Platelet Disorders: General Considerations

Definition, Etiology, PathogenesisTop

Disorders of platelets may be caused by low platelet counts (thrombocytopenia), high platelet counts (thrombocytosis), or abnormal platelet function.

1. Thrombocytopenia is usually defined as a platelet count <150×109/L. It may be classified as:

1) Thrombocytopenia caused primarily by excess destruction of platelets:

a) Immune: Primary or secondary immune thrombocytopenia (ITP); drug-induced immune thrombocytopenia (eg, quinine/quinidine, sulfonamides, vancomycin, abciximab, antibiotics); heparin-induced thrombocytopenia (HIT), which can be associated with thrombosis. Secondary ITP can be caused by infections (HIV, hepatitis C, Helicobacter pylori), concomitant autoimmune diseases (eg, systemic lupus erythematosus, antiphospholipid syndrome), and non-Hodgkin lymphoma, among others.

b) Nonimmune: Thrombotic microangiopathies, including thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS), sepsis, disseminated intravascular coagulation (DIC), Kasabach-Merritt syndrome, and others.

2) Thrombocytopenia caused by impaired platelet production: Thrombocytopenia may be incidentally found in the complete blood count in a patient with a variety of clinical conditions. Bone marrow aspiration and biopsy reveal reduced megakaryocyte counts or their abnormal morphology. Other diagnostic studies depend on the suspected underlying condition. Treatment of inherited diseases may require platelet concentrate transfusions, while treatment of acquired disease should include elimination of the causative factors, treatment of the underlying condition, and administration of a platelet concentrate when necessary. Of note, repeated platelet transfusion is likely to be associated with refractoriness; thus, transfusion should be used sparingly:

a) Inherited: Rare, sometimes familial, may present in childhood. Examples include Bernard-Soulier syndrome, Fanconi anemia, Alport syndrome.

b) Acquired: More frequent, it may be caused by drugs (myelosuppressive chemotherapy, linezolid, interferons, and many others), alcohol misuse and other toxins, viral infections, cobalamin and/or folate deficiency, bone marrow disorders (leukemia, aplastic anemia, lymphoid neoplasm, myelodysplastic syndrome, cancer metastasis, myelofibrosis), bone marrow infiltration (Gaucher disease, tuberculosis), radiation, amegakaryocytic thrombocytopenia, or cyclic thrombocytopenia (regular decreases in platelet counts every 21-39 days, most frequently in young women).

3) Thrombocytopenia caused by sequestration of platelets: Hypersplenism; rarely at other sites, such as large hemangiomas.

4) Thrombocytopenia caused by dilution developing after massive transfusion or fluid resuscitation.

5) Physiologic thrombocytopenia of pregnancy, also called gestational thrombocytopenia (platelet counts are usually >70×109/L; the condition requires no treatment and resolves spontaneously after delivery).

Pseudothrombocytopenia is a laboratory artifact caused by in vitro platelet agglutination (clumping) in the typical blood collection tube, which contains ethylenediaminetetraacetic acid (EDTA). It can cause significant underestimation of platelet counts. Examination of the blood film may be done for any patient with thrombocytopenia to exclude platelet clumping. Most automated analyzers will recognize platelet clumping and not report a falsely reduced level. Platelet counts are often accurate when the blood is collected in tubes containing citrate or heparin. Other causes of pseudothrombocytopenia include sampling-related factors (prolonged draw time, inappropriate mixing, vial overfill, sample obtained from an IV line or proximally to an IV line [dilution]), platelet satellitism around white blood cells, and macrothrombocytopenia.

2. Thrombocytosis is defined as a platelet count >400×109/L:

1) Primary thrombocytosis: Essential thrombocythemia or other myeloproliferative neoplasms (see Myeloid Neoplasms).

2) Secondary (reactive) thrombocytosis may be caused by surgery, solid tumors, iron deficiency anemia, hemolytic anemia, chronic inflammatory or infectious diseases, acute blood loss, or splenectomy. It is usually asymptomatic, causes no bleeding or thrombosis, and resolves after successful treatment of the underlying condition.

3. Qualitative disorders of platelet function cause impaired platelet aggregation assessed by platelet aggregometry. Patients may have normal or slightly reduced platelet counts:

1) Inherited: Rare abnormalities of platelet surface receptors (eg, Bernard-Soulier syndrome, Glanzmann thrombasthenia), membrane, cytoskeleton, or degranulation.

2) Acquired: Most commonly drug-induced (acetylsalicylic acid, ticlopidine, clopidogrel, prasugrel, ticagrelor, glycoprotein IIb/IIIa antagonists, fibrinolytic agents, or other drugs) or caused by uremia, myeloproliferative neoplasms, acute leukemia, or monoclonal gammopathy.

Note: In patients with severe bleeding due to a qualitative platelet disorder, tranexamic acid or desmopressin 0.3 microg/kg may be effective. Platelet concentrates may be considered for patients who do not respond adequately to medical treatments. Repeated doses of desmopressin are limited by tachyphylaxis and hyponatremia. Data from clinical trials are lacking.

Clinical FeaturesTop

Cutaneous and mucosal bleeding: petechiae on the skin of extremities, trunk (rarely the face), and oral mucosa; gingival bleeding; epistaxis; menorrhagia and urinary and/or genital bleeding. Life-threatening gastrointestinal or intracranial hemorrhages may occur, and excessive bleeding after tissue injury may be observed. In patients with thrombocytopenia bleeding tends to occur only when platelet counts are <20×109/L or if other risk factors are present (eg, antiplatelet medications, anticoagulation, recent trauma).