Transcript Document

Thrombocytopenia
Jason Corbeill PA-C
Platelet facts
Chunks of cytoplasmic fragments of a
megakaryocyte (in bone marrow)
 Surface contains receptors
 Cytoplasm contains secretory granules
 Lives 8-10 days
 1/3 is sequestered in spleen (emergency
pool)
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Platelet function
1. ACTIVATES and releases messenger
molecules/effector enzymes
 2. ADHERES to area of broken vessel
utilizing Von Willebrand factor.
 3. Recruits additional platelets
(AGGREGATION) with fibrinogen binding
to platelet surface receptors.
 4. PROMOTES thrombin production
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The numbers
Normal is 150-400k
 Below 125 or so is concerning
 Below 50k is very concerning and
surgeries should be postponed
 Below 10-20k requires PLT transfusion-risk
for spontaneous bleed.
 Refer to hematologist
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Signs/Symptoms of low platelets
Bleeding in areas of weak structural
support (mucous membranes)
 Bleeding in areas of dependency (ankles)
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Signs/Symptoms cont.
Petechiae—small 2-5mm deep red –
purple flat, non palpable lesions usually in
dependent areas
 Purpura—areas of confluent petechiae—
can be a few centimeters
 “blood blisters”—purpura in mouth
 Gingival bleeding
 menorrhagia
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Signs/Symptoms cont
GI bleeding
 Easy bruising
 Hematuria
 CNS bleed
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3 mechanisms causing a low
platelet count :
Accelerated destruction
 Impaired production
 Abnormal distribution (hypersplenism)
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Differential of thrombocytopenia
due to accelerated destruction
EDTA clumping—lab abnormality
 ITP-idiopathic (immune) thrombocytopenic
purpura and it’s mimics.
 HUS-TTP
 DIC/sepsis
 Alcohol induced
 Hereditary
 HIT (heparin induced thrombocytopenia)
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A word about true ITP
Caused by splenic destruction of PLT due
to autoantibody (immune response) that
views the platelet as foreign
 Red and white cells are normal
 Bone marrow is normal
 No splenomegaly
 No lymphadenopathy
 Peripheral smear is normal (exc low PLT)
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Mimics of ITP via immunologic
pathway
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Lupus
Lymphoma
CLL
Infections (including HIV)
Sarcoidosis
Solid tumors
Mononucleosis
Drugs—quinine, quinidine, gold, heparin,
sulfonamides
Treatment for true ITP
Prednisone 1mg/kg
 IVIG
 WinRho if Rh D positive
 Splenectomy
 Vincristine
 Cyclophosphamide
 Rituxan
 Romiplostim (Nplate)
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A word about HUS-TTP
Hemolytic Uremic Syndrome-Thrombotic
Thrombocytopenic Purpura
Precipitated by an antibody causing
excessive VWF multimers leading to
excessive platelet aggregation
 Small vessel endothelial damage is likely
precipitationg factor
 Platelets are used up in forming
microscopic thrombi
 Microangiopathic hemolytic anemia as
result
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Signs/symptoms HUS-TTP
Neurological deficits—confusion, etc
 Renal failure
 Thrombocytopenia
 Elevated LDH
 Anemia
 Schistocytes on peripheral smear
 Helmet cells/burr cells on peripheral smear
 Purpura/petechiae
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HUS-TTP treatment
Plasmapheresis--Plasma exchange of
40mL/kg daily until PLT > 100k and fall in
LDH.
 Supportive care
 No platelet transfusion!!!
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Special Exam Slide
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HELLP syndrome
– Hemolysis Elevated Liver enzymes Low
Platelets
– Preeclampsia/eclampsia
– Recover after delivery
– May need plasmapheresis
Many words about DIC
(disseminated intravascular
coagulation)
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Under normal circumstances…
– Tissue Factor released at site of injury
– Leads to formation of thrombin at site of
tissue injury
– Leads to activation of platelets and
coagulation cascade at site of tissue injury
DIC
– Leads to local thrombin->fibrinogen->fibrin
plug
– Plasmin eventually dissolves plug
– Whole process is tightly regulated by
inhibitory proteins (antithrombin, Tissue factor
pathway inhibitor)
DIC
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In DIC however..
– Tissue factor released at injury site
– Leads to formation of thrombin at site of
tissue injury and throughout the entire
vasculature
– Leads to activation of platelets/coagulation
cascade throughout the entire vasculature
– Leads to platelet, fibrin deposition throughout
entire vasculature.
DIC
Plasmin, antithrombin, TFPI unable to
keep up with out-of-control coagulation
cascade.
 Results in tissue ischemia, consumption of
platelets, fibrinogen, coagulation factors V
and VII, prothrombin.
 Leads to bleeding as all components of
clotting cascade used up in useless clots.
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DIC—but wait, there’s more!
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Not only does one have an out-of-control
activation of the clotting cascade in DIC
but there is also a second component.
DIC-Fibrinolysis
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Eventually, plasminogen makes plasmin
and the widespread fibrin clots begin to
break down
– Releases fibrin split (degradation) products
– FSP enhances bleeding by inhibiting platelet
aggregation
– Plasmin also breaks down remaining
circulating clotting factors and fibrinogen
worsening bleeding even more.
DIC labs
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So, lab values should show both a
consumptive bleeding diathesis AND a
fibrinolytic process.
– prolonged PT (intrinsic pathway/PTT (extrinsic
pathway)
– Low fibrinogen (it’s being used to make fibrin)
– Low platelets
– Elevated FSP/D-dimer
– Low antithrombin
DIC—why?
Release of tissue factor into circulation
 Extensive vascular endothelial injury
exposing tissue factor
 Enhanced release of tissue factor by
monocytes in response to various
cytokines/endotoxins.
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DIC-Why?
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Infections—bacterial/viral
– Acute uncompensated DIC
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Malignancy—Trousseau’s syndrome
(chronic compensated DIC)
– More thrombotic than bleeding
Aortic aneurysms/hemangiomas
 Abruptio placentae/retained dead fetus
 Trauma
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DIC-Why?
Snake bites
 Heat stroke
 HELLP
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DIC signs/symptoms
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So patients with DIC should show
signs/symptoms leading to release of
tissue factor and the resultant widespread
thrombus formation and bleeding
diathesis.
DIC signs/symptoms
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Bleeding—from everywhere
Septic shock
Renal failure
Respiratory failure—pulmonary hemorrhage/
ARDS
Hepatic dysfunction
CNS changes
Evidence of cancer/acute promyelocytic
leukemia
DIC-Treatment
Underlying cause
 Plasma transfusion ?
 Platelet transfusion—only if severe
bleeding?
 ? Heparin to promote antithrombinthrombin binding.
 ? Antithrombin infusion
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Thrombocytopenia due to impaired
production
Invasion of marrow by malignant cells
 Bone marrow hypoplasia
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– Due to chemo, drugs
 Chloramphenicol, gold, phenytoin, sulfonamides
Thrombocytopenia due to impaired
production
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Treatment
– Platelet transfusions
– Treat underlying cause
– Hold offending drug
– Amicar—plasmin inhibitor
Thrombocytopenia due to abnormal
distribution
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Hypersplenism
– Normally 30% of platelets reside in the spleen
– In cases of splenomegaly the spleen will
sequester more platelets, resulting in a
decrease in circulating platelets
– Caused by portal hypertension/lymphoma
Thrombocytopenia due to abnormal
distribution
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Treatment of hypersplenism:
– Splenectomy
– Remember to vaccinate for encapsulated
organisms prior to splenectomy
Cases
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1. So, 35 y/o female truck driver presents
to outpatient clinic with bruises.
Cases
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2. 55 y/o male in ED s/p MVA with
multiple open fractures. Postoperatively
develops PLT 15k, bleeding from
everywhere.
Cases
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45 y/o female teacher admitted with plt
count 20.