Idiopathic Thrombocytopenic Purpura Case File

Idiopathic Thrombocytopenic Purpura Case File

Eugene C. Toy, MD, Edward Yeomans, MD, Linda Fonseca, MD, Joseph M. Ernest, MD

Case 32

A 20-year-old G1P0 at 32 weeks’ gestation presents for her first prenatal visit. One year ago, she was hospitalized overnight for symptomatic anemia. At that time she had heavy menses which lasted longer than usual for her just prior to her hospitalization. She also states that she bruises easily. She denies any family history of bleeding disorders or any other significant medical history.

Her antepartum course has been complicated by some spotting in the first trimester. She is feeling fetal movement, and denies leaking of fluid, vaginal bleeding, or contractions. She also states that she has not experienced any headaches, nausea or vomiting, or problems with her eyesight. Her blood pressure in clinic is 120/60 mm Hg with a heart rate of 80 beats per minute, and a negative urine protein. Her abdomen is soft and nontender, with a fundal height of 32 cm. On her extremities, there are several bruises at various stages. Ultrasound shows normal fetal anatomy and is consistent with her last menstrual period. Routine prenatal labs drawn at 32 weeks were normal except for a platelet count of 40,000/mm3.

➤ What is the most likely diagnosis?

➤ What is the next step?

➤ What are potential complications of the patient’s disorder?

ANSWERS TO CASE 32:

Idiopathic Thrombocytopenic Purpura

Summary: This is a 20-year-old G1P0 at 32 weeks’ gestation with a past history of menorrhagia, symptomatic anemia requiring transfusion, and easy bruising. She denies any family history of bleeding disorders.

➤ Most likely diagnosis: Idiopathic thrombocytopenic purpura (ITP).

➤ Next step: Evaluate the patient for bleeding disorders.

➤ Potential complications: Hemorrhage, neonatal thrombocytopenia.

ANALYSIS

Objectives

1. Review the differential diagnosis of thrombocytopenia.
2. Outline the evaluation and management of ITP in pregnancy.
3. Describe the indications for and efficacy of treatment modalities for ITP in pregnancy.
4. Discuss delivery mode and neonatal complications associated with ITP in pregnancy.

Considerations

This is a 20-year-old G1P0 with a past history of symptomatic anemia who now presents with thrombocytopenia at 32 weeks. Causes of thrombocytopenia that should be considered in this patient include preeclampsia and HELLP syndrome, gestational thrombocytopenia, and ITP. Less common causes include systemic lupus erythematosus, antiphospholipid antibody syndrome, HIV-associated thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), and medication use.1 In this patient who is normotensive with negative urine protein, the likelihood of preeclampsia or HELLP syndrome is low. Gestational thrombocytopenia is relatively unlikely since this is usually asymptomatic and platelet count rarely drops below 70,000/mm3. Lupus and TTP can be ruled out by lack of associated symptoms or signs. Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin IgG and IgM, and beta glycoprotein) and HIV can be ruled out by laboratory evaluation. ITP is the most likely diagnosis in this patient since platelet count is less than 50,000/mm3; there are no symptoms or signs of systemic disease and no evidence of HIV, antiphospholipid antibodies, or medication use.

APPROACH TO

Idiopathic Thrombocytopenic Purpura

DEFINITIONS

THROMBOCYTOPENIA: This is defined by some authorities as a platelet count of less than 150 × 109/L (150,000/mm3) and by others as a platelet count of less than 100 × 109/L (100,000/mm3). It is one of the most common hematologic complications of pregnancy.

GESTATIONAL THROMBOCYTOPENIA: This entity can be difficult to distinguish from ITP, and it occurs much more commonly than ITP (7/100 compared to 1/1000). GTP usually has a platelet count above 70 × 109/L, produces no symptoms, is confined to pregnancy, remits after pregnancy, and is very rarely associated with fetal or neonatal thrombocytopenia.1

PLATELET GLYCOPROTEINS: These act as antigens on the platelet surface. A large number of platelet glycoproteins have been identified, among which are IIb/IIIa, Ib/IX, Ia/II, IV, and V. In ITP, autoantibodies bind to these glycoprotein antigens resulting in rapid clearance from the circulation, predominately in the liver and spleen. An increase in megakaryocytes in the bone marrow cannot compensate for the destruction of platelets and the peripheral platelet count drops, sometimes to very low levels.2

CLINICAL APPROACH

Thrombocytopenia, defined as a platelet count of less than 150 × 109/L (150,000/mm3), is one of the most common hematologic complications of pregnancy. Idiopathic thrombocytopenic purpura accounts for only a small percentage of thrombocytopenia occurring in pregnancy; however, it does carry substantial risks for both the mother and fetus. Therefore, it is necessary that obstetricians be aware of the diagnosis of this disease and its treatment.

Pathologically, ITP is an autoimmune disorder in which IgG antibodies are formed to platelet antigens. Up to 50% to 60% of patients with the disorder have antibodies to platelet glycoproteins IIb/IIIa. Both direct and indirect tests are available for measuring the antiplatelet antibodies. For the direct test, the patient’s platelets are combined with anti-IgG 125I and the resulting level of radioactivity is measured. For the indirect test, the patient’s plasma is combined with normal platelets. A wash is then applied, and the radioactivity measured as with the direct test. These antiplatelet antibody assays have a specificity above 90%; however, IgG antibody levels are not elevated in all patients with ITP. In up to 30% of patients, there are normal levels of plateletassociated IgG but elevated levels of platelet-associated C3. The utility of antiplatelet antibody testing is uncertain.4 Therefore, ITP remains primarily a clinical diagnosis of exclusion and confirmatory laboratory studies are not required.

The established criteria for diagnosis of ITP originally described by Cines et al.3 include the following:

• Normal blood count indices apart from thrombocytopenia

• Bone marrow biopsy which shows increased size and number of megakaryocytes

• Peripheral blood smear showing an increased percentage of large platelets

• Normal coagulation panel

• No other obvious causes of thrombocytopenia (ie, preeclampsia, TTP)

Bone marrow biopsy is usually not required to make the diagnosis. Once a diagnosis of ITP has been made, the pregnant patient is generally treated according to the guidelines for nonpregnant adults. These guidelines are based on the patient’s current platelet count and symptomatology (presence of petechiae or easy bruising), and include stepwise introduction of corticosteroids, immunosuppressive therapy, and splenectomy. The current recommendations from the American Society of Hematology4 are shown in Table 32–1.

If platelet count is less than 50,000/mm3, prednisone is usually recommended at a starting dose of 1 to 2 mg/kg. Intravenous immunoglobulin (IVIg) should be considered as first-line treatment in patients with platelet counts less than 10,000/mm3 or in those with platelet counts between 10,000 and 30,000/mm3 accompanied by significant bleeding. It would be appropriate second-line therapy for those with similar platelet counts who have not shown improvement following 2 to 4 weeks of prednisone treatment. Splenectomy should be reserved for those patients in the second trimester

IVIg = Intravenous immunoglobulin

who have failed glucocorticoid and IVIg therapy, are bleeding, and have platelet counts of less than 10,000/mm3. One key difference between the treatment of ITP in pregnant and nonpregnant adults is that the alternative immunosuppressive agents such as cyclophosphamide, vincristine, vinblastine, danazol, and azathioprine are usually avoided during pregnancy.

The goal of therapy in patients with ITP in pregnancy is to induce remission and support the platelet count until delivery can occur. Neither corticosteroids nor IVIg provide cures for a patient with ITP. Studies of the efficacy of corticosteroids have found a transient response in 75% of patients, but in only 14% to 33% of cases was the response sustained.

While the antiplatelet antibodies responsible for ITP are of the IgG class and can cross the placenta, there is little correlation between maternal and neonatal platelet count. If maternal platelet count is less than 50,000/mm3, the fetus has a 6% to 10% risk of thrombocytopenia at birth, and only a 1% to 5% risk of severe thrombocytopenia.5 The overall risk of intraventricular hemorrhage (IVH) is less than 1%. Due to this relatively low risk of IVH, cordocentesis and fetal scalp sampling to assess fetal platelet count prior to deciding on route of delivery are no longer recommended. The presence and level of platelet-associated IgG are also not predictive of neonatal platelet count. Finally, there is substantial evidence that shows that vaginal delivery of women with ITP does not increase neonatal morbidity. Thus, cesarean section should be reserved for obstetrical indications.6

Comprehension Questions

32.1 A 25-year-old patient at 24 weeks’ gestation presents to your office with a known history of ITP and a platelet count of 30,000/mm3. She denies bleeding. The only notable physical examination finding is the presence of mild purpura on her lower extremities. Which of the following is the most appropriate treatment for this patient?

A. No treatment

B. Prednisone

C. IVIg

D. Splenectomy

32.2 A 32-year-old woman with known ITP at 34 weeks’ gestation presents to your office for consultation regarding a plan for labor and delivery. What should you recommend?

A. Percutaneous umbilical blood sampling weekly.

B. Elective cesarean delivery at 37 weeks.

C. Awaits spontaneous labor.

D. Induce labor at 37 weeks.

32.3 Which of the following is helpful for the diagnosis of ITP?

A. Antiplatelet antibodies

B. Normal complete blood count except for thrombocytopenia

C. Presence of small platelets on peripheral smear

D. A coagulation panel suggestive of DIC

ANSWERS

32.1 B. In a patient with a platelet count of 30,000 who is either asymptomatic or has only mild purpura, prednisone is the most appropriate initial therapy. IVIg might be considered in this patient if she does not respond to the prednisone, or if her clinical circumstances worsen. This patient is not an appropriate candidate for splenectomy.

32.2 C. Multiple studies have failed to show reduction in intracranial hemorrhage among infants of mothers who underwent elective cesarean section. Induction of labor increases the risk of cesarean. The best choice is to await spontaneous labor, reserving cesarean for obstetric indications.

32.3 B. While the presence of antiplatelet antibodies is supportive, there is a subset of ITP patients in whom the antiplatelet antibody level will not be elevated. In ITP, the peripheral smear shows enlarged platelets. The coagulation panel is normal in patients with ITP.

Clinical Pearls

See US Preventive Services Task Force Study Quality levels of evidence in Case 1

➤ Patients with ITP have isolated thrombocytopenia, enlarged platelets on peripheral smear, and no other cause of thrombocytopenia (Level II-3).

➤ Patients with ITP may or may not have elevated antiplatelet antibody levels; the diagnosis is clinical (Level III).

➤ Treatment of ITP is generally not indicated with platelet count above 50,000 (Level III).

➤ If indicated, treatment should consist of prednisone and/or IVIg depending on platelet count and symptoms (Level III).

➤ Neither maternal platelet count nor antiplatelet antibody levels are reliable predictors of neonatal thrombocytopenia (Level II-3).

➤ Cesarean section is not beneficial in reducing neonatal intracranial hemorrhage (Level II-3).

REFERENCES

1. ACOG Practice Bulletin No. 6. Thrombocytopenia in Pregnancy, September 1999. 

2. Sukenik-Halevy R, Ellis MH, Fejgin MD. Management of immune thrombocytopenic purpura in pregnancy. Obstet Gynecol Survey. 2008;63:182-188. 

3. Cines DB, Blanchett VS. Immune thrombocytopenic purpura. N Eng J Med. 2002;346:995. 

4. George JN, Woolf SH, Raskob GE, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996;88:3-40. 

5. Kelton JG. Idiopathic thrombocytopenia purpura complicating pregnancy. Blood Rev. 2002;16:43-46. 

6. Gernsheimer T, McCrae KR. Immune thrombocytopenic purpura in pregnancy. Curr Opin Hematol. 2007;14:574-580.

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