http://bloodjournal.hematologylibrary.org/cgi/reprint/88/1/3.pdf; Nejm 2002;346:995; Ann IM 1997;126:319

Cause:

• Autoimmune direct antiplatelet antibodies; part of hemolytic anemia spectrum (Nejm 1977;297:517), SLE, lymphoma, CLL, cancer, HIV; a type II direct cytotoxic antibody (Types of Hypersensitivity Reactions)
• Hapten type and innocent bystander immune reactions (type III, IgG immune complexes—Nejm 1985;313:1375; 1984;311:635) involving: transfusions (Nejm 1972;287:291); drugs like gold, heparin (Nejm 1976;295:237), quinidine, thiazides, sulfas, rarely vancomycin (Nejm 2007;356:904); perhaps transient viral infections

Pathophys:Antiplatelet IgG coats platelets, decreases half-life from 3-5 d to, < half-day because macrophages gobble up; delayed (type IV) hypersensitivity reaction may also play some role

Chronic form, 70% women, 70% <40 yr; childhood type onset around age 5 yr, usually abrupt onset, remits in 70% w/i 6 mo; M = F

Sx:Easy or spontaneous bruising

Si:Petechiae, purpura

Remission spontaneously in 85% children, 10% adults

Spontaneous bleeding only when platelet counts <10000-20000 (Nejm 1997;337:1870); in pregnant patients, follow antibody levels and platelet counts (Nejm 1990;323:229, 264)

r/o other causes of thrombocytopenia:

• Impairments of production: hypoproliferative, eg, pernicious anemia, PNH; or ineffective production, eg, alcoholics
• Impairments of distribution, eg, splenic pooling
• Consumption, eg, immune destruction (ITP); vascular destruction (DIC); or delayed-onset heparin-induced thrombocytopenia assoc w high thrombotic risk (Nejm 2006;355:809; Ann IM 2002;136:210)

Lab:

Chem:Plasma glycocalicin increased (50-250% of normal range), a fragment of platelet membranes, increased in all consumptive thrombocytopenias (Nejm 1987;317:1037)

Hem:Platelets decreased in number, increased in size (immature). Bleeding time unnecessary but will be normal because, though numbers decreased, stickiness is increased. Coomb's test may often be positive since low-grade hemolytic anemia may be present as well (Nejm 1977;297:517); as Evan's syndrome, seen in SLE, pregnancy.

Serol:HIV, possibly ANA

Path:Marrow shows increased megakaryocytes numbers but usually not indicated except over age 60 yr

Rx:

Consider when platelet counts consistently <30 000/cc (Ann IM 1997;126:307; Nejm 1993;328:1226); sequence choices below (Nejm 2010:363:1959)

1st: Prednisone ~100 mg po qd × 1-2 wk or to response then taper; or, in resistant cases, dexamethasone 40 mg po daily × 4 d helped 85%, and 50% long-term remission (Nejm 2003;349:831); if platelet count at 10 d <90K, then q 28 d repeats may help (Nejm 1994;330:1560)

2nd: Splenectomy works in 75% (60% complete and 15% partial remissions) (but only 14% of SLE—Ann IM 1985;102:325); response is predicted by response to high-dose iv IgG (1 gm/kg iv qd × 2) (Nejm 1997;336:1494); must balance against later fear and risk of sepsis (death in 1-2% lifelong before pneumovax, unknown what it is now)

3^rd: Rituximab (monoclonal antibody vs CD20 and B cells) though lots of adv effects, including 3% mortality (Ann IM 2007;146:25)

Transient: Immunoglobulin rx w plasmapheresis transient help; or IgG, high-dose iv IgG if spleen intact, will overwhelm RES and produce transient remission, eg, for surgery, very expensive (Nejm 1982;306:1254) $3000-4000/dose; or iv anti-Rh(D) IG, which costs half as much and, in Rh-positive pts, saturates spleen w coated rbc’s so can’t consume platelets (Med Let 1996;38:6); Fc receptor monoclonal IgG (Nejm 1986;314:1236)

Maybe: thrombopoietin-mimetic agents (Nejm 2010;363:1889, 1959; 2007;357:2237) like eltrombopag (Promacta) 50-75 mg po qd, FDA approved oral medication for ITP; or cyclophosphamide, azathioprine, colchicine, danazol, dapsone, cyclosporine, vincristine, vinblastine; all of doubtful help (Ann IM 2004;140:112). Or similar romiplostim

in pregnancy, steroids iv, immune globulin, and cesarean section all potentially useful but only justified if sx in mother (Nejm 1990;323:229, 264)

in children: usually just observation; rarely iv immune globulin or steroids at 4 mg/kg/d × 4 d