B3.066 - CBCL Thrombocytopenia Flashcards
What is TTP
pentad characterization 1. fever 2. thrombocytopenia 3. transient neuro deficits 4. renal failure 5. microangiopathic hemolytic anemia
what causes TTP
deficiency in ADAMTS13, which cleaves/degrades very high molecular weight vWF, leading to more clotting
who is at higher risk for TTP
african american women and pregnant women
what genetic tests can you do fro TTP
mutations in ADAMTS13
common causes of TTP
ADAMTS13 mutations (Upshaw-Schulman syndrome) HIV Autoimmune disorders preglancy some drugs
symptoms of TTP
malaise bleeding altered mental status low grade fever petechiae pallor jaundice confusion seizures
tests for TTP
ADAMTS13 activity and circulating ADAMTS13 antibody negative coombs polychromasia elevated LDH elevated bilirubin bc of heme metabolism elevated BUN with kidney failure
differential for TTP
sepsis vasculitis
how do you differentiate sepsis from TTP
sepsis will have normal ADAMTS13 levels
how do you differentiate vasculitis from TTP
not usually associated with microthrombi or hemolytic anemia
how do you differentiate TTP from malignant hypertension
retinopathy grade III or IV seen in malignant HT not TTP
how do you differentiate TTP from Autoimmune hemolytic anemia
positive coombs test spherocytes rather than schistocytes on PBS, no MAHA
first line of treatment for TTP
plasma exchange
what type of plasma is given for TTP and what line of therapy is it and what do you have to be careful of
fresh frozen plasma 2nd line, careful not to overload patient so you have to give slowly
are antiplatelets helpful in TTP
no
is a platelet transfusion helpful in TTP?
no
what is aHUS
characterized by microangiopathic hemolytic anemia and thrombocytopenia, prominent in renal insufficiency
how does aHUS happen
associated with defects in complement factor H, membrane cofactor CD46 or factor I. Deficiency of complement regulatory proteins leads to activation of alternative complement system
what proteins are associated with activation of alternative complement system in aHUS
factor H factor I membrane cofactor protein thrombomodulin
what factors are associated with aberrant activation of alternative complement pathway
factor B Factor C3
secondary aHUS
initiated by coexisting disease or condition
triggering events that can cause aHUS
strep pneumo HIV malignancies pregnancy rheumatologic disease drugs like cyclosporine and tac stem cell transplantation
presentation of aHUS
microangiopathic hemolytic anemia thrombocytopenia renal failure neurological manifestations are less common no abdominal pain and diarrhea
lab tests for aHUS
*BUN markedly elevated *Tests for complement *negative culture *ADAMSTS13>10% CBC Peripheral smear (schistocytes) elevated LDH elevated bilirubin negative coombs normal PT, PTT,
what is diagnostic for aHUS
absence of other diseases negative culture no TTP criteria C3 and C4 measurements, factors H,I,B, MCP, and antibody for factor H
treatment for aHUS
plasma therapy Eculizumab (neutralizing Ab to C5) supportive therapy
Glansmans thrombopenia
Gp2b3a defect, autosomal recessive
Bernards soulier syndrom
Gp1b deficiency, autosomal recessive
how does alcohol affect platelets
B12 or B9 deficiency can lead to lower platelets, they need nutrients to be created can be toxic to BM
what are platelets
small non nucleated blood cells derived from bone marrow megakaryocytes
what do alpha granules contain
procoagulant factor V Fibrinogen vWF PF4 Growth factors
what do dense granules of platelets contain
ADP serotonin calcium
what is this
normal peripheral blood smear
what is bernard soulier syndrome
mutation of Gp1b
what is glanzmans thrombasthenia
mutation of glycoprotein 2b3a
what is this and what are the arrows pointing to
normal bone marrow
megkaryocytes
normal platelet count
150,000-400,000
platelet function tests
PFA-100
Platelet aggregation test
bleeding test
what does PFA-100 do
screening test of platelet function that measures platelet adhesion and aggregation
if collagen/epinephrine test result is abnormal what does that mean
could be due to aspirin resistance
if only collagen/epinephrine test is normal then
platelet dysfunction exists
it the collagen/epinephrine test is abnormal what happens
you perform APD collagen test to confirm, it that is abnormal too then platelet dysfunction probably exists
platelet aggregation test measure what
ability of various agonists to platelets to induce in vitro actvaton
how does the platelet aggregation test work
when agonist is added the platelets aggregate and absorb less light so the transmission increases and it is detected by the photocell
causes of thrombocytopenia
decreased platelet production/survival
sequestration
dilution
thrombocytopenia
lymphoma
metastatic carcinoma
aplastic anemia
TTP
note: schistocytes
symptoms of thrombocytopenia
petechiae and ecchtmoses
gum and nose bleeding
GI bleeding, hematuria, excessive menstrual flow
Subarachnoid hemorrhage and intracerebral hemorrhage rare but serious
petechiae
