Download MBBS Pathology PPT 4 Idiopathic Autoimmune Thrombocytopenic Purpura Lecture Notes

Idiopathic (Autoimmune) Thrombocytopenic Purpura(ITP)

Acute ITP

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Self limited disorder following viral infection (HIV, CMV, HEPATTIS C,

RTI)

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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

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who has sudden onset of generalized petechiae and purpura
Recover within few weeks to 6 months

1

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Chronic ITP
? More common in adult woman in child Bearing age (20-40yrs)
? Insidious onset
? Associated with SLE, AIDS, Auto immune thyroiditis

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Pathogenesis of chronic ITP

Formation of Ig G humoral auto antibodies against gp IIb ? IIIa /

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Ib ? IX in spleen

In 80% cases these Ab demonstrated in plasma / on platelet

surface

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Opsonized platelet are recognized by the Fc receptor on splenic

macrophages, ingested, and destroyed

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ITP (Pathophysiology)(cont.)

4

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SYMPTOMS

? Petechiae

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? Bruises or purpura
? Bleeding of mucous membranes: epistaxis, gingival bleeding
? Acute gastrointestinal bleeding
? Menorrhagia
? Hematuria

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? Acute CNS hemorrhage: the rarest but MOST FEARED

consequence of low platelets

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Lab diagnosis
Platelet count reduced(10,000-50,000)
Peripheral smear-Reduced platelet with giant platelet
Bone marrow ? increased megakaryocytes

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Large non lobulated single nuclei (immature forms) with

reduced granularity presence of vacuole

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Treatment(Cont.)

1.

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IVIG

2.

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High-dose corticosteroids

3.

splenectomy

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4.

Platelet transfusion

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32
Thrombotic Thrombocytopenic

Purpura

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Definition

? Syndrome of Coomb's negative microangiopathic hemolysis

and thrombocytopenia in the absence of an alternative

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explanation for these manifestations.

? Presence of Fever, Neurological and renal abnormalities :

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classic Pentad.
Pathogenesis
? Endothelial damage from immunological damage by diverse

condition like pregnancy metastatic cancer chemotherapy hiv

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? Release of procoagulant like vwf from endothelium
? Formation of micro thrombi

Diagnosis

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? Primary diagnostic criteria

? Thrombocytopenia ( often below <20,000)

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? Microangiopathic hemolytic anemia

? Negative Coomb's test.

? Fragmented red cells (schistocytes) on peripheral smear

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? LDH elevation is the hal mark of RBC destruction and

tissue injury related to ischemia.

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? examination of biopsy (gingival) demonstrate microthrombi

in arterioles, capil ary and venules not associated with

inflammatory changes in vessel wal

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? Bone marrow shows mild myeloid and megakaryocytic

hyperplasia

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George,Blood Aug 2000

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ADAMTS13 (a disintegrin and metalloproteinase with a

thrombospondin type 1 motif, member 13)--also known as von

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Willebrand factor-cleaving protease (VWFCP)--is a zinc-containing

metalloprotease enzyme that cleaves von Willebrand factor (vWf), a

large protein involved in blood clotting.

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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

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? Tests for ADAMTS13 deficiency or inhibitors are not readily available

and lack standardization.

Differential Diagnosis

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? Disseminated intravascular coagulation.
? Sepsis: cytomegalovirus, rocky mountain spotted fever,

meningococcemia.

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? Preeclampsia/eclampsia, HELLP.
? Disseminated malignancy.
? Hemolytic-uremic syndrome
? Evans syndrome

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? Malignant hypertension.
Treatment

? Plasma exchange:

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? Untreated TTP has 80-90% mortality.

? Removes ULvWF multimers, autoantibody and replaces

metalloproteinase.

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? Randomized controlled trial (Rock et al, 1991)

? FFP as the replacement fluid is most widely used and cost effective.

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Treatment

? Cryosupernatant plasma (Rock et al 2000)

?Theoretically superior to FFP in refractory disease

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?Removal of cryoprecipitate from donor plasma

results in removal of vWF ( only 18%), with no

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change in metalloproteinase concentration.

? Solvent-detergent plasma (Moake et al 1998)

?Lacks high molecular weight forms of VWF

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?Inactivates lipid-enveloped viruses.

?Drawback: parvovirus & hep A not inactivated.
DIC (Disseminated Intravascular Coagulation)

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? An acute, subacute or chronic thrombo hemorrhagic disorder

occurring as a secondary complications in a variety of diseases.

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? As a consequence of the thrombotic diathesis, there is consumption of

platelets, fibrin & Clotting Factors & secondary activation of

fibrinolytic mechanism.

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Causes of DIC

Major disorders associated with DIC

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1. Obstetric complications

Abruptio Placentae

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Retained dead fetus

Septic abortions

Amniotic fluid embolism

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Toxemia

2. Infections

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Gm ?ve sepsis

Meningococcemia

Rocky mountain spotted fever

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Histoplasmasis

Aspergillosis

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Malaria

3. Neoplasms

Carcinoma of pancreas, stomach, prostate & lung

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AML ? M3
4. Massive Tissue injury

Traumatic

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Burns

Extensive injury

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5. Miscel aneous

Acute intravascular hemolysis, snake bite, giant

hemangiomas, shock, stroke, liver disease.

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PATHO-PHYSIOLOGY

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Two major mechanism triggers DIC
1) Release of TF/ thromboplastin substances

into circulation

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TF ? Released from placenta, Granules of leukemic

cells (AML)

Mucus released from adenocarcinomas(Directly

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activate Factor X)

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2) Endothelial Injury

Release of TF, Pl- aggregation, increased intrinsic

pathway activity.

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widespread endothelial injury may be produced by

deposition of Ag ? Ab complexes (SLE),

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Temperature extremes (burns, heat stroke) or

micro-organisms (meningococci, rickettsiae)
Clinical course
Acute DIC associated with Bleeding diathesis initial y

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obstetric complications

Trauma

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endotoxic shock

Amniotic fluids embolism

Chronic DIC associated with thrombotic disorders

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(cancer)

Retained dead fetus

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Carcinomatosis

Massive tissue

Sepsis

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Endothelial

destruction

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Injury

Release of TF

Widespread microvascular

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thrombosis

Activation

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of plasmin

Vascular

MHA

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occlusion

Consumption

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of CF & Plt

Ischemic tissue

damage

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Fibrinolysis Proteolysis

of CF

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FDP

(-) of Thrombin Plt aggre

Bleeding

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& fibrin polymerization
Thrombi are most often found in the brain, heart, lungs, kidneys,

adrenals, spleen, and liver, in decreasing order of frequency, but any

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tissue can be affected.

Affected kidneys may have small thrombi in the glomeruli that evoke

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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

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with pulmonary edema and fibrin exudation, creating "hyaline

membranes" reminiscent of acute respiratory distress syndrome

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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.

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In meningococcemia, fibrin thrombi within the microcirculation of the

adrenal cortex are the probable basis for the massive adrenal

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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

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neoplasm because of stasis and recurrent trauma to fragile blood

vessels

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LAB FINDINGS IN DIC

TEST

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RESULTS

PLATELET COUNT

MARKEDLY REDUCED

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PROTHROMBIN TIME

MARKEDLY INCREASED

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APTT

MARKEDLY INCREASED

FDP

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MARKEDLY INCREASED

FIBRINOGEN

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NORMAL / DECREASED

AT II

MARKEDLY DECREASED

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PROTEIN C

MARKEDLY DECREASED
?RX Fresh frozen plasma

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Heparin