Critical Care Obstetrics part 32 doc

Pregnancy, antithrombin III defi -ciency and venous thrombosis: report of another case.. Risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or post partum: a p

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

suf-fi 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 prophy-lactic 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 tri-mester [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 con-sidered 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 pneu-matic compression boots or graduated elastic compression stock-ings, 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 associ-ated 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

recom-mended for particularly high - risk patients, such as those with

recent PE, iliofemoral thrombosis or mechanical heart valve

pros-theses Because a more uniform therapeutic heparin level is

desir-able, 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

pro-phylactic level (5000 units every 12 hours); this dose is not

associ-ated 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

prot-amine 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

prot-amine 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

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 parturi-tion [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 success-ful 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 contraindi-cated 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, anticoagu-lant 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

dihydroergota-mine 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

com-pression, 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

clini-cal 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

anticoagula-tion, antepartum prophylactic or intermediate - dose LMWH or

minidose or moderate - dose UFH, plus postpartum

anticoagula-tion 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

out-comes 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

pro-teins 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

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

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 embo-lism 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

con-fi rmed a high risk of recurrent thrombosis among APS patients [214] As such, most experts recommend long - term thrombopro-phylaxis in patients with APS who have experienced a thrombotic event

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complications occurred at time of fi lter placement No

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Surgical i ntervention

With pregnancy, surgical intervention may be indicated in some

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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

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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

anticoagula-tion If these patients remain untreated during pregnancy, 68%

will develop thromboembolism [188,200,203,204] In patients

who require high doses of heparin to achieve anticoagulation,

prophylactic biweekly doses of AT III concentrate may be

neces-sary [203] Many patients require lifelong anticoagulation, which

is best achieved by oral anticoagulants when not pregnant and

heparin throughout pregnancy

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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

underesti-mated, 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

hemor-rhage 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

ante-partum 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

syn-drome, 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 abrupplacenta-tion may be clear For example, shearing forces are most likely respon-sible for abruption resulting from trauma There is strong evi-dence 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 hema-toma which splits the decidua [9] As the hemahema-toma 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 placen-tal 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% recur-rence 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