Diseases involvingBlood Platelets.

Kriti Baba ShresthaRoll no: 235th Batch, 3rd YearDepartment of Oral Pathology.

Purpura• Nonthrombocytopenic Purpura• Thrombocytopenic Purpura

Primary Thrombocytopenia

Thrombotic Thrombocytopenic Purpura

Wiskott-Aldrich Syndrome

Thrombocytasthenia• Familial Thrombasthenia• Thrombocytopathic Purpura• Thrombocythemia

CONTENTS:

PURPURAPurpura is defined as a purplish discoloration of the skin and mucous membranes due to the spontaneous extravasation of the blood.It is a symptom rather than a disease entity. Purpura mainly results if the blood platelets are defective or deficient, as the clotting mechanism is the important function of blood platelets.

Classification:- 1) Nonthrombocytopenic Purpura

2) Thrombocytopenic Purpura a. Primary or ‘essential’ purpura b. Secondary or symptomatic purpura

Fig: Oral PurpuraFig: Purpura on lower extremities

It is the type of purpura which is not mediated through changes in the blood platelets, but rather through alteration in the capillaries themselves that results in many instances in increased permeability.

The most common cases or conditions causing this form of purpura are:

I. Autoimmune a. Allergic purpuras b. Drug-induced vascular purpura c. Purpura fulminans

II. Infections

a. Bacterial (meningococcemia and septicemia due to other organisms, typhoid fever, scarlet fever, diphtheria etc.

b. Viral (small pox, influenza, measles, others)

III. Structural malfunctionsa. Hereditary hemorrhagic telangiectasiab. Hereditary disorders of connective tissue ( osteogenesis imperfecta, Ehlers-Danlos

syndrome etc.)c. Acquired disorders of connective tissue (scurvy, Cushing's disease, senile purpura)

Nonthrombocytopenic Purpura

IV. Miscellaneousa. Autoerythrocyte sensitization and related syndromes (DNA

hypersensitivity cutaneous hyper-reactivity of hemoglobin)b. Paraproteinemias (hyperglobunemic purpura, Waldenstrom’s purpura)c. Purpura simplex and related disordersd. Purpura in association with certain skin disease( ‘orthostatic’ and

‘mechanical’ purpura)

Fig: Nonthrombocytopenic Purpura

It is a disease in which there is an abnormal reduction in the number of circulating blood platelets.

Development of the focal hemorrhages into various tissues and organs, including the skin and mucous membranes.

There are two basic forms of thrombocytopenia :

a. Primary (of unknown etiology)b. Secondary (which may be due to various situations)

Thrombocytopenic Purpura

Fig: Secondary thrombocytopenia

Primary thrombocytopenia is thought to be an autoimmune disorder in which a person becomes immunized and develops antibodies against his/her own platelets.

In some cases in it appears to be absence of a platelet-stimulating or megakaryocyte-ripening factor.

The various manifestations of Primary and Secondary thrombocytopenic purpura are near Identical so may be described together.

Primary Thrombocytopenia(werlhof’s disease,purpura hemorrhagica and idiopathic purpura)

Age : Primary thrombocytopenia occurs before 3rd decade of life, greatest incidence before 1st decade.

Secondary thrombocytopenia has no particular age predilection.

Sex: Female> Male (especially women of child bearing age) Characterized by the spontaneous appearance of purpuric or

hemorrhagic lesions of the skin of varying size from tiny, red pinpoint petchiae to large purplish ecchymoses.

Bruising tendency Epistaxis, hematuria, gastrointestinal bleeding, producing melana. Hemiplegia

Clinical Features:

Severe and profuse gingival hemorrhage (prominent) which may be spontaneous and often arise in the absence of skin lesion.

Petchiae also occur on oral mucosa, commonly at palate. appear as numerous tiny, grouped clusters of reddish spots

of a millimeter or less in diameter.

Actual ecchymoses do occur occasionally.

Tendency of excessive bleeding.

Oral manifestations:

Platelet count is usually >60,000 per cubic millimeter. Bleeding time is prolonged, up to 1 hour or more. Capillary fragility is increased. Positive Tourniquet test. Red and white blood cells normal unless secondarily

affected by frequent episode of hemorrhage or drugs. Normal coagulation time. Giant platelets may be seen in peripheral smear which may

suggest congenital thrombocytopenia.

Laboratory Findings

No specific treatment. Splenectomy proved to be beneficial. Corticosteroids used in many cases with excellent results

though recession may be temporary. Prognosis for the patients are fairly good, since recession is

common. In the secondary thrombocytopenia, correction or the

removal of the etiologic factors is essential.

Treatment and Prognosis

It is a life threatening multisystem disorder of an obscure nature but may be immunologically mediated.

1st described by Eli Moschcowitz in 1924.

It is characterized by microangiopathic hemolysis and platelet aggregation/hyaline thrombi in micro-circulation, whose formation is unrelated to coagulation activity.

The endothelia of kidney and brain are particularly vulnerable to TTP.

Thrombotic Thrombocytopenic Purpura (Moschcowitz disease)

Age: usually in young adults. Sex: female>male. (associated with pregnancy, HIV, cancer,

bacterial infections, bone marrow transplantation etc.) Characterized by thrombocytopenia, hemolytic anemia, fever,

transitory neurologic dysfunction and renal failure.

Histologic Features Widespread microthrombi in the arterioles, venules, and

capillaries throughout body. Intravascular thrombi composed of loose aggregates of platelets

organized into amorphous plugs replaced by fibrin. Characteristic microscopic gingival changes as occlusive

subintimal deposits of PAS(periodic acid-Schiff) positive material at arteriolocapillary junction.

Clinical Features

Fig: thrombotic thrombocytopenic purpura

On blood examination thrombocytopenia and anemia noted. Fragmented RBCs consistent with hemolysis noticed in

peripheral smear. Reticulocyte count elevated. Prothrombin time and activated partial thromboplastin time

(aPTT) are in normal limits. LDH levels increased. Indirect bilirubin elevated (due to extensive hemolysis). Urinalysis shows protienuria and microscopic hematuria).

Treatment and Prognosis Disease uniformly fatal Survival supported by modern therapeutic drugs and

techniques including corticosteroids, platelets, aggregation inhibitors, Splenectomy and exchange transfusions.

Laboratory finding

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive genetic condition with variable, commonly includes immunoglobulin M (IgM) deficiency.

This syndrome results from an X-linked genetic defect in a protein now termed as Wiskott-Aldrich Syndrome protein (WASp) whose function seems to bridge between signaling and actin polymerization in the cytoplasm.

Wiskott-Aldrich Syndrome(Hypogammaglobulinemia M)

Usually seen exclusively in young boys. Characterized by thrombocytopenic purpura, eczema,

usually beginning from the face. Petechiae and a purpuric rash or ecchymoses of the skin

may be the early sign. Manifest boils, otitis media, bloody diarrhea, respiratory

infection. Occurrence of a lymphoreticular malignant neoplasm,

commonly a malignant lymphoma. Increased susceptibility to infection appears related to an

antibody deficiency.

Clinical features

Spontaneous bleeding of the gingiva (most frequently seen). Gastrointestinal bleeding and Epistaxis also can be seen. Palatal Petechiae may also be present.

Laboratory Findings Both qualitative and quantitative abnormality of platelets. Prolonged bleeding time (due to thrombocytopenia between

18,000-80,000 / cubic millimeter) Alteration in size and shape of the platelets. (smaller) Quantitatively, decreased production and defective maturation

of platelets since normal megakaryocyte seen in marrow. Accelerated platelet clearance from peripheral blood.

Oral Manifestations

Fig: Wiskott-Aldrich syndrome

No specific treatment for the disease. Death usually occurs within the first 5 years of life as a result of secondary infection or hemorrhage.

Treatment with some antibiotics and platelet transfusion. Bone marrow transplantation. Transfer factor.

The eventual prognosis, however, is poor.

Treatment And Prognosis

Thrombocysthenia is the term used to designate a variety of diseases characterized by a qualitative defect in blood platelets.

Some forms are congenital and/or familial, while others are acquired.

A. Familial ThrombastheniaB. Thrombocytopathic PurpuraC. Thrombocythemia

THROMBOCYTASTHENIA

It is a hereditary, chronic hemorrhagic disease transmitted as an autosomal recessive trait.

There appears to be at least 7 forms of Glanzmann disease, thus accounting for the heterogeneous nature of the various description of the condition.

Clinical Features No sex predilection, though in female onset of menarche

may be critical event. Exhibit usual characteristics of excessive bleeding either

spontaneous or due to minor trauma. Purpuric hemorrhage of skin, epistaxis, gastrointestinal

bleeding Hemarthrosis also been reported.

Familial Thrombasthenia (Glanzmann Thrombasthenia or disease)

Fig: familial Thrombasthenia

Spontaneous bleeding from the oral cavity, particularly gingival bleeding.

Often seen in these patients as are palatal petechiae.

Laboratory Findings Prolonged bleeding time Clot retraction characteristically impaired. Platelet count and clotting time are normal. Reduced amounts of certain membrane glycoprotein on the

surface of platelets which is responsible for haemostatic defect.

Oral Manifestation

Fig: microscopic view

Treatment

No specific treatment.

However, Perking and his co-workers discussed this disease and reported two cases of patients requiring oral surgery who were treated with microfibrillar collagen preparation and with a fibrinolytic inhibitor, c- aminocaproic acid, to control post operative hemorrhage.

It is a group of rare diseases of unknown etiology in which the patient manifests a bleeding tendency referable to qualitative defects in the blood platelets.

Not related to thrombocytopenia as the platelet count is normal, though these two diseases are clinically indistinguishable.

Thrombocytopathic Purpura (Thrombocytopathia)

Severe bleeding tendency and bruise easily after only minor trauma.

Spontaneous ecchymoses (common)

Petechial hemorrhage (rare).

Epistaxis and bleeding into gastrointestinal tract are frequent clinical findings.

In females, sometimes severe menstrual bleeding occurs which may require blood transfusion.

Clinical Features

Spontaneous gingival bleeding (most common). Mucosal ecchymoses (occasional). Excessive and prolonged bleeding from dental extractions.

Can be serious management plan.

Laboratory Findings Bleeding time may be normal or prolonged. Platelet counts nearly normal. Failure of normal aggregation. Variety of platelet defect seen within its different forms for

eg: in ‘storage pool disease’, there is deficiency in nonmetabolic storage pool of platelet adenine nucleotides.

Oral Manifestations

Fig: Thrombocytopathia

No satisfactory treatment for the disease.

Conventional haemostatic agents and blood transfusion aid in controlling the severe hemorrhage.

Death due to prolonged bleeding is rare but could obviously occur.

Treatment

Thrombocythemia is a condition characterized by an increase in the number of circulating blood platelets.

A number of cases have been reported to occur in association with the polycythemia and myeloid leukemia, anemia, tuberculosis and sarcoidosis, rheumatoid arthritis, bronchial carcinoma with osseous metastases.

As in the thrombocytopenia, 2 forms are recognized:-a. Primary or Essential thrombocythemia

b. Secondary thrombocythemia

Thrombocythemia (Thrombocytosis)

Primary thrombocythemia is of unknown etiology. Secondary thrombocythemia may occur after,• Traumatic injury• Inflammatory conditions• Surgical procedures• Parturition

It may be due to over production of the proinflammatory cytokines, such as IL-1, IL-22, that occurs in inflammatory, infections, malignant stages.

These cytokines may be involved in relative thrombocytosis.

No age or gender predilection. Asymptomatic in some cases. Invariably shows the bleeding tendency though the blood

platelet count is elevated. Epistaxis and bleeding into gastrointestinal tract as well in

genitourinary tract and Central Nervous System are common. In skin: hemorrhage are seen.

Oral Manifestations Spontaneous gingival bleeding (common), petechiae (rare). Excessive and prolonged gingival bleeding after dental

extractions. Oral hemorrhage.

Clinical Features

Markedly increased platelet count.◦ Interferes with the formation of the thromboplastin.

Abnormal platelets aggregation in response to several aggregating agents.

Normal:-.Clotting time

.Prothrombin time .Clot retraction .Tourniquet test.Bleeding time prolonged. In Primary thrombocythemia ,RBC and WBC count normal

and are altered in Secondary thrombocythemia depending the associated condition.

Laboratory Findings

Administration of Radioactive Phosphorous {P32} (most common).

Blood transfusion in case of severe hemorrhage. Certain cytotoxic drugs, Heparin during thrombotic

episodes, Corticosteroids and Aspirin have been used with some degree of success.

Treatment

Fig: primary thrombocythemia

Fig: secondary thrombocythemia

Shafer’s Textbook of Oral Pathology Oral And Maxillofacial Pathology, Neville. Internet sources.

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