Ask The Hematologist

James N. George, M.D.

Dr. George is the Presidential Professor in the Hematology-Oncology section of the Department of Medicine at the University of Oklahoma Health Sciences Center.

THE PATIENT

It was a Friday afternoon five years ago when Emily, a 25-year-old white woman, was urgently admitted to the hospital at 35 weeks of her first pregnancy. Her routine obstetrical examination had been normal two days earlier. The next day she had her annual laboratory evaluation at the hospital where she works; she did not feel well and went home early. On the following morning she was confused, had difficulty completing sentences, and noted hematuria. Emily's obstetrician called her at home after checking the previous day's laboratory results and told her to go immediately to the hospital: her hematocrit was 21 percent and her platelet count was 7,000/ L.

On admission, Emily was overtly confused and did not recognize her husband. She had no other neurologic abnormalities; her weight was normal; her blood pressure was high (139/82); urinalysis demonstrated proteinuria and hematuria; serum creatinine was high at 1.2 mg/dL; bilirubin was 1.5 mg/dL, AST was 140 U/L, ALT was 44 U/L, and LDH was 2379 U/L; coagulation studies were normal. An emergency caesarean section was done because of fetal distress. The baby's platelet count was 276,000/ L; he is now a healthy five-year-old boy.

THE QUESTION

Did Emily have severe preeclampsia or HELLP (hemolysis, elevated liver function tests, low platelets) syndrome that would resolve spontaneously following delivery? Or did she have thrombotic thrombocytopenic purpura (TTP) requiring urgent plasma exchange treatment? This decision is always difficult. Although preeclampsia and HELLP syndrome can cause microangiopathic hemolysis and thrombocytopenia, we considered TTP more likely because of Emily's profound confusion and the severity of her thrombocytopenia and anemia with many fragmented red cells. The absence of severe hypertension and very abnormal liver function was evidence against preeclampsia and HELLP syndrome. If our initial impression had been preeclampsia or HELLP syndrome, we would have deferred plasma exchange treatment, because of its risk for major complications. These syndromes may worsen immediately following delivery, but spontaneous improvement will occur within several days.

CLINICAL COURSE

Plasma exchange treatment was begun Friday night. Although Emily's confusion cleared promptly, she continued to have severe thrombocytopenia and anemia during the next week in spite of daily, then twice daily, plasma exchanges and steroids, supporting our initial impression of TTP. Emily recovered 16 days after delivery. Thirty-four days after the plasma exchange treatment was stopped, Emily felt nauseated and noticed petechiae on her forearm. Her platelet count had fallen to 25,000/ L from 242,000/ L six days previously; her hematocrit remained normal and she had no neurologic symptoms. We restarted prednisone, 200 mg/day, but the following day her platelet count had fallen further to 16,000/ L and her LDH increased from normal to 877 U/L. Therefore we resumed daily plasma exchange treatment and she recovered promptly. Several weeks later, Emily had chills and fever; her platelet count was 38,000/ L; this time she had central venous catheter-related sepsis caused by Staphylococcus epidermidis. During the next seven months, Emily had three more episodes of TTP, all beginning with symptoms of nausea and abdominal pain. Gallstones had been demonstrated at the onset of her third episode but cholecystectomy had been deferred until a stable remission from TTP was achieved. However, because of the recurrent symptoms of cholecystitis and also because inflammation may trigger recurrent episodes of TTP, cholecystectomy was planned. Since there are reports that splenectomy may diminish recurrences of TTP, splenectomy was performed at the same time. Emily has had no further episodes of TTP since her surgery.

MORE QUESTIONS

What is the appropriate treatment for patients with TTP who do not respond promptly to initial plasma exchange and steroids? Because TTP may have an autoimmune etiology, more intensive immunosuppressive treatment with rituximab is now an increasingly common consideration.

What is the cause of relapsing TTP? Emily's course was consistent with a severe acquired deficiency of ADAMTS13 caused by autoantibodies. This was confirmed by Dr. Bernhard LE4mmle: at the time of her initial presentation, Emily's ADAMTS13 activity was undetectable and she had ADAMTS13 inhibitory activity. Absent ADAMTS13 activity alone may not be sufficient to cause TTP; other precipitating conditions or risk factors may be required. Pregnancy is prominent among conditions that can trigger TTP; inflammatory conditions may also trigger TTP. Female gender, African-American race, and obesity are risk factors for TTP. About half of patients who present with severe ADAMTS13 deficiency may relapse. Most relapses occur within the first year and usually only one relapse occurs.

What is the importance of follow-up measurements of ADAMTS13 activity? Some patients with acquired TTP have persistently absent or abnormal ADAMTS13 activity for many years after apparent complete recovery. Emily's current ADAMTS13 level is abnormal at 35 percent. The clinical importance of these observations is unknown.

ONE MORE QUESTION, AND A HAPPY ENDING

What is the risk of future pregnancies in women who have recovered from TTP? Recurrence of acquired TTP with a subsequent pregnancy is uncommon, but because pregnancy may trigger TTP, frequent prenatal evaluations including platelet counts are important. One year after her surgery Emily called, happy to announce her second pregnancy. Her pregnancy was uncomplicated; her second boy is healthy. Emily has remained well and she has had one more uncomplicated pregnancy with a healthy baby girl born this year.

FURTHER READING

- McMinn JR, George JN. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy. Journal of Clinical Apheresis 2001; 16: 202- 209.

- Vesely SK, Li X, McMinn JR, Terrell DR, George JN. Pregnancy outcomes after recovery from thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Transfusion 2004; 44: 1149-1158.

Emily’s Story
http://moon.ouhsc.edu/jgeorge
Here Emily (our patient’s pseudonym) tells her experience with TTP. This Web site also has stories of other patients describing TTP, ITP, and drug-induced thrombocytopenia, as well as a database of all published case reports of drug-induced thrombocytopenia.

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