aka Primary Immune Thrombocytopenic Purpura

I. Pathophysiology/Epidemiology

  1. Autoantibody-mediated platelet destruction, though not all anti-platelet autoantibodies are pathogenic!
  2. Childhood form: abrupt onset, male:female 1:1, tends to be clinically benign and self-limited
  3. Adult form: gradual onset most common in 2nd and 3rd decades of life; female:male 3:1, tends to be chronic

II. Clinical features: none are pathognomonic; dx is one of "exclusion"

  1. Thrombocytopenia
  2. Bone marrow normal though can see lack of adaptive excess of megakaryocytes
  3. No other known causes of thrombocytopenia
  4. Gradual onset
  5. No Px stigmata; in particular, palpable spleen is unusual
  6. Bleeding is usually from nose, gums, & subcutaneous (purpura)
  7. Serious bleeding is rare; us. ass'd with plats <10k
  8. Splenomegaly is usually absent

III. Natural history:

  1. May occur in an acute, self-limited form but more commonly chronic, in which early remissions uncommon without tx
  2. 25% of those tx'd with steroids have apparently permanent remission
  3. 33% have persistent thrombocytopenia despite all tx. inc. splenectomy
  1. 5% of these pts will die from bleeding in course of 3-10y f/u

IV. Workup:

  1. Bone marrow aspiration usually not necessary if no sx & plat's not too low
    1. Traditionally has been standard in kids with ITP to r/o leukemia as cause of thrombocytopenia; however, in a series of 332 bone marrow aspirations done on kids with provisional dx of ITP and "typical features" on CBC (normal Hb, WBC, ANC, and platelets < 50k), no cases of leukemia were identified. In 135 bone marrow aspirations done on kids with provision dx of ITP but without "typical features" on CBC, 3 cases of leukemia were identified as well as 8 cases of aplastic anemia (Arch. Pediat. Adol. Med. 152:345, 1998--AFP)
  1. Platelet IgG and antiplatelet Ab's can be checked but are not sensitive or specific for ITP

V. Tx:

  1. Give all pts pneumococcal vaccine in case they eventually need splenectomy!
  2. Pts with >50k platelets rarely have clinically important spont. bleeding, even with invasive procedures, so no tx is necessary. This is prob true even for those with plats 30-50k (Blood 77:31, 1991). You still need to monitor platelets; the risk of subsequent severe thrombocytopenia is unknown.
  3. Pts with <50k platelets or symptomatic:
  1. Corticosteroids
  1. Prednisone 1mg/kg/d as initial tx--66% will respond with plats to >50k, us. within 1 wk, but will often relapse when dose is reduced
  2. In an uncontrolled trial in 125 adults with newly-diagnosed ITP and platelet counts < 20k (or 20-50k with significant mucosal bleeding) tx'd with dexamethasone 40mg PO QD (equivalent to 240mg of prednisone) x 4d, 85% responded (i.e. increase of platelet count of 30k or more and platelet count 50k or greater by day 10) (NEJM 349:831, 2003--JW)
  1. IVGG 1g/kg/d x 2d will incr. platelets counts in most pts in 3d; useful in acute bleeding as well as before procedures where bleeding is anticipated.
  2. Platelet transfusions: survival time is short; useful only in controlling severe bleeding; IVGG may improve survival of transfused platelets.
  3. Splenectomy
  1. Indicated for ITP unresponsive to other tx
  2. Steroid tx for more than several months is to be avoided
  3. Response us. occurs within sev. days; mortality 0.2% in ITP pts
  4. Response to IVIG predicts response to splenectomy (rise to over 50k platelet count with IVIG correlated with 90% response rate to splenectomy; NEJM 336:1494, 1997-JW)
  1. When no response to all the above:
  1. Remember that goal is prevention of bleeding, e.g. plats to >30k, not normalization of plat. count!
  2. Investigate for presence of accessory spleens (nuclear med. scan)
  3. Not much data, but some have tried: azathioprine 2mg/kg QD, cyclophosphamide 2mg/kg QD (work pretty well), vincristine, vinblastine, danazol (don?t work so well), anti-RhD Ig in Rh-pos. pts (may work as well as IVGG)
  1. Thrombopoietin agonists
    1. Stimulate platelet production
    2. Specific agents
      1. Romiplostim ("Nplate")
      2. Eltrombopag ("Promacta") 50mg QD
        1. Associated with adverse effects of nausea/vomiting and mild transaminase increases in placebo-controlled trials.
  1. Tx of ITP in pregnancy:
  1. Infant can get thrombocytopenia b/c maternal Ab cross the placenta (incidenceof neonatal platelet counts < 50k in retrospective studies is 12-15%), & thus will be at risk for cerebral hemorrhage (incidence about 1% per ACOG 9/99) whose risk might be less with c/s. The newborn's platelet count may continue to decrease in the first few days after delivery
  2. Neonatal thrombocytopenia may worsen in the days after delivery
  3. Fetal platelet counts can be checked with PUBS: consider c/s if <50k. Checking it with fetal scalp sampling in labor may give erroneously low results.
  4. Risk factors for neonatal thrombocytopenia:
  1. Previous thrombocytopenic infant (2)
  2. s/p splenectomy: RR = 6! (2)
  3. Pts with no h/o thrombocytopenia in whom plats < 80k develop in pregnancy in the absence of other causes of thrombocytopenia, e.g. preeclampsia
  4. Maternal plats <50k (1, 3), though another study found no correlation (2)
  5. Antenatal tx with IVGG (1) or steroids (1,2) don't affect baby's platelets
  6. Presence of circulating PAIgG (2,3) and SPB-IgG (3)

(1) Am. J. Perinatol. 11:423, 1994. 29 moms w/ITP. 12.5% of infants had plats <50k

(2) Ann. Hematol. 68:39, 1994. 39 moms w/ITP. 19.5% of infants had ?low plats?

(3) Autoimmunity 16:209, 1993. 63 moms w/ITP. Abstract doesn?t give incidence of low plats in baby

(4) Obs. Gyn. Survey 48:781, 1993. Meta-analysis. 288 babies; 10.1% had plats <50k

(5) NEJM 329:1463, 1993. 31 moms w/ITP and plats <150 at delivery. 7% of babies had plats <50k. Of the babies born to 15 moms w/ITP and plats >150 at delivery, 2 had plats <50k. No ICH or other adverse outcome detected.

Other findings of study (5):

  1. 756 women with incidental thrombocytopenia of pregnancy. Only 1 infant born to these pts had plats <50; prob was due to trisomy 21.
  2. 216 women with hypertension of pregnancy and plats <150. Only 4 of their babies had plats <50 at birth.
  3. 18 women with potential for alloimmune neonatal thrombocytopenia; 15 had previously-affected infants; 9 babies had plats <50; 6 had plats < 20; 2 had ICH. Only 3 moms had plats <150 at birth

(NEJM 331:1207, 1994)