B3.067 Thrombocytopenia Flashcards
what are thrombotic microangiopathies (TMAs)
heterogeneous set of conditions linked by a common histopathologic finding of endothelial damage resulting in microvascular thromboses
what is microangiopathic hemolytic anemia (MAHA)
non-immune hemolytic anemia resulting from intravascular red cell fragmentation with schistocytosis
what is the result of TMAs
thrombocytopenia secondary to consumption
organ damage
how does TMA present on a renal biopsy
multiple thrombi observed in glomerular capillaries and in arterioles (red staining)
major causes of TMAs
thrombotic thrombocytopenic purpura (TTP)
hemolytic uremic syndrome (HUS)
misc (drugs, radiation, BMT, infections, autoimmune conditions)
subsets of HUS
typical: E.coli strain O157:H7 infection, endothelial damage by shiga like toxin
atypical: alternative complement pathway inhibitor deficiencies
pentad of TTP
fever thrombocytopenia microangiopathic hemolytic anemia transient neuro deficits renal failure
deficiency associated with TTP
deficiency in plasma enzyme ADAMTS13 which normally degrades very high MW multimers of vWF
in absence of ADAMTS13, multimers accumulate in plasma and tend to promote platelet activation and aggregation
epidemiology of TTP
incidence 0.04-0.004/1000 0.4/1000 in pregnant women 0.25-0.7/1000 among ticlopidine users (can stimulate production of Ab against ADAMTS13) F:M is 1.5:1 highest in African American women
common causes/ risk factors of TTP
def of ADAMTS13 -autoantibodies -genetic mutations ticlopidine/clopidogrel HIV infection autoimmune disorders pregnancy
diagnostic testing for TTP
CBC- Hb, Hct, platelet count peripheral smear- schistocytes LDH- elevated bilirubin- elevated PT, PTT, fibrinogen- normal Coombs test- normal BUN and creatinine- mild elevation urinalysis- proteinuria, hematuria, leukocytes confirmatory test for ADAMTS13 activity
differentiating sepsis from TTP
normal level of ADAMTS13
differentiating vasculitis from TTP
not usually associated with microthrombi or hemolytic anemia
what is vasculitis
inflammatory dysfunction of blood vessels in numerous organs that can be associated with anemia or thrombocytopenia
what is malignant hypertension
potentially life threatening disorder caused by organ damage as a result of severe high blood pressure
differentiating malignant hypertension from TTP
grade 3 or 4 retinopathy seen in malignant hypertension
differentiating autoimmune hemolytic anemias from TTP
spherocytes rather than schistocytes
positive Coombs test
differentiating immune thrombocytopenic purpura (ITP) from TTP
ITP does not have evidence of multisystem disease
differentiating DIC from TTP
increased PT
decreased fibrinogen
increased fibrin degradation products and D-dimer
^^^in DIC
first line treatment for TTP
plasma exchange
decreases mortality rate from 90% of patients to 10%
discuss fresh frozen plasma for TTP
second choice therapy
should be done immediately
less effective than plasma exchange due to inability to deliver appropriate volumes
splenectomy in TTP
reserved for refractory cases for patients who relapse
what is atypical HUS
characterized by MAHA and thrombocytopenia, and prominent renal insufficiency
associated with defect in complement factor H, membrane cofactor protein (CD46), or factor I
hereditary or acquired (autoimmune antibodies)
pathogenesis of atypical HUS
deficiency of complement regulator proteins leading to activation of alternative complement system
aberrant activation of alternative complement pathway
leads to endothelial damage
acquired causes of atypical HUS
s. pneumo HIV malignancies systemic rheumatologic diseases pregnancy drugs (cyclosporine, tacrolimus) stem cell transplant
presentation of atypical HUS
MAHA thrombocytopenia renal failure no ab pain or diarrhea neuro manifestations less common
lab test results in atypical HUS
CBC peripheral blood- schistocytes LDH- elevated bilirubin- elevated PT, PTT, fibrinogen- normal Coombs- negative BUN and creatinine- markedly elevated tests for complement and complement inhibitory proteins negative culture for E.coli ADAMTS13 > 10%
diagnostic criteria of aHUS
- absence of other diseases associated with TMA
- no criteria for Stx-HUS
- no criteria for TTP
- measurement of C3 and C4, factors H, I, B, MCP and antibody for factor H
treatment of aHUS
plasma therapy
eculizumab- neutralized Ab to C5
supportive therapy
