During pregnancy, most venous thromboses are confined to the deep veins of the lower extremity. Approximately 70 percent of cases are located in the iliofemoral veins without involvement of the calf veins. Isolated iliac vein and calf vein thromboses occur in approximately 17 and 6 percent of cases, respectively (Chan, 2010).
The signs and symptoms vary greatly and depend on the degree of occlusion and the intensity of the inflammatory response. Most cases during pregnancy are left sided. Ginsberg and coworkers (1992) reported that 58 of 60 antepartum women—97 percent—had left leg thromboses. Blanco-Molina and coworkers (2007) reported left-leg involvement in 78 percent. Our experiences at Parkland Hospital are similar—approximately 90 percent of lower extremity thromboses involved the left leg. Greer (2003) hypothesizes that this results from compression of the left iliac vein by the right iliac and ovarian artery, both of which cross the vein only on the left side. Yet, as described in Chapter 53 (Pregnancy-Induced Urinary Tract Changes), the ureter is compressed more on the right side!
Classic thrombosis involving the lower extremity is abrupt in onset, and there is pain and edema of the leg and thigh. The thrombus typically involves much of the deep-venous system to the iliofemoral region. Occasionally, reflex arterial spasm causes a pale, cool extremity with diminished pulsations. Conversely, there may be appreciable clot, yet little pain, heat, or swelling. Importantly, calf pain, either spontaneous or in response to squeezing or to Achilles tendon stretching—Homans sign—may be caused by a strained muscle or contusion. Between 30 and 60 percent of women with a confirmed lower-extremity acute deep-vein thrombosis have an asymptomatic pulmonary embolism (Clinical Presentation).
Clinical diagnosis of deep-vein thrombosis is difficult, and thus other methods are imperative for confirmation. In one study of pregnant women, the clinical diagnosis was confirmed in only 10 percent (Hull, 1990). Shown in Figure 52-2 is one diagnostic algorithm recommended by the American College of Chest Physicians that can be used for evaluation of pregnant women (Guyatt, 2012). With a few modifications, we follow a similar evaluation at Parkland Hospital.
Algorithm for evaluation of suspected deep-vein thrombosis in pregnancy. CT = computed tomography; MR = magnetic resonance. (Adapted from the American College of Chest Physicians, Guyatt, 2012.) aSigns and symptoms include swelling of the entire leg, with or without flank, buttock, or back pain.
In pregnant women with suspected deep-vein thrombosis, the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists (2012) recommend compression ultrasonography of the proximal veins as the initial diagnostic test. According to the American College of Chest Physicians, this noninvasive technique is currently the most-used first-line test to detect deep-vein thrombosis (Guyatt, 2012). The diagnosis is based on the noncompressibility and typical echoarchitecture of a thrombosed vein.
For nonpregnant patients with suspected thrombosis, the safety of withholding anticoagulation has been established for those who have normal serial compression examinations over a week (Birdwell, 1998; Heijboer, 1993). Specifically, isolated calf thromboses that extend into the proximal veins in about a fourth of patients will do so within 1 to 2 weeks of presentation. Moreover, these are usually detected by serial ultrasonographic compression.
In pregnant women, the important caveat is that normal findings with venous ultrasonography results do not always exclude a pulmonary embolism. This is because the thrombosis may have already embolized or because it arose from iliac or other deep-pelvic veins, which are less accessible to ultrasound evaluation (Goldhaber, 2004). Thrombosis associated with pulmonary embolism during pregnancy frequently originates in the iliac veins. Although serial investigations are recommended by many, Le Gal and colleagues (2012) recently studied the use of nonserial proximal and distal compression ultrasonography in 226 pregnant and postpartum women with suspected deep-vein thrombosis. Deep-vein thrombosis was diagnosed in 10 percent. Of the 177 women without a deep-vein thrombosis and who were not anticoagulated, two had an objectively confirmed thrombosis diagnosed within three months. Thus, these preliminary data suggest that a negative single complete compression ultrasonography study may safely exclude the diagnosis of deep-vein thrombosis in most pregnant women.
Magnetic Resonance Imaging
This imaging technique allows excellent delineation of anatomical detail above the inguinal ligament. Thus, in many cases, magnetic resonance (MR) imaging is immensely useful for diagnosis of iliofemoral and pelvic vein thrombosis. The venous system can also be reconstructed using MR venography as discussed in Chapter 46 (Fig. 46-5, Guidelines for Diagnostic Imaging During Pregnancy). Erdman and associates (1990) reported that MR imaging was 100-percent sensitive and 90-percent specific for detection of venographically proven deep-vein thrombosis in nonpregnant patients. Importantly, almost half of those without deep-vein thrombosis were found to have nonthrombotic conditions that included cellulitis, myositis, edema, hematomas, and superficial phlebitis.
Khalil and coworkers (2012) used magnetic resonance venography to study the natural history of pelvic vein thrombosis after vaginal delivery. Among the 30 asymptomatic patients who were all within four days of delivery, 30 percent had a definitive thrombosis in either the iliac or ovarian veins, and another 37 percent had a suspected thrombosis. Our experience with hundreds of postpartum MR scans does not support these findings. Thus, although the clinical significance of their findings is uncertain, it seems clear that some degree of pelvic vein intraluminal filling defect may be a normal finding.
These specific fibrin degradation products are generated when fibrinolysin degrades fibrin, as occurs in thromboembolism (Chap. 41, Pregnancy-Induced Coagulation Changes). Their measurement is frequently incorporated into diagnostic algorithms for venous thromboembolism in nonpregnant patients (Kelly, 2002; Wells, 2003). Screening with the d-dimer test in pregnancy, however, is problematic for a number of reasons. As shown in the Appendix (Serum and Blood Constituents), depending on assay sensitivity, d-dimer serum levels increase with gestational age along with substantively elevated plasma fibrinogen concentrations (McCrae, 2014). Levels are also affected by multifetal gestation and cesarean delivery (Morikawa, 2011). In a serial study of 50 healthy women, Kline and colleagues (2005) found that d-dimer levels increased progressively during pregnancy. Also, 22 percent of women in midpregnancy and no women in the third trimester had a d-dimer concentration below 0.50 mg/L—a conventional threshold used to exclude thromboembolism. d-Dimer concentrations can also be elevated in certain pregnancy complications such as placental abruption, preeclampsia, and sepsis syndrome. For these reasons, their use during pregnancy remains uncertain, but a negative d-dimer test should be considered reassuring (Lockwood, 2012; Marik, 2008).
Invasive contrast venography is the gold standard to exclude lower extremity deep-vein thrombosis (Chunilal, 2001). It has a negative-predictive value of 98 percent, and as discussed in Chapter 46 (Therapeutic Radiation), fetal radiation exposure without shielding is approximately 3 mGy (Nijkeuter, 2006). That said, venography is associated with significant complications, including thrombosis, and it is time consuming and cumbersome. Because of this, noninvasive methods are used primarily to confirm the diagnosis, and venography is seldom used today.
Optimal management of venous thromboembolism during pregnancy has not undergone major clinical study to provide evidence-based practices. There is, however, consensus for treatment with anticoagulation and limited activity. If thrombophilia testing is performed, it is done before anticoagulation because heparin induces a decline in antithrombin levels, and warfarin decreases protein C and S concentrations (Lockwood, 2002).
Anticoagulation is initiated with either unfractionated or low-molecular-weight heparin. Although either type is acceptable, most recommend one of the low-molecular-weight heparins. In its recently revised guidelines, for example, the American College of Chest Physicians suggests preferential use of low-molecular-weight heparin during pregnancy because of better bioavailability, longer plasma half-life, more predictable dose response, reduced risks of osteoporosis and thrombocytopenia, and less frequent dosing (Bates, 2012).
During pregnancy, heparin therapy is continued, and for postpartum women, anticoagulation is begun simultaneously with warfarin. Recall that pulmonary embolism develops in as many as 60 percent of patients with untreated venous thrombosis, and anticoagulation decreases this risk to less than 5 percent. In nonpregnant patients, the mortality rate is approximately 1 percent (Douketis, 1998; Pollack, 2011).
Over several days, leg pain dissipates. After symptoms have abated, graded ambulation should be started. Elastic stockings are fitted, and anticoagulation is continued. Recovery to this stage usually takes 7 to 10 days. Graduated compression stockings should be continued for 2 years after the diagnosis to reduce the incidence of postthrombotic syndrome (Brandjes, 1997). This syndrome can include chronic leg paresthesias or pain, intractable edema, skin changes, and leg ulcers.
This agent should be considered for the initial treatment of thromboembolism and in situations in which delivery, surgery, or thrombolysis may be necessary (Labor and Delivery) (American College of Obstetricians and Gynecologists, 2011). Unfractionated heparin (UFH) can be administered by one of two alternatives: (1) initial intravenous therapy followed by adjusted-dose subcutaneous UFH given every 12 hours; or (2) twice-daily, adjusted dose subcutaneous UFH with doses adjusted to prolong the activated partial thromboplastin time (aPTT) into the therapeutic range 6 hours postinjection (Bates, 2012). As shown in Table 52-5, the therapeutic dose for subcutaneous UFH is usually 10,000 units or more every 12 hours.
TABLE 52-5Anticoagulation Regimen Definitions ||Download (.pdf) TABLE 52-5 Anticoagulation Regimen Definitions
|Anticoagulation Regimen ||Definition |
|Prophylactic LMWH* ||Enoxaparin, 40 mg SC once daily |
Dalteparin, 5,000 units SC once daily
Tinzaparin, 4,500 units SC once daily
|Therapeutic LMWH† ||Enoxaparin, 1 mg/kg every 12 hours |
Dalteparin, 200 units/kg once daily
Tinzaparin, 175 units/kg once daily
Dalteparin, 100 units/kg every 12 hours
May target an anti-Xa level in the therapeutic range of 0.6–1.0 units/mL for twice daily regimen; slightly higher doses may be needed for a once-daily regimen.
|Minidose prophylactic UFH ||UFH, 5,000 units SC every 12 hours |
|Prophylactic UFH ||UFH, 5,000–10,000 units SC every 12 hours |
UFH, 5,000–7,500 units SC every 12 hours in first trimester
UFH 7,500–10,000 units SC every 12 hours in the second trimester
UFH, 10,000 units SC every 12 hours in the third trimester, unless the aPTT is elevated
|Therapeutic UFH† ||UFH, 10,000 units or more SC every 12 hours in doses adjusted to target aPTT in the therapeutic range (1.5–2.5) 6 hours after injection |
|Postpartum anticoagulation ||Prophylactic LMWH/UFH for 4–6 weeks or vitamin K antagonists for 4–6 weeks with a target INR of 2.0–3.0, with initial UFH or LMWH therapy overlap until the INR is 2.0 or more for 2 days |
|Surveillance ||Clinical vigilance and appropriate objective investigation of women with symptoms suspicious of deep vein thrombosis or pulmonary embolism |
For intravenous therapy, there are a number of acceptable protocols. In general, UFH is initiated with a bolus intravenous dose of 70 to 100 U/kg, about 5000 to 10,000 U, followed by continuous intravenous infusions beginning at 1000 U/hr or 15 to 20 U/kg/hr, titrated to achieve an aPTT of 1.5 to 2.5 times control values (Brown, 2010). Intravenous anticoagulation should be maintained for at least 5 to 7 days, after which treatment is converted to subcutaneous heparin to maintain the aPTT to at least 1.5 to 2.5 times control throughout the dosing interval. For women with antiphospholipid syndrome, aPTT does not accurately assess heparin anticoagulation, and thus anti-factor Xa levels are preferred.
The duration of full anticoagulation varies, and there are no studies that have defined the optimal duration for pregnancy-related thromboembolism. In nonpregnant patients with venous thromboembolism, evidence supports a minimum treatment duration of 3 months (Kearon, 2012). For pregnant patients, the American College of Chest Physicians recommends anticoagulation throughout pregnancy and postpartum for a minimum total duration of 3 months (Bates, 2012). Lockwood (2012) recommends that full anticoagulation be continued for at least 20 weeks followed by prophylactic doses if the woman is still pregnant. Prophylactic doses of subcutaneous unfractionated heparin can range from 5000 to 10,000 units every 12 hours titrated to maintain an anti-factor Xa level of 0.1 to 0.2 units, measured 6 hours after the last injection. If the venous thromboembolism occurs during the postpartum period, Lockwood (2012) recommends a minimum of 6 months of anticoagulation treatment.
This is a family of derivatives of unfractionated heparin, and their molecular weights average 4000 to 5000 daltons compared with 12,000 to 16,000 daltons for conventional heparin. None of these heparins cross the placenta, and all exert their anticoagulant activity by activating antithrombin. The primary difference is their relative inhibitory activity against factor Xa and thrombin (Garcia, 2008). Specifically, unfractionated heparin has equivalent activity against factor Xa and thrombin, but low-molecular-weight heparins (LMWH) have greater activity against factor Xa than thrombin. They also have a more predictable anticoagulant response and fewer bleeding complications than unfractionated heparin because of their better bioavailability, longer half-life, dose-independent clearance, and decreased interference with platelets (Tapson, 2008). These LMWH compounds are cleared by the kidneys and must be used cautiously when there is renal dysfunction.
A number of studies have shown that venous thromboembolism is treated effectively with LMWH (Quinlan, 2004; Tapson, 2008). Using serial venograms, Breddin and associates (2001) observed that these compounds were more effective than UFH in reducing thrombus size without increasing mortality rates or major bleeding complications. Several different treatment regimens using adjusted-dose LMWH for treatment of acute venous thromboembolism are recommended by the American College of Obstetricians and Gynecologists (2011) and are listed in Table 52-5.
Pharmacokinetics in Pregnancy
Low-molecular-weight heparins available for use in pregnancy include enoxaparin, tinzaparin, and dalteparin. Enoxaparin (Lovenox) pharmacokinetics were studied by Rodie and coworkers (2002) in 36 women with venous thromboembolism during pregnancy or immediately postpartum. The dose was approximately 1 mg/kg given twice daily based on early pregnancy weight. Treatment was monitored by peak anti-factor Xa activity 3 hours postinjection, with a target therapeutic range of 0.4–1.0 U/mL. In 33 women, enoxaparin provided satisfactory anticoagulation. In the other three women, dose reduction was necessary. None developed recurrent thromboembolism or bleeding complications. Smith and colleagues (2004) reported similar results with tinzaparin (Innohep) given as a once-daily 50 U/kg dose. They found that a dosage of 75 to 175 U/kg/day was necessary to achieve peak anti-factor Xa levels of 0.1 to 1.0 U/mL.
Dalteparin (Fragmin) pharmacokinetics were studied by Barbour (2004) and Jacobsen (2003) and their associates in longitudinal studies of 13 and 20 pregnant women, respectively. Both groups of investigators concluded that conventional starting doses of dalteparin—100 U/kg every 12 hours—were likely insufficient to maintain full anticoagulation and that slightly higher doses than that shown in Table 52-5 may be required. As an aside, several groups of investigators have found in preliminary studies that dalteparin use is associated with shorter labors (Ekman-Ordeberg, 2010; Isma, 2010). If these observations are verified, then the mechanism of action may involve increased cytokine secretion as in vitro studies suggest.
Standard prophylactic and therapeutic dosages recommended by the American College of Obstetricians and Gynecologists (2011) for various LMWHs are listed in Table 52-5. Whether such dosages require adjustments during the course of pregnancy is controversial (Cutts, 2013). Some suggest periodic measurement of anti-factor Xa levels 4 to 6 hours after an injection with dose adjustment to maintain a therapeutic level. According to Bates and coworkers (2012), large studies using clinical end points that demonstrate an optimal therapeutic range or that show dose adjustments increase therapy safety or efficacy are lacking. Moreover, assay measurement accuracy and reliability are uncertain; correlations with bleeding and recurrence risks are lacking; and assay costs are high. Accordingly, the American College of Chest Physicians has concluded that routine monitoring with anti-Xa levels is difficult to justify.
Early reviews by Sanson (1999) and Lepercq (2001), each with their colleagues, concluded that low-molecular-weight heparins were safe and effective. Despite this, in 2002, the manufacturer of Lovenox warned that its use in pregnancy had been associated with congenital anomalies and an increased risk of hemorrhage. After its own extensive review, the American College of Obstetricians and Gynecologists (2002) concluded that these risks were rare, that their incidence was not higher than expected, and that no cause-and-effect relationship had been established. It further concluded that enoxaparin and dalteparin could be given safely during pregnancy, and subsequent reports have continued to confirm their safety (Andersen, 2010; Bates, 2012; Deruelle, 2007; Galambosi, 2012).
Nelson-Piercy and coworkers (2011) assessed the safety profile of tinzaparin through a comprehensive study of 1267 pregnant women treated at 28 participating hospitals in North America and Europe. There were no maternal deaths or complications from regional analgesia. Although thrombocytopenia developed in 1.8 percent, there were no cases of heparin-induced thrombocytopenia (Superficial Venous Thrombophlebitis). The allergy incidence was 1.3 percent. Osteoporotic fractures in three women (0.2 percent) were judged to be related to tinzaparin (Low-Molecular-Weight Heparin). A total of 43 women (3.4 percent) required medical intervention for bleeding. Of the 15 stillbirths, four were judged as possibly being related to tinzaparin use. But, none of the neonatal deaths or congenital abnormalities was attributed to tinzaparin. The authors concluded that tinzaparin during pregnancy was safe for mother and fetus.
Like unfractionated heparin, LMWHs are safe during breast feeding. Although there may be detectable levels of these drugs in breast milk, the bioavailability when ingested orally is poor, and there is no anticoagulant effect in the infant (Lim, 2010).
Caveats are that LMWHs should be avoided in women with renal failure (Krivak, 2007). Moreover, when given within 2 hours of cesarean delivery, these agents increase the risk of wound hematoma (van Wijk, 2002). Lee and Goodwin (2006) described development of a massive subchorionic hematoma associated with enoxaparin use. Forsnes and associates (2009) reported a woman who developed a spontaneous thoracolumbar epidural hematoma that required surgical drainage.
Women receiving either therapeutic or prophylactic anticoagulation should be converted from LMWH to the shorter half-life UFH in the last month of pregnancy or sooner if delivery appears imminent. The purpose of conversion to UFH has less to do with any risk of maternal bleeding at the time of delivery, but rather with neuraxial blockade complicated by an epidural or spinal hematoma (Chap. 25, Timing of Epidural Placement). The American College of Chest Physicians recommends that women scheduled for a planned delivery who are receiving twice-daily adjusted-dose subcutaneous UFH or LMWH discontinue their heparin 24 hours before labor induction or cesarean delivery. Patients receiving once-daily LMWH should take only 50 percent of their normal dose on the morning of the day before delivery (Bates, 2012). The American College of Obstetricians and Gynecologists (2013) advises that adjusted-dose subcutaneous LMWH or UFH can be discontinued 24 to 36 hours before an induction of labor or scheduled cesarean delivery. The American Society of Regional Anesthesia and Pain Medicine advises withholding neuraxial blockade for 10 to 12 hours after the last prophylactic dose of LMWH or 24 hours after the last therapeutic dose (Horlocker, 2010).
If a woman begins labor while taking UFH, clearance can be verified by an aPTT. Reversal of heparin with protamine sulfate is rarely required and is not indicated with a prophylactic dose of heparin (Thromboprophylaxis). For women in whom anticoagulation therapy has temporarily been discontinued, pneumatic compression devices are recommended (American College of Obstetricians and Gynecologists, 2011).
Anticoagulation with Warfarin Compounds
Warfarin derivatives are generally contraindicated because they readily cross the placenta and may cause fetal death and malformations from hemorrhages (Chap. 12, Acitretin). Like UFH and LMWH, however, they do not accumulate in breast milk and do not induce an anticoagulant effect in the infant and are thus safe during breast feeding.
Postpartum venous thrombosis is usually treated with intravenous heparin and oral warfarin initiated simultaneously. The initial dose of warfarin is usually 5 to 10 mg for the first 2 days. Subsequent doses are titrated to achieve an international normalized ratio (INR) of 2 to 3. To avoid paradoxical thrombosis and skin necrosis from the early anti-protein C effect of warfarin, these women are maintained on therapeutic doses of UFH or LMWH for 5 days and until the INR is in a therapeutic range (2.0–3.0) for 2 consecutive days (American College of Obstetricians and Gynecologists, 2013; Stewart, 2010). Warfarin skin necrosis has been described in a postpartum patient with protein S deficiency (Cheng, 1997).
Treatment in the puerperium may require larger doses of anticoagulant. Brooks and colleagues (2002) compared anticoagulation in postpartum women with that of age-matched nonpregnant controls. The former required a significantly larger median total dose of warfarin—45 versus 24 mg—and a longer time—7 versus 4 days—to achieve the target INR. Moreover, the mean maintenance dose was slightly higher in postpartum women compared with that in the control group—4.9 versus 4.3 mg.
Several oral anticoagulants have recently become available. These inhibit thrombin—dabigatran, or factor Xa—rivaroxaban and apixaban. Preliminary studies in nonpregnant patients have been very promising (Cohen, 2013; Schulman, 2013). In one study of nearly 2500 nonpregnant subjects, anticoagulation with apixaban significantly reduced the risk of recurrent venous thromboembolism without increasing major bleeding complications (Agnelli, 2013). Currently, there are no studies of these newer agents during pregnancy, and thus the human reproductive risks are unknown (Bates, 2012).
Complications of Anticoagulation
Three significant complications associated with anticoagulation are hemorrhage, thrombocytopenia, and osteoporosis. The latter two are unique to heparin, and their risk may be reduced with low-molecular-weight heparins. The most serious complication is hemorrhage, which is more likely if there has been recent surgery or lacerations. Troublesome bleeding also is more likely if the heparin dosage is excessive. Unfortunately, management schemes using laboratory testing to identify when a heparin dosage is sufficient to inhibit further thrombosis, yet not cause serious hemorrhage, have been discouraging.
There are two types—the most common is a nonimmune, benign, reversible thrombocytopenia that develops within the first few days of therapy and resolves in approximately 5 days without therapy cessation. The second is the severe form of heparin-induced thrombocytopenia (HIT), which results from an immune reaction involving IgG antibodies directed against complexes of platelet factor 4 and heparin. When severe, HIT paradoxically causes thrombosis, which is the most common presentation.
The incidence of HIT is approximately 3 to 5 percent in nonpregnant individuals. Interestingly, however, Fausett and coworkers (2001) reported no cases among 244 heparin-treated pregnant women compared with 10 among 244 nonpregnant patients. Accordingly, the American College of Chest Physicians estimates that the incidence of HIT in obstetrical patients is less than 0.1 percent (Linkins, 2012). In the latest guidelines, moreover, the American College of Chest Physicians recommends against platelet count monitoring when the risk of HIT is considered to be less than 1 percent. In others, they suggest monitoring every 2 or 3 days from day 4 until day 14 (Linkins, 2012). Kelton and colleagues (2013) have recently provided a scholarly review of HIT.
When HIT is diagnosed, heparin therapy is stopped and alternative anticoagulation initiated. LMWH may not be entirely safe because it has some cross reactivity with unfractionated heparin. The American College of Chest Physicians recommends danaparoid—a sulfated glycosaminoglycan heparinoid (Bates, 2012; Linkins, 2012). In a review of nearly 50 pregnant women with either HIT or a skin rash, Lindhoff-Last and associates (2005) concluded that danaparoid—available only from Canada—was a reasonable alternative. However, they reported two fatal maternal hemorrhages and three fetal deaths. Magnani (2010) reviewed 30 case reports of pregnant women treated with danaparoid. Although it was effective, two patients died related to bleeding, three patients suffered nonfatal major bleeds, and three women developed thromboembolic events unresponsive to danaparoid.
Other agents are fondaparinux and argatroban (Kelton, 2013; Linkins, 2012). Argatroban is a direct thrombin inhibitor available in this country to treat HIT (Chapman, 2008; Tapson, 2008). Fondaparinux is a pentasaccharide factor Xa inhibitor that is also used for HIT (Kelton, 2013). Successful use in pregnancy has been reported (Knol, 2010; Mazzolai, 2006). Tanimura and coworkers (2012) successfully used argatroban, and later fondaparinux, to manage HIT in a pregnant woman with hereditary antithrombin deficiency. Interestingly, heparin-dependent antibodies do not invariably reappear with subsequent heparin use (Warkentin, 2001).
Bone loss may develop with long-term heparin administration—usually 6 months or longer—and is more prevalent in cigarette smokers (Chap. 58, Adrenal Gland Disorders). UFH can cause osteopenia, and this is less likely with LMWH (Deruelle, 2007). Women treated with any heparin should be encouraged to take a daily 1500-mg calcium supplement (Cunningham, 2005; Lockwood, 2012). In one study, Rodger and colleagues (2007) found that long-term use for a mean of 212 days with dalteparin was not associated with a significant decrease in bone mineral density.
Anticoagulation and Abortion
The treatment of deep-vein thrombosis with heparin does not preclude pregnancy termination by careful curettage. After the products are removed without trauma to the reproductive tract, full-dose heparin can be restarted in several hours.
Anticoagulation and Delivery
The effects of heparin on blood loss at delivery depend on several variables: (1) dose, route, and timing of administration; (2) number and depth of incisions and lacerations; (3) intensity of postpartum myometrial contractions; and (4) presence of other coagulation defects. Blood loss should not be greatly increased with vaginal delivery if the episiotomy—if any—is modest in depth, there are no lacerations, and the uterus promptly contracts. Unfortunately, such ideal circumstances do not always prevail. For example, Mueller and Lebherz (1969) described 10 women with antepartum thrombophlebitis treated with heparin. Three women who continued to receive heparin during labor and delivery bled remarkably and developed large hematomas. Thus, heparin therapy generally is stopped during labor and delivery. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists (2012) recommend restarting UFH or LMWH no sooner than 4 to 6 hours after vaginal delivery or 6 to 12 hours after cesarean delivery. It is our practice, however, to wait at least 24 hours if there are significant lacerations or following a major surgical procedure.
Slow intravenous administration of protamine sulfate generally reverses the effect of heparin promptly and effectively. It should not be given in excess of the amount needed to neutralize the heparin, because it also has an anticoagulant effect. Serious bleeding may occur when heparin in usual therapeutic doses is administered to a woman who has undergone cesarean delivery within the previous 24 to 48 hours.