Etiology and Management of Hemorrhage 319 blood transfusion. Prophylaxis for thromboembolism should also be considered and initiated before surgery. Compression stockings placed before induction of anesthesia, prophylactic low molecular weight heparin or unfractionated heparin are also acceptable [137] . The importance of close postpartum observation cannot be overemphasized, and in most cases these patients should be recovered in an ICU setting. Frequently, because of prolonged operative time combined with massive transfusion, there is a risk for laryngeal edema, pulmonary edema, delayed extubation and prolonged ventilation. Continuous vital sign determination and pulse oximetry along with hourly urine output measurement are warranted after signifi cant hemorrhage and blood or product replacement. Patients with periods of prolonged hypotension during surgery should also be followed postoperatively for evi- dence of the full Sheehan ’ s syndrome or forme fruste of this syndrome. Bleeding d isorders Consumptive and dilutional coagulopathies secondary to exten- sive blood loss and crystalloid replacement are the most common bleeding disorders associated with postpartum hemorrhage. Other obstetric causes of disseminated intravascular coagulopa- thy (acute fatty liver of pregnancy, abruption, anaphylactoid syn- drome of pregnancy) or thrombocytopenia (HELLP syndrome, TTP) may cause or contribute to major hemorrhage. Inherited and acquired bleeding disorders unrelated to pregnancy must also be considered. These include abnormalities of the coagula- tion system and qualitative or quantitative platelet disorders. The most common disorders are discussed below. Idiopathic t hrombocytopenia p urpura ( ITP ) The differential diagnosis of thrombocytopenia in the gravid patient includes gestational thrombocytopenia, autoimmune dis- orders such as systemic lupus erythematosus or antiphospholipid syndrome, HELLP syndrome (hemolysis, elevated liver enzymes and low plateletes), folate defi ciency, and viral illnesses including human immunodefi ciency virus. The most common cause in pregnancy is gestational thrombocytopenia which accounts for 70% of cases when low platelets are discovered [138] . Heparin - induced thrombocytopenia should also be considered in chroni- cally anticoagulated patients. Idiopathic thrombocytopenia purpura is an autoimmune dis- order resulting in increased platelet destruction. The incidence of ITP is 1 – 2 per 1000 deliveries and accounts for 3% of cases of thrombocytopenia at delivery [139] . The fetal risk of severe thrombocytopenia is 5 – 10%, and the neonatal nadir occurs between days 2 and 5 after delivery [140] . With ITP, the average platelet lifespan is greatly reduced, being a tenth of the normal 7 – 10 days. Circulating platelets are therefore younger, larger, and functionally superior compared to normal platelets. Platelet average blood loss of 1435 mL when hysterectomy was performed at the time of elective repeat cesarean section [48] . At emergency hysterectomy for postpartum bleeding, mean blood loss attrib- uted to the procedure was 2183 mL, with a mean loss of 2125 mL by the time of decision for hysterectomy [131] . Adequate hemo- stasis is not always achieved, and further procedures may be necessary. Uterine artery embolization has been performed for ongoing bleeding following hysterectomy, both with and without success [122,132] . Re - look laparotomy may also be required; this has been reported in up to 13% of patients [133] . The incidence of febrile morbidity is high, with rates of 5 – 85% in different series. Hysterectomy is indicated if conservative procedures such as embolization or uterine devascularization fail to control bleeding. The time lapse between delivery and successful surgery is the most important prognostic factor. If the primary procedure fails, it is recommended that hysterectomy is performed promptly, without attempts at another conservative measure [132] . In severely shocked patients with life - threatening hemorrhage, hys- terectomy is in most circumstances the fi rst - line treatment [109] . Hysterectomy may therefore be associated with a higher mortality than other surgical procedures [132] . Uterine atony is the major indication for peripartum hysterec- tomy, although other factors such as placenta accreta and abrup- tion are frequently present [132] . Many studies have described the profound hemorrhage associated with placenta previa, with a recent analysis [134] revealing blood loss greater than 3000 mL in 23% of patients with this condition. In this series, approximately 10% of patients required greater than fi ve units of blood products and hysterectomy [134] . Surgical re - exploration secondary to postoperative bleeding is needed in up to 7% of patients with placental invasion [135,136] . Other indications for peripartum hysterectomy include placenta previa, uterine rupture, and other genital tract lacerations. Trauma sustained at vaginal delivery may result in concealed bleeding and is therefore associated with a worse outcome; hemorrhage at cesarean section is more readily recognized and more promptly remedied. A subtotal hysterectomy can generally be performed if bleeding is from the uterine body. It is generally simpler than a total hys- terectomy – the cervix and vaginal angles can be diffi cult to iden- tify in women who have labored to full dilation. There is also less risk of injury to the ureter and bladder. One study reported the incidence of urinary tract injury to be 13% for subtotal hysterec- tomy, compared to 25% for total hysterectomy [133] . If placenta accreta is suspected, the use of prophylactic ureteral stents may help determine the location of the ureters and assist with diffi cult dissection planes. In addition, perioperative intentional cystot- omy may improve visualization of bladder invasion. If bleeding is from the lower segment (placenta previa, trauma), the cervical branch of the uterine artery must be ligated, and a total hyster- ectomy will be necessary. Anesthetic considerations include the need for general endotracheal anesthesia in anticipation of pro- longed surgical time, placement of a lumbothoracic epidural catheter for postpartum pain relief, and readiness for massive Chapter 22 320 of perineal hematoma in this group was found to be 7% com- pared to 2.2 per 1000 in the general population [149,150] . This disorder is characterized by quantitative or qualitative defi ciency in the production of von Willebrand factor (vWF), which has a central role in hemostasis [151] . First, it stabilizes the coagulation factor VIIIc, which otherwise is rapidly metabolized. Second, it mediates platelet adhesion following vascular injury. If there is a lack of functional vWF, the plasma level of factor VIIIc is low (normal range 50 – 150 IU/dL), and the bleeding time is prolonged. Bleeding problems are usually mild (epistaxis, menor- rhagia) and the underlying problem may go undetected. However, life - threatening hemorrhage may occur post partum. There are three types of vWD. Types 1 and 3 are quantitative defi ciencies. Type 1 is found in approximately 70% of affected individuals, and is autosomal dominant. It is a partial defi ciency state of vWF, and factor VIII levels are usually in the range 5 – 40 IU/dL. Type 3 is rare and autosomal recessive; there is almost a complete lack of vWF leading to very low levels of factor VIII with severe bleeding problems. Type 2 consists of qualitative differences, with several different subtypes which are inherited as autosomal dominant mutations. Thrombocytopenia may occur in type 2 disease in pregnancy; increased synthesis of abnormal multimers of vWF may cause increased platelet aggregation. In normal pregnant women and those with type 1 disease, vWF and factor VIII levels rise signifi cantly in the second half of preg- nancy. Therefore it is rare that women with mild vWD need treatment in pregnancy. However, women with other types of vWD and low factor levels have an inadequate response. Factor VIII levels should be checked at the initial prenatal care visit and again in the third trimester. Following delivery, there is a rapid fall - off in factor VIII levels, resulting in a high rate of secondary postpartum hemorrhage. Postpartum hemorrhage in women with vWD generally occurs if the factor VIII level is < 50 IU/dL. Prophylactic treatment is therefore required during labor and in the early postpartum period to maintain concentrations above this threshold. Although there is no consensus on levels that are safe for regional anesthe- sia, if the coagulation profi le is normal and factor VIII level is greater than 50 IU/dL, regional anesthesia can be safely adminis- tered [148] . The aim is to maintain higher levels for 3 – 4 days after vaginal delivery and 4 – 5 days after cesarean section. There are two options for treatment. The fi rst is intravenous infusion of desmopressin (DDAVP; 1 - deamino - 8 - arginine vasopressin), which acts by increasing factor VIII and vWF release into the plasma from storage sites, raising plasma concentrations by 3 – 5 times within 30 minutes. These levels are usually maintained for 8 – 10 hours and infusions therefore need to be given 1 – 2 times daily. Patients with type 1 disease generally respond well, but response is variable in type 3. DDAVP is contraindicated in some subtypes of type 2 because transient thrombocytopenia may result. DDAVP does not appear to cross the placenta in detectable amounts [152] . Caution should be exercised when administering DDAVP during the third stages of labor. In most cases, fl uid bolus with the addition of oxytocin is used immediately after counts are generally between 50 and 75 × 1 0 9 /L, but may fall to exceedingly low levels, particularly following viral infections. Exacerbations of ITP may occur at any time during pregnancy. In non - pregnant patients, spontaneous severe bleeding is rare with platelet counts greater than 10 × 1 0 9 /L, and signifi cant bleed- ing following trauma unusual with platelet counts above 50 × 1 0 9 /L. Case series from the 1950s and 1960s reported no increased incidence of postpartum hemorrhage or placental abruption in patients presenting with spontaneous bleeding from other sites [141] . Cesarean section and genital tract lacerations are associated with increased blood loss and an increased need for blood transfusion. Platelet counts should be monitored regularly. Antenatally, treatment is generally recommended with platelet counts of less than 30 × 1 0 9 /L or at any level if there is clinically signifi cant bleeding. The minimal safe platelet count for delivery is unknown. US guidelines demonstrate a diversity of expert opinion [142] ; a minimum count between 10 and 50 × 1 0 9 /L (mean 27 × 1 0 9 /L) was recommended for vaginal delivery and 30 – 50 × 1 0 9 /L (mean 44 × 1 0 9 /L) for cesarean section. A lower limit of 80 × 1 0 9 /L is generally agreed for regional analgesia. The most common medical treatments for ITP are corticoste- roids and intravenous immunoglobulin. High - dose steroids are associated with an increased risk of hypertension in pregnancy and immunoglobulin is extremely expensive. Intravenous anti - D antibodies (WinRho) were introduced in 1995 for the treatment of ITP in non - pregnant patients. The fi rst study evaluating anti - D immunoglobulin in pregnant women occurred in 1993 with a pilot study of eight Rh - positive women with ITP in the second and third trimester. A 75% response rate was demonstrated and no adverse fetal effects were noted [143] . In cases of ITP resistant to conventional therapy, anti - D immunoglobulin should be con- sidered. Platelet levels increase approximately 3 – 5 days after therapy has been initiated, with peak levels on day 8 [144] . Side effects are rare, with a small risk of hemolysis in the mother and fetus along with a 4% risk of fever, chills and body aches. Platelet transfusions should only be given for life - threatening bleeding or essential surgery; transfused platelets are rapidly destroyed in patients with ITP. Splenectomy remains the defi nitive treatment. In pregnancy, this may be technically diffi cult, but is indicated in women who are resistant to medical treatment. Von Willebrand ’ s d isease Von Willebrand ’ s disease (vWD) is the most common inherited bleeding disorder [145] . The prevalence of vWD has been reported to be as high as 1.3%, with menorrhagia presenting as the most common symptom in the majority of women with this disorder. Pregnant women with this disorder have no increased risk of antepartum hemorrhage; however, the reported incidence of primary postpartum hemorrhage ranges between 22% and 59% [146,147] , with an incidence of 20 – 28% for secondary post- partum hemorrhage [148] . There is also an increased risk of peri- neal hematoma in women with vWD. In small studies, the rate Etiology and Management of Hemorrhage 321 ity [161] . These antibodies are inhibitory, and partially or com- pletely suppress factor VIII procoagulant activity. It is a rare disorder, and bleeding is generally severe with high morbidity and mortality. The incidence is reported as 1.48 per million per year [162] . This disease affects approximately 1 in 350,000 pregnant women [163] . In pregnant women, the time to achieve remission is longer than for non - pregnant patients but there are higher rates of spontaneous remission [164] . The risk of death from hemor- rhage is higher in patients with this disorder than in hemophiliacs with factor VIII inhibitors. Between 7% and 11% of cases are related to pregnancy, and most occur after the fi rst delivery [165] . Presentation is with major bleeding, generally within the fi rst 3 months post partum. Hemorrhage may be apparent at several different sites, including multiple soft tissue hematomas, large ecchymoses, excessive vaginal loss, and postoperative bleeding. Investigations show a prolonged aPTT, together with a normal prothrombin time, bleeding time, and platelet count. In the majority of patients, inhibitors spontaneously disappear and there is complete remis- sion within a few months; however, sometimes these antibodies may persist for years. Until their disappearance, patients are at high risk for further bleeding episodes. Hemorrhage is controlled by raising the plasma level of factor VIII, to overpower the inhibitory action. Inhibitors bind less readily to porcine factor VIII than human factor VIII, so the former is generally fi rst - line management. Porcine factor VIII has been shown to have excellent effi cacy, with a greater than 85% rate of hemostatic control in these patients [166] . Other treatment options include bypassing agents. In a large cohort study evaluating the effi cacy of factor VIII inhibitor bypassing activty (FEIBA), complete response was achieved in 76% of severe and 100% of moderate bleeding episodes in these patients [167] . The other bypassing agent used for aquired hemo- philia is recombinant factor VIIa. Used as a fi rst - line agent, this demonstrated effi cacy within 8 hours in the majority of cases [168] . Several doses may be required. Both agents are associated with thrombotic events and should be administered according to the manufacturer ’ s recommendations based on individual case - by - case situations. There is no validated laboratory monitoring technique for these agents. DDAVP may also be used to increase endogenous factor VIII release from cellular stores. This agent is best used in patients with low inhibitory anti - factor VIII titers and measurable factor VIII levels. The response is unpredictable and it is best used for minor bleeds [169] . Plasmapheresis may be necessary if inhibitor levels are high. Disappearance of inhibitors can be enhanced by treatment with immunosuppressive agents such as corticosteroids, cyclophosphamide, rutiximab and aza- thioprine. In patients with complete remission, there has been no recurrence in subsequent pregnancies. However, as this is a rare disorder, few cases have as yet been documented. Secondary p ostpartum h emorrhage Secondary or delayed postpartum hemorrhage is defi ned as blood loss of 500 mL or more from the genital tract occurring more than delivery. With the addition of DDAVP, synergistic action from both agents can cause fl uid retention and hyponatremia [153] . The second treatment option consists of factor VIII and vWF replacement. Fresh frozen plasma contains both factors, but large volumes are required to stop or prevent bleeding. Cryoprecipitate contains 5 – 10 times higher concentration of both factors. Factor VIII preparations for use in vWD must also contain some vWF, otherwise the half - life of factor VIII is 1 hour or less. Recombinant factor VIII therefore cannot be given, but commercial preparations containing both factors are available. Tranexamic acid may also be useful in women with non - life - threatening postpartum hemorrhage. This agent exerts its effect by competitevely inhibiting the conversion of plasminogen to plasmin, therefore inhibiting the degredation of fi brin This agent does cross the placenta but has not been associated with adverse fetal effects [154,155] . The average time of presentation of postpartum hemorrhage in women with vWD is 15+/ − 5 days and hemorrhage may occur despite prophylaxis. These women benefi t from frequent visits for the fi rst weeks after delivery and may require additional therapy at these times [156] . Hemophilia Hemophilia A (factor VIII defi ciency) and hemophilia B (factor IX defi ciency) are X - linked disorders [157] . Some women have levels that are within the normal range ( > 50 IU/dL), but inactiva- tion of the normal chromosome (lyonization) may result in low factor levels [145] . The overall frequency for these disorders is approximately 1 in 100,000 births [158] . There is also an increased risk of primary and secondary postpartum hemorrhage in hemo- philia carriers, with reported rates of 19% and 11% respectively, occurring mostly when factor levels are < 50 IU/dL. Although hemorrhage is rare in women with factor levels > 50%, severe bleeding may occur with levels between 5% and 30% after surgery or delivery [159] . In small reports, hemophilia A and B were noted to have higher postpartum hemorrhage rates compared to women with other bleeding disorders and required up to 4 days of factor replacement [160] . Carriers of hemophilia A generally experience a pregnancy - induced rise in factor VIII levels. However, factor IX levels are unaffected by pregnancy. Treatment is indicated for labor when factor levels are < 50 IU/dL for both types of hemophilia. DDAVP may be used or appropriate factor concentrates. If the diagnosis is not known in the face of hemorrhage, fresh frozen plasma can be used pending test results. Hemophilia A carriers synthesize normal amounts of vWF, and therefore recombinant factor VIII is effective in these patients. Affected fetuses are at risk for extra - and intracranial hemorrhage, but cesarean delivery does not reduce this risk. Fetal scalp electrodes and operative delivery should be used cautiously. Acquired h emophilia Acquired hemophilia is caused by the presence of autoantibodies to factor VIII in people with previously normal factor VIII activ- Chapter 22 322 blood component therapy, will minimize serious sequelae of hemorrhage. References 1 Chang J , Elam - Evans , LD , Berg CJ , et al. Pregnancy - related mortality surveillance – United States. 1991 – 1997 . MMWR 2003 ; 52 ( 2 ): 1 – 8 . 2 Berg CJ , Chang J , Callaghan WM , et al. Pregnancy related mortality in the United States, 1991 – 1997 . Obstet Gynecol 2003 ; 101 ( 2 ): 289 – 296 . 3 Clark SL , Belfort MA , Dildy GA , Herbst MA , Meyers JA , Hankins GD . Maternal death in the 21st century: causes, prevention, and relationship to cesarean delivery . Am J Obstet Gynecol 2008 ; 199 ( 1 ): 36 ; discussion 91 – 92. 4 AbouZahr C . Global burden of maternal death and disability . Br Med Bull 2003 ; 67 : 1 – 11 . 5 Bonnar J . Massive obstetric haemorrhage . Bailli è re ’ s Best Pract Res Clin Obstet Gynaecol 2000 ; 14 : 1 – 18 . 6 Ananth CV , Savitz DA , Bowes WA , et al. Infl uence of hypertensive disorders and cigarette smoking on placental abruption and uterine bleeding during pregnancy . Br J Obstet Gynaecol 1997 ; 104 : 572 – 578 . 7 Domissee J , Tiltman AJ . Placental bed biopsies in placental abrup- tion . Br J Obstet Gynaecol 1992 ; 99 : 651 – 654 . 8 Rana A , Sawhney H , Gopalan S , et al. Abruptio placentae and cho- rioamnionitis, Microbiologic and histologic correlation . Acta Obstet Gynecol 1999 ; 78 : 363 – 369 . 9 Baron F , Hill WC . Placenta previa, placenta abruptio . Clin Obstet Gynecol 1998 ; 41 : 527 – 532 . 10 Ananth CV , Smulian JC , Dimissie K , et al. Placental abruption among singleton and twin births in the U.S.: risk factors . Am J Epidemiol 2001 ; 153 : 771 – 778 . 11 Lowe TW , Cunningham FG . Placental abruption . Clin Obstet Gynecol 1990 ; 33 : 406 – 413 . 12 Ananth CV , Wilcox AJ . Placental abruption and perinatal mortality in the United States . Am J Epidemiol 2001 ; 153 : 332 – 337 . 13 Pritchard JA , Cunningham FG , Pritchard SA , Mason RA . On reduc- ing the frequency of severe abruptio placentae . Am J Obstet Gynecol 1991 ; 165 : 1345 – 1351 . 14 Ananth CV , Oyelese Y , Prasad V , Getahun D , Smulian JC . Evidence of placental abruption as a chronic process: associations with vaginal bleeding early in pregnancy and placental lesions . Eur J Obstet Gynecol Reprod Biol 2006 ; 128 ( 1 – 2 ): 15 – 21 . 15 Goddijn - Wessel TA , Wouters MG , van de Molen EF , Spujbroek MD , Steegers - Theunssen RP . Hyperhomocystenemia – a risk factor for placental abruption or infarction . Eur J Obstet Gynecol Reprod Biol 1996 ; 66 : 23 – 29 . 16 Ananth CV , Berkowitz GS , Savitz DA , et al. Plaental abruption and adverse perinatal outcomes . JAMA 1999 ; 282 : 1646 – 1651 . 17 Gibbs JM , Weindling AM . Neonatal intracranial lesions following placental abruption . Eur J Pediatr 1994 ; 153 : 195 – 197 . 18 Nyberg DA , Cyr DR , Mack LA , Wilson DA , Shuman WP . Sonographic spectrum of placental abruption . AJR 1987 ; 148 : 161 – 164 . 19 Dhanraj D , Lambers D . The incidences of Kleihauer – Betke test in low risk pregnancies and maternal trauma patients . Am J Obstet Gynecol 2004 ; 190 : 1461 – 1463 . 24 hours after delivery and up to 6 weeks post partum. The potential severity of this condition should not be underestimated; secondary postpartum hemorrhage may result in the rapid onset of hemorrhagic shock [123] . The peak time for presentation is the second postpartum week, with the third postpartum week the next most common. The great majority of women therefore present with this complication as outpatients. The reported incidence is 0.5 – 1.3% of deliveries [170] . Common causes include retained placental tissue, endometritis, and genital tract tears. Rare causes include arteriovenous fi stulae and false aneurysms, possibly resulting from surgical trauma and healing at the site of cesarean section incision [123] . Scar dehis- cence has also been described. Genital tract malignancy, includ- ing choriocarcinoma, may also cause excessive bleeding during the postpartum period. Bleeding disorders may also present in this way, as discussed above. Acquired hemophilia is a rare but potentially lethal cause of secondary postpartum hemorrhage. Initial acute management of excessive bleeding from the pla- cental bed involves medical treatment. As for primary post- partum hemorrhage, the fi rst - line agents are intramuscular ergometrine/ergotamine and intravenous infusion of oxytocin. Prostaglandins E - 2, F - 2 α , and misoprostol have been used and good responses have been reported. Antibiotics are commonly given, although positive microbial cultures are not frequently found. Uterine curettage is commonly performed. However, this is not without risk; uterine perforation is reported in 3% of women with secondary postpartum hemorrhage, and has occurred in patients up to 28 days after delivery. Histologic confi rmation of products of conception occurs only in about a third of cases; however, an apparent therapeutic benefi t may be achieved even in its absence. Ultrasound is no more accurate in the diagnosis of retained placental tissue than clinical assessment. If bleeding is not controlled by these means, further surgical intervention is necessary. As for primary hemorrhage, ligation of the uterine vasculature, hysterectomy, and arterial embolization have all been successfully performed, although there is little evi- dence to show which is the optimum procedure. Women with genital tract trauma may also undergo these procedures if primary suturing is unsuccessful or not feasible. Angiography performed prior to embolization may also result in the diagnosis of vascular causes of secondary hemorrhage where otherwise no underlying cause could be identifi ed [123] . A case series of 14 patients revealed a false aneurysm of the uterine artery in two women and an arteriovenous fi stula in one woman. Conclusion Hemorrhage is a common complication of pregnancy and remains one of the most frequent causes of maternal morbidity and mortality. 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Eur J Obstet Gynecol Reprod Biol 2004 ; 115 : 39 – 42 . 105 Pal M , Biswas AK , Bhattacharya SM . B - Lynch brace suturing in primary post - partum hemorrhage during caesarean section . J Obstet Gynaecol Res 2003 ; 29 : 317 – 320 . 106 Ferguson JE II , Bourgeois FJ , Underwood PB Jr . B - Lynch suture for postpartum hemorrhage . Obstet Gynecol 2000 ; 95 : 1020 – 1022 . 107 Habek D , Kulas T , Bobi - Vukovi M , Selthofer R , Vuji B , Ugljarevi M . Successful of the B - Lynch compression suture in the management of massive postpartum hemorrhage: case reports and review . Arch Gynecol Obstet 2006 ; 273 ( 5 ): 307 – 309 . 108 Ochoa M , Allaire AD , Stitely ML . Pyometria after hemostatic square suture technique . Obstet Gynecol 2002 ; 99 ( 3 ): 506 – 509 . 109 Tamizian O , Arulkumaran S . The surgical management of postpar- tum haemorrhage . Curr Opin Obstet Gynecol 2001 ; 13 : 127 – 131 . 110 Dildy GA 3rd . Postpartum hemorrhage: new management options . 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Radiology 1998 ; 208 : 359 – 362 . 123 Pelage JP , Soyer P , Repiquet D , et al. Secondary postpartum haemor- rhage: treatment with selective arterial embolisation . Radiology 1999 ; 212 : 385 – 389 . 124 Alanis M , Hurst BS , Marshburn PB , Matthews ML . Conservative management of placenta increta with selective arterial embolization preserves future fertility and results in a favorable outcome in sub- sequent pregnancies . Fertil Steril 2006 ; 86 ( 5 ): 1514 . 125 Soncini E , Pelicelli A , Larini P , Marcato C , Monaco D , Grignaffi ni A . Uterine artery embolization in the treatment and prevention of Chapter 22 326 158 Mannucci PM , Tuddenham EGDF . Medical progress: the hemophil- ias – from royal genes to gene therapy . N Engl J Med 2001 ; 344 : 1773 – 1779 . 159 Kulkarni R , Lusher JM . Intracranial and extracranial hemorrhages in newborns with hemophilia: a review of the literature . J Pediatr Hematol Oncol 1999 ; 21 : 289 – 295 . 160 Yang MY , Ragni MV . Clinical manifestations and management of labor and delivery in women with factor IX defi ciency . Haemophilia 2004 ; 10 ( 5 ): 483 – 490 . 161 Shobeiri SA , West EC , Kahn MJ , Nolan TE . Postpartum acquired hemophilia (factor VIII inhibitors): a case report and review of the literature . Obstet Gynecol Surv 2000 ; 55 : 729 – 737 . 162 Collins P , Macartney N , Davies R , Lees S , Giddings J , Majer R . A population based, unselected, consecutive cohort of patients with acquired haemophilia A . Br J Haematol 2004 ; 124 : 86 – 90 . 163 Collins PW . Treatment of acquired hemophilia A . J Thromb Haemost 2007 ; 5 ( 5 ): 893 – 900 . 164 Solymoss S . Postpartum acquired factor VIII inhibitors: results of a survey . Am J Hematol 1998 ; 59 : 1 – 4 . 165 Kadir RA , Koh MB , Lee SA , Pasi KJ . Acquired haemophilia, an unusual cause of severe postpartum haemorrhage . Br J Obstet Gynaecol 1997 ; 104 : 854 – 856 . 166 Morrison AE , Ludlam CA , Kessler C . Use of porcine factor VIII in the treatment of patients with acquired hemophilia . Blood 1993 ; 81 : 1513 – 1520 . 167 Collins PW , Hirsch S , Baglin TP , et al., for the UK Haemophilia Centre Doctors ’ Organisation. Acquired haemophilia A in the UK: a two year national surveillance study by UK Haemophilia Centre Doctors Organisation . Blood 2007 ; 109 : 1870 – 1877 . 168 Hay CR , Negrier C , Ludlam CA . The treatment of bleeding in acquired haemophilia with recombinant factor VIIa: a multicentre study . Thromb Haemost 1997 ; 78 : 1463 – 1467 . 169 Mudad R , Kane WH . DDAVP in acquired hemophilia A: case report and review of the literature . Am J Hematol 1993 ; 43 : 295 – 299 . 170 Hoveyda F , MacKenzie IZ . Secondary postpartum haemorrhage: incidence, morbidity and current management . Br J Obstet Gynaecol 2001 ; 108 : 927 – 930 . 145 Economides DL , Kadir RA , Lee CA . Inherited bleeding disorders in obstetrics and gynaecology . 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Am J Obstet Gynecol 2001 ; 185 : 896 – 902 . 151 Mannucci PM . How I treat patients with von Willebrand disease . Blood 2001 ; 97 : 1915 – 1919 . 152 Ray JG . DDAVP use during pregnancy: an analysis of its safety for mother and child . Obstet Gynecol Surv 1998 ; 53 : 450 – 455 . 153 Chediak JR , Alban GM , Maxey B . von Willebrand ’ s disease and pregnancy: management during delivery and outcome of offspring . Am J Obstet Gynecol 1986 ; 155 : 618 – 624 . 154 Walzman M , Bonnar J . Effects of tranexamic acid on the coagulation and fi brinolytic systems in pregnancy complicated by placental bleeding . Arch Toxicol 1982 ; 5 (suppl): 214 – 220 . 155 Lindoff C , Rybo G , Astedt B . Treatment with tranexamic acid during pregnancy, and the risk of thrombo - embolic complications . Thromb Haemost 1993 ; 70 : 238 – 240 . 156 Roque H , Funai E , Lockwood CJ . von Willebrand disease and preg- nancy . J Matern Fetal Med 2000 ; 9 : 257 – 266 . 157 Kadir RA , Economides DL , Braithewaite J , Goldman E , Lee CA . The obstetric experience of carriers of haemophilia . Br J Obstet Gynaecol 1997 ; 104 : 803 – 810 . 327 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 23 Severe Acute Asthma Michael A. Belfort 1 & Melissa Herbst 2 1 Department of Obstetrics and Gynecology, Division of Maternal - Fetal Medicine, University of Utah School of Medicine, Salt Lake City, UT and HCA Healthcare, Nashville, TN, USA 2 Maternal - Fetal Services of Utah, St. Mark ’ s Hospital, Salt Lake City, UT, USA Introduction Asthma is one of the most frequent chronic illnesses encountered in pregnant patients. A recent report found that 9% of the US population reported a diagnosis of asthma at some point in their lifetime [1] . Four to eight per cent of pregnant women have a diagnosis of asthma [2,3] . The prevalence appears to be increas- ing as demonstrated by the 3% rise reported in the 1997 – 2001 US survey when compared to the previous survey [3] . With the con- tinuing increase in the number of pregnant patients with asthma, it is important that providers understand the issues surrounding the care of these women during pregnancy. Asthma is a chronic infl ammatory disease of the airways that is manifested as a hyperresponsiveness of the airway to a wide variety of stimuli resulting in airway obstruction that is partially or completely reversible [4] . Most patients with asthma have the classic triad of symptoms: the simultaneous occurrence of cough, shortness of breath, and wheezing [5] . The pathophysiology of asthma is still not fully understood. However, it is known that asthma is a chronic infl ammatory disorder of the airways result- ing from infl ammation causing episodes of wheezing, breathless- ness, chest tightness, and cough [6] . A number of different cells are involved and include mast cells, eosinophils, and T lympho- cytes. These all interact to increase airway sensitivity leading to infl ammation and variable airfl ow limitation that is generally reversible with treatment [6] . Diagnosis The diagnosis of asthma is considered in patients who present with episodic, reversible, occurrences of cough, wheeze, dyspnea, hyperventilation or combination of the above [5,7] . As the symp- toms are often non - specifi c in nature, the role of a history, physi- cal, and laboratory evaluation are important to confi rm the diagnosis. Patients often give a history of episodic events or symp- toms which can be related to exposure to specifi c triggers. These triggers include allergens, upper respiratory tract infections, med- ications (such as aspirin and β − blockers), environmental pollut- ants, occupational exposures (chlorine - based cleaning products), exercise, cold air, emotional stress, and gastroesophageal refl ux [8,9] . On physical exam during these events, widespread high - pitched, musical wheezes occurring at various points in the respi- ratory cycle are characteristic but not specifi c [5] . These wheezes are often quickly resolved with the use of β - agonists. While the history and physical examination can identify patients with asthma in the majority of cases, it remains important that pul- monary function testing is performed so as to confi rm the diag- nosis and assist in the determination of management [5] . The mainstay of pulmonary function testing is spirometry. Spirometry allows the measurement of forced expiratory volume in one second (FEV 1 ) and forced vital capacity (FVC). FEV 1 is the most important in the assessment of airfl ow obstruction and its severity. This value is constructed based upon the percentage of the predicted forced expiration for that patient as determined by her demographic characteristics. While such testing is important in the initial evaluation, it is impractical for continued manage- ment due to logistic constraints. Peak expiratory fl ow rate (PEFR) however can easily be obtained through a peak fl ow meter. It is measured during a maximal exhalation that has immediately fol- lowed a maximal inhalation [5] . This measurement correlates well with FEV 1 . The peak fl ow meter is easy to use, inexpensive, disposable and portable making it ideal for the determination of severity, therapy response, and for monitoring disease course [10] . It is important to note however that PEFR does have limita- tions. These include its dependence upon effort and proper technique, making consistent observation and monitoring of technique essential [11 – 13] . A chest X - ray should be considered to exclude other causes of respiratory diffi culty [5] . Once the diagnosis of asthma is made, the same information used to deter- mine the diagnosis can be utilized to determine severity. Chapter 23 328 no change in forced vital capacity [10] (Figure 23.1 ). There is a 20% increase in oxygen consumption, and a 15% increase in metabolic rate achieved through a 40 – 50% increase is resting minute ventilation. This increase in minute ventilation is due to an increase in tidal volume rather than a change in respiratory rate which is unchanged. This hyperventilation increases arterial oxygen tension and decreases carbon dioxide tension. This mild respiratory alkalosis leads to a compensatory decrease in sodium bicarbonate as the kidneys maintain acid – base balance [7] . The normal values of an arterial blood gas are altered in pregnancy (see Table 23.2 ). Normal values for FEV 1 and PEFR remain unchanged in pregnancy since there are no changes in airway mechanics; therefore most people accept that the standard ranges used outside of pregnancy can be used during pregnancy for management decisions [22,10] . One study did suggest that PEFR and FEV 1 are lower in pregnancy in the supine position as com- pared to seated, and therefore, it is recommended that patients are positioned in as close to a seated position as possible during acute attacks [23] . Others have found that hypoxemia may be exacerbated during an acute attack due to the decrease in func- tional residual capacity [24] . Lastly, evaluation of arterial blood gases during an acute asthma attack must be done bearing in mind the underlying respiratory alkalosis. The classifi cation of asthma severity is important for the choice of therapy as well as for patient monitoring. The classifi cation is based upon diagnostic criteria: symptoms, occurrences, and FEV 1 /PEFR. In their 2004 report the National Asthma Education and Prevention Program (NAEPP) Working Group on Asthma in Pregnancy proposed the following classifi cation for asthma in pregnancy: mild intermittent, mild persistent, moderate persis- tent, and severe persistent [14] (Table 23.1 ). Patients can be reclassifi ed up or down based upon repeat evaluation and their therapy can be modifi ed accordingly. Respiratory c hanges in p regnancy Pregnancy causes both physical and functional changes which can affect symptoms and infl uence therapy. Physical changes occur at the macroscopic and microscopic level. Starting in the fi rst trimester, the subcostal angle changes from 68 ° to as much as 108 ° [15,16] . The diaphragm may rise up to 4 cm and there may be an increase in chest diameter of 2 cm or more as pregnancy pro- gresses [17] . Diaphragmatic excursion increases up to 2 cm which results in a more barrel - chested appearance [17] . Histologic examination performed by Toppozado et al. showed that the upper respiratory mucosa of pregnant patients demonstrated hyperemia, glandular hyperactivity, increased phagocytic activity and increased mucopolysaccharide content [18] . Such changes are likely due to the increase in estrogen levels and lead to symp- tomatic nasal stuffi ness and more common epistaxis [19] . These physical changes, along with other pregnancy adaptations, lead to many functional respiratory changes. With diaphragmatic elevation, there is a progressive 20% decrease in functional resid- ual capacity along with decreases in expiratory reserve, residual volume, and functional reserve capacity [7,20,21] (Figure 23.1 ). However, because diaphragmatic function is unchanged, there is Table 23.1 Defi nition of asthma severity. * Severity classifi cation Symptoms (A: daytime/B: night - time) Exacerbations Lung function testing Mild intermittent A: ≤ Two times per week Brief (lasting 1 hour to a few days) FEV 1 or PEFR ≥ 80% predicted B: ≤ Two times a month Intensity varies PEFR day - to - day variability < 20% Mild persistent A: ≥ Two times per week but not daily Brief (lasting 1 hour to a few days) FEV 1 or PEFR ≥ 80% predicted B: > Two times per month May affect activity PEFR day - to - day variability 20 – 30% Moderate persistent A: Daily ≥ Two times/week and may last days FEV 1 or PEFR > 60 but < 80% predicted B: > Once/week Affects activity PEFR day - to - day variability > 30% Severe persistent A/B: Continual Frequent FEV 1 or PEFR ≤ 60% predicted Limits physical activity PEFR day - to - day variability > 30% * From the National Institutes of Health [14] . FEV 1 , forced expiratory volume in one second. PEFR, peak expiratory fl ow rate. Table 23.2 Arterial blood gas values in pregnant and non - pregnant patients. Non - pregnant Pregnant pH 7.38 – 7.42 7.40 – 7.45 PaO 2 (mmHg) 90 – 100 104 – 108 PaCO 2 (mmHg) 35 – 45 27 – 32 HCO 3 (mEq/L) 22 – 26 18 – 31 . prenatal care visit and again in the third trimester. Following delivery, there is a rapid fall - off in factor VIII levels, resulting in a high rate of secondary postpartum hemorrhage. Postpartum. risk of antepartum hemorrhage; however, the reported incidence of primary postpartum hemorrhage ranges between 22% and 59% [146,147] , with an incidence of 20 – 28% for secondary post- partum hemorrhage. experience of carriers of haemophilia . Br J Obstet Gynaecol 1997 ; 104 : 803 – 810 . 327 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy.