aka Primary Immune Thrombocytopenic Purpura
- Autoantibody-mediated platelet destruction, though not all anti-platelet autoantibodies are pathogenic!
- Childhood form: abrupt onset, male:female 1:1, tends to be clinically benign and self-limited
- 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"
- Bone marrow normal though can see lack of adaptive excess of megakaryocytes
- No other known causes of thrombocytopenia
- Gradual onset
- No Px stigmata; in particular, palpable spleen is unusual
- Bleeding is usually from nose, gums, & subcutaneous (purpura)
- Serious bleeding is rare; us. ass'd with plats <10k
- Splenomegaly is usually absent
III. Natural history:
- May occur in an acute, self-limited form but more commonly chronic, in which early remissions uncommon without tx
- 25% of those tx'd with steroids have apparently permanent remission
- 33% have persistent thrombocytopenia despite all tx. inc. splenectomy
- 5% of these pts will die from bleeding in course of 3-10y f/u
- Bone marrow aspiration usually not necessary if no sx & plat's not too low
- 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)
- Platelet IgG and antiplatelet Ab's can be checked but are not sensitive or specific for ITP
- Give all pts pneumococcal vaccine in case they eventually need splenectomy!
- 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.
- Pts with <50k platelets or symptomatic:
- 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
- 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)
- 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.
- Platelet transfusions: survival time is short; useful only in controlling severe bleeding; IVGG may improve survival of transfused platelets.
- Indicated for ITP unresponsive to other tx
- Steroid tx for more than several months is to be avoided
- Response us. occurs within sev. days; mortality 0.2% in ITP pts
- 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)
- When no response to all the above:
- Remember that goal is prevention of bleeding, e.g. plats to >30k, not normalization of plat. count!
- Investigate for presence of accessory spleens (nuclear med. scan)
- 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)
- Thrombopoietin agonists
- Stimulate platelet production
- Specific agents
- Romiplostim ("Nplate")
- Eltrombopag ("Promacta") 50mg QD
- Associated with adverse effects of nausea/vomiting and mild transaminase increases in placebo-controlled trials.
- Tx of ITP in pregnancy:
- 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
- Neonatal thrombocytopenia may worsen in the days after delivery
- 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.
- Risk factors for neonatal thrombocytopenia:
- Previous thrombocytopenic infant (2)
- s/p splenectomy: RR = 6! (2)
- Pts with no h/o thrombocytopenia in whom plats < 80k develop in pregnancy in the absence of other causes of thrombocytopenia, e.g. preeclampsia
- Maternal plats <50k (1, 3), though another study found no correlation (2)
- Antenatal tx with IVGG (1) or steroids (1,2) don't affect baby's platelets
- 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):
(NEJM 331:1207, 1994)