Download MBBS Pathology PPT 4 Idiopathic Autoimmune Thrombocytopenic Purpura Lecture Notes

--- Content provided by​ FirstRanker.com ---

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

RTI)

--- Content provided by‌ FirstRanker.com ---

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

--- Content provided by​ FirstRanker.com ---

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

1

--- Content provided by‍ FirstRanker.com ---

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

--- Content provided by​ FirstRanker.com ---

Pathogenesis of chronic ITP

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

--- Content provided by⁠ FirstRanker.com ---

Ib ? IX in spleen

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

surface

--- Content provided by​ FirstRanker.com ---

Opsonized platelet are recognized by the Fc receptor on splenic

macrophages, ingested, and destroyed

--- Content provided by⁠ FirstRanker.com ---

ITP (Pathophysiology)(cont.)

4

--- Content provided by FirstRanker.com ---

SYMPTOMS

? Petechiae

--- Content provided by​ FirstRanker.com ---

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

--- Content provided by FirstRanker.com ---

? Acute CNS hemorrhage: the rarest but MOST FEARED

consequence of low platelets

--- Content provided by‍ FirstRanker.com ---

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

--- Content provided by‌ FirstRanker.com ---

Large non lobulated single nuclei (immature forms) with

reduced granularity presence of vacuole

--- Content provided by⁠ FirstRanker.com ---

Treatment(Cont.)

1.

--- Content provided by‌ FirstRanker.com ---

IVIG

2.

--- Content provided by​ FirstRanker.com ---

High-dose corticosteroids

3.

splenectomy

--- Content provided by‌ FirstRanker.com ---

4.

Platelet transfusion

--- Content provided by​ FirstRanker.com ---

32
Thrombotic Thrombocytopenic

Purpura

--- Content provided by⁠ FirstRanker.com ---

Definition

? Syndrome of Coomb's negative microangiopathic hemolysis

and thrombocytopenia in the absence of an alternative

--- Content provided by⁠ FirstRanker.com ---

explanation for these manifestations.

? Presence of Fever, Neurological and renal abnormalities :

--- Content provided by‍ FirstRanker.com ---

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

condition like pregnancy metastatic cancer chemotherapy hiv

--- Content provided by​ FirstRanker.com ---

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

Diagnosis

--- Content provided by​ FirstRanker.com ---

? Primary diagnostic criteria

? Thrombocytopenia ( often below <20,000)

--- Content provided by​ FirstRanker.com ---

? Microangiopathic hemolytic anemia

? Negative Coomb's test.

? Fragmented red cells (schistocytes) on peripheral smear

--- Content provided by‍ FirstRanker.com ---

? LDH elevation is the hal mark of RBC destruction and

tissue injury related to ischemia.

--- Content provided by​ FirstRanker.com ---

? examination of biopsy (gingival) demonstrate microthrombi

in arterioles, capil ary and venules not associated with

inflammatory changes in vessel wal

--- Content provided by​ FirstRanker.com ---

? Bone marrow shows mild myeloid and megakaryocytic

hyperplasia

--- Content provided by FirstRanker.com ---

George,Blood Aug 2000

--- Content provided by‍ FirstRanker.com ---

--- Content provided by​ FirstRanker.com ---

--- Content provided by​ FirstRanker.com ---

--- Content provided by‌ FirstRanker.com ---

ADAMTS13 (a disintegrin and metalloproteinase with a

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

--- Content provided by‍ FirstRanker.com ---

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

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

large protein involved in blood clotting.

--- Content provided by​ FirstRanker.com ---

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

--- Content provided by‌ FirstRanker.com ---

? Tests for ADAMTS13 deficiency or inhibitors are not readily available

and lack standardization.

Differential Diagnosis

--- Content provided by​ FirstRanker.com ---

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

meningococcemia.

--- Content provided by FirstRanker.com ---

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

--- Content provided by‌ FirstRanker.com ---

? Malignant hypertension.
Treatment

? Plasma exchange:

--- Content provided by‌ FirstRanker.com ---

? Untreated TTP has 80-90% mortality.

? Removes ULvWF multimers, autoantibody and replaces

metalloproteinase.

--- Content provided by‌ FirstRanker.com ---

? Randomized controlled trial (Rock et al, 1991)

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

--- Content provided by⁠ FirstRanker.com ---

Treatment

? Cryosupernatant plasma (Rock et al 2000)

?Theoretically superior to FFP in refractory disease

--- Content provided by FirstRanker.com ---

?Removal of cryoprecipitate from donor plasma

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

--- Content provided by⁠ FirstRanker.com ---

change in metalloproteinase concentration.

? Solvent-detergent plasma (Moake et al 1998)

?Lacks high molecular weight forms of VWF

--- Content provided by FirstRanker.com ---

?Inactivates lipid-enveloped viruses.

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

--- Content provided by⁠ FirstRanker.com ---

? An acute, subacute or chronic thrombo hemorrhagic disorder

occurring as a secondary complications in a variety of diseases.

--- Content provided by⁠ FirstRanker.com ---

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

platelets, fibrin & Clotting Factors & secondary activation of

fibrinolytic mechanism.

--- Content provided by‌ FirstRanker.com ---

Causes of DIC

Major disorders associated with DIC

--- Content provided by FirstRanker.com ---

1. Obstetric complications

Abruptio Placentae

--- Content provided by​ FirstRanker.com ---

Retained dead fetus

Septic abortions

Amniotic fluid embolism

--- Content provided by FirstRanker.com ---

Toxemia

2. Infections

--- Content provided by​ FirstRanker.com ---

Gm ?ve sepsis

Meningococcemia

Rocky mountain spotted fever

--- Content provided by​ FirstRanker.com ---

Histoplasmasis

Aspergillosis

--- Content provided by‍ FirstRanker.com ---

Malaria

3. Neoplasms

Carcinoma of pancreas, stomach, prostate & lung

--- Content provided by​ FirstRanker.com ---

AML ? M3
4. Massive Tissue injury

Traumatic

--- Content provided by‍ FirstRanker.com ---

Burns

Extensive injury

--- Content provided by FirstRanker.com ---

5. Miscel aneous

Acute intravascular hemolysis, snake bite, giant

hemangiomas, shock, stroke, liver disease.

--- Content provided by‌ FirstRanker.com ---

PATHO-PHYSIOLOGY

--- Content provided by‌ FirstRanker.com ---

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

into circulation

--- Content provided by FirstRanker.com ---

TF ? Released from placenta, Granules of leukemic

cells (AML)

Mucus released from adenocarcinomas(Directly

--- Content provided by‌ FirstRanker.com ---

activate Factor X)

--- Content provided by FirstRanker.com ---

2) Endothelial Injury

Release of TF, Pl- aggregation, increased intrinsic

pathway activity.

--- Content provided by​ FirstRanker.com ---

widespread endothelial injury may be produced by

deposition of Ag ? Ab complexes (SLE),

--- Content provided by FirstRanker.com ---

Temperature extremes (burns, heat stroke) or

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

--- Content provided by‌ FirstRanker.com ---

obstetric complications

Trauma

--- Content provided by⁠ FirstRanker.com ---

endotoxic shock

Amniotic fluids embolism

Chronic DIC associated with thrombotic disorders

--- Content provided by FirstRanker.com ---

(cancer)

Retained dead fetus

--- Content provided by​ FirstRanker.com ---

Carcinomatosis

Massive tissue

Sepsis

--- Content provided by‍ FirstRanker.com ---

Endothelial

destruction

--- Content provided by​ FirstRanker.com ---

Injury

Release of TF

Widespread microvascular

--- Content provided by​ FirstRanker.com ---

thrombosis

Activation

--- Content provided by‌ FirstRanker.com ---

of plasmin

Vascular

MHA

--- Content provided by⁠ FirstRanker.com ---

occlusion

Consumption

--- Content provided by‌ FirstRanker.com ---

of CF & Plt

Ischemic tissue

damage

--- Content provided by‍ FirstRanker.com ---

Fibrinolysis Proteolysis

of CF

--- Content provided by​ FirstRanker.com ---

FDP

(-) of Thrombin Plt aggre

Bleeding

--- Content provided by​ FirstRanker.com ---

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

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

--- Content provided by FirstRanker.com ---

tissue can be affected.

Affected kidneys may have small thrombi in the glomeruli that evoke

--- Content provided by FirstRanker.com ---

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

--- Content provided by‌ FirstRanker.com ---

with pulmonary edema and fibrin exudation, creating "hyaline

membranes" reminiscent of acute respiratory distress syndrome

--- Content provided by‍ FirstRanker.com ---

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.

--- Content provided by‍ FirstRanker.com ---

In meningococcemia, fibrin thrombi within the microcirculation of the

adrenal cortex are the probable basis for the massive adrenal

--- Content provided by‌ FirstRanker.com ---

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

--- Content provided by‍ FirstRanker.com ---

neoplasm because of stasis and recurrent trauma to fragile blood

vessels

--- Content provided by‍ FirstRanker.com ---

LAB FINDINGS IN DIC

TEST

--- Content provided by​ FirstRanker.com ---

RESULTS

PLATELET COUNT

MARKEDLY REDUCED

--- Content provided by⁠ FirstRanker.com ---

PROTHROMBIN TIME

MARKEDLY INCREASED

--- Content provided by‌ FirstRanker.com ---

APTT

MARKEDLY INCREASED

FDP

--- Content provided by​ FirstRanker.com ---

MARKEDLY INCREASED

FIBRINOGEN

--- Content provided by⁠ FirstRanker.com ---

NORMAL / DECREASED

AT II

MARKEDLY DECREASED

--- Content provided by​ FirstRanker.com ---

PROTEIN C

MARKEDLY DECREASED
?RX Fresh frozen plasma

--- Content provided by‍ FirstRanker.com ---

Heparin