Cause:Von Willebrand factor cleaving protease (ADAMTS-13) IgG inhibitor (acquired type) or deficiency (familial type) (Nejm 1998;339:1578, 1585, 1629)
Pathophys:VonW factor multimers, which build up due to lack of cleaving protease, cause platelet aggregation/consumption, and fibrin arteriolar plugging (Nejm 1998;339:1578, 1585, 1629; 1982;307:1432)
Incidence is 4/million; 1/1000 autopsies, male/female: 2:3. Associated with IgG platelet antibodies in Graves' and Hashimoto's diseases (Ann IM 1981;94:27); with E. coli0157:H7 infections (Ann IM 1995;123:698); occasionally w drugs, eg, ticlopidine rx (Jama 1999;281:806; Ann IM 2000;132:794), or rarely clopidogrel (Plavix) (Nejm 2000;342:1766)
Sx:Fever, abdominal pain, bleeding esp in urine and gi tract, syncope (95%), headaches (34%), visual changes (8%) from retinal hemorrhages, seizures (8%)
Si:Fever usually (80%) <102°F; purpura; retinal hemorrhages; neurologic si's in 90% (Curr Concepts Cerebro Dis 1977;12:17); coma (31%), mental changes (26%), paresis (20%), aphasia (11%), dysarthria (7%)
<90 d in 80%, 90-365 d in 13%, >1 yr in 7%. Mortality ~90% without rx, 10% with rx (Nejm 1991;325:398); nearly 20% of cases are recurrent, 36% recurrence over 10 yr (Ann IM 1995;122:569)
Renal failure; occasionally Stokes-Adams attacks due to bundle of His degeneration
Lab:
Chem:Bilirubin (85%) and BUN (90%) elevated; LDH markedly incr
Hem: Smear shows microangiopathic anemia with red cell fragments, burr cells, helmets, and nucleated rbc's. Hgb <10.4 gm. Retics increased a lot, eg, ~20%. Platelets <120 000 (97%). WBC ~4000-5000 or less. Clot studies normal except mildly increased fibrin breakdown products. VonW factor cleaving protease deficiency or inhibitor present (unlike HUS)
Noninv:EKG and EEG, both may be nonspecifically abnormal
Path:Gingival biopsy may show fibrin plugs; 60% false neg, 0% false pos (Ann IM 1978;89:500). Marrow shows increased megakaryocyte numbers
Urine:Active nephritic sediment with protein, rbc's, wbc's, casts
Rx:
(Nejm 1991;325:398)
Plasma (which has vonW factor cleaving protease) as FFP, cryosupernatant, solvent-treated plasma, or plasma exchange (Am J Med 1999;107:573)
Immunosuppression to inhibit IgG antibody to vonW factor-clearing protease, w: