Thrombocytopenia in pregnancy

1. Thrombocytopenia in pregnancy Dr .hassanali Vahedian ardakani Medicaloncologist Hemaotologist

2. تعريف ITP • : ترومبوسيتوپني ناشي از تخريب پلاكت توسط آنتي بادي ضدپلاكتي و رد ساير علل ترومبوسيتوپني • تشخيص ITP بر اساس شرح حال ، معاينه فيزيكي ، CBC و لام خون محيطي انجام ميشود و در موارد تيپيك بررسي بيشتر توصيه نميشود. كريترياي تشخيصي ITP: • * ترومبوسيتوپني + PBS نرمال ( به جز ترومبوسيتوپني ) • * عدم وجود اختلال همراه يا مصرف دارو

3. آزمايشات : • PBS در تمام بيماران انديكاسيون دارد ( يافته ها Plt كاهش يافته با مورفولوژي نرمال RBC و WBC ) • بررسي مغز استخوان ( BMB,BMA ) ( جهت R/O MDS ) • انديكاسيون ها : • * سن بالاي 50 سال • * يافته ها ي غير طبيعي در لام خون محيطي • * در بيماراني كه نياز به اسپلنكتومي دارند • * در بيماري كه به درمان با پردنيزولون پاسخ نميدهد ( سه هفته درمان )

4. 3- اندازه گيري آنتي بادي ضدپلاكتي توصيه نميشود. 4- سرولوژي HIV و HBSAg و HCVAbدر تمام بيماران • 5- پروفايل اتوايميون در صورتيكه در شرح حال و معاينه شواهدي از بيماري اتوايميون داشته باشيم • ( ANA ,Anti Phospholipid Antibody) . • 6- Thyroid function test جهت بررسي هيپر يا هيپوتيروئيدي قبل از اسپلنكتومي الكتيو انجام شود. • 7- Coomb's test, LDH در صورت وجود آنمي جهت R/O Evans Syndrome

5. The only goal of treatment is to prevent serious bleeding. • A normal platelet count is not a goal of treatment for ITP

6. هدف درمان رسيدن Plt در محدوده نرمال نيست . • 1- Plt >30000 و بدون علائم باليني و خونريزي نياز به درمان ندارد . • PlanObservation • 2- Plt <30000 يا Plt 30000 – 50000 با خونريزي مخاطي و يا ريسك فاكتوري كه منجر به خونريزي شود مثل فشار خون كنترل نشده Peptic ulcer disease ،‌ يا شرايط شغلي خطرناك نياز به درمان دارند. • * Tab prednisolon 1-2mg/kg/day PO 3w taper (4-6w) • Or Dexamethasone 40mg/day PO or IV 4-8 DAY

7. 3- انديكاسيونهاي بستري بيماران ITP علائم خونريزي شامل خونريزي گوارشي – خونريزي مغزي – هماچوري ماسيو – هماتوم داخلي و يا نياز به جراحي اورژانسي داشته باشد. * Plt < 10000 * وجود بولهاي هموراژيك در مخاط ( wet purpura ) در موارد بستری ياAmp Dexamethasone 40mg/day 1 4 taper 4 – 6w   4- درمان موارد ITP + Bleeding Amp methylprednisolon 1gr/day divided dose 1 -3 ± IVIG 1gr/kg/day 1 -2 Or winRho 50 – 75 µg/kg 3 – 5 min مثبت و طحال دارند RH در بيماراني كه ± Vincristin 2mg stat + Plt transfusion + Aminocaproic acid 0.5 gr/h q2 – 4h ( به جز هماچوري) در صورت مقاوم بودن به موارد فوق و ادامه خونريزي اسپلنكتومي اورژانس Amp Novo seven

8. انديكاسيونهاي اسپلنكتومي • عدم پاسخ به درمان با پردنيزولون به مدت 4 هفته • ( Plt < 30000 ) • بعد از سه ماه درمان پلاكت كمتر از 30000 باشد • جهت حفظ پلاكت ( 30000 ≤ ) نياز به تجويز طولاني مدت پردنيزولون باشد ( >10mg/day>6m )

9. اقدامات قبل از اسپلنكتومي • دو هفته قبل از جراحي واكسن پنوموكوك واكسن H . آنفولانزا ، واكسن مننگوكوك دريافت كند ( اگر دو هفته بعد از درمان پلاكت كمتر از 30000 باشد ) • Plt < 30000 جهت آماده سازي قبل از عمل • Prednisolon 1 – 2 mg/kg/day + IVIG 1 gr/kg/day 1 2 • + Plt transfusion if plt < 10000 ( قبل از جراحي در اتاق عمل )

10. Thrombocytopenia in pregnancy • Asymptomatic thrombocytopenia is observed near term in about 5 percent of normal pregnancies, and • thrombocytopenia, sometimes severe, develops in about 15 percent of women with preeclampsia

11. Major causes of thrombocytopenia during pregnancy

12. Thrombocytopenia discovered incidentally during a normal pregnancy and its distinction from idiopathic (immune) thrombocytopenic purpura (ITP) • Thrombocytopenia associated with preeclampsia/eclampsia and the HELLP syndrome and their distinction from thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS)

13. Thrombocytopenia in pregnancy • Pseudothrombocytopenia Anytime Examine blood smear for platelet clumps, or giant platelets. Repeat platelet count in citrate or heparin anticoagulant. Usually caused by agglutinins dependent upon EDTA, the standard anticoagulant for blood counts. • Gestational thrombocytopenia Typically late in gestation, frequency increases as term approaches Based on 5 criteria: • [1] Mild thrombocytopenia (most >100,000/µL, rarely <70,000/µL) • [2] No thrombocytopenia outside of pregnancy • [3] Occurs late in gestation • [4] No fetal/neonatal thrombocytopenia • [5] Postpartum resolution

14. GESTATIONAL THROMBOCYTOPENIA • — Incidental thrombocytopenia of pregnancy, also termed gestational thrombocytopenia, is defined by the following five criteria: • Mild and asymptomatic thrombocytopenia • No past history of thrombocytopenia (except possibly during a previous pregnancy) • Occurrence during late gestation • No association with fetal thrombocytopenia • Spontaneous resolution after delivery

15. Platelet counts are typically >70,000/microL, with about two-thirds being 130,000 to 150,000/microL • The frequency of gestational thrombocytopenia in women admitted for labor and delivery is 5 percent. • neonatal thrombocytopenia did not occur in infants born to mothers with gestational thrombocytopenia

16. Many, if not all, of the features of gestational thrombocytopenia are similar to those of mild ITP, suggesting a possible immunologic etiology. • Several observations support the hypothesis that gestational thrombocytopenia may be a mild and transient manifestation of ITP

17. If the mother's thrombocytopenia is not severe and only occurs during late pregnancy or at term, if her platelet count returns to normal following delivery, and if the infant's platelet count is normal, gestational thrombocytopenia is an appropriate diagnosis.

18. Immune thrombocytopenic purpura ITP. • Anytime Presence of isolated thrombocytopenia with no evidence for alternative etiologies. May be indistinguishable from gestational thrombocytopenia if mild and occurs late during pregnancy. Platelet count may improve after delivery

19. ITP is the more likely diagnosis if thrombocytopenia occurs early during pregnancy or if the platelet count is very low (ie, <50,000/microL) . • Accordingly, for women with mild thrombocytopenia who do not need treatment, the distinction from ITP may not be important during the pregnancy • the distinction between ITP and gestational thrombocytopenia may not be possible during the pregnancy

20. 50 women referred for thrombocytopenia discovered during pregnancy; 24 (38 percent) infants were thrombocytopenic either at birth or during the first two weeks of life

21. ITP DURING PREGNANCY AND DELIVERY •  Early in pregnancy the management of ITP is the same as if the patient were not pregnant, using prednisone as initial therapy to treat patients whose platelet counts are less than 30,000 to 50,000/microL, depending upon the presence or absence of symptoms (ie, bleeding) .

22. Patients with chronic ITP who have persistent platelet counts less than 30,000 to 50,000/microL and who are not being treated prior to their pregnancy may need no treatment during their pregnancy, except in preparation for delivery.

23. Splenectomy should be deferred if possible, because the severity of thrombocytopenia may spontaneously improve after delivery .Furthermore, splenectomy may increase the risk of fetal death and premature labor in early pregnancy and uterine enlargement presents technical problems in performing a splenectomy later during pregnancy.

24. Rituximab is increasingly being used to treat ITP in non-pregnant patients. However, there is insufficient experience to know the safety of rituximab administered during pregnancy. It is therefore recommended to avoid rituximab during pregnancy unless the mother's health is critically dependent upon use of this medication • Intravenous immune globulin (IGIV, IVIG) is an alternative TEMPORARY therapy that may help to delay splenectomy, although splenectomy remains the most effective treatment for severe, symptomatic ITP.

25. The greatest concern for ITP during pregnancy comes as term approaches and the risks of thrombocytopenia in the newborn infant must be considered. • a summary of published case series suggests that there is an approximately 10 and 5 percent risk that the newborn infant will have a platelet count of <50,000 or <20,000/microL

26. The severity of ITP in the mother appears to correlate with the risk for thrombocytopenia in the infant. Neonatal thrombocytopenia may be predicted by the following situations: • The mother has had a splenectomy • The mother's platelet count has been <50,000/microL at some time during the pregnancy

27. A platelet count >50,000/microL is considered safe for delivery (vaginal or cesarean)

28. Counseling of pregnant women with ITP •  The following observations provide support for counseling of women with ITP who are pregnant, or who anticipate pregnancy: • Although thrombocytopenia may occur in the infant, it is uncommon. Ninety percent of infants will have safe (>50,000/microliter) or normal platelet counts. • Even when severe thrombocytopenia occurs in the newborn infant, bleeding problems are almost always mild and can be effectively treated

29. Since intracranial hemorrhage is very rare in infants born to mothers with ITP, the occurrences should be investigated for other causes of thrombocytopenia, • Cesarean delivery should be reserved for standard obstetrical indications only

30. Major causes of thrombocytopenia during pregnancy

31. Preeclampsia After 20 weeks gestation Systolic or diastolic hypertension plus proteinuria

32. Criteria for the diagnosis of preeclampsia

35. Timing of delivery is based upon gestational age, maternal and fetal condition, and the severity of preeclampsia. • General management of antepartum women with mild preeclampsia consists of frequent laboratory monitoring (platelet count, liver and renal function tests), assessment of maternal blood pressure and symptoms, and frequent evaluation of fetal growth and well-being.

36. We recommend antenatal glucocorticoids ( betamethasone) be given to women diagnosed with preeclampsia between 24 and 34 weeks of gestation • We suggest delivery rather than expectant management of all women with preeclampsia who are ≥37 weeks of gestation • Magnesium sulfate is more effective than phenytoin for prevention of eclamptic seizures. we suggest use of magnesium sulfate to prevent eclampsia in women with mild preeclampsia • Mild preeclampsia is associated with good maternal and fetal pregnancy outcomes. The major consequences of severe preeclampsia are increased rates of maternal liver and kidney dysfunction, induced labor, cesarean delivery, preterm birth, fetal growth restriction, and difficulty breathing in the neonate.

38. HELLP syndrome After 20 weeks gestation Diagnostic criteria for preeclampsia are present in 85 percent of cases • Hemolysis: Microangiopathic hemolytic anemia with schistocytes, with other signs of hemolysis: increase serum LDH and indirect bilirubin, decreased haptoglobin • Elevated liver function tests: Serum AST ≥70 IU/L • Low platelets: Platelet count ≤100,000/µL

39. HELLP syndrome and severe preeclampsia are probably part of a disease spectrum. We require the presence of all of the following criteria to diagnose HELLP : • Microangiopathic hemolytic anemia with characteristic schistocytes (also called helmet cells) on blood smear .Other signs suggestive of hemolysis include an elevated LDH or indirect bilirubin and a low serum haptoglobin concentration (≤25 mg/dL). • Platelet count ≤100,000 cells/microL • Serum LDH ≥600 IU/L or total bilirubin ≥1.2 mg/dL • Serum AST ≥70 IU/L

40. Differential diagnosis — HELLP syndrome may occasionally be confused with other diseases complicating pregnancy: acute fatty liver of pregnancy, gastroenteritis, hepatitis, appendicitis, gallbladder disease, idiopathic thrombocytopenic purpura, lupus flare, antiphospholipid syndrome, hemolytic-uremic syndrome, or thrombotic thrombocytopenic purpura

41. DIAGNOSIS — The diagnosis of HELLP syndrome is based upon the presence of the laboratory abnormalities comprising its name. Laboratory work-up includes ; • Complete blood count with platelet count • Peripheral smear • AST, bilirubin, LDH • We suggest obtaining these laboratory tests in all pregnant women with gestational hypertension, preeclampsia, or proteinuria with symptoms of preeclampsia

42. Severe maternal disease (eg, multiorgan dysfunction, disseminated intravascular coagulation, liver infarction or hemorrhage, renal failure, abruptio placenta) or nonreassuring fetal status is an indication for prompt delivery regardless of gestational age. • For pregnancies ≥34 weeks of gestation, we recommend delivery rather than expectant management . In this population, the potential risks of preterm birth are outweighed by the risks associated with HELLP syndrome.

43. For pregnancies less than 34 weeks of gestation in which maternal and fetal status is reassuring, we suggest delivery after a course of glucocorticoids to accelerate fetal pulmonary maturity rather than expectant management or prompt delivery • For gestations less than 30 to 32 weeks with an unfavorable cervix, we suggest cesarean delivery to avoid a potentially long induction • We recommend not giving dexamethasone for treatment of HELLP syndrome . Dexamethasone does not accelerate resolution of laboratory abnormalities or reduce the risk of maternal complications.

44. DIAGNOSTIC CRITERIA — The diagnosis of TTP-HUS is generally made on clinical grounds from the following characteristic clinical and laboratory findings : • Microangiopathic hemolytic anemia Thrombocytopenia • Acute renal insufficiency of varying degrees of severity • Neurologic abnormalities, usually fluctuating • Fever

45. Confirming the diagnosis • For the purposes of treatment, only the presence of microangiopathic hemolytic anemia and thrombocytopenia without other cause is sufficient to make an initial diagnosis of TTP-HUS and initiate treatment with plasma exchange

46. TTP

47. : about 12 percent of TTP in pregnancy occurs in the first trimester, • 56 percent in the second trimester, and • 33 percent in the third trimester/postpartum, • whereas preeclampsia-HELLP does not occur before 20 weeks of gestation and most cases are diagnosed in the third trimester

48. Idiopathic TTP-HUS is associated with markedly reduced levels of ADAMTS13 (<10 percent), often along with the presence of an autoantibody directed against ADAMTS13. However, results of these tests should not influence the initial treatment decision to initiate plasma exchange.

49. TTP/HUS Typically late in gestation, frequency increases as term approaches. May occur after delivery Thrombocytopenia and microangiopathic hemolytic anemia without an alternative etiology. • May be indistinguishable from severe preeclampsia or HELLP syndrome. Severe neurologic abnormalities and acute renal failure support the diagnosis of TTP/HUS. Persistent abnormalities ≥3 days after delivery also support the diagnosis of TTP/HUS.

50. For patients with severe thrombocytopenia and microangiopathic hemolytic anemia, plasma exchange may be indicated if the fetus cannot be delivered or if improvement does not follow delivery. The third postpartum day is often considered the limit for only supportive therapy or glucocorticoids without plasma exchange in anticipation of a spontaneous recovery