Sickle cell vasoocclusive crisis and acute chest syndrome at term pregnancy.

Abstract: Women with sickle cell anemia are surviving longer and may desire pregnancy. Rare, life-threatening complications of sickle cell anemia, such as acute chest syndrome, may occur at the time of delivery. A 22-year-old woman with sickle cell (HbS/[beta]+ thalassemia) at 35 weeks of gestation presented with shortness of breath and generalized pain. She was diagnosed with vasoocclusive crisis and acute chest syndrome, managed with exchange transfusion and cesarean delivery, and discharged home with her newborn one week later. Prompt recognition of life-threatening complications of sickle cell anemia in a pregnant woman and collaborative medical and obstetric management are essential to optimize maternal and fetal outcome.

Key Words: sickle cell disease, acute chest syndrome, pregnancy, sickle cell vasoocclusive crisis

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Life-threatening complications of sickle cell anemia include acute hemolytic crisis and acute chest syndrome. Physiologic changes of pregnancy can increase cardiopulmonary stress in sickle cell anemia patients. We report a pregnant woman with respiratory failure due to acute hemolytic crisis and acute chest syndrome, requiring critical care management with emergency exchange transfusion, intubation and cesarean delivery.

Case Report

A 22-year-old African-American woman, gravida 1, para 0, presented at 35 weeks of gestation to the emergency department with fever, shortness of breath, cough, chest pain and diffuse body aches. She had sickle cell anemia (HbS/B+ thalassemia) and had no prior blood transfusions or episodes of acute chest syndrome. The patient was hospitalized one week prior for painful crisis and pneumonia, and treated with oral antibiotics and analgesics.

Physical examination revealed an ill-appearing patient. Blood pressure was 110/65 mm Hg, heart rate 125 beats per minute, respiratory rate 22 per minute, temperature 38.9[degrees]C and an oxygen saturation of 91% on room air. No jugular venous distention was noted. Heart sounds were normal. Lung examination revealed bibasilar rales. Uterine fundus size was consistent with a 35-week pregnancy. Diffuse tenderness of all extremities was noted.

Laboratory data revealed a white blood cell count 19.4 X [10.sup.3]/[mm.sup.3] (reference range 4.5-10.8) with neutrophil predominance, platelet count of 290,000/[mm.sup.3] (reference range 150,000-450,000), hemoglobin 8.2 g/dL (reference range 13.5-17.5), lactate dehydrogenase (LDH) 469 U/L (reference range 100-250 U/L), alanine aminotransferase (ALT) 11 U/L (reference range 0-40) and a total bilirubin level of 3.3 mg/dL (reference range 0.1-1.2 mg/dL). Chest x-ray showed bilateral lower lobe infiltrates. Fetal heart tracing was normal.

Supplemental oxygen, IV fluids, analgesics and broad spectrum antibiotics were administered. Over the next 24 hours, the patient developed worsening tachycardia, tachypnea and hypoxemia (Sa[O.sub.2] 70% on room air). Laboratory data showed a rising white blood cell count of 23.5 X [10.sup.3]/[mm.sup.3], LDH 1004 U/L, and decrease in hemoglobin to 7.7 g/dL. Platelet count was stable. Prothrombin time was normal. ALT was 17 U/L. Urinalysis was unremarkable. Repeat chest x-ray showed worsening lower lobes infiltrates. Fetal monitoring demonstrated transient bradycardia.

The patient was evaluated by the medical intensive care team and transferred to the Medical Intensive Care Unit (MICU). A 7 U red blood cell exchange transfusion was performed. Hemoglobin rose to 10.5 g/dL. She remained tachypneic, requiring 100% [O.sub.2] via face mask. Fetal decelerations developed five hours later. The patient was intubated and underwent an emergency cesarean delivery. The neonate weighed 2.3 kg and had Apgar scores of 3, 7 and 8. The neonate required two hours of continuous positive airway pressure (CPAP) for respiratory distress.

Following delivery, the patient remained intubated. Repeat chest x-ray showed diffuse bilateral infiltrates. Sputum culture revealed influenza B. On the second MICU day, a falling hemoglobin and rising LDH indicated persistent hemolytic crisis and she underwent a second exchange transfusion. She was extubated five days post delivery and discharged home with her newborn on the seventh hospital day.

Discussion

We describe the management of a pregnant patient with two life-threatening complications of sickle cell anemia, acute chest syndrome and hemolytic crisis. Acute chest syndrome is a rare but important cause of respiratory failure in a pregnant woman with sickle cell anemia.

Acute chest syndrome is the most common cause of death in adults with sickle cell anemia. (1) Microvascular sludging, pulmonary parenchymal infarction, bone marrow infarction and embolization contribute to sickling, regional hypoxia and ischemic damage. (2) Infection with chlamydophilia, mycoplasma, and viruses may play a role in the pathogenesis. Acute chest syndrome usually presents with fever, tachypnea, chest pain, cough, wheezing, new pulmonary infiltrates, hypoxemia, and leukocytosis. It may be difficult to differentiate acute chest syndrome from pneumonia; however, the presence of chest pain and significant respiratory distress should prompt consideration of the more severe condition of acute chest syndrome.

In pregnant patients with sickle cell anemia, complications may occur at any time during gestation, labor and delivery, or the puerperium. (3) This is believed to be secondary to hormonal modifications, hypercoagulable state, and increased susceptibility to infection. Complications related to microvascular sickling in the placental circulation include miscarriages, placental abruption, preeclampsia, preterm labor, intrauterine growth retardation, and low birth weight. (4)

The risk of maternal death is highest during the third trimester and peripartum period. (5)

The management of vasoocclusive crisis in pregnancy requires measures to prevent and treat known precipitants of microvascular sickling such as hypoxia, hypothermia, acidosis, dehydration, and stress, in addition to the intercurrent illness.

The goal of transfusion therapy with either simple transfusion of red blood cell units or exchange transfusion is to reduce the proportion of sickling blood cells (HbS less than 30%). In an exchange transfusion, 6 to 8 U of blood are exchanged by removing the patient's blood and administering normal red blood cells (HbA). Transfusion therapy in a pregnant woman with sickle cell anemia has been recommended in cases of preeclampsia, twin pregnancy, spontaneous abortions, intrauterine growth retardation and previous perinatal mortality. (6) The decision for simple transfusion or exchange transfusion depends on hemoglobin level and the severity of the complication. Simple transfusion may be sufficient in severe anemia and may be initiated when exchange transfusion cannot be completed in case of imminent delivery. Exchange transfusion is recommended for acute chest syndrome, multiorgan failure and neurologic complications. (6) The advantages of exchange transfusion include rapid replacement of blood cells without altering viscosity and avoiding iron overload. Concerns are the need for large vascular access, cost and availability of services. The role of prophylactic transfusion therapy is controversial. (7)

Prior series of outcomes of pregnant patients with sickle cell anemia reported 11.5% maternal mortality and up to 52.7% fetal mortality. (8) With advances in care, more recent reports suggest a decline in maternal mortality to 0 to 2% and a perinatal mortality to about 5%. (4)

Our patient presented at term with acute respiratory failure due to the acute chest syndrome. Her clinical deterioration in oxygenation and radiographic progression in the setting of a hemolytic crisis was consistent with acute chest syndrome; influenza was the likely contributory factor. The fetal bradycardia was a strong sign of deterioration in maternal condition. Other conditions such as preeclampsia and HELLP syndrome were excluded by clinical and laboratory evaluation. We initiated exchange transfusion to treat and optimize the maternal condition before emergent delivery.

Conclusion

The management of the pregnant patient with complications of sickle cell anemia requires close collaboration between the obstetrics and medicine physicians. Prompt recognition of the hemolytic crisis with acute chest syndrome and initiation of critical care management and transfusion support are necessary for enhanced maternal and fetal outcome.

References

1. Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease: life expectancy and risk factors for early death. N Engl J Med 1994;330:1639-1644.

2. Vichinsky EP, Neumayr LD, Earles AN, et al. Causes and outcomes of the acute chest syndrome in sickle cell disease: National Acute Chest Syndrome Study Group. N Engl J Med 2000;342:1855-1856.

3. Martin JN Jr, Martin RW, Morrison JC. Acute management of sickle cell crisis in pregnancy. Clin Perinatol 1986;13:853-868.

4. Hassell K. Pregnancy and Sickle Cell Disease. Hematol Oncol Clin North Am 2005;19:903-916.

5. Leborgne-Samuel Y, Kadhel P, Ryan C, et al. [Sickle cell disease and pregnancy.] Rev Prat 2004;54:1578-1582.

6. Danielson CF. The role of red blood cell exchange transfusion in the treatment and prevention of complications of sickle cell disease. Ther Aphe 2002;6:24-31.

7. ACGO Committee. ACGO Practice Bulletin: Clinical Management Guidelines for Obstetrician-Gynecologists. Obstet Gynecol 2005;106:203-210.

8. Sun PM, Wilburn W, Raynor BD, et al. Sickle cell disease in pregnancy: twenty years of experience at Grady Memorial Hospital, Atlanta, Georgia. Am J Obstet Gynecol 2001;184:1127-1130.

Success rests with the courage, endurance, and above all, the will to
become the person you are, however peculiar that may be ... Then you
will be able to say, I have found my hero and he is me.
--George Sheehan

Dany Elsayegh, MD, and Janet M. Shapiro, MD

Department of Medicine, St. Luke's and Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons.

Reprint requests to Dr. Janet Shapiro, Director, Medical Intensive Care Unit, St. Luke's Hospital MU 316, 1111 Amsterdam Avenue, New York, NY 10025. Email: [e-mail]

Accepted June 27, 2006.

RELATED ARTICLE: Key Points

* Life-threatening complications of sickle cell disease may occur in the pregnant patient near term.

* Management of acute chest syndrome at term pregnancy may include exchange transfusion before cesarean delivery to optimize maternal and fetal outcome.