Download Case Series: Recombinant factor VIIa utilized in successful

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Case Series: Recombinant factor VIIa utilized in successful treatment of disseminated intravascular
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coagulation secondary to anaphylactoid syndrome of pregnancy
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Ira S. Frye, MD1,2, Casey Sager1,,2, Alicia Daly M.D.1,2, Pierre Barbot, MD1,2, Elizabeth Luce, MD3, Liana
Rinzler, MD3 and Gareth K. Forde, M.D., Ph.D1,2
1. Grand Rapids Medical Education & Partners, Grand Rapids, MI
2. Michigan State University Medical School, Grand Rapids, MI
3. Department of Obstetrics and Gynecology, Spectrum Health, Grand Rapids, MI
Corresponding author: Gareth K. Forde, MD/PhD
330 Barclay NE Suite 102
Grand Rapids, MI 49503
Phone: 616-391-1929
Fax: 616-391-3174 Email:
Email: [email protected]
For Reprint Information: Gareth K. Forde, MD/PhD
330 Barclay NE Suite 102
Grand Rapids, MI 49503
Phone: 616-391-1929
Fax: 616-391-3174
Email: [email protected]
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Case Series: Recombinant factor VIIa utilized in successful treatment of disseminated intravascular
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coagulation secondary to anaphylactoid syndrome of pregnancy
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Abstract:
BACKGROUND: Anaphylactoid syndrome of pregnancy (ASP), also known as amniotic fluid
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embolism (AFE) is a rare, yet life-threatening complication of pregnancy. In about half the cases,
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disseminated intravascular coagulation (DIC) occurs with ASP. Recombinant factor VIIa treatment
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has been successfully used a few times in the past to treat DIC associated with ASP.
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CASES: Case 1 details a 36-year-old woman at 39 weeks and 2 days gestation that
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developed seizures, hypotension and bradycardia with noted fetal distress following an
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augmentation of labor. Case 2 describes a 30 year-old woman who presented for a scheduled
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induction of labor at 39 weeks and 1 day gestation and experienced sudden onset of severe back
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pain, shortness of breath, and tachycardia. Both women developed disseminated intravascular
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coagulapathy (DIC), which was successfully managed with recombinant factor VIIa.
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CONCLUSION: Recombinant factor VIIa treatment has some risks, but is cases such as the
two women presented in this report, its use can be lifesaving.
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Introduction:
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Anaphylactoid syndrome of pregnancy (ASP), also known as amniotic fluid embolism (AFE), is a
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hazardous complication of pregnancy, associated with mortality rates exceeding 25% with a large
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portion of survivors left with neurologic morbidity [1]. Expeditious recognition and aggressive
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management are of the utmost importance. The clinical manifestations of ASP include fetal
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compromise, shortness of breath, hypotension, seizures and disseminated intravascular coagulation (DIC)
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[1]. ASP is poorly understood and been associated with risk factors including multiparity,
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tumultuous labor, advanced maternal age, placental pathologies, and cesarean deliveries [1, 3]. The
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estimated incidence of ASP is 7.7 per 100,000 births [3]. Although today the estimated mortality
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rates range between 20-40%, older reports quote a mortality rate as high as 61% despite prompt
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and aggressive treatment [1, 2]. Management, while mostly supportive, has recently grown to
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include more aggressive treatments such as recombinant factor VIIa along with a ventricular assist
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device, inhaled nitric oxide, cardiopulmonary bypass, and intraaortic balloon pump with
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extracorporeal membrane oxygenation [1].
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The following report details the successful treatment of two cases of DIC from ASP using
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recombinant factor VIIa.
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Case 1:
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A 36-year-old, gravid 4, para 3, abortus 0, Caucasian female at 39 weeks 2 days gestation presented
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to labor and delivery with uterine contractions. On admission, she was contracting intermittently
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and dilated to 5-6 cm, at -3 station and 80% effaced with a fetus in the vertex position. Pitocin
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augmentation was initiated and an epidural was placed for pain management. At 7-8 cm dilated, an
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amniotomy was performed, which returned a small amount of clear fluid. Fetal cardiotocography
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revealed reassuring fetal heart tones and contractions every two to three minutes. Thirty minutes
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after amniotomy the patient complained of not feeling well and the physician on call was paged.
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Upon arrival of the physician, the patient had a seizure and became hypotensive and bradycardic.
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Non reassuring fetal heart tones were documented. Within minutes, she had another seizure and
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cardiovascular collapse, with cyanosis and an irregular cardiac rhythm. Amniotic fluid embolism
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was suspected and the patient was taken to the operating room for an emergent cesarean section.
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In the operating room, the patient had an unobtainable blood pressure and intermittent pulse. Her
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abdomen was prepped for delivery as the anesthesiologist established cardiovascular lines and
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began aggressive fluid resuscitation. Cardiovascular collapse was diagnosed and a code was called.
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As the code team assessed the cardiovascular and respiratory status of the patient, an emergent
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cesarean section was performed. During the c-section, respiratory failure ensued and hand
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ventilation was started. A limp male fetus weighing 4015 grams was delivered. The umbilical cord
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pH was 7.1. Immediately after delivery of the infant, cardiopulmonary resuscitation was initiated.
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The patient developed ventricular tachycardia and defibrillation was administered to establish a
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sinus rhythm. However, perfusion remained poor with intermittent peripheral pulses. Epinephrine,
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bicarbonate and calcium were administered. At this point, disseminated intravascular
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coagulopathy was suspected and the abdomen was closed in the standard fashion. The intensive
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care team assumed care of the patient.
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The patient’s initial coagulation panel revealed a prothrombin time (PT) of >120 seconds, activated
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partial thromboplastin time (aPTT) >150 seconds, international normalized ratio of >13.5 and a
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fibrinogen of <50. Blood transfusion protocol was activated and the patient received eight units of
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packed red blood cells. The patient continued to bleed despite the efforts of the ICU team and
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intravenous recombinant factor VIIa (Novoseven®) was ordered. The patient received one 4.8 mg
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vial of the recombinant factor VIIa (equivalent to 51.6
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panel demonstrated a PT of 11.6 seconds, aPPT of 43 seconds, INR 1.2 and fibrinogen of 157. The
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patient was then sufficiently stable to be transferred to interventional radiology where bilateral
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uterine artery embolization was performed. Throughout the embolization procedure, the
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coagulation panel continued to normalize and by late the next morning all values were in the
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normal range.
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An inferior vena cava filter was placed two days post-op, and the patient remained on assisted
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ventilation for three days following the delivery. During this time, she required additional packed
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RBC and fresh frozen plasma transfusions for continued bleeding. At one point during her recovery,
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the patient developed intermittent fevers and was put on Ertapenem. Despite these complications,
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the patient’s status improved and she was discharged on hospital day 11.
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The baby was on a ventilator for a short amount of time before support was discontinued.
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Following extubation, the infant did well.
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Case 2
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A 30-year-old gravid 5, para 2, abortus 2, was admitted for a scheduled induction of labor for
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suspected macrosomia at 39 weeks and 1 day. She had a past medical history significant for
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previous gestational diabetes, migraines, depression, and asthma (controlled with an albuterol
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inhaler PRN). After initiation of oxytocin, she progressed to approximately 4 cm dilation. Shortly
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thereafter she developed sudden onset of severe back pain, shortness of breath, and tachycardia.
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Fetal heart tones decreased to the 60s. The patient was taken to the operating room for an
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emergent cesarean section and delivered a live-born female weighing 4074 grams with cord pH of
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6.78.
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After closure of the hysterotomy the patient was noted to be hypotensive and was unable to
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maintain normal oxygen saturations. She developed cardiac arrest and chest compressions were
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initiated. Concurrently, her surgery was completed. The patient’s uterus remained firm throughout
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the resuscitation. Because she continued to bleed from both her skin incision and vagina, a large
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Foley catheter was transvaginally inserted into the uterus. Once a pulse was regained,
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interventional radiology was consulted for an emergent uterine artery embolization.
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Throughout the resuscitation, the patient received 12 units of packed red blood cells, 10 units of
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fresh frozen plasma, two six-packs of platelets, and two units of cryoprecipitate. Despite aggressive
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resuscitation with blood products, the hemorrhaging continued and the ICU team decided to
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administer recombinant factor VIIa. Prior to the first dose of factor VIIa, the patient’s PT was
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>120.0, INR was >13.5, aPTT was >150 and fibrinogen was <50. Recombinant factor VIIa
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(Novoseven®) 4.8 mg was given followed by a second dose 30 minutes later. Repeat labs were
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drawn two hours later, and displayed a PT of 10.5, INR of 1.0, and aPTT of 45. The patient’s
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coagulation panel continued to normalize throughout her hospital stay.
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After uterine artery embolization, the patient was transferred to the ICU where she was treated for
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a number of complications including acute respiratory failure, acute renal failure, hypertension, and
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endomyometritis. She also developed new onset of seizure on postoperative day 12. The patient
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was transferred from the ICU to a general medical bed on postoperative day 16 and discharged
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home on postoperative day 19.
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The baby was resuscitated with positive pressure ventilation by mask due to apparent neonatal
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respiratory depression. She was taken to the NICU, and over the course of her stay she was treated
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for suspected hypoxic ischemic encephalopathy, neonatal depression, indirect hyperbilirubinemia,
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and ABO incompatibility. Baby was discharged home on hospital day 8 and at the time
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of discharge it was noted that baby had recovered very quickly from any apparent neurological
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problems.
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Discussion:
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Prior to this case series, there have been only three documented case reports in which recombinant
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factor VIIa was effectively used in the treatment of DIC secondary to amniotic fluid embolism [4-6].
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Rapid recognition and aggressive resuscitation of patients experiencing ASP and resultant
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coagulopathy are key aspects of survival. Management is usually initiated with intravenous
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crystalloids followed by packed red blood cells. If further resuscitation is needed then both plasma
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and platelets and platelets are usually replaced [7]. During management, measurements of
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complete blood cell counts and coagulation parameters are often used to guide further blood
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product support [7]. However, when supportive measures are not enough, as was the case with our
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two patients, alternatives such as recombinant factor VIIa can be employed to stabilize patients [6].
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The additional time gained by normalizing the patient’s coagulopathy can prove invaluable. For
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example, hemodynamically stable patients, are better candidates for transfer to interventional
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radiology for embolizing the uterine arteries to control bleeding. In general DIC typically follows
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massive hemorrhage. ASP occurs because amniotic fluid contains tissue factor, the protein that
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activates the extrinsic pathway of coagulation. It is thought that DIC is a common complication of
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ASP, because tissue factor in amniotic fluid comes in contact with factor VII in maternal plasma,
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triggering the coagulation cascade, eventually exhausting it, and resulting in hemorrhage.
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Replacing depleted factor VII restores clotting potential[8].
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As noted in the literature, recombinant factor VIIa is a powerful procoagulant that does not come
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without its risks to include myocardial infarction, deep vein thrombosis and pulmonary embolism
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[9]. Our report helps illustrate that recombinant factor VIIa can be an effective tool in the treatment
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of DIC and severe postpartum hemorrhage secondary to ASP.
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