Idiopathic thrombotic thrombocytopenic purpura (TTP)
is associated with microangiopathic hemolytic anemia, thrombocytopenia,
and microvascular thrombosis that results in variable injury of
the central nervous system, kidney, and other organs. Most cases
of TTP are caused by autoantibodies to ADAMTS13, a metalloprotease
that cleaves von Willebrand factor (VWF) and inhibits VWF-dependent
platelet aggregation. TTP is usually fatal if untreated. Most patients respond
to plasma exchange, although many have relapsing disease. Clinically
similar thrombotic microangiopathy can occur with normal ADAMTS13 levels.
Secondary thrombotic microangiopathy occurs in association with
metastatic cancer, infections, organ transplantation, and certain
drugs. Secondary thrombotic microangiopathy has a lower likelihood
of responding to plasma exchange and a lower survival rate.
Heparin-induced thrombocytopenia (HIT) is a significant complication of
treatment with heparin, especially unfractionated high-molecular-weight
heparin. It is associated with mild to moderate thrombocytopenia,
although the main concern is the high frequency of both arterial
and venous thrombotic complications. HIT is an immune complex-based
disorder involving heparin/platelet factor 4 (PF4) complexes.
Immediate cessation of heparin is required, but the risk of subsequent
thrombosis remains high. Direct thrombin inhibitors are the present-day
treatment of choice to limit thrombotic complications.
Acronyms and Abbreviations
Acronyms and abbreviations that
appear in this chapter include: ADAMTS, a disintegrin and metalloprotease
with thrombospondin type 1 repeats; APS, antiphospholipid syndrome;
aPTT, activated partial thromboplastin time; DDAVP, desmopressin,
diarrhea-associated hemolytic uremic syndrome; D–HUS,
diarrhea-negative hemolytic uremic syndrome; GP, glycoprotein; HELLP,
hemolysis, elevated liver enzymes, and low platelet count; HIT,
heparin-induced thrombocytopenia; HUS, hemolytic uremic syndrome;
Ig, immunoglobulin; LDH, lactate dehydrogenase; MCP, membrane cofactor
protein; MTHFR, methylenetetrahydrofolate reductase; PF4, platelet
factor 4; PT, prothrombin time; SLE, systemic lupus erythematosus;
TTP, thrombotic thrombocytopenic purpura; VWF, von Willebrand factor.
Thrombotic microangiopathy refers to a combination
of microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis,
regardless of cause or specific tissue involvement. Various kinds
of thrombotic microangiopathy differ in pathogenesis and prognosis,
but can be difficult to distinguish because their clinical features
Thrombotic thrombocytopenic purpura (TTP) is
a form of thrombotic microangiopathy in which tissue injury can
affect any organ but often results in neurologic damage and fever.
Renal involvement is common but oliguric renal failure is not. TTP usually
is associated with acquired autoantibodies that inhibit a disintegrin
and metalloprotease thrombospondin type 1 repeats (ADAMTS)13.
Congenital TTP, or Upshaw-Schulman syndrome,
refers to TTP that is caused by inherited deficiency of ADAMTS13.
Hemolytic uremic syndrome (HUS) refers to thrombotic
microangiopathy that mainly affects the kidney and usually causes
oliguric or anuric renal failure. Diarrhea-associated or typical HUS
(D+HUS) is caused by enteric infection
with Shiga toxin-producing Gram-negative bacilli, and usually is
associated with a prodrome of diarrhea. Diarrhea-negative or atypical HUS
(D–HUS) is not associated with diarrhea
or Shiga toxin-producing organisms and occurs ...