Critical Care Obstetrics part 32 doc

Thromboembolic Disease 299 Postpartum m anagement Conversion from heparin to warfarin anticoagulation should be initiated post partum in the hospital to minimize the maternal risk of complications. Once the patient has delivered and is suffi ciently stable, full heparin anticoagulation should be resumed. Then, oral warfarin therapy should be started with 10 – 15 mg orally per day for 2 – 4 days, followed by 2 – 15 mg/day as indicated by the INR or PT [109] . Heparin and warfarin therapy should be overlapped for the fi rst 5 – 7 days post partum until an INR of approximately 2. 0 – 3.0 has been achieved. One approach is to give the warfarin sodium at 6 p.m., then draw an INR or PT at 6 a.m. the following day, adjusting the dose for the subsequent day ’ s warfarin according to that morning ’ s results. Once the patient is therapeutically anticoagulated, heparin is discontinued. Postpartum suppression of lactation with estrogen is associated with a much higher incidence of thromboembolic complications and is contraindicated [175,176] . Prophylaxis of t hromboembolism The dosage of heparin needed during pregnancy appears to increase because of increases in heparin - binding proteins, plasma volume, renal clearance, and heparin degradation by the placenta. All contribute to a decreased bioavailability of heparin. Due to a lack of adequate prospective trials, a number of different prophylactic regimens have been proposed. Low - dose prophylaxis with UFH may be administered via 5000 – 7500 units every 12 hours during the fi rst trimester, 7500 – 10,000 units every 12 hours during the second trimester, followed by 10,000 units every 12 hours during the third trimester unless the aPTT is elevated. Alternatively, LMWH may be used. For low - dose prophylaxis, dalteparin 5000 units once or twice daily or enoxaparin 40 mg once or twice daily may be used. Adjusted - dose prophylaxis may be accomplished with either dalteparin 5000 – 10,000 units every 12 hours or enoxaparin, 30 – 80 mg every 12 hours [165] . An increase from 5000 units to 7500 – 10,000 units in the third trimester [42] is often recommended [177] . Except for doses exceeding 8000 units, laboratory monitoring is not usually required [42] . Caution should be used in the patient with dimin- ished renal function, such as seen during pre - eclampsia, which may elevate heparin levels. Employing perioperative (cesarean) prophylaxis may be considered for certain patients, such as individuals who are obese, have diffi culty ambulating or have been at prolonged bed rest. Conservative mechanical methods, such as intermittent pneumatic compression boots or graduated elastic compression stockings, may be used. A recent decision analysis investigated the use of thromboprophylaxis after cesarean delivery. The authors compared four methods: universal subcutaneous heparin prophylaxis, heparin prophylaxis only for patients with a genetic thrombophilia, use of pneumatic compression stockings, and no thromboprophylaxis. Use of pneumatic compression stockings after cesarean delivery was the strategy with the lowest numbers of adverse events. Universal prophylaxis with heparin was associated with an excess risk of heparin - induced thrombocytopenia clotting profi le and hematocrit should be drawn. There are three basic choices in the approach to anticoagulant management in such patients. 1 Continue therapeutic anticoagulation. This approach is recommended for particularly high - risk patients, such as those with recent PE, iliofemoral thrombosis or mechanical heart valve prostheses. Because a more uniform therapeutic heparin level is desirable, the patient may be changed from subcutaneous injection to continuous IV infusion. A heparin level of 0.4 units/mL or a low therapeutic aPTT (close to 1.5 times normal) may be desirable in these surgical patients. 2 Reduce the subcutaneous heparin dose. In patients at lower risk of thromboembolism, the heparin dose can be reduced to a prophylactic level (5000 units every 12 hours); this dose is not associated with increased surgical bleeding. 3 Stop or withhold heparin administration. For patients at increased risk for operative bleeding (i.e. suspected placenta accreta) and at relatively low risk of clot propagation, heparin may be temporarily withheld or its effects reversed with protamine sulfate. Non - pharmacologic prophylaxis (e.g. pneumatic compression stockings) may be substituted during the intraop- erative period. With patients who are anticoagulated and in whom rapid reversal is deemed essential, protamine sulfate can be used to reverse either UFH or LMWH. One milligram of protamine sulfate neu- tralizes 100 units of heparin. To determine the proper dose of protamine, several approaches are available. One is to calculate the amount of circulating heparin by estimating the plasma volume at 50 mL/kg of body weight and multiplying the plasma volume by the heparin concentration [17] . In most institutions, however, this procedure may not be technically feasible. If heparin level is not available, the amount of protamine sulfate to give should be underestimated or slowly titrated to the whole - blood clotting time because of the short half - life (rapid metabolism) of heparin and the irreversible anticoagulant effect of excess protamine. No single dose should exceed 50 mg. A 50 mg dose is almost never needed because it would neutralize 5000 units of circulating heparin, an amount highly unlikely to be present. Protamine sulfate should be administered IV over 20 – 30 minutes to prevent hypotension. In patients receiving adjusted - dose subcutaneous heparin, a dose of 5 – 10 mg of protamine sulfate is often suffi cient; further doses may be given, depending on the aPTT value. It should be emphasized that for vaginal delivery, even signifi cantly prolonged aPTT values rarely result in clinical hemorrhage, and thus do not require protamine sulfate therapy. Patients who present for delivery on warfarin anticoagulant are at heightened risk for bleeding with either vaginal or operative delivery. Parental vitamin K can help to regenerate the clotting factors within 12 hours. If there is little time or reversal is not adequate, fresh frozen plasma can be given to supply clotting factors. Regardless, the pregnant woman should be sta- bilized and be suffi ciently able to clot before operative delivery is initiated. Chapter 21 300 study to prevent postoperative DVT in non - pregnant patients, a dose of 1 IU/kg/h reduced the incidence of DVT from 22% to 4%. Thrombolytic t herapy Defi brinating agents may be indicated in cases of life - threatening thromboembolism [191 – 194] . Streptokinase, urokinase, and tissue plasminogen activator activate plasminogen, which sets in motion the body ’ s natural fi brinolytic system. Although helpful in early management of massive PE, thrombolysis plus heparin may not yield improved mortality over heparin alone [191] . Because of the potential risk of bleeding, thrombolytic therapy has not been recommended within 10 days of surgery or parturition [193] . Recommended treatment schedules vary, but all consist of an IV loading dose followed by continuous infusion for 12 – 72 hours, depending on the clinical situation [192] . Thrombolytic therapy is followed by anticoagulant therapy to prevent recurrence. A review of 172 patients by Turrentine et al. demonstrated that thrombolytic therapy could be used relatively safely during pregnancy in selected clinical situations (Table 21.13 ) and that these agents were partially or completely successful in 86 – 90% of recipients [194] . Nonetheless, the authors sug- gested that traditional therapies should be used fi rst and, if unsuccessful, thrombolytic agents should be reserved for life - or limb - threatening VTE with the understanding of the increased risk of bleeding complications. Ancrod, derived from Malayan pit viper venom, is contraindicated in pregnancy. Animal studies have shown a high incidence of fetal death. Postpartum hemorrhage from the placental site also occurs at a greater frequency. Inferior v ena c ava fi lter p lacement The safe placement of inferior vena cava fi lters to prevent PE has been reported during pregnancy. Eleven patients with DVT and who were presumed to have an increased risk of PE underwent placement of a temporary inferior vena cava fi lter between 1998 and 2004. All the fi lters were placed at the suprarenal inferior vena cava prior to delivery. During fi lter placement, anticoagulant therapy was continued and then stopped intrapartum. No induced thrombosis and bleeding per VTE [178] . Another group performed a decision analysis comparing no thromboprophylaxis to intermittent pneumatic compression and confi rmed that mechanical thromboprophylaxis is estimated to a cost - effective strategy [179] . Early postoperative ambulation is also important in preventing thromboembolism. Low - dose heparin is accepted as prophylaxis for a variety of surgical procedures [180] . Although in some general surgical or orthopedic patients dihydroergotamine in combination with heparin is felt to be more effective than heparin alone [181,182] , its use in pregnant or parturient women has not been studied. Thus, its use cannot be recommended. The combination of mechanical methods, especially pneumatic compression, and low - dose heparin may be the optimal approach for high - risk patients [183,184] . LMWH has been found useful in abdominal surgery; one dose is given preoperatively, followed by additional doses once every 24 hours [185,186] . According to the ACCP recommendations, patients with a history of a single episode of VTE, associated with a transient risk factor that is no longer present, should undergo antepartum clinical surveillance and postpartum anticoagulation [55] . In patients with a history of a single episode of VTE and thrombophilia or a strong family history and not currently on lifelong anticoagulation, antepartum prophylactic or intermediate - dose LMWH or minidose or moderate - dose UFH, plus postpartum anticoagulation is recommended. Intermediate - dose LMWH is defi ned as dalteparin 5000 U SC q12 h or enoxaparin 40 mg SC q12 h. Minidose heparin is UFH 5000 U SC q12 h and moderate - dose UFH is UFH SC q12 h in doses adjusted to target an anti - Xa level of 0.1 – 0.3 U/mL [55] . Therapeutic anticoagulation is necessary during pregnancy for those patients with mechanical heart valves [187] or inherited defi ciency of a natural anticoagulant such as AT III [188] . In women with AT III defi ciency, successful outcomes have been achieved with the use of subcutaneous and IV heparinization, accompanied by infusion of AT III concentrate at the time of abortion or delivery [188] . AT III defi ciency should be considered when heparin requirements increase beyond typical dosages. Without such therapy, maternal morbidity or mortality and fetal loss are extremely high. Defi ciencies of proteins C and S are also associated with thrombotic tendency [189] . In patients with medical histories remarkable for VTE, a system- atic comprehensive approach to thrombophilic screening should be pursued. Knowledge of an individual ’ s thrombophilic status can be used to better predict VTE recurrence risk [24] . Antiplatelet agents such as aspirin and dipyridamole may be helpful in preventing thrombosis in the arterial circulation and with some prosthetic heart valves. There is no known role for these agents in the prevention of pregnancy - associated VTE disease. Perioperative prophylaxis with dextran appears benefi cial in some surgical patients, but the risk of bleeding is higher than with heparin, and dextran ’ s usefulness in pregnant patients has not been established [187] . A potential but currently unproven approach in pregnancy for intrapartum prophylaxis in patients without an active thrombotic process is ultra - low - dose IV heparin [190] . In a randomized Table 21.13 Maternal and perinatal outcome in 172 patients who received thrombolytic therapy during pregnancy. n % Hemorrhage 14 8 Preterm birth 10 6 Perinatal deaths 10 6 Maternal deaths 2 1 Reproduced by permission from Turrentine MA, Braeems G, Ramirez MM. Use of thrombolytics for the treatment of thromboembolic disease during pregnancy. Obstet Gynecol 1995; 50: 534 – 541. Thromboembolic Disease 301 of opinion regarding heparin prophylaxis during pregnancy, there is uniform agreement that anticoagulant therapy is war- ranted in the puerperium [35,37,38,205 – 211] . For patients with recurrent thromboembolism or a family history of these defi ciencies, prenatal screening for AT III, protein C, and protein S appears reasonable. Antiphospholipid s yndrome ( APS ) Individuals presenting with clinical signs of thrombosis or embolism which is objectively confi rmed should receive heparin, either unfractionated or low molecular weight, according to accepted therapeutic regimens. Since minimal doses of heparin may prolong the aPTT without a therapeutic level being achieved, it is best to follow these patients with anti - factor Xa levels to ensure adequacy of therapy. Patients with APS and a prior thrombosis appear to have a risk of recurrent thrombosis that is substantially higher than the recurrent risk with most other thrombophilias. Retrospective studies have shown that up to 70% of APS patients have recurrent thrombotic events during the 5 – 6 years following their initial thrombosis [212,213] . Prospective studies have confi rmed a high risk of recurrent thrombosis among APS patients [214] . As such, most experts recommend long - term thromboprophylaxis in patients with APS who have experienced a thrombotic event. References 1 Berg CJ , Atrash HK , Koonin LM , Tucker M . Pregnancy - related mortality in the United States, 1997 – 1990 . Obstet Gynecol 1996 ; 88 : 161 – 167 . 2 Chang J , Elam - Evans LD , Berg CJ , et al. Pregnancy - Related Mortality Surveillance – United States 1991 – 1999 . MMWR 2003 ; 52 ( SSO2 ): 1 – 8 . 3 Bonnar J . Can more be done in obstetric and gynecologic practice to reduce morbidity and mortality associated with venous thrombo- emblism? Am J Obstet Gynecol 1999 ; 180 ( 4 ): 784 – 791 . 4 Toglia MR , Weg JG . Venous thromboembolism during pregnancy . N Engl J Med 1996 ; 335 : 108 – 114 . 5 Gherman RB , Goodwin TM , Leung B , Byrne JD , Hethumumi R , Montoro M . 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Subsequently, all the fi lters were removed [195] . Placement of a vena cava fi lter has also been successfully performed during early labor followed by vaginal delivery without incident [196] . Surgical i ntervention With pregnancy, surgical intervention may be indicated in some clinical situations, such as replacement of a thrombosed cardiac valve prosthesis, thrombectomy for acute iliofemoral thrombosis, embolectomy of a life - threatening massive PE, vena cava interruption for recurrent venous emboli despite adequate anticoagulation, or when anticoagulation is absolutely contraindicated. Embolectomy is a heroic measure, which may occasionally be life saving. Transvenous catheter embolectomy has been performed successfully for expeditious management of massive PE with cardiovascular collapse [197] . There are a variety of methods for interruption of the vena cava. These include complete ligation, Te fl on clips, and devices inserted transvenously, such as the umbrella fi lter or the Greenfi eld fi lter [198] . Special c onsiderations Antithrombin III d efi ciency The fi rst evidence of an inherited AT III defect is frequently a thromboembolic event. Pregnant patients with inherited AT III defi ciency often require therapeutic anticoagulation through the pregnancy and the puerperium [188,189,199 – 204] . In addition to heparin therapy throughout pregnancy [199,201,202,204] , IV administration of AT III concentrate may be necessary to minimize the patient ’ s risk of a thromboembolism [188,189] . This can be accomplished with fresh frozen plasma, but AT III concentrate is preferable [199,201,202] . The loading dose of AT III is 50 – 70 units/kg. This is followed by 20 – 30 units/kg/day to maintain an AT III level of 80% of normal [200] . The higher the AT III level, the less heparin will be required for therapeutic anticoagulation. 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Ann Intern Med 1992 ; 117 : 303 – 308 . 213 Khamastha MA , Cuadrado MJ , Mujic F , et al. The management of thrombosis in antiphospholipid antibody syndrome . N Engl J Med 1995 ; 332 : 993 – 997 . 214 Schulman S , Svenungsson E , Granqvist S . Duration of Anticoagulation Study Group. Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy . Am J Med 1998 ; 104 : 332 – 338 . 308 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 22 Etiology and Management of Hemorrhage Irene Stafford 1 , Michael A. Belfort 2 & Gary A. Dildy III 3 1 Maternal - Fetal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA 2 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 3 Maternal - Fetal Medicine, Mountain Star Division, Hospital Corporation of America, Salt Lake City, UT and Department of Obstetrics and Gynecology, LSU Health Sciences Center, School of Medicine in New Orleans, New Orleans, LA, USA In patients with major obstetric hemorrhage, three measures must be promptly taken: identify the cause, arrest the bleeding and management of hypovolemia, anemia and coagulopathy. Continued hemorrhage, particularly if concealed or underestimated, may result in the onset of irreversible shock. Although the percentage of death caused by hemorrhage decreased by approximately one - third between 1979 – 1986 and 1991 – 1997, it continues to be a leading cause of pregnancy - related mortality [1 – 3] . An estimated 140,000 women worldwide die every year from postpartum hemorrhage, with over 50% of these occurring within the fi rst 24 hours after delivery [4] . Postpartum hemorrhage remains among the top three causes of maternal deaths in the United States, with life - threatening hemorrhage occurring in 1 in 1000 deliveries [5] . The major obstetric causes for antepartum hemorrhage are placental abruption and placenta previa, while postpartum hemorrhage is most commonly caused by uterine atony, retained placenta, and genital tract lacerations. Other less common but sometimes more serious causes include uterine rupture, uterine inversion and abnormal placental inva- sion (placenta accreta, increta, and percreta). Management of these conditions along with management of hemorrhage related to inherited or acquired bleeding disorders will be discussed in this chapter. Conditions caused by pregnancy (HELLP syndrome, acute fatty liver of pregnancy, amniotic fl uid embolism) and disseminated intravascular coagulation are discussed in other chapters. Massive hemorrhage may also result from surgical causes in pregnant or postpartum women. These include liver rupture in HELLP syndrome, and rupture of aortic, splenic, and renal artery aneurysms. Although rare, these should be considered in patients with hemorrhagic shock and concealed bleeding in whom an obstetric cause such as abruption, pelvic hematoma or uterine rupture is unlikely. Placental a bruption Placental abruption is defi ned as the premature separation of a normally situated placenta, and may be partial or complete. The underlying mechanism is unknown, but most explanations center around vascular or placental abnormalities, including increased fragility of vessels, vascular malformations or abnormal placenta- tion [6,7] . Often, in the acute setting, the etiology of abruption may be clear. For example, shearing forces are most likely respon- sible for abruption resulting from trauma. There is strong evidence linking abruption to abnormal fi rst - trimester changes, suggesting that abruption may be chronic in nature. Abnormal serum analytes and placental biology studies support this notion [8] . Hemorrhage occurs into the decidua basalis, forming a hematoma which splits the decidua [9] . As the hematoma expands, further placental separation ensues. Large Epidemiol ogic studies report an incidence ranging from 5.9 to 6.5 per 1000 singleton births and 12.2 per 1000 twin births [10] . Discrepancies in rates of abruption are reported, mainly because abruption can also be discovered upon histologic examination of the placenta in other- wise normal pregnancies. Pre - eclampsia is the most common risk factor and is found in approximately 50% of women with placental abruption [11] . Other risk factors include preterm premature rupture of membranes, polyhydramnios, advanced maternal age, cocaine use, smoking, multiparity, chorioamnionitis, blunt trauma and possibly thrombophilias. Black women are more at risk than other population groups [12,13] . Bleeding in the fi rst trimester has been linked with increased rates of abruption later in pregnancy [14,15] and there is approximately a 10% recurrence rate during a subsequent pregnancy. Placental abruption is associated with multiple adverse perinatal outcomes including a ninefold increased risk of intrauterine fetal demise, a threefold rise in preterm birth and a twofold increase in growth restriction. The risk of stillbirth has been found to correlate with the extent of placental separation, with higher rates of death associated with . thromboembolism following anticoagulant therapy . Am J Med 1998 ; 104 : 332 – 338 . 308 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan. of the value of monitoring heparin treatment with the activated partial thrombo- plastin time . N Engl J Med 1972 ; 287 : 324 – 327 . 124 Hyers TM , Hull RD , Weg JG . Antithrombotic therapy. Dallas, TX, USA 2 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,

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