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Qualitative Platelet Defects

Deficiency of granule stores. The term storage pool deficiency (SPD) refers to patients with deficiencies in platelet content of dense granules (*-SPD), alpha-granules (*-SPD) or both groups of granules ("-SPD) platelet diseases, platelet defects, bleeding. By electron microscopy, *-SPD platelets have a marked decrease in dense granules, and the total platelet and granule ATP and ADP contents are decreased. Other dense granule substance including serotonin, calcium, and pyrophosphate are also decreased. *-SPD has been reported in association with other inherited systemic disorders, such as the Hermansky-Pudlak syndrome.

Defects in platelet signal transduction (primary secretion defects). Signal transduction events reflect those processes resulting from the initial interaction of agonists with specific receptors on platelets and leading to processes such as G-protein activation and activation of effectors such as PLC and PLA2. If the key Components in platelet signal transduction mechanisms are the surface receptors, the G-proteins that modulate their link with intracellular effectors, and the effectors, evidence now exists for specific platelet abnormalities.

Defects in thromboxane Az production. A major platelet response during activation is liberation of parahidrotic acid from phospholipids and its subsequent enzymatic oxygenation to TxA2. Patients have been described with defects in the liberation of arachidonic acid as

Treatment of platelet function disorders. In patients with severe vWD and afibrinogenemia the treatment for bleeding episodes and management during surgical procedures is replacement of the deficient plasma factor. Milder cases of vWD are treated with 1-desamino-D-arginine vasopressin (DDAVP) which induces a rise in plasma vWF and factor VIII.

Congenital Disorders of Platelet Function

Disorders of platelet function are characterized by mucocutaneous bleeding manifestations that are highly variable among patients with different underlying defects; excessive hemorrhage may follow surgical procedures or trauma. Platelet counts and morphology are normal in most patients. While the majority of patients have a prolonged bleeding time, it is not always the case. Platelet aggregation and secretion studies provide evidence for the defect.

 

Table 1. Classification of congenital disorders of platelet function

1. Defects in platelet-vessel wall interaction (disorders of adhesion)

a. von Willebrand disease (deficiency or defect in plasma vWF)

b. Bernard-Soulier syndrome (deficiency or defect in GPIb)

2. Defects in platelet-platelet interaction (disorders of aggregation)

a. Congenital Afibrinogenemia (deficiency of plasma fibrinogen)

b. Glanzmann's thrombasthenia (deficiency or defect in GPIIb-IIIa)

3. Disorders of platelet secretion and signal transduction

a. Abnormalities of Granules

i. Storage pool deficiency

ii. Quebec platelet disorder

b. Signal transduction defects (primary secretion defects)

i. Defects in platelet-agonist interaction (receptor defects)

ii. Defects in G-protein activation

iii. Defects in phosphatidylinositol metabolism

iv. Defects in calcium mobilization

v. Defects in protein phosphorylation (pleckstrin)

c. Abnormalities in arachidonic acid pathways and thromboxane A2 synthesis

i. Impaired liberation of arachidonic acid

ii. Cyclooxygenase deficiency

iii. Thromboxane synthase deficiency

4. Disorders of platelet coagulant-protein interaction

a. Defect in factor Va-Xa interaction on platelets (Scott Syndrome)

5. Miscellaneous congenital disorders

a. May-Hegglin anomaly

b. Down's syndrome

 

Acquired Disorders of Platelet Function

Acquired defects in platelet function (Table 2) are encountered far more frequently than inherited abnormalities. The biggest offenders leading to impaired platelet function are numerous drugs, (Table 3). For several, this has been largely an in vitro effect on platelet aggregation responses without convincing evidence.

 

Table 2. Acquired defects in platelet function

Drugs and other agents

Uremia

Myeloproliferative Disorders

Preleukemia and acute leukemias

Dysproteinemias

Cardiopulmonary bypass

Acquired storage-pool deficiency

Antiplatelet antibodies

Liver disease

 

Several nonsteroidal anti-inflammatory agents also impair platelet function by inhibiting the cyclooxygenase enzyme and may prolong the bleeding time. These include indomethacin, ibuprofen sulfinpyrazone, meclofenamic acid, phenylbutazone, and sulindac. Compared with aspirin, the inhibition of cyclooxygenase by these agents is generally short-lived and reversible. In the case of ß-lactam antibiotics, the effect on platelet function and hemostasis is generally manifested during high dose Parenteral therapy lasting several days.

 

Table 3. Pharmacologic agents affecting platelet function (other than antithrombotic agents)

Non-steroidal anti-inflammatory Agents

$-lactam antibiotics 

Penicillins

Cephalosporins

Antibiotics

Nitrofurantoin

Cardiovascular Drugs

$-Adrenergic Blockers (propranolol)

Vasodilators (Nitroprusside, nitroglycerin)

Calcium Channel Blockers (Verapamil)

 Quinidine

Psychotropic Drugs

Tricyclic Antidepressants (Imipramine)

Phenothiazines (Chlorpromazine)

Anesthetics

Local (eg, Dibucaine)

General (eg, Halothane)

Chemotherapeutic Agents

Mithramycin, BCNU, Daunorubicin

Dextrans

Radiographic Contrast Media

(This is a partial list Adapted from Rao and Carvalho

 

Chronic Renal Failure/Uremia. Bleeding has been a frequent and sometimes serious complication of uremia, but its incidence has declined, possibly because of better treatment of the underlying disorders procedures. It remains a serious concern in uremic Patients undergoing surgery or invasive. Bleeding in uremia is generally mucocutaneous, and rarely may be intracranial or pericardia/. The BT is prolonged in uremia, and this has been useful in separating bleeders from non-bleeders.