Factor V deficiency in pregnancy complicated by Rh immunization and placenta previa

890

Case Report

three vessels. On the fetal side of the placenta the amniotic membrane was absent from large parts of the placental surface creating a smaller sac discontinuous from the chorion plate. No inflammation was found in membranes or placenta.

Discussion Polyhydramnios is a symptom of a continuity of conditions. As suggested above, traditionally the underlying conditions are divided into maternal, fetal, and placental causes. Nevertheless, approximately 60% of cases of polyhydramnios arc idiopathic in origin ( I ) . The most common known causes of polyhydramnios are matcrnal diabetes (1.3-36.1Y0) (1, 4). twin and triplet pregnancies, gastroentestinal obstructions, CNS-rnalformations, and fetal chromosomal disorders (1, 2, 4). Rarer conditions leading to polyhydramnios are placental tumors, fetal tumors, and rare fetal disorders including fetal infection (1). Because of these conditions and the fact that polyhydramnios increases the risk of preterm delivery (up to 30% of these pregnancies end up in early delivery (4)) as well as the risk of intrapartum complications, especially amniotic cord complication and abruptio placentae (I), the perinatal morbidity and mortality are high. Incidences of neonatal mortality between 16% and 69% are reported in different materials ( 1 ), just one reason why pregnancies complicated with polyhydramnios must be taken very seriously. Traditionally a volume of amniotic fluid of 2000 ml has been the lower limit of polyhydramnios. However, the exact volume of amniotic fluid is impossible to measure without using invasive procedures, which are today considered contraindicated. Two new methods of estimating amniotic fluid volume both based on the ultrasound examination have been developed: The traditional one-pocket measurement (the vertical depth of the largest fluid pocket measuring more than 8 cm=polyhydramnios), and the more recently developed four-quadrant technique, in which the largest pockets of the four abdominal quadrants are measured, added, and expressed as the amniotic fluid index (AFI), an AFI of more than 24 indicating polyhydramnios (5). In a study by Phelan et al. (5), in which both the onepocket technique and the AFI were used in a material of 112 non-diabetic pregnancies, it was shown that AFI was significantly better correlated to pregnancy outcome than the onepocket technique. In our case two different clinicians have used different methods of diagnosing polyhydramnios. However, there is no doubt that the patient suffered from severe polyhydramnios. The treatment of choice in most cases of polyhydramnios is controlled removal of amniotic fluid by sterile amniocentesis (I). An alternative is close observation without active treatment. The recently introduced pharmacological treatment by the NSAID indomethasin would - in this case - not seem rational, as its effect is mainly on the kidneys of the fetus not removing the already produced amniotic fluid between the separated membranes. A number of different authors have in the past described the features of amnion rupture, mostly in association with the amniotic band syndrome (the amputation or malformation of a limb because of amniotic band@) (3). There are few reports of amniotic rupture without the amniotic band syndrome, whether this is because of the rareness of the condition or because it is seldom recognized. To our knowledge no cases of amniotic rupture with severe intermembraneous polyhydramnios but without amniotic band syndrome have been reported in the literature in the recent past. This might be because of the extreme rareness of the condition, or the condition might ‘hide’ among the numerous less severe idiopathic cases only to be revealed during a cesarean section but not to be recognized during vaginal delivery. Q Actu Ohsiet Gynecol Scand 76 (1997)

References 1 . Cardwell MS. Polyhydramnios. A review. Obstet Gynccol Surv 1987; 42: 612-17. 2. Ben-Chetrit A, Hochner-Cclnikier D, Ron M et al. Hydramnios in the third trimester of pregnancy: A change in the distribution of accompanying fetal anomalies as a result of early ultrasonographical prenatal diagnosis. Am J Obstet Gynecol 1990; 612: 1344 5. 3. Moerman P, Fryns JP, Vandenberghe K et al. Constrictive amniotic bands, amniotic adhesions, and limb-body wall complex: discrete disruption sequences with pathogenic overlap. Am J Med Genet 1992; 42: 470-9. 4. Phelan JP, Park YW, Ahn MO et al. Polyhydramnios and perinatal outcome. J Perinatol 1990; 10: 347-50. 5 . Phelan JP, Smith CV, Broussard P et al. Amniotic fluid volume assessment with the four-quadrant technique at 3-2 weeks gestation. J Reprod Med 1987; 32: 540-2.

Address for correspondence: S . Krue, M.D. Peder Nielsens Vej 22, G1. Balle DK-8600 Silkeborg Denmark

Factor V deficiency in pregnancy complicated by Rh immunization and placenta previa A case report and review of the literature GIUSEPPENOIA’, SARADE CAROLIS’,VALERIODE STEFANO~. SERGIOFERRAZZANI~. LIDIA DE SANTIS’,BRIGIDACARDUCCI’. MARCODE SANTIS~ AND ALESSANDRO CARUSO’ From the Departments of lobstetrics and Gynecology and *Hematology, Catholic University of Rome, Rome, Italy Acta Ohstet Gynecol Scand 1997; 76: 89e-892. Q Acta Obstet Gynecol Scand 1997 Key words: factor V deficiency; fresh frozen plasma; placenta previa; prenatal invasive procedures; Rh immunization Submitted 2 Septemher, I996 Accepted 12 Decemher. I996

Labor and postpartum are described as possible hemorrhagic risk factors in women with factor V deficiency. The overall prevalence of hemorrphagic complications is reported to be 78%. Prophylactic transfusions of blood and plasma can reduce these complications. We describe the management in a particular case in which severe factor V deficiency in pregnancy was associated with a hemorrhagic condition as vaginal bleeding due to placenta previa, anemia and Rh immunization. Satisfactory hemostasis was achieved by infusion of 15-20 mVkg body weight of fresh frozen plasma before amniocentesis, condocentesis, cesarean section and during puerperium. Intravascular direct fetal transfusion was done to correct fetal anemia. Good A bbreviutions: FV: factor V; FFP: fresh frozen plasma. FT:prothrombin time; PTT: partial thromboplastin time; H b hemoglobin.

Case Report Hb

PTT/PT

(gIdl)

bet)

FFP I Whole blood funits)

Delivery

I

T 14

12

891

with Factor V (FV) deficiency (1-6). Postpartum hemorrhage should be anticipated and may be controlled by transfusion of fresh frozen plasma (FFP) (3-5). The present study describes the management of pregnancy in a patient with severe congenital FV deficiency, Rh immunization, and vaginal bleeding due to placenta previa.

10

8

Case report

6

A 33-year-old primigravid woman, was admitted to our Department with severe congenital FV deficiency, Rh immunization, and placenta previa at 27 weeks’ gestation. Her history revealed repeated episodes of epistaxis. Factor V deficiency was diagnosed at the age of 16 years. The father and one sister were also affected by FV deficiency. Blood and plasma transfusions were necessary after a severe episode of epistaxis and the first sexual relationship. On admission, hematological analysis was as follows: FV 3%, partial thromboplastin time 73.5”, prothrombin time 36” (20%), normal international ratio 2.83, sideropenic anemia (Hemoglobin 8.2 g/dl), (Fig. l), platelet count 210000/mm3, indirect antiglobulin titers 1:16. Fetal ultrasound did not reveal any indirect evidence of anemia. Amniocentesis was performed at 29 weeks’ gestation following maternal prophylaxis with FFP (five units). The deviation from linearity from the optical density reading at 450 nm (the AOD 450 reading) of the amniotic fluid was at the upper limit of the first Liley’s zone. One episode of mild vaginal bleeding occurred with spontaneous regression. One week later, the indirect antiglobulin titers rose ( 1:512). Cordocentesis was thus performed, following maternal prophylaxis with F F P (eight units). Fetal blood values obtained were: Hemoglobin= 12.5 g/ dl, platelet count= 234000/mm3, blood group=B positive, and Direct Coombs test=positive ( 2 + ) . FFP (15 ml, 0 negative) was infused in order to restore any possible fetal FV deficiency. At 32 weeks’ gestation the patient presented with vaginal bleeding due to placenta previa; FFP (six units) was adminis-

4

2 0

-

27 28 29 30 31 -1

Weeks of gestation --b

Hb

-+-

PTT

-vT

I

Postpartum days

0Fresh frozen plasma (FFP) Whole blood

Fig. 1. Variation of prothrombin time (PT), partial thromboplastin time (PTT), hemoglobin (Hb), before and following fresh frozen plasma and whole blood transfusions.

maternal and neonatal outcomes were observed. Adequate amounts of fresh frozen plasma administered before amniocentesis, cordocentesis, and during cesarean section and puerperium were found satisfactory as prophylaxis for severe maternal hemorrphage in a woman with vaginal bleeding due to placenta previa. As regards the fetus, affected by Rh hemolytic disease, the invasive procedures were useful and probably lifesaving. Few reports have been published regarding labor in patients

Table I. Summary of the literature describing pregnant patients with Factor V deficiency Plasma or blood transfusion Authors

Pregnancies Pts No. No

Prophylaxis

Therapy

Stohlman et al., 1951 (1) Brink and Kingsley, 1952 (2)

1 2 3

Yes Yes

Horder, 1955 (8)

4

Yes

Fajardo and Silvert, 1957 (3)

5

6

Phillips and Little, 1962 (4)

6

7 8 9 10

7

Rush and Ellis, 1965 (5) Langer et al., 1982 (6)

Present report

8 9

10

11 12 twins 13 14 15 16 17 18

Yes

Yes Yes

Hemorrhagic complications Postpartum hemorrhage Bloody discharge for 2 months post partum Postpartum hemorrhage Extensive hernoperitoneum associated with a tuba1 pregnancy Postpartum hemorrhage, vaginal hematoma and moderate shock Postpartum hemorrhage

Yes Yes

Yes Yes

Yes

Yes

Postpartum hemorrhage and shock Postpartum hemorrhage, supracervical isterectorny, trachelectomy complicated by pelvic hematoma lntrapartum and postpartum hemorrhage Postpartum hemorrhage and vaginal hematoma

NIS

N/S Yes

Postpartum hemorrhage Postpartum hemorrhage and shock

Yes

Postpartum hemorrhage

Yes

Postpartum hemorrhage

Yes Yes Yes Yes

Mode of delivery VD VD VD VD

VD with forceps VD VD VD VD VD VD with forceps NIS VD VD VD VD

cs

N/S=not specified; Pts=patients; VD=vaginal delivery; CS=cesarean section.

0 Acta Obstet Gynecol Scand 76 (1997)

892

Case Report

tered. Two days later, having submitted the mother to plasma transfusion (seven units), fetal hemoglobin trend was evaluated at cordocentesis. Fetal hemoglobin was 6.7 g/dl. Fetal anemia was certainly related to Rh immunization, since no fetal-maternal hemorrhage had been detected by the Kleihauer-Betke test. Blood and plasma were administered (47 ml of packed red cclls. 25 ml uf F F P 0 negative) and fetal hemoglobin levels increased to 9.2 gidl. A cesarean section was planned in view of recurrent vaginal blccding, fclal distress and breech presentation. Preoperative treatment included phenobarbital administration to prevent fetal intracranial hemorrhage (7) and FFP (five units). Intrapartum hemorrhage (1000 ml) occurred and whole blood transfusion was perrormed. An intrabdominal drainagc was placed. The patient received four units of F F P after cesarean section. A live female infant, (2150 g), was delivered at 32 weeks' gestation and required exchange transfusions for treatment of anemia in the first two days of life. At birth FV levels were 60'% During puerperium the patient was managed with F F P (six units twice daily) for the first four days. A pelvic hemoperitoneum (0 4.2 cm in the Douglas's pouch by ultrasonography) was diagnosed one week after delivery, but it regressed spontaneously within two wceks. On the sixteenth day, the patient had an episode of vaginal bleeding managed with oxytocics and two units of F F P were administered. The woman and the infant wcre discharged in good health on the nineteenth postpartum day and on the twenty-fifth day of life, respectively.

Discussion Labor and postpartum are described as possible hemorrhagic risk factors in women with FV deficiency. In Table I a summary of the literature describing pregnant patients with FV deficiency is reported (I 6 , 8). The overall prevalence of hemorrhagic complications was ~X'%I. Vaginal hematoma occurred when forceps were used, and three cases of maternal shock were described due to postpartum hemorrhage. Langer et al., 1982, ( 6 ) after having observed a shock from postpartum hemorrhage, managed the following three spontaneous deliveries of the same patient, with prophylactic administration of F F P (one liter) during labor and 24 hours after delivery (250 ml). Hemorrhage was prevented at delivery achieving FV levels of 7-8'1/0, eight hours after fresh frozen plasma ( 6 ) . However, three of four pregnancies, which were uneventful a t delivery, were managed with prophylactic transfusions of blood or plasma (2, 4, 6). In this report we present a particular case in which a hemorrhagic diathesis was associated with vaginal bleeding due to placenta previa, and sideropenic anemia. On the other hand, thc presence uf fctal hemolytic disease (Rh immunization) necessitated prenatal diagnostic and therapeutic invasive procedures, that could have determined severe hemorrhagic complications both to the mother and to the fetus if affected by FV deficiency. We supposed that Rh immunization in this woman might have been due to accidental exposure to Rh-positive red cells, probably consequent to previous transfusions. We are aware that blood products present a risk of hepatitis and HIV transmission despite their accurate control, but in the present case maternal hemorrhage was likely to occur because of FV deficiency, concomitant bleeding due to placenta previa and invasive procedures. According to Langer et al., 1982, ( 6 ) in this case an amount of FFP between 15 and 20 mlikg body weight in the various administrations was given to achieve a level not lower than 5%) eight hours after transfusion, with a peak of 12% immediately after infusion. A total dose of 8.5 units of plasma and three units of whole blood was needed for prevention and control of bleeding. The previous papers about pregnancy and FV deficiency did not calculate the FV levels after plasma or blood infusion (1-4, 8). 8 Actcc Ohstet Gynecol Sccmd 76 (1997)

In the present case, adequate amounts of FFP administered before amniocentesis, cordocentesis, and during cesarean section and puerperium were found satisfactory as prophylaxis for severe hemorrhage. As regards the fetus, affected by R h hemolytic disease. the invasive procedures carried out were useful and probably lifesaving. Because of the risk of fetomaternal transplacental hemorrhage that accompanies fetal blood sampling, amniocentesis and, because the indirect antiglobulin titers rose, cordocentesis were performed. Fetal hemoglobin resulted 6.7 g/dl at 32 weeks' gestation and rose to 9.2 gidl after direct intravascular transfusion. At birth, the infant required exchange transfusions. During cordocentesis FFP was also administered to the fetus in view of FV deficiency, because of the imminent risk of severe hemorrhage at the needle insertion site. The fetal blood sample was insufficient for antenatal testing for F V level. At birth, FV levels were 6O%, probably in the normal range for a preterm infant, as the normal range is not reported in the literature. Good maternal and neonatal outcomes were observed. Placenta previa occurring in a woman with FV deficiency required aggressive prophylactic and therapeutic measures. Despite increased patient and physician anxiety, active management resulted in good maternal and neonatal outcomes.

References 1. Stohlman F, Harrington WJ, Maloney WC. Parahemophilia, (Owren's disease). Report of a case in a woman with studies on other members of her family. J Lab Clin Med 1951; 38: 842-5. 2. Brink AJ, Kingsley CS. Familial disorder of blood coagulation due to deficiency of labile factor. Quart J Med 1952; 21: 19-31. 3. Fajardo LF, Silvert D. Pregnancy and AC-globulin deficiency. Am J Obstet Gynecol 1957; 74: 909-14. 4. Phillips LL, Little WA. Factor V deficiency in obstetrics. Obstet Gynecol 1962; 19: 507~12. 5. Rush B, Ellis H. The treatment of patient with factor V deficiency. Thromb Diath Haemorrh 1965; 14: 74-82. 6 . Langer R, Caspi E, Kaufman S, Fried K, Leiba YH. Management of labor in a patient with factor V deficiency. Isr J Med Sci 1982; 18: 701-3. 7. De Carolis S, De Carolis MI', Caruso A, Oliva G, Romagnoli C, Ferrazzani S et al. Antenatal phenobarbital in preventing intraventricular hemorrhage in premature newborns. Fetal Ther 1988; 3: 224-9. 8. Horder M H . Isolierter Factor V-Mangel bedingt durch einen spezifischen Hemmkorper. Acta Haeinatol 195.5; 13: 235-41. Atldress for correspondence: Sara De Carolis, M.D. Department of Obstetrics and Gynecology Catholic University of Rome Largo Gemelli 8 00168 Rome Italy