Critical Care Obstetrics part 50 pot

Systemic Lupus Erythematosus and Antiphospholipid Syndrome 479 Intravenous immunoglobin (IVIg) is another option for moderate to sever fl are and is particularly helpful in controlling hema- tologic and renal disease [94,95] . There are few reports of IVIG use for SLE fl are during pregnancy. However, the safety of IVIG in pregnancy has been well documented in its frequent use for other conditions in pregnancy including including alloimmune thrombocytopenia, immunologic thrombocytopenia purpurpa, and red blood cell antigen alloimmunization. In non - pregnant patients, both cyclophosphamide and mycophenolate mofetil (MMF) may be used in severe SLE exacerbations to control disease, reduce irreversible tissue damage, and reduce glucocorticoid doses [96 – 98] . In particular, severe proliferative lupus nephritis may be treated more effectively with cyclophosphamide, usually in combination with glucocorticoids [96] . Their use during pregnancy should be avoided, particularly during the fi rst trimester [57] . Antiphospholipid s yndrome in p regnancy The diagnosis of APS is based on the presence of one or more characteristic thrombotic or obstetric features of the condition; laboratory testing for antiphospholipid antibodies (aPLs) is used to confi rm or refute the diagnosis. The International Consensus Statement was recently updated in 2006 and provides simplifi ed criteria for the diagnosis of APS [99] . Patients with bona fi de APS must manifest at least one of two clinical criteria (vascular thrombosis or pregnancy morbidity) and at least one of two laboratory criteria (positive lupus anticoagulant (LAC) or medium to high titers of IgG or IgM isotype anticardiolipin (aCL) antibodies, and/ or IgG or IgM isotype anti β 2 - glycoprotein I - antibodies, confi rmed on two separate occasions, at least 6 weeks apart. Thrombosis may be either arterial or venous and must be confi rmed by an imaging or Doppler study or by histopathology. Pregnancy morbidity is divided into three categories: (i) otherwise unexplained fetal death (10 weeks ’ gestation or greater); (ii) preterm birth (34 weeks gestation) for severe pre - eclampsia or placental insuffi ciency; or (iii) three or more otherwise unexplained, consecutive pre - embryonic or embryonic pregnancy losses. Autoimmune thrombocytopenia and amaurosis fugax are often associated with APS but are not considered suffi cient diagnostic criteria. APS may exist as an isolated immunologic derangement (primary APS) or in combination with other autoimmune diseases (secondary APS), most commonly SLE. The p athogenesis of a ntiphospholipid s yndrome The mechanism(s) by which aPLs cause thrombosis is complex and involves alterations in the coagulation cascade, platelets, and endothelial function. Interference with normal hemostasis occurs via interaction with phospholipids or phospholipid - binding protein components such as β 2 - glycoprotein I (which has anticoagulant properties), prostacyclin, prothrombin, protein C, annexin V, and tissue factor [100] . Antiphospholipid antibodies also appear to activate endothelial cells, indicated by increased Long - term use of all NSAIDs has been associated with decreased fetal urinary output and oligohydramnios as well as neonatal renal insuffi ciency [79] . Given these risks, chronic use of adult dosages of aspirin and other NSAIDs should be avoided during pregnancy. Acetaminophen - and narcotic - containing prepara- tions are acceptable alternatives if analgesia is needed during pregnancy. Other t reatments Several new treatment regimens including cyclosporin, high - dose intravenous immune globulin (IVIG), mycophenolate mofetil, and thalidomide have been studied in the treatment of non - pregnant patients with SLE [1] . Only IVIG has been used during pregnancy without reports of adverse fetal effects. Obviously, thalidomide is strictly contraindicated during pregnancy because of its known potent teratogenicity. Complete immunoablative therapy followed by bone marrow stem cell transplantation has also been studied in patients with the most severe, unresponsive SLE [1] . Treatment of SLE fl are d uring p regnancy Mild to moderate symptomatic exacerbations of SLE without CNS or renal involvement may be treated with initiation of glucocorticoids or an increase in the dose of glucocorticoids. Relatively small doses of prednisone (e.g. 15 – 30 mg/day) will result in improvement in most cases. For severe exacerbations without CNS or renal involvement, doses of 1.0 – 1.5 mg/kg/day of prednisone in divided doses should be used, and a good clinical response can be expected in 5 – 10 days. Thereafter, glucocorticoids may be tapered by several different approaches (Table 36.3 ). Severe exacerbations, especially those involving the CNS or kidneys, are treated more aggressively, usually with intravenous pulse glucocorticoid therapy The initial regimen involves a daily intravenous dose of methylprednisolone at 10 – 30 mg/kg (about 500 – 1000 mg) for 3 to 6 days. Thereafter, the patient is treated with 1.0 – 1.5 mg/kg/day of prednisone in divided doses, rapidly tapered over the course of 1 month. One can expect that 75% of patients will respond favorably to this approach. This regimen may be repeated every 1 – 3 months in severe cases as an alternative to cytotoxic drugs. Table 36.3 Suggested Methods for Tapering Prednisone. 1. Consolidate to a single morning dose of prednisone. Reduce the daily dose by 10% per week, as tolerated. When a dose of 20 to 30 mg/day is reached, reduce by 2.5 - mg increments per week. If the patient remains asymptomatic at a dose of 15 mg/day, reduce the dose by 1 - mg increments per week to a dose of 5 to 10 mg/day. 2. Consolidate to a single morning dose of prednisone. Taper to 50 to 60 mg/ day by reducing the dose 10% per week. Thereafter eliminate the alternate - day dose by tapering it 10% per week, as tolerated. Thereafter, taper the remaining every other day dose by 10% per week, as tolerated. Chapter 36 480 In the original description of APS, the sole obstetric criterion for diagnosis was fetal loss ( > 10 menstrual weeks gestation) [123,124] . At least 40% of pregnancy losses reported by women with LA or medium to high positive IgG aCL occur in the fetal period [122,125 – 127] . LACs are associated with fetal loss after the fi rst trimester, with ORs ranging from 3.0 to 4.8 while ACA display a wider range of ORs, 0.86 – 20.0 [120] . APS - related pregnancy loss has also been extended to include women with early recurrent pregnancy loss (RPL) including those occurring in the pre - embryonic ( < 6 menstrual weeks of gestation) and embryonic periods (6 – 9 menstrual weeks of gestation) [99] . In serologic evaluation of women with RPL, 10 – 20% have detectable aPLs [128 – 133] . Women with APS followed prospectively also have demonstrated high rates of premature delivery for gestational hypertension or pre - eclampsia and uteroplacental insuffi ciency as manifested by fetal growth restriction, oligohydramnios, and non - reassuring fetal surveillance [122,134] . Women with APS identifi ed because of a prior fetal death and/ or thromboembolism seem to have more serious complications in subsequent pregnancies than those with early RPL [135] . Prospective treatment trials of APS during pregnancy have been comprised mainly of women with early RPL and no other APS - related medical problems [130 – 132,136 – 138] . Accordingly, the rates of obstetric complications were relatively low with fetal death, pre - eclampsia, and preterm birth occurring in 4.5% (0 – 15%), 10.5% (0 – 15%), and 10.5% (5 – 40%), respectively. Only 1 of 300 women suffered a thrombotic event and no neonatal deaths due to complications of prematurity were reported. Based on these data, it seems unlikely that early RPL, fetal death, and preterm birth resulting from severe pre - eclampsia or placental insuffi ciency are a result of the same pathophysiologic mechanism. Treatment of a ntiphospholipid s yndrome d uring p regnancy Treatment goals for APS during pregnancy should include: (i) improvement in maternal and fetal/neonatal outcome by pre- venting pregnancy loss, pre - eclampsia, placental insuffi ciency, and preterm birth; and (ii) reduction or elimination of thromboembolism. Early enthusiasm for treatment with glucocorticoids to reduce the risk of pregnancy loss waned after publication of a small, randomized trial found maternally administered heparin to be as effective as prednisone [136] . Contemporary management (Table 36.4 ) should include treatment with either unfractionated heparin or low molecular weight heparin (LMWH) plus low dose aspirin (LDA) at 50 – 80 mg per day. [130 – 132,136 – 139] . A meta - analysis of trials using unfractionated heparin and LDA [140] reported a 54% improvement in the live birth rate. Another using enoxaparin treatment resulted in an increased live birth rate, as compared to LDA (RR 10.0, 95% CI 1.56 – 64.20) [140] . Despite treatment, other aPL - related adverse pregnancy outcomes still occur. In a prospective observational study of 150 women treated with LDA and either unfractionated heparin or enoxaparin after embryonic cardiac activity was identifi ed to expression of adhesion molecules, secretion of cytokines, and production of arachidonic acid metabolites [101] . The fi ndings that some aCLs cross - react with oxidized low - density lipoprotein [102] and that human aCLs bind to oxidized, but not reduced, cardiolipin [103] imply that aPLs may participate in oxidant - mediated injury of the vascular endothelium. They also bind perturbed cells, such as activated platelets [104] or apoptotic cells [105] , which typically lose normal membrane symmetry and express anionic phospholipids on their surface. Some APS - related pregnancy complications, particularly fetal loss, are probably related to abnormal placental function due to narrowing and thrombosis in decidual spiral arteries [106 – 108] . These abnormalities might result from thrombosis during the development of normal maternoplacental circulation via interference with trophoblastic annexin V [108] or by impairing trophoblastic hormone production or invasion [109] . Thrombosis as a mechanism for earlier pregnancy loss seems less likely. Whether aPLs per se are the cause of adverse obstetric outcomes is also a matter of debate. Investigators working with murine models have found that passive transfer of aPLs results in clinical manifestations of APS, including fetal loss and thrombocytopenia [110 – 112] . aPLs have also been demonstrated to have a procoagulant effect [113] . It is not until recently that investigations into aPL - related pregnancy loss have focused on a role for the complement system, a component of the innate immune system, which has been shown to cause and perpetuate obstetric complications [114 – 117] . Studies in a mouse model have shown that passive transfer of aPL antibodies results in activation of the complement cascade, in turn leading to an increase in complement activation fragments which are extremely deleterious to the fetus [115,116] . Follow - up studies have found that inactivation and inhibition of the complement cascade prevent fetal loss and growth restriction even after addition of aPL antibodies [116] . TNF - α , an infl ammatory factor released via complement activation, may also play a role as TNF - α defi cient mice fail to have pregnancy loss when treated with aPLs [118] . Clinical f eatures of APS d uring p regnancy Venous thrombotic events (VTEs) associated with aPLs include deep venous thrombosis (DVT) and acute pulmonary emboli (APE); cerebral vascular accidents and transient ischemic attacks are the most common arterial events. A meta - analysis of 18 studies examining the thrombotic risk among SLE patients with LAC, found odds ratios (ORs) of 6.32 (95% CI 3.71 – 10.78) for VTE and 11.6 (95% CI 3.65 – 36.91) for recurrent VTE [119] . By contrast aPLs were associated with a lower OR of 2.50 (1.51 – 4.14) for an acute VTE, and 3.91 (95% CI 1.14 – 13.38) for recurrent VTE. A meta - analysis of studies in the general population identifi ed a range of ORs for arterial and venous thromboses in patients with LAC of 8.6 – 10.8 and 4.1 – 16.2, respectively [120] . The com- parable numbers for aCL were 1 – 18 and 1 – 2.5. Up to 30% of patients may have recurrence, supporting the use of long - term prophylaxis [121] . The risk of VTE in pregnancy and the puerperium may be as high as 5% despite treatment [122] . Systemic Lupus Erythematosus and Antiphospholipid Syndrome 481 induced osteoporosis and heparin - induced thrombocytopenia (HIT). Osteoporosis resulting in fracture occurs in 1 – 2% of women treated during pregnancy [148] . Women treated with heparin should be encouraged to take daily supplemental calcium and vitamin D (e.g. prenatal vitamins). It also seems prudent to encourage daily axial skeleton weight - bearing exercise (e.g. walking). Immune - mediated HIT is much less common but potentially more serious. Most cases have their onset 3 – 21 days after heparin initiation and are relatively mild in nature [149] . A more severe form of HIT paradoxically involves venous and arterial thromboses resulting in limb ischemia, cerebrovascular accidents, and myocardial infarctions, as well as venous thromboses [150] . It may occur in up to 0.5% of patients treated with unfractionated sodium heparin [149] . Low molecular weight heparin (LMWH) is much less likely to be associated with HIT, compared with unfractionated sodium heparin [151] . Other pregnancy complications associated with APS occur in spite of appropriate treatment [122,141] . In a recent observational study of 107 pregnancies complicated by APS, pre - eclampsia occurred in 20%, preterm birth in 24%, and growth restriction in 15% of treated women [141] . Pregnancy losses continue to occur in 20 – 30% of cases in spite of heparin prophylaxis being given [122,136,139] . Several alternative therapies have been suggested in these so - called refractory cases. Glucocorticoids, often in high doses, have sometimes been added to regimens of heparin and low - dose aspirin. While there are anecdotal reports of success, this practice has never been studied in appropriately designed trials and the combination of glucocorticoids and heparin may increase the risk of osteoporotic fracture [136] . Hydroxychloroquine has been shown to diminish the thrombogenic properties of aPL in a murine thrombosis model [152] . There are few case reports and no trials of APS patients being treated during pregnancy with hydroxychloroquine. Intravenous gammaglobulin (IVIG) has been reported to improve outcome in women with APS who have previously failed treatment with heparin and LDA [153] . However, in randomized controlled trials, the live birth rates in women receiving IVIG treatment during pregnancy were lower when compared to live birth rates in women receiving LDA and LMWH [154] . In another small trial, IVIG added to heparin and LDA was not superior to heparin and LDA alone [155] . Thus, IVIG is not recommended as fi rst - line therapy for APS. Healthy women with recurrent embryonic and pre - embyronic loss and low titers of aPL do not require treatment [156] . The controlled trial of Pattison and colleagues [131] included a majority of such women and found no difference in live birth rates using either low - dose aspirin or placebo. Postpartum and c atastrophic a ntiphospholipid s yndrome Catastrophic antiphospholipid syndrome is a rare but devastating syndrome characterized by multiple simultaneous vascular occlu- sions throughout the body, often resulting in death. The diagnosis should be suspected if at least three organ systems are affected either pregnancy loss or 34 weeks, the live birth rate was 71%, gestational hypertension occurred in 17%, abruption in 7% and IUGR in 15% [141] . The safe and effective dose of heparin anticoagulation during pregnancy for women with APS is debated but should depend on individual patient history. Because of their substantial risk of recurrence [84,142,143] , most authorities recommend full, adjusted dose anticoagulation during pregnancy for women with APS and a history of thromboembolism [144,145] . In contrast, women diagnosed with APS without a history of thromboembolism are probably less likely to have a fi rst episode during pregnancy. Women with early RPL alone, without a history of thromboembolism, have been treated with both low - dose prophylaxis and adjusted - dose anticoagulation regimens [140] . Live rates have exceeded 70% using either strategy [130,136] . Women with a history of fetal death alone may be at higher risk for thromboembolism during pregnancy [146] and should probably receive higher doses of heparin prophylaxis. It has been recommended to treat such women with generous thromboprophylaxis (e.g, 15 000 – 20 000 units of standard heparin or 60 mg of enoxaparin in divided doses daily) [122,136,147] . Women with APS should be counseled about the potential risks of heparin therapy during pregnancy including heparin - Table 36.4 Subcutaneous Heparin Regimens Used for Antiphospholipid Syndrome During Pregnancy (132 – 134, 138 – 141). Prophylactic Regimens Recommended in women with no history of thrombotic events – diagnosis of recurrent preembryonic and embryonic loss or prior fetal death or early delivery because of severe preeclampsia or severe placental insuffi ciency Standard Heparin 7,500 – 10,000 U every 12 hours in the fi rst trimester, 10,000 U every 12 hours in the second and third trimesters Low Molecular Weight Heparin 1) Enoxaparin 40 mg once daily or dalteparin 5000 U once daily 2) Enoxaparin 30 mg every 12 hours or dalteparin 5000 U every 12 hours Anticoagulation Regimens Recommended in women with a history of thrombotic events Standard Heparin Every 8 – 12 hours adjusted to maintain the midinterval heparin levels * in the therapeutic range Low Molecular Weight Heparin 1) Weight adjusted (enoxaparin 1 mg/kg every 12 hours or dalteparin 200 U/kg every 12 hours) 2) Intermediate dose (enoxaparin 40 mg once daily or dalteparin 5000 U once daily until 16 weeks of gestation and every 12 hours from 16 weeks onwards * Heparin levels = anti factor Xa levels. Women without a lupus anticoagulant in whom the activated partial thromboplastin time (aPTT) is normal can be observed using the aPTT. Chapter 36 482 5 Prokunina L , Castillejo - Lopez C , Oberg F , et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans . Nat Genet 2002 ; 32 : 666 – 669 . 6 Ruiz - Irastorza G , Lima F , Alves J , et al. Increased rate of lupus fl are during pregnancy and the puerperium: a prospective study of 78 pregnancies . Br J Rheumatol 1996 ; 35 ( 2 ): 133 – 138 . 7 Petri M , Howard D , Repke J . Frequency of lupus fl are in pregnancy. The Hopkins Lupus Pregnancy Center experience . Arthritis Rheum 1991 ; 34 : 1538 – 1545 . 8 Petri M . Hopkins Lupus Pregnancy Center: 1987 to 1996 . Rheum Dis Clin North Am 1997 ; 23 ( 1 ): 1 – 13 . 9 Johns KR , Morand EF , Littlejohn GO . Pregnancy outcome in systemic lupus erythematosus (SLE): a review of 54 cases . Aust NZ J Med 1998 ; 28 ( 1 ): 18 – 22 . 10 Kleinman D , Katz VL , Kuller JA . Perinatal outcomes in women with systemic lupus erythematosus . J Perinatol 1998 ; 18 ( 3 ): 178 – 182 . 11 Wong KL , Chan FY , Lee CP . Outcome of pregnancy in patients with systemic lupus erythematosus. A prospective study . Arch Intern Med 1991 ; 151 ( 2 ): 269 – 273 . 12 Aggarwal N , Sawhney H , Vasishta K , Chopra S , Bambery P . Pregnancy in patients with systemic lupus erythematosus . Aust NZ J Obstet Gynaecol 1999 ; 39 ( 1 ): 28 – 30 . 13 Derksen RH , Bruinse HW , de Groot PG , Kater L . Pregnancy in systemic lupus erythematosus: a prospective study . Lupus 1994 ; 3 ( 3 ): 149 – 155 . 14 Georgiou PE , Politi EN , Katsimbri P , Sakka V , Drosos AA . Outcome of lupus pregnancy: a controlled study . Rheumatology (Oxf) 2000 ; 39 : 1014 – 1019 . 15 Huong DL , Wechsler B , Vauthier - Brouzes D , Beaufi ls H , Lefebvre G , Piette JC . Pregnancy in past or present lupus nephritis: a study of 32 pregnancies from a single centre . Ann Rheum Dis 2001 ; 60 ( 6 ): 599 – 604 . 16 Lockshin MD , Reinitz E , Druzin ML , Murrman M , Estes D . Lupus pregnancy. Case - control prospective study demonstrating absence of lupus exacerbation during or after pregnancy . Am J Med 1984 ; 77 : 893 – 898 . 17 Mintz R , Niz J , Gutierrez G , Garcia - Alonso A , Karchmer S . Prospective study of pregnancy in systemic lupus erythematosus: results of a multidisciplinary approach . J Rheumatol 1986 ; 13 : 732 – 739 . 18 Urowitz MB , Gladman DD , Farewell VT , Stewart J , McDonald J . Lupus and pregnancy studies . Arthritis Rheum 1993 ; 36 ( 10 ): 1392 – 1397 . 19 Bobrie G , Liote F , Houillier P , Grunfeld JP , Jungers P . Pregnancy in lupus nephritis and related disorders . Am J Kidney Dis 1987 ; 9 : 339 – 343 . 20 Carmona F , Font J , Moga I , et al. Class III - IV proliferative lupus nephritis and pregnancy: a study of 42 cases . Am J Reprod Immunol 2005 ; 53 : 182 – 188 . 21 Hayslett JP , Lynn RI . Effect of pregnancy in patients with lupus nephropathy . Kidney Int 1980 ; 18 : 207 – 220 . 22 Tandon A , Ibanez D , Gladman DD , Urowitz MB . The effect of pregnancy on lupus nephritis . Arthritis Rheum 2004 ; 50 : 3941 – 3946 . 23 Germaine S , Nelson - Piercy C . Lupus nephritis and renal disease in pregnancy . Lupus 2006 ; 15 : 148 – 155 . 24 Le Huong D , Wechsler B , Vauthier - Brouzes D , et al. Outcome of planned pregnancies in systemic lupus erythematosus: a prospective study on 62 pregnancies . Br J Rheumatol 1997 ; 36 ( 7 ): 772 – 777 . and confi rmed if there is histolopathologic evidence of acute thrombotic microangiopathy affecting small vessels. Renal involvement occurs in 78% of patients. Most have hypertension and 25% eventually require dialysis. Other common manifestations described by Asherson [157] include adult respiratory distress syndrome (66%), cerebral microthrombi and microin- farctions (56%), myocardial microthrombi (50%), dermatologic abnormalities (50%), and disseminated intravascular coagulation (25%). Death from multiorgan failure occurs in 50% of patients [157] . The pathophysiology of catastrophic antiphospholipid syndrome is poorly understood. However, the onset may be pre- saged by several factors including infection, surgical procedures, discontinuation of anticoagulant therapy, and the use of drugs such as oral contraceptives [157 – 159] . Early and aggressive treatment of catastrophic APS is necessary to avoid death. Patients should be transferred to an intensive care unit where supportive care can be provided. Hypertension should be aggressively treated with appropriate antihypertensive medica- tion. While no treatment has been shown to be superior to another, a combination of anticoagulants (usually heparin) and steroids plus either plasmapheresis or intravenous immune globulin has been successful in some patients [157,159,160] (Table 36.5 ). Streptokinase and urokinase have also been used to treat acute vascular thrombosis [157] . Women suspected of catastrophic APS during pregnancy should probably be delivered. References 1 Ruiz - Irastorza G , Khamashta MA , Castellino G , Hughes GR . Systemic lupus erythematosus . Lancet 2001 ; 357 : 1027 – 1032 . 2 Ruiz - Irastorza G , Khamashta MA . Evaluation of systemic lupus erythematosus activity during pregnancy . Lupus 2004 ; 13 : 679 – 682 . 3 D ’ Cruz DP , Khamashta M , Hughes GRV . Systemic lupus erythematosus . Lancet 2007 ; 369 : 587 – 596 . 4 Russell AI , Cunninghame Graham DS , Shepherd C , et al. Polymorphism at the C - reactive protein locus infl uences gene expression and predisposes to systemic lupus erythematosus . Hum Mol Genet 2004 ; 13 : 137 – 147 . Table 36.5 Proposed Protocol For Acute Treatment of Catastrophic Antiphospholipid Syndrome (159, 161, 162). 1. Intravenous heparin should be initiated and adjusted to achieve an activated partial thromboplastin time (aPTT) 2 – 3 times greater than the mean. Heparin levels may be necessary for women with the LAC because they demonstrate a prolonged aPTT without anticoagulation. 2. Intravenous methylprednisolone should be initiated at a dosage of 10 – 30 mg/kg/day. 3. Plasmapheresis should be initiated with the replacement of 40 mL of plasma per kilogram of body weight or up to 3 liters per exchange. This should be repeated three times weekly for 2 to 6 weeks. The simultaneous administration of immunosuppressive agents may block potential rebound in production of autoantibodies. 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Antiphospholipid antibody - associated recurrent pregnancy loss: treatment with heparin and low - dose aspirin is superior to low - dose aspirin alone . Am J Obstet Gynecol 1996 ; 174 : 1584 – 1589 . 131 Pattison NS , Chamley LW , Birdsall M , Zanderigo AM , Liddell HS , McDougall J . Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial . Am J Obstet Gynecol 2000 ; 183 : 1008 – 1012 . 132 Rai R , Cohen H , Dave M , Regan L . Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies) . BMJ 1997 ; 314 : 253 – 257 . 133 Yetman DL , Kutteh WH . Antiphospholipid antibody panels and recurrent pregnancy loss: prevalence of anticardiolipin antibodies compared with other antiphospholipid antibodies . 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Induction of thrombosis in a mouse model by IgG, IgM and IgA immunoglobulins from patients with the antiphospholipid syndrome . Thromb Haemost 1995 ; 74 : 1361 – 1367 . 114 Girardi G , Berman J , Redecha P , et al. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome . J Clin Invest 2003 ; 112 : 1644 – 1654 . 115 Holers VM , Girardi G , Mo L , et al. Complement C3 activation is required for antiphospholipid antibody - induced fetal loss . J Exp Med 2002 ; 195 ( 2 ): 211 – 220 . 116 Salmon J , Girardi G . Antiphospholipid antibodies and pregnancy loss: a disorder of infl ammation . J Reprod Immunol 2008 ; 77 : 51 – 56 . 117 Xu C , Mao D , Holers VM , et al. A critical role for murine complement regulator crry in fetomaternal tolerance . Science 2000 ; 287 : 498 – 501 . Chapter 36 486 149 Kelton JG . Heparin - induced thrombocytopenia: an overview . Blood Rev 2002 ; 16 ( 1 ): 77 – 80 . 150 Warkentin TE , Kelton JG . 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Antiphospholipid syndrome in pregnancy. Obstetric concerns and treatment . Rheum Dis Clin North Am 1997 ; 23 ( 1 ): 71 – 84 . 148 Dahlman TC . Osteoporotic fractures and the recurrence of thromboembolism during pregnancy and the puerperium in 184 women undergoing thromboprophylaxis with heparin . Am J Obstet Gynecol 1993 ; 168 ( 4 ): 1265 – 1270 . 487 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 37 Trauma in Pregnancy James W. Van Hook Department of Obstetrics and Gynecology, Division of Maternal - Fetal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA Introduction Acts of violence, accidental injury, and war make trauma in pregnancy a global problem. In the United States alone, major trauma affects up to 8% of pregnant patients, with life - threatening maternal injuries complicating 3 – 4 per 1000 deliveries [1] and is the leading cause of non - obstetric maternal death in the United States [2,3] . The US maternal death rate, secondary to trauma, was recently reported at 1.9/1000 live births [4] , and abuse of a pregnant woman occurs in as many as 10% of pregnancies [5] . Thus, a multidisciplinary approach for the management of pregnant trauma victims is of great importance. In this chapter, we will discuss trauma itself and outline issues that relate to diagnosis, care and treatment of the pregnant trauma victim and her fetus. Maternal p hysiologic a daptations a pplicable to t rauma d uring p regnancy Physiologic adjustments of pregnancy can have a signifi cant impact on the pathophysiologic responses to trauma exhibited by the mother and her fetus. At the same time the physiologic changes of pregnancy may alter the clinician ’ s ability to accurately diagnose the extent of the trauma and can infl uence maternal outcome. Although thoroughly reviewed throughout this text, the reiteration of physiologic changes of pregnancy as they may relate to the pregnant trauma patient are an important component of any discussion of trauma during gestation. The primary physiologic changes, applicable to the pregnant trauma victim, are summarized in Table 37.1 . Key considerations peculiar to pregnancy include recognition of the expanded intravascular volume and its affect on cardiovascular changes and the recognition of hypovolemia. Additionally the gravid uterus may alter the mechanism of injury such as penetrating abdominal trauma and may affect certain diagnostic or therapeutic interventions such as thoracostomy tube placement and direct peritoneal lavage. Next we will review several aspects of pregnancy physiologic changes as they relate to traumatic injury Aortocaval compression, for example, by mid - pregnancy or later necessitates consideration of supine positioning of the gravid trauma victim. These and other related issues make the use of the expertise of the obstetrician, the trauma specialist and other subspecialists to optimize care of the pregnant accident victim. Management of t rauma The American College of Surgeons has long advocated a stan- dardized approach to the initial management of the trauma victim [42] . Resuscitation is based upon a systematic survey and intervention method. A modifi ed basic algorithm for initial resuscitation of the pregnant trauma patient is provided in Figure 37.1 . Primary s urvey The primary survey encompasses the immediate evaluation of the pregnant or non - pregnant trauma patient. The initials “ A - B - C - D - E ” are used to describe the steps of the primary survey (Figure 37.1 ) [1,6,7,8] . Little is different in performing the primary survey during pregnancy as compared to the non - pregnant individual. Foremost in the primary survey is stabilization of a proper airway ( “ A ” ). If an adequate functioning airway is not present, chin lift (with a stabilized neck and cervical spine) and oral or nasal airway insertion may be necessary. Early endotracheal intubation by qualifi ed personnel must be performed if the just - described mea- sures fail. Because of the potential for aspiration, intubation should be more aggressively pursued in the pregnant trauma victim than in her non - pregnant counterpart [9] . After airway stabilization, adequate respiration ( “ B ” ) must be established. Supplemental oxygen is given as necessary and its adequacy assessed via pulse oximetry. Arterial blood gas determination, if Chapter 37 488 Primary survey Airway Breathing Circulation Disability (alert, voice, pain, unresponsive) Expose Initial therapy CPR? Oxygenation (ventilation) Volume Gestational age? Uterine size <20 weeks Secondary survey Immediate investigations Pregnancy secondary to other issues Uterine size >20 weeks Lateral displacement of uterus Secondary survey Immediate investigations (fetus alive?) Consider uterine evacuation with unsuccessful resuscitation Figure 37.1 Initial resuscitation of the pregnant trauma patient. CRP, cardiopulmonary resuscitation. (See text for sources of data.) Parameter Change Implications Plasma volume Increases by 45 – 50% Relative maternal resistance to limited blood loss Red cell mass Increases by 30% Dilutional anemia Cardiac output Increases by 30 – 50% Relative maternal resistance to limited blood loss Uteroplacental blood fl ow 20 – 30% shunt Uterine injury may predispose to increased blood loss Increased uterine vascularity Uterine size Dramatic increase Increased incidence of uterine injury with abdominal trauma Change in position of abdominal contents Supine hypotension Minute ventilation Increases by 25 – 30% Diminished P a CO 2 Diminished buffering capacity Functional residual volume Decreased Predisposition to atelectasis and hypoxemia Gastric emptying Delayed Predisposition to aspiration See text for sources of data. Table 37.1 Trauma - related maternal adaptation to pregnancy. . 487 Critical Care Obstetrics, 5th edition. Edited by M. Belfort, G. Saade, M. Foley, J. Phelan and G. Dildy. © 2010 Blackwell Publishing Ltd. 37 Trauma in Pregnancy James W. Van Hook Department. ; 16 ( 1 ): 77 – 80 . 150 Warkentin TE , Kelton JG . Delayed - onset heparin - induced thrombocytopenia and thrombosis . Ann Intern Med 2001 ; 135 ( 7 ): 502 – 506 . 151 Warkentin TE. (56%), myocardial microthrombi (50% ), dermatologic abnormalities (50% ), and disseminated intravascular coagulation (25%). Death from multiorgan failure occurs in 50% of patients [157] . The

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