Platelet disorders

PLATELET DISORDERS

QUANTITATIVE AND QUALITATIVE DISORDERS

QUALITATIVE PLATELET

DISORDERS• THROMBOCYTOPENIA• THROMBOCYTOSIS

THROMBOCYTOPENIA MOST COMMON CAUSE OF ABNORMAL

BLEEDING AND GENERALLY ATTTRIBUTED TO THE FF. CAUSES:1. Decrease platelet production2. Decreased platelet survival time due to

increase destruction and/or consumption3. Increased platelet sequestration by the

spleen, &4. Dilution of the platelet count by multiple

blood transfusions.

DECREASED PLATELET PRODUCTION

1. CONGENITAL HYPOPLASIA OF THE MEGAKARYOCYTES IN THE BM

a) FANCONI SYNDROME- d/t pancytopeniab) TAR SYNDROME- thrombocytopenia w/ absent

radiic) NEWBORNS AS A RESULT OF INTRAUTERINE

EXPOSURE TO DRUGS (THIAZIDES) AND VIRAL INFECTIONS (RUBELLA)

2. ACQUIRED HYPOPLASIA OF MEGAKARYOCYTES

DUE TO THERAPEUTIC AGENT ACTIONS THIAZIDE DIURETICS, ESTROGEN HORMONE AND

ALCOHOL SELECTIVELY DECREASES MEGAKAYOCYTE PRODUCTION

3. INFILTRATION OF THE BM BY MALIGNANT CELLS

Thrombocytopenia associated to such oncogenic conditions is due to marrow replacement or toxin inhibitors of thrombopoiesis produced by the abnormal cells.

4. INEFFECTIVE THROMBOPOIESIS Characterize by normal to increased marrow

megakaryocytes in association with decreased circulating platelets.

Due to defective platelet formation, abnormal marrow release of platelets, or destruction of platelets in the BM.

Found in Px w/:a) Megaloblastic Anemia b) DiGuglielmo’s Syndromec) Paroxyxmal nocturnal hgburiad) Myelodysplastic syndromes and leukemia

HEREDITARY CONDITIONS ASSTD W/ INFFECTIVE PLATELET PRODUCTIONa) Autosomal dominant thrombocytopeniab) May-Hegglin anomalyc) Wiscott-Aldrich syndrome

5. DISORDERS OF THE CONTROL OF THROMBOPOEISIS

Not common; Result from an impairment in the mechanism that control platelet production.

Cyclic Thrombocytopenia is a condition in which thrombocytopenia and normal platelet counts alternate at regular intervals

DECREASE PLATELET SURVIVAL TIME INCREASE PLATELET DESTRUCTION: IMMUNOLOGIC

THROMBOCYTOPENIA1. IDIOPATHIC THROMBOCYTOPENIC PURPURA

(ITP) THROMBOCYTOPENIA OCCURS IN THE ABSENCE OF

ANY DISEASE ASSOCIATED WITH DECREASE PLATELET OR TOXIN EXPOSURE.

a) Acute ITP – 2-6 years old; after recovery from viral infection; self limiting

i. STAINED BLOOD SMEAR presents: young, large platelet w/ abnormal shapes

ii. Dec. Platelet survival time- due to destruction by immune complexes or foreign Ag adsorbed by platelets as a result of an infection

iii. Spontaneous remission

b) Chronic ITP- adult; mostly 20-40 years womenii. Circulating platelet are young w/ short

lifespan and IgG are elevated.iii. Thrombocytopenia is due to clearing of the Ab

coated platelets by slpeen and liver. iv. Tx is costicosteroid therapy or splenectomyv. Rare remission

c) Recurrent ITP- found in Px that does not experience permanent remission ff the CITP Tx.

ii. Characterized by alternating intercals of thrombocytopenia and normal platelet count.

iii. Tx Immunosuppressive drugs and plasmapheresis

d) Neonatal ITP- transplacental passage of antiplatelet Ab and occurs most freq when mother is thrombocytopenic at the time of delivery

2. DRUG INDUCED IMMUNOLOGIC THROMBOCYTOPENIA

a) Antibiotics, hypnotics, analgesics, heavy metals, diuretics, chloroquine, digitoxin, heparin and tolbutamide

b) Both the drug and Ab must be present in the system at the same time for platelets destruction.

c) Thrombocytopenia will occur after 12 hour of drug intake but the time can be still delayed

d) Megakaryocyte in the BM is normale) Removal of the fending drug is usually

curative to normalize platelet

3. IMMUNOLOGIC THROMBOCYTOPENIA Condition that is

indistinguishable to chronic ITP

4. POST TRANSFUSION PURPURA

Occurs 7-10 days after blood transfusion containing platelets.

Result from sensitization of individuals negative for the platelet Ag PIA1 . This Ag is found 97% in normal population.

Primary immunization occurs during pregnancy.

5. ISOIMMUNE NEONATAL

THROMBOCYTOPENIA

Analogous to HDN Non-immunologic since

thrombocytopenia is due to increase platelet consumption

Occurs as a result of maternal antiplatelet Ab produces in response to fetal Ag inherited from the father.

Usually affects the first child and platelet Ag PIA1 has most often been asstd.

6. Inc. platelet consumption; non-immunologic thrombocytopenia

Thrombotic thrombocytopenic purpura (TTP)- unknown exact cause; serious dse

a) Hemolytic anemia- trauma to RBC

b) Changing neurologic Sxc) Fever &d) Renal abnormalitiese) DIC-When progress*caused by thrombi in the capillaries and arterioles through out the body.Peripheral blood smear: poikilocytosis and normoblasts*most commonly found in women (40 yrs. Mean age)

7. Hemolytic uremic syndrome

Resembles TTP Primary in children Intravascular clotting

is confined to kidney Tx- dialysis, plasma

transdusion or exchange & antihypersensitive therapy

7. NONIMMUNOLOGIC THROMBOCYTOPENIA Thrombocytopenia may be present in a number

of rickettsial, bacterial, viral or malarial infections- due to Increase consumption of platelets and less commonly as a result of decrease production.

Thrombocytopenia related to cardiopulmonary bypass can result from DIC, dilution, sequestration, platelet destruction in the oxygenerator and increase fibrinolysis.

INCREASED PLATELET SEQUESTRATION

An abnormal distribution of platelets may also cause thrombocytopenia.

Normally the spleen pools approximately one-third of the total spleen (splenomegaly).

An increased percentage of the platelets will be found in the spleen, thereby producing thrombocytopenia.

Increased splenic pooling is differentiated from destruction of platelets

thrombocytopenia

DILUTION OF THE PLATELET COUNT

Multiple transfusions

Splenic pool

Transfusion

THROMBOCYTOSIS A platelet count increased above normal

will be found as a result f a variety of circumstances.

Reactive thrombocytosis

REACTIVE THROMBOCYTOSIS

Generally responds when the lying disorder is treated.

Following splenectomy, the platelet count will generally rise during the first postoperative week, peak at about 2 to 3 weeks, and return to normal over a period of several months.

Thrombocytosis following major surgery usually occurs during the first postoperative week, with the platelet count generally decreasing to normal levels within about 2 weeks.

Within about a day or so following acute blood loss, a reactive thrombocytosis may occur as a result of increased bone marrow stimulation.

Marked increase in the platelet count

Associated with thrombotic and /or hemorrhagic

complications.

Common in myeloproliferative disorder that includes:

Essential thrombocytosis

Chronic Myelogenous Leukemia

Polycythemia Vera

Myeloid Mataplasia

AUTONOMOUS THROMBOCYTOSIS

AUTONOMOUS THROMBOCYTOSIS

Thrombocythemia

Middle age patients (both

male and female)

bleeding or thrombosis with bleeding episodes

predominating (Gastrointestinal

hemorrhage)

Bleeding in

arterial and

venous circulat

ion

Splenomegaly is

a frequent finding

QUALITATIVE PLATELET DISORDER

Hereditary Qualitative Platelet Disorder

Acquired Qualitative Platelet Disorder

Functional Platelet Disorder

Platelet Adhesion

Platelet Aggregation

Platelet Secretion

orRelease Reaction

PLATELET ADHESION DEFECTS Bernard-Soulier Syndrome Inherited as an autosomal recessive

trait Bruising and moderate to severe

bleeding

** CHARACTERISTICS ** Giant Platelets (20 um in diameter)

Coarse granulation and vacuoles Mild thrombocytopenia

PLATELET

Lack glycoprotein 1b (GP1b)

Lack glycoprotein V AND IV

Function as Receptor in

vonWillebrand factor

Unable to adhere normally

to vascular endothelium

Do not bind coagulation

factor XI normally

CHARACTERISTICSo MEGAKARYOCYTE (in BM) =

Normal to slightly increasedo PLATELET- Bleeding time is PROLONGED

but clot refraction is NORMAL- Platelet aggregation is

NORMAL with ADP, epinephrine and collagen, but ABNORMAL ristocetin and thrombin

- DECREASED platelet retention in glass beads column

vonWillebrand’s Disease- ABSENT or ABNORMAL form of

vonWillebrand factor = impaired platelet adhesion

- NORMAL in Aggregation studies with ADP, collagen and epinephrine

- ABNORMAL ristocetin-induced aggregation

PLATELET AGGREGATION DEFECTS

An aggregation disorder is when platelets do not bind with fibrinogen and other proteins in order to stick to other platelets. As a result the platelets cannot form a plug to stop the bleeding from a damaged blood vessel.

A defect of platelet aggregation associated with an abnormal distribution of glycoprotein IIb-IIIa complexes within the platelet: the cause of a lifelong bleeding disorder.

platelet aggregation studies show a defective primary response in the presence of collagen, epinphrine, ADP, and thrombin but normal response with ristocen

Diagnose: platelet retention is markedly increased platelet count is generally normal but may occasionally be slightly decreased. clot retraction is decreased to absent bleeding time is prolonged

Blood tests show: that bleeding time is much longer than normal that the platelets do not clump together at all (platelet aggregation is absent).

Wright stain blood smear: it appear as morphologically normal and show aggregating agents.

Also called Glanzmann’s thrombosthenia-is major inherited bleeding disorder

characterized by the failure of platelets to aggregate when stimulated with adenosine diphosphate (ADP) or other physiologic agonists.

It is inherited or passed down from a child's parent(s). This

disorder causes moderate to severe bleeding symptoms: Bleeding from the mouth Bleeding with dental procedures Nose bleeds Bruising or small purplish red dots under the skin Bleeding for a long time after an injury or surgery Girls or women may have heavy periods Infant boys may have bleeding after circumcision

PLATELET SECRETION DEFECTS

A secretion disorder is when the

damaged blood vessel takes more time for

the bleeding to stop due to missing

chemicals that signals the platelets to stick

together. As a result, it takes a lot longer for

the bleeding from a damaged blood vessel

to stop. This is the most common platelet

disorder.

Two groups:1.Storage pool disorder

defective platelet release reaction due to a lack of dense bodies and/or granules.

mild to moderate bleeding tendency, and easy bruising

Abnormalities of the dense bodies or a granules

2. Aspirin-like defects

platelets have normal granules but defective release

deficiency of the enzyme cyclo-oxygenase or thbormalrombozane synthetase

have a prolonged bleeding time and abnormal aggregation with ADP, epinephrine, and collagen.

Three platelet function disorders involve platelet secretion:1. Alpha Granule Deficiency, called Gray Platelet

Syndrome, there is a lack of important proteins within the alpha granule inside the platelet. This problem slows down normal platelet adhesion, aggregation and repair of the blood vessel

2. Dense Granule Deficiency, called Delta Storage Pool Deficiency, there is a lack of storage granules for certain substances needed for normal platelet activation. Their absence slows down platelet activation and blood vessel constriction.

3. Abnormalities of the granule secretory mechanism occur when the normal granules fail to release their contents when platelets are activated.

HEREDITARY FORMS OF PLATELET DYSFUNCTION

- Very large platelets & abnormalities in platelets adhesion & aggregation*Ehlers-Danlos Syndorme

Hereditary Afibrinogenemia- prolonged bleeding time - abnormal platelet aggregation with ADP *glycoprotein storage disease type 1 (G-6-PD deficiency)

- bleeding time is also prolonged - platelet defects may be secondary to the

metabolic defect

ACQUIRED QUALITATIVE PLATELET DISORDERS

- Acquired disorders of platelet function are associated with a number of conditions & with the ingestion of certain drugs.

• Uremia- metabolites that are toxic to the platelets accumulate in the plasma.

- Platelet release reaction, aggregation, retention are all abnormal & bleeding time is prolonged.

- Platelet dysfunction & abnormal platelet-vessel wall interaction

- Dialysis is of temporary therapeutic value; the administration of cryoprecipitates will aid in controlling major bleeding episodes.

Platelet dysfunction & bleeding disorders will be present in the various paraproteinemia.

Multiple myeloma & Waldenstrom’s macroglobinemia-abnormalities of the platelet aggregation & reduced platelet retention are thought to be due to:

- coating of the platelet membrane - vessel walls with the abnormal

proteins

Acute myeloblastic leukemia

Megakaryocyte in the BM may be small & somewhat abnormal

Resultant platelets abnormal - defective platelet aggregation- defective release mechanism

Myeloproliferative disorders

(polycytothemia vera, chronic myelogeneous leukemia, myeloid metaplasia, & essential thrombocythemia)

-Display fuctional abnormalities in addtion to thrombocytosis

-Common complications:-bleeding and/or thrombosis

Myeloid metaplasia-bleeding time is prolonged-defective platelet adhesion, aggregation, & storage pool

deficiencies Abnormal platelet aggregation- polycythemia vera Thrombocythemia- platelets appear in large &

morphologically abnormal Prolonged bleeding time & defective aggregation-

chronic myelogenous leukemia

Inc. amounts of fibrinogen degradation products

- Present in DIC, fibrinogenolysis, & liver disease

- Inhibit ADP induced platelet aggregation

Fragments D & E -absorb onto the platelet surface,

interfere with platelet function & will inhibit thrombin induced platelet aggregation

Platelet associated antibodies

Iodiophatic thormbocytopenia purpura Autoimmune disorders

-systemetic lupus erythromatosis - Antibodies have been shown to cause

platelet lysis, platelet aggregation & serotonin release

Drugs Inhibit platelet function Aspirin - inhibit release reaction & secondary wave of

the aggregation - Direct result of aspirin’s ability to inactive the

enzyme cyclo-oxygenase - Effect of aspirin : lasts for the life of the platelet - Presence of aspirin: defective platelet aggregation

with ADP, epinephrine & collagen - Other drugs that induce qualitative platelet

abnormalities: -antihistamines, antidepressants & antibiotics,

heparin dextran & other plasma expanders, ethanol & certain local anesthetics