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)
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
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
Signs/Symptoms of low platelets
Bleeding in areas of weak structural
support (mucous membranes)
Bleeding in areas of dependency (ankles)
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
Signs/Symptoms cont
GI bleeding
Easy bruising
Hematuria
CNS bleed
3 mechanisms causing a low
platelet count :
Accelerated destruction
Impaired production
Abnormal distribution (hypersplenism)
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)
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)
Mimics of ITP via immunologic
pathway
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)
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
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
HUS-TTP treatment
Plasmapheresis--Plasma exchange of
40mL/kg daily until PLT > 100k and fall in
LDH.
Supportive care
No platelet transfusion!!!
Special Exam Slide
HELLP syndrome
– Hemolysis Elevated Liver enzymes Low
Platelets
– Preeclampsia/eclampsia
– Recover after delivery
– May need plasmapheresis
Many words about DIC
(disseminated intravascular
coagulation)
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
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.
DIC—but wait, there’s more!
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
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
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.
DIC-Why?
Infections—bacterial/viral
– Acute uncompensated DIC
Malignancy—Trousseau’s syndrome
(chronic compensated DIC)
– More thrombotic than bleeding
Aortic aneurysms/hemangiomas
Abruptio placentae/retained dead fetus
Trauma
DIC-Why?
Snake bites
Heat stroke
HELLP
DIC signs/symptoms
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
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
Thrombocytopenia due to impaired
production
Invasion of marrow by malignant cells
Bone marrow hypoplasia
– Due to chemo, drugs
Chloramphenicol, gold, phenytoin, sulfonamides
Thrombocytopenia due to impaired
production
Treatment
– Platelet transfusions
– Treat underlying cause
– Hold offending drug
– Amicar—plasmin inhibitor
Thrombocytopenia due to abnormal
distribution
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
Treatment of hypersplenism:
– Splenectomy
– Remember to vaccinate for encapsulated
organisms prior to splenectomy
Cases
1. So, 35 y/o female truck driver presents
to outpatient clinic with bruises.
Cases
2. 55 y/o male in ED s/p MVA with
multiple open fractures. Postoperatively
develops PLT 15k, bleeding from
everywhere.
Cases
45 y/o female teacher admitted with plt
count 20.