Download MBBS (Bachelor of Medicine, Bachelor of Surgery) Pathology PPT 4 Idiopathic Autoimmune Thrombocytopenic Purpura Lecture Notes
Idiopathic (Autoimmune) Thrombocytopenic Purpura(ITP)
Acute ITP
Self limited disorder following viral infection (HIV, CMV, HEPATTIS C,
RTI)
1 - 4 wk after exposure to a common viral infection
The peak age is 1-4 yr
The classic presentation of ITP is a previously healthy 1-4 yr old child
who has sudden onset of generalized petechiae and purpura
Recover within few weeks to 6 months
1
Chronic ITP
? More common in adult woman in child Bearing age (20-40yrs)
? Insidious onset
? Associated with SLE, AIDS, Auto immune thyroiditis
Pathogenesis of chronic ITP
Formation of Ig G humoral auto antibodies against gp IIb ? IIIa /
Ib ? IX in spleen
In 80% cases these Ab demonstrated in plasma / on platelet
surface
Opsonized platelet are recognized by the Fc receptor on splenic
macrophages, ingested, and destroyed
ITP (Pathophysiology)(cont.)
4
SYMPTOMS
? Petechiae
? Bruises or purpura
? Bleeding of mucous membranes: epistaxis, gingival bleeding
? Acute gastrointestinal bleeding
? Menorrhagia
? Hematuria
? Acute CNS hemorrhage: the rarest but MOST FEARED
consequence of low platelets
Lab diagnosis
Platelet count reduced(10,000-50,000)
Peripheral smear-Reduced platelet with giant platelet
Bone marrow ? increased megakaryocytes
Large non lobulated single nuclei (immature forms) with
reduced granularity presence of vacuole
Treatment(Cont.)
1.
IVIG
2.
High-dose corticosteroids
3.
splenectomy
4.
Platelet transfusion
32
Thrombotic Thrombocytopenic
Purpura
Definition
? Syndrome of Coomb's negative microangiopathic hemolysis
and thrombocytopenia in the absence of an alternative
explanation for these manifestations.
? Presence of Fever, Neurological and renal abnormalities :
classic Pentad.
Pathogenesis
? Endothelial damage from immunological damage by diverse
condition like pregnancy metastatic cancer chemotherapy hiv
? Release of procoagulant like vwf from endothelium
? Formation of micro thrombi
Diagnosis
? Primary diagnostic criteria
? Thrombocytopenia ( often below <20,000)
? Microangiopathic hemolytic anemia
? Negative Coomb's test.
? Fragmented red cells (schistocytes) on peripheral smear
? LDH elevation is the hal mark of RBC destruction and
tissue injury related to ischemia.
? examination of biopsy (gingival) demonstrate microthrombi
in arterioles, capil ary and venules not associated with
inflammatory changes in vessel wal
? Bone marrow shows mild myeloid and megakaryocytic
hyperplasia
George,Blood Aug 2000
ADAMTS13 (a disintegrin and metalloproteinase with a
thrombospondin type 1 motif, member 13)--also known as von
Willebrand factor-cleaving protease (VWFCP)--is a zinc-containing
metalloprotease enzyme that cleaves von Willebrand factor (vWf), a
large protein involved in blood clotting.
The unprocessed form of von Willebrand factor interacts easily
with cel fragments called platelets, which circulate in the bloodstream
and are essential for blood clotting
? Tests for ADAMTS13 deficiency or inhibitors are not readily available
and lack standardization.
Differential Diagnosis
? Disseminated intravascular coagulation.
? Sepsis: cytomegalovirus, rocky mountain spotted fever,
meningococcemia.
? Preeclampsia/eclampsia, HELLP.
? Disseminated malignancy.
? Hemolytic-uremic syndrome
? Evans syndrome
? Malignant hypertension.
Treatment
? Plasma exchange:
? Untreated TTP has 80-90% mortality.
? Removes ULvWF multimers, autoantibody and replaces
metalloproteinase.
? Randomized controlled trial (Rock et al, 1991)
? FFP as the replacement fluid is most widely used and cost effective.
Treatment
? Cryosupernatant plasma (Rock et al 2000)
?Theoretically superior to FFP in refractory disease
?Removal of cryoprecipitate from donor plasma
results in removal of vWF ( only 18%), with no
change in metalloproteinase concentration.
? Solvent-detergent plasma (Moake et al 1998)
?Lacks high molecular weight forms of VWF
?Inactivates lipid-enveloped viruses.
?Drawback: parvovirus & hep A not inactivated.
DIC (Disseminated Intravascular Coagulation)
? An acute, subacute or chronic thrombo hemorrhagic disorder
occurring as a secondary complications in a variety of diseases.
? As a consequence of the thrombotic diathesis, there is consumption of
platelets, fibrin & Clotting Factors & secondary activation of
fibrinolytic mechanism.
Causes of DIC
Major disorders associated with DIC
1. Obstetric complications
Abruptio Placentae
Retained dead fetus
Septic abortions
Amniotic fluid embolism
Toxemia
2. Infections
Gm ?ve sepsis
Meningococcemia
Rocky mountain spotted fever
Histoplasmasis
Aspergillosis
Malaria
3. Neoplasms
Carcinoma of pancreas, stomach, prostate & lung
AML ? M3
4. Massive Tissue injury
Traumatic
Burns
Extensive injury
5. Miscel aneous
Acute intravascular hemolysis, snake bite, giant
hemangiomas, shock, stroke, liver disease.
PATHO-PHYSIOLOGY
Two major mechanism triggers DIC
1) Release of TF/ thromboplastin substances
into circulation
TF ? Released from placenta, Granules of leukemic
cells (AML)
Mucus released from adenocarcinomas(Directly
activate Factor X)
2) Endothelial Injury
Release of TF, Pl- aggregation, increased intrinsic
pathway activity.
widespread endothelial injury may be produced by
deposition of Ag ? Ab complexes (SLE),
Temperature extremes (burns, heat stroke) or
micro-organisms (meningococci, rickettsiae)
Clinical course
Acute DIC associated with Bleeding diathesis initial y
obstetric complications
Trauma
endotoxic shock
Amniotic fluids embolism
Chronic DIC associated with thrombotic disorders
(cancer)
Retained dead fetus
Carcinomatosis
Massive tissue
Sepsis
Endothelial
destruction
Injury
Release of TF
Widespread microvascular
thrombosis
Activation
of plasmin
Vascular
MHA
occlusion
Consumption
of CF & Plt
Ischemic tissue
damage
Fibrinolysis Proteolysis
of CF
FDP
(-) of Thrombin Plt aggre
Bleeding
& fibrin polymerization
Thrombi are most often found in the brain, heart, lungs, kidneys,
adrenals, spleen, and liver, in decreasing order of frequency, but any
tissue can be affected.
Affected kidneys may have small thrombi in the glomeruli that evoke
only reactive swelling of endothelial cells or, in severe cases,
microinfarcts or even bilateral renal cortical necrosis.
Numerous fibrin thrombi may be found in alveolar capillaries associated
with pulmonary edema and fibrin exudation, creating "hyaline
membranes" reminiscent of acute respiratory distress syndrome
In the central nervous system, fibrin thrombi can cause microinfarcts,
occasionally complicated by simultaneous hemorrhage, which can
sometimes lead to variable neurologic signs and symptoms.
In meningococcemia, fibrin thrombi within the microcirculation of the
adrenal cortex are the probable basis for the massive adrenal
hemorrhages seen in Waterhouse-Friderichsen syndrome.
An unusual form of DIC occurs in association with giant hemangiomas
(Kasabach-Merritt syndrome), in which thrombi form within the
neoplasm because of stasis and recurrent trauma to fragile blood
vessels
LAB FINDINGS IN DIC
TEST
RESULTS
PLATELET COUNT
MARKEDLY REDUCED
PROTHROMBIN TIME
MARKEDLY INCREASED
APTT
MARKEDLY INCREASED
FDP
MARKEDLY INCREASED
FIBRINOGEN
NORMAL / DECREASED
AT II
MARKEDLY DECREASED
PROTEIN C
MARKEDLY DECREASED
?RX Fresh frozen plasma
Heparin
This post was last modified on 07 April 2022