Increased Platelet Destruction- Immune System


Terms in this set (...)

2 general causes of platelet destruction
Increase platelet destruction due to immunologic responses

Increase destruction caused by mechanical damage or consumption
ITP definition
Immune (idiopathic) Throbocytopenic purpura
Acute ITP incidence
primarily a disorder in children (2-5 years old)
occasionally in adults
Clinical features of ITP
abrupt onset of bruising, petechiae, sometimes mucosal bleeding.
Thrombocytopenia 1-3 weeks after infection
infections associated with ITP
upper respiratory and GI tract viral infection
Rubella, Rubeola , chickenpox, may follow live virus vaccination
diagnosis of ITP
does NOT require bone marrow biopsy
normal WBC and RBC morphology
only show signs of bleeding
no family history of bleeding
pathophysiology of ITP
antibodies against viral antigens flag platelets for destruction by RE cells in spleen
Autoantibodies detected to the platelet surface glycoproteins GPIIb and GPIIIa, GP Ia/IIa and megakaryocyte antibodies Gp IIb/IIIa and GP Ib/IX become target of autoantibodies
Symptoms of ITP mild
mild cases: scattered petechiae
Symptoms of ITP severe
3-4% cases are severe
generalized purpura, GI bleeding, hematuria, retinal hemorrhage
25-50% cases are at risk for intracranial hemorrhage (plt count less than 4000)
chronic ITP
thrombocytopenia persists >6 months
highest incidence of chronic ITP
women 20-40 years old
Symptoms of chronic ITP
mucocutaneous bleeding
Recurrent epistaxis
Easy bruising
Platelet numbers between 30,000/μL and 80,000/μL
Periods of remission and exacerbation
range from near normal to fewer than 20,000/μL
platelets appear normal, although larger in diameter than usual
increased mean platelet volume
Bone Marrow in ITP
megakaryocytic hyperplasia.
Megakaryocytes are increased in size
RBC and WBC precursors are normal in number and morphology.
Coagulation tests abnormal platelet function.
Immunologic drug-induced thrombocytopenia
Antibody induced by the drug interacts with the platelets in the presence of the drug
platelet count drops rapidly <10,000
-abrupt onset of bleeding
-affects the fetus and mom (if pregnant)
Hapten Induced Antibodies
hapten too small to induce an immune response
Antibodies act as hapten combines with a plasma protein or protein constituent thus acting as a complete antigen
examples of hapten drugs causing thrombocytopenia
penicillin and derivatives
platelet counts in Hapten induced Antibodies
fewer than 10,000/uL and even fewer than 1,000/uL
bone marrow in Hapten induced antibodies
megakaryocytes are normal to increased
immune complex-induced thrombocytopenia
Heparin binds to platelet factor 4 (PF4), heparin neutralizing protein produced and released by platelets
Conformational change occurs in PF4 resulting in exposure of neoepitopes,
which in some individuals leads to production of antibodies
Incidence of HIT
plt count seldom < 40,000/uL
10-30% of PTs develop thrombotic complications
effects occur 7-10 days after initiation of heparin therapy
Heparin Resistance
-occurs in patients who had experienced heparin anticoagulation
-at certain heparin dose and requires increasing amounts of heparin
-seen before thrombocytopenia
pathophysiology of Heparin resistance
in vivo activation of platelets and release of PF4 and B-thromboglobulin from alpha granules
-both neutralize heparin leading to normalization of PTT
Detection of HIT: platelet function tests
Lack sensitivity
Detected by means of platelet aggregation
Excellent specificity
Detection of HIT: platelet aggregation
specificity 100% but sensitivity is low (50%)
Excellent specificity and low sensitivity
Functional assay
Detection of HIT: Serotonin release assay
*gold standard for HIT detection
Drawback is use of radioactive serotonin
Functional assay
Detection of HIT: ELISA
*low specificity
Better sensitivity than platelet aggregation
lower specificity than SRA because detects non pathologic anti PF4-heparin antibodies
Neonatal Alloimmune Thrombocytopenia (NAIT)
Occurs when mother lacks platelet specific antigen (human platelet antigen (e.g.HPA-1a[P1A1])
mechanism of NAIT
-fetal platelet antigens might pass from fetal to maternal circulation
----leading the mother to make antibodies to fetal antigen.
-These antibodies cross the placenta and cause thrombocytopenia in fetus.
-Similar to hemolytic disease of newborn
Initial signs of NAIT
petechiae and purpuric hemorrhages, plts<30,000/uL
Infants recover in most cases 1-2 wks when antibodies clear up and platelet levels increase
-Affected newborns have normal to decreased platelet numbers at birth
Falling platelet count due to maturation of the RE system and accelerated removal of antibody labeled platelets by cells of RE system
Incidence of NAIT
diagnosis of ITP or SLE is a prerequisite
passive transplacental transfer of antibodies from mother with ITP or SLE
post-transfusion purpura (PTP)
Rare disorder that develops 1 week after transfusion of platelet containing products
--Rapid onset of severe thrombocytopenia
--Moderate to severe hemorrhage that may be life threatening
--Recipient's plasma is found to contain alloantibodies to antigens on platelets or platelet membranes
Incidence of PTP
--multiparous middle aged women
--Antibody is directed to HPA-1a antigen or P1A2 or epitopes GPIIb/IIIa in 90% of cases
--Need to have been previously exposed to foreign platelet antigens
Treatment of PTP
plasmapheresis and exchange transfusion
IVIG treatment of choice
Secondary thrombocytopenia, Presumed to be Immune Mediated
Found in patients receiving biologic response modifiers such as interferons, colony stimulating factors and interlukin-2
inducing conditions of secondary thrombocytopenia
Chronic lymphocytic leukemia
Systemic lupus erythematosus
Bone marrow of secondary thrombocytopenia
Larger than normal number of megakaryocytes
Increased level of platelet-associated IgG