Early cord clamping Controlled traction of the umbilical cord Meticulous surgical hemostasis Care to minimize maternal genital and perineal trauma Oral tranexamic acid Combined oral contraceptive pills Close collaboration between hematologists, obstetricians, and anesthetists

The Take-home message Bleeding Disorders are not rare Reduces quality of life Not aware of their symptoms and do not seek medical advice Lack of awareness among caregivers Its treatment needs teamwork

Thank you for your attention مرکز جامع درمان هموفیلی ایران پایین تر از میدان فاطمی تقاطع زرتشت و فلسطین 02188898742