Formation of a hemostatic plug can be broken down into primary hemostasis and secondary hemostasis. Primary hemostasis involves platelet adhesion, change in platelet shape, platelet aggregation, and secretion of platelet factors. Secondary hemostasis involves the activation of the coagulation cascade. Platelets play a vital role in the formation of a hemostatic plug. Platelets are originally produced in the bone marrow as fragments of the cytoplasm from megakaryocytes, which circulate in the blood for 7–10 days. The normal circulating platelet count is 150,000–450,000/μL and approximately 15,000–45,000/μL platelets are made per day to maintain a steady state. At any given time, up to one-third of all platelets are transiently sequestered in the spleen. The likelihood of bleeding is inversely proportional to platelet function and count.
If the endothelial cell continuity is disrupted, and the underlying matrix is exposed, a series of events are coordinated to seal the injured area. Platelets play a primary role in this process by interacting with subendothelial von Williebrand factor (vWF) via a membrane glycoprotein (1b) complex. Platelets adhere to each other via GP IIb/IIIa—platelet aggregation. Platelets also contain alpha and dense granules, which contain hemostatic proteins and proaggregatory factors, respectively. Furthermore, once platelets are activated to form a hemostatic plug, they recruit additional platelets through the release of proaggregatory materials and synthesis of thromboxane A2 and arachidonic acid.
It is imperative to take a detailed family history, and history and physical for these patients to determine if the disease is caused by an inherited, acquired, or primary and secondary hemostatic disorder. Primary disorders will commonly have epistaxis, bleeding gums, and metromenorrhagia. Physical exam may show areas of easy bruising, purpuric spots, petechiae, ecchymosis, hemarthrosis, and enlarged spleen due to sequestering of platelets. Additionally, a peripheral smear, coagulation studies, bleeding time, and CBC can aid in the diagnosis of the type of platelet dysfunction. It is important to remember spurious thrombocytopenia may occur due to clumping of platelets in the specimen, or dilutional thrombocytopenia due to replacement of fluid or blood without concomitant platelet replacement.
Thrombocytopenia can be further subdivided into increased destruction, decreased production, and distribution in circulation. Due to the plethora of platelet disorders, only the most commonly encountered types will be discussed below.
Reduced Platelet Production
Aplastic anemia is a failure of total cell line production that often occurs within the bone marrow. Several disease states can cause decreased production including tuberculosis, leukemia, and granulomatous disorders that result in bone marrow failure. Additionally aplastic anemia can occur due to radiation or chemotherapy in cancer patients. Toxic chemicals may also lead to platelet production failure. Furthermore, several common drugs such as alcohol, estrogens, diuretics, and various antibiotics cause reduced cell lines. Infiltration of the bone marrow by hematopoietic malignancies, such as leukemias, lymphomas, or myeloproliferative disorders can reduce bone marrow volume, and space that would normally be ...