HYPERTENSION IN PREGNANCY

Vol. 23, No. 1, pp. 121127, 2004

Septic Pelvic Thrombophlebitis and Preeclampsia Are

Related Disorders#
Christy M. Isler, M.D.,1,* Brian K. Rinehart, M.D.,2
Dom A. Terrone, M.D.,2 J. Holt Crews, M.D.,2
Everett F. Magann, M.D.,2 and James N. Martin Jr., M.D.2
1

Department of Obstetrics and Gynecology, East Carolina University Brody School of

Medicine, Greenville, North Carolina, USA
2
Department of Obstetrics and Gynecology, University of Mississippi Medical Center,
Jackson, Mississippi, USA

ABSTRACT
Objective: To elicit factors associated with the postpartum development of septic
pelvic thrombophlebitis in a single large referral tertiary patient population. Methods:
A nine-year single institution retrospective case review of all patients with enigmatic
fever and septic pelvic thrombophlebitis was analyzed. Results: A total of 55 patients
with septic pelvic thrombophlebitis were provided care during the study interval. The
average gestational age at delivery was 36.8 4.3 weeks. The most prevalent
concurrent medical complication of pregnancy was preeclampsia (45%) while
chorioamnionitis affected only 13%. The average length of ruptured membranes
was 22.8 56.8 hours (median 10.5, 95% confidence interval [CI] 7.0 38.7 hours),
with 22% of patients undergoing amnion rupture at the time of cesarean delivery.
Prolonged (> 24 hours) amnion rupture occurred in only 9% of patients. Most affected
patients were delivered abdominally (91%) but a minority delivered vaginally (9%).

Presented at the Twentieth Annual Meeting of the Society for Maternal-Fetal Medicine, Miami,
Florida, February 1 5, 2000.
*Correspondence: Christy M. Isler, M.D., OB-GYN Publication Office, Department of Obstetrics
and Gynecology, University of Mississippi Medical Center, 2500 North State St., Jackson, MS
39216-4505, USA; Fax: (601) 984-6773; E-mail: islerc@mail.ecu.edu.
121
DOI: 10.1081/PRG-120029858
Copyright D 2004 by Marcel Dekker, Inc.

1064-1955 (Print); 1525-6065 (Online)

www.dekker.com

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Isler et al.
Antibiotic therapy for presumed infection was initiated at 27.4 24.6 hours
postpartum. Subsequently intravenous heparin therapy was initiated 128.9 54.2
hours thereafter enigmatic fever defervesed 37.2 36.8 hours later (median 34.0, 95%
CI 27.2 47.3 hours). Patients received 6.3 1.8 days of heparin therapy. Conclusion:
In this series, septic pelvic thrombophlebitis was frequently preceded by cesarean
delivery and commonly associated with preeclampsia. Unexpectedly, a small number
of patients suffered prolonged rupture of membranes or chorioamnionitis. We
speculate that the cesarean delivery of a population of at-risk patients with
preeclampsia may predispose them to develop septic pelvic thrombophlebitis.
Key Words: HELLP
thrombophlebitis.

syndrome;

Preeclampsia;

Pregnancy;

Septic

pelvic

INTRODUCTION
Septic pelvic thrombophlebitis is a disorder characterized by inflammation of the
pelvic veins with infected thromboses, most often following an obstetrical procedure
such as cesarean section or septic abortion. Optimal diagnosis and management of this
disorder remains elusive. Schulman et al. (1) described the diagnosis as one of
exclusion, and recommended an empiric trial of heparin after failure of antimicrobial
agents to produce defervescence of fever in these patients with no obvious site of
infection. Although historically there was much debate concerning medical (2,3) versus
surgical (4,5) management of this disease, it seems clear that the modern management
of septic pelvic thrombophlebitis primarily involves medical management with surgical
therapy reserved for patients who fail primary therapy. Current controversies concern
how clinical versus radiologic diagnosis of this condition differ, whether anticoagulation therapy is a necessary adjunct to broad spectrum antibiotic therapy, and
how long to continue antibiotic and/or anticoagulation therapy after presumptive
diagnosis is made (6 8).
The purpose of this study was to elicit factors associated with the postpartum
development of septic pelvic thrombophlebitis in a large, single institution, tertiary
referral center which provides medical care primarily for a population of underserved
socioeconomically disadvantaged patients in central Mississippi.

MATERIALS AND METHODS

A retrospective chart review was performed for all women discharged from the
University of Mississippi Medical Center between January 1990 and December 1998
with the diagnosis of septic pelvic thrombophlebitis. Each identified chart was
individually scrutinized to ascertain that each patient satisfied the diagnostic criteria
for septic pelvic thrombophlebitis which included a persistent puerperal enigmatic
febrile course (> 72 hours) despite broad spectrum antibiotic therapy (> 48 hours) and
absent evidence by culture or radiologic study of an infectious etiology (determined
by urine culture and chest x-ray supporting physical examination findings). In view of
the controversy regarding efficacy for radiologic techniques to support diagnosis of

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septic pelvic thrombophlebitis and an institutional bias by the Department of

Radiology against such, imaging studies were infrequently undertaken and not
required for diagnosis.
Medical records were individually reviewed for demographic information including
maternal age, race, parity, body mass index, and gestational age. All concurrent medical
complications of pregnancy were noted. Both mild and severe preeclampsia were
diagnosed using the criteria established by The American College of Obstetricians
and Gynecologists. The diagnosis of hemolysis, elevated live enzymes, low platelets
(HELLP) syndrome was based upon the documentation of hemolysis (lactate
dehydrogenase > 600 IU/L or progressive anemia), hepatic dysfunction (elevated aspartate
aminotransferase >70 IU/L), and thrombocytopenia (platelet count < 100,000 cells/mL).
Labor characteristics including length of membrane rupture, the presence of chorioamnionitis, and route of delivery were specifically targeted. The diagnosis of chorioamnionitis was based upon an elevated temperature accompanied by uterine tenderness and fetal
tachycardia. The postpartum course was examined for timing and length of febrile course
as it related to delivery and institution of antibiotic and heparin therapy. The use of blood
cultures and imaging studies were reviewed and their results noted.

RESULTS
During the study period, there were 32,542 deliveries at University Medical Center
with 7453 of these patients delivered abdominally. The medical records of 55 patients
met the criteria for diagnosis of septic pelvic thrombophlebitis (1.7 per 1000
deliveries). The average maternal age was 21.5 5.1 years and the racial distribution
included 85% African American, 11% Caucasian, and 4% Native-American. Most
patients (78%) were nulliparous. Patients generally were obese with an average body
mass index of 43.0 kg/m2 which corresponds to an average weight of 185 47 pounds.
Average gestational age at delivery was 36.8 4.3 weeks. The most prevalent medical
complication of pregnancy was preeclampsia, occurring in 45% compared to an
institutional incidence of 13.1% during the study period (see Table 1). Of the 25
patients with preeclampsia, 11 patients (44%) had mild preeclampsia, and 14 patients
(56%) had severe preeclampsia, with 3 of these 14 patients having HELLP syndrome.
The patients with HELLP syndrome received intravenous high dose dexamethasone for
therapy (10 mg every 12 hours until evidence of disease resolution was present).
Diabetes mellitus was present in 2%, while chronic hypertension was present in 5%.
Table 1.

Comparison of study and institutional rates of pregnancy complications.

Pregnancy complication

Study rate (%)

Institutional rate (%)

Preeclampsia
Chronic hypertension
Diabetes mellitus
Chorioamnionitis
Cesarean section (total)
Repeat cesarean section

45
5
2
13
91
9

13
8
2
6
25
10

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The average time interval between amnion rupture and delivery in study subjects
was 22.8 56.8 hours (median 10.5, 95% CI 7.0 38.7 hours), with 22% of patients
undergoing rupture of membranes at cesarean and 9% of patients experiencing
prolonged (> 24 hours) rupture of membranes. A diagnosis of chorioamnionitis was
made in 13% of patients. Cesarean was the mode of delivery in 91% of the study
population with the two most common indications being arrest of labor (44%) and
nonreassuring fetal status (20%). All patients undergoing cesarean delivery received
one dose of prophylactic intraoperative antibiotics or, if chorioamnionitis were present, therapeutic peripartum antibiotic therapy was begun preoperatively and continued postpartum.
The average time after delivery for onset of new febrile morbidity (> 100.4F)
necessitating institution of antibiotic therapy was 27.4 24.6 hours. All patients
received triple antibiotic coverage with ampicillin, gentamicin, and clindamycin for
persistence of fever greater than 100.4F. Four patients received vancomycin instead of
ampicillin due to a history of penicillin allergy. Antibiotic therapy was discontinued
after a patient eventually became afebrile for >24 hours. Thirty-eight patients had
blood cultures performed, of which 7 (18%) were positive. The most common
organisms isolated were gram negative rods (two patients with Escherichia coli, one
patient with Enterobacter, one patient with Citrobacter), although gram positive cocci
(one patient with Group B Streptococcus and one patient with Staphylococcus aureus)
and anaerobes (one patient with Bacteroides) were also isolated.
After a presumptive diagnosis of septic pelvic thrombophlebitis was made, heparin
therapy was begun. An intravenous heparin bolus followed by continuous intravenous
infusion sufficient to maintain an activated partial thromboplastin time 1.5 to 2 times
normal was initiated 128.9 54.2 hours after the first antibiotics were started. Patients
defervesced to become afebrile 37.2 36.8 hours later (median 34.0, 95% CI 27.2
47.3 hours). Defervescence occurred at less than 24 hours after heparin institution in
41.8% of patients, 72.7% within 48 hours, 89.8% within 72 hours, and 100% became
afebrile within 96 hours. Collectively, the patients studied received 6.3 1.8 days of
heparin therapy before discontinuation and discharge from the hospital. Five patients
received less than 7 days of heparin infusion because they left the hospital against
medical advice.
Imaging studies were obtained at the discretion of the physician staff. Only two
of 34 patients in the series who underwent abdominal/pelvic CT scanning were
reported to have significant findings. Both of those studies revealed a right ovarian
vein thrombosis.
All patients were afebrile for > 24 hours prior to hospital discharge. No patient was
discharged on antibiotic or anticoagulation therapy. There were no known recurrent
febrile episodes, although not all patients received follow-up care at our institution. No
patient required surgical therapy.

DISCUSSION
Septic pelvic thrombophlebitis is reported to occur in 1 in 2000 deliveries (3).
Gibbs et al. found this disorder to be more common after postcesarean endometritis,
affecting 2% of patients with this diagnosis (9). Classically, the disorder is divided into

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two distinct syndromes. The first scenario has been called enigmatic fever and
includes patients with persistent spiking fevers despite appropriate antibiotic coverage
who are otherwise asymptomatic (10). These patients do not have severe abdominal
pain or sepsis, and typically do not have a clot present on diagnostic studies. These
patients have been hypothesized to have multiple small clots present in small diameter
vessels. In contrast, patients with ovarian vein thrombosis have persistent spiking
fevers despite appropriate antibiotic coverage but are clinically ill. They typically have
severe abdominal pain, radiologically evident thrombosis of the vascular system, and
often exhibit signs of sepsis (11).
Despite the differences in clinical presentation between these two syndromes,
treatment has traditionally been similar. Patients are continued on broad spectrum
antibiotic coverage while intravenous continuous infusion heparin is administered.
Surgical therapy with ligation or excision of the thrombosed vessel is instituted if the
patient does not improve with medical therapy. Recently Brown and coworkers have
questioned whether anticoagulation is necessary (8) given the imprecision of the
therapy. Patients in their series had radiologic documentation of pelvic vein thrombosis
with some patients responding to antibiotics alone while other patients had protracted
febrile courses despite heparin anticoagulation and antibiotic therapy.
This investigation used clinical criteria to establish the diagnosis of septic pelvic
thrombophlebitis and found radiologic studies not particularly helpful in guiding
management. Many investigations have examined the efficacy of radiologic studies in
diagnosing septic pelvic thrombophlebitis by visualization of clot in the ovarian vessels.
When imaging studies are used to clarify the diagnosis, it appears that computed
tomography scanning and magnetic resonance imaging are superior to ultrasonography
(12). Our radiology department at the medical center typically does not recommend
routine imaging of a patient with suspected septic pelvic thrombophlebitis due to the
low sensitivity and specificity of radiologic diagnosis for this condition.
Traditionally, septic pelvic thrombophlebitis has been associated with antecedent
cesarean delivery, especially when the cesarean is performed in the presence of
chorioamnionitis. Our review confirms that abdominal delivery is overwhelmingly the
route of delivery for these patients (91% compared with an institutional rate of 24%),
but, chorioamnionitis was detected in only 13% of cases. In fact, a greater number of
patients had rupture of membranes performed at the time of cesarean section (22%)
than those who experienced prolonged rupture of membranes >24 hours (9%).
An unexpected finding during this review was the association of septic pelvic
thrombophlebitis with preeclampsia. Compared with our institutional rate of 13 15%,
the rate of preeclampsia in this series was 45%. Other vascular diseases, such as
diabetes mellitus and chronic essential hypertension, did not occur at an increased rate
in this patient population. As preeclampsia has also been associated with an increased
risk of deep venous thrombosis, we speculate that endothelial dysfunction and damage
are the predisposing factors. This would correlate with the presumed pathologic
mechanism of septic pelvic thrombophlebitis which Collins (5) defined and verified
histologically. There is damage to the intimal lining of affected veins by bacterial
invasion and the clotting process is activated, only to have the formed clots
subsequently invaded by microorganisms. Any preexisting endovascular damage, such
as surgery or preeclampsia, presumably can predispose the patient to this pathologic
sequence. An alternate hypothesis addressing the association of septic pelvic

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thrombophlebitis and preeclampsia is the high incidence of thrombophilias among

preeclamptic patients predisposing them to thrombophlebitis.
The average time to defervescence after initiation of heparin therapy in our patient
population was 37.2 hours. This response is more consistent with investigators who
used clinical criteria to diagnose septic pelvic thrombophlebitis (2.5 days) (3,11) than
those who used clinical criteria with radiologic confirmation for diagnosis (134 hours)
(8). This may be a reflection on the diagnostic degree of certainty or may represent the
extent of disease. Dunihoo et al. (13) proposed a spectrum of disease with initial milder
disease, represented by septic thrombophlebitis in the small veins, progressing to
ovarian vein thrombophlebitis. This concept of a disease spectrum has not been
supported by some investigators (6,7). It is possible that patients with visible clot on
radiologic studies may represent the syndrome of acute ovarian vein thrombosis, as
opposed to enigmatic fever. Thrombosis in small pelvic veins, consistent with
enigmatic fever, would not be easily visualized with CT scan or magnetic resonance
imaging (14,15).
In conclusion, this review confirms the association of septic pelvic thrombophlebitis and cesarean section, though not the association with chorioamnionitis. The
optimal management of this disorder has yet to be determined. The frequent
coexistence of preeclampsia observed in this study needs to be investigated further.
Perhaps there is a subset of patients with preeclampsia who also have a genetically
based incompetence of vascular systems to compensate adequately for the combined
stresses of cesarean delivery, parturition, and preeclampsia. We support the idea of
further follow-up studies using more rigorous diagnostic criteria to clarify this poorly
understood condition.

ACKNOWLEDGMENT
Supported in part by the Vicksburg Hospital Medical Foundation, Vicksburg,
Mississippi.

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