Platelet counts below 150×10 to the ninth per liter reflects thrombocytopenia.

Classification includes: decreased production, increased platelet destruction, disorders of platelet distribution and dilution.

Decreased production may be secondary to bone marrow failure, bone marrow infiltration, bone marrow depression, megakaryocytic depression, nutritional deficiency, and hereditary causes.

Decreased platelet production can be seen with viral infections, following drug administration, during of the course of a malignant hematologic disease, after chemotherapy, after radiation, as a result of alcohol toxicity, drug toxicity, vitamins B12 or folic acid deficiency, infections, systemic lupus erythematosus, and granulomatous diseases.

Ineffective thrombopoiesis may be seen with megaloblastic anemias caused by B12 or folic acid deficiencies, and also in iron deficiency.

Iron deficiency results in decreased megakaryocytic size and the suppression of megakaryocyte proliferation and size.

Increased platelet destruction can be seen in immunologic conditions such as idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, systemic lupus erythematosus, HELLP syndrome, and antiphospholipid syndrome.

May be secondary to the use of extracorporal circulation as in, cardiac bypass surgery.

May be associated with heparin induced thrombocytopenic events.

Heparin induced thrombocytopnenia (HIT) is the most common drug induced thrombocytopenia.

HIT and antiphospholipid syndrome are two thrombotic syndromes with antibodies against complexes of charged molecules causing thrombocytopenia: in both syndromes IgG antibodies against positively charged endogenous proteins beta-2 glycoprotein 1 (GPI) . In the antiphospholipid syndrome, and platelet factor 4 (PF4) in HIT.

Some viral infections can affect both platelet production and destruction.

Sepsis is the main cause of thrombocytopenia in severely ill or intensive care unit patients.

Bacterial sepsis increases platelet destruction by platelet attachment to bacterial antigen-antibody immune complexes.

Thrombocytopenia is common following viral infections, parasitic infections, bacterial infections, hepatitis vaccination by 1-3 weeks.

Increased platelet destruction may be immune or non immune mediated.

Immune destruction includes: idiopathic thrombocytopenia purpura, SLE, chronic lymphocytic leukemia, lymphoma, drug induced-heparin, quinidine, gold, penicillamine, cimetidine, infectious -HIV, other viruses and malaria, post transfusion purpura and neonatal purpura.

Neonatal autoimmune thrombocytopenia occurs in mothers with chronic immune thrombocytopenia with transplacental passage of maternal IgG platelet autoantibodies.

Immune thrombocytopenia common complication of HIV infection with autoantibodies that recognized a restricted peptide sequence GPIIIa49-66 in platelet membrane glycoprotein IIIa.

Immune thrombocytopenic purpura commonly involves antibody mediated platelet destruction.
Autoantibodies to platelets in HIV infection have the ability to induce reactive oxygen species through activation of 12-lipooxygenase and NADPH oxidase, leading to platelet fragmentation.

Non immune destruction mechanisms include: thrombotic thrombocytopenia purpura/hemolytic uremic syndrome, cavernous hemangioma following cardiac bypass surgery and hypersplenism.

Drugs associated with thrombocytopenia include:quinidine, sulfonamides, heroin, morphine, and snake venom.

Morphine induced thrombocytopenia is associated with complement activation.

Occurs in up to 20% of medical ICU and 35% of surgical ICU admissions.

35-59% of patients with sepsis have thrombocytopenia.

20-30% of patients with solid tumors or lymphomas treated with chemotherapy have a platelet count <50,000/microL and approximately 10% have platelet counts between 10,000 and 20,000/microL.

Most common drug induced immune mediated thrombocytopenia is caused by quinidine as an outpatient and vancomycin as an in-patient.

A risk factor for acute myocardial infarction in Kawasaki disease.

Cytomegalovirus, H5N1, and HIV viral infections are associated with thrombocytopenia.

Development of thrombocytopenia associated with poorer clinical outcomes, and increased 30 day and 1 year mortality in acute myocardial infarction.

Frequent complication of advanced chronic liver disease.

In chronic liver disease low platelet count due to portal hypertension, hypersplenism, decreased thrombopoietin production and bone marrow suppression.

Alcohol suppresses bone marrow production.

Pregnancy is associated with a lower platelet count, and gestational thrombocytopenia is caused by hemodilution and increased platelet activation and clearance.

During the third trimester of pregnancy platelet counts decrease by approximately 10%.

Risk of bleeding may depend on underlying cause with spontaneous bleeding from chemotherapy induced thrombocytopenia only when platelet counts less than 10,000/microL, whereas the risk of bleeding much higher in patients with myelodysplastic

Clinical manifestations include the presence of petechiae or purpura.

Petechiae refers to small, hemorrhagic purplish spots on the skin or mucous membranes, while purpura refers to extensive areas of red or dark purple discoloration of the skin.

Use of prophylactic platelet transfusions is standard of care to reduce the risk of clinically significant bleeding in hypoproliferative thrombocytopenia.

PLADO Trial data suggest that platelet counts, hematocrits, coagulation factors, and clinical treatment categories may all predict increased risk of bleeding.

In the presence of thrombocytopenia, hematocrit levels are inversely associated with risk of bleeding.

Analysis of coagulation assays demonstrated an increased overall risk for bleeding for patients with abnormal INR and aPTT.

There is an increased bleeding risk in patients with hypoproliferative thrombocytopenia treated with chemotherapy or allogeneic transplant vs patients undergoing autologous SCT.

Increased overall risk with hypoproliferative thrombocytopenia and bleeding correlates with profoundly low platelet counts (<5000), hematocrit of <25%, INR >1.2, and aPTT >30 seconds.

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